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Biomedical subjects

L Buelta

Publications and source records attributed to L Buelta.

At least 19 recordsLinked to original sources

Predictors of axillary lymph node metastases in patients with invasive breast carcinoma by a combination of classical and biological prognostic factors.

The presence of axillary lymph node metastases (ALNMs) is the most important prognostic factor in breast carcinoma. If ALNMs were predictable without performing axillary lymph node dissection (ALND), this procedure would not be necessary in selected patients. Using a combination of some of the new biological markers with the classical ones, our objective was I) to identify the best set of predictors of ALNMs, and II) to define predictive models with either high or low probability of ALNMs. We studied 102 patients with invasive breast carcinoma. All patients underwent ALND, and at least 10 axillary lymph nodes per case were obtained. In the primary tumour we evaluated size, histological subtype and grade, lymphatic/vascular invasion and margin. Hormone receptor status, MIB1 index, microvessel density, c-erbB-2 and cathepsin D expression were assessed by immunohistochemistry, and DNA ploidy and S-phase by flow cytometry. Risk factors for ALNMs were estimated by nonlinear logistic regression analysis. The best predictors of ALNMs were: tumour size > 2 cm [OR 6.45, 95% confidence interval (CI) 21.74 to 1.91], presence of lymphatic/vascular invasion [OR 4.95, CI (14.50 to 1.69)], infiltrative margin [OR 9.87 CI (37.44 to 2.60)] and high MIB-1 index [OR 8.39, CI (33.47 to 2.10)]. Two subsets had a very high risk of ALNMs: I) tumour size > 2 cm, with lymphatic/vascular invasion and infiltrative margin; 26 (89.66%) of 29 patients of this subgroup had ALNMs, and (II) tumour size > 2 cm, with lymphatic/vascular and high MIB1 index.; eight of the nine (89%) patients of this subgroup had ALNMs. We could also identify a two-variable model with a very low risk of ALNMs constituted by tumour with circumscribed margin and low MIB-1 index. Of the 19 patients showing these features, only 1 (5.26%) had ALNMs. Therefore, pathological features of the primary tumour can help to assess the risk for ALNM in invasive breast carcinoma. Such risk assessment might avoid regional surgical overtreatment.

Adenocarcinoma↗

Cathepsin D in host stromal cells is associated with more highly vascular and aggressive invasive breast carcinoma.

AIMS: To determinate the relationship between tumoral angiogenesis and cathepsin D (CD) expression in tumour and host stromal cells of invasive breast carcinoma, and to examine its association with classical prognostic factors such as lymph node status, histological grade, tumour size, mitotic rate, peritumoral lymphovascular invasion and oestrogen receptor (ER) status. METHODS AND RESULTS: Sections from 102 invasive breast carcinoma were cut from the archival formalin-fixed, paraffin-embedded tissue blocks and stained using immunohistochemistry for the endothelial cell adhesion molecule (CD31) and CD. Microvessel density was assessed by counting vessels in the three most vascular areas at x400 field. The counts were expressed as the highest counts within any x400 field. The evaluation of immunostaining for CD was performed separately in both the parenchymal and stromal cells. Microvessel density was correlated positively with histological grade and peritumoral lymphovascular invasion, and correlated inversely with ER status. Positive CD staining of tumour cells was more frequent in positive ER tumours and was not significantly associated with the other classical prognostic factors. However, moderate to strong staining of host cells was correlated with higher histological grade, higher mitotic index and lack of ER protein. There was a statistically significant association between CD expression of host stromal cells and higher vessel count. CONCLUSIONS: CD in host stromal cells is associated with more aggressive tumours and with a higher intratumoral microvessel density. Evaluation of CD in combination with angiogenic activity may be of some help in more accurately predicting the biological behaviour of breast carcinoma.

Adult↗

Selective nuclear morphometry as a prognostic factor of survival in renal cell carcinoma.

In the present study, we sought to determine the predictive value of selective nuclear morphometry (SNM) for patient outcome in renal cell carcinoma (RCC). Tumor samples of 140 renal adenocarcinomas diagnosed and treated with radical nephrectomy and hilar lymphadenectomy between 1970 and 1988 with a minimum follow up of 5 years in all the cases were studied by SNM. The morphometric analysis was performed in the most malignant tumor selected zone. Selection was based on cytological criteria including nuclear grade. Nuclear morphometric features analyzed were: area, perimeter, major diameter, major and minor diameter of the equivalent ellipse, volume of the equivalent ellipse and sphere, circumference diameter, and shape factors. The results showed that in the selected zone tumor nuclei were larger than in the zones selected at random. There was an inverse correlation between morphometric parameters and survival and a direct one between tumoral grade and stage. Tumors of the long-term survival group of patients presented nuclei with smaller morphometric measurements than tumors of short term survival group, with significant differences between them (p < 0.05). In the survival analysis carried out by the Kaplan-Meier method significant differences existed between different groups formed from break point for: area, perimeter, major diameter, major and minor diameter of the ellipse, volume of the ellipse and sphere, circumference diameter and perimeter shape factor. In the multivariate analysis carried out by the Cox method, the feature with the most predictable value related to survival, was the tumor stage. Morphometric value with the highest punctuation in the test was major nuclear diameter. The rest of the morphometric values (except elliptic shape factor and elongation factor) were also significant but they did not improve prognostic information of the major nuclear diameter. SNM offers a useful aid in a more objective grading of RCC. Multivariate Cox analysis revealed additional value of karyometry to tumor stage. SNM can be a useful tool for stratification of patients with RCC.

Adolescent↗

Prognostic factors in supraglottic laryngeal carcinoma.

We carried out a retrospective study of patients with supraglottic carcinomas who were treated surgically at the Marques de Valdecilla Hospital (Santander, Spain) between 1978 and 1987 and who were followed up for at least 5 years. The Kaplan-Meier survival curves were calculated for 24 clinical, histologic, and morphometric parameters. Multivariate analysis was then performed by means of the Cox regression model. In the univariate analysis, survival was related to presence of capsule rupture of the involved lymph nodes (p = 0.00001), number of metastatic lymph nodes (p = 0.0002), postoperative TNM stage (p = 0.004), grade of cell differentiation (p = 0.001), presence of intratumoral necrosis (p = 0.01), and type of invasion (p = 0.04). The nuclear area did not have an influence on survival. Only the presence or absence of capsule rupture of the metastatic lymph nodes and the grade of cell differentiation were included in the final Cox model and proved to be parameters with independent prognostic significance.

Aged↗

Constitutive expression of bcl-2 in B cells causes a lethal form of lupuslike autoimmune disease after induction of neonatal tolerance to H-2b alloantigens.

The bcl-2 protooncogene has been shown to provide a survival signal to self-reactive B cells, but it fails to override their developmental arrest after encounter with antigen. Furthermore, constitutive expression of bcl-2 in B cells does not promote the development of autoimmune disease in most strains of mice, indicating that signals other than those conferred by bcl-2 are required for long-term survival and differentiation of self-reactive B cells in vivo. To further examine the factors that are required for the pathogenesis of autoimmune disease, we have assessed the effect of bcl-2 overexpression on the development of host-versus-graft disease, a self-limited model of systemic autoimmune disease. In this model, injection of spleen cells from (C57BL/6 x BALB/c)F1 hybrid mice into BALB/c newborn parental mice induces immunological tolerance to donor tissues and activation of autoreactive F1 donor B cells through interactions provided by allogeneic host CD4+ T cells. BALB/c newborns injected with spleen cells from (C57BL/6 x BALB/c)F1 mice expressing a bcl-2 transgene in B cells developed high levels of anti-single-stranded DNA and a wide range of pathogenic autoantibodies that were not or barely detectable in mice injected with nontransgenic spleen cells. In mice injected with transgenic B cells, the levels of pathogenic autoantibodies remained high during the course of the study and were associated with long-term persistence of donor B cells, development of a severe autoimmune disease, and accelerated mortality. These results demonstrate that bcl-2 can provide survival signals for the maintenance and differentiation of autoreactive B cells, and suggest that both increased B cell survival and T cell help play critical roles in the development of certain forms of systemic autoimmune disease.

Aging↗

Epidermoid carcinoma of the lung in stage I: factors of prognostic interest.

Factors affecting stage I epidermoid cancer of the lung were studied in a series of 29 patients treated only by surgery and followed up for ten years. A set of 13 variables with a possible influence on prognosis were investigated. The application of the Cox Univariate Analysis to the different variables showed the grade of cell differentiation and the mitotic index to be predictors. In the Cox Multivariate Analysis, the proportional regression equation revealed two independently significant variables (p < 0.01), which were the Mitotic Index and Nuclear Area. Grouping patients on the basis of the prognostic variables indicated allows a better prediction for survival to be made for this series of patients.

Age Factors↗

Nuclear morphometry in prognosis of renal adenocarcinoma.

Nuclear morphometry was carried out on 95 parenchymatous adenocarcinomas of the kidney treated by radical nephrectomy and hilar lymphadenectomy and followed up for at least five years. The study assessed nuclear area, nuclear perimeter, major diameter, nucleolar area, nuclear shape factor, and nuclear size. There was a significant statistical correlation between survival and the morphometric parameters and between the parameters themselves except for nuclear shape factor. The multiple regression proved that nuclear area is the factor which shows the greatest statistical significance for prognosis. Taking a mean nuclear area of 35 microns 2 allowed two prognostic groups to be established regardless of stage, with those below the threshold having a good prognosis and those above it having a poor prognosis: 96.7 percent of patients with a good prognosis survived after five years (60 months) compared with 17.2 percent of those with a poor prognosis.

Actuarial Analysis↗

Self-limited autoimmune disease related to transient donor B cell activation in mice neonatally injected with semi-allogeneic F1 cells.

BALB/c mice injected at birth with 10(8) semi-allogeneic (C57BL/6 x BALB.IgHb)F1 spleen cells develop a lupus-like syndrome in which autoantibodies bear exclusively the donor allotype. We have analyzed the evolution of donor B cell chimerism and the autoimmune manifestations during the first year of life in these mice. Anti-DNA, -histone, and -cardiolipin IgG antibodies as well as circulating immune complexes appeared in the second week of life, reached the highest values around the sixth week, and then progressively dropped to normal values after the sixth month in most mice. The kinetics of the evolution of the autoimmune manifestations, as well as the kinetics of serum donor Ig allotype, were parallel to the kinetics of donor B cell chimerism, which was particularly prominent in the spleens in early weeks of life, and progressively decreased after remission of the autoimmune syndrome. Membrane-proliferative glomerulonephritis, which was followed as the more representative histological abnormality in this model, was particularly evident after 10 weeks of life, but disappeared by the end of the follow-up. Interestingly, when mice with a self-limited disease were re-injected with 10(8) F1 spleen cells i.v., a flare in the serological manifestations was observed. In these re-injected mice a predominance of anti-DNA, IgG1 antibodies bearing exclusively the donor allotype was also observed, as in the early weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The value of nuclear area as a prognostic factor in T1 papillary transitional cell carcinoma of the bladder.

In a series of 131 T1 papillary transitional cell carcinomas of the bladder, the nuclear areas of 100 nuclei (50 from the external papillary zone and 50 from the internal papillary zone) were measured. An attempt was made to correlate retrospectively the value of the mean nuclear area with histological grade and with survival. A higher value was obtained for the mean nuclear area of the internal papillary zone than for that of the external papillary zone. A better survival rate was found after 10 years' follow-up for those tumours whose mean nuclear area in the internal papillary zone was < or = 28 microns2, which suggests that it is in this zone that the nuclear area should be measured. A correlation was observed between the increase in the mean nuclear area value and higher histological grade.

Breast Neoplasms↗

Prognostic correlation of morphometric values with survival in invasive transitional cell carcinoma of the bladder.

A morphometric study was made of 95 invasive bladder tumours, differentiating 34 papillary and 61 solid carcinomas. In the invasive papillary tumours, the deeper the zone of the tumour measured, the higher the value of the mean nuclear area. A higher histological grade was also seen to correspond to a higher mean nuclear area value except for Grade IV tumours, whose nuclear area was no larger than that for Grade III tumours. This led us to separate Grade IV tumours from transitional cell carcinomas and classify them as undifferentiated. A better prognosis was found for those tumours whose mean nuclear area was < or = 30 microns2 in category T2. For T3 and T4A tumours no conclusive results were obtained in this respect.

Anthropometry↗

Kidney cortical necrosis induced by mitomycin-C: a morphologic experimental study.

Experimental studies on mitomycin-C nephrotoxicity are scanty and mention the occurrence of cortical hemorrhage, tubular necrosis, or hydronephrosis secondary to papillomatous hyperplasia of the uroepithelium. To our knowledge, only one experimental study has mentioned morphological lesions similar to the hemolytic uremic syndrome in the human. In the present study 40 female Wistar rats were studied following unilateral renal perfusion of the left kidney with 2 mg/kg of mitomycin-C. Renal lesions corresponded to cortical necrosis with the presence of large bizarre nuclei. The presence of these nuclear atypias supports a direct toxic effect (alkylation) of the mitomycin or its metabolites on cells.

Animals↗

[Prognosis factors in adenocarcinoma of the kidney. I. Staging, clinical and macroscopic factors of the tumor].

In 95 cases of renal adenocarcinoma (32 stage I, 18 II, 26 III, and 19 IV) submitted to radical nephrectomy and hilar lymphadenectomy with a follow-up of 5 years, we evaluated the prognostic value of the Robson classification (p less than 0.01), categories T (p less than 0.01), N (p less than 0.01), M (p less than 0.01) and V (p = NS), 3 clinical parameters (sex, age, duration of symptoms and signs) which proved to be of no prognostic value, and 6 macroscopic features of the tumor (solid or cystic nature of the tumor, presence of intrarenal tumor satellite modules, ureteric invasion, tumor size, site and intrarenal location of the tumor). Four of the foregoing proved to influence prognosis.

Adenocarcinoma↗

[Prognosis factors in adenocarcinoma of the kidney. II. Microscopic factors].

The prognostic value of several microscopic parameters were evaluated in 95 cases of renal adenocarcinoma (32 stage I, 18 II, 26 III and 19 IV) submitted to radical nephrectomy and hilar lymphadenectomy with a 5-year follow-up. No prognostic significance was observed for cell type, architectural pattern, borders, and degree of peritumoral lymphocyte infiltration. A worse prognosis was observed for the high (G 3 + 4) in comparison with the low (G 1 + 2) nuclear grade (p less than 0.01). However, analysis according to stage revealed this parameter only affected prognosis in those cases pertaining to intermediate stages II and III. The mean proliferation rate was 2.97 mitoses/10 fields (500 x). A worse prognosis was observed for a proliferation rate greater than 5 mitoses/10 fields (500 x) in comparison to those with a lower rate (p less than 0.01) but evolves parallel to stage.

Adenocarcinoma↗

[Prognosis factors in adenocarcinoma of the kidney. III. Nuclear area].

Nuclear morphometry was performed with the MOP-Videoplan morphometry device in 95 cases of renal adenocarcinoma submitted to radical nephrectomy and hilar lymphadenectomy with a 5-year follow-up. For each case, 100 nuclei were randomly selected and delineated (magnification: 1,000x). A statistically significant correlation (p less than 0.05) was observed for the nuclear area and the overall as well as stage-related survivorship. Using a nuclear size of 35 microns 2, the study population can be divided into two groups: those with a good and those with a poor prognosis regardless of stage. A statistically significant difference was observed for the overall as well as the stage-related survivorship for the group with a nuclear area less than 35 microns 2 (good prognosis) in comparison with the group with a nuclear area greater than 35 microns 2.

Adenocarcinoma↗

Xanthomatous endometritis.

A further case of xanthomatous endometritis, characterized by the presence of histiocytic cells in the endometrium, in the absence of carcinoma is described. This lesion seems to be a rare complication of hematometra with cervical occlusion. The foam cells would appear to be macrophages, components of a nonspecific inflammatory reaction, which have phagocytosed breakdown elements of retained endometrial hemorrhage.

Dilatation and Curettage↗

Staging of carcinoma of the colon and rectum.

A retrospective study was carried out upon 393 patients diagnosed from the 1 January 1970 through 1 December 1978 for carcinoma of the colon and rectum, 90 per cent of whom had a complete follow-up study during a five year period or until death. A classification system by stage, which has given us good results since there are no crossovers in the survival evolution of the different subgroups, is described. The system shows great uniformity since a linear equation with a slope of 15.76 per cent and a linear correlation coefficient (r) = -0.999 relates almost perfectly the decrease in survival time as the stages advance.

Carcinoma↗

Metastasis of malignant neoplasms to skeletal muscle.

Malignant neoplasms were found at 194 of 723 autopsies carried out at the Marqués de Valdecilla National Medical Center in the period 1980-1982, and in 50 of these there was secondary involvement of skeletal muscle. In 16 cases (8.2%) the primary tumour and/or its metastases had invaded skeletal muscle, but in 34 (17.5%) true macroscopic or microscopic metastases were present. It was this latter finding which prompted us to carry out a detailed analysis. Below are given the percentages of malignant neoplasms of each type in which the tumours had metastasized to skeletal muscle and, in brackets, the number of metastases found in skeletal muscle as a percentage of all metastatic tumours. Acute leukaemias 17.2% (14.7%), lymphomas 20.6% (17.6%), carcinomas 17.7% (64.6%): for the various sub-categories of carcinoma the figures were: epidermoid carcinoma 10% (5.8%), adenocarcinoma 29.6% (47%) and anaplastic carcinoma 5.8% (2.9%). The muscles most commonly involved were the diaphragm (67.6%) and the iliopsoas (29.4%). The patients ranged in age from 26 to 84 years, mean age 62.8 years. The male/female ratio was 2.8/1. In advanced cancer an appreciable percentage of metastases occur in skeletal muscle.

Adult↗