Radical vaginal trachelectomy: a fertility-preserving option for young women with early stage cervical cancer.
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Adult↗
Biomedical subjects
Marie Plante
Publications and source records attributed to Marie Plante.
HRT use among women tested for BRCA1/2 mutations following publication of the women's health initiative study results.
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Attitude to Health↗
Mucinous ovarian tumors of Mullerian-type: an analysis of 17 cases including borderline tumors and intraepithelial, microinvasive, and invasive carcinomas.
Mullerian-type mucinous tumors (MMTs) of the ovary are characterized by a papillary architecture similar to that of serous tumors and a content of endocervical-like mucinous epithelium. The latter may be admixed with other mullerian-type epithelia, including those of serous, endometrioid, and squamous types, and indifferent eosinophilic epithelial cells. We analyzed 17 MMTs, including 12 borderline tumors, 2 intraepithelial carcinomas, 2 microinvasive carcinomas, and 1 invasive carcinoma. Fourteen of 16 tumors (88%) with available staging were stage I; the remaining two cases (both borderline) were stage IIa and IIIc. Endometriosis was identified in eight cases (47%). Only two patients (12%) had bilateral tumors, a frequency of bilaterality lower than in previous studies. Five patients (31%) had conservative treatment consisting of a cystectomy or unilateral salpingo-oophorectomy. All patients had a favorable outcome, with no recurrences or disease-related deaths, regardless of the presence of high mitotic index, intraepithelial carcinoma, microinvasion, bilaterality, conservative treatment, or advanced stage. This indolent behavior of MMTs is similar to that previously reported, but additional cases of invasive carcinomas in this category are needed to better define their outcome.
Adenocarcinoma, Mucinous↗
No evidence of false reassurance among women with an inconclusive BRCA1/2 genetic test result.
BACKGROUND: Little is known about how women who receive an inconclusive result from BRCA1/2 testing interpret their result. Clinical observations suggest that some of them may be falsely reassured and, consequently, may not adhere to recommended surveillance. The purpose of this study is to evaluate whether women with inconclusive BRCA1/2 test results are falsely reassured. METHODS: Participants were adult women with a family history suggestive of a germ-line mutation in either the BRCA1 or the BRCA2 gene who underwent genetic testing in the context of the interdisciplinary research program INHERIT BRCAs. Data were collected using self-administered questionnaires at genetic counseling and 1 month after result disclosure. Reassurance was assessed through indicators of cancer risk perception, cancer worry, relief following result disclosure, painfulness of the test result, and its effect on quality of life. RESULTS: Five-hundred women (105 carriers, 140 noncarriers, and 255 inconclusive) were included in this analysis. Compared to noncarriers, women with inconclusive results had higher cancer risk perception, were more worried about cancer, were less relieved by their test result, and perceived their quality of life as being more adversely affected by it. CONCLUSION: The differences observed between noncarriers and women who received an inconclusive result run counter to the hypothesis that the latter are falsely reassured following BRCA1/2 testing. For clinicians, our findings show the value of taking precautions to fully explain to women that inconclusive results do not rule out the possibility that they still may face a higher risk of developing breast and/or ovarian cancer.
Adult↗
The functional UGT1A1 promoter polymorphism decreases endometrial cancer risk.
UDP-glucuronosyltransferase (UGT) 1A1 is involved in the inactivation of estradiol (E(2)) and its oxidized metabolites. These metabolites have been shown to contribute to the development of endometrial cancer in animal studies. Thus UGT1A1 represents a candidate gene in endometrial carcinogenesis. In this study, we established the substrate specificity of UGT1A1 for E(2) and its 2- and 4-hydroxylated metabolites. Intrinsic clearances indicated that UGT1A1 had a preference for the glucuronidation of 2-hydroxyestradiol, a metabolite associated with antiproliferative activity. Expression analysis demonstrated that UGT1A1 is present in the nonmalignant endometrium. Subsequently, we sought to determine whether the common UGT1A1 promoter allele, UGT1A1*28 [A(TA)(7)TAA], which decreases gene transcription, was associated with endometrial cancer risk in a case-control study nested within the Nurses' Health Study (222 cases, 666 matched controls). Conditional logistic regression demonstrated a significant inverse association with the UGT1A1*28 allele and endometrial cancer risk. Compared with women homozygous for the UGT1A1*1 [A(TA)(6)TAA] allele, the adjusted odds ratio (OR) was 0.81 [95% confidence interval (CI), 0.56-1.16] for the UGT1A1*1/*28 genotype and 0.40 (95% CI, 0.21-0.75) for the homozygous UGT1A1*28 genotype (P(trend) = 0.007). There was a suggestion of an interaction by menopausal status [OR = 0.39 (95% CI, 0.18-0.85) for premenopausal women and OR = 0.79 (95% CI, 0.55-1.13) for postmenopausal women who carry the UGT1A1*28 allele (P(interaction) = 0.05)]. These observations suggest that lower expression of UGT1A1 decreases the risk of endometrial cancer by reducing the excretion of 2-hydroxyestradiol, the antiproliferative metabolite of E(2), in the endometrium.
Adult↗
Primary villoglandular adenocarcinoma of cloacogenic origin of the vulva.
Primary villoglandular adenocarcinomas of the vulva are rare, and only seven cases have been described to date. Hypotheses about the origin of this neoplasm remain highly speculative. We report the case of a 58-year-old woman who developed this very uncommon malignant tumor. Immunohistochemical studies of the tumor revealed positive staining for cytokeratins 7 and 20 and a negative staining for estrogen and progesterone receptors. Special stains showed the presence of intracellular mucin. No other primary lesion was found on clinical evaluation and extensive investigation. The patient was first treated by radical hemivulvectomy, followed by ipsilateral inguinal lymph node dissection and laparoscopic right salpingo-oophorectomy for an incidental finding of an ovarian cyst. The patient remained free of disease 16 months after the initial surgery.
Adenocarcinoma↗
Vaginal radical trachelectomy: an oncologically safe fertility-preserving surgery. An updated series of 72 cases and review of the literature.
OBJECTIVE: To review the oncological results and complication rate of our first consecutive 72 completed cases of vaginal radical trachelectomies (VRT). METHODS: From October 1991 to October 2003, we have planned 82 VRT in patients with early-stage cervical cancer (stages IA, IB, and IIA). The VRT was preceded by a complete laparoscopic pelvic node dissection and laparoscopic parametrectomy. RESULTS: The planned procedure was successfully completed in 72 cases and was abandoned in 10 cases (12%) because of either positive nodes discovered at the time of surgery (4), positive endocervical margins (5) or extensive tubal adhesions (1). The median age of the remaining 72 patients was 31 and most (75%) were nulliparous. The majority of the lesions were stage IA2 (32%) or IB1 (60%) and 54% were grade 1. In terms of histology, 58% were squamous and 42% were adenocarcinomas. Vascular space invasion was present in 20% of cases, and 90% of the lesions measured </=2 cm. An average of 32 lymph nodes has been removed laparoscopically. The mean follow-up is 60 months (6-156). The intraoperative complication rate was low (6%) and the postoperative morbidity was also low mainly involving bladder hypotonia (16%) and vulvar edema (12%). There were no bladder or ureteral injuries. The average hospital stay was 3 days. Excluding one patient with a small cell neuroendocrine tumor who rapidly recurred and died, there were two recurrences (2.8%) and one death (1.4%). The actuarial recurrence-free survival is 95%. Tumor size >2 cm was statistically significantly associated with a higher risk of recurrence (P = 0.03). The recurrence-free survival of the nine patients who did not have the planned VRT because of more advanced disease was statistically significantly less (P = 0.003). CONCLUSION: VRT is an oncologically safe procedure in well-selected patients with early-stage disease. Lesion size >2 cm appears to be associated with a higher risk of recurrence. The morbidity of the procedure is low and it allows fertility preservation.
Adult↗
Changes in health-related behaviours following BRCA 1/2 genetic testing: the case of hormone replacement therapy.
OBJECTIVE: To determine hormone replacement therapy (HRT)use among women at high risk for breast cancer and ovarian cancer, before genetic testing for the cancer susceptibility genes BRCA1 and BRCA2, and 1 year following disclosure of the test results. METHODS: Participants were 209 French-Canadian women (from 67 high-risk families) who were tested for BRCA1/2 mutations as part of the multidisciplinary research program INHERIT BRCAs (INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility). Use of HRT was recorded at the first genetic counselling session and through a self-administered questionnaire 1 year after result disclosure. RESULTS: At the genetic counselling session, approximately 15% of women (31/209) reported using HRT, a proportion that is significantly lower than the 25% observed among similarly aged women from the general Quebec population (P < .001). Further analyses, based on the generalized estimating equations models, were carried out to evaluate variations in HRT use from the first genetic counselling session up to 1 year post-disclosure of BRCA1/2 test results. These analyses indicated a trend toward decreased HRT use among BRCA1/2 mutation carriers (P = .08). CONCLUSIONS: Women at high risk for breast cancer and ovarian cancer tend to avoid HRT when BRCA1/2 mutations are either suspected or confirmed. Further studies are needed to assess the actual risk of HRT use among women at high risk of breast cancer, and to develop clinical guidelines regarding its use in this population of women.
Adult↗
Vaginal radical trachelectomy in the treatment of cervical cancer: the role of frozen section.
Vaginal radical trachelectomy (VRT) is a new, alternative surgical procedure to radical hysterectomy for early stage invasive cervical carcinoma in women who desire to preserve fertility. The specimen includes the cervix, parametria, and the vaginal cuff. This study was designed to determine the indications and the best method for evaluating the resection margins of VRT specimens intraoperatively by frozen-section examination. We reviewed 61 VRT specimens planned between October 1991 and January 2002 in our center. A complementary radical hysterectomy is recommended when the tumor extends to within <5 mm of the margin. Of 61 patients, 56 were eligible (5 excluded; 53 VRT and 3 VRT followed by hysterectomy). Of 56 cases, 17 had no macroscopic or microscopic residual tumor. Of 27 cases with a nonspecific macroscopic lesion, more than one-half had no residual microscopic tumor, and the others had minimally (<1 mm) invasive residual carcinoma. In the remaining two cases with a macroscopic tumor, a longitudinal rather than a transverse frozen section was preferred, because it allowed the evaluation of the distance between the tumor and the endocervical margin. We recommend a frozen section, using a longitudinal section, only in those VRT specimens with a grossly visible lesion.
Female↗
Specificity and regioselectivity of the conjugation of estradiol, estrone, and their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho-glucuronosyltransferases expressed in endometrium.
Uridine diphospho-glucuronosyltransferases (UGTs) inactivate and facilitate the excretion of estrogens to glucuronides (-G), the most abundant circulating estrogen conjugates. The identity of the conjugated estrogens formed by all known overexpressed UGTs (n = 16) was analyzed by comparison with retention time and mass fragmentation of authentic standards by HPLC tandem mass spectrometry methods. Six UGTs, namely 1A1, 1A3, 1A8, 1A9, 1A10, and 2B7, were found to glucuronidate estradiol (E(2)) and estrone (E(1)), their hydroxyls (OH), and their methoxy derivatives (MeO). Addition of glucuronic acid was catalyzed by specific UGTs at positions 2, 3, and 4 of the estrogens, whereas only E(2) was conjugated at position 17 by UGT2B7. Kinetic parameters indicate that the conjugation of E(2) at position 3 was predominantly catalyzed by 1A1, 1A3, and 1A8 and by 1A8 for E(1). Conjugation of 2-OHE(1)/E(2) and 2- and 4-MeOE(1)/E(2) was selective at position 3, mostly catalyzed by 1A1 and 1A8. Of all UGTs, UGT2B7 demonstrated the highest catalytic activities for estrogens and at least 10- to 50-fold higher activity for the conjugation of genotoxic 4-hydroxycatecholestrogens at position 4, compared with the conjugation of E(2), E(1), and 2-hydroxycatecholestrogens. Its presence was further shown in the endometrium by RT-PCR and immunohistochemistry, localizing in the same cells expressing CYP1B1, involved locally in the formation of 4-hydroxycatecholestrogens. Data show that several UGT enzymes detected in the endometrium are involved in the glucuronidation of E(2) and its 2-OH, 4-OH, and 2-MeO metabolites that exert various biological effects in the tissue.
Cell Line↗
Sentinel node evaluation in gynecologic cancer.
The sentinel node evaluation has revolutionized the modern surgical management of cutaneous melanoma and breast cancer. In gynecologic oncology, sentinel node mapping has been mainly studied in vulvar and cervical cancer. In vulvar cancer, data from 12 studies including 353 cases indicate that the sentinel node detection rate is 92% and the negative-predictive value is 99%. Three groin recurrences have been documented so far (< 1%). The technique has more recently been studied in cervical cancer. Data from 12 studies including 323 cases indicate a lower sentinel node detection rate of 80% to 86% and a negative-predictive value of 99%. Three false-negative cases have been reported so far (< 1%). Review of the literature suggests that the combined approach with blue dye and lymphoscintigraphy is superior to the blue dye alone for sentinel node detection. It also suggests that the sentinel node mapping technique is feasible in vulvar and cervical cancer and that it may become a valuable alternative to the traditional groin and pelvic lymphadenectomy. However, results have not been duplicated in large multi-institutional trials, and the technique should still be performed in the context of clinical trials. Complications of the sentinel node mapping technique are rare and usually benign but physicians should be aware of the serious risk of anaphylactic reaction to the blue dye (1% to 2%). Before this technique becomes a standard approach in the management of gynecologic malignancies, more data will be needed to clarify some of the related controversies.
Female↗
Innovations in the treatment of invasive cervical cancer.
Invasive cervical cancer is characterized by basement membrane-invading lesions capable of metastasizing through the lymphatic and vascular systems. Treatment methods were reviewed by panelists at the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), and new opportunities for translational research were discussed. Reviews encompassed hysterectomy with or without lymph node dissection or cervical conization in cases with microinvasion and radical trachelectomy with or without lymph node dissection as fertility-sparing surgery. Chemoradiation is used to treat advanced cervical malignancies, and the risks and benefits of radiotherapy are significant. Pelvic exenteration is used to treat certain types of recurrences. Use of the Miami pouch for continent urinary diversion was highlighted. Gynecologic oncologists expect novel in vivo imaging techniques currently being developed to help guide therapy choices within the next decade. The most significant research priorities are large group-randomized trials involving fertility-sparing procedures and the management of microinvasive carcinoma (MICA); better identification of candidates for chemoradiation; and the development of innovative approaches to exenteration. Improving diagnostic technologies, refining the criteria by which therapies are chosen, and preserving fertility remain challenges in selecting the most appropriate treatment for invasive cervical cancer. Research advances in both diagnosis and treatment are expected to improve therapy and outcomes.
Combined Modality Therapy↗
Laparoscopic sentinel node mapping in early-stage cervical cancer.
OBJECTIVE: We aimed to determine the feasibility and accuracy of sentinel node (SN) mapping and its ability to predict the status of the regional nodal basin. METHODS: From October 2000 to September 2002, 70 patients undergoing radical surgery for early-stage cervical cancer (stage IA, IB, and IIA) were offered lymph node mapping for identification of the sentinel node. All patients underwent SN identification laparoscopically followed by a complete laparoscopic pelvic node and parametrial dissection. The SN mapping was done after intracervical blue dye injection in all cases and was combined with preoperative lymphoscintigraphy following intracervical Tc-99 injection and intraoperative SN detection with a miniaturized laparoscopic gamma probe in 29 cases (42%). RESULTS: The blue dye technique alone (n = 70) identified at least 1 SN in 61 (87%) of the patients. The rate of SN detection by side of dissection was 74%, 70% on the left side and 77% on the right side. Bilateral SN were identified in 60% of cases. In the subgroup of patients who had the combined technique (n = 29), the rate of SN detection increased from 79 to 93% (P = 0.04). The bilateral SN detection rate increased from 55 to 72% when adding lymphoscintigraphy (P = 0.03). In the last 15 cases of the series, the SN detection rate reached 93% (14/15) and this was statistically significant compared to the detection rate of the first 55 cases (P < 0.01). A total of 135 SN were identified, with the majority (88%) being located at three main sites: the external iliac, obturator, and bifurcation. Thirty-six patients (51%) had 2 SN identified, and 16 (24%) had 3 SN or more. Twelve (17%) patients had positive lymph nodes. In those cases, the rate of SN detection per side of dissection in patients with normal appearing nodes at laparoscopy was 75%, whereas it was only 56% in patients with macroscopically involved lymph nodes (P = NS). The false negative rate was 0. The negative predictive value of SN mapping was 100% and the sensitivity was 93% with the combined technique. Two patients had allergic reactions to the blue dye (3%). CONCLUSION: Sentinel node mapping with the combined blue dye technique and lymphoscintigraphy in patients with cervical cancer is laparoscopically feasible and is highly accurate. The detection rate improves significantly with experience and with the use of lymphoscintigraphy.
Antimony↗
Metastatic gastrointestinal tract cancer presenting as ovarian carcinoma.
OBJECTIVES: (1) To assess if there has been an increase of metastatic gastrointestinal (GI) cancers presenting as ovarian cancer; (2) to determine from which areas of the GI tract malignancies are most frequently associated with ovarian metastasis; (3) to determine if a higher proportion of premenopausal women present with an ovarian tumour of GI tract origin. METHODS: A retrospective chart review of women presenting to the Hôtel-Dieu de Québec Hospital from January 1993 to June 2002, searching for the diagnosis of ovarian metastasis of GI origin at the time of primary surgery. RESULTS: Colon cancer accounted for 65% of the malignancies found to have ovarian metastases at the time of primary surgery, with an increased percentage of cases in recent years. Metastatic GI cancer mimicking ovarian primary was equally as frequent in pre- and postmenopausal women. The use of the cancer antigen (CA) 125/carcinoembryologic antigen (CEA) ratio may help to discriminate GI carcinoma from ovarian carcinoma. CONCLUSION: Because GI tumours may present as advanced ovarian cancer, increased vigilance is required in order to make the right diagnosis and offer the best treatment.
CA-125 Antigen↗
A phase II trial of JM-216 in cervical cancer: an NCIC CTG study.
OBJECTIVE: BMS-182751 (JM-216) is an orally bioavailable platinum compound with activity in platinum-sensitive and platinum-resistant preclinical models. The objective was to determine its activity in recurrent/metastatic squamous cell carcinoma of the cervix. METHODS: We conducted a phase II study of BMS-182751 given at a dose of 30 mg/m(2) daily for 14 days every 5 weeks. RESULTS: Eighteen patients (pts) with advanced/recurrent squamous cancer of the cervix not amenable to curative therapy with measurable disease who had received no prior chemotherapy for systemic disease were entered, all of whom are evaluable for response and toxicity. Median age was 47 years (35-74 years); all pts had received prior pelvic irradiation (RT); 4 pts had received cisplatin as adjustment therapy with radiation; PS was 0 (6 pts), 1 (7 pts), and 2 (5 pts); sites of disease included nodes (10 pts), pelvis (5 pts), lung (4 pts), and bone (3 pts). Median number of cycles was two (1-6) with 8 pts receiving three or more cycles. Toxicity was modest and usually grade 1 or 2 in severity with the most frequent drug related toxicity being nausea (56%), fatigue (50%), anorexia (39%), diarrhea (39%), vomiting (39%), constipation (28%), and altered taste (22%). Six pts had grade 3 or 4 granulocytopenia and only 1 pt, grade 3 or 4 thrombocytopenia. Two pts had grade 2 or 3 creatinine increases. There were no treatment-related deaths. One pt with a treatment-free interval of 30 years achieved a partial response, while 12 pts had a best response of stable disease. CONCLUSIONS: BMS-182751 is generally well tolerated, but has limited activity in pts with recurrent cervical cancer.
Administration, Oral↗
New opportunities to preserve fertility in cancer treatment.
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Breast Neoplasms↗
Ovarian thecoma associated with a large quantity of ascites and elevated serum CA 125 and CA 15-3.
BACKGROUND: Elevation of tumour marker CA (cancer antigen) 125 associated with Meigs' or atypical Meigs' syndrome is widely recognized. Other tumour markers are available to assist in distinguishing between benign and malignant ovarian masses in the preoperative diagnosis. CASE PRESENTATION: A 57-year-old woman presented with a suspicious pelvic mass and abundant ascites. Preoperative tumour markers CA 125 and CA 15-3 were elevated at 1750 U/mL and 60 U/mL, respectively. The woman underwent surgery, and 9 L of straw-coloured ascites were drained along with a solid-cystic ovarian mass. The final pathology disclosed an ovarian thecoma. Six months later, both tumour markers were normal. CONCLUSION: This first report of 2 elevated tumour markers associated with atypical Meigs' syndrome cautions us not to rely on tumour markers to differentiate benign from malignant masses.
Ascites↗