Albert J. Peters

Vaginal recurrences of endometrial carcinoma: The prognostic value of staging by a primary vaginal carcinoma system

Fifty-five of 1716 women with endometrial carcinoma seen consecutively at three institutions prior to 1986 were found to have an isolated post-hysterectomy vaginal recurrence. Their therapy included external radiation therapy (RT) and brachytherapy for 26 women, external RT alone for 17, brachytherapy only for 4, and no RT for 8. Combined external RT/brachytherapy doses ranged from 2000 to 10,000 cGy with a median of 6000 cGy. The 3- and 5-year actuarial survival rates are 48% and 31% for the entire group, and the 3- and 5-year pelvic control rates are 52% and 42%. The 5-year survival and pelvic control rates for those who received greater than or equal to 6000 cGy in total RT dose are 47% and 68%, compared with 12% and 10% for those receiving less than 6000 cGy (p = 0.002 and p = 0.004). For patients receiving their second RT course, the 5-year survival rate is 16%, compared with 48% for those not previously irradiated. The Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma was applied to each recurrence. There were 15 Stage I cases (vaginal mucosa), 32 Stage II cases divided between 15 Stage IIA (subvaginal infiltration) and 17 in Stage IIB (parametrial infiltration), and 8 Stage III cases (pelvic wall involvement). The 3-year actuarial survival and pelvic control rates using this staging system are: Stage I: 85%/100%; Stage II: 41%/43%, Stage IIA: 59%/53%, Stage IIB: 26%/35%; Stage III: 13%/0%. These outcome endpoints are significantly better for Stage I than Stage II patients (p = 0.01 & 0.0004) and for Stages I and IIA compared to Stages IIB and III (p = 0.0005 & 0.002). The pre-treatment variables of age, interval since hysterectomy, initial stage, and location did not predict for survival, but a higher rate of pelvic control was observed for apical than for suburethral recurrences (56% vs. 20%). Grade III histology was highly correlated with poor survival (p = 0.0006). This vaginal carcinoma staging system appears to have value in predicting treatment outcome for patients with post-hysterectomy vaginal recurrences.

ANALYSIS OF FAILURE PATTERNS IN STAGE III ENDOMETRIAL CARCINOMA AND THERAPEUTIC IMPLICATIONS

The poor outcome of certain patients with Stage III endometrial carcinoma has led some investigators to direct adjuvant therapy to the abdominal cavity. To better define failure patterns, a review of 126 patients with Stage III endometrial carcinoma treated at four institutions was performed. Seventy-four patients were diagnosed at surgery with pathologic Stage III disease, whereas 52 patients presented with clinical Stage III disease. Most patients received external beam irradiation to the pelvis with a variety of boost techniques. Site of disease, grade, depth of invasion, and pathology were examined for prognostic significance. Actuarial techniques were used to analyze survival and recurrences. For the 52 clinical Stage III patients, 5-year survival was 36%. The median survival of 20 patients who were treated with radiation therapy (RT) following biopsy was 9 months. Pelvic control was poor in these patients, with 16/18 evaluable patients failing locally. Thirty-two patients who underwent resection with adjunctive RT had a 5-year survival of 48%. Local failure occurred in 40% of patients, whereas 38% of patients had abdominal failure. Isolated abdominal failure was infrequent with 6% failing as isolated recurrence, and 16% failing as the only site of distant disease. For 74 pathologic Stage III patients, 5-year survival was 54%. Local failure resulted in 20% of patients, and isolated abdominal failure occurred in 7% of patients. The subset of patients with ovarian or tubal involvement included 42 patients, with a 5-year survival of 60%. Further analysis of this subset by grade and depth of myometrial penetration was found to be prognostically significant. Twenty-four patients who were Stage III because of parametrial or pelvic peritoneal involvement had a 5-year survival of 44%. Local control and survival is improved in Stage III patients treated with surgical resection. The high rate of distant metastases in both abdominal and extra-abdominal sites has significant therapeutic implications.

Endometrial adenocarcinoma histologic subtypes: Clinical and pathologic profile

All cases of endometrial adenocarcinoma treated at the Geisinger Medical Center from January 1970 to June 1980 were retrospectively reviewed in an attempt to elucidate the clinical and pathologic profiles of the various histologic subtypes. Complete clinical and pathologic data was available in 418 cases of stage I endometrial adenocarcinoma. The frequency of the histologic subtypes were adenocarcinoma 66%, adenoacanthoma 16%, adenosquamous 5%, papillary 8%, clear cell 3%, and secretory 2%. Absolute 5-year survival was adenocarcinoma 88%, adenoacanthoma 91%, adenosquamous 62%, papillary 63% (P less than 0.01), clear cell 43% (P less than 0.001), and secretory 89%. When comparing the clinical and pathologic profile of the various histologic subtypes, adenosquamous (52%, P less than 0.001) and clear cell (43%, P less than 0.05) were associated with the highest percentage of grade 3 differentiation. Adenosquamous (38%, P less than 0.05) and clear cell (36%) also had the highest percentage of deep myometrial invasion. Papillary subtype (46%, P less than 0.05) was associated with the highest percentage of nulliparity. There was no difference among the subtypes when comparing menopausal status, exogenous estrogen, obesity, hypertension, diabetes, or uterine size. In summary, (1) adenocarcinoma and adenoacanthoma are the most frequent subtypes; (2) adenosquamous, papillary, and clear cell have decreased 5-year survival; (3) the decreased 5-year survival in adenosquamous and clear cell subtypes appears to be associated with increased grade 3 differentiation and deep myometrial invasion while the poor prognosis associated with papillary subtype was not related to grade or myometrial invasion.

Patterns of failure in patients with stage I, grade 3 carcinoma of the endometrium

Patients with high grade, early stage endometrial carcinoma are reported to have worse survival and local control rates than those with low grade carcinomas. To define failure patterns further in patients with FIGO Stage I, grade 3 endometrial carcinomas, the patients from three institutions who received adjuvant or definitive radiation (RT) were analyzed. Of 119 patients meeting the criteria of Stage I, grade 3 endometrial carcinoma, 57 patients received preoperative radiation, 49 patients received postoperative radiation, and 10 patients received definitive radiation with 5-year actuarial survival rates of 64%, 73%, and 65%, respectively. Three additional patients received both preoperative and postoperative treatment. The overall local control rate was 88% with a median follow-up of 70 months. Of 36 patients who failed, 14 had a component of local failure, and 31 had a component of distant failure. Eighteen of 31 distant failures involved metastatic spread to the abdominal cavity. Recurrence patterns by method of treatment are documented. Patients with high grade tumors do have a propensity for distant metastasis. Clinical investigation into the value of systemic therapy is necessary.

Color Doppler ultrasonography assessment of tubal patency: a comparison study with traditional techniques

OBJECTIVE To compare the results of color Doppler ultrasonic hysterosalpingography (color US-HSG) and x-ray-HSG with chromoperturbation at the time of laparoscopy. DESIGN Open, uncontrolled study of women seeking evaluation for infertility from August 1989 to July 1991. SETTING Clinical environment. PATIENTS Two hundred thirty-eight infertile women. INTERVENTION Saline was administered transcervically during transvaginal color Doppler sonography in 238 women. Traditional x-ray-HSG was performed in 89 women. Laparoscopy with chromoperturbation was done in 121 women. Forty-nine women had all three procedures performed. MAIN OUTCOME MEASURES The frequency of diagnosis of bilateral tubal patency, bilateral tubal occlusion, and unilateral tubal patency after color US-HSG and x-ray-HSG was compared with chromoperturbation. The diagnostic efficacy of color US-HSG and x-ray-HSG was compared with chromoperturbation. RESULTS Correlation between color US-HSG and x-ray findings with chromoperturbation occurred in 81% versus 60% (P = 0.0008) of all women studied. In 49 women who had all three procedures performed, color US-HSG results correlated with chromoperturbation more often than x-ray-HSG (82% versus 57%, P = 0.0152). CONCLUSION Color US-HSG is an alternative technique to x-ray-HSG in diagnosing tubal occlusion as a cause of infertility.

Prevalence of out-of-phase endometrial biopsy specimens†

Objective: We attempted to determine the prevalence of out-of-phase endometrial biopsy specimens among fertile and infertile women and women with recurrent pregnancy loss, histologic dating of biopsies was compared with four reference points for expected ovulation. These reference points included last menstrual period, next menstrual period, luteinizing hormone testing, and ultrasonographic documentation of ovulation. Study Design: Four hundred eight-five endometrial biopsies were performed 7 days after documented ovulation-based ultrasonographic evidence for follicle collapse. The histologic dating was referenced to the last menstrual period, next menstrual period, and ultrasonographic documentation of ovulation. One hundred thirty-two of these women also performed urinary luteinizing hormone surge testing before ovulation and serum progesterone determinations. A comparison of the prevalence of out-of-phase biopsy specimens among groups was determined with the χ 2 test and Fishers exact test. Results: The prevalence of out-of-phase endometrial biopsy specimens ranged from 42% when last menstrual period was ued to 26% with next menstrual period, to 21 % with luteinizing hormone testing, and to 4% with ultrasonographic documentation of ovulation. Serum progesterone values among women with a diagnosis of out-of-phase biopsy specimens by any of the reference dates progesterone were similar to those with in-phase biopsy specimens. Conclusions: The accuracy of histologic endometrial dating was best determined by ultrasonographic monitoring rather than by last menstrual period, next menstrual period, or luteinizing hormone testing in infertile populations and in those with recurrent pregnancy loss. Additionally, because no significant difference in out-of-phase biopsy specimens exists between fertile and infertile patients and recurrent pregnancy loss, those with the role of this procedure is called into question.

Hysterosalpingography with color Doppler ultrasonography

To assess the accuracy of the diagnosis of tubal occlusion with the use of color Doppler flow ultrasonography and hysterosalpingography, 129 infertile women were studied. All 129 women had the procedure performed with an ATL Ultramark 9 (Advanced Technology Laboratories, Bothel, Wash.) color Doppler ultrasonography machine. Eighty-five of the 129 women also had an additional study including x-ray hysterosalpingography and/or chromopertubation. Of these 85 women, 58 had pelviscopic examination with chromopertubation. The frequency of diagnosis of tubal occlusion was compared among the three methods. When results of ultrasonography-hysterosalpingography were compared with those of x-ray hysterosalpingography and/or chromopertubation, 69 of 85 (81%) studies showed agreement, and 50 of 58 (86%) ultrasonography-hysterosalpingography findings agreed with observations at chromopertubation. The frequency of comparable findings between x-ray hysterosalpingography and chromopertubation is 75%. These data suggest that ultrasonography-hysterosalpingography is at least as accurate as x-ray hysterosalpingography in diagnosing tubal occlusion. In addition, ultrasonography-hysterosalpingography is safer and more cost-effective than x-ray hysterosalpingography and chromopertubation.

Comparison of the methods of artificial insemination on the incidence of conception in single unmarried women.

OBJECTIVE To compare pregnancy rates after intrauterine insemination (IUI) versus pericervical insemination in absolute male factor infertility using each patient as her own control. DESIGN Ovulatory women with patent fallopian tubes without male partners were alternately inseminated with cryopreserved donor semen using either IUI or pericervical insemination techniques. A total of 81 cycles, which included up to 4 cycles per patient were performed. In this manner a comparison between the efficacy of each method could be evaluated. SETTING The donor insemination program at the Center For Assisted Reproduction at Northwestern University Medical School. PATIENTS Twenty-six single, healthy, unmarried women with patent fallopian tubes and < 40 years of age without male partners (absolute male factor infertility). MAIN OUTCOME MEASURES Positive quantitative serum subunit of human chorionic gonadotropin followed by the presence of an intrauterine gestational sac seen by transvaginal ultrasonography. RESULTS Fourteen (54%) of 26 patients conceived including two (14%) miscarriages within four insemination cycles. Seven (17.5%) patients after IUI, and 7 (17.1%) patients after pericervical insemination conceived. The pregnancy rates were similar regardless of the order of insemination method. CONCLUSION These findings reveal that there is no statistical difference in the pregnancy outcome between these two methods of insemination in absolute male factor infertility.

Quality assurance for sperm concentration using latex beads

OBJECTIVE To provide a simple, universally applicable method of quality assurance for sperm counting, thereby reducing intercounting chamber variation. DESIGN By using a known concentration of latex beads, the sperm:bead ratio can be used to calculate the actual sperm count. MAIN OUTCOME MEASURES The mean sperm and bead counts were determined in both a Spot-lite hemocytometer (Baxter Diagnostics, McGaw Park, IL) and a Makler chamber (Polymedco Inc., Yorktown, NY) from 21 different ejaculates mixed with a known concentration of beads. The hemocytometer chamber was used as the standard counting chamber because it consistently yielded a low variation in sperm count. The adjusted sperm concentration of the Makler chamber was calculated using the following formula [hemocytometer beads]/[Makler beads] x [Makler sperm]. RESULTS Observed mean +/- SD sperm counts were significantly different between the hemocytometer chamber (110.6 +/- 66.2 x 10(6)/mL) and Makler chamber (173.3 +/- 103.5 x 10(6)/mL). However, calculated Makler chamber sperm counts (118.1 +/- 76.1 x 10(6)/mL) was not statistically different from observed hemocytometer sperm counts. CONCLUSION This novel approach to sperm counting using a known concentration of latex beads as a reference material can be used to reduce variation in sperm counting between observers, counting chambers, and possibly computerized sperm analyzers.

Variation in antisperm antibody results using different assays

PROBLEM: The detection of various types of antisperm antibodies (ASA) in the serum varies among different assays. This variation may influence the diagnosis and management of infertile couples who are tested for such immunologic factors. This prospective study was conducted to determine the variation in the results of ASA as measured by the sperm immobilization (SI), sperm agglutination (SA), and the indirect immunobead (IB) assays.