Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis.

PURPOSE: Limited information is available regarding factors that predispose to complications following postoperative pelvic radiotherapy (RT) for endometrial cancer. To address this issue, patients with clinically staged I/II endometrial cancer who received postoperative RT following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node sampling (LNS) were studied. PATIENTS AND METHODS: From 1960 through 1990, 235 patients with adenocarcinoma of the endometrium received postoperative RT after surgical staging. Multiple factors were evaluated to determine associations with severe complications. Pretreatment factors included age, stage, comorbidities. Treatment-related factors consisted of LNS, total RT dose, volume of RT fields, dose per fraction, total number of RT fields, number of RT fields treated per day, machine energy, and addition of vaginal implant. RESULTS: The 5-year actuarial risk of a severe complication was 5.5%. Factors associated with an increased risk of complications in univariate analysis included age more than 65 years (11% v 2%), use of only one portal per day (40% v 3%), use of anteroposterior/posteroanterior fields (23% v 4%), total dose > or = 50 Gy (8% v 2%), and LNS (11% v 3%). In a multivariate analysis, only older age, LNS, and the use of one field per day were significant. Increased risks associated with a total dose > or 50 Gy and the anteroposterior/posteroanterior technique were entirely attributable to the use of one field per day. A subanalysis among patients who had adequate RT techniques (eg, multiple fields treated per day) showed a significant increase in complications (7% v 1%) for those with and without LNS, respectively. CONCLUSIONS: Severe complications associated with adjuvant RT for endometrial cancer were increased among patients who were older or underwent LNS or received suboptimal RT technique. Pelvic RT using proper methods can be delivered with acceptable risks.

On the occurrence and transport of estriol-3-sulfate in human breast cyst fluid: the metabolic disposition of blood estriol-3-sulfate in normal women.

The high concentration of estriol-3-sulfate (E3-3S) in human breast cyst fluid has been confirmed in 14 women with multiple cysts. The concentrations of E3-3S found in individual cysts drained within a short time span from the same patient were variable, the ratios ranging from unity to 40. After the iv administration of [14C]estriol or [3H]E3-3S, only minor accumulation of either isotope was detected in the cyst fluids aspirated 6.5-30 h later. Since surprisingly small amounts of isotopes were found in blood, the metabolism of [3H]E3-3S was studied in 2 normal women. The test compound was injected iv, and blood samples were taken at intervals up to 7.5 h. In addition, total urine was collected for 3 days. The blood clearance of [3H]E3-3S was rapid, with the half-life ranging from 15-30 min. However, E3-3S was only a minor component of the urine, indicating rapid tissue extraction and metabolism rather than renal excretion for the compound. The studies indicate that E3-3S of human breast cyst fluid does not equilibrate rapidly with other body pools and that its uptake, if any, from the blood would be against a gradient.

Endometrial adenocarcinoma.

Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for some 36,000 cases of invasive cancer each year. Hyperplastic lesions of the endometrium follow a continuum, with the risk of progression to carcinoma being related to the severity of the disorder. Risk factors associated with the development of adenocarcinoma include hyperplasia, obesity, menstrual abnormalities, diabetes, hypertension, prior pelvic irradiation, sequential oral contraceptive use, diet, and exogenous estrogen use. There is also some evidence of genetic predisposition, and some data indicating the possibility of specific genetic abnormalities and activation of oncogenes as factors determining the etiology of the disease. At this time there is no accepted screening test for endometrial carcinoma, though the role of immunochemistry techniques for screening and follow-up has just begun to be realized. Dilatation and curettage along with hysteroscopy remain the major means of diagnosis. A variety of prognostic variables including tumor cell type, histologic grade, depth of myometrial invasion, status of peritoneal cytology, presence of disease in preformed vascular spaces, presence of adnexal metastases, and presence of cervical involvement have been defined. Although the treatment plan for each patient must be individualized, the mainstay of treatment remains total abdominal hysterectomy with bilateral salpingo-oophorectomy. Metastatic and recurrent disease is usually treated with hormonal therapy and systemic chemotherapy. Radiation therapy like surgery in recurrent disease is only applicable for the treatment of local recurrences.

Continuous fetal tissue pH measurement in labor.

Fifty-one women in labor had continuous monitoring of fetal scalp tissue pH, fetal heart rate by ECG, and uterine contractions. A miniature pH electrode secured by a double spiral fetal ECG electrode was used for measurement of fetal pH every 15 seconds. The results were correlated with fetal scalp blood pH values obtained simultaneously. Fetal scalp sampling is intermittent, requires repeated scalp incisions, is subject to errors due to air mixing and coagulation of the blood sample, and is uncomfortable for the parturient. Placement of the tissue pH electrode allows continuous data recording with the minimum discomfort to the patient and the least number of fetal scalp incisions. Clinical use of the tissue pH electrode might be a practical alternative to fetal scalp samples, if the data obtained accurately reflect fetal status.

A formula for predicting the risk of a positive second-look laparotomy in epithelial ovarian cancer: implications for a randomized trial.

OBJECTIVE: To develop a formula to predict the risk of a positive second-look laparotomy. METHODS: A retrospective review was performed on 89 patients who underwent second-look surgery following a complete clinical remission after cis-platin- or carboplatin-based chemotherapy. Logistic regression was used to develop a formula to predict the probability of a positive second look based on age, stage, grade of tumor, residual disease after initial surgery, and histologic type. RESULTS: We identified three groups based on estimated probabilities: low probability (0.25 or less), intermediate probability (0.26-0.74), and high probability (0.75 or more). The low-probability group had an 8% chance of a positive second look, the high-probability group had an 82% chance of a positive second look, and the intermediate-probability group had the correct outcome predicted only 61% of the time. Survival curves paralleled these results and were significantly different for each group. CONCLUSIONS: Using known prognostic factors, a formula can aid in implementation of a randomized clinical trial to test the efficacy of second-look laparotomy. This formula could exclude patients not suitable for randomization and give the investigator a better idea of the expected survival of various subgroups.

Postmenopausal bleeding from unusual endometrial polyps in women on chronic tamoxifen therapy.

There are recent reports of postmenopausal bleeding from endometrial polyps in women receiving tamoxifen therapy for breast cancer. We describe four additional patients who presented with vaginal bleeding, and emphasize the pathology. These polyps demonstrated cystically dilated glands in all cases and stromal decidualization in two; in one instance, metastatic breast carcinoma was present in the polyp. The mechanisms by which tamoxifen may affect the development of these polyps are discussed.

Prognostic significance of squamous differentiation in stage I endometrial adenocarcinoma.

The prognostic implication of benign and malignant squamous differentiation was examined in 267 consecutive patients with stage I endometrial carcinoma. Patients with adenosquamous carcinoma had a significantly poorer ten-year survival rate (54.7%) than patients with adenocarcinoma (70.5%) or adenoacanthoma (87.4%). This was related to a tendency for adenosquamous carcinoma to be associated with poorly differentiated glandular elements and to deeply invade the myometrium. The mean depth of myometrial penetration was 57% for adenosquamous carcinoma compared with 24% for adenocarcinoma and 19% for adenoacanthoma. To examine the prognostic significance of malignant squamous differentiation independently of the grade of the associated glandular component, the subgroup of patients with well-differentiated adenocarcinoma was compared. Patients with well-differentiated adenosquamous carcinoma persisted in having a worse prognosis (58.3% ten-year survival rate), compared with adenocarcinoma (84.3% ten-year survival rate), which was explained by the propensity of adenosquamous carcinoma to deeply invade the myometrium.

A single clonal abnormality of chromosome 1 found in an adenocarcinoma of the uterus.

Adenocarcinomas usually have a complex genome comprised of multiple chromosomal alterations. These neoplasms rarely express a single genomic change. We report the first case of an endometrial adenocarcinoma demonstrating a single genomic variation in chromosome 1 associated with a 2 1/2-year survival. The finding of this anomaly may be important in determining the etiology and clinical behavior of uterine malignancies.

Karyotypic analysis of 32 malignant epithelial ovarian tumors.

The identification of recurrent specific cytogenetic findings in various malignancies has provided an improved means to diagnose and treat patients. To date, no characteristic markers have been found for epithelial ovarian cancer. This is due, in part, to several contributory factors, including the inability to identify optimal growth conditions for culture and the fact that most analyses of advanced-stage tumors are obtained from malignant effusions rather than from solid tissue. In addition, many reports include previously treated patients. In this study, 32 untreated solid epithelial ovarian tumors, including 8 tumors of low malignant potential (LMP), were obtained from primary and metastatic sites at initial surgical staging. Using a 2-culture plastic technique for tissue growth, we achieved a 96% short-term culture success rate. Only 4 normal 46,XX karyotypes were identified. Diploid or near-diploid genomes were associated with few cytogenetic alterations. Complex karyotypic morphologies were consistently associated with advanced or poorly differentiated tumors. Nonrandom cytogenetic aberrations most commonly involved chromosomes 1 and 6. A novel translocation, t(1;6)(p10;p10), was identified in both a metastatic LMP tumor and a poorly differentiated invasive tumor. This cytogenetic rearrangement can potentially be regarded as a clinically relevant early marker for tumorogenesis. Finally, karyotypes from both primary and metastatic sites were subject to a comparative analysis in 11 patients. In 4 cases, greater chromosomal complexity was associated with the primary site.

Is chromosome 10 a primary chromosomal abnormality in endometrial adenocarcinoma?

Seven cases of endometrial adenocarcinoma (EC) are reported. Two of these cases exhibited diploid chromosome ranges and showed simple rearrangements involving a chromosomal abnormality of chromosome 10. In four cases, the chromosome number ranged between 50 and 70; rearrangements were more complex, with many abnormalities such as homogeneously stained regions, minutes, dicentrics, and ring chromosomes. In one case, two subpopulations of cells were detected, one in a diploid chromosome range with chromosome 10 altered, and the second, very pleomorphic. These abnormalities are probably due to the evolution of a destabilized genome and represent a consequence of the advanced stage of the disease. The importance of simple abnormalities as clues to the primary chromosomal change, and the possibility that chromosome 10 represents the primary chromosomal alteration event in EC, are discussed.

Chromosome analysis and comparison of the benign cystic and malignant squamous component of an ovarian teratoma.

Teratoma, the most common ovarian germ-cell tumor, presumably arises from a single germ cell and is composed of tissues representing all germ layers (ectoderm, mesoderm, and endoderm). Benign cystic teratomas (dermoid cyst) represent over 95% of ovarian teratomas and are comprised of entirely mature adult tissues. When malignant, almost all mature teratomas contain squamous carcinoma. We report for the first time the karyotypic comparison of an ovarian teratoma in a 36-year-old female with tissue separately taken from the benign cystic and malignant squamous components. The malignant squamous component revealed two distinct karyotypic populations: one diploid and the other polyploid. Both, however, demonstrated two common markers. The polyploid population also demonstrated numerous additional abnormalities with multiple copies of chromosome 20. Though many of the chromosomal aberrations were unique to the benign component, several karyotypes showed the same markers noted in the malignant squamous component. The significance of this finding is that it may serve to identify those histologically benign teratomas destined to undergo malignant transformation.

Endocervical carcinoma.

The past two decades have seen an increase in the incidence of endocervical carcinoma. Numerous studies have increased understanding of these tumors; hormonal therapy, human papilloma virus, and other cofactors have been implicated in the etiology of endocervical carcinoma. Early diagnosis is difficult: precursor lesions to adenocarcinoma in situ are still poorly defined and understood, and there may be a rapid transit time from in situ to invasive carcinoma. The definition of microinvasive adenocarcinoma is not uniformly agreed upon, and at this time the recommendation is not to use the term. Histologic typing and grading of adenocarcinoma may be useful in the prediction of prognosis for patients. Therapy is based upon stage of disease, the most beneficial results being obtained from either radical surgery or combination surgery and radiation therapy.

Colposcopic screening of women with atypical Papanicolaou smears.

A retrospective study was done on 575 patients with atypical Papanicolaou smears obtained during a ten-year period (1974-83) at Bellevue Hospital-New York University Medical Center. The smears were classified into three categories. The first consisted of 463 patients (81%) with inflammatory atypia specifically treated for Trichomonas, Monilia, Chlamydia, Gardnerella and atrophic vaginitis. Of them, 162 patients (35% of the group) had persistent inflammatory atypia 90 days after the beginning of therapy and were subjected to colposcopic examination. The second group consisted of 86 patients (15%) with squamous atypia. That group underwent colposcopic examination. The third group, 26 patients (4%), had endocervical atypia and underwent colposcopy and endocervical curettage. Overall, of 162 patients with persistent inflammatory atypia, 36 (22%) were found to have cervical intraepithelial neoplasia (CIN); of 86 with squamous atypia, 60 (70%) had CIN; and of 26 with endocervical atypia, 15 (58%) had CIN. Fifty-eight (28%) of all the patients with CIN had lesions of severity greater than CIN 1. It appears that all patients with persistent inflammation or squamous or endocervical atypia would benefit from colposcopic screening.

Residual trophoblastic tissue as a source of highly atypical cells in the postpartum cervicovaginal smear.

A cervicovaginal smear containing atypical cells, which were interpreted as dysplastic cells, was obtained from a women one-year postpartum. These cells were seen singly, in small groups and in clusters embedded in an amorphous pink matrix. They had amphophilic cytoplasm and increased nuclear/cytoplasmic ratios, as well as hyperchromatic nuclei with variably prominent nucleoli, features that are characteristic of trophoblastic cells. No evidence of dysplasia was seen on subsequent colposcopic examination or cervical biopsy. Endocervical curettage yielded fragments of exfoliated endometrium and residual trophoblastic tissue associated with a placental implantation site. Although involution of the placental site is generally complete by six to seven weeks postpartum, maternal-fetal tissue may in fact continue to be exfoliated for several months or longer after delivery. If seen on a cervicovaginal smear, these cells can be highly atypical and may be mistaken as dysplastic or malignant. The cytologic features that characterize trophoblasts and their persistence in postpartum cervicovaginal smears are discussed.

Atypia in cervical cytology as a risk factor for intraepithelial neoplasia.

All Papanicolaou smears obtained during the years 1977 to 1982 were reported by a descriptive cytologic interpretation instead of a numerical report. All smears showing "atypia" were reviewed and found to fall into one of three categories: inflammatory atypia, squamous atypia, and endocervical atypia. Patients with the latter two categories and those with persistent inflammatory atypia after specific therapy underwent colposcopy and directed biopsies if indicated. Colposcopically directed biopsies revealed that 29% of patients with atypical Papanicolaou smears had underlying cervical intraepithelial neoplasia. There was no statistically significant difference in the incidence of underlying cervical intraepithelial neoplasia among patients in each of the three categories of atypia. Of those with intraepithelial neoplasia, 35% had lesions of greater severity than grade 1 cervical intraepithelial neoplasia. We conclude that all patients with squamous, endocervical, and persistent inflammatory atypia on Papanicolaou smear should undergo colposcopic evaluation to rule out intraepithelial neoplasia.

Treatment of primary ovarian angiosarcoma with ifosfamide and doxorubicin.

Angiosarcoma originating in the female genital tract is exceedingly rare with only 15 cases of angiosarcoma of the ovary described to date. All have been highly aggressive tumors, and no response to treatment has ever been reported. A case of primary ovarian angiosarcoma is described in which a short remission was achieved with intensive chemotherapy using ifosfamide and doxorubicin.

Endometrial carcinoma presenting with ascites.

Three examples of endometrial carcinoma presenting with ascites are reported. The patients were in the eighth decade, had no vaginal bleeding, and were considered to have ovarian cancer preoperatively. Laparotomy revealed gross omental tumor and normal appearing ovaries. The endometrial cancers were grossly undetected and were uniformly noninvasive of the myometrium. They projected into the uterine cavity, two in polyps, and one covering a submucous leiomyoma. The fallopian tubes were the most likely route of spread to the abdominal cavity.