Yi-Chun Lee

Is body mass index an independent risk factor of survival among patients with endometrial cancer

Objective:To evaluate whether body mass index (BMI) is an independent risk factor for survival in patients with endometrial adenocarcinoma. Methods:Women treated for endometrial cancer at the State University of New York (SUNY), Downstate and Kings County Hospital between January 1982 and September 2003 were eligible. Patients were divided into groups based upon their histology at the time of diagnosis. The first included patients with low-grade endometrioid adenocarcinoma (FIGO grades 1 and 2); the second included grade 3 endometrioid adenocarcinoma; and the third contained papillary serous and clear cell carcinomas. Data regarding BMI, patient age, race, grade, and stage of disease and overall survival, were assessed by survival analysis, with P < 0.05 considered significant throughout. Results:The analysis included 442 patients. Mean BMI was 32.6 ± 8.2. There were 312 patients (70%) treated for low-grade endometrial adenocarcinoma; 64 patients (14%) for grade 3 endometrioid adenocarcinoma; and 71 patients (16%) for papillary serous and clear cell adenocarcinoma. Increased BMI was associated with improved overall survival (P = 0.003). BMI was also correlated to tumor grade, stage at diagnosis, age, and race. Tumor grade, stage, age, and race were correlated to survival. Statistical analyses revealed the majority of the association between BMI and survival can be attributed to the association between BMI and these other risk factors for survival in endometrial cancer. Conclusions:Increased BMI is associated with survival advantage among patients with endometrial cancer. Because of the relationship between obesity and other confounding variables obesity alone is not an independent predictor of survival.

Angiogenesis in early-invasive and low-malignant-potential epithelial ovarian carcinoma.

Objective To evaluate angiogenesis in ovaries of women with stage I invasive and low-malignant-potential epithelial ovarian carcinoma. Methods Ovarian specimens of 49 consecutive women with primary stage I invasive (n = 15) or stage I low-malignant-potential epithelial ovarian carcinoma (n = 34) were stained immunohistochemically for factor VIII–related antigen. Microvessel counts were tested for correlation with patient age, race, parity, previous oral contraceptive use, histologic type, tumor grade, tumor size, ascites, tumor excrescences, and disease-free and overall survival. Statistical analysis included multiple linear regression, Student t tests, factorial analysis of variance, and Cox proportional hazards regression, with P < .05 considered statistically significant. Results Microvessel counts of ovarian specimens of women with stage I invasive epithelial ovarian carcinoma (median 30, range 17–73) were significantly higher than those of women with stage I low-malignant-potential epithelial ovarian carcinoma (median 10, range 5–23), (P < .001). Among women with low-malignant-potential disease, microvessel counts did not differ significantly between serous and mucinous carcinomas (median 10, range 5–23 versus median 11, range 5–20, respectively, P = .78). There was no correlation between microvessel counts and age, tumor grade, tumor size, ascites, or tumor excrescences. Conclusion Angiogenesis as assessed by microvessel counts is more intense in stage I invasive ovarian epithelial carcinoma compared with stage I low-malignant-potential carcinoma, and might assist in differentiating between these histopathologic entities.

Surgical resection of vulvar metastases of endometrial cancer: a presentation of two cases.

Objective. Endometrial cancer generally carries a good prognosis. However, 10% to 15% of patients will manifest recurrent disease. One half of these recurrences are confined to the vagina. Whereas pelvic recurrence is most common in patients who do not receive postoperative adjuvant radiation therapy, distant metastases predominate among patients who received postoperative radiation therapy. Surgical resection of disease may be possible, therapeutic and even curative, in select patients with isolated cancer recurrence. Case 1. A 63-year-old patient presented 7 years after treatment of endometrial cancer with a vulvar lesion and groin mass. The lesions were successfully resected and confirmed to be recurrent endometrial cancer. Adjuvant radiation and chemotherapy were prescribed leading to a complete clinical response. This patient survived without evidence of disease for 1 year. However, she eventually died 8 months later because of a disease recurrence. Case 2. An 83-year-old patient with a history of a hysterectomy for endometrial cancer and radiation therapy for a vaginal vault recurrence presented with an exophytic labial mass. After radical wide excision of her vulvar mass and bilateral groin dissection, final pathology revealed that the mass was consistent with recurrent endometrial cancer. This patient remains without evidence of disease 18 months after treatment of disease recurrence. Conclusions. Uncommon sites of recurrence of endometrial cancer may include the vulva. These rare metastases may be amenable to surgical resection with adjuvant therapy as indicated.

Sulfatase Activity in Normal and Neoplastic Endometrium

Background: Dehydroepiandrosterone sulfate (DHEAS) is metabolized to active androgens and estrogens, which may have a role in the development of endometrial cancer. Methods: We studied DHEAS conversion to dehydroepiandrosterone (DHEA) in normal and neoplastic endometrium utilizing gas chromatography-mass spectral (GC-MS) analysis. Endometrial homogenate was incubated with known amounts of DHEAS for 4 h at 37°C. Methanol extract was separated from debris by centrifugation, concentrated to 200 μl and 1 μl injected into the GC-MS instrument, equipped with a CP-Sil 8 column. DHEAS and DHEA areas were calculated by autoquantization and DHEA/DHEAS ratio was used for comparing sulfatase activity among normal endometrium (n = 6), Stage I endometrioid carcinoma (EC) (n = 15), Stage I mixed mesodermal Müllerian tumor (MMMT) (n = 6) and Stage I uterine papillary serous carcinoma (UPSC) (n = 7). Results: DHEA/DHEAS ratios in normal endometrium, EC, MMMT and UPSC were 1.45 ± 1.10, 5.63 ± 3.27, 2.88 ± 0.99, and 3.04 ± 1.76, respectively. Sulfatase activity was significantly higher in EC when compared with normal endometrium (p < 0.001), MMMT (p < 0.05), and UPSC (p < 0.05). The enzyme activity did not differ significantly between low-grade and high-grade EC tumors (5.8 ± 2.77 and 5.49 ± 3.84, respectively, p > 0.05). Conclusion: Stage I EC have higher sulfatase activity than normal endometrium, and Stage I MMMT and UPSC tumors.

Effect of Gonadotropin-Releasing Hormone Agonist Treatment upon Angiogenesis in Uterine Leiomyoma

Objective: To assess the effect of gonadotropin-releasing hormone (GnRH) agonist treatment upon angiogenesis in uterine leiomyomata. Methods: Uterine leiomyomata specimens of 49 consecutive patients who underwent myomectomy or hysterectomy following presurgical treatment with (n = 23) and without (n = 26) GnRH agonist were stained immunohistochemically with antibody to factor VIII-related antigen. For each subject, age, parity, number of Lupron treatments, leiomyoma size (cm), and mean microvessel counts calculated from three fields (×400) were recorded. Differences in patient age, parity, microvessel counts and leiomyoma size between GnRH agonist treated and untreated patients were tested by unpaired Student’s t test. Differences among the various number of doses were tested by one-way ANOVA, with Bonferonni and Neuman-Keuls post hoc tests between specific dose-number groups. The relationship between microvessel counts and leiomyoma size was tested by Pearson correlation test. Multivariate stepwise regression tested the relationship between the number of Lupron doses and microvessel counts, correcting for age, parity, and leiomyoma size. p < 0.05 was considered significant. Results: Patient age and parity were similar in GnRH treated and untreated patients (mean 43.3 ± 6.6 versus 43.9 ± 7.5 years and median 2 (range 0–7) versus 1 (range 0–5), p = 0.78 and p = 0.45, respectively). Microvessel counts of leiomyomata specimens treated presurgically with GnRH agonist therapy (median 22.7, range 6.7–65.7) were not significantly different from microvessel counts of specimens without presurgical GnRH agonist treatment (median 19.8, range 6–53; p = 0.77). No correlation between leiomyoma size and microvessel counts was noted (r = 0.06, P = 0.7). Conclusion: Angiogenesis as assessed by microvessel counts in surgically removed leiomyomata is not affected by presurgical medical management with GnRH agonist therapy.

Hydronephrosis as a prognostic indicator of survival in advanced cervix cancer.

Objective: To determine whether hydronephrosis is an independent prognostic indicator of survival among patients with advanced cervical carcinoma. Moreover, we wanted to demonstrate the relationship between unilateral and bilateral hydronephrosis and overall survival. Methods: Retrospective analysis of 197 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical carcinoma or higher treated between 1990 and 2007 was conducted. Inclusion criteria were clinical staging according to FIGO criteria, standardized radiation treatment and cisplatin-based chemosensitization regimens. Associations between hydronephrosis and covariates-age, race, histopathologic diagnosis, pelvic sidewall involvement, stage, nodal involvement, and Gynecologic Oncology Group/Eastern Cooperative Oncology Group performance status (PS)-were determined. Statistical analysis including Kaplan-Meier, log-rank test, proportional hazards regression, Fisher exact test, and Mann-Whitney test were used where appropriate, with P < 0.05 considered significant. Results: Of 143 included patients, 73 patients had no hydronephrosis (HN), 39 patients had unilateral HN, and 31 patients had bilateral HN. Twenty-nine patients (40%) with no HN died compared to 24 patients (61.5%) with unilateral HN and 21 patients (67.7%) with bilateral HN. Median time to death was significantly shorter for patients with unilateral HN (27 months; 95% confidence interval [CI], 10-48) and bilateral HN (12 months; 95% CI, 6-23) versus patients without HN (68 months; 95% CI, 39-∞; P < 0.001). Unadjusted hazard ratio (HR) for HN (both unilateral and bilateral) was 2.4 (95% CI, 1.5-3.8); P < 0.001. Of potential covariates evaluated, PS and sidewall involvement were significantly associated with HN (P = 0.021 and P = 0.014, respectively). Proportional hazards regression revealed that controlling for use of radiation, chemotherapy, and for PS, HN was still significantly associated with poor prognosis (HR unilateral HN = 2.0, 95% CI, 1.2-3.5; HR bilateral HN = 3.2, 95% CI, 1.7-6.0); P ≤ 0.001. Conclusion: Hydronephrosis is an independent poor prognostic indicator of survival in patients with advanced cervical cancer. Bilateral hydronephrosis compared to unilateral involvement confers a worse overall prognosis. Additional studies are needed to determine if FIGO staging should be amended.

Sonographic and Magnetic Resonance Imaging Findings of an Isolated Vaginal Leiomyoma

Leiomyomas represent the most common uterine neoplasms, noted clinically in 20% to 30% of all women older than 30 years, and are found in 75% of hysterectomy specimens. 1 Although rare, the most common mesenchymal neoplasm of the vagina is the leiomyoma. 2 The mean patient age at detection of a vaginal leiomyoma, is approximately 40 years, with a reported range between 19 and 72 years. 2 Vaginal leiomyomas vary from 0.5 to 15 cm in diameter, averaging approximately 3 cm in size, and may occur anywhere within the vagina, usually in a submucosal location. Although these rare lesions are often asymptomatic, larger tumors may be associated with pain, dystocia, dyspareunia, or obstructive urinary symptoms. We report the sonographic and magnetic resonance imaging (MRI) findings of a patient with an isolated vaginal wall leiomyoma.

Type 2 11β-hydroxysteroid dehydrogenase activity in human ovarian cancer

Abstract In the ovary cortisol-cortisone inter-conversion is catalyzed by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD). Its role in carcinomas of human ovary is unknown. The majority of ovarian cancers are derived from ovarian surface epithelium and the inflammation caused by successive ovulation seems to a play a role in the development of cancer. Cortisol is known to act as anti-inflammatory agent and its metabolism by type 1 and type 11β-HSD may control the inflammatory action by cortisol in ovary. We undertook this study to investigate type 2 11β-HSD activity which functions exclusively oxidative direction, in normal ovarian tissue compared to ovarian epithelial cancer. Ovarian tissue was obtained from patients undergoing hysterectomy for both benign and malignant disease. Tissue was placed immediately on dry ice and subsequently transferred to a freezer where they were maintained at −70xa0°C. NAD dependent 11β-HSD activity was then determined in this tissue. T-test was performed to determine statistical significance. Mean type 2 enzyme activity was 0.87xa0±xa01.65xa0pmol/minxa0g tissue in normal ovarian tissue versus a mean enzyme activity of 2.96xa0±xa01.37xa0pmol/mimxa0g tissue in from cancer specimens. This difference was statistically significant with a p-value of 0.03. Type 2 1β-HSD activity in ovarian cancer specimens was significantly higher than enzyme activity measured in normal post-menopausal ovarian tissue. Decreased cortisol levels due type 2 1β-HSD activity may play a role neoplastic transformation as well as tumor proliferation in ovarian cancer by eliminating anti-inflammatory action of cortisol.

Color Doppler Imaging and 3-Dimensional Sonographic Findings of Urinary Bladder Leiomyoma

Leiomyomas of the genitourinary tract may originate from the renal pelvis, bladder, urethra, or epididymis. 1 Interestingly, leiomyomas of the bladder are more common among women (76% of cases).2 Development is usually endovesical (63%), yet extravesical (30%) and intramural cases are not rare.3 Patients may be asymptomatic or may have obstructive urinary symptoms, irritative symptoms, hematuria, flank pain, or, rarely, dysmenorrhea or dyspareunia. 2-5 Leiomyomas of the bladder have been reported in association with neurofibromatosis type 1, in which leiomyomas occur most often in the gastrointestinal tract (proximal small bowel) and tend to be multiple.6 Rarely, urinary bladder leiomyomas have been diagnosed during pregnancy 7,8 and in a woman with a previous hysterectomy. 9 Diagnostic imaging modalities used include both transabdominal and transvaginal sonography, computed tomography, and magnetic resonance imaging.10-12 Although asymptomatic, nonobstructive, and nonproblematic leiomyomas may be managed expectantly, treatment is surgical by a transurethral approach, laparoscopy, or laparotomy 1-4 We present color Doppler imaging and 3-dimensional sonographic findings of a woman with a urinary bladder leiomyoma.

NAD Dependent 11β-Hydroxysteroid Dehydrogenase Activity in Human Endometrium and Endometrial Tumors

Background: The isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2, regulated by ovarian steroids, catalyze the interconversion of glucocorticoids and their 11-keto metabolites. The role of these enzymes in malignancies of human endometrium is unknown. We compare NAD dependent 11β-HSD (type 2) activity levels among normal human endometrium and endometrial carcinomas of differing grades and histologies. Methods: NAD dependent 11β-HSD activity was determined in endometrial tissue obtained from patients undergoing hysterectomy for benign or malignant disease (endometroid, serous and carcinosarcomas). Student’s t test was utilized with p < 0.05 considered significant. Data are presented as mean ± SD. Results: NAD dependent 11β-HSD activity was present in all endometrial samples. The activities were 0.61± 0.27 in normal (n = 9), 0.43 ± 0.29 in endometrioid endometrial carcinoma (n = 14), 0.50 ± 0.26 in uterine serous carcinoma (n = 6) and 0.25 ± 0.37 in carcinosarcomas (n = 9). NAD dependent 11β-HSD activity was lower in the carcinosarcoma group as compared to normal endometrial tissue (p = 0.03). Conclusions: NAD dependent type 2 11β-HSD activity was demonstrated in all normal and endometrial tumors. Enzyme activity in endometroid and uterine serious carcinoma tumors was similar to enzyme activity in normal endometrium. In contrast, carcinosarcomas show significantly lower enzyme activity compared to normal tissue.