Apoptosis y expresión de Bcl-2 y Bax en el endometrio eutópico de pacientes con endometriosis / Apoptosis and Bcl-2 and Bax in normal endometrium of patients with endometriosis

El objetivo de este trabajo es investigar una posible predisposición de las células endometriales de pacientes con endometriosis (EDT), a ser resistentes a la muerte celular programada. Se evaluó apoptosis y expresión de las proteínas Bcl-2 y Bax en 30 cortes de tejido de endometrio eutópico, 14 de mujeres con EDT y 16 de controles (C). Para la determinación de apoptosis, se utilizó el kit Apoptag-Plus basado en la localización y tinción de los extremos 3'-OH de los fragmentos de ADN. Los resultados se expresan como nº de células apoptóticas (CA)/campo a 630x de aumento. Se detectaron CA sólo en el epitelio glandular. Se observó menor cantidad de CA en tejido endometrial proveniente de pacientes con EDT: 2,26 ñ 0,53 vs 9,37 ñ 1,69 en los C (p<0,001). Esta disminución se conservó a lo largo del ciclo menstrual. En la fase proliferativa tardía, los resultados fueron de: 7,08 ñ 0,92 vs 1,9 ñ 0,73 (p<0,05), para las muestras provenientes de mujeres C y pacientes con EDT respectivamente; mientras que en el endometrio secretorio los niveles de apoptosis detectados fueron de 11,6 ñ 1,74 en los C vs 2,7 ñ 0,82 en EDT (p<0,001). No se observaron diferencias significativas de apoptosis en endometrio de acuerdo al grado de la enfermedad. La evolución de los productos de protooncógenes, bcl-2 y bax se realizó utilizando metodologías de inmunohistoquímica. Se halló incrementada la expresión de la proteína antiapoptótica Bcl-2 en el endometrio proliferativo proveniente de pacientes con EDT comparado con el C. La expresión del antagonista de Bcl-2, Bax, aumentó durante la fase secretoria tanto en muestras provenientes de pacientes como de C, y se halló ausente durante la fase proliferativa. De los resultados se desprende que las células endometriales de pacientes con EDT poseen características apoptóticas alteradas que las harían más susceptibles a crecer en un sitio ectópico. Estas no se ven modificadas a lo largo del ciclo menstrual. La proteína Bcl-2 estaría implicada en la protección de la apoptosis de las células endometriales eutópicas de pacientes con EDT durante la fase proliferativa del ciclo menstrual. La proteína Bax estaría involucrada en la regulación de la muerte celular programada que se produce en el endometrio eutópico previo a la menstruación. La resistencia a la muerte celular programada que posee el endometrio eutópico de pacientes con EDT, estaría relacionada con la etiología y/o fisiopatología de la enfermedad

Citopunción ecoguiada de lesiones mamarias no palpables. Ventajes y limitaciones / Cytopuncture guided of nonpalpable breast lessions. Advantes and limitations

La nueva imagenología mamaria ha descubierto un grupo de lesiones no palpables que puede alcanzar hasta el treinta por ciento de los casos examinados

Primary hormonal treatment for early endometrial carcinoma.

Four cases of clinical Stage I endometrial carcinoma initially treated with hormonal therapy are included in this study. Three of them resulted in tumor regression and two of them permitted a subsequent three pregnancies. All patients are alive and without evidence of disease with a median follow-up of 35.7 months (range 17 to 72 months). We believe this is a promising approach through which we may be able to offer a conservative treatment maintaining high survival rates and preserving childbearing potential. Diagnostic and therapeutic data for fertility-desiring patients with endometrial carcinoma are analyzed in this study.

Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results.

OBJECTIVE: To determine if three courses consisting of 50 mg/m2 cis-platinum, 1 mg/m2 vincristine, and 25 mg/m2 bleomycin (day 1-3) at 10-day intervals can improve survival before Wertheim-Meigs + radiotherapy. MATERIAL: Two hundred five unselected stage Ib patients (having tumors > 2 cm in diameter) were divided into two groups at random: (1) The group control consisted of 103 patients (56 bulky, > 4 cm diameter) treated with Wertheim-Meigs (if the tumor was resectable with free surgical margins) + adjuvant radiotherapy to whole pelvis (extended field radiation was used only in patients with paraaortic lymph node metastases). When the tumor was unresectable, a surgical staging was performed and radiotherapy was the chosen treatment. (2) Neoadjuvant (102 patients, 61 bulky) had neoadjuvant chemotherapy and then the same treatment as the control patients. RESULTS: After 67 (31-102) months of follow-up, no difference was seen in tumors > 2 and < 4 cm in both groups (C = 77% vs N = 82%), but statistically significant differences were seen in survival and disease-free survival, in bulky tumors, and between patients with neoadjuvant chemotherapy + Wertheim-Meigs + radiotherapy (80%) and the control (61%). This was due to an increased operability that was substantially improved in bulky tumors in the neoadjuvant chemotherapy group (61/61, 100%) vs control (48/56, 85%; P < 0.01). After 7 years of follow-up, the outcome of the unresectable bulky control group of patients is significantly worse (14%) than that of the resectable group (69%; P < 0.001). With regard to recurrences, a significant decrease in pelvic failures in the neoadjuvant chemotherapy group was observed (P < 0.001). Survival was improved in bulky resectable cases (N = 81% vs C = 69%, P < 0.05). Pathological findings for the surgical specimens revealed differences between both groups because all the risk factors such as parametrial and lymph node metastases, tumor bulk, and vascular embolism had been decreased (P < 0.001). CONCLUSION: Neoadjuvant chemotherapy can improve survival because of increased operability with free survival margins and a decrease in pathologic risk factors in unselected, bulky (> 4 cm diameter) stage Ib patients.

Epithelial alterations adjacent to invasive squamous carcinoma of the vulva.

The slides of 64 vulvectomy specimens from vulvar squamous carcinoma were reviewed in order to study the histopathologic changes adjacent to the neoplasia. Normal epithelium was found in 7 cases (11%) and epithelial alterations adjacent to carcinoma in 59 (89%). The epithelial alterations found were: nonneoplastic epithelial disorder (NNDV) in 38 cases (59%) and vulvar intraepithelial neoplasia (VIN) in 19 (30%). The distribution of NNDV was: 20 cases of epithelial hyperplasia (EH) (31%), 6 of lichen sclerosus (9%) and 12 of the mixed type (19%). Sixteen cases of VIN 3 (25%) were undifferentiated, and three cases were differentiated VIN. Eighteen of 19 VIN cases were associated with NNDV, and 8 cases of undifferentiated VIN were associated with human papillomavirus infection. There was no apparent relationship between the associated lesions and tumor size, depth of invasion, lymph node metastases and clinical stage. Nevertheless, we found a significantly higher frequency of associated lesions in poorly differentiated tumors (P > .01). The most important finding was a high association between EH (50%) and VIN (30%) with carcinoma. VIN cases were almost always (95%) associated with EH.

Histologic predictive factors. Therapeutic impact in vulvar cancer.

In 59 cases of vulvar invasive squamous cell carcinoma treated with radical vulvectomy and inguino-femoral lymphadenectomy, seven histologic parameters were evaluated to establish their predictive value in the development of lymph node metastasis. The most significant was vascular involvement, observed in 86% of cases with lymph node metastases (P < .000004). Depth of stromal invasion and tumor thickness were highly significant, with P < .008 and < .007, respectively, with 0% lymph node metastases in tumors thinner than 1 mm and 62% and 60%, respectively, in those thicker than 5 mm. The growth pattern correlated with lymph node metastases but was not statistically significant. The histologic grade correlated with positive lymph nodes, with P < .04. The amount of keratin (P < .91) was not related. These histologic factors allow the identification of patients with a lower risk of developing lymph node metastases and in whom conservative surgery on the vulva and inguino-femoral lymph nodes is feasible.

Tratamiento multidisciplinario del cáncer de la mama localmente avanzado no inflamatorio: resultados preliminares / Multimodal treatment for locally advanced non inflamatory breast cancer: preliminary results

Desde 1985 hemos tratado 99 pacientes con cáncer de mama estadio III (operables e inoperables) con una misma estrategía, combinando QT primaria, radioterapia, cirugía y QT de consolidación. Hubo 75 estadios IIIB y 24 estadios IIIA. En 11 casos se pudo realizar cirugía conservadora. Tuvimos 6 respuestas patológicas completas. Cuarenta y ocho pacientes han cumplido 2 años de tratadas y se consideraron evaluables. La mediana de SV fue d3e 60-66 meses. El porcentaje de SV en este grupo es 45,8 por ciento. Se analiza la incidencia de los distintos factores pronóstico en la SV. No se observó recidiva local en los casos en que se conservó la mama. Tuvimos muy baja toxicidad y se concluye con la necesidad de buscar tratamientos sistémicos más agresivos que podrían incidir en un futuro incremento de SV

Is subradical surgical treatment for carcinoma of the cervix uteri stage IB logical?

Twenty-eight patients with squamous carcinoma of the cervix FIGO stage Ib were treated with three courses of neoadjuvant chemotherapy with a VBP modified scheme. Clinical responses showed that the percentage of complete and moderate responses exceeds 95% of the cases. Clinical response was also related to tumor bulk measurement by ultrasound scanning. Twenty-three of the patients were then subjected to the Wertheim-Meigs operation. Pathological findings of surgical specimens showed absence of residual lesion in 6 patients (26.1%) and carcinoma smaller than 0.5 cm in 5 patients (21.7%). Tumor response to neoadjuvant chemotherapy was excellent in NG3, MG3 tumors when lymphoplasmomonocytic infiltration was present. In accord with this result a new protocol was developed.

[Carcinoma and fibroadenoma of the breast]. / Carcinoma y fibroadenoma de mama.

Eight cases of breast carcinoma coexisting with fibroadenoma were retrieved from the files of the Division of Pathology from 1957 to 1987. In 3 patients (Group I) the lesion was within the fibroadenoma and in the remaining 5 patients, adjacent to it (Group II: synchronic carcinomas). All patients were females. During the same period, 987 fibroadenomas and 2004 carcinomas were diagnosed: 0.30% of the fibroadenomas developed carcinoma within the epithelial component and 0.15% of the carcinomas originated in the fibroadenoma's epithelium. The mean age was 39 years for in situ lesions and 45.5 years for infiltrating carcinoma with a general mean age of 43.3 years, 20 years older than the peak age of fibroadenoma. In Group I, there were 3 in situ lesions, 1 lobular and 3 ductal (Table 1). Two of the three patients had another coexisting gynecologic malignancy. In Group II all cases had infiltrating carcinomas, one lobular, 3 ductal and 1 mixed lobular and ductal (Table 1). The adjacent breast tissue showed associated pathology in all cases: multiple fibroadenomas, fibrocystic diseases, sclerosing adenosis, infiltrating ductal carcinoma and/or lobular hyperplasia. Different hypotheses from the literature were analysed concerning an association between carcinoma and fibroadenoma. A casual association is suggested by the low percentage of carcinomas developing in fibroadenomas as well as the low percentage of carcinomas originating from fibroadenomas.

Results of a phase II trial with neoadjuvant chemotherapy in carcinoma of the cervix uteri.

Results of a Phase II trial with neoadjuvant chemotherapy in carcinoma of the cervix uteri (VBP modified scheme) show that 85.7% of patients given this therapy were NED in Stage IIb versus 54% of a nonrandomized control group given conventional therapy. In Stage IIIb the averages are 66.6% vs. 31% in the control group. Analysis of the ecographic data has shown that if a critical prechemotherapy volume (120 cm3) is exceeded, the prognosis is unfavorable, especially in cases treated with radiotherapy as second-line treatment.

Melanoma of the vulva. The experience at Buenos Aires University.

Nine cases of vulvar melanoma were studied: the histologic variants, depth of invasion and prognostic significance of these factors and of node involvement were analyzed. The histologic types were in situ melanoma (one case), superficial spreading melanoma (two cases) and nodular melanoma (six cases). The mean age of the patients was 64.9 years. Eight patients were treated with radical surgery and one with chemotherapy only. We found a good prognosis for in situ melanoma with free margins; a tendency for superficial spreading melanoma to recur, though it has a good prognosis when it does not exceed Clark level II; and an ominous prognosis for nodular melanoma, probably because of its late diagnosis.

Relevance of microinvasion in carcinoma of the vulva.

Retrospective analysis of 22 cases of Stage I invasive carcinoma of the vulva showed 11 cases in which the depth of tumor invasion was 5 mm or less. All of these patients were treated with radical vulvectomy and lymphadenectomy. In 3 cases positive groin node metastases were discovered. A fourth patient with minimal stromal invasion (less than 5 mm) was prospectively managed with vulvectomy alone and subsequently developed groin node metastasis leading to death from disseminated tumor. Depth of the invasion alone, therefore, is not a reliable indicator of the likelihood of groin node involvement, and lymphadenectomy should continue to be considered for all patients with invasive squamous cell carcinoma of the vulva.