Sérgio Mancini Nicolau

Sentinel lymph node in endometrial cancer

The aim of this study was to evaluate the possibility of identifying the sentinel lymph node and involvement of neoplastic cells in patients with endometrial carcinoma limited to the uterus, and also its correlation with the conditions of other pelvic and para-aortic lymph nodes. Forty patients with endometrial carcinoma, clinical staging I and II, were submitted to complete surgical staging through laparotomy, as recommended by FIGO in 1988. The sentinel node was investigated using patent blue dye in the myometrial subserosa. The sentinel node was excised and submitted to frozen section examination of specimen, stained with hematoxylin and eosin (H&E). Afterward, selective bilateral para-aortic and pelvic lymphadenectomy, total hysterectomy with bilateral salpingo-oophorectomy were performed. The lymph nodes excised were examined by means of paraffin-embedded slices stained with H&E and of imunohistochemistry with antikeratin antibody AE1/AE3. The sentinel lymph node was identified in 77.5% of patients (31/40), and 16.1% (5/31) presented neoplastic involvement in the node. In 25 cases of negative sentinel node, 96% (24/25) had no neoplastic involvement, and 4% (1/25) had other lymph node affected (false negative). In nine cases with no sentinel node identified, 55.5% (5/9) had lymph node involvement. The results of this study allow us to conclude that it is possible to identify the sentinel node using the methods described, and the pathologic examination significantly represents the same conditions of other pelvic and para-aortic lymph nodes.

Histologic Studies of the Effects of Circulating Hot Saline on the Uterus Before Hysterectomy

STUDY OBJECTIVE To evaluate a new device for endometrial ablation. DESIGN (Canadian Task Force classification II-1). SETTING University-affiliated hospital. PATIENTS Thirty-two women scheduled for hysterectomy. INTERVENTIONS Endometrial ablation and hysterectomy. MEASUREMENTS AND MAIN RESULTS The new device for endometrial ablation was evaluated by studying depth of necrosis after staining for the oxidative enzyme NADH. Uniform endomyometrial necrosis was achieved at a depth of 2 to 4 mm with 90 degrees C saline circulated for 10 minutes. CONCLUSION The procedure was successful in all patients, and there were no adverse clinical sequelae. (J Am Assoc Gynecol Laparosc 6(3):269-273, 1999)

Study on the prevalence of human papillomavirus in the anal canal of women with cervical intraepithelial neoplasia grade III

OBJECTIVE The objective was to evaluate the prevalence of human papillomavirus (HPV) in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade III. STUDY DESIGN Two groups were compared. In group I (study group), 40 women who had undergone cervical biopsy with a histopathological result indicating CIN III were evaluated. Group II (control) consisted of 40 women with normal results from colposcopic examination and colpocytological tests. The women in group I who presented high-grade neoplasia in colpocytological tests underwent collection of material from the uterine cervix and anal canal for investigating HPV DNA using the Hybrid Capture II technique. Colposcopy and cervical biopsy were then performed. If CIN III was confirmed, HPV DNA was investigated in the material collected. In group II, colpocytological tests and colposcopy were performed and, if normal, the procedure was similar to that followed for group I, except that no biopsy was performed. RESULTS In group I, 39 women (97.5%) were positive for HPV in the uterine cervix and 14 women (35%) in the anal canal. In group II, only four women (10%) had a positive HPV test, for both the uterine cervix and the anal canal. CONCLUSIONS The prevalence of HPV in the anal canal of the women with CIN III was greater than in the women without CIN III.

Progesterone receptor (PROGINS) polymorphism and the risk of ovarian cancer.

The present case-control study evaluates the role of the progesterone receptor (PR) polymorphism known as PROGINS as a risk factor for ovarian cancer development and investigates the association between these genetic variants and clinical/pathologic variables of ovarian cancer. PROGINS polymorphism was examined, by polymerase chain reaction, in a total of 80 patients with ovarian cancer and 282 control subjects. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 71.3, 15.0 and 13.8% in ovarian cancer patients and 78.37, 21.63 and 0% in controls, respectively. The chi(2)-test showed a higher incidence of the T2/T2 genotype (P=0.001) in the ovarian cancer group. In addition, women carrying a mutated allele (T2) showed approximately 2.2 times higher risk of ovarian cancer development as compared to women who have a variant allele (odds ratio (OR)=2.2; 95% CI=1.80-3.54). Regarding the clinical and pathologic findings observed within the cancer group, there was a significant correlation between PROGINS polymorphism and patients with a familial history (chi(2)=6.776; P=0.009; Fischer exact test, P=0.01). In this regard, patients with familial antecedents have a 4.7 times higher likelihood to have at least one risk allele (T2) as compared with patients without familial antecedents (OR=4.69; 95% CI=1.38-15.87). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of ovarian cancer.

Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The χ2 test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

Evaluation of Hydro ThermAblator for endometrial destruction in patients with menorrhagia.

OBJECTIVE To describe endometrial destruction with the Hydro ThermAblator. DESIGN (Canadian Task Force classification II-1). SETTING University-affiliated hospital. PATIENTS Twenty-six women with uncontrolled menorrhagia. INTERVENTION Endometrial ablation with saline heated to 90 degrees C and circulated in the uterine cavity for 10 minutes under hysteroscopic control. MEASUREMENTS AND MAIN RESULTS All patients tolerated the procedure well, all but one was satisfied with the results, and there were no significant side effects or complications. Seventy-seven percent of women were either amenorrheic or hypomenorrheic after 6 months, and 88% were amenorrheic or hypomenorrheic after 1 year, including one patient who was treated a second time; 87.5% were amenorrheic or hypomenorrheic at 18 months. One woman had persistent menorrhagia and was treated by hysterectomy. CONCLUSION In this study, endometrial ablation was performed successfully with the Hydro ThermAblator in 25 of 26 women. (J Am Assoc Gynecol Laparosc 6(3):275-278, 1999)

Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT): A review of 47 cases

OBJECTIVE Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of 47 patients with SCCOHT. METHODS We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes. RESULTS Median age at diagnosis was 30 years (range 5-46). All patients underwent surgery with unilateral salpingo-oophorectomy (USO) performed in 26 patients (55%), and hysterectomy with bilateral salpingooophorectomy (BSO) in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-up was 13.2 months (range, 0.1 to 210.7) with a median overall survival of 14.9 months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis. CONCLUSION Our findings suggest that aggressive therapy including multi-agent chemotherapy and possibly radiotherapy may extend survival. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations.

Can mobile units improve the strategies for cervical cancer prevention

Cervical cancer is a serious public health problem in women in developing countries because of absence or ineffectiveness of screening programs. Several biases to access medical care and inequity of public health system in a continental country like Brazil limit the implementation of adequate programs to appropriately prevent the cervical cancer. Therefore, the aim of this study was to evaluate the results of applying the mobile unit (MU) for cervical cancer screening. From May 2003 to May 2004, a cervical cancer screening was offered to women aged 20–69 years, residing in 19 municipal districts of the Barretos county region, in São Paulo. Out of the 9,560 examination available, 2,964 (31%) women underwent screening. The medium distance traveled by the MU was 45 km. The medium time spent by women in the MU for completion of the questionnaire and doing the exam was 20 minutes. It was observed that 17.0% of women screened had never had the test or had not had it repeated within the last 3 years. The negative response was more common among women aged 20 to 29 years and 60 to 69 years and among women with less schooling and lower socio‐economic income (P < 0.05). MU can significantly overcome the chronic deficiency of public health system accessibility offering opportunity to these women to participate in screening programs. Diagn. Cytopathol. 2010;38:727–730.

Heparanase-2 expression in normal ovarian epithelium and in benign and malignant ovarian tumors.

Introduction: Studies have highlighted the changes that take place in the environment between the cell and the extracellular matrix during the process of neoplastic expansion. Several papers have associated the expression of heparanase 1 with various malignant tumors. Heparanase 2 is probably related to loss of cell adhesion. Objective: The aim of this study was to evaluate the expression of heparanase 2 in epithelial neoplasia of the ovaries and in samples of normal ovarian tissue. Methods: Seventy-five ovary specimens were analyzed and divided into 3 groups: 23 malignant and 35 benign epithelial ovarian neoplasia and 17 without ovarian disease. We used 2 methodological techniques for evaluating the immunoexpression of heparanase 2. The first followed the qualitative criterion of positive or negative in relation to enzymatic expression, and the second involved computerized quantification of this expression, performed on the same slides. Results: In the quantitative analysis, we found positivity indices for heparanase 2 expression of 72.2% and 87.3% in the samples of benign and malignant neoplasias, respectively. In these, the intensity of expression and the expression index were 147.2 and 121.2, respectively, for the benign neoplasia and 134.1 and 118.0 for the malignant neoplasia. Qualitatively, its expression was strong or moderate in 44.2% of the benign and 78.2% of the malignant tumors; its expression in all of the nonneoplastic samples was negative, with the exception of one that was weakly positive. Conclusions: Heparanase 2 is involved in neoplastic proliferation, but it was not exclusively associated with the malignant process. Furthermore, there was no difference in its expression between benign and malignant ovarian epithelial neoplasia.

Atypical glandular cells of undetermined significance: Cytologic predictive value for glandular involvement in high grade squamous intraepithelial lesions

OBJECTIVE To verify the cytologic predictive value of a diagnosis of atypical glandular cells of undetermined significance (AGUS) in high grade squamous intraepithelial lesions (HSIL) cases. STUDY DESIGN In a retrospective study, 98 cases of HSIL were reviewed. All patients were referred for colposcopy and directed biopsy to confirm the cytologic diagnoses. Loop excision of the transformation zone was performed to treat clinical lesions. Sensitivity, specificity, positive and negative predictive value were evaluated. Kappa statistics and logistic regression analysis were used to evaluate the findings statistically. RESULTS By logistic regression analysis, we found that the chance of finding squamous intraepithelial lesions involving glands in AGUS smears was 5.32 times higher than in those with no AGUS. It was 5.74 times higher in cervical intraepithelial neoplasia (CIN) 3 lesions than in CIN 2. CONCLUSION The cytologic predictive value for HSIL involving glands is statistically significant when specific and objective criteria are used for the AGUS diagnosis.