A six-year experience with anal cytology in women with HPV in the lower genital tract: utility, limitations, and clinical correlation.

This study assessed the utility and limitations of anal cytology as a screening method for women infected with human papilloma virus (HPV) in the lower genital tract. Furthermore, this study aimed to establish risk factors for pathological anal cytology/biopsy findings, the prevalence of anatomopathological lesions associated with positive anal brushings, and the frequency of concomitant lesions of the lower genital tract. A cross-sectional, retrospective, descriptive study in 207 women with HPV-associated lesions of the lower genital tract and 25 women with immunosuppression was carried out. Anal cytology, high resolution anoscopy, and biopsy of suspicious lesions were performed. In total, 232 anal brushings were performed: 184 (79.3%) were negative, 24 (10.34%) showed atypical squamous cells of undeterminated significance, 18 (7.7%) showed low-grade squamous intraepithelial lesions, and 6 (2.6%) showed high-grade squamous intraepithelial lesion. Cytohistological correlation was obtained for 70 cases. The sensitivity of anal cytology in detecting intraepithelial lesions was 70%, whereas the specificity was 93%. The sensitivity of the method for detecting high-grade lesions (84%) was higher, than that for detecting low-grade lesions (66%). The most frequently associated pathology was vulvar lesion. It is important to perform anal brushings in women who have had lower genital tract biopsies for HPV-associated lesions due to the high prevalence of anal lesions in such patients. Anal cytology is useful for detecting high-grade lesions but the sensitivity for detecting low-grade lesions is low. It is of the utmost importance to perform high-resolution anoscopy and biopsy in women with suspicious lesions in order to confirm the pathology.

AgNOR, p16 and human papillomavirus in low-grade squamous intra-epithelial lesions of the uterine cervix. Preliminary report.

It has been shown that infection with high-risk human papillomaviruses (HR-HPV) is related to the development of cervical cancer. The persistence of the virus in intra-epithelial lesions of cervix uteri (SILs) is the basis for the application of HPV testing for screening and management of patients. Most infections by HR-HPVs resolve spontaneously, however, and do not progress to dysplasia or cancer. p16INK4a is a useful biomarker of cervical intra-epithelial neoplasia and could be a marker for the progression of low-grade squamous intra-epithelial lesions (LSILs) to high-grade squamous intra-epithelial lesions (HSILs), because it correlates independently with increasing SIL grade. We conducted a preliminary histological study of 28 patients diagnosed with LSIL, HSIL or nondysplastic epithelium (NDE) from whom 28 biopsies of uterine cervix and 28 endocervical brushed biopsies were taken. Argyrophilic nucleolar organizer region (AgNOR) and p16INK4a assays were performed on the biopsies, and endocervical brushings were used for HPV typing. The high risk HPV group showed that the number of patients with AgNOR areas greater than 3.3 µm(2) and with expression of p16INK4a were statistically greater than the number of lower risk patients. None of the biopsies of LR-HPV carriers expressed p16 and AgNOR areas> 3.3 µm(2) simultaneously. Four LSILs and the NDE of this group expressed neither of the two markers. If the correlation between AgNOR areas and p16INK4a is good, we may be able to develop a low cost simple technology for studying patients infected with HR-HPV and diagnosed with LSIL of uncertain behavior.

Metastases to the uterine cervix from a gastric carcinoma presenting with obstructive renal failure: a case report.

Metastases to the uterine cervix are infrequent(1-3). Except for cases of endometrial primary carcinoma, the most common origin of neoplastic dissemination to the uterine cervix is the ovary, followed by the breast(1,2). Primary gastrointestinal tumors are rare, and in most of these cases cervical metastases are associated with adnexal bilateral masses (Krukenberg's tumors)(1).

Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge.

OBJECTIVE: The aim of this study was to analyze diagnostic criteria, response to chemotherapy, rate and site of relapse, and overall survival (OS) in neuroendocrine cervical carcinoma. METHODS: Twenty patients were included. Stage was Ia(2) in 1 case, Ib(1) in 4, Ib(2) in 4, II in 5, IIIb in 2, IVa in 2, and IVb in 2. Patients with stage Ib(2) or greater received neoadjuvant chemotherapy (NCH). Eighteen patients were operated on. Immunohistochemistry was performed on the surgical specimens. Statistical analysis included the Kaplan-Meier method and the chi(2) and log-rank tests. RESULTS: The response to NCH was <50% in 2/13 cases (15.3%), >50% in 9/13 (69.4%), and complete in 2/13 (15.3%). Cytokeratin was positive in 17/18 cases, neuron-specific enolase in 15/18, chromogranin in 9/18, and synaptophysin in 8/18. Tumor was pure in 12 cases. Two cases had simultaneous ovarian carcinoma. Positive nodes were observed in 9/20 pts (45%). Tumors <4 cm had no recurrences. Pure tumors >4 cm had distant relapses (6/11). Mixed tumors >4 cm had 2/6 pelvic and 3/6 lung metastases. OS was 39%. When the initial tumor volume was <4 cm OS was 76%, and it was 18% for tumors >4 cm (P < 0.05). OS was 58% when the residual tumor after NCH was <2 cm and 21% when it was >2 cm (P < 0.05). When the tumor was pure OS was 54% and 19% when it was mixed (P < 0.05). OS was 72% among pts with negative nodes and 11% for those with positive nodes (P < 0.01). CONCLUSIONS: (1) Stage IV was frequent (20%); (2) Response to NCH was high; (3) The pattern of relapse differs for mixed tumors; (4) For tumors <4 cm outcome is similar to that of squamous carcinoma.

Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis.

OBJECTIVE: To evaluate and compare spontaneous apoptosis and Bcl-2 and Bax expression in eutopic endometrium from women with and without endometriosis. DESIGN: Apoptosis and Bcl-2 and Bax expression were examined in eutopic endometrium from women with and without endometriosis. SETTING: Instituto de Biología y Medicina Experimental-CONICET, Department of Gynecology and Department of Gynecological Pathology, Clínicas University Hospital, Buenos Aires, Argentina. PATIENT(S): Women with untreated endometriosis (n = 14) and controls (n = 16). INTERVENTION(S): Collection of endometrial samples during diagnostic or therapeutic laparoscopy. MAIN OUTCOME MEASURE(S): Apoptotic cells were detected with use of the dUTP nick-end labeling (TUNEL) assay; Bcl-2 and Bax expressions were assessed with use of immunohistochemical techniques. RESULT(S): Spontaneous apoptosis was significantly lower in eutopic endometrium from patients with endometriosis, compared with healthy controls (2.26 +/- 0.53 and 9.37 +/- 1.69 apoptotic cells/field, respectively) and was independent of cycle phase. An increased expression of Bcl-2 protein was found in proliferative eutopic endometrium from patients with endometriosis. Bax expression was absent in proliferative endometrium, whereas there was an increase in its expression in secretory endometrium from both patients and controls. CONCLUSION(S): Women with endometriosis show decreased number of apoptotic cells in eutopic endometrium. The abnormal survival of endometrial cells may result in their continuing growth into ectopic locations.

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

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.

Accidental ovarian autograft after a laparoscopic surgery: case report.

OBJECTIVE: To report an autograft of ovarian tissue in the incision of the surgical trocar during laparoscopic surgery and to assess the potentiality of grafting of ovarian parenchyma in nonpelvic tissue in humans. DESIGN: A case report. SETTING: Instituto de Fertilidad y Ginecología de Buenos Aires (IFER), Buenos Aires, Argentina. PATIENT(S): Infertile patient undergoing surgery due to an endometriotic cyst of the left ovary. INTERVENTION(S): Laparoscopic cystectomy. Accidental retention of a portion of the capsule and adjacent ovarian tissue of the endometrioma in SC cellular tissue. Months after surgery, a SC tumor was formed under the surgical incision. It was subsequently excised. MAIN OUTCOME MEASURE(S): Observation of tumor growth during menstrual cycles and ovulation induction; anatomopathologic study of the tissue after its extirpation. RESULT(S): The tumor grew spontaneously in the periovulatory period and during treatments of ovulation induction. The anatomopathologic report of the tumor, removed 15 months after the first surgery, revealed functioning ovarian tissue with vessels of neoformation. CONCLUSION(S): This is the first description of autografted ovarian tissue in humans. We describe that the ovary can maintain its ovulatory function even in the absence of its pedicel. Also, we suggest that extirpation of surgical material through the incision of the trocar is not recommended, as the possibility of "sowing" or of autografts may occur.

[Reproducibility of nuclear grade in breast neoplasm. A multicenter experience]. / Reproducibilidad del grado nuclear en el cáncer de mama. Una experiencia multicéntrica.

Nuclear grade is considered a valuable prognostic factor in mammary carcinomas. Since the histological diagnosis of most of these tumors is made by "non expert" pathologists, it was considered interesting to find out the reproducibility of general pathologists to define the nuclear grade. In order to do this, a series of 15 mammary carcinomas, 10 of them randomly selected and 5 because they were considered difficult to classify for nuclear grade, were examined separately by 10 general pathologists. In a first round of observation, each one of them graded the cases according to their own criteria as used routinely, and for a second round they followed a written guide. An analysis of variance was applied to the data and no significant differences were found between observers, neither in the randomly selected cases nor in the total series. The written guide, surprisingly, instead of lowering the differences, increased them. Analysis of the individual performance of observers showed two of them having a great variation between both rounds of observation, and this was considered to influence the results of the whole group. Interobserver performance to discriminate high grade tumors (G3) from the rest, showed a good correlation in all the participants. These results allow us to conclude that in this series, examined by general pathologists, an acceptable reproducibility was observed, specially when high risk tumors were being identified.

Syringoma of the vulva. A case report.

Syringoma of the vulva, especially as the multiple form, is a rare disorder. A review of the diagnoses in 4,500 patients from the Vulvar Clinic, Hospital de Clínicas José de San Martín, First Chair of Gynecology, Buenos Aires University, revealed only three cases, two of which were asymptomatic. The third patient, with multiple lesions and severe discomfort, is presented. With cryotherapy the lesions healed, and the patient was asymptomatic even during warm weather.

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

Results of a prospective randomized trial with neoadjuvant chemotherapy in stage IB, bulky, squamous carcinoma of the cervix.

A prospective randomized trial was carried out in patients with squamous carcinoma of the cervix uteri, stage Ib bulky. The protocol considers two arms: the control group (75 patients) and the neoadjuvant one (76 patients). All the patients were classified according to the FIGO staging system and in order to determine the tumor size objectively, an ultrasound scanning was done. After this a Wertheim-Meigs operation followed by adjuvant whole-pelvis irradiation was performed. In the neoadjuvant group the same procedures were carried out but three courses of chemotherapy with the "quick" VBP scheme were given before the treatment. The new therapeutic strategy proved to be very useful in bulky tumors in which the clinical examination showed a cervix increased in size and the ultrasound scanning a volume larger than 60 c.c. (> 4 x 4 x 4 cm). In those cases statistically significant differences were found between both groups when free disease interval and survival were considered. These were due to the fact that operability has been improved and the parametrial extension has been decreased as well as other risk factors such as vascular embolism, lymph node involvement, tumor-cervix quotient, and tumor volume. The use of this new strategy is not justified in small tumors (< 3-4 cm in diameter) because in those cases, survival is not improved with neoadjuvant therapy.

Lymph node metastases in carcinoma of the cervix uteri: response to neoadjuvant chemotherapy and its impact on survival.

One hundred and sixty-nine patients with squamous cancer of the cervix uteri treated with three courses of neoadjuvant chemotherapy with the modified VBP scheme are presented. All were subjected to a Wertheim-Meigs operation with paraaortic lymph-adenectomy. The incidence of lymph node metastases is analyzed according to clinical stage, tumor volume, residual tumor in the surgical specimen, and clinical response to neoadjuvant chemotherapy. A significant decrease in the incidence of lymph node involvement was observed in good responders. Survival rates, after 2 years of follow-up, improved in those cases with small residual tumor, negative parametria, and negative nodes.