Clinical experience with epoetin alfa in the management of hemoglobin levels in orthopedic surgery and cancer. Implications for use in gynecologic surgery.

Recombinant human erythropoietin (r-HuEPO, epoetin alfa) is used for treatment of anemia associated with chemotherapy for non-myeloid malignancies, chronic renal failure and zidovudine treatment in patients infected with the human immunodeficiency virus and for anemic patients undergoing elective, noncardiac, nonvascular surgery. Epoetin alfa has been shown to safely increase preoperative hemoglobin (Hb) levels in anemic patients undergoing elective noncardiac, nonvascular surgery and is more effective than preoperative autologous blood donation in reducing the need for perioperative blood transfusions in orthopedic surgery patients. Epoetin alfa was shown to significantly increase Hb levels and decrease transfusion requirements in gynecologic cancer patients undergoing chemotherapy. A once-weekly regimen of 40,000 IU per dose was effective in these patients. In addition to decreasing transfusion requirements and increasing Hb, epoetin alfa for relieving anemia-related fatigue and improving quality of life was demonstrated in clinical trials in anemic cancer patients receiving chemotherapy. With regard to quality of life in orthopedic surgery patients, a novel instrument to measure the effect of Hb management on postoperative recuperative power (i.e., vigor, functional ability) has been validated and may prove to be useful in optimizing rehabilitation and discharge planning. Extensive clinical experience with epoetin alfa in anemic patients undergoing major elective orthopedic surgery or those with gynecologic cancer provides a strong basis for its use in gynecologic surgery.

Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies.

BACKGROUND: The use of methotrexate for the treatment of women with tubal ectopic pregnancies is now common practice. However, the clinical and hormonal determinants of the success of this treatment are not known. METHODS: We studied 350 women with tubal ectopic pregnancies who were treated with methotrexate intramuscularly according to a single-dose protocol. Pretreatment serum concentrations of human chorionic gonadotropin and progesterone, the size and volume of the gestational mass, fetal cardiac activity, and the presence of fluid (presumably blood) in the peritoneal cavity were correlated with the efficacy of therapy, as defined by resolution of the ectopic pregnancy without the need for surgical intervention. RESULTS: There was no relation between the women's age or parity, the size or volume of the conceptus, or the presence of fluid in the peritoneal cavity and the efficacy of treatment. Among the 320 women in whom treatment was successful (91 percent), the mean (+/-SD) serum chorionic gonadotropin and progesterone concentrations were 4019+/-6362 mIU per milliliter and 6.9+/-6.7 ng per milliliter (21.9+/-21.3 nmol per liter), respectively, as compared with 13,420+/-16,590 mIU per milliliter and 10.2+/-5.5 ng per milliliter (32.4+/-17.5 nmol per liter) (P<0.001 and P=0.02) in the 30 women in whom treatment was not successful. Fetal cardiac activity was present in 12 percent of the successfully treated cases and 30 percent of those in which treatment was not successful (P=0.01). Regression analysis revealed the pretreatment serum chorionic gonadotropin concentration to be the only factor that contributed to the failure rate. CONCLUSIONS: Among women with tubal ectopic pregnancies, a high serum chorionic gonadotropin concentration is the most important factor associated with failure of treatment with a single-dose methotrexate protocol.

Practice management in obstetrics and gynecology residency curriculum.

OBJECTIVE: To establish the current level of instruction in practice management in obstetrics and gynecology residency programs; review recommendations of medical school practice management executives and current and former residents on design of practice management instruction programs; and develop recommendations for future management instruction by residency programs in obstetrics and gynecology. METHODS: A questionnaire was sent to 101 practice plan executives of obstetrics and gynecology departments at medical schools in the United States and Canada. A modified version was sent to 44 current obstetrics and gynecology residents and 72 former residents from the University of Tennessee, Memphis. RESULTS: The response rates were 71% (practice executives), 93% (current residents), and 81% (former residents). There were no formal management programs at 87% of responding institutions, although most respondents (62%) thought there should be mandatory participation in management programs, probably given by organizations outside the university. Potential subjects that received high ratings were current procedural terminology and diagnosis coding, managed care, billing procedures, contractual agreements between medical doctors, patient record management, and practice economics. CONCLUSION: Residency programs should establish formal practice management instruction programs and make participation mandatory. Funding should come from the medical school and university. Instructional help should come from extradepartmental organizations and individuals.

A multicenter randomized comparison of laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy in abdominal hysterectomy candidates.

OBJECTIVE: To compare intraoperative and postoperative outcomes between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy among patients who are not eligible for vaginal hysterectomy. METHODS: Study subjects were randomly assigned to undergo laparoscopically assisted vaginal hysterectomy or standard abdominal hysterectomy. Intraoperative and postoperative management was similar for each group. Surgical characteristics, complications, length of hospital stay, charges, and convalescence were analyzed. RESULTS: Sixty-five women at three institutions underwent laparoscopically assisted vaginal hysterectomy (n = 34) or abdominal hysterectomy (n = 31). Three patients in the laparoscopic group required conversion to abdominal hysterectomy. Mean operating time was significantly longer for laparoscopically assisted vaginal hysterectomy (179.8 versus 146.0 minutes). There were no differences in blood loss or incidence of intraoperative complications. There was a higher incidence of wound complications in the abdominal hysterectomy group, but no significant difference in the frequency of postoperative complications. Laparoscopically assisted vaginal hysterectomy required a significantly shorter mean hospital stay (2.1 days) and convalescence (28.0 days) than abdominal hysterectomy (4.1 days and 38.0 days, respectively). There were no significant differences in mean hospital charges between the study groups (laparoscopic $8161, abdominal $6974). CONCLUSION: Except for operating time, there are no differences between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy regarding intraoperative characteristics among abdominal hysterectomy candidates. Postoperatively, laparoscopically assisted vaginal hysterectomy requires a shorter hospital stay and convalescence. Hospital charges are similar between the procedures. A larger number of cases will help determine the indications for laparoscopically assisted vaginal hysterectomy.

Chlamydia in pregnancy: a randomized trial of azithromycin and erythromycin.

OBJECTIVE: To determine side effect profiles and cure rates of azithromycin compared with erythromycin in the treatment of chlamydial cervicitis complicating pregnancy. METHODS: Pregnant patients with positive DNA antigen assays for Chlamydia trachomatis were randomized to either azithromycin, 1 g oral slurry in a single dose, or erythromycin, 500 mg every 6 hours for 7 days. Repeat assays were planned for 3 weeks after therapy. Side effects, compliance, and treatment efficacy were assessed. RESULTS: One hundred six women were enrolled, and eighty-five women completed the protocol. Significantly fewer gastrointestinal side effects were noted in the azithromycin group than in the erythromycin group (11.9% versus 58.1%, P < or = .01). Enhanced compliance was noted with azithromycin, because it was given in a single observed dose. Similar treatment efficacy was noted between azithromycin and erythromycin (88.1% versus 93.0%, P > .05). CONCLUSION: Compared with erythromycin, azithromycin is associated with significantly fewer gastrointestinal side effects in pregnancy. This association, along with the ease of administration and similar efficacy, suggests that azithromycin should be considered for the initial treatment of chlamydial cervicitis in pregnancy.

Single serum progesterone as a screen for ectopic pregnancy: exchanging specificity and sensitivity to obtain optimal test performance.

OBJECTIVE: To investigate the diagnostic accuracy of screening serum P in diagnosis of ectopic pregnancy (EP) and to identify a cutoff value that provides the best compromise between test sensitivity and specificity. DESIGN: Retrospective analysis. SETTING: University hospital. INTERVENTIONS: Observation only. PATIENTS: First trimester pregnant women at risk for EP. MAIN OUTCOME MEASURE: Single P measurements were obtained from 3,674 pregnancies with outcomes defined as EP, viable intrauterine pregnancy (IUP), and spontaneous abortion (SAB). Diagnostic accuracy of the test was analyzed by generating receiver operating characteristic (ROC) curves, which quantify the ability of the test to distinguish EP and SAB from IUP. RESULTS: Diagnostic accuracy for EP versus IUP was 88.7% +/- 0.1% (mean +/- SEM); for SAB versus IUP, 93.8% +/- 0.4%; and for SAB + EP versus IUP, 92.8% +/- 0.4%. Diagnostic accuracy for SAB versus EP was only 39.4% +/- 0.2%. In the interval of 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L), P missed 5.3% of the EPs and incorrectly included 84.3% of the viable IUPs; in the interval of 20.0 to 24.9 ng/mL (63.6 to 79.2 nmol/L), sensitivity improved in that only 3.5% of the EPs were missed but 88.8% of viable IUPs were included incorrectly. A cutoff value of > or = 17.5 ng/mL (55.7 nmol/L), the median point of the 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L) interval, missed only 35 of 423 (8.3%) total EPs in the study. CONCLUSION: Analysis of ROC curves demonstrates that single serum P has high diagnostic accuracy for differentiating accidents of pregnancy (SAB and EP) from viable IUP, both individually (SAB versus IUP and EP versus IUP) and collectively (SAB + EP versus IUP); it cannot efficiently discriminate SAB versus EP. We conclude that for P > or = 17.5 ng/mL (55.7 nmol/L), patients thought to be at risk for EP may be followed reasonably without ultrasound or further invasive diagnostic studies.

Peritoneal closure at vaginal hysterectomy: a reassessment.

OBJECTIVE: To evaluate the clinical outcome of patients who underwent vaginal hysterectomy with or without peritoneal closure. METHODS: This study was a randomized trial. Using computer-generated numbers, all patients undergoing vaginal hysterectomy without oophorectomy were randomized to either no peritoneal closure (n = 57) or routine peritoneal closure (n = 49). Patients were followed-up for a minimum of 1 year for development of complications and postoperative dyspareunia. At 4-6 postoperative weeks, the distance between the ovaries and the vaginal cuff was measured by ultrasound. RESULTS: Postoperative complications were similar in both groups. The incidence of deep-thrust dyspareunia at 6 and 12 months was also similar. No statistical differences between the two groups were noted in the ovary to vaginal cuff distances either overall or when patients with dyspareunia were considered separately. CONCLUSION: The data in this study do not support the use of reperitonealization on a routine basis. However, because of a lack of statistical power, larger studies will be required to confirm this theory.

Methods of and attitudes toward screening obstetrics and gynecology patients for domestic violence.

OBJECTIVE: Our purpose was to define screening behaviors of obstetrician-gynecologists and barriers to screening their patients for domestic violence. STUDY DESIGN: A questionnaire was developed to collect information on current practices and attitudes regarding screening for domestic violence. A randomly selected sample of obstetrician-gynecologists was surveyed. Respondents were also asked to rank a series of 19 potential barriers that may affect screening. RESULTS: Of 6568 physicians sampled, 962 (14.6%) returned questionnaires. Of the respondents, 77.6% were male and 22.4% were female. Male physicians were less likely to screen for domestic violence (25.9% vs. 18.9%). Thirty-four percent said that they had no training in abuse. Physicians indicating they had received training in abuse were more likely to screen for domestic violence. The lack of education was identified as the most common barrier physicians have to screening. The feeling that abuse was not a problem in their patients (46%), lack of time to deal with abuse (39.2%), and frustration that the physician cannot help the victim (34.2%) were other common barriers. CONCLUSION: The majority of obstetrician-gynecologists do not screen their patients for current or past domestic violence. If universal screening is to become a reality, educational tools and training materials are needed to overcome physician barriers.

GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group.

OBJECTIVE: To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas. METHODS: This was a phase III, stratified, randomized, double-blind, placebo-controlled, parallel-group, 12-week multicenter study. Enrolled patients had hemoglobin levels of 10.2 g/dL or less and/or hematocrit values of 30% or less. Patients were entered into one of two strata based on their pre-study hematocrit level: stratum A, hematocrit less than or equal to 28%, and stratum B, hematocrit greater than 28%. Patients within each stratum were randomized to one of three treatment arms: leuprolide acetate depot 7.5 mg, leuprolide acetate depot 3.75 mg, or placebo. All patients received iron orally. Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36% or greater. RESULTS: Three hundred nine patients were entered into the study, of whom 265 were evaluated. Using our response criteria, a significantly greater number of patients in both leuprolide acetate groups (combined strata) responded to therapy than did those in the placebo group: 74% in each leuprolide acetate group versus 46% in the placebo group (P < .001). Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group (P < .01). Hot flashes and vaginitis were reported significantly more often (P < .001) in the leuprolide acetate-treated groups than in the placebo group. CONCLUSION: Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas, in reducing uterine-myoma volume, and in alleviating bleeding and other leiomyoma-related symptoms.

Medical management should be routinely used as primary therapy for ectopic pregnancy.

It does not appear that methotrexate can or should be used to totally replace laparoscopic salpingostomy. However, given its success rate in selected patients, its cost-effectiveness, and its low incidence of side effects, methotrexate therapy certainly can be used as an alternative therapy. The next step in developing this treatment option will be to conduct a randomized clinical trial comparing laparoscopic salpingostomy with intramuscular methotrexate. This type of study will answer questions regarding the patient's health related quality of life and economic impact of the two treatment modalities. For now, it seems prudent to offer methotrexate to those patients with an unruptured ectopic gestational mass 3.5 cm or less in greatest dimension.

Ultrasonography: usefulness in localization of the Norplant contraceptive implant system.

Norplant is a levonorgestrel-containing contraceptive system that consists of six small capsules (2.4 x 34 mm), which are placed subdermally. Owing to the relative newness of this contraceptive modality, problems with removal of the Norplant implants are just beginning to be reported; these consist primarily of inability to locate and remove all six implant capsules upon discontinuation. Ultrasonographic images of 14 women with the Norplant system in place were obtained in the axial and longitudinal planes. On axial view the capsules consisted of discrete circular individual areas of high echogenicity with prominent posterior shadowing. Capsules scanned in a longitudinal plane demonstrated echogenicity of the superior and inferior capsular walls, giving a tubular appearance. It was possible to demonstrate the depth of capsule placement, spatial relation to surrounding capsules, and orientation in relation to the skin surface. Ultrasonography therefore may provide a useful, noninvasive method for localization of nonpalpable Norplant implants, thus facilitating removal.

Use of GnRH agonist before hysterectomy: a cost simulation.

OBJECTIVE: To evaluate the potential savings in cost of care derived from performing vaginal hysterectomies instead of abdominal hysterectomies in selected women with fibroid uteri equivalent in size to a 14-18 week gestation. METHODS: Women 35-46 years of age undergoing hysterectomy for fibroid uteri were selected to allow application of conversion rates gained in a separate randomized study using leuprolide acetate depot 3.75 mg. Statewide public data for North Carolina's hospital discharges provided relative rates of hospital charges and leiomyomas for all hysterectomies, by age. Professional charges were omitted from the analysis. Estimated savings were projected to the national level. RESULTS: During 1992 in North Carolina, 18,110 inpatient hysterectomies were performed for women of all ages; 28.1% of these were for uterine leiomyomas. For women 35-46 years old (12.7% of all hysterectomies), there were 1904 abdominal and 390 vaginal hysterectomies; the mean total charge for abdominal hysterectomy was $5590, and $4732 for the vaginal alternative. These statewide data provide missing elements to allow a national estimate of the potential savings of using GnRH agonist preoperatively. The projected national savings, if 1987 utilization data are used, was $4.6 million, nearly 1.4% of the inpatient charges. The 1992 value of these savings is $6.7 million. CONCLUSION: The use of preoperative GnRH agonist therapy before hysterectomy for patients with a uterine size equivalent to a 14-18 week gestation represents a significant cost-saving alternative, increasing the use of vaginal hysterectomy and resulting in potential savings in direct inpatient medical care charges.

Synthetic hygroscopic cervical dilator use in patients with unsatisfactory colposcopy.

OBJECTIVE: To assess the ability of a synthetic hygroscopic cervical dilator to make an unsatisfactory colposcopic examination satisfactory, thereby avoiding cervical conization. MATERIALS: From April 1991 to March 1993, 30 women with unsatisfactory colposcopic examinations underwent repeat colposcopy after a synthetic hygroscopic cervical dilator had been placed in the endocervical canal for approximately 2 hours. RESULTS: The reasons for initial unsatisfactory colposcopy in the 30 patients were squamocolumnar junction not seen in its entirety (18 patients, 60%), lesion not seen in its entirety (ten, 33%), and neither transformation zone nor lesion seen in their entirety (two, 7%). Complications were encountered in one patient from whom the dilator could not be removed completely. Of 29 patients undergoing repeat colposcopy, 23 (79%) had satisfactory examinations. In 15 of 30 patients, conization was avoided; it was required in six of 30 (20%) women for persistent unsatisfactory colposcopy (including the patient in whom the dilator broke) and in nine of 30 (30%) for other indications. CONCLUSIONS: This experience suggests that a synthetic hygroscopic cervical dilator can be used in patients with an unsatisfactory colposcopy to achieve a satisfactory examination, thus avoiding cervical conization.

Basic laparoscopic knowledge among gynecologic laparoscopists.

OBJECTIVE: Our purpose was to assess the basic knowledge of laparoscopy and laparoscopic sterilization among gynecologic laparoscopists. STUDY DESIGN: A four-part multiple-choice test designed for use in residency training, covering basic aspects of laparoscopy and laparoscopic sterilization, was distributed to 155 registrants at a gynecologic surgery postgraduate course. Test results were compared among subgroups, as well as with results for 23 residents who had taken the test before their rotation in laparoscopic sterilization. RESULTS: Residents scored higher than practitioners on all test segments. No practitioner achieved the 85% correct passing score required of residents. Practitioner scores did not increase as the number of laparoscopic sterilizations performed per year increased, but higher test scores were associated with more recent completion of residency. CONCLUSION: Basic knowledge of laparoscopic sterilization among practicing gynecologists, as measured by a test designed for residents, is less than that of the residents.

Outpatient hysterectomy: determinants of discharge and rehospitalization in 133 patients.

OBJECTIVE: This study examines our continuing experience in performing vaginal hysterectomies and laparoscopy-assisted vaginal hysterectomies with an outpatient protocol. The purpose was to review factors associated with discharge and hospitalization. STUDY DESIGN: Surgical records from all women entering our previously reported outpatient hysterectomy protocol were reviewed. Demographics, surgical indications, intraoperative data, and postoperative data were studied, and their associations with patient discharge and hospitalization were determined. Specific attention was directed to complications. RESULTS: The study group consisted of 133 women. Twelve women (9.0%) were not discharged from the hospital and 5 (3.8%) required readmission. Surgical indications, the type of hysterectomy, and the requirement for pain medication revealed no association with hospitalization. The occurrence of an intraoperative complication (p < 0.000), the need for transfusion (p = 0.043), and postoperative antiemetics (p = 0.013) were statistically associated with hospitalization. In addition, low hematocrit values and elevated temperatures on the first and second postoperative days were associated with hospitalization. CONCLUSION: Long-term experience with outpatient hysterectomy reveals a hospitalization rate of 12.8%. Complications, blood loss, elevated temperatures, and postoperative nausea are the major determinants of patient discharge and hospitalization. Readmission rates continue to remain low.

Medical management of ectopic pregnancy.

By combining diagnostic modalities such as serial human chorionic gonadotropin titers, transvaginal sonography, and suction curettage, most unruptured ectopic pregnancies can be diagnosed without laparoscopy. When the diagnosis can be made in this manner, methotrexate may be the treatment of choice. It certainly should be considered as an alternative form of treatment in patients with an unruptured ectopic pregnancy. A randomized clinical trial comparing systemic methotrexate with laparoscopic salpingostomy in patients who are methotrexate eligible would be helpful.

Gonadotropin-releasing hormone agonist use before hysterectomy.

OBJECTIVE: Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy. STUDY DESIGN: Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist. RESULTS: All patients in the two groups with a pretreatment hemoglobin < 11.0 gm/dl randomized to agonist had a significant (p < 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p < 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms. CONCLUSION: The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin < 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity.