Taxane-based chemotherapy enhances response to neoadjuvant treatment for stage II and III breast cancer.

Reducing primary tumor volume is the main role of neoadjuvant chemotherapy for breast cancer. We evaluated the benefit of adding docetaxel to anthracyclin as neoadjuvant therapy. This study is a retrospective cohort analysis comparing the efficacy of neoadjuvant chemotherapy in patients subjected to docetaxel and epirubicin or 5-fluoruracil, epirubicin and cyclophosphamide combinations (DE and FEC group, respectively). The mean number of chemotherapy delivered was similar in both groups (P = 0.8). A total of 316 patients were treated (151 in FEC group and 165 in DE group). Primary endpoint was the clinical and pathological response to therapy. Breast conserving surgery rate was compared. In T1/2 staged patients, the complete clinical response rate was 7.5% in FEC group and 32% in DE group (P = 0.002), and the breast conserving surgery rate was 72 and 73% in FEC and DE groups, respectively (P = 0.9). In the subset of patients staged as T3 and T4a-c, objective response was higher in DE group (P < 0.0001 and P = 0.008, respectively). Breast conserving surgery rate was 38 and 63% in FEC and DE groups, respectively, in T3 staged patients and, 20.5 and 37% in T4a-c staged patients (P = 0.003 and 0.08). Despite the similar number of chemotherapy cycles delivered in both groups, the presence of microscopic axillary lymph node involvement after chemotherapy was less frequent in DE group. Neoadjuvant chemotherapy with DE combination is more effective in terms of clinical and pathological response propitiating higher breast conserving surgery rate than FEC combination in stage II and III breast cancer.

Primary adenocarcinoma of the fallopian tube as an incidental finding during surgery in a postmenopausal patient with unspecific pelvic pain.

Primary fallopian tube carcinoma (PFTC) is a rare gynecologic neoplasm and is usually diagnosed late and presents classically with a characteristic group of symptoms. We describe a case of a 76-year-old woman who underwent TVS requested by the family physician due to unspecific pelvic pain. An adnexal mass was found with morphology associated with high levels of CA125 suggestive of a malignant tumor. During laparotomy, a mass located in the left tube was found. Histopathology confirmed PFTC. Total hysterectomy, salpingo-oophorectomy and adjuvant chemotherapy with carboplatin/paclitaxel were performed. The patient has not yet presented any signs of recurrence.

Breast conserving surgery after neoadjuvant therapy for large primary breast cancer.

AIM: The aim of this study was to evaluate the safety of breast conserving surgery in patients with breast tumours satisfactorily downstaged after neoadjuvant therapy. METHODS: A retrospective cohort study was undertaken to analyze the loco-regional recurrence (LRR) after breast conserving surgery. We enrolled 88 patients with breast cancer subjected to neoadjuvant therapy (NAT group) who achieved an objective response due to neoadjuvant treatment and compared them with 191 patients with early breast cancer (EBC group) who were submitted to primary conserving surgery. Lumpectomy or quadrantectomy with axillary lymph node dissection was performed in all patients who received adjuvant radiotherapy. Systemic adjuvant therapy was offered to all patients. The mean periods of observation were 61.3 months in the NAT group and 67.5 months in the EBC group. RESULTS: The mean age was 53 years in the NAT group and 56 years in the EBC group (p=0.04). There was no histological type and histological grade difference between groups. In the NAT group, the mean diameter of residual tumour was lower and the mean volume of breast tissue resection was higher than in the EBC group (p=0.01 and p=0.002, respectively). The ipsilateral recurrence rate was 7.9% in the NAT group and 7.8% in the EBC group (p=0.9). The most important predictive factor of recurrence in the NAT group was the age of patient. CONCLUSION: Breast conserving therapy is a safe procedure in satisfactorily downstaged breast cancer after neoadjuvant therapy.

Microinvasive carcinoma of the cervix. Analysis of prognostic factors.

INTRODUCTION: Superficially invasive neoplasias of the uterine cervix are a matter of controversy in terms of their definition, prognostic factors and selection of treatment to minimize the risk of recurrences. We reviewed our treatment to determine whether any factors affect this risk. PATIENTS AND METHODS: The present study was conducted on 59 patients seen at our service, 22 of them with early stromal invasion (IA1) and 37 with microinvasive carcinoma (IA2) according to FIGO criteria (1995). Ten patients were submitted to conization as definitive treatment, although for three of them treatment was complemented with Wertheim-Meigs surgery due to recurrence in the remaining cervix. The other 49 patients were submitted to total abdominal hysterectomy. RESULTS: Forty-four patients underwent diagnostic or therapeutic conization, and 14 of them presented involvement of the endocervical margin. Seven patients presented recurrence with involvement of the endocervical margin in five. The age of recurrence ranged from 40 to 70 years, with a mean of 52.3 years, as opposed to a general mean of 42.3 (p<0.05). Angiolymphatic invasion was positively correlated to recurrence and death (p<0.01) as well as depth of invasion. CONCLUSIONS: We conclude that the presence of a cone with an involved endocervical margin represents a high risk of recurrence and that this condition occurs in older patients who are prone to present more extensive lesions. Thus, age should be regarded as an important risk factor. Angiolymphatic invasion and depth of invasion have a poor prognosis in terms of recurrence and death.

Chemotherapy in the treatment of locally advanced cervical cancer and pregnancy.

BACKGROUND: Carcinoma of the cervix is the most common malignant tumor associated with pregnancy. The initial stages and premalignant lesions apparently present the same prognosis in pregnant and nonpregnant women; however, there are limited data regarding outcome for locally advanced cervical cancer in pregnancy. CASE: A 26-year-old woman, gravida 4, para 3, at 14 weeks and 4 days' gestation, was diagnosed with a FIGO stage IIB squamous cell carcinoma of the cervix, treated by primary chemotherapy with cisplatin and bleomycin, until pregnancy resolution at 38 weeks. The newborn infant is currently 3 years old and presents no evidence of abnormalities in neuropsychomotor development. CONCLUSION: The present case demonstrates that chemotherapy was harmless for the child up to the present time. However, a longer follow-up is needed to determine the safe outcome of this child.

Colposcopic scoring system for biopsy decisions in different patient groups.

Colposcopic scoring system have been used for distinguishing low-grade from high-grade cervical lesions. However, none of the previous studies have reported colposcopic scoring systems for biopsy decisions in different patient groups. The purpose of our study was to evaluate the safety of biopsy decisions using the colposcopic score elaborated by Stellato and Paavonen (IL) in 21 nonpregnant HIV infected patients (NP+) and 36 uninfected patients (NP-), 12 HIV infected pregnant patients (P+) and 20 uninfected pregnant patients (P-) in the diagnosis of cervical intraepithelial neoplasias (CIN) and HPV infection. The receiving operator curve was used for the establishment of a cut-off point in the scoring system graduation. The chi-square test was used for the statistical analysis. We obtained a safety cut-off value in the colposcopic scoring system for each patient group: 4.5 for NP+; 4.0 for NP- and 3.5 for P+ and P- patients. The sensitivity and specificity of the colposcopic score for the detection of high-grade lesions for each group were respectively: 87.5 and 92.3% for NP+ patients; 90.9 and 92% for NP- patients; 100 and 87.5% for P+ patients and 100 and 91.7% for P- patients. Our results suggest that the colposcopic scoring system is a practical tool for a colposcopy-guided punch biopsy decision and detection of high-grade cervical lesions in different patient groups. Further studies are needed to prove its clinical utility.

NK cell activity in the presence of IL-12 is a prognostic assay to neoadjuvant chemotherapy in cervical cancer.

OBJECTIVE: Little is known about the impact of neoadjuvant chemotherapy on cell-mediated immunity in patients with advanced cervical cancers. PATIENTS AND METHODS: We have studied 24 patients with advanced cervical cancer submitted to neoadjuvant chemotherapy (CT) using cis-platinum (100 mg/m(2)/cycle) and bleomycin (30 mg/cycle). The cell-mediated immunity parameters available before and after CT were NK cells, CD4(+)/CD28 and CD8(+)/CD28 T-lymphocyte numbers, PBMC cytotoxicity, and modification of this parameter with "in vitro" addition of IL-12. RESULTS: The number of NK cells was higher before CT (P < 0.008) in 13 patients who presented a good clinical response to treatment, compared to 11 patients with a poor clinical response. In addition, PBMC cytotoxicity (P < 0.001), CD4(+) and CD8(+) T-lymphocyte values (P < 0.0047), and CD8(+)/CD28(+) cells were also higher in the group with a good response compared with the group with a poor response. Addition of IL-12 to the medium increased the lytic capacity of PBMC after CT only in the group with a good clinical response (P < 0.05). CONCLUSIONS: NK cell numbers, CD8(+) T-cell levels, and CD8(+)/CD28(+) cell levels can be used as prognostic factors before CT. Our results suggest that patients with a poor response have lower lytic activity per NK cell and are refractory to IL-12 stimulation, probably as a result of the reduced expression of IL-12 receptors or of an intracellular defect in the mechanism of transduction. These observations also provide support for human clinical trials of IL-12 and neoadjuvant CT in patients with cervical cancer.

Hemangiosarcoma of the breast followed by term pregnancy.

AIMS AND BACKGROUND: Primary angiosarcoma of the breast is an unusual neoplasm which is generally associated with a dismal prognosis. Given the poor prognosis and the predominance in the third and fourth decades of life when fertility tends to decrease, reports of term pregnancies after treatment of this disease are rare. METHODS AND STUDY DESIGN: We report a case of angiosarcoma of the breast in a 17-year-old patient with a recurrent breast nodule treated by local surgery only. After three years of follow-up without evidence of disease recurrence she became pregnant. RESULTS: A girl weighing 2,430 g was delivered at 38 weeks and two days. The patient has been free of disease for five years now. CONCLUSIONS: Our experience of the present case shows the lack of full information about this tumor. Pregnancy does not seem to interfere negatively with the course of the disease.

Successful preservation of fertility subsequent to a complete pathologic response of a squamous cell carcinoma of the uterine cervix treated with primary systemic chemotherapy.

This is the first report about a successful pregnancy following treatment for advanced cervical cancer.

Reduced immunologic cell performance as a prognostic parameter for advanced cervical cancer.

The proliferative response of lymphocytes to mitogens is known to be decreased in cancer patients; this phenomenon is thought to play an important role in disease progression, but it has not been studied as a prognostic factor in cervical cancer patients receiving treatment. Fourteen patients with advanced cervical cancer submitted to chemotherapy with cis-platinum (100 mg/m2/cycle) and bleomycin (30 mg/cycle) over three cycles every 4 weeks were evaluated. Mean follow-up time was 30 months. The following laboratory tests carried out on peripheral blood lymphocytes collected before and at the end of chemotherapy were used as prognostic factors: proliferative response of lymphocytes to phytohemagglutinin (PHA) and stimulated with interleukin 12 (IL-12), capacity of gamma interferon production (IFN-gamma), and variations in memory T cell (CD45-RO) and naive T cell (CD45-RA) subsets. A clear correlation was obtained between response to treatment, survival rates, and PHA-induced proliferative response. A significant difference was observed in the number of CD45-RO lymphocyte at the pre-chemotherapy period and IFN-gamma production at the post-chemotherapy period in the group of good responders to treatment. The use of IL-12 produced a leveling in both groups for lymphocyte proliferation, i.e., a recovery from the deficiency presented by the lymphocyte of the poor responders group. The parameters of immunologic assays, especially proliferative response, appears to be correlated with prognosis and survival rates and therefore are good discriminating factors for the selection of groups of patients that will benefit from this type of treatment. IL-12 seems to play an important role in the regulation of the antitumor immune response and should be considered for therapeutic use.

Vaginal hysterectomy for correcting genital prolapse. Long-term evaluation.

OBJECTIVE: To determine whether a transvaginal hysterectomy with anterior and posterior repair is effective in the long term in treating uterovaginal prolapse and stress urinary incontinence (SUI). STUDY DESIGN: Seventy-four patients subjected to vaginal hysterectomy for the treatment of severe genital prolapse, on average five years before the study, were contacted by letter for evaluation. Four of these patients had died, and 47 (67.1%) responded to the letter. The mean age of the patients at the time of reevaluation was 66.1 +/- 10.6 years, and mean parity was 6.6 deliveries. RESULTS: All patients but two presented some degree of genital prolapse at the time of reevaluation, with three cases of total vaginal vault prolapse. White patients (87.2%) predominated over African (black) patients (12.8%). SUI associated with prolapse persisted in 14 of the 20 patients, and 6 others had this complaint after surgical correction (22.2% of previously continent patients). CONCLUSION: The rate of unsuccessful surgical correction of severe genital prolapse was very high (95.7%), and cure of SUI was low (30%), with SUI actually arising after surgical correction in 25% of continent patients. In addition to parity, there seems to be a racial factor linked to the onset and maintenance of this pathology, with a higher prevalence among white patients.

A morphometric study of maternal smoking on apoptosis in the syncytiotrophoblast.

OBJECTIVES: To study syncytiotrophoblast apoptosis in the placenta of smoking and non-smoking pregnant women. METHODS: Twelve neonates, pregnancies and placentas were available for study. Eight mothers smoked during pregnancy and the remaining four were non-smokers used as control subjects. The main outcome measure was the apoptotic syncytiotrophoblast index for each group. Apoptosis was detected by immunohistochemistry using the TUNEL method and quantitatively measured using a Merz grid. The apoptotic syncytiotrophoblast index was calculated as the ratio of mean apoptotic labeling to percent terminal villus area using high-power field microscopy. RESULTS: Significant differences in apoptotic syncytiotrophoblast index were observed between the control group (15.06+/-3.72) and the smoker group (1.66+/-1.74) (P < 0.0001, Mann-Whitney test), but no differences were detected in clinical or morphometric data between groups. CONCLUSIONS: The human placental syncytiotrophoblast undergoes apoptosis and this process is associated with inhibition of apoptosis by the smoking habit. The same way as the presence of trophoblast apoptosis is associated with modifications of the maternal-fetal exchange, the inhibitory effect of the smoking habit on syncytiotrophoblast could be responsible for the poor prognosis of pregnancy in the presence of maternal smoking.

Differential diagnosis of axillary masses.

Axillary masses are uncommon alterations when detected as an isolated finding. We evaluated 31 patients with isolated axillary masses. Patients with alterations of the breasts or the upper limbs or with Ipsilateral chest lesions were excluded from the study. Nine patients had occult breast cancer, 5 of them in the contralateral breast. Seven had metastatic lymph nodes of non-ductal origin, and 1 had carcinoma of apocrine cells with metastasis to the axilla. Four patients had benign lymphadenopathy which disappeared spontaneously, and 4 others had ruptured infundibular follicular cyst, nodular fibromatosis, inflammatory tuberculous and inflammatory rheumatoid lymphadenitis. Five had an ectopic breast (2 with a fibroadenoma and 3 with fibrocystic changes). One patient had an axillary lipoma. The mean age of patients with malignant pathology was 55.1 +/- 10.9 years, and the mean age of patients with a benign pathology was 43.1 +/- 14.7 (P < 0.01). Chest X-ray and bilateral mammography are useful when the cause of the mass cannot be determined by taking a detailed history of neoplastic or infectious antecedents, by careful physical examination of the skin of the arms, trunk and neck, or by palpation of the breasts and thyroid. Fine needle aspiration biopsy distinguishes between benign and malignant pathologies. In cases of indeterminate neoplasia, complete axillary dissection for diagnosis is indicated.

Natural killer cells and interleukin-12 in patients with advanced cervical cancer under neoadjuvant chemotherapy.

Patients with advanced cervical cancer have deficient natural killer (NK) cell activity, usually as a consequence of tumor invasion, which results in tumor NK cell sequestration. The reason for the occurrence of such alterations in patients under chemotherapy is unknown. We evaluated the activity and number of NK cells and T cell subpopulations in ten patients before and three weeks after neoadjuvant chemotherapy (CT). The schedule used was cis-platinum (100 mg/m2 per cycle) and bleomycin (15 mg/cycle), repeated every 28 days. Although there were similar levels of NK cells before and after CT in both groups, we observed greater cytotoxicity of peripheral blood lymphocytes and increased levels of CD4+ and CD8+ T cells (P < 0.01) in five patients who presented a good clinical response when compared to the group with a poor response. IL-12, known to increase NK cell activity when added to peripheral blood lymphocyte cultures, markedly increased lytic activity before and after CT only in the group with a good clinical response. These results suggest that NK cells from the poorly responding patient group express less lytic activity per NK cell and are insensitive to IL-12 stimulation, probably as a result of reduced IL-12 receptor expression or a defective intracellular transduction mechanism. The present findings may be useful as a prognostic factor in clinical practice and also provide support for human clinical trials of IL-12 and neoadjuvant CT for the treatment of malignant cervical tumors.

Natural killer cells and interleukin-12 in patients with advanced cervical cancer under neoadvanced chemotherapy

Patients with advanced cervical cancer have deficient natural killer (NK) cell activity, usually as a consequence of tumor invasion, which results in tumor NK cell sequestration. The reason for the occurrence of such alterations in patients under chemotherapy is unknown. We evaluated the activity and number of NK cells and T cell subpopulations in ten patients before and three weeks after neoadjuvant chemotherapy (CT). The schedule used was cis-platinum (100 Mg/M2 per cycle) and bleomycin (15 mg/cycle), repeated every 28 days. Although there were similar levels of NK cells before and after CT in both groups, we observed greater cytotoxicity of peripheral blood lymphocytes and increased levels of CD4+ and CD8+ T cells (P<0.01) in five patients who presented a good clinical response when compared to the group with a poor response. IL- 12, known to increase NK cell activity when added to peripheral blood lymphocyte cultures, markedly increased lytic activity before and after CT only in the group with a good clinical response. These results suggest that NK cells from the poorly responding patient group express less lytic activity per NK cell and are insensitive to IL- 12 stimulation, probably as a result of reduced IL-12 receptor expression or a defective intracellular transduction mechanism. The present findings may be useful as a prognostic factor in clinical practice and also provide support for human clinical trials of IL- 12 and neoadjuvant CT for the treatment of malignant cervical tumors.

Evaluation of long-term results of surgical correction of stress urinary incontinence.

A total of 109 patients submitted to surgery for the correction of urinary stress incontinence (USI) by two different techniques, i.e. anterior colporrhaphy (group I, n = 57) when cystocele grade II/III was present, and Burch procedure (group II, n = 52) when cystocele grade I was present, were reevaluated an average of 5 years after surgery (range: 54-66 months). The curve constructed with the reevaluation data showed a sharp superiority of the Burch technique in terms of correction of USI and associated genital prolapses. There was a progressive recurrence rate that stabilized at 5 years, with values of 78.9% in group I and 40% in group II. Anterior colporrhaphy was ineffective for the correction of any of these parameters in group I. The data clearly show the need to improve the presurgical diagnostic methods for the selection of patients that will benefit from treatment: detailed history of the current disease and auxiliary tests such as Q-tip test, transvaginal ultrasound, and urodynamic study. Other factors were associated with ineffective treatment in both groups, such as hypoestrogenism (20/109), excessive weight gain (19/109) and chronic intestinal constipation and/or coughing present in 36 patients, with recurrence in 28 of them.

[Use of polimerase chain reaction for neonatal diagnosis of human immunodeficiency virus type 1 (HIV-1) perinatal infection]. / Uso da reação em cadeia da polimerase (PCR) para o diagnóstico neonatal de infecção perinatal pelo vírus da imunodeficiência humana tipo 1 (HIV).

The polymerase chain reaction (PCR) was evaluated for its ability to diagnose perinatal HIV-1 infection before the development of signs or symptoms of the disease in thirty-seven infants (median age of 5.5 days) born to HIV-1 infected women. Of 30 children with complete follow up (median of 25 months), 9 (30%) had serological and clinical features of HIV-1 infection and 21 (70%) were uninfected. Among the infected infants, 5/9 (56%) had positive neonatal PCR tests and 4/9 (44%) had negative PCR tests. None of the 21 uninfected children had positive PCR tests. The prognosis of HIV-1 disease in infected infants with a positive neonatal PCR positive test was similar to that of infected infants with a negative PCR test. In spite of not identifying all the infected infants, the PCR test is a useful tool for early diagnosis of HIV-1 perinatal infection, detecting infected newborns during gestation.