A review of 71 cases of solid carcinoma of the stomach selected from 2,738 cases of surgically resected poorly differentiated adenocarcinomas (PDAs) was undertaken. The average age of the patients, which included 47 men and 24 women, was 62 years. The clinicopathologic features of solid carcinomas were similar to those of the differentiated type adenocarcinomas. The solid carcinomas were divided into 42 of the solid alveolar type and 29 of the free-cell type; 32 of the former (76%) had foci of overt differentiated areas, while most of the latter type lacked such foci and had some signet-ring cells. Many tumors of both types had a prominent venous permeation and lymph node metastasis even in the early stage of invasion. The 5-year survival rates were 37% in all cases, 44% in cases with carcinoma with a limited invasion of the submucosa or the muscularis propria, and 27% in carcinoma invading down to the subserosa. These survival rates were poor in comparison with the 110 cases of ordinary PDA (diffuse type of Lauren) selected as controls. These findings suggest that tumors of the solid alveolar type are transformed from the differentiated type of adenocarcinoma, while those of the free-cell type are originally from PDAs. It is also suggested that solid carcinomas did show a high incidence of venous permeation and lymph node metastasis and that the prognosis for this type of carcinoma is poor.

We studied cellular proliferation by measuring the tritiated thymidine labeling index (TLI) in slices of primary invasive breast carcinomas. Estrogen receptor (ER) and progesterone receptor (PgR) were measured by ligand-binding assay.

A thymidine labeling study of cell kinetics of 61in situ breast carcinomas showed relationships between histological characteristics and kinetics. The thymidine labeling index (TLI) was significantly lower in cribriform-papillary intraductal carcinoma (median 1.30%, geometric mean 1.18%, mean 1.83 ± 0.45%) and lobular carcinomain situ (median 1.43%, geometric mean 1.12%, mean 1.63 ± 0.46%) than in comedo intraductal carcinoma (median 4.40%, geometric mean 3.74%, mean 5.15 ± 0.86%). The results for solid intraductal carcinoma, which is a less well defined and more heterogeneous entity, were intermediate (median 2.45%, geometric mean 2.40%, mean 3.32 ± 0.80%). When invasive carcinoma was also available for kinetic study, the TLI ofin situ and invasive components were usually similar (r = 0.66). The data indicate that the TLI usually does not change during the transition fromin situ to invasive carcinoma. Cribriform-papillary intraductal carcinoma is a slowly proliferating entity that gives rise to slowly proliferating invasive carcinomas with relatively high levels of estrogen and progesterone receptors. Lobular carcinomain situ similarly has low proliferative rates and gives rise to slowly proliferating invasive carcinomas. Intraductal comedocarcinoma has relatively high proliferative rates and gives rise to invasive carcinomas with high proliferative rates that often are receptor-negative. Nine of the 11in situ carcinomas that were associated with invasive tumor and subsequent local recurrence or metastasis had TLIs above the median, and seven were comedo type with high TLIs. Our observations from thymidine labeling are consistent with a viewpoint regarding cribriform-papillary intraductal carcinoma as relatively bland, and comedo intraductal carcinoma as a distinctly more dangerous entity. Solid intraductal carcinoma seems to resemble cribriform-papillary more closely than comedo intraductal carcinoma.

The prime importance of axillary node status in predicting recurrence and survival has been appreciated for a long time. More recently routine measurements of estrogen and progesterone receptors have added to our prognostic abilities. The next generation of prognostic markers to be used in the routine clinical setting will be measures of tumor aggressiveness which will prompt therapeutic decisions. The technique of flow cytometry can provide clinicians with two new important pieces of information. First, it gives a measurement of the percentage of cells in S phase of the DNA replicative cycle, in other words, how fast a tumor is growing. Second, it assesses the aneuploidy, or total amount of extra DNA in the tumor cell, which appears to correlate with malignant aggressive tumor behavior.

Carcinoma of the urinary bladder is among the more frequent neoplasms in the United States, with an estimated 37,100 new cases diagnosed in 1982, 27,000 in males and 10,100 in females.' In addition, more than 2,000 new cases of carcinoma of the renal pelvis and ureter would be expected during the same one-year period. 1.2 The urethra is less often the site of the presenting carcinoma, but carcinoma in situ of the urethra may coexist with invasive bladder carcinoma, and subsequently become invasive after treatment of the bladder carcinoma. 5 Both stage and histologic grade? influence the course of the disease and response to therapy. The proliferative rate of urothelial carcinoma could be another determinant of prognosis. Prior studies have shown that normal epithelium and carcinomas of the urinary bladder can be labeled in vitro with tritiated thymidine and S-phase cells thereby detected.v Veenema, Fingerhut, and Craff! and Hainau and Dornbernowsky? reported that carcinomas of high histologic grade had a;high thymidine labeling index (TLI) compared with low-grade carcinomas. Histologically low-grade carcinomas with high TLI tended to have rapid clinical courses. 10 Flat transitional cell carcinomas were

The S-phase fraction (SPF) measured by flow cytometry of DNA and the thymidine labeling index (TLI) measured autoradiographically indicate the proportion of carcinoma cells currently synthesizing DNA and reflect the rate of proliferation. The TLI and SPF are lognormally distributed. The median TLI performed to maximize precursor uptake is near 5% (5 labeled carcinoma cells per 100), the mean near 7%, and the range from less than 1% to near 40%. Corresponding values for the SPF measured by DNA flow cytometry are slightly higher when appropriate measures are taken to reduce background debris counts and other artefacts. Residual elevation of SPF above TLI may result from S-phase arrested cells. Flow cytometric histograms show that clearly aneuploid cell lines exist in 50–80% of primary breast carcinomas. Aneuploid breast carcinomas have higher mean TLI than diploid breast carcinomas, and therefore proliferate more rapidly. They also more frequently lack estrogen receptor (ER). Carcinomas with minimal nuclear anaplasia, particularly those of tubular, mucinous, infiltrating lobular and adenocystic types have low TLI and SPF, whereas carcinomas with highly anaplastic nuclei, including medullary carcinomas, have high TLI and SPF. TLI and SPF correlate inversely with ER and PgR content, have no relationship to axillary lymph nodal status, and have a weak positive correlation with tumor size and a weak negative correlation with age. High TLI predicts a high risk of early relapse after primary therapy for both node-negative and node-positive carcinomas. Carcinomas that produce brain metastases have particularly high TLI. Current evidence suggests that high SPF and aneuploidy may prove to have prognostic significance like TLI.

Cerebral vasoconstrictor responsiveness to 100% oxygen inhalation was measured in 149 subjects, including normal healthy volunteers and those with risk factors for cerebral arteriosclerosis (N = 87). Test results were compared among patients with hemispheric stroke and vertebrobasilar insufficiency (N = 62) with the 133Xe inhalation method. Normal volunteers without risk factors (N = 49), aged 25 to 86 years, showed symmetrical vasoconstriction. Asymptomatic subjects with risk factors (N = 38) and those with vertebrobasilar insufficiency (N = 25) had decreased hemispheric gray matter flow (Fg) values during rest, but vasoconstrictor responsiveness to 100% oxygen inhalation was not significantly reduced. In patients with acute hemispheric infarction, regional vasoconstrictor responsiveness to 100% oxygen inhalation was lost and/or paradoxically reversed; in patients with chronic hemispheric infarction, it was decreased. Testing vasomotor responses during hyperoxia is safe, clinically helpful, and demonstrates impaired vasomotor reactivity in infarcted regions.

To determine whether autolytic loss of estrogen (ER) and progesterone (PgR) receptors might affect results of assays performed on primary carcinoma samples taken from fresh mastectomy specimens rather than from biopsy specimens, a group of 71 cases were examined, in which both types of samples were assayed. The comparisons showed a small significant reduction in the proportion of positive ER assay results in mastectomy-primary specimens compared with biopsy specimens, although the frequency of high-binding ER results in the mastectomy-primary specimens was not reduced. The number of positive PgR assays on mastectomy-primary specimens was not reduced in comparison with biopsy specimens. Correlation coefficients for ER values in the paired data were r = 0.836 for biopsy versus mastectomy, and r = 0.795 for primary tumor versus nodal metastasis. For PgR biopsy versus mastectomy r = 0.664, and for PgR primary versus node r = 0.352. The mean quantitative ER and PgR values were significantly higher in axillary lymph nodal metastases than in primary carcinomas, and the higher nodal receptor levels were explained in part by significantly higher tumor cellularity. It is concluded that while loss of ER sufficient to cause a false-negative interpretation may possibly occur in a few cases during the course of mastectomy, as a general rule, significant losses do not occur. The performance of assays on axillary metastases in mastectomy specimens is advantageous because of their high cellularity.

The thymidine labeling index (TLI) was measured in vitro in 278 primary breast carcinomas. In 227 operable women treated by radical mastectomy, TLI's below the median of 4.55% carried a probability of relapse of 20% at four years, in contrast to 52% for TLI's above the median (P = 0.0001). The probability of relapse was significantly related to the TLI independent of TNM pathologic stage, axillary lymph nodal status alone, estrogen receptor (ER) content, or menopausal status. The abilities of the TLI and nodal status to predict early relapse were equally strong and independent, whereas other variables tested had less or no independent predictive capacity. The predictive value of the ER content depended largely on its relationship to the TLI, and ER was related to the probability of relapse in the below median TLI group only. The TLI can select a subgroup of node-negative patients with a relapse-expectancy of approximately 50% at four years.

Resting-state regional gray matter flow (Fg) values and cerebral vasoconstrictor responses induced by 100% oxygen inhalation were measured with the 133 Xe inhalation method in normal healthy volunteers aged between 15 and 86 years and in patients with senile dementia of Alzheimer's type (SDAT) or multi-infarct dementia (MID). Cross-sectional analysis revealed that there were linear decreases of oxygen responses with advancing age in 84 normal volunteers between the second to ninth decades. Eleven patients with SDAT showed bilateral and symmetrical reductions of resting-state Fg values compared with 22 age-matched normal healthy volunteers. Eight patients with MID showed no significant reduction of mean Fg values compared with normal controls and patients with SDAT. Oxygen vasoconstrictive responses in SDAT were symmetrical and similar to those seen in age-matched controls. Compared with patients with SDAT, patients with MID showed reduced oxygen vasoconstrictive responses that were asymmetrical between hemispheres as well as heterogeneous within hemispheres. Testing cerebral vasoconstrictor responses by 100% oxygen inhalation is helpful for differentiating SDAT from MID.

Five postmenopausal women were treated with conjugated equine estrogens, 1.25 mg tablets for 25 days, and medroxyprogesterone acetate, 10 mg tablets, in combination with the last 10 estrogen doses. Twenty-five endometrial biopsy specimens were incubated in vitro with tritiated thymidine and radioautographic slides were prepared. Within five days of estrogen treatment the thymidine labeling index (TLI) in both glands and stromal cells increased from a very low resting state to relatively high levels of DNA synthesis and cell proliferation. Within five days after addition of progestin, epithelial TLIs decreased to low levels and returned to minimal baseline levels four days after the last steroid dose. Analysis of variances indicated significant changes in epithelial cells (P less than 0.0001) confirming that the proliferative effect of estrogens was suppressed during the progestin phase. Stromal TLI changes were not significant (P = 0.46).

A virilizing granulosa cell tumor of the ovary contained large amounts of testosterone and progesterone and small amounts of estrogens. Assays for progesterone receptor were positive, but estrogen receptor could not be detected. The presence of progesterone receptor in the tumor is consistent with recent evidence for a role of the receptor in the physiology of the Graafian follicle, and suggests the possibility that progestational therapy may be effective in advanced stage granulosa cell tumor.

Programs have been developed, using a single compartmental analysis model, that provide rapid computer derivation for values of both local cerebral blood flows (LCBF) and local tissuc:blood partition coefficients (LA) using inhaled stable xenon gas (Xes) as the indicator. These programs are planned for utilization of raw data points derived from serial computed tomography scans made between the 3rd and 9th min after 35% Xes inhalation, while concentrations of end-tidal Xes (PEXes) are concurrently monitored. Double integration and least squares fitting permitted estimation of corresponding arterial (assumed from PEXes) and tissue Xes concentrations at each scanning interval during Xes saturation. Derived estimates for LA and LCBF values for each region of interest mathematically approximate values saturated to infinity. The method described can be utilized for any freely diffusible indicator. Cross-sectional analysis of results obtained in 13 normal healthy volunteers between 20 and 80 years of age showed no age-related changes in LA values but progressive decreases in blood flow of cortex, basal ganglia, and white matter with advancing age. In senile dementia of Alzheimer's type (SDAT. n=8) LA values were likewise found to be unchanged, but cortical and thalamic gray matter LCBF values were significantly reduced compared to age-matched normal volunteers.

The S-phase fractions (SPFs) of epithelial cells in 100 resected colorectal carcinomas were measured by in vitro exposure to tritiated thymidine and autoradiography. The frequency distribution of SPFs was gaussian with a median of 17.8 per hundred in 90 unirradiated carcinomas, whereas in ten carcinomas given radiation therapy preoperatively, it was positively skewed with a median of 6.9. Analysis of the unirradiated carcinomas showed no relationship between SPF and various clinical and morphologic features that included age, race, sex, site, size, Dukes' stage, histologic grade of the tumor, number of metastasis-bearing regional lymph nodes, presence of adenomas of the large bowel, survival or relapse-free survival of the patient, or SPF or adjacent normal colorectal crypts. The results show no evidence that colorectal carcinomas can be divided into kinetic subsets. The spatial orientation of labeled cells in autoradiographs indicated presence of a nonproliferative fraction of cells in many tumors that may modulate response to radiation therapy and chemotherapy.

The clinical and morphologic features of a recurrent, multifocal, adult, extracardiac rhabdomyoma are reported. This benign skeletal muscle neoplasm is composed of large round to polyhedral cells containing cross striations. The ultrastructural features consist of hypertrophic Z bands, intranuclear inclusions, and numerous mitochondria with linear, intracristal inclusions. The low thymidine labeling index and long potential doubling time correspond wi th the length of time for clinical recurrence.

The fractions of tumor cells in S phase(DNAsynthesis)were measured by in vitro thymidine labeling and autoradiography in 48 breast carcinomas after relapse. The S-phase fractions (SPF's), expressed as S-phase cells/i 00 cells, had a lognor mal distribution with a geometric meanof 6.5 and a medianof 7.4. Paired SPF measurementson the primary and relapsed breast carcinomasof i 4 patients showed that the SPF usually increased over time. The SPF after relapse correlated nega tively with the interval between primary therapy and relapse and with duration of survival after relapse. Low SPF's were associated with older age, minimal nuclear anaplasia, and estrogen receptor positivity, but SPFwas the only variable that could be shown to have independent prognostic significance. Therefore, the prognostic powers of the estrogen receptor status and nuclear grade appear to result from their correla tions with the SPF. Either low SPF or ‘presence of estrogen receptor predicted responseto hormonaltherapy.