Survival Effect of Maximal Cytoreductive Surgery for Advanced Ovarian Carcinoma During the Platinum Era: A Meta-Analysis.

PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy. MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication. RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P < .001). Each 10% increase in maximal cytoreduction was associated with a 5.5% increase in median survival time. When actuarial survival was estimated, cohorts with ≤ 25% maximal cytoreduction had a mean weighted median survival time of 22.7 months, whereas cohorts with more than 75% maximal cytoreduction had a mean weighted median survival time of 33.9 months-an increase of 50%. The relationship between platinum dose-intensity and log median survival time was not statistically significant. CONCLUSION: During the platinum era, maximal cytoreduction was one of the most powerful determinants of cohort survival among patients with stage III or IV ovarian carcinoma. Consistent referral of patients with apparent advanced ovarian cancer to expert centers for primary surgery may be the best means currently available for improving overall survival.

Prevention of adhesion formation after radical oophorectomy using a sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier.

OBJECTIVES: To evaluate the efficacy of a hyaluronate-carboxymethylcellulose (HA-CMC) barrier for prevention of pelvic adhesion formation in women undergoing primary cytoreductive surgery with radical oophorectomy for locally advanced epithelial cancer. METHODS: Between 3/1/01 and 3/1/02, all patients undergoing primary surgery for locally advanced FIGO Stage III-IV epithelial ovarian cancer were prospectively offered study enrollment. Radical oophorectomy (en bloc rectosigmoid colectomy) with total pelvic peritonectomy was performed as clinically indicated. Intestinal continuity was reestablished via stapled anastomosis following complete cytoreduction of pelvic disease. The entire pelvic peritoneal defect was covered with subdivided sheets of HA-CMC (6.5 cm x 5.0 cm) using a 'quilting' technique. The abdominal wall incision site was not treated with adhesion preventive measures. At second-look surgery, four-quadrant pelvic (treated area) and abdominal wall (untreated internal control) adhesion scores were assigned using a previously validated scoring system. Statistical analysis for differences in mean pelvic and abdominal wall adhesion scores was performed using Student's t test. RESULTS: Fourteen patients satisfied all inclusion criteria. Abdominal wall adhesions were noted in 92.9% of patients. In the pelvis, the dorsal peritoneal surfaces were the most common sites of adhesion formation (42.9%). Overall, the mean pelvic (treated) adhesion score was statistically significantly lower (0.91, SD +/- 1.04) than the mean abdominal wall (untreated control) score (5.56, SD +/- 4.55, P = 0.02). There were no instances of intestinal anastomotic leak, and no peri-operative complications directly attributable to HA-CMC were observed. CONCLUSIONS: Placement of a HA-CMC barrier is associated with a significant reduction in the extent and density of pelvic adhesion formation following radical oophorectomy and pelvic peritonectomy for locally advanced epithelial ovarian cancer.

Ovarian cancer surgery in Maryland: volume-based access to care.

PURPOSE: To characterize the patterns of primary surgical care for ovarian cancer in a statewide population according to annual surgeon and hospital case volume. METHODS: The Maryland hospital discharge database was accessed for annual surgeon and hospital ovarian cancer case volume for the time intervals: 1990-1992, 1993-1995, 1996-98, and 1999-2000. Annual surgeon case volume was categorized as low (/=10). Annual hospital case volume was categorized as low (/=20). Logistic regression models were used to evaluate for significant trends in case volume distribution over time and factors associated with access to high-volume care. RESULTS: Overall, 2417 cases were performed by 531 surgeons at 49 hospitals. The distribution according to annual surgeon case volume was low (56.3%), intermediate (9.2%), and high (34.5%). Between 1993 and 2000, there was no significant increase in the proportion of cases performed by high-volume surgeons (OR = 1.03, 95% CI = 0.81-1.33, P = 0.79). Access to high-volume surgeons was positively associated with care at high-volume hospitals and negatively associated with residence >/=50 miles from a high-volume hospital. The overall hospital volume case distribution was low (49.6%), intermediate (27.6%), and high (22.8%). There was a statistically significant decrease in access to high-volume hospitals between 1990 and 1998 (OR = 0.39, 95% CI = 0.30-0.50, P < 0.0001). CONCLUSION: A large proportion of primary ovarian cancer surgeries are performed by low-volume surgeons at low-volume hospitals. In light of positive volume-outcomes data for malignancies treated with technically complex operative procedures, increased efforts to concentrate the surgical care of women with ovarian cancer are warranted. Condensed abstract. A large proportion of primary ovarian cancer surgeries are performed by low-volume surgeons at low-volume hospitals. In light of positive volume-outcomes data for malignancies treated with technically complex operative procedures, increased efforts to concentrate the surgical care of women with ovarian cancer are warranted.

Inability of immunohistochemistry to predict clinical outcomes of endometrial cancer patients.

INTRODUCTION: Despite optimal surgery, some patients with early endometrial carcinoma develop recurrence and die of disease. A number of immunohistochemical (IHC)-identified cell products (markers) have been proposed as predictors of recurrence. This study characterizes a large series of endometrial carcinomas with previously described markers as well as markers that have not been investigated in endometrial carcinoma. PATIENTS AND METHODS: Women who had undergone surgery for endometrial carcinoma were identified and specimens accessed. Tissue blocks were evaluated for ten IHC markers. Results were correlated with last known clinical status. RESULTS: Mean follow-up was 43 months; complete data were available on 117 patients. Two women died of other causes; of the remaining 115, eight died of disease and six were alive with recurrence at last follow-up (12%). Vascular endothelial growth factor staining independently predicted recurrence and death. However, in multivariate analyses, only FIGO stage predicted outcome. DISCUSSION: Our goal was to identify markers to predict which women with endometrial carcinoma were likely to have disease recurrence. We evaluated cell-cycle regulatory proteins, growth factors, hormone receptors, and angiogenic factors, but did not identify any marker that independently predicted outcome in multivariate analysis. This may reflect the few negative outcomes in our population.

FIGO stage IIIC endometrial carcinoma: resection of macroscopic nodal disease and other determinants of survival.

The objective of this study was to evaluate the potential survival benefit of debulking macroscopic adenopathy and other clinical prognostic factors among patients with node-positive endometrial carcinoma. Demographic, operative, pathologic, and follow-up data were abstracted retrospectively for 41 eligible patients with FIGO stage IIIC endometrial cancer. Survival curves were generated using the Kaplan-Meier method and statistical comparisons were performed using the log rank test, logistic regression analysis, and the Cox proportional hazards regression model. All patients had positive pelvic lymph nodes and 20 patients (48.8%) had positive para-aortic lymph nodes. Postoperatively, all patients received whole pelvic radiation therapy, 17 received extended-field radiation therapy, and 15 patients received chemotherapy. The median disease-specific survival (DSS) time for all patients was 30.6 months (median follow-up 34. 0 months). Patients with completely resected macroscopic lymphadenopathy had a significantly longer median DSS time (37.5 months), compared to patients left with gross residual nodal disease (8.8 months, P = 0.006). On multivariate analysis, independent predictors of DSS were gross residual nodal disease (HR 7.96, 95% CI 2.54-24.97, P < 0. 001), age > or = 65 years (HR 6.22, 95% CI 2.05-18.87, P = 0.001), and the administration of adjuvant chemotherapy (HR 0.22, 95% CI 0.07-0.76, P = 0.016). We conclude that in patients with stage IIIC endometrial carcinoma, complete resection of macroscopic nodal disease and the administration of adjuvant chemotherapy, in addition to directed radiation therapy, are associated with improved survival.

Endometriosis-associated ovarian carcinoma: differential expression of vascular endothelial growth factor and estrogen/progesterone receptors.

BACKGROUND: Multiple epidemiologic and histologic studies have suggested that ovarian endometriosis can give rise to malignant ovarian tumors, primarily those of epithelial origin. The progression of endometriosis to endometriosis-associated ovarian carcinoma (EAOC) has not been investigated thoroughly and is poorly understood at best. Using immunohistochemical methods, we compared the differential expression patterns of various cytokines and growth factors in atypical endometriosis (AE) and EAOC. METHODS: Using the Johns Hopkins Pathology Data Bank, tissue blocks from patients diagnosed with EAOC or AE were identified. Tissue blocks were stained for 4 markers: vascular endothelial growth factor (VEGF), Ki-67, estrogen receptor (ER), and progesterone receptor (PR). RESULTS: Seventeen cases of EAOC and 8 cases of AE were identified. Staining for VEGF was documented in 16 of 17 (94%) EAOC tissue blocks and in only 1 of 8 (12.5%) AE tissue blocks (P < 0.0001). Only 4 of the 17 (23%) EAOC tissue blocks exhibited positive staining for ER, compared with 8 of 8 (100%) AE tissue blocks (P = 0.0005). Positive staining for PR was noted in only 6 of 17 (35%) EAOC samples but was present in 8 of 8 (100%) AE samples (P = 0.003). Seventy percent of EAOC samples exhibited positive staining for Ki-67, compared with 37.5% of AE samples (P = 0.19). CONCLUSIONS: EAOC appears to be associated with overexpression of VEGF and reduced expression of both ER and PR. Variations in VEGF expression may be associated with the malignant transformation of endometriosis and may present both diagnostic and therapeutic options for the treatment of ovarian malignancies.

Clinically occult recurrent ovarian cancer: patient selection for secondary cytoreductive surgery using combined PET/CT.

OBJECTIVE: The aim of this study was to evaluate the utility of combined positron emission tomography/computed tomography (PET/CT) for identifying ovarian cancer tumor masses > or =1 cm in patients with clinically occult recurrent disease by conventional CT imaging. METHODS: Twenty-two patients with epithelial ovarian cancer, rising serum CA125 levels, and negative or equivocal conventional CT imaging > or =6 months after primary therapy underwent combined PET/CT imaging followed by surgical reassessment. Fisher's exact test was used to measure the ability of PET/CT to predict macroscopic disease > or =1 cm. RESULTS: The median patient age was 55 years, and 91% of patients had FIGO Stage IIIC/IV disease. The median increase in serum CA125 was 24 U/ml (range 10 to 330 U/ml). Conventional CT was reported as negative (n = 15) or equivocal (n = 7) in all cases. Eighteen patients were ultimately found to harbor recurrent ovarian cancer measuring > or =1 cm at the time of surgery, with a median maximal tumor diameter of 2.3 cm (range 1.5 to 3.2 cm). The overall patient-based accuracy of PET/CT in detecting recurrent disease > or =1 cm was 81.8%, with a sensitivity of 83.3% and positive predictive value of 93.8% (P = 0.046). Of patients with recurrent ovarian cancer > or =1 cm, complete cytoreduction to no gross residual tumor was accomplished in 72.2%. CONCLUSION: PET/CT imaging demonstrates high sensitivity and positive predictive value in identifying potentially resectable, macroscopic recurrent ovarian cancer among patients with biochemical evidence of recurrence and negative or equivocal conventional CT findings. In appropriately selected patients, early identification of macroscopic recurrent disease may facilitate complete surgical cytoreduction.

Cystic paracervical mass as an unusual sequela of graft-versus-host disease. A case report.

BACKGROUND: Bone marrow transplantation is used in the treatment of a variety of malignancies. One common sequela is graft-versus-host disease (GvHD.) CASE: A case of vaginal GvHD in a postmenopausal woman manifested as a 2-cm, cystic, paracervical mass. The patient was followed with consecutive pelvic ultrasounds and pelvic examinations until 27 months after transplantation, when the mass increased in size to 4 x 3 cm. Exploratory laparotomy with total abdominal hysterectomy revealed a 3 x 3-cm phlegmon within the proximal part of the vagina. Presumably, this resulted from vaginal GvHD, causing a midvaginal stricture with obstruction of cervical/uterine effluent. CONCLUSION: An awareness of the gynecologic manifestations of GvHD is critical for clinicians caring for women undergoing bone marrow transplantation.

Micropapillary serous ovarian carcinoma: surgical management and clinical outcome.

OBJECTIVES: The objectives of this study were to characterize the prognostic features of micropapillary serous ovarian carcinoma (MPSC), examine the clinical impact of surgical staging, and define the role of cytoreductive surgery for patients with advanced disease. METHODS: Fifty-one patients with MPSC were identified from hospital and tumor registry databases. Demographic, operative, pathologic, and follow-up data were abstracted retrospectively. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using the log rank test, logistic regression analysis, and the Cox proportional hazards regression model. RESULTS: The median age at diagnosis was 45 years, and follow-up extended to a median of 43.0 months. Stage I/II disease was present in 25.5% of patients and no disease-related deaths were observed in this group. Stage III disease was discovered in 29.4% of patients with tumor clinically confined to the ovaries. Stage III/IV disease (74.5% of cases) was associated with median progression-free and overall survival times of 32.8 and 114.2 months, respectively. Menopausal status and the anatomic extent of disease were significantly associated with survival outcome. However, the strongest independent predictor of survival for patients with advanced disease was the amount of residual tumor. Median overall survival for patients with optimal cytoreduction (residual disease 1 cm residual tumor (P < 0.0002). CONCLUSIONS: MPSC carries a significant risk of extraovarian spread; however, adequately sampled Stage I/II disease is associated with a favorable prognosis. Optimal cytoreduction is associated with improved survival and should be the primary therapeutic objective for patients with advanced-stage MPSC.

Struma ovarii associated with pseudo-Meigs' syndrome and elevated serum CA 125.

BACKGROUND: Struma ovarii, presenting as pseudo-Meigs' syndrome with an elevated CA 125 level, is a rare condition. CASE: A 65-year-old patient presented with ascites, hydrothorax, right ovarian mass, and elevated CA 125 level. These findings were suspicious for an ovarian malignancy. The mass was removed and revealed struma ovarii, a specialized ovarian teratoma composed predominantly of mature thyroid tissue. In the setting of ascites and hydrothorax, the condition is known as pseudo-Meigs' syndrome. This is the second reported case in the English language literature of pseudo-Meigs' syndrome with an elevated CA 125 level resulting from struma ovarii. CONCLUSION: Struma ovarii is a rare cause of ascites, hydrothorax, and an elevated CA 125 level.

Positron emission tomography for detecting clinically occult surgically resectable metastatic ovarian cancer.

BACKGROUND: The specific indications for PET imaging in patients with ovarian cancer have yet to be precisely defined. While PET has limited sensitivity for detecting small-volume (<1 cm) metastatic disease, accurate identification of larger tumor nodules may have a significant impact on clinical management and the selection of patients for cytoreductive surgery. CASES: The cases of two patients with suspected recurrent Stage IIIC serous ovarian cancer based solely on elevated CA125 levels and one patient with an apparent Stage IC poorly differentiated ovarian sex cord-stromal tumor who had macroscopic surgically resectable disease (>1 cm) identified by PET after negative or equivocal computed tomography are presented. CONCLUSION: PET imaging may be a useful technique for identifying potentially surgically resectable, macroscopic metastatic ovarian cancer when computed tomography findings are negative or equivocal.

Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis.

PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy. MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication. RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P <.001). Each 10% increase in maximal cytoreduction was associated with a 5.5% increase in median survival time. When actuarial survival was estimated, cohorts with < or = 25% maximal cytoreduction had a mean weighted median survival time of 22.7 months, whereas cohorts with more than 75% maximal cytoreduction had a mean weighted median survival time of 33.9 months--an increase of 50%. The relationship between platinum dose-intensity and log median survival time was not statistically significant. CONCLUSION: During the platinum era, maximal cytoreduction was one of the most powerful determinants of cohort survival among patients with stage III or IV ovarian carcinoma. Consistent referral of patients with apparent advanced ovarian cancer to expert centers for primary surgery may be the best means currently available for improving overall survival.

Aberrant expression of homeobox gene HOXA7 is associated with müllerian-like differentiation of epithelial ovarian tumors and the generation of a specific autologous antibody response.

Autologous serum antibodies to molecules that are aberrantly expressed in tumors represent potential biomarkers for early diagnosis of cancer. In this study, we identified the homeobox gene HOXA7 as encoding an antigen in epithelial tumors of the ovary. These tumors are thought to arise from the simple epithelium lining the ovarian surface, but they often resemble the specialized epithelia derived from the müllerian ducts. Expression of HOXA7 was detected in ovarian tumors exhibiting müllerian-like features and correlated with the generation of anti-HOXA7 antibodies by patients. In contrast, it was observed that healthy women lack anti-HOXA7 antibodies (P < 0.0001) and that HOXA7 expression is absent from normal ovarian surface epithelium. Interestingly, HOXA7 expression was detected in the müllerian-like epithelium lining inclusion cysts in normal ovaries and in the müllerian duct-derived epithelium of normal fallopian tubes. Furthermore, ectopic expression of HOXA7 enhanced the epithelial phenotype of immortalized ovarian surface epithelial cells, as indicated by the appearance of cobblestone morphology, induction of E-cadherin expression, and down-regulation of vimentin. These findings associate aberrant HOXA7 expression with the müllerian-like differentiation of epithelial ovarian tumors and suggest diagnostic utility of serum antibodies to HOXA7.

Complete surgical cytoreduction of advanced ovarian carcinoma using the argon beam coagulator.

OBJECTIVE: The aim of this study was to evaluate the utility of the argon beam coagulator (ABC) in achieving optimal (< or =1 cm) disease status and facilitating the conversion of optimal but visible disease (0.1-1.0 cm) to microscopic residual disease (complete cytoreduction) among patients with advanced ovarian carcinoma. METHODS: All patients undergoing their primary attempt at surgical cytoreduction for Stage IIIB-IV epithelial ovarian carcinoma between October 1, 1997 and June 30, 2000 were identified from the tumor registry database. Data were abstracted retrospectively and included: the size/location of precytoreduction disease, surgical procedures performed, the anatomic regions in which the ABC was used for cytoreduction, the size/location of residual tumor, and the date of last follow-up and disease status. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using the chi(2) test, Fisher's exact test, log rank test, and multivariate logistic regression. RESULTS: Forty-five patients were identified (FIGO Stage IIIB = 8, Stage IIIC = 29, Stage IV = 8). Overall, optimal cytoreduction was achieved in 84.4% of patients; 60.0% had only microscopic residual and 24.4% had residual disease 0.1-1.0 cm. The ABC was used to facilitate cytoreduction in 31 patients. Optimal disease status was achieved in 93.6% of cases in which the ABC was used compared with 64.3% for non-ABC cases (P < 0.023). ABC use was also associated with a higher rate of complete cytoreduction (74.2%) compared with non-ABC cases (28.6%, P < 0.004). Among patients left with optimal disease (< or =1 cm), conversion to only microscopic residual was achieved in 79.3% of cases using the ABC and 44.4% of cases without ABC use (P < 0.044). The ABC was associated with a statistically significantly higher rate of complete cytoreduction for disease located in the lesser sac/gastrocolic ligament (90.9% vs 14.3%), abdominal peritoneum (95.5% vs 50.0%), bowel mesentery (80.0% vs 0), and pelvis (89.3% vs 50.0%). Multivariate analysis revealed that use of the ABC (P = 0.006) and disease in three or fewer anatomic regions (P = 0.014) were independent predictors of a microscopic residual surgical outcome. Complete cytoreduction was associated with a significant advantage in median progression-free survival (22.2 months) compared with patients with optimal but visible (0.1-1.0 cm) residual disease (12.3 months) and those with suboptimal (>1.0 cm) residual disease (6.3 months, P < 0.001). Among ABC cases, the mean estimated blood loss was 527 ml, and major postoperative complications occurred in 9.7% of patients. CONCLUSIONS: The ABC is a useful adjunct to conventional tumor reductive techniques and appears to significantly increase the feasibility of achieving both optimal disease status and complete cytoreduction of all visible tumor in patients with macroscopic metastatic ovarian carcinoma.

Ablation of metastatic ovarian carcinoma with the argon beam coagulator: pathologic analysis of tumor destruction.

OBJECTIVE: The aim of this study was to characterize the histopathologic effects of electrosurgical tumor destruction of metastatic ovarian carcinoma using the argon beam coagulator (ABC) and evaluate the depth of tissue damage produced by a range of power settings and tissue interaction times. METHODS: Epithelial ovarian carcinoma tumor specimens (1 cm(3)) were harvested intraoperatively. Following surgical excision, electrosurgical destruction of tumor was effected using the ABC at three power settings (60, 80, and 100 W) and three tissue interaction time intervals (1, 3, and 5 s), yielding nine experimental groups of 16 samples each (n = 144). Samples were formalin-fixed, cross-sectioned, stained with hematoxylin and eosin, and examined microscopically for histologic characteristics and depth of tissue destruction. RESULTS: Microscopic evaluation revealed that the total depth of destruction (TDD) produced by the ABC was composed of three distinct zones of tissue injury: vaporization, carbonized eschar (ESC), and coagulative necrosis (NEC). For each power setting, the mean TDD increased in a linear fashion as the interaction time interval increased from 1 to 5 s (60 W, 1.71 to 2.43 mm; 80 W, 2.24 to 3.69 mm; 100 W, 3.21 to 5.58 mm). By regression analysis, both power setting and tissue interaction time were independently associated with increasing TDD, with power having the strongest effect. At all power settings and interaction time intervals, the incremental change in TDD was primarily a function of the degree of tissue vaporization, which increased from 0.59 mm at 60 W (1 s) to 3.22 mm at 100 W (5 s). For all experimental groups, the ratio of NEC/ESC was highly consistent, ranging from 1.03 to 1.33 (P > 0.05, Bonferroni multiple comparisons procedure), and demonstrated that for each resulting ESC, an equivalent or greater degree of underlying NEC was also present. CONCLUSIONS: The destruction of ovarian carcinoma tumor tissue produced by the ABC is dependent upon both power setting and tissue interaction time. Increasing depth of destruction is due predominantly to a deeper level of tissue vaporization. The NEC/ESC ratio provides a reliable means of estimating the true depth of tumor destruction produced by the ABC and may contribute to increased safety and efficacy of electrosurgical cytoreduction of using this technique.

Management of pelvic hemorrhage.

Massive pelvic hemorrhage is a potential complication in any patient undergoing obstetric or gynecologic surgery. This article reviews the management of pelvic hemorrhage in obstetrics and gynecology, briefly discussing the blood supply to the pelvis and the physiology of normal coagulation and focusing on the causes and treatment of specific vascular injuries incurred during pelvic surgery.

Leiomyomatosis peritonealis disseminata and ovarian Brenner tumor associated with tamoxifen use.

Tamoxifen is frequently administered as adjuvant therapy for breast carcinoma and produces weak estrogen agonist effects in estrogen sensitive tissues. In addition to producing a measurable increase in the risk of endometrial carcinoma, tamoxifen has also been associated with increasing size of uterine leiomyomata as well as the development of new leiomyomata. As the indications for tamoxifen therapy expand, surveillance for additional potential associated adverse outcomes is warranted. A 44-year-old woman with a history of bilateral breast carcinoma presented with leiomyomatosis peritonealis disseminata and a right ovarian Brenner tumor 18 months after beginning adjuvant tamoxifen therapy. Although a causal link cannot be proven, this case is the second reported association between leiomyomatosis peritonealis disseminata, an ovarian Brenner tumor, and tamoxifen use for the treatment of breast carcinoma. Given the hormonal sensitivity of leiomyomatosis peritonealis disseminata, both mutagenic and mitogenic effects of tamoxifen on this rare entity must be considered. In the setting of continued hormonal treatment for breast carcinoma, the management of leiomyomatosis peritonealis disseminata presents unique clinical challenges.

Impact of increasing Papanicolaou test sensitivity and compliance: a modeled cost and outcomes analysis.

OBJECTIVE: To model the impact of increasing screening compliance or implementing liquid-based cytology in populations with known compliance patterns and risk profiles on rates of detection of cervical precancers. METHODS: An adaptation of a time-varying Markov model was used to follow a theoretic cohort of 100,000 women from age 20 through age 80. Separate analyses of all women, white, and black women were completed using three compliance rates (self-reported, Healthy People 2000, and Healthy People 2010 compliance) and two Papanicolaou test sensitivities (conventional Papanicolaou smear and liquid-based cytology). RESULTS: All populations benefited from both increased compliance and liquid-based cytology use. Increasing compliance to Healthy People 2010 goals resulted in 23%, 21.7%, and 17% reductions in cervical cancer incidence for all women, white, and black women, respectively. Substituting liquid-based cytology for traditional Papanicolaou smear collection and processing with no change in compliance resulted in 32%, 32%, and 33% reductions in cervical cancer incidence for the same three subpopulations. In addition, cost-effectiveness of the liquid-based technology indirectly related to the risk profile of the population: for black women, the cost-effectiveness ratio was $10,335 per life year saved, whereas for white women, the ratio was $17,967 per life year saved. CONCLUSION: Using liquid-based cytology in all populations would be cost-effective in improving outcomes from cervical cancer. In high-risk populations, this new technology may represent the most cost-effective approach to improve cervical cancer outcomes.

Extended surgical staging for uterine papillary serous carcinoma: survival outcome of locoregional (Stage I-III) disease.

OBJECTIVE: The aim of this study was to evaluate survival outcome in patients with locoregional uterine papillary serous carcinoma (UPSC) after extended surgical staging (ESS). METHODS: All patients diagnosed with FIGO Stage I-III UPSC undergoing ESS (vertical incision, peritoneal cytology, TAH/BSO, omental biopsy, lymph node sampling, peritoneal biopsy) between 1/1/89 and 12/31/98 were identified retrospectively from the tumor registry database. Pathologic features predictive of regional extrauterine spread were evaluated using the log-rank test. The Kaplan-Meier method was used to generate survival curves, and median survival determinations were compared using the log-rank test or the proportional hazards regression model. RESULTS: Twenty-six patients with locoregional UPSC were identified: FIGO Stage I (n = 11), Stage II (n = 7), and Stage III (n = 8). The median age at diagnosis was 66 years. Preoperative endometrial pathology correctly identified the presence of UPSC in 76.9% of cases. The only pathologic feature found to be predictive of regional extrauterine spread (Stage III) was myometrial invasion > or =50% (P = 0.028). Adjuvant radiation therapy (RT) was administered to 6/18 patients with Stage I/II disease and 5/8 patients with Stage III disease. Platinum-based chemotherapy was administered to 5 patients with Stage III disease. All recurrences of Stage I/II disease were located within the pelvis (16.7%). For Stage III disease, all recurrences occurred at distant sites (42.9%). The median follow-up time for surviving patients was 39.0 months (mean = 45.0 months). For all patients, the overall 5-year survival rate was 61.2%. According to FIGO stage, the overall 5-year survival rates were Stage I, 81.8%; Stage II, 64.3%; and Stage III, 31.3%. No significant differences were detected in the risk of death by stage, although there was a trend toward worse survival with Stage III disease: Stage I hazard ratio [HR] = 1.00, Stage II HR = 1.68, 95% confidence interval [CI] = 0.23-12.03, Stage III HR = 3.63, 95% CI = 0.65-20.12. CONCLUSIONS: Patients with locoregional UPSC following ESS have a more favorable prognosis than previously thought. The additional information provided by ESS facilitates the selection of adjuvant therapy. Whole pelvic RT is recommended for patients with Stage I/II disease. Pathologic Stage III disease portends a significant risk of distant recurrence. For these patients, administration of adjuvant chemotherapy should be considered in addition to directed RT.

Significance of "normal" endometrial cells in cervical cytology from asymptomatic postmenopausal women receiving hormone replacement therapy.

OBJECTIVE: The aim of this study is to assess the significance of normal endometrial cells identified in screening Pap smears from asymptomatic postmenopausal women taking hormone replacement therapy (HRT). METHODS: Endometrial histology reported from 93 asymptomatic postmenopausal women receiving HRT noted to have normal endometrial cells on a screening Pap smear was reviewed. Information regarding HRT, endometrial sampling, and interval between the sentinel Pap and sampling was extracted from the record. RESULTS: Endometrial biopsies were obtained an average of 1.7 months after the Pap smears. Eighteen of the ninety-three histology specimens (19%, 95% CI: 12--27%) identified abnormalities, in four cases precancerous or cancerous lesions. These 18 abnormalities included 7 endometrial polyps; 7 cases of simple hyperplasia, 1 with atypia; 3 cases of complex hyperplasia, 1 with atypia; and 1 endometrial adenocarcinoma. CONCLUSION: Normal endometrial cells identified on a screening Pap smear in this population may be an indication of endometrial disease.