[Show abstract][Hide abstract] ABSTRACT: Chromosomal instability as manifested by increases in aneuploidy and structural chromosome aberrations is believed to play a critical role in the intermediate to late stages in the development of cervical malignancies. The current study was designed to determine the role of tetraploidy in the formation of aneuploidy and ascertain the occurrence of these alterations during the earlier stages of cervical carcinogenesis. Cervical cell samples, with diagnoses ranging from Normal to high-grade lesions, (HSIL) were obtained from 143 women and were evaluated for chromosomal alterations using dual-probe fluorescence in situ hybridization. Cervical cells from a subset of the group were also evaluated for chromosomal instability in the form of micronuclei. The frequencies of cells exhibiting either tetrasomy or aneusomy for Chromosomes 3 and 17 increased significantly with disease progression and displayed distinctive patterns where aneusomy was rarely present in the absence of tetrasomy. The frequencies of micronuclei that formed through either chromosomal loss or breakage increased significantly in both the low-grade and high-grade diagnostic categories and were highly correlated with both the number of tetrasomic and aneusomic cervical cells. In addition, a unique chromosomal alteration involving a significant non-random loss of Chromosome 17 specific to near-tetraploid aneusomic cells (trisomy 17 and tetrasomy 3) was observed. We conclude that tetraploidy and chromosomal instability are related events occurring during the early stages of cervical carcinogenesis that predispose cervical cells to the formation of aneuploidy frequently involving the loss of Chromosome 17.
[Show abstract][Hide abstract] ABSTRACT: Cervical cancer constitutes a major health problem in Mexico and other developing countries. The purpose of our study was to assess the experience of a comprehensive national oncological reference center on pelvic exenteration for post-radiotherapy recurrent or persistent cervical cancer, describing the prognostic value of time to recurrence, procedure complications, and survival. Medical records from 42 patients with post-radiotherapy recurrent or persistent cervical cancer who underwent a pelvic exenteration with curative purposes from 1984 to 1989 were retrospectively reviewed. Histological diagnoses were squamous cell carcinoma (32 patients), adenosquamous carcinoma (9 patients), and adenocarcinoma (1 patient). Average follow up was of 56.3 mo after the procedure and global survival at 5 yr was 65.8%. Survival for patients with early recurrence was 56.9% vs 78% for patients with late recurrence (p = 0.05). Complications were observed in 65.3% of the cases with a surgical mortality of 4.8%. Pelvic exenteration is a surgical procedure with high morbidity in spite of the recent medical advances. Pelvic exenteration should not be indicated with palliative purposes owing to the high rate of complications. Patients with tumor persistence or early recurrence have a worse prognosis. In well-selected cases, exenteration may provide a survival benefit.
Medical Oncology 02/2006; 23(2):219-23. DOI:10.1385/MO:23:2:219 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated expression of matrix metalloproteinases (MMPs) plays a critical role in extracellular matrix (EM) degradation in tumor development and prognosis of different human carcinomas. In cervical carcinoma (Ce Ca), the role of these proteinases in the biological development of this neoplasm is controversial. In the present study, we compared the secretion of MMP-2, MMP-3 and MMP-9 among 29 benign and premalignant cervical lesions (cervicitis and cervical intraepithelial neoplasias) and 46 tumoral explants of Ce Ca. The explants were cultured for 48 h. The gelatinases secreted into conditioned medium were revealed by zymography and quantified by densitometry. The results showed high levels of MMP-3 and MMP-9 in tumoral explants. In contrast, only the pro-MMP-2 was higher in benign cervical lesions, although both active and inactive MMP-2 species are associated with advanced clinical stages in tumoral samples, and only the secretion of MMP-3 was associated with unresponsiveness to radiotherapy. We can conclude that the expression of MMPs is related to the invasive process in Ce Ca and suggest that they may play a role in degradation of the EM during local invasion. In addition, MMP-3 secretion could be a marker of poor prognosis in Ce Ca.
International Journal of Gynecological Cancer 03/2004; 14(2):333-40. DOI:10.1111/j.1048-891x.2004.014218.x · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor cells exhibit phenotypic and genotypic differences in comparison to normal cells. These differences can be used to identify proteins important for tumor growth and, therefore, potentially used in the diagnosis and follow-up of patients. The objective of this work was to investigate the electrophoretic pattern of cytoplasm membrane proteins from normal and malignant cervix using polyacrylamide-SDS gels. A highly reproducible protein pattern was found in the 29 samples of normal cervix whereas three well-defined patterns of protein bands were observed in the 48 tumor specimens (pattern I: 25%, pattern II: 29.2% and pattern III: 45.8%). A low concentration or absence of high molecular weight proteins was observed (p<0.5) in tumor samples. None of the tumor protein patterns correlated with the clinicopathologic characteristics of patients. Nine out of 11 patients (82%) showing the pattern III had a complete clinical response whereas only 55% (11 out of 20) of those with patterns I and II showed a complete response. However, this difference was non-significant (p=0.1247). In conclusion, we demonstrate that there is a gain and loss of cytoplasmic membrane proteins in tumors, shown as different protein band patterns. These findings could have clinical and biological significance that must be further evaluated.
Journal of experimental & clinical cancer research: CR 07/2001; 20(2):231-7. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cervical carcinoma is a common disease for which the prognosis has not been substantially improved with standard locoregional treatments. Three stage IB patients with untreated cervical carcinoma were treated with high-dose chemotherapy and refrigerated peripheral blood stem cell support using the ICE program (Ifosfamide 10 g/m2 plus mesna at 100% of the ifosfamide dose; Carboplatin at 1.5 g/m2 and Etoposide 2.1 g/m2). Patients received the treatment in an adjuvant setting after radical hysterectomy with pelvic lymph-node dissection and postoperative cisplatin-based standard-dose chemotherapy. All patients underwent postoperative radiotherapy. The treatment was well-tolerated, all patients had rapid hematologic recovery, and the most frequent complications were grade 3 mucositis and neutropenic fever. The three patients are disease-free at 58, 60, and 63 months of follow-up. Our results show that adjuvant high-dose chemotherapy could be effective to reduce the likelihood of relapse in high-risk patients. High-dose chemotherapy deserves a formal evaluation in high-risk cervical cancer.
International Journal of Gynecological Cancer 08/1999; 9(4):333-336. DOI:10.1046/j.1525-1438.1999.99047.x · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia.
The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members.
No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically.
In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 63(6):665-702. · 0.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endometrial cancer (EC) is the second most common gynecologic malignancy worldwide in the peri and postmenopausal period. Most often for the endometrioid variety. In early clinical stages long-term survival is greater than 80%, while in advanced stages it is less than 50%. In our country there is not a standard management between institutions. GICOM collaborative group under the auspice of different institutions have made the following consensus in order to make recommendations for the management of patients with this type of neoplasm.
The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of four days in which a debate was held. These statements are the conclusions reached by agreement of the participant members.
Screening should be performed women at high risk (diabetics, family history of inherited colon cancer, Lynch S. type II). Endometrial thickness in postmenopausal patients is best evaluated by transvaginal US, a thickness greater than or equal to 5 mm must be evaluated. Women taking tamoxifen should be monitored using this method. Abnormal bleeding in the usual main symptom, all post menopausal women with vaginal bleeding should be evaluated. Diagnosis is made by histerescopy-guided biopsy. Magnetic resonance is the best image method as preoperative evaluation. Frozen section evaluates histologic grade, myometrial invasion, cervical and adnexal involvement. Total abdominal hysterectomy, bilateral salpingo oophorectomy, pelvic and para-aortic lymphadenectomy should be performed except in endometrial histology grades 1 and 2, less than 50% invasion of the myometrium without evidence of disease out of the uterus. Omentectomy should be done in histologies other than endometriod. Surgery should be always performed by a Gynecologic Oncologist or Surgical Oncologist, laparoscopy is an alternative, especially in patients with hypertension and diabetes for being less morbid. Adjuvant treatment after surgery includes radiation therapy to the pelvis, brachytherapy, and chemotherapy. Patients with Stages III and IV should have surgery with intention to achieve optimal cytoreduction because of the impact on survival (51 m vs. 14 m), the treatment of recurrence can be with surgery depending on the pattern of relapse, systemic chemotherapy or hormonal therapy. Follow-up of patients is basically clinical in a regular basis.
Screening programme is only for high risk patients. Multidisciplinary treatment impacts on survival and local control of the disease, including surgery, radiation therapy and chemotherapy, hormonal treatment is reserved to selected cases of recurrence. This is the first attempt of a Mexican Collaborative Group in Gynecology to give recommendations is a special type of neoplasm.
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 62(6):583, 585-605. · 0.31 Impact Factor