Scott Kamelle

Diagnostic accuracy of ultrasound above and below the beta-hCG discriminatory zone

OBJECTIVE To evaluate clinical use and accuracy of transvaginal ultrasound for diagnosing intrauterine pregnancies, spontaneous miscarriages, and ectopic pregnancies in women who present with beta-hCG concentrations above or below an established discriminatory zone. METHODS Ultrasound diagnosis at presentation was compared with final clinical diagnosis in 333 consecutive pregnant women who presented to an emergency department with vaginal bleeding or abdominal pain. The sensitivity, specificity, predictive value, and overall diagnostic accuracy of ultrasound were calculated. RESULTS Transvaginal ultrasound was nondiagnostic in 59 (17.7%) of 333 subjects and 43 (67.2%) of 64 subjects with beta-hCG levels below 1500 mIU/mL at presentation. Preliminary ultrasound diagnoses were reported significantly more frequently when presenting beta-hCG levels were above 1500 mIU/mL (253 [94.1%] of 269 subjects) compared with levels below 1500 mIU/mL (21 [32.8%] of 64 subjects: P < .001; relative risk (RR) 3.4 [95% confidence interval (CI) 2.23, 5.18]). The proportion of accurate preliminary ultrasound diagnoses was significantly higher in subjects who presented with beta-hCG levels above 1500 mIU/mL (227 [91.5%] of 248 subjects) compared with levels below 1500 mIU/mL (18 [28.6%] of 63 subjects: P < .001; RR 2.9 [95% CI 2.04, 4.15]). Sensitivity of transvaginal ultrasound diagnosis of intrauterine pregnancy, spontaneous miscarriage, and ectopic pregnancy in women who presented with beta-hCG levels below 1500 mIU/mL was 33.3%, 28.2%, and 25.0%, respectively. CONCLUSION The sensitivity, predictive value, and accuracy of transvaginal ultrasound for diagnosing complications of early pregnancy were poor when beta-hCG levels were below the discriminatory zone at presentation. Ultrasound impressions should be correlated with beta-hCG concentrations.

Impact of individual physicians on enrollment of patients into clinical trials.

&NA; The National Cancer Institute is committed to increasing enrollment of cancer patients in clinical treatment trials. The factors that achieve successful results are poorly understood. This study analyzes the role of individual physicians in recruitment of patients in clinical trials. A retrospective review was undertaken of all patients with untreated endometrial, cervical, or ovarian cancer potentially eligible for a multi‐institutional phase III trial cared for by the Section of Gynecologic Oncology at the University of Oklahoma from July 1, 1998 to September 30, 1999. Patient variables assessed included age, insurance status, cancer diagnosis, and enrollment onto clinical trial. There was no difference in faculty patients with regard to cancer type, age, or insurance status. There was a significant difference (p < 0.01) between faculty in offering protocol therapy and likelihood of successfully enrolling patients. Successful enrollment was correlated with faculty experience and principal investigator status. This study shows that availability of patients, patient variances, support staff, and institutional commitment are secondary to individual physician factors in determining successful enrollment of patients onto clinical trials.

Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists

The anti-cancer activities and toxicities of retinoic acid (RA) and synthetic retinoids are mediated through nuclear RA receptors (RARs) and retinoid X receptors (RXRs) that act as transcription factors. Heteroarotinoids (Hets), which contain a heteroatom in the cyclic ring of an arotinoid structure, exhibit similar anti-cancer activities, but reduced toxicity in vivo, in comparison to parent retinoids and RA. A new class of Flexible Hets (Flex-Hets), which contain 3-atom urea or thiourea linkers, regulate growth and differentiation similar to RA, but do not activate RARs or RXRs. In addition, Flex-Hets induce potent apoptosis in ovarian cancer and in head and neck cancer cell lines through the intrinsic mitochondrial pathway. In this study, 4 cervical cancer cell lines were growth inhibited by micromolar concentrations of Flex-Hets to greater extents than RAR/RXR active retinoids. The most potent Flex-Het (SHetA2) inhibited each cell line of the National Cancer Institute’s human tumor cell line panel at micromolar concentrations. Oral administration of Flex-Hets (SHetA2 and SHetA4) inhibited growth of OVCAR-3 ovarian cancer xenografts to similar extents as administration of a RAR/RXR-panagonist (SHet50) and Fenretinide (4-HPR) in vivo. None of these compounds induced evidence of skin, bone or liver toxicity, or increased levels of serum alanine aminotransferase (ALT) in the treated mice. Topical application of Flex-Hets did not induce skin irritation in vivo, whereas a RAR/RXR-panagonist (NHet17) and a RARγ-selective agonist (SHet65) induced similar irritancy as RA. In conclusion, Flex-Hets exhibit improved therapeutic ratios for multiple cancer types over RAR and/or RXR agonists.

Retinoids and steroids regulate menstrual phase histological features in human endometrial organotypic cultures.

OBJECTIVE To determine whether organotypic cultures of human endometrium can be manipulated with hormones to exhibit histological features resembling different menstrual cycle phases. DESIGN Human menstrual cells were collected and cultured in monolayer and organotypic cultures. SETTING Healthy volunteer in an academic research environment. PATIENT(S) An individual premenopausal woman. INTERVENTION(S) Endometrial cultures were grown in collagen gels for 4 weeks, and exposed to various steroid and retinoid treatments. MAIN OUTCOME MEASURE(S) Histological features and expression of cytokeratins, vimentin, and reticulin. RESULT(S) Cultures developed multiple glands and surface epithelium that exhibited positive cytokeratin and negative vimentin staining. Single stromal cells inside the collagen exhibited negative cytokeratin and positive vimentin staining. Networks of reticulin fibers produced by the cells were increased by estrogen, decreased by progesterone, and unaffected by retinoids. Contraction of the collagen gels was inhibited by retinoids that activated retinoic acid receptors (RARs), but not by a retinoid specific for retinoid X receptors (RXRs). The combination and timing of retinoid and steroid hormone treatments were demonstrated to induce tissue architecture and histological features that resembled either proliferative or secretory phases. CONCLUSION(S) Growth of menstrual cells in collagen can be manipulated with retinoids and steroids to resemble histological features of the proliferative and secretory phases.

Panniculectomy with simultaneous gynecologic oncology surgery

From July 1996 to May 2000, obese patients scheduled to undergo gynecologic oncologic procedures at Froiedtert Memorial Hospital or Waukesha Memorial Hospital in Milwaukee, Wisconsin, were offered a panniculectomy when warranted. To evaluate the benefits and risks associated with this procedure, the authors conducted a retrospective study of the 41 patients who underwent paniculectomy. The average age of the women was 55 years. Their average weight was 126 kg (range, 80-196) with a mean body mass index (BMI) of 48 kg/m2.-Three-fourths of the patients had class III obesity (N = 30). Seventy-eight percent were hypertensive, and 29% had diabetes. Prior abdominal surgery had been performed in 63%. Early postoperative complications included fever of unknown etiology (N = 6; 15%) and oliguric acute renal failure that improved by the time of discharge (N = 2). One woman developed deep venous thrombosis, which was successfully treated with low-molecular-weight heparin. Two patients had wound infections while in the hospital. One was a cellulitis, and the other was a drain site infection. In addition, three women developed wound infections later in the postoperative period, including two cases of cellulitis and one seroma. Two patients died of complications related tosurgery. One woman with a BMI of 44.3 kg/m2 had a suspected myocardial infarction while undergoing a total abdominal hysterectomy with pelvic lymphadenectomy. She died on the third postoperative day. A second patient underwent total abdominal hysterectomy with pelvic and para-aortic lymph node dissection. She experienced no problems postoperatively but had a massive pulmonary embolism just as she was leaving the hospital on postoperative day 5. She died after 3 days in the intensive care unit. A univariate analysis of possible risk factors for complications found that diabetes was significantly associated with early postoperative complications (P = .05). Increasing patient age led to a significantly greater risk for late postoperative complications (P = .05), and a higher BMI increased the risk of wound infection (P = .06).

Reticulin expression demonstrates hormonal responsiveness in a model of cycling human endometrium

Objective: To demonstrate hormonal responsiveness of our tridimensional model of cycling human endometrium by staining for reticulin in the extracellular matrix. Methods: Cultures of exuded human menstrual cells were grown inside and on top of collagen I gels. The media surrounding the gels were supplemented with physiologically relevant concentrations of steroid hormones and retinoids in various doses and combinations. Results: Networks of reticulin fibers are built up by proliferative-phase estrogen and then broken down during the secretory phase as progesterone concentrations rise. The collagen gels curled into structures containing lumens lined with epithelial layers surrounded by single stromal cells, multiple glands, and networks of reticulin fibers. The networks of reticulin fibers expressed in the cultures were increased by estradiol (E2), and decreased by progesterone. Conclusions: Expression of reticulin fibers in our organotypic resembles the changing patterns that occur during the menstrual cycle. This model has considerable potential to be further modulated by hormones, retinoids, and carcinogens to resemble hyperplasia, cancer, endometriosis, and pregnancy, thus offering service to all fields of obstetrics and gynecology.

Adenoca of the uterus with cervical extension and adenoca of the cervix: are the clinical presentations truly different?

Abstract Objective: To identify the preoperative differences between patients with stage 2 endometrial cancer and with adenoca of the cervix. Methods: Seventy-four records were reviewed, and the following data were abstracted: abnormal Pap smear (APAP); abnormal bleeding, dysfunctional and postmenopausal (VAGBLD); postcoital bleeding (PCB); pelvic pain (PAIN); and dyspareunia (DYSP). Student t , χ 2 , and Cox proportional hazard tests were utilized. Results: There were 40 cervical cancers (54%) and 34 endometrial cancers (46%). Preoperatively, 23 patients (31%) had questionable cancer origin. Patients with cervical cancer were younger (50 versus 58, P = 0.05) and weighed less (162 versus 185, P = 0.08). Patients with cervical adenoca were more likely to present with APAP ( P = 0.02; RR 3.7, CI: 1.2–11.5), PCB ( P = 0.03; RR 8.0, CI: 1.1–7.1), and a smoking history ( P = 0.04; RR 2.9, CI: 1.0–8.5). Patients with uterine cancer had pelvic pain ( P = 0.04; RR 3.4, CI: 1.0–11.6). There were no significant differences in incidences of VAGBLD, DYSP, gravidity, or age at menarche. Predictors for cervical cancer APAP, PCB, age, and smoking remained significant upon multivariate analysis, as did the predictors PAIN ( P = 0.007) and age ( P = 0.05) for uterine cancer. Conclusion: Patients with cervical cancer were more likely to be younger, weigh less, and present with APAP and PCB, whereas uterine cancer patients were more apt to present with pelvic pain.

Hormone replacement practice patterns among Oklahoma physicians

Abstract Objective: To determine hormone replacement (HRT) patterns among ob-gyns (OBs), family practitioners (FPs), and internists (IMs). Methods: Anonymous written surveys were sent to OBs, FPs, and IMs within the state of Oklahoma. Practice patterns were compared using X 2 tests. A P value of 0.05 was considered significant. Results: Five hundred twenty-five of 1,341 surveys were returned, and 42.1% of OBs, 25.2% of FPs, and 16.3% of IMs stated that they prescribe HRT to 90% of their postmenopausal patients (OBs versus FPs P = 9×10 -4 ; OBs versus IMs P = 1×10 -6 ). Urban physicians prescribed HRT to > 90% of their postmenopausal patients (urban 38.8%, rural 19.9%, P = 5×10 -4 ). A trend towards increased HRT prescribing was seen for physicians in practice 5 years or less compared with those in practice longer ( P = 0.06). Multiple logistics regression found specialty ( P = 0.02), urban practice ( P = 0.01), and years in practice ( P = 0.05) as independent predictors for prescribing HRT to 91–100% of postmenopausal patients. Unopposed estrogen was the favored HRT for all specialties in postmenopausal women with prior hysterectomies. Women with a history of endometriosis who received a hysterectomy were more likely to receive unopposed estrogen for HRT if they were postmenopausal (77.6%) than if they were premenopausal (68.4%). Finally, differences were seen between specialties in requiring a mammogram before starting HRT (OBs 66.9%; FPs 84.7%; IMs 91.7%; OBs versus FPs P = 1×10 -4 ; OBs versus IMs P = 3×10 -7 ; FPs versus IMs ( P = 0.05). Conclusions: Significant differences exist between the practice patterns of OBs, FPs, and IMs. This indicates a need for OBs to promote the benefits of HRT to physicians who are not ob-gyns.