Biomedical subjects
R Estape
Publications and source records attributed to R Estape.
Primary malignant melanoma of the uterine cervix: case report and review of the literature.
This is a case report and review of the literature on primary melanoma of the cervix. There have been only 26 published cases of primary cervical melanoma and most are poorly documented and doubtful. The patients' ages ranged from 26 to 78 years old with a mean age of 55 +/- 13 years. The main presenting symptom was vaginal bleeding (83.0%). The majority of the patients, 88%, presented in stage I or II. Treatment varied from a simple excision of a cervical mass to a radical hysterectomy with lymph node dissection and adjuvant radiation or chemotherapy. Our patient presented with vaginal bleeding and was diagnosed as having stage IIa cervical melanoma. She underwent a radical hysterectomy, partial vaginectomy, and pelvic and paraaortic lymph node dissection. She received adjuvant radiation therapy and her survival was 29 months. The prognosis of primary cervical melanoma is usually poor and unpredictable. We recommend a radical hysterectomy and vaginectomy, if necessary, to obtain negative surgical margins of at least 2 cm. We advocate lymphadenectomy only for grossly positive nodes.
Primary uterine angiosarcoma.
OBJECTIVE: The aim of this study was to report the first case of primary uterine angiosarcoma described in a Hispanic American woman and to review the literature on uterine angiosarcomas. We review characteristic presenting symptoms, gross and microscopic pathologic findings, and treatment outcomes where available. METHODS: A case report is presented with a review of the English language literature via a Medline search. The key phrases used in the search were uterine angiosarcoma, hemangiosarcoma, hemangioendothelioma, and primary uterine neoplasm. RESULTS: Since the first report in 1902, there have been 19 reported cases of primary uterine angiosarcoma considered valid. Many early cases are questioned due to the lack of ultrastructural and immunohistochemical evidence available in later cases. Seventy-four percent (14 of 19) of these patients are perimenopausal with a mean age of 55 years (range 17-76 years). The common presenting findings are a pelvic mass, menorrhagia, and weight loss. Varying regimens of surgery, chemotherapy, and radiation have been utilized with limited success. CONCLUSIONS: Primary uterine angiosarcomas tend to exhibit a highly malignant behavior. The predominant prognostic factor seems to be the size of the tumor at diagnosis and the presence of extrapelvic disease. Recurrence occurs on average at 8.2 months. Of evaluable patients (n = 14), at 12 months the survival was only 43%. Although radiation and chemotherapy are options being utilized, no consensus exists for optimal therapy given the few cases from which to draw conclusions. Regardless of treatment, outcome is usually poor.
The impact of intraoperative autologous blood transfusion during type III radical hysterectomy for early-stage cervical cancer.
OBJECTIVE: The aim of this study was to determine the effects on transfusion rates, perioperative complications, and survival of using intraoperative autologous blood transfusions for patients undergoing type III radical hysterectomy and lymphadenectomy. STUDY DESIGN: A retrospective analysis was conducted on 156 patients treated with type III radical hysterectomy and lymphadenectomy at the University of Miami School of Medicine from 1990 to 1997. One group of patients (n = 50) had intraoperative autologous blood transfusions and the other (n = 106) did not. RESULTS: The group that received intraoperative autologous blood transfusion had a significant reduction in homologous blood transfusions (12% vs 30%; P =.02). Patient demographic data, histologic parameters, and operative factors were similar between the 2 groups. There was a higher percentage of patients with positive pelvic lymph nodes in the group that did not receive intraoperative autologous blood transfusion (10% vs 30%; P =.02). Seven patients in the intraoperative autologous blood transfusion group (14%) died with disease present and all the recurrences in this group were local. CONCLUSION: The use of intraoperative autologous blood transfusions during type III radical hysterectomy and lymphadenectomy appears to be safe and effective without compromising rates and patterns of recurrence.
Trends in the management of pelvic abscesses.
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Significance of intraperitoneal cytology in patients undergoing radical hysterectomy.
The incidence and prognostic significance of positive intraperitoneal cytology taken during a radical hysterectomy was reviewed. A prospective study looking at intraperitoneal cytology was conducted by using 400 consecutive radical hysterectomies from January 1988 through June 1996. All selected patients had peritoneal washings performed prior to a radical hysterectomy with pelvic and para-aortic lymphadenectomy. A single pathologist reviewed all cytological and histologic specimens. A total of 400 patients were included in the study. Only 7 of 400 (1.8%) had positive intraperitoneal cytology. Four had squamous cell cancer and 3 had adenocarcinoma. Five had stage IB cervical cancer and the remainder were stage IIA. Three had positive nodes. Six of 7 had tumor size greater than 3 cm. Three of 7 had > 50% invasion and 2 of 7 had lymphovascular space invasion. No other risk factors were present in these specimens. Six of 7 recurred within 18 months of surgery. Recurrences were local or retroperitoneal; none were upper abdomen or intraperitoneal. The incidence of positive peritoneal cytology during radical hysterectomy is 1.8%. The cost of these cytology specimens did not offer an advantage to the current surgical-pathological factors used to determine prognosis and adjuvant therapy.
Urinary complications of Miami pouch: trend of conservative management.
OBJECTIVE: Continent urinary diversions have become popular among gynecologic oncologists. Much information has been gained concerning the complications and current management of patients with continent ileocolonic reservoirs. The high mortality rate associated with reoperation has led clinicians to adopt a trend toward conservative means of management. The purpose of this study was to evaluate the applicability of conservative management of complications related to the creation of the continent ileocolonic reservoir Miami pouch. STUDY DESIGN: Patients who underwent creation of the Miami pouch at the Division of Gynecologic Oncology, University of Miami School of Medicine, since 1988 have been included in this study. Management of complications, with particular emphasis on the conservative treatment, has been reviewed in detail for each patient. Open surgery and conservative treatment have been compared. RESULTS: Seventy-seven patients underwent creation of the Miami pouch from February 1988 to September 1997. Sixty (77.9%) patients were affected by recurrent cervical cancer; 72 (93.5%) were previously radiated. The perioperative mortality rate was 11.7% (9 patients). Six of these patients died as a result of sepsis; all of them underwent reoperation at least once. The most common urinary complications were ureteral stricture or obstruction (22.1%), difficult catheterization (19.5%), and pyelonephritis (13%). Conservative management strategies used for these complications included percutaneous nephrostomy, stent placement, balloon dilatation, radiologically (ultrasonography, fluoroscopy, computed tomography) guided placement of catheters, and antibiotic treatment. Eighty percent of the complications associated with the ileocolonic reservoir were resolved with conservative treatment, whereas 16.9% required surgical revision. CONCLUSION: On the basis of these findings, conservative management of urinary reservoir complications should always be considered before surgical intervention is attempted. The exact time to engage in open revision should be individualized on the basis of the clinical condition of each patient. It is our belief that the conservative approach should be instituted whenever possible but surgical intervention not be delayed when absolutely indicated.
Hereditary and sporadic ovarian cancer: genetic testing and clinical implications (review).
The two most common forms of hereditary ovarian cancer are: the breast ovarian cancer syndrome, and ovarian cancer associated with HNPCC (hereditary nonpolyposis colorectal cancer) syndrome. Studies have shown that these diseases may be associated with mutations in a number of tumor suppressor genes, mainly BRCA1 and BRCA2. Malfunction of the protein products of these genes have also been found to be involved in sporadic ovarian cancer, which makes up the majority of ovarian cancer cases. HNPCC-ovarian cancer associated families reveal frequent mutations in at least four genes (hMSH2, hMLH1, hPMS1, and hPMS2) involved in the repair of mismatched DNA. With ovarian cancer being such an important health issue, the push is on to design reliable screening tests to detect defective inherited or somatic alleles in individual carriers. So far, most progress has been demonstrated in those patients with family histories of the disease who are at increased risk. The ramifications of such research may impact a variety of scientific, clinical, legal, ethical, and psychosocial issues. In addition to current treatment modalities, positive results of these tests may indicate the need for increased clinical surveillance, prophylactic treatment, and genetic counseling of patients on an individual basis. It remains to be seen whether the technology can be made reliable enough to not only benefit high-risk individuals but also the general population.
In vitro antigene therapy targeting HPV-16 E6 and E7 in cervical carcinoma.
Human papillomavirus (HPV) infection is believed to play a central role in cervical carcinogenesis. Specifically, two viral oncoproteins, E6 and E7, possess transforming ability and have been shown to interact with the cellular tumor suppressors p53 and p105, the retinoblastoma (Rb) gene product. To test the hypothesis that E6 and E7 play an active role in the maintenance of the malignant phenotype and may be ideal targets for antigene therapy, we tested the antiproliferative effects of phosphorothioate oligodeoxynucleotides (oligos) targeting HPV-16 E6 and E7 in cervical cancer cell lines and primary tumor explants. The ATP cell viability assay was used to measure growth effects of 27-mer antisense oligos targeting the ATG translational start region of HPV-16 E6 and E7 sequences in HPV-16-positive cell lines SiHa and CaSki and four advanced, primary cervical tumor explants. A random oligo sequence, an HPV-18-positive and HPV-negative cell line, one histologically confirmed endometrial and two ovarian tumors were used as negative controls. HPV type was confirmed by hybrid capture techniques. Cell lines and sterile (staging laparotomy) tumor cells were plated at 5000 cells/0.1 ml and 100,000 cells/0.5 ml in 96-well plates or soft agar, respectively, and incubated at 37 degrees C with a single treatment of oligos at 0-16 microM. E6/E7 combinations at a fixed ratio of 1:1 were used at 0-8 microM for each oligo. Cellular ATP was measured by luciferin/luciferase fluorescence on Day 6. HPV-16 E6 and E7 oligos showed antiproliferative effects in all HPV-16-positive cell lines and primary tumor explants (IC50s 6.9-9.5 microM for cell lines, 9.1-12.1 microM primary cervical tumors), while the HPV-negative C33-A cell line and HPV-18-positive cell line HeLa were relatively insensitive to the HPV-16 oligos (IC50s > 30 microM extrapolated). The endometrial and two ovarian primary tumors were also insensitive to the HPV E6 and E7 oligos (IC50s > 25 microM extrapolated). Random oligos had little effect on cell growth at concentrations up to 16 microM (< 25% inhibition), except in CaSki (@50% inhibition at 16 microM). Combinations of E6 and E7 demonstrated mixed synergistic and antagonistic effects as determined by combination indices (CI) derived from median effect parameters. In the HPV-16-positive primary cervical tumors and the cell line SiHa, E6/E7 combinations were synergistic at low doses (< 25% growth inhibitory dose range) and antagonistic at doses above this. For the HPV-16-positive cell line CaSki, however, E6/E7 combinations were antagonistic at all dose ranges. Phosphorothioate oligos directed against the viral oncogenes E6 and E7 were shown to have antiproliferative effects specific to HPV-containing cancer cells. These specific antiproliferative effects suggest that HPV-16 E6 and E7 sequences play an active role in the malignant growth properties of cervical cancer cells and may be ideal targets for antigene therapy.
p53 interference and growth inhibition in p53-mutant and overexpressing endometrial cancer cell lines.
BACKGROUND: The presence of p53 mutations and associated mutant p53 overexpression has been demonstrated in many cancer systems. Whether the overexpression of mutant p53 represents cause or effect, and whether p53 mutation contributes actively to the malignant phenotype is a matter of controversy. We examined the growth effects of oligonucleotides designed to interfere with p53 expression and/or activity in p53-mutant/overexpressing endometrial cancer cell lines. METHODS: Phosphorothioate oligonucleotides were used to target p53-related sequences in two p53-mutant/overexpressing endometrial cancer cell lines (KLE and RL95-2) and a normal fibroblast control. The ATP cell viability assay was used to measure growth effects after 6-day treatments with 27-mer and 14-mer sense (S) or antisense (AS) phosphorothioate oligodeoxyribonucleotides (oligos) targeting the promoter/ATG region of p53 and/or the p53 consensus (CON) DNA binding sequence. These sequences were designed to interfere with p53 expression and activity, respectively. Random sequences of the p53 27- and 14-mer were used as controls for nonspecific oligo effects, and a normal fibroblast cell line was used to compare oligo effects and serve as a negative p53 immunostaining control. RESULTS: Mean +/- SE IC50 (50% growth inhibition) of the S, AS p53, and p53 CON oligos were 4.2 +/- 1.3, 4.7 +/- 0.9, and 7.6 +/- 1.4 microM, respectively, for the two endometrial cell lines combined. The AS and S p53 oligos demonstrated dose-dependent inhibitory effects in both cell lines, while p53 CON produced variable effects alone and in combination with p53 AS. In KLE, a uniform inhibitory dose response was seen with p53 CON oligos. In RL95-2, the approximate IC50 for p53 CON was 0.5-1.0 microM, but at increasing doses above this, an inverse dose response was consistently observed. Combinations of p53 AS and p53 CON oligos produced predominantly synergistic growth inhibition. Although combinations of p53 AS and p53 CON in KLE were synergistic at low doses, antagonistic effects occurred at higher concentrations. Oligos had little effect on normal fibroblast growth, with calculated IC50 > 16 microM. Equimolar combinations of p53 S and AS were antagonistic, indicating that antiproliferative effects were sequence-specific. Random oligos demonstrated some nonspecific inhibitory effects, with >25% growth inhibition at 16 microM and beyond. Immunoperoxidase staining for mutant p53 after exposure to 16 microM concentrations of p53 AS oligos demonstrated reductions in p53 staining but persistent overexpression relative to wild-type (fibroblast) cells. CONCLUSION: Phosphorothioate oligos directed against p53 sequences in two p53-mutant endometrial cancer cell lines demonstrated antiproliferative effects. Combined anti-p53 and anti-p53 binding site oligos resulted in predominantly synergistic antiproliferative effects. The activity of sense oligos, the variable responses to p53 CON, and the persistent overexpression of mutant p53 at high concentrations of growth-inhibiting anti-p53 oligos suggest that, while promising, the antineoplastic effects of these oligos occur through complex and incompletely understood mechanisms.
Radical hysterectomy for invasive cervical cancer. A 25-year prospective experience with the Miami technique.
BACKGROUND: The Miami modification of the traditional Wertheim-Meigs radical hysterectomy was used to treat Stage IB-IIA cervical cancer in a 25-year prospective study involving 978 patients. METHODS: The modifications included: vaginal reconstruction and closure using bladder and rectosigmoid serosa, retroperitoneal drainage through abdominal suction catheters, and suspension of the denuded ureters with the ipsilateral obliterated hypogastric artery. RESULTS: The overall corrected 5-year survival rate was 90.1%, with a surgical mortality rate of 1.4% and an overall urinary fistula rate of 1.4%. This fistula rate was significantly better than a 4.4% incidence rate in a literature survey. Although not measured, the Miami modification appeared to lengthen the vagina. CONCLUSIONS: Therefore, it was concluded that radical hysterectomy with the Miami modifications can be done safely in most patients with Stage IB-IIA cervical cancer.
Radical hysterectomy for stage IB adenocarcinoma of the cervix: the University of Miami experience.
The treatment of adenocarcinoma of the cervix has traditionally followed that of squamous cancer. A 25-year review of 88 radical hysterectomies for Stage IB adenocarcinoma of the cervix at the University of Miami/Jackson Medical Center (UM) is compared to over 1600 cases reported in the literature. Adenocarcinoma represented 10.4% of 978 radical hysterectomies performed at UM from July 1965 to December 1990. In a survey of the literature, patients with Stage IB cervical adenocarcinoma treated by radical surgery alone had a statistically better 5-year survival than those treated by radiation alone (79% vs 67%, respectively; P < or = 0.05). Furthermore, no additional benefit was achieved by combining the two therapeutic modalities. The corrected 5-year survival at UM is 81% for Stage IB adenocarcinoma of the cervix treated with radical hysterectomy, a number consistent with the cumulative data base. Radical surgery is an acceptable primary therapy in Stage IB adenocarcinoma of the cervix.
Surgical management of advanced and recurrent cervical cancer.
Since the early 1940s, the incidence of cervical cancer has dramatically decreased due in large part to the work of Papanicolaou and Traut. Successful treatment can now be done using simple or radical surgical intervention for early invasive lesions and radiation therapy for more advanced lesions. However, despite current advances in screening and early treatment, local recurrences still happen and are difficult to treat. The natural history of cervical cancers is that of a slowly growing, locally invasive tumor. As such, it lends itself to radical surgical resection in selected patients prior to distant metastasis. Current advances in intraoperative and postoperative monitoring, as well as improved surgical techniques and devices, have decreased the morbidity and mortality of radical surgical procedures to acceptable levels. Current data associated with these procedures for advanced or recurrent cervical cancer are described.
The Janeway Lecture. Gynecologic oncology in the last quarter century.
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