The outcome of stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma.

PURPOSE: The aim of this study was to compare survival and recurrence in clinical and surgical stage I-II papillary serous (PS), clear cell (CC), and endometrioid (EM) cancers of the endometrium and examine the prognostic utility of myometrial invasion. METHODS: Clinical, surgicopathologic, and survival data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. Prognostic variables examined included age, stage, grade, myometrial invasion, lymph-vascular space invasion (LVSI), and histology. PS and CC histologic subtypes were compared as both common category and discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Statistical analyses were performed using chi(2), Fisher's exact, and Wilcoxon rank sum tests, Cox regression analysis, and Kaplan-Meier survival analysis. RESULTS: PS tumors accounted for 9%, CC for 3%, and EM for 88% of cases. Recurrences were more frequent among PS (38%) and CC (22%) compared with EM (9%) (P < 0.001 and 0.08, respectively), and PS recurred more frequently than EM3 alone (20%) (P = 0.06). Among PS, CC, and EM3 patients with recurrences there were no statistical differences in the proportion that received preoperative or postoperative radiotherapy or chemotherapy. Prognostic factors for shorter survival included age >=60, surgical stage III+IV, presence of LVSI, histology (PS, CC, or EM3), and >=50% myometrial invasion. The estimated 5-year survival of PS+CC patients with <2 mm myometrial invasion is 0.56 compared to 0.93 for EM patients (P < 0. 001). PS + CC tumors confined to the endometrium had a 5-year survival of 0.60 compared to 0.98 and 1.00 for EM and EM3, respectively. The 5-year survival for surgically staged IA patients (0.57) was not different from stages IB and IC combined (0.53) (P = 0.72). The 5-year survival for surgical stage I + II PS + CC patients (0.56) was comparable to that for clinical stage I + II PS + CC patients (0.46) and remained significantly smaller than that for EM patients (0.86) (P < 0.001). CONCLUSION: Recurrences are more frequent among PS and CC tumors compared with EM and among PS compared with EM3. When controlled for surgical stage I-II tumors, 5-year survival for PS + CC patients remains comparable to that of clinical stage I-II patients and below that of EM. Prognostic factors for survival in PS and CC patients include age, stage, and LVSI. PS, CC, and EM3 subtypes together are predictors of poor survival. Thorough extended surgical staging is indicated in PS and CC tumors, and prospective trials of aggressive adjuvant therapies for surgical stage I-II tumors are needed to improve outcome in PS and CC patients.

Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma.

PURPOSE: The aim of this study was to identify similarities and differences in epidemiologic and surgicopathologic staging results for papillary serous (PS) and clear cell (CC) endometrial cancers compared with endometrioid (EM) carcinoma of the endometrium. METHODS: Clinical and surgicopathologic data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. PS and CC histologic subtypes were compared both as a common category and as discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Fisher's exact test was used to compare proportions with unordered categories (2x2 tables), while the chi(2) test for trend was used to compare proportions in 3x2 tables with ordered categories. Differences in medians were compared with the Wilcoxon rank-sum test. RESULTS: PS tumors accounted for 8%, CC for 2%, and EM for 90% of cases. Overall, 14% of tumors were changed to a different postoperative histology including 64% of PS, 50% of CC, and 8% of EM. Postoperative histology changes were 4% for EM1 and 21% for EM3. PS, CC, and EM3 had more surgical sampling performed than for other EM. Rates for lymph node dissections were similar for EM3 (81%), PS (72%), and CC (67%) tumors, although metastases were more frequent for PS and CC compared with EM3. When PS tumors were confined to the endometrium, paraaortic metastases occurred in 13%. LVSI increased with EM grade and was highest for PS and CC. Upstaging to surgical stage III-IV occurred in 47% of PS, 39% of CC, and 12% of EM. The majority of PS and CC tumors were confined to the inner one-third of the myometrium, compared with EM tumors, where grade correlated with depth of myometrial invasion. Extrauterine metastases occurred in 55% of PS and 45% of CC tumors confined to the inner one-half, compared with 17% of EM3. CONCLUSION: Frequent changes from preoperative to postoperative histology and grade may contribute to misassignment of preoperative and intraoperative risk as determined by depth of myometrial invasion for PS and CC patients. The higher frequency of extrauterine metastases in PS and CC tumors compared with EM3, despite similar surgical sampling rates, supports a more virulent behavior. The poor correlation between depth of myometrial invasion and risk for extrauterine metastases helps to explain poorer survival in PS and CC patients, in addition to more frequent upstaging. These results support routine extended surgical staging for women with preoperative or intraoperative diagnosis of PS and CC tumors. Intraoperative assessment of tumor grade and histology may be indicated and warrants further investigation.

A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery.

OBJECTIVE: Our aim was to determine the relative efficacy and complications of low-dose heparin and intermittent pneumatic calf compression for the prevention of postoperative venous thrombosis in patients undergoing surgery for gynecologic malignancy. STUDY DESIGN: Randomized trial comparing 107 patients treated with low-dose heparin to 101 patients treated with intermittent pneumatic calf compression was performed. All patients were evaluated with iodine-125 fibrinogen scanning of the legs. Clinical and laboratory variables associated with bleeding complications were recorded prospectively. RESULTS: Venous thrombosis was diagnosed in seven patients receiving low-dose heparin and in four receiving intermittent pneumatic calf compression (p = 0.54). Low-dose heparin patients received more blood transfusions postoperatively (p = 0.02), had increased volume of retroperitoneal drainage (p = 0.02), and the activated partial thromboplastin time was more frequently prolonged (p = 0.001). CONCLUSIONS: Low-dose heparin and intermittent pneumatic calf compression provide similar reduction in reducing the incidence of postoperative venous thrombosis. However, low-dose heparin is more frequently associated with postoperative bleeding complications.

A controlled trial of two low-dose heparin regimens for the prevention of postoperative deep vein thrombosis.

Venous thromboembolism is a serious complication following gynecologic surgery and is particularly common in patients with malignancy. A previous study of subcutaneous low-dose heparin given as one dose preoperatively and every 12 hours postoperatively failed to show a benefit in gynecologic oncology patients. In the present study, two more intense regimens of low-dose heparin were evaluated. Three hundred four patients were assigned randomly to receive no prophylaxis (controls), subcutaneous heparin 5000 units 2 hours before surgery and every 8 hours postoperatively (low-dose heparin) (regimen I), or 5000 units heparin subcutaneously every 8 hours preoperatively (between two and nine doses) and every 8 hours postoperatively (regimen II). All patients had thromboembolism surveillance with the fibrinogen uptake test and clinical evaluation. Eighty-four percent had a malignancy. Thromboemboli were diagnosed in 19 of 103 control patients, ten of 104 regimen I patients, and six of 97 regimen II patients, a statistically significant difference (P less than .008). When compared with the control group, the study groups had no evidence of increased bleeding complications or alteration of laboratory coagulation indicators.

Variables associated with postoperative deep venous thrombosis: a prospective study of 411 gynecology patients and creation of a prognostic model.

Deep venous thrombosis is a major complication following gynecologic surgery. Assessing a patient's risk of developing deep venous thrombosis is important for patient selection and in choosing appropriate prophylactic methods. Four hundred eleven patients undergoing major gynecologic surgery were evaluated prospectively. All known variables associated with deep venous thrombosis were recorded. Deep venous thrombosis was diagnosed by 125I fibrinogen leg counting of all patients. Univariate analysis of all variables identified the following to be significantly related (P less than .05) to postoperative deep venous thrombosis: a prior history of deep venous thrombosis, leg edema or venous stasis changes, venous varicosities, degree of preoperative ambulation, type of surgery, nonwhite race, recurrent malignancy, prior pelvic radiation therapy, age above 45 years, excessive body weight, intraoperative blood loss, and duration of anesthesia. A stepwise logistic regression analysis of these variables was performed. The following preoperative prognostic factors remained significant: type of surgery, age, leg edema, nonwhite patients, severity of venous varicosities, prior radiation therapy, and prior history of deep venous thrombosis. Duration of anesthesia was also important when intraoperative factors were considered in the analysis. Using these factors, a prognostic model was created and tested. The model resulted in a degree of concordance of 0.82 and allows one to evaluate the risks of postoperative deep venous thrombosis for an individual patient.

Indium 111 platelet imaging for the detection of deep venous thrombosis and pulmonary embolism in patients without symptoms after surgery.

Indium 111 platelet imaging for the detection of deep vein thrombosis and pulmonary emboli was performed in 171 patients after abdominal and pelvic surgery. Fifteen patients were found to have inadequate circulating blood pools of indium 111 platelets, making the study nondiagnostic. Of 156 patients with technically satisfactory images, 46 (29.5%) had images consistent with deep venous thrombosis and/or pulmonary emboli. The incidence, time of occurrence, and location of thromboemboli was similar to those of other reports of postoperative patients groups studied by iodine 125 fibrinogen uptake testing. Eighty patients had normal indium 111 platelets and 30 patients had diffusely distributed indium 111 platelets found in the operative field, suggesting accumulation in a postoperative hematoma. None of these results was confused with a diagnosis of deep venous thrombosis. When compared with another accurate diagnostic test in 23 patients, indium 111 platelet imaging was found to have a sensitivity of 100% and specificity of 90%. The technique of indium 111 platelet imaging is performed easily in patients after surgery with some limitations as to the use of donor platelets and the occasionally altered imaging of the operative site. This diagnostic technique enjoys the distinct advantage in that it allows surveillance of the legs, pelvis, abdomen, and chest by a single method, making it a near-ideal method of postoperative thromboembolism surveillance.

Complications of low-dose heparin prophylaxis in gynecologic oncology surgery.

The clinical and laboratory effects of low-dose heparin prophylaxis was prospectively studied in a controlled trial of 182 patients undergoing major surgery for gynecologic malignancy. Low-dose heparin was given in 5000 U subcutaneously two hours preoperatively and every 12 hours for seven days postoperatively. Low-dose heparin-treated patients had a significantly increased daily retroperitoneal hemovac drainage. Although not statistically significant, low-dose heparin was associated with increased estimated intraoperative blood loss, transfusion requirements, and wound hematomas. Fifteen percent of patients receiving low-dose heparin were found to have an activated partial thromboplastin time greater than 1.5 times the control value. In these patients, all clinical bleeding parameters were significantly increased. Low-dose heparin-treated patients also had significantly prolonged activated partial thromboplastin time and lower final platelet counts as compared with the control patients. When using low-dose heparin for thromboembolism prophylaxis, patients should be closely observed for clinical hemorrhagic complications. Activated partial thromboplastin times and platelet counts should be monitored throughout therapy.

Perioperative external pneumatic calf compression as thromboembolism prophylaxis in gynecologic oncology: report of a randomized controlled trial.

Postoperative venous thromboembolic complications are a major problem for the gynecologic oncologist. External pneumatic calf compression (EPC), when applied intraoperatively and left on the patient's legs for 5 days postoperatively, has been previously demonstrated to significantly reduce the incidence of venous thromboembolic complications in patients undergoing surgery for pelvic malignancies. The purpose of this study is to evaluate whether a short perioperative course of EPC is also effective in preventing venous thromboembolic complications. One hundred ninety-four patients participated in a randomized controlled trial of perioperative external pneumatic calf compression. 125I-labeled fibrinogen scanning and impedance plethysmography were used as prospective surveillance methods in both groups. Venous thromboembolic complications were diagnosed in 12.4% of control group patients and in 18.6% of EPC group patients. External pneumatic calf compression when used only in the perioperative period appears to be of no benefit in reducing the incidence of postoperative venous thromboembolic complications.

The natural history of postoperative venous thromboemboli in gynecologic oncology: a prospective study of 382 patients.

Three hundred eighty-two patients who underwent major operations for gynecologic malignancy were studied prospectively to determine the natural history of postoperative venous thromboemboli. Iodine 125-labeled fibrinogen leg counting, to diagnose deep venous thrombosis, was performed daily. Sixty-three patients (17%) developed postoperative venous thromboembolic complications. Deep venous thrombosis initially arose in the calf veins in 52 patients. Twenty-seven percent of these thrombi lysed spontaneously. Four percent of thrombi in the calf veins progressed to deep venous thrombosis in the femoral vein, and 4% resulted in pulmonary emboli. Nine other patients developed proximal deep venous thrombosis without prior thrombosis in the calf veins. One patient with proximal deep venous thrombosis also had a pulmonary embolus. Two patients with no evidence of deep venous thrombosis on prospective 125I-labeled fibrinogen leg counting developed pulmonary emboli, including one fatal pulmonary embolus that was found at autopsy to have arisen from the internal iliac veins. Fifty percent of all venous thromboemboli were detected within 48 hours of operation, although two patients developed significant deep venous thrombosis and pulmonary emboli after discharge from the hospital. These results add important information to our understanding of this disease process, and raise issues related to appropriate treatment and prophylaxis of venous thromboembolism in patients after gynecologic operations.

Prevention of postoperative venous thromboembolism by external pneumatic calf compression in patients with gynecologic malignancy.

One hundred seven patients undergoing major surgery for gynecologic malignancy participated in a controlled trial evaluating the effectiveness of pneumatic calf compression in the prevention of postoperative deep venous thrombosis and pulmonary embolism. External pneumatic calf compression was applied intraoperatively and for five postoperative days. All patients were prospectively screened for deep venous thrombosis with impedance plethysmography and 125I-fibrinogen leg counting. Deep venous thrombosis and/or pulmonary emboli were detected in 18 of 52 control group patients (34.6%) whereas in seven of 55 (12.7%) of those treated with external pneumatic calf compression (P less than .005). External pneumatic calf compression was most effective during the first five days postoperatively and also reduced the incidence of deep venous thrombosis in patients at highest risk. When applied during surgery and for five days postoperatively, external pneumatic calf compression significantly reduces the incidence of postoperative venous thrombosis.

Anticoagulation therapy for venous thromboembolism in patients with gynecologic malignancy.

Anticoagulation therapy in 74 patients with gynecologic malignancy and venous thromboembolism was evaluated as to hemorrhagic complications, recurrent thrombosis, and completion of prescribed course. Clinically significant bleeding complications occurred in 25 patients and the course of anticoagulant therapy was not completed in 29 patients because of bleeding complications or death within 3 months. Venous thromboembolism recurred in 11% of patients. Risk factors associated with hemorrhagic complications and unsuccessful completion of anticoagulation therapy include advanced age, advanced stage of malignancy, incomplete surgical resection of tumor, and systemic chemotherapy. Complications of anticoagulant therapy were found to be excessive when compared to those in reports dealing with noncancer patients and may exceed the benefits of therapy in certain patients. Alternative methods of management for this group of high-risk patients are discussed.

Venous thromboembolism prophylaxis in gynecologic oncology: a prospective, controlled trial of low-dose heparin.

One hundred eighty-five patients undergoing operation for gynecologic malignancy participated in a randomized controlled trial of low-dose heparin prophylaxis. Prospective surveillance for deep venous thrombosis was performed with daily fibrinogen 125I counting in the legs and impedance plethysmography. Twelve of 97 (12.4%) patients in the control group and 13 of 88 (14.8%) patients in the low-dose heparin group developed a venous thromboembolic complication. There was no statistical difference in the incidence of proximal deep vein thrombosis, calf vein thrombosis, or pulmonary emboli between the control and low-dose heparin groups. Low-dose heparin does not afford any prophylactic benefit to patients undergoing major pelvic operative procedures for gynecologic malignancy.