Brachytherapy for early endometrial carcinoma: a comparative study with long-term follow-up.

The current study was undertaken to evaluate the effect of preoperative uterine or postoperative vaginal brachytherapy compared to no adjuvant therapy on the disease-free interval, sites of recurrence, and survival in favorable stage IB endometrial carcinoma. One hundred and forty-six patients with FIGO grade 1 and 2 endometrial carcinoma and 1-33% myometrial invasion treated between 1974 and 1992 were retrospectively studied. The use of brachytherapy varied among the treating physicians during the study period. A Kaplan-Meier survival analysis was used to estimate disease-free survival and differences between treatment groups were evaluated with the Mantel-Cox statistic. Recurrent disease occurred in 7 patients (5.3%). Vaginal recurrences accounted for 6 of the 7 sites of recurrences. Recurrences occurred in 1.3% of grade 1 vs. 8.7% of grade 2 tumors (P = 0.04). Among 69 grade 2 tumors, recurrences occurred in 7.5% of those treated with brachytherapy vs. 10.3% of those not treated (P = 0.68). Brachytherapy did not affect the disease-free or overall survival. No serious complications directly related to therapy occurred. Vaginal recurrences occur even in early endometrial carcinoma. This study demonstrates no apparent benefit to brachytherapy. A larger study would be required to see a recurrence or survival difference.

Profile of women 45 years of age and younger with endometrial cancer.

OBJECTIVE: The clinical characteristics and outcomes of endometrial cancer patients 45 years of age and younger were compared with those of patients older than 45 years of age. METHODS: We performed a cross-sectional study of 301 consecutive endometrial cancer patients referred to our center from 1989 to 1994. Of the 289 patients eligible for study, 40 were 45 years of age or younger (group A) and 249 were older than 45 years of age (group B). RESULTS: The majority of patients in both groups presented with stage I disease. Of the women with stage I disease, patients in group A were more likely than those in group B to have low-grade disease localized to the endometrium (P < .001; relative prevalence 3.39; confidence interval [CI] 1.88, 6.12). However, the distribution of stages I to IV overall was the same for the two groups (P = .269). Although univariate analysis revealed that 11% of the patients in group A and 2% in group B had synchronous ovarian malignancies (P = .007; relative prevalence 5.42; CI 1.39, 21.14), multivariate logistic regression found that nulliparity, not age, was an independent risk factor for synchronous ovarian malignancy (P = .017; relative prevalence 6.15; CI 1.52, 25.61). There were no statistically significant differences by age in the prevalence of high-risk endometrial histology (serous and clear cell carcinoma) or in survival. CONCLUSION: The overall distribution of tumor stage and survival were the same for the younger and older women; this finding contradicts previous reports that suggest that young women with endometrial cancer are at lower risk. Additionally, nulliparity, which occurs with a higher prevalence in younger women who develop endometrial cancer, is associated statistically with the development of synchronous ovarian malignancies.

Accuracy of frozen-section (intraoperative consultation) diagnosis of ovarian tumors.

OBJECTIVE: Frozen-section evaluation of ovarian tumors can be used to establish a histopathologic diagnosis and guide the surgeon to perform the appropriate surgical procedure. A retrospective study was conducted to determine the accuracy of frozen-section diagnosis of ovarian tumors. STUDY DESIGN: Frozen- and permanent-section diagnoses were divided into three categories (benign, borderline, and malignant). The sensitivity, specificity and predictive values, and 95% percent confidence intervals of each frozen-section diagnosis were determined. RESULTS: Three hundred eighty-three ovarian tumors that underwent frozen-section evaluation between June 1983 and June 1993 were studied. The final histopathologic diagnosis was 61.1% benign, 7.6% borderline, and 31.3% malignant. Frozen section was accurate in 92.7% of all cases and inaccurate in 7.3%. The sensitivity for malignant tumors was 92.5% tumors (95% confidence intervals 87.7% to 97.2%), the sensitivity for borderline tumors was 44.8% (95% confidence interval 26.4% to 63.2%). The specificity for benign tumors was 92.0% (95% confidence interval 88.6% to 95.4%) but increased to 97.9% (95% confidence interval 96.1% to 99.7%) if borderline tumors were excluded. The positive predictive value and 95% confidence intervals were 92.0% (88.6% to 95.4%) for benign tumors, 65% (43.6% to 86.5%) for borderline tumors, and 99.1% (97.3% to 100.0%) for malignant tumors. Thirteen of 16 (81%) ovarian lymphomas and tumors metastatic to the ovary were correctly identified by intraoperative frozen section. The sensitivity for borderline serous tumors was 64.3% and for borderline mucinous tumors 30.8% (p = 0.48). CONCLUSION: With the exception of borderline tumors, the sensitivity and specificity of frozen-section diagnosis of ovarian tumors are high. Borderline tumors remain difficult to accurately diagnose at frozen section because of the extensive sampling required. Frozen-section diagnoses have important implications regarding the type and extent of surgery performed at the initial operation.

Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma.

OBJECTIVE: To evaluate the usefulness of serum assays for CA 125 to detect recurrent endometrial carcinoma. METHODS: Two hundred sixty-six patients were studied with 1101 post-treatment assays. Patients were categorized as low, medium, or high risk based on surgical-pathologic findings. CA 125 values were analyzed with respect to each patient's disease status. RESULTS: Serial CA 125 levels were elevated (greater than 35 U/mL) in 19 of 33 patients (58%) with recurrent disease. Among 236 surgically treated patients, 97 (41.1%), 42 (17.8%), and 97 (41.1%) were considered low, medium, and high risk, respectively. None of the low-risk and only two (4.7%) of the medium-risk patients developed recurrent disease. One of the latter patients was detected based on an elevated CA 125 level alone. Twenty-seven (27.8%) of the high-risk patients developed recurrent disease, 23 of whom had elevated pre-treatment CA 125. Fifteen of 16 (94%) with recurrent disease had an elevated CA 125 level. Nine of 12 patients with papillary serous carcinoma experienced recurrence; eight of these nine had elevated CA 125 levels at diagnosis and recurrence, in contrast to only one patient with a normal pre-treatment level (P = .018). False elevations were noted in 13 patients, 12 of whom had received radiation therapy. CONCLUSIONS: CA 125, if elevated at diagnosis of endometrial carcinoma, is an important marker for recurrent disease. The use of serial CA 125 assays is most beneficial in diagnosing recurrence in a high-risk population, including patients with papillary serous carcinomas. False elevations may occur following radiation therapy.

Accuracy of frozen section for lymph node metastasis in patients undergoing radical hysterectomy for carcinoma of the cervix.

The efficacy of frozen section in detecting metastases in pelvic and or periaortic lymph nodes during radical hysterectomy is unknown. The finding of positive nodes may result in termination of the operative procedure. In this study, we attempted to determine the accuracy of frozen sections in this situation. Intraoperative pathology consultation records were examined for 127 patients undergoing surgical exploration for radical hysterectomy between 1977 and 1992. Microscopic slides of lymph nodes were reviewed for accuracy. Metastasis diameters were measured and blocks cut five close microtome levels deeper. In 19 cases (15%) positive nodes were documented on permanent section, with metastases ranging in size from less than 1 to 19 mm. Thirteen cases of node metastasis were diagnosed at frozen section. All were suspicious to the pathologist on palpation and gross inspection after bisection. Six cases were missed by sampling error on frozen section; in 4, metastases were smaller than 1 mm; in 1, between 2 and 3 mm; and in 1, 19 mm. The sensitivity was 68%, the false-negative rate was 32%, and the specificity was 100%. No cases were false positive at frozen section. The frequency of nodal metastasis and detection rate by frozen section did not differ significantly between carcinoma types. No micrometastases (< 2 mm) were detected by frozen section. All micrometastases were no longer present within five microtome levels. Frozen section diagnosis of pelvic node metastasis is a highly specific procedure which should alter intraoperative management of early-stage cervical cancer.

Primary radiation therapy for endometrial carcinoma: a case controlled study.

PURPOSE: Primary radiation therapy is generally considered inferior to a surgical approach for patients with endometrial carcinoma and is reserved for patients with a high operative risk. These patients are usually elderly, have multiple medical problems and frequently die of intercurrent disease. To evaluate the efficacy of primary radiation therapy a case controlled analysis comparing corrected survival of patients treated with primary radiation to patients treated with surgical therapy with or without radiation therapy was performed. METHODS AND MATERIALS: Sixty-four patients treated with primary radiation therapy were retrospectively studied. A Kaplan-Meier product limit survival analysis was used to estimate survival among patients treated with primary radiation therapy. A case control study matched by clinical stage, tumor grade, and time of diagnosis was performed. The Mantel-Cox statistic was used to evaluated the equality of the survival curves. RESULTS: Primary radiation therapy was used to treat 9.0% of the patients with endometrial carcinoma during the study period. Cardiovascular disease, diabetes, age greater than 80 and morbid obesity were the most common indications. Ninety percent of patients had either Stage I or II disease. Forty-eight of the 64 patients (75%) completed treatment which included both teletherapy and brachytherapy. Ten patients received brachytherapy only. Twelve complications, both acute and chronic, occurred in eleven patients (17%). Intercurrent disease accounted for 13 of the 36 (36%) of the deaths. Clinical stage of disease and histologic grade of the tumor were significant predictors of survival, p = 0.0001 and p = 0.013, respectively. The case controlled study of Stage I and II patients treated by primary radiation therapy matched to surgically treated controls showed no statistical difference in survival. Dilatation and curettage after the completion of radiation therapy was predictive of local control, p = 0.003. CONCLUSION: Although surgery followed by tailored radiation therapy has become widely accepted therapy for Stage I and II endometrial carcinoma, even in patients who are a poor operative risk, the survival with primary radiation therapy is not statistically different.

Serous papillary carcinoma of the cervix.

Two cases of serous papillary carcinoma of the cervix are reported. Both patients had clinical stage IB disease. One patient underwent radical hysterectomy and bilateral pelvic lymphadenectomy. The second patient was treated with pelvic radiation therapy after exploration demonstrated uterosacral ligament metastasis. Both patients are alive at 35 months after treatment with local therapy alone. In contrast to ovarian, tubal, and endometrial serous carcinomas, local therapy appears to be effective treatment for serous carcinomas of the cervix.

Isolated parenchymal splenic metastasis in epithelial ovarian cancer.

Metastatic parenchymal splenic disease in patients with ovarian cancer is unusual. It is most commonly seen in the presence of large-volume upper abdominal disease when parenchymal involvement occurs by surface extension. A patient with isolated parenchymal splenic metastasis and no peritoneal disease in the abdomen at primary surgery is described.

Squamous cell carcinoma arising in a mature cystic teratoma with metastasis to the paraaortic nodes.

Accurate surgical staging is critical to the management of early ovarian cancers. A patient with squamous cell carcinoma arising from a mature cystic teratoma was found to have paraaortic nodal metastasis as her only evidence of extraovarian disease. Extended field radiation therapy to the pelvis and paraaortic nodes with concomitant cisplatin and adjuvant chemotherapy failed to control her disease. Inadequate surgical staging may explain the recurrences in apparent stage I disease.

Preoperative CA-125 levels predict poor prognostic pathologic features in early stage, FIGO grade 1 and 2 endometrial adenocarcinoma.

Preoperative CA-125 levels were studied in patients with favorable histology and early clinical stage endometrial adenocarcinoma to determine its ability to predict the presence of poor pathologic prognostic features on final pathology. One hundred and one patients with clinical stage I (N = 65) or II (N = 19) or diagnosed by endometrial curettage (EMC) only (N-17) with grade 1 or 2 endometrial adenocarcinoma without gross cervical involvement underwent preoperative CA-125 levels. Final pathology was reviewed for five poor prognostic pathologic features: FIGO grade 3 histology, unfavorable histologic type (sarcoma, clear cell, or papillary serous), invasion into the outer third of the myometrium, extension to the cervix, and extra-uterine metastases. Fifteen patients (14.9%) had CA-125 levels greater than 30 IU ml-1. Of these 15 patients, 12 had one or more of the five poor prognostic pathologic features (positive predictive value 80.0%, specificity 95.8%, P < 0.0001). However, since 30 of the 101 patients were found to have one or more of these poor prognostic pathologic features the sensitivity was only 40.0%. When clinical stage I patients were analyzed separately three patients (4.6%) had CA-125 levels greater than 30 IU ml -1 (positive predictive value 100%, specificity of 100%, sensitivity of 21.4%, P = 0.008). For patients with clinical stage II carcinoma, CA-125 was not predictive of pathologic findings except as a negative predictor of disease in a subgroup of patients whose endocervical curettage (ECC) demonstrated carcinoma unattached to endocervical tissue. In patients diagnosed by EMC only, an elevated CA-125 level was associated with poor prognostic pathologic features (P = 0.001). An elevated preoperative CA-125 reliably predicts advanced disease even in patients with apparently favorable histology and clinical stage, however the sensitivity of this method remains low.

A complication involving a braided hook-wire localization device.

At the authors' institution, needle localization of breast lesions with a braided hook wire involves the wire being cut 1-2 cm from the point of entry before dissection, to avoid contamination of the sterile field with the nonsterile portion of wire. During dissection, the wire is brought through the skin into the area of dissection. In one patient, fragments of wire filaments were left within the breast. Braided hook wires must be cut cleanly, the cut surface should be wiped before dissection, and the surgical area should be cleansed before closure.

False-positive elevation of CA-125 in papillary serous carcinoma of the endometrium treated with postoperative whole abdominal radiation.

Two patients with Stage I papillary serous carcinoma of the endometrium treated with postoperative whole abdominal radiation developed elevated CA-125 levels. In neither patient was evidence of recurrent disease identified. Hepatic veno-occlusive disease, a known complication of whole abdominal radiation and certain chemotherapy regimens, was confirmed by liver biopsy in both cases. CA-125 levels may not be reflective of disease status in this setting.

Accuracy of frozen-section diagnosis at surgery in clinical stage I and II endometrial carcinoma.

OBJECTIVES: The purpose of our study was to determine if frozen section accurately identifies certain poor prognostic pathologic factors in endometrial carcinoma that are known to be associated with pelvic and paraaortic nodal metastasis, including deep myometrial invasion, poorly differentiated tumor, cervical invasion, adnexal involvement, and poor histologic type. STUDY DESIGN: The frozen-section pathologic results of 199 patients with clinical stage I and II endometrial cancer were retrospectively compared with permanent-section pathologic findings. RESULTS: The depth of myometrial invasion (superficial third vs deep two thirds) was accurately determined by frozen-section diagnosis at surgery in 181 of 199 cases (91.0%). The sensitivity of frozen-section diagnosis for deep myometrial invasion was 82.7%, and the specificity was 89.1%. The following tumor characteristics were accurately determined on frozen section at surgery: poorly differentiated tumor (95.0%), cervical invasion (94.0%), adnexal involvement (98.5%), and histologic type (94.0%). Frozen section underestimated deep myometrial invasion in 17.3% of patients with this characteristic and poorly differentiated tumor in 26.3% when compared with permanent-section diagnosis. In patients with unfavorable histologic types, papillary serous and adenosquamous carcinomas were the most commonly misdiagnosed histologic types by frozen section at surgery (70.6%). However, when the preoperative curettage pathologic findings were included, these inaccuracies in tumor grade and histologic type dropped to 15.8% and 35.3%, respectively. Only 13 of 199 patients (6.5%) were not correctly identified by frozen section at surgery as having poor prognostic pathologic features. CONCLUSION: Frozen section diagnosis at surgery is an important procedure that enables the surgeon to identify patients at high risk for pelvic and paraaortic nodal metastasis.

Is calcium oxalate an adequate explanation for nonvisualization of breast specimen calcifications?

This study was initiated to determine whether the apparent calcium loss during histologic breast specimen processing could be explained by the presence of birefringent, transparent calcium oxalate crystals (type I). In previous investigations, the authors had noted a possible loss of 26.2% of calcium during the processing and sectioning of breast specimens. Two hundred thirteen histologic slides prepared from blocks demonstrating calcium radiographically but not histologically were reviewed with polarized light. An additional 506 slides from 19 malignancies appearing as microcalcifications were also reviewed with polarized light. Only one slide from each group (0.2% and 0.5% from the malignant and benign groups, respectively) demonstrated birefringent calcium oxalate (type I). Thus, the presence of calcium oxalate does not sufficiently explain the non-visualization of calcium, which is due instead to processing of breast specimens.

Papillary serous carcinoma of the peritoneum following endometrial cancer.

Two cases of advanced papillary serous carcinoma of the peritoneum occurred after hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma. Careful resectioning of the original ovarian specimens failed to demonstrate a previously undiagnosed ovarian malignancy. In both cases, CA 125 levels, which were being followed routinely because of the previous endometrial cancer, rose before the diagnosis of peritoneal carcinoma and corresponded closely to patient response to therapy.

High-dose, short-duration cisplatin/doxorubicin combination chemotherapy for advanced ovarian epithelial cancer.

Sixty-one patients with epithelial ovarian cancer were treated with intensive high-dose, short-course chemotherapy that consisted of cisplatin (120 mg/m2) and doxorubicin (70 mg/m2) every 3 weeks for four cycles. Patients in complete clinical remission were offered second-look laparotomy (SLL). Patients with minimal or no residual disease at SLL were randomized to either cyclophosphamide (1000 mg/m2 every 21 days for six cycles) or whole-abdominal radiation therapy. All patients completed therapy with a median leukocyte nadir 1.3/microliter and platelet nadir of 90/microliters. Forty-five patients (74%) had a complete clinical response. Results of twenty-two of 36 second-look procedures (64%) showed no evidence of disease (NED). After SLL, 19 patients received six courses of cyclophosphamide and 16 patients received whole-abdominal radiation. Nine patient who refused SLL and one patient with negative SLL findings refused additional treatment. The median survival time for all patients was 51.3 months. High-dose intensive chemotherapy regimens have high response rates, but survival needs to be compared with traditional low-dose regimens. Although high-dose cisplatin and doxorubicin were myelosuppressive, the resulting complications were manageable. There was no significant difference between the mean survival times of patients receiving Cytoxan, abdominal radiation, or no treatment as second-line therapy.

Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses.

Focal (irregular, partial) fatty infiltration of the liver may simulate neoplastic or other hypodense masses on CT. On the basis of previous observations of the phenomenon that differences in X-ray attenuation diminish with increasing energy of X-rays used, we performed a preliminary study to determine if dual-energy CT could be used to discriminate between fatty infiltration and hypodense liver masses. Dual-energy CT at 140 and 80 kVp was performed in 14 patients undergoing liver biopsy and in seven control subjects with presumedly normal liver. Attenuation measurements were taken, and the changes in attenuation between 140 and 80 kVp were calculated. The mean changes in attenuation were 3.5 H for normal liver (n = 7), 2.5 H for hypodense liver masses (n = 6), 13 H for fatty liver (n = 5), 0.3 H for fatty liver combined with hemochromatosis or hemosiderosis (n = 3), and 2 H for the spleen (n = 18). The change in attenuation increased as the fat content in the liver increased. Analysis of variance showed a statistically significant difference (p less than .001) between fatty liver and the other groups. A difference greater than 10 H was unique to fatty infiltration. These results suggest that dual-energy CT may help to differentiate focal fatty infiltration of the liver from low-density neoplastic or other lesions, but only if the iron content of the liver is not increased.

Adenoid cystic carcinoma of the vulva: a radiosensitive tumor.

A patient with adenoid cystic carcinoma of the vulva treated primarily with surgery developed multiple local and distant recurrences in which radiotherapy repeatedly achieved complete local control. The patient survived 11.5 years from original diagnosis and 9.5 years from primary recurrence before dying of pulmonary metastases. Adenoid cystic carcinoma of the vulva is a highly radiosensitive tumor. Adjuvant radiotherapy should be considered as a part of the primary therapy, to improve local control, on the basis of the much larger experience with adjuvant radiotherapy with this tumor in the head and neck. Also on the basis of head and neck tumors, it is unlikely that radiotherapy will affect survival.

Breast specimen microcalcifications: radiographic validation and pathologic-radiologic correlation.

A prospective analysis of specimens from location and biopsy of mammographically suspect microcalcifications in 108 patients was carried out to determine if microcalcifications were lost during histopathologic processing and the clinical relevance of such loss. Nine hundred sixty-eight paraffin blocks were prepared from 425 gross tissue slices containing calcifications identified at radiography of the specimens. Calcium was apparently lost both during preparation of the blocks (13.6%) and after slide preparation (12.6%), for a total possible loss of 26.2%. All specimens demonstrated calcification histologically. One pathology report was amended because of information obtained after recuts, but all cancers were detected on original slides whether or not calcifications were identified initially. The results indicate that, by following the suggestions offered to ensure adequate histopathologic sampling of calcification seen at mammography, most if not all of the calcification present can be detected on the original slide.