Deficiency of mature B and T lymphocyte subsets in the blood of non-Hodgkin lymphoma patients

The expression of mature B-cell markers and T markers was determined in lymphocytes isolated from the peripheral blood (PBL) of 20 healthy and 51 patients with non-Hodgkin malignant lymphoma (NHL). The disease was classified as newly diagnosed, in remission, or being treated with chemotherapy and of low-, intermediate-, or high-grade malignancy. To avoid technical problems associated with artifacts involving cytophilic immunoglobulins (Ig), we defined mature B-cells by means of three criteria: a) expression of high surface density of Ig sufficient to allow polar movement of receptors to form a cap in an indirect immunofluorescence (IF) assay, b) expression of high density of the human leukocyte antigens DR (HLA-DR) under capped conditions, and c) expression of a 41H.16 marker exclusive to surface Ig+ B-cells. Percentages of PBL able to cap surface Ig (sIg) (lambda, K), HLA-DR (7H.3), and 41H.16 markers were significantly reduced (p less than 0.001) in all of the patients, regardless of treatment status, and the numbers of sIg+-capping cells were similarly reduced in the patients, regardless of the grade of malignancy. Studies with ring fluorescence showed mean percentages of cells expressing OKT3 and OKT4 determinants significantly reduced (P less than 0.001) but OKT8+ cells not significantly different from control. The OKT4/OKT8 ratio was reduced in all patients and did not differ significantly in relation to the degree of malignancy. We conclude that, in NHL, essentially all patients have severe abnormalities in the number of B- or T-cells needed for normal immune responses.     

Prognostic factors for recurrent breast cancer: univariate and multivariate analyses including histologic grade and amplification of the c-erbB-2 proto-oncogene.

Post-recurrence survival was examined in 62 breast cancer patients who had undergone curative radical mastectomies between 1974 and 1976 and suffered recurrences within 127 months of surgery. The prognostic value of 11 clinical, histological and genetic factors, including histologic grade of malignancy and amplification of oncogenes was analyzed using univariate and multivariate analyses. Not only the site of first recurrence, clinical stage and size of primary tumor at initial surgery, and disease-free period, but also histologic grade and amplification of the c-erbB-2 proto-oncogene were significant prognostic indicators of recurrent breast cancer. Multivariate analysis using Cox's regression model, histologic grade and amplification of c-erbB-2 in the primary tumor, as well as clinical stage at surgery and site of first recurrence, were shown to be major independent prognostic factors of recurrent breast cancer. Because post-recurrence prognosis was strongly influenced by the clinical, histological and genetic status of the primary breast cancer, appropriate evaluation of the primary tumor for the grade of aggressiveness of the cancer cells, as well as the extent of cancer spread, seem to be important.     

Natural history of human breast cancer: Recent data and clinical implications

Summary This study of the natural history of human breast cancer was based on the analysis of a series of 3000 patients treated by radical mastectomy at a single institution (Institut Gustave Roussy) at a time when adjuvant chemotherapy was not prescribed. The follow-up of the patients ranged from 15 to 30 years; for each patient the tumor size, the number of involved axillary nodes, and the histological grade were prospectively registered.A highly significant correlation was found between tumor size and the probability of distant metastatic dissemination. The distribution of tumor sizes at metastatic spread was log-normal with a median diameter equal to 3.5 cm.The patients were subdivided into 3 groups according to the histological grade. In each subgroup there was a significant correlation between tumor size and the probability of distant spread; the distributions were log-normal and the median size was markedly larger for grade 1 tumors. Moreover the proportion of grade 1 tumors was higher in small tumors than in large ones while the reverse was observed for grade 3 tumors; these data suggest that during their growth tumors progress towards higher grades.One of the chief fundamental characteristics of a tumor seems to be its propensity for axillary node invasion. The orderly pattern of nodal involvement makes it possible to calculate the tumor size at invasion of the first axillary node in each subset of patients. A strong and highly significant correlation exists between the size of the tumor at initation of distant metastasis and at invasion of the first lymph node. However the capacity for lymphatic spread is, on average, acquired much earlier than the capacity for metastatic spread.With a simple model based on these data it was possible to compute the proportion of patients with occult metastases as a function of tumor size, histological grade, and number of involved axillary nodes.Early invasion of axillary nodes is associated with a rapid growth rate of the primary tumor (or a high S-phase fraction). However each of these variables has an independent prognostic significance; the S-phase fraction appears as one of the strongest prognostic indicators.A model of tumor growth was used to assess the impact of screening procedures on the proportion of patients with distant metastases. The predictions of the model are consistent with the results of the screening programs. The model was used to predict the influence of the interval between mammographies on the proportion of patients with distant metastases and on the size of these metastases. Since the curability of distant metastases by adjuvant chemotherapy is, to a large extent, governed by their size, the model can predict the cumulative effect of screening procedures and adjuvant chemotherapy on the proportion of patients with overt distant metastases.     

Haemodynamic Evaluation of Cerebral Gliomas Using XeCT

Summary The purpose of this study was to characterize regional blood flow (BF) in untreated cerebral gliomas (CG) using stable Xe-enhanced computed tomography (XeCT). XeCT of 38 patients with untreated CG were analyzed and compared with CT and magnetic resonance images (MRI) and histopathological findings. Individual averaged BF values for tumour in 29 high grade gliomas (HGGs) and 9 low grade gliomas (LGGs) were intermediate between averaged BF values for cortex and white matter in the non-tumour bearing hemisphere. All averaged BF values for cyst and central necrosis were very low. In 27 HGGs, BF in tumour was relatively high in ring-enhancement lesions on CT and MRI, but was low even in viable tumour centers showing no contrast enhancement. In the other 2 HGGs, BF was low in tumour center and relatively high in tumour periphery regardless of homogeneous enhancement. In 5 HGGs, averaged BF value of the cortex outside surrounding oedema was higher than that of cortex in the non-tumour bearing hemisphere. In LGGs, BF distribution in tumour was homogeneously low in 3 small-sized and heterogeneous in 6 large-sized lesions including moderately high and low BF regions. These differences in BF pattern between HGGs and LGGs on XeCT might be helpful in considering to some extent the histopathology of untreated cerebral glioma pre-operatively.     

Sinus catarrh and histological grade in breast cancer

Histological grading of 52 primary breast carcinomas and analysis of the findings in the corresponding axillary nodes showed that primaries of high grade tend to have more nodes showing sinus catarrh than those of low grade. This is in keeping with previous reports linking sinus cararrh to aggressive tumour growth.     

Fragmentation of biliary stones with a 308 nm excimer laser

The use of a XeCl excimer laser (308 nm) for biliary stone fragmentation is reported. Laser energy is delivered via UV grade fused silica fibers to the target stones immersed in normal saline solution. Sixty biliary calculi--pigment (n = 40), and cholesterol (n = 20)--were fragmented in vitro. The total energy delivered per unit mass of the stone is kept constant. Two energy fluences (80 and 110 mJ/mm2) at two repetition rates (5 and 20 Hz) delivered through fibers of two core sizes (300 and 600 microns) are utilized to study the effect of different laser parameters on the fragmentation process. Although both pigment and cholesterol stones are susceptible to excimer laser fragmentation, higher fragmentation efficiency is obtained for the pigment stones than for the cholesterol stones. Our study suggests that higher energy fluence and larger fiber core size result in higher fragmentation efficiency for pigment stones. Fragmentation thresholds at stone surface for a variety of biliary calculi of known composition were measured. The threshold energy fluence is approximately 3 mJ/mm2 and 17 mJ/mm2 for pigment and cholesterol stones, respectively. Our study indicates that the 308 nm excimer laser may be effective as a laser lithotriptor with low threshold and good efficiency for biliary stone fragmentation.     

Pathological changes of high-grade prostatic intraepithelial neoplasia and prostate cancer after monotherapy with bicalutamide 150 mg

OBJECTIVES:To evaluate the morphological changes induced by a 3-month course of neoadjuvant bicalutamide 150 mg/day before radical prostatectomy (RP) on prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN). PATIENTS AND METHODS: In all, 90 patients with cT1-T2 prostate cancer and HGPIN on prostatic biopsy were randomized to receive bicalutamide (150 mg/day for 3 months) before RP, or to have immediate surgery. Surgical specimens were assessed for the histopathological features of cancer, HGPIN and benign epithelium in a blinded manner. The volumes of prostate cancer and HGPIN were evaluated using a stereological (i.e. grid) method. RESULTS: Compared with the bicalutamide-treated group, the ratio of stroma to epithelium, evaluated by visual microscopic assessment in the normal epithelium of the three prostate zones, was significantly lower in the control group, at 2.27 (sd 1.13), than in the treated group, at 1.87 (sd 0.72) (P = 0.048). The mean (sd) tumour volume was significantly lower in the bicalutamide-treated than in the control group, at 0.914 (0.13) vs 1.47 (0.24) mL (P = 0.044). Similarly, the mean (sd) volume of HGPIN was significantly lower in the bicalutamide-treated than in the control group, at 0.34 (0.06) vs 0.62 (0.07) mL (P = 0.003). At RP, specimen Gleason scores in the bicalutamide-treated group were similar to those in the control group, and were no different from the biopsy Gleason scores. CONCLUSIONS: Involution and epithelial shrinkage of prostate cancer and HGPIN were evident after neoadjuvant treatment with bicalutamide 150 mg. There was no evidence of the emergence of higher-grade cancer after treatment.     

Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder

OBJECTIVE: To assess the contemporary inter-institutional accuracy of urinary cytology in predicting the recurrence of transitional cell carcinoma (TCC) of the bladder, in a large multi-institutional cohort from four continents, as cystoscopy and urinary cytology represent the 'gold standards' for surveillance of TCC recurrences, but the ability of cytology to predict recurrence varies. PATIENTS AND METHODS: Ten institutions contributed 2542 patients with a history of superficial TCC, of whom 898 had TCC recurrence. Age- and gender-adjusted logistic regression models were used to evaluate the association between urine cytology and TCC recurrence. The predictive accuracy derived from the logistic regression model was tested using the area under the receiver operating characteristic curve. The resulting predictive accuracy estimates were internally validated with 200 bootstrap re-samples. RESULTS: The mean (range across institutions) age of the patients was 65 (48-69) years and 75 (67-87)% were men. Cytology was positive in 19 (10-38)% of patients; recurrence was identified in 35 (27-54)% of patients. The sensitivity was 38-65% across institutions. Urinary cytology varied significantly in its ability to predict recurrence of bladder cancer. Institution-specific predictive accuracy adjusted for gender and age was 0.627-0.893. Stratifying by grade and stage only partly attenuated the discrepancies between centres. CONCLUSIONS: The variability of urinary cytology results was very appreciable among the 10 centres and ranged from poor (63%) to excellent (89%).     

Grade Failure and Special Education Placement in Sexual Offenders’ Educational Histories

A sample of 701 adult men underwent assessment following illegal or clinically significant sexual behaviors or interests. Patients were categorized on the basis of phallometric (penile) responses in the laboratory to erotic stimuli depicting adults, pubescent children, and prepubescent children; histories of sexual offenses; and self-reported sexual interests. Comprising the categories were men sexually interested in prepubescent children (pedophiles; n = 114), men sexually interested in pubescent children (hebephiles; n = 377), men sexually interested in adults and who had committed a sexual offense against an adult (teleiophilic offenders; n = 139), and men sexually interested in adults and who had no known history of any sexual offenses (teleiophilic nonoffenders; n = 71). Patients' assessments included IQ testing and self-reported academic history, which included any grade failures and assignment to special education classes. Relative to the teleiophilic offenders, both the pedophilic and the hebephilic groups showed approximately double the odds of failing a grade or being enrolled in special education, both before and after covarying IQ. No significant differences were detected between the teleiophilic offenders and the teleiophilic nonoffenders. These data are consistent with the hypothesis that an erotic age preference for children sometimes results from a perturbation of neurodevelopment occurring early in life.     

PCNA and Ki-67 in Central Nervous System Tumors: Correlation with the Histological Type and Grade

Determination of proteins in the control of proliferation in normal cells helps a better understanding of cellular transformation and proliferation mechanisms. Measurement of proliferative activity is important in determining the tumor grade, recurrence span and malignancy. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two of the nuclear markers used to demonstrate the proliferative phase of the cell cycle.In the present study, 63 central nervous system (CNS) tumors of various histologic types, diagnosed in Çukurova University Medical Faculty, Department of Pathology and graded according to WHO grading system were examined for PCNA and Ki-67 monoclonal antibodies using immunohistochemistry. Results were analyzed with statistical methods. Distribution of PCNA and Ki-67 LI (labeling index) values were determined for different tumor types. The highest PCNA and Ki-67 LI values were detected in medulloblastoma, malignant meningioma, primitive neuroectodermal tumor (PNET) and glioblastoma (GBM) groups, while pilocytic astrocytoma, meningioma, craniopharyngioma and oligodendroglioma showed the lowest values.In such tumors, the correlation between the increasing grade and PCNA and Ki-67 LI values were statistically significant. A correlation between the clinical outcome and Ki-67 and PCNA LI values was also detected.Conclusively, both markers can be used to evaluate the tumor grade and to asses the possibility of recurrence and malignancy in CNS tumors.