Validez diagnóstica del sistema vesical imaging-reporting and data system (VI-RADS): estudio con datos de la vida real / Diagnostic validity of the vesical imaging-reporting and data system (VI-RADS): A real-world study

Objetivo: Recientemente se ha generalizado el uso del sistema vesical imaging-reporting and data (VI-RADS). Nos propusimos validar el rendimiento diagnóstico del VI-RADS para diferenciar el cáncer vesical músculo-iinvasivo (CVMI) del cáncer vesical no músculo-invasivo (CVNMI) en un contexto de práctica clínica real. Métodos Entre diciembre de 2019 y febrero de 2022 se revisaron los pacientes con sospecha de cáncer vesical primario. Se incluyeron los pacientes con un protocolo de RM multiparamétrica adecuado para VI-RADS antes de cualquier tratamiento invasivo. La estadificación local de los pacientes se realizó mediante resección transuretral, segunda resección o cistectomía radical como tratamiento de referencia. Dos expertos en radiología genitourinaria cegados a los datos clínicos e histopatológicos evaluaron las imágenes de RM multiparamétrica de forma independiente y retrospectiva. Se analizó el rendimiento diagnóstico de ambos radiólogos y la concordancia entre lectores. Resultados De los 96 pacientes, 20 (20,8%) tenían CVMI y 76 (79,2%) tenían CVNMI. La exactitud diagnóstica del CVMI fue alta para los dos radiólogos. El primer radiólogo tenía un área bajo la curva (ABC) de 0,83 y 0,84, una sensibilidad de 85% y 80% y una especificidad de 80,3% y 88,2% para VI-RADS≥3 y≥4, respectivamente. El segundo radiólogo tenía un área bajo la curva (ABC) de 0,79 y 0,77, una sensibilidad del 85% y el 65% y una especificidad del 73,7% y el 89,5% para VI-RADS≥3 y≥4, respectivamente. La concordancia de la puntuación VI-RADS global entre los dos radiólogos fue moderada (K=0,45). Conclusión El sistema VI-RADS tiene un alto poder diagnóstico para diferenciar el CVMI de CVNMI antes de la resección transuretral. La concordancia entre los radiólogos es moderada. (AU)

Objective: Preoperative Vesical Imaging-Reporting and Data System (VI-RADS) becomes widespread. We aimed to validate the diagnostic performance of VI-RADS in differentiating muscle-invasive (MIBC) from non-muscle-invasive bladder cancer (NMIBC) in a real-world setting. Methods Between December 2019 and February 2022 suspected primary bladder cancer patients were reviewed. Those with proper multiparametric MRI (mpMRI) protocol for VI-RADS before any invasive treatment were included. Patients were locally staged according to transurethral resection, second resection, or radical cystectomy as the reference standard. Two experienced genitourinary radiologists who were blinded to clinical and histopathological data evaluated the mpMRI images independently and retrospectively. The diagnostic performance of both radiologists and the interreader agreement were analyzed. Results Among 96 patients, 20 (20.8%) had MIBC, and 76 (79.2%) had NMIBC. Both radiologists had great diagnostic performance in diagnosing MIBC. The first radiologist had an area under curve (AUC) of 0.83 and 0.84, the sensitivity of 85% and 80%, and the specificity of 80.3% and 88.2% for VI-RADS≥3 and≥4, respectively. The second radiologist had an area under curve (AUC) of 0.79 and 0.77, the sensitivity of 85% and 65%, and the specificity of 73.7% and 89.5% for VI-RADS≥3 and≥4, respectively. The overall VI-RADS score agreement between the two radiologists was moderate (K=0.45). Conclusion VI-RADS is diagnostically powerful in differentiating MIBC from NMBIC prior to transurethral resection. The agreement between radiologists is moderate. (AU)

Diagnostic validity of the vesical imaging-reporting and data system (VI-RADS): a real-world study.

OBJECTIVES: Preoperative Vesical Imaging-Reporting and Data System (VI-RADS) becomes widespread. We aimed to validate the diagnostic performance of VI-RADS in differentiating muscle-invasive (MIBC) from non-muscle-invasive bladder cancer (NMIBC) in a real-world setting. METHODS: Between December 2019 and February 2022 suspected primary bladder cancer patients were reviewed. Those with proper multiparametric MRI (mpMRI) protocol for VI-RADS before any invasive treatment were included. Patients were locally staged according to transurethral resection, second resection, or radical cystectomy as the reference standard. Two experienced genitourinary radiologists who were blinded to clinical and histopathological data evaluated the mpMRI images independently and retrospectively. The diagnostic performance of both radiologists and the interreader agreement were analyzed. RESULTS: Among 96 patients, 20 (20.8%) had MIBC, and 76 (79.2%) had NMIBC. Both radiologists had great diagnostic performance in diagnosing MIBC. The first radiologist had an area under curve (AUC) of 0.83 and 0.84, the sensitivity of 85% and 80%, and the specificity of 80.3% and 88.2% for VI-RADS ≥3 and ≥4, respectively. The second radiologist had an area under curve (AUC) of 0.79 and 0.77, the sensitivity of 85% and 65%, and the specificity of 73.7% and 89.5% for VI-RADS ≥3 and ≥4, respectively. The overall VI-RADS score agreement between the two radiologists was moderate (κ = 0.45). CONCLUSION: VI-RADS is diagnostically powerful in differentiating MIBC from NMBIC prior to transurethral resection. The agreement between radiologists is moderate.

Are the current nomograms sufficient to predict shockwave lithotripsy outcomes?

INTRODUCTION AND OBJECTIVES: To investigate factors affecting SWL outcomes, validate three current nomograms (Kim JK, Triple D and S3HoCKwave) and compare the predictive ability of the nomograms for SWL outcomes in upper urinary tract stones. PATIENTS AND METHODS: Medical records of patients with renal and proximal ureteral stones treated with SWL between March 2013 and October 2020 were retrospectively reviewed. Factors affecting SWL success were analyzed with multivariate logistic regression analysis and the three predictive scoring systems compared with the area under the curve (AUC). RESULTS: A total of 580 patients were included in our study. The overall stone free rate was 61% and 144/580 patients (24.8%) were stone free after one session. In multivariate logistic regression analysis, stone location at upper calyx (OR:2.988; 95%Cl: 1.350-6.612; p = 0.007), middle calyx (OR:3.036; 95%Cl: 1.472-6.258; p = 0.003), and lower calyx (OR:2.131; 95%Cl: 1.182-3.839; p = 0.012), as well as number of stones (OR:1.663; 95%Cl: 1.140-2.425; p = 0.008), maximum diameter of stone (OR:1.156; 95%Cl: 1.098-1.217; p < 0.001) and maximum Hounsfield Unit (OR:1.001; 95%Cl: 1.001-1.002; p < 0.001) were independent risk factors of SWL failure. The AUCs of the Kim JK, Triple D and S2HoCKwave scores for predicting SWL success were 0.678, 0.548, and 0.626 respectively. CONCLUSIONS: Stone location, number, maximal diameter, and maximum HU were independent predictive factors for SWL outcome in the treatment of upper urinary tract stones. Current nomograms, "Kim JK nomogram", "Triple D score" and "S3HoCKwave score" can predict treatment success after SWL, but all of them have poor discrimination according to AUC analysis.

La radiómica mejora la utilidad del ADC en la diferenciación entre el oncocitoma renal y el carcinoma cromófobo de células renales: resultados preliminares / Radiomics improves the utility of ADC for differentiation between renal oncocytoma and chromophobe renal cell carcinoma: preliminary findings

Objective Differentiation between renal oncocytoma (RON) and chromophobe renal cell carcinoma (chRCC) remains challenging. We aimed to assess the accurate apparent diffusion coefficient (ADC) radiomics features in differentiating these tumors.Materials and methods This single-center retrospective study included 14 patients with histopathologically proven RON (n=6) and chRCC (n=8) who underwent magnetic resonance imaging. Features were extracted from ADC maps. Features with an intraclass correlation coefficient >0.90, an intergroup p<0.01 and interrater differences with normal distribution underwent agreement and receiver operating characteristic curve analyses.Results Overall, 6 features qualified for further analysis and Bland-Altman plots revealed acceptable agreement for all. Only 1 first order feature and 5 high order texture features successfully predicted RON with more than 90% sensitivities and specificities more than 80%.Conclusion Squared mean ADC and certain gray level run length matrix features extracted by radiomics of ADC mapping provide quite high diagnostic precision in terms of distinguishing between RON and chRCC (AU)

Objetivo La diferenciación entre el oncocitoma renal (OR) y el carcinoma de células renales cromófobo (CCRcr) sigue siendo un desafío. Nuestro objetivo es evaluar la precisión de las características radiómicas del coeficiente de difusión aparente (ADC) para diferenciar estos tumores.Materiales y métodos Este estudio retrospectivo unicéntrico incluyó a 14 pacientes con OR (n = 6) y CCRcr (n = 8) confirmado por informe histológico que recibieron una resonancia magnética. Las características se extrajeron de los mapas de ADC. Las características con un coeficiente de correlación intraclase > 0,90, un p < 0,01 intergrupo y diferencias interevaluadores con distribución normal se sometieron a análisis de concordancia y de curva característica de funcionamiento del receptor.Resultados En total, se obtuvieron seis características para el análisis posterior y los gráficos de Bland-Altman revelaron una concordancia aceptable para todas ellas. Sólo una característica de primer orden y cinco características de textura de orden superior predijeron con éxito el OR con una sensibilidad superior al 90% y una especificidad superior al 80%.Conclusión La media cuadrada del ADC y ciertas características de la matriz de longitud de secuencia de nivel de gris extraídas por la radiómica del mapa de ADC proporcionan una precisión diagnóstica bastante alta en cuanto a la distinción entre OR y CCRcr (AU)

Radiomics improves the utility of ADC for differentiation between renal oncocytoma and chromophobe renal cell carcinoma: Preliminary findings.

OBJECTIVE: Differentiation between renal oncocytoma (RON) and chromophobe renal cell carcinoma (chRCC) remains challenging. We aimed to assess the accurate apparent diffusion coefficient (ADC) radiomics features in differentiating these tumors. MATERIALS AND METHODS: This single-center retrospective study included 14 patients with histopathologically proven RON (n = 6) and chRCC (n = 8) who underwent magnetic resonance imaging. Features were extracted from ADC maps. Features with an intraclass correlation coefficient >0.90, an intergroup p < 0.01 and interrater differences with normal distribution underwent agreement and receiver operating characteristic curve analyses. RESULTS: Overall, 6 features qualified for further analysis and Bland-Altman plots revealed acceptable agreement for all. Only 1 first order feature and 5 high order texture features successfully predicted RON with more than 90% sensitivities and specificities more than 80%. CONCLUSION: Squared mean ADC and certain gray level run length matrix features extracted by radiomics of ADC mapping provide quite high diagnostic precision in terms of distinguishing between RON and chRCC.

Measuring 3D Cochlear Duct Length on MRI: Is It Accurate and Reliable?

BACKGROUND AND PURPOSE: Prior studies have evaluated cochlear length using CT to select the most suitable cochlear implants and obtain patient-specific anatomy. This study aimed to test the accuracy and reliability of cochlear lateral wall length measurements using 3D MR imaging. MATERIALS AND METHODS: Two observers measured the cochlear lateral wall length of 35 patients (21 men) with postlingual hearing loss using CT and MR imaging. The intraclass correlation coefficient (with 95% confidence intervals) was used to evaluate intraobserver and interobserver reliability for the 3D cochlear measurements. RESULTS: The mean age of the participants was 39.85 (SD, 16.60) years. Observer 1 measured the mean lateral wall length as 41.52 (SD, 2.25) mm on CT and 41.44 (SD, 2.18) mm on MR imaging, with a mean difference of 0.08 mm (95% CI, -0.11 to 0.27 mm), while observer 2 measured the mean lateral wall length as 41.74 (SD, 2.69) mm on CT and 42.34 (SD, 2.53) mm on MR imaging, with a mean difference of -0.59 mm (95% CI, -1.00 to -0.20 mm). An intraclass correlation coefficient value of 0.90 (95% CI, 0.84-0.94) for CT and 0.69 (95% CI, 0.46-0.82) for MR imaging was obtained for the interobserver reliability for the full-turn cochlear lateral wall length. CONCLUSIONS: CT-based 3D cochlear measurements show excellent intraobserver and interobserver reliability, while MR imaging-based lateral wall length measurements have good-to-excellent intraobserver reliability and moderate interobserver reliability. These results corroborate the use of CT for 3D cochlear measurements as a reference method and demonstrate MR imaging to be an alternative acquisition technique with comparably reliable results.

Partial regression of a hydatiform mole with coexisting live fetus in a twin gestation: case report.

Pregnancies resulting in viable fetuses are extremely rare in accompanying a hydatiform mole, often due to the development of maternal complications, including preeclampsia and vaginal bleeding. The risk for gestational trophoblastic neoplasm is another concern because of the delayed evacuation of the molar tissue. In this paper, the authors present a case of complete mole hydatiform with a live co-twin fetus (CHMLF) resulting in the delivery of a healthy male infant with the partial regression of the molar tissue and the decline of serum beta human chorionic gonadotropin (P-hCG) during the pregnancy. In the management of CHMLF, each patient must be considered individually and eligible patients can be followed in the absence of serious maternal complications. Serial ultrasound examinations and close clinical and laboratory surveillance of the mother are certainly indicated.

Adverse effects of aflatoxin B1 on skeletal muscle development in broiler chickens.

Detrimental effects of in ovo administrated of aflatoxin B1 (AFB1) on the embryonic development of skeletal muscle were determined using histological methods. A total of 420 eggs of a Ross broiler parent stock were incubated and divided into 4 groups: (1) control, (2) 5 ng AFB1/egg group, (3) 15 ng AFB1/egg group, (4) 40 ng AFB1/egg group. Test solutions were injected via the air-sac, just prior to setting the eggs in the incubator. Five eggs from each group were opened on different days of incubation (11d, 13d, 17d and 21d). Developmental stages of embryos were determined according to the Hamburger-Hamilton scale and embryos were weighed. Skeletal muscle tissue samples were dissected and fixed, sectioned and stained with Crossman's trichrome and AgNOR. The mean relative embryo, leg muscle and breast muscle weights of AFB1-treated groups were lower than the control group and decreased with increasing AFB1. The nucleus area and AgNOR area of the AFB1-treated groups were also lower than the control group whereas there were no significant differences in AgNOR numbers and AgNOR area/nucleus area among the treatment groups. It was concluded that in ovo administrated of AFB1 adversely affected the embryonic development of skeletal muscle and that affected animals might therefore be more susceptible to skeletal and muscle disorders during the growing period.

Effect of cigarette smoke and alpha-tocopherol (vitamin E) on fertilization, cleavage, and embryo development rates in mice: an experimental in vitro fertilization mice model study.

OBJECTIVE: The objective was to elucidate the effects of cigarette smoke per se or vitamin E on mice exposed to cigarette smoke, with regard to fertility and cleavage rates, and embryo development in an experimental in vitro fertilization (IVF) mice model. STUDY DESIGN: Female and male mice, weighing 18-25 g and aged 14-16 weeks, were separated and divided into cigarette smoke-exposed (SE) and non-smoke-exposed (NSE) groups. A specially designed cage with a cigarette smoking machine was constructed. The SE (20 cigarettes/day) group was put in the cage for 10 weeks. SE and NSE female and male mice were given 50mg/kg of vitamin E intraperitoneally for 10 weeks and were cross-mated thereafter so as to produce seven different subgroups of mice population as follows: group I-NSE male and female mice (control); group II-SE female mice and NSE male mice; group III-NSE female with SE male mice; group IV-SE male and SE female mice; group V-SE female mice treated with vitamin E and SE only male mice; group VI-SE only female and male mice treated with vitamin E; and finally group VII-vitamin E-treated SE male and female mice. Following superovulation with FSH, follicles of female mice were obtained via laparotomy under high-dose ether. Male mice testicles were retrieved via the same surgical procedure. Both gametes were obtained and used for IVF. Fertilization, cleavage rates, and day 3 embryo grading were assessed in four groups. RESULTS: With regard to fertilization rate, group II (36%) significantly differed from group I (85%, p=0.002), group III (68.7%, p=0.04), but not from group IV (20.6%, p=0.34). Taking embryo development rate into consideration, group II (32%) had a lower percentage of embryo development compared with group I (75%, p<0.01) and group III (62.5%, p<0.001), but not group IV (17.2%, p=0.42). Percentages of embryo cleavage, embryo development, and day 3 grade I embryos did differ among four of the groups (p>0.05). CONCLUSIONS: Fertilization and cleavage rates were mainly affected in the SE female mice population. The impact of vitamin E on fertilization, cleavage, and embryo development rates was not relevant among SE male and SE female mice.

Analysis of a dimethacrylate copolymer (bis-GMA and TEGDMA) network by DSC and 13C solution and solid-state NMR spectroscopy.

In this work the effect of dilution with TEGDMA on the kinetics of Bis-GMA polymerization and on the extent of polymerization or degree of conversion was studied using (a) DSC and (b) NMR. The systems with lower viscosity and lower Tg exhibited higher extent of polymerization. For Bis-GMA/TEGDMA mixtures the calculated Tg values were found to be higher than the experimental values suggesting that a dilution effect is predominant rather than intermolecular hydrogen bonding. Solid state NMR has been shown to be a convenient method for measuring the total amount of conversion in a mixed monomer system. The disappearance of the NMR solution spectrum was used to reveal overall polymerization kinetics.

Titrations in non-aqueous media: potentiometric investigation of symmetrical and unsymmetrical tetra-aryl porphyrins with 4-nitrophenyl and 4-aminophenyl substituents in nitrobenzene solvent.

The basicity of the symmetrical and unsymmetrical tetraphenylporphyrins, namely 5,10,15,20-tetraphenylporphyrin (I) (references), 5-(4-nitrophenyl)-10,15,20-triphenylporphyrin (II), a mixture of 5,10-bis(4-nitrophenyl)-15,20-diphenylporphyrin and 5,15-bis(4-nitrophenyl)-10,20-diphenylporphyrin (III), 5,10,15-tris(4-nitrophenyl)-20-phenylporphyrin (IV), 5,10,15,20-tetrakis(4-nitrophenyl)porphyrin (V), 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (VI), a mixture of 5,10-bis(4-aminophenyl)-15,20-diphenylporphyrin and 5,15-bis(4-aminophenyl)-10,20-diphenylporphyrin (VII), 5,10,15-tris(4-aminophenyl)-20-phenylporphyrin (VIII) and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (IX), was investigated potentiometrically in nitrobenzene solvent. This investigation showed that these compounds are basic rather than acidic. Although they can not be titrated even with tetrabuthylammonium hydroxide, they can easily be titrated with perchloric acid to give well shaped and stoichiometric end-points. In addition they all undergo two proton reactions per porphyrin molecule. However, compounds VI, VII, VIII and IX each shows a second end-point to give three, four, five and six proton reactions, respectively, per porphyrin molecule. Half neutralization potentials (measures of their basicity) of these compounds are: I=368, II=409, III=432, IV=461, V=520, VI=340, VII=302, VIII=238 and IX=225 mV versus Ag/AgCl in methanol. These potentials clearly indicate that, if para-hydrogen with respect to the porphyrin core of tetraphenylporphyrin (I) is replaced with an acidifying nitro group (II, III, IV and V) the basicity of I decreases. This decrease is approximately proportional to the number of nitro groups. Each nitro group decreases the half neutralization potential by about 35 mV. On the other hand, if para-hydrogen indicated above is replaced with a basifying amino group (VI, VII, VIII and IX) the basicity increases. This increase is also approximately proportional to the number of amino groups. Each amino group increases the half neutralization potential by about 36.7 mV. The values 35 and 36.7 mV indicate that in nitrobenzene solvent the electron releasing power of an amino group to the porphyrin system is a little stronger than the electron withdrawing power of a nitro group from the porphyrin system. All these observations reveal that the nitrogen atoms at the core of the porphyrin molecules are strongly influenced by changes at the periphery of the molecules, which is a very good indication that the substituted phenyl groups and the cores of the porphyrins are nearly in the same plane.

S-phase fraction combined with other patient and tumor characteristics for the prognosis of node-negative, estrogen-receptor-positive breast cancer.

Women with estrogen-receptor (ER)-positive breast cancer and no axillary lymph-node involvement are considered to have excellent overall prognosis. However, this population is not homogeneous with regard to risk of recurrence; in fact, some of these patients have a prognosis no better than that of many women with ER-negative tumors or positive axillary nodes. Consequently, better tumor markers and better use of those currently available are needed to distinguish patients who would benefit from more aggressive therapy from those for whom such therapy is unnecessary. A well-defined cohort of over 4000 breast cancer patients from National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-14 who had ER-positive tumors and no axillary lymph-node involvement was analyzed to ascertain the usefulness of tumor cell S-phase fraction for prognosis. The significance of clinical tumor size, patient age at surgery, ER and progesterone receptor (PgR) expression, and nuclear grade was also explored. Statistical methods based on smoothing splines were used to relate treatment failure and mortality rates to patient and tumor characteristics. Models for 5- and 10-year disease-free survival (DFS) and overall survival were developed and summarized. The attenuation of the prognostic importance of covariates over time was investigated. After other characteristics were accounted for, a strong association was found between S-phase fraction and DFS, as well as survival. Tumor size, patient age at surgery, and PgR status were also significantly associated with outcome. The diversity of risk in the B-14 population was more extreme than is generally recognized. The prognostic capabilities of S-phase, tumor size, and PgR status were sharply attenuated as the time from surgery increased.

Reduced phosphorylation of topoisomerase II in etoposide-resistant human leukemia K562 cells.

In this report we examine biochemical and genetic alterations in DNA topoisomerase II (topoisomerase II) in K562 cells selected for resistance in the presence of etoposide (VP-16). Previously, we have demonstrated that the 30-fold VP-16-resistant K/VP.5 cell line exhibits decreased stability of drug-induced topoisomerase II/DNA covalent complexes, requires greater ATP concentrations to stimulate VP-16-induced topoisomerase II/DNA complex formation, and contains reduced mRNA and protein levels of the M(r) 170,000 isoform of topoisomerase II, compared with parental K562 cells. K/VP.5 cells grown in the absence of VP-16 for 2 years maintained resistance to VP-16, decreased levels of topoisomerase II, and attenuated ATP stimulation of VP-16-induced topoisomerase II/DNA binding, compared with K562 cells. Sequencing of cDNA coding for two consensus ATP binding sites and the active site tyrosine in the K/VP.5 topoisomerase II gene indicated that no mutations were present in these domains. In addition, single-strand conformational polymorphism analysis of restriction fragments encompassing the entire topoisomerase II cDNA revealed no evidence of mutations in the gene for this enzyme in K/VP.5 cells. Nuclear extracts from K562 (but not K/VP.5) cells contained a heat-labile factor that potentiated VP-16-induced topoisomerase II/DNA covalent complex formation in isolated nuclei from K/VP.5 cells. Immunoprecipitated topoisomerase II from K/VP.5 cells was 2.5-fold less phosphorylated, compared with enzyme from K562 cells. Collectively, our data suggest that acquired VP-16 resistance is mediated, at least in part, by altered levels or activity of a kinase that regulates topoisomerase II phosphorylation and hence drug-induced topoisomerase II/DNA covalent complex formation and stability.

DNA flow cytometric analysis of primary operable breast cancer. Relation of ploidy and S-phase fraction to outcome of patients in NSABP B-04.

Between 1971 and 1974, 1665 women with primary operable breast cancer were randomized into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial (B-04) conducted to evaluate the effectiveness of several different regimens of surgical and radiation therapy. No systemic therapy was given. Cells from archival paraffin-embedded tumor tissue taken from 398 patients were analyzed for ploidy and S-phase fraction (SPF) using flow cytometry. Characteristics and outcome of patients with satisfactory DNA histograms were comparable to those from whom no satisfactory cytometric studies were available. In patients with diploid tumors (43%), the mean SPF was 3.4% +/- 2.3%; in the aneuploid population (57%), the SPF was 7.9% +/- 6.3%. Only 29.9% +/- 17.3% of cells in aneuploid tumors were aneuploid. Diploid tumors were more likely than aneuploid tumors to be of good nuclear grade (P less than 0.001) and smaller size (P equals 0.03). More tumors with high SPF were of poor nuclear grade than were tumors with low SPF (P equals 0.002). No significant difference in 10-year disease-free survival (P equals 0.3) or survival (P equals 0.1) was found between women with diploid or aneuploid tumors. Patients with low SPF tumors had a 13% better disease-free survival (P equals 0.0006) than those with a high SPF and a 14% better survival (P equals 0.007) at 10 years than patients with high SPF tumors. After adjustment for clinical tumor size, the difference in both disease-free survival and survival between patients with high and low SPF tumors was only 10% (P equals 0.04 and 0.08, respectively). Although SPF was found to be of independent prognostic significance for disease-free survival and marginal significance for survival, it did not detect patients with such a good prognosis as to preclude their receiving chemotherapy. The overall survival of patients with low SPF was only 53% at 10 years. These findings and those of others indicate that additional studies are necessary before tumor ploidy and SPF can be used to select patients who should or should not receive systemic therapy.

Effect of local or systemic treatment prior to primary tumor removal on the production and response to a serum growth-stimulating factor in mice.

This report indicates that not only does the preoperative administration of cyclophosphamide or radiation prevent the kinetic changes observed in a distant tumor focus following tumor removal but that the preoperative administration of the antiestrogen tamoxifen and the luteinizing hormone-releasing hormone analogue Zoladex are equally effective in that regard. It also provides evidence indicating that serum obtained from mice treated with those therapies when transferred to a recipient bearing a tumor of a similar type to that in the donor fails to stimulate DNA synthesis in the tumor of the recipient. In contrast, an increase in labeling index occurs following transfer of serum obtained following tumor removal from untreated mice. Moreover, when tumor-bearing mice were treated by each of the four modalities prior to receiving serum obtained from untreated donors following removal of a tumor, no kinetic changes were observed in the tumor of the serum recipient.

Presence of a growth-stimulating factor in serum following primary tumor removal in mice.

The effect of removal of a primary tumor on the kinetics of cells in a metastasis was evaluated using six different tumors (C3H, MXTa, MXTb, MC54, CD8, and 3LL) which varied relative to their origin, histology, and the strain of mice in which they were carried. There was an increase in the labeling index (LI) of distant tumor focus ("metastasis") associated with the removal of each of the tumor types and unrelated to operative and anesthetic trauma. Information presented supports the presence of a serum growth factor as being responsible for the phenomenon. Serum obtained from mice following removal of a tumor, when transferred to a recipient with the same type of tumor as in the donor, resulted in an increase in the LI of the tumor. Multiple injections of serum failed to add to the increase but did prolong its presence, suggesting that there is a finite population of cells, most likely in the G1-G0 phase, which are capable of responding to the stimulating factor. The transfer of serum obtained following removal of a tumor type different from that in recipients resulted in findings which indicate that tumors producing a stimulating growth factor are those capable of responding to it. Serum obtained from animals with unremoved tumors or less than 18 h after removal failed to substantially augment the LI of tumors in recipients. It is postulated that the growth factor released by a tumor is in an inactive form which becomes activated over time. Observations indicate that medium conditioned by the growth of C3H tumor contains a growth-stimulating factor which is capable of increasing the LI of a C3H tumor in a recipient in a fashion similar to that obtained following tumor removal. That finding indicates the capability of the tumor to elaborate growth-stimulating material which may be similar to that found in serum. The findings presented refute the premise that removal of a primary tumor is a local phenomenon with no other biological consequences. They indicate that, following primary tumor removal, metastatic behavior may be affected by an interplay of growth factor(s) which can influence the outcome of a host to its tumor.

The use of FITC-conjugated monoclonal antibodies for determination of S-phase cells with fluorescence microscopy.

A method is modified to determine the DNA synthesizing cells in primary human breast tumors and cells with idiopathic thrombocytopenic purpura (ITP) with FITC-conjugated monoclonal antibody against bromodeoxyuridine (FITC-M-anti-BrdUrd) and fluorescence microscopy. The DNA synthesizing cells were also determined from a portion of the same tissues by classical tritiated thymidine labeling (3HdThd) and autoradiography. The results from bromodeoxyuridine labeling index (BrdUrd-LI) and tritiated thymidine labeling index (3HdThd-LI) obtained from the same tissues were compared. The mean BrdUrd-LI for breast tumor was 5.4 +/- 1.0% and the mean 3HdThd-LI was 5.5 +/- 1.1%. Similarly, the labeling indexes obtained from mononuclear leukocytes of healthy donors had means of 0.5 +/- 0.1% and 0.6 +/- 0.1% for BrdUrd-LI and 3HdThd-LI, respectively. The change in the proliferation rate of mononuclear leukocyte population in the samples obtained from patients with ITP could be observed by both methods. The mean BrdUrd-LI of mononuclear leukocytes for this hematological disorder was 5.4 +/- 0.8%. These results suggest that was 6.1 +/- 0.8%. These results suggest that this relatively simple technique offers an alternative method for determining the DNA synthesizing cells in a given cell population.