Perioperative outcomes in a nationwide sample of patients undergoing surgical treatment of ovarian endometriomas.

OBJECTIVE: To evaluate the perioperative outcomes of premenopausal women undergoing cystectomy or oophorectomy for ovarian endometriomas (OMAs) and other benign neoplasms. DESIGN: Retrospective cohort study. SETTING: Clinical database containing information from 580 US hospitals. PATIENT(S): Women 18 to 50 years old who underwent ovarian cystectomy or oophorectomy for benign indications between 2010 and 2020. INTERVENTION(S): We compared procedure route, length of hospital stay, and complication rates by surgical indication (OMA vs. other benign neoplasms) and surgical procedure (cystectomy vs. oophorectomy). MAIN OUTCOME MEASURE(S): Thirty-day perioperative adverse events following adnexal surgery, including conversion to laparotomy, blood transfusion, ileus, urinary tract injury, bowel injury, readmission, and death. RESULT(S): We identified 120,208 ovarian cystectomies (28,182 OMAs and 92,026 other indications) and 53,476 oophorectomies (8,622 OMAs and 44,854 other indications). During cystectomy, patients with OMAs more commonly experienced conversion to laparotomy (5.1% vs. 3.1%) and readmission (8.5% vs. 7.1%). For oophorectomies, patients with OMAs less frequently had minimally invasive surgery (55.8% vs. 64.8%) or outpatient procedures (33.8% vs. 41.8%). Urinary tract and bowel injuries were rare. Multivariable logistic regression demonstrated that the presence of OMA predicted composite complications during cystectomy (adjusted odds ratio [aOR] 1.23, 95% confidence interval [CI] 1.18-1.28) but not during oophorectomy (aOR 1.05, 95% CI 0.99-1.12). Patients with OMAs had 1.37 times the odds of a composite complication during oophorectomy than during cystectomy (95% CI 1.28-1.47). CONCLUSION(S): Patients undergoing ovarian cystectomy for OMAs had higher rates of perioperative adverse events than patients undergoing ovarian cystectomy for other benign neoplasms. Laparotomies were performed more often during oophorectomies for OMAs than for other benign indications.

Ovarian cancer prognosis in women with endometriosis: a retrospective nationwide cohort study of 32,419 women.

BACKGROUND: Contradicting results regarding ovarian cancer prognosis in women with endometriosis have been reported in the literature. Owing to the small sample size of previous studies, larger studies are required to elucidate the role of endometriosis in ovarian cancer prognosis. OBJECTIVE: This study aimed to evaluate the survival rate in women with ovarian cancer with or without histologically proven endometriosis in a Dutch population-based cohort. STUDY DESIGN: All women with ovarian cancer diagnosed between 1990 and 2015 were identified from the Netherlands Cancer Registry. We linked these women with the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief) to identify all women with histologically proven endometriosis. We compared the prognosis of patients with ovarian cancer with and without histologically proven endometriosis. Primary outcome was the overall survival with subgroup analyses stratified by histologic ovarian cancer subtype and stage. Multivariable Cox proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals. RESULTS: We included 32,419 patients with ovarian cancer, of whom 1979 (6.1%) had histologically proven endometriosis. The median age of histologic endometriosis diagnosis was 53 years (interquartile range, 46-62). Of all women with ovarian cancer and endometriosis, 81.2% received a diagnosis of synchronous endometriosis and ovarian cancer. The endometriosis cohort was younger at ovarian cancer diagnosis, had more favorable tumor characteristics, and more often had surgical treatment for ovarian cancer than the women without endometriosis. These variables were included in the multivariable model as confounders. Women with histologically proven endometriosis had a significantly better prognosis in both crude and adjusted analyses (hazard ratio, 0.46; 95% confidence interval, 0.43-0.49; P<.0005, and adjusted hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P<.05, respectively). CONCLUSION: Women with ovarian cancer and histologically proven endometriosis had longer overall survival than women with ovarian cancer without endometriosis, even after adjustment for confounders. Future studies on ovarian cancer treatment and prognosis should consider stratifying by endometriosis status to elucidate its role. Furthermore, women diagnosed as having ovarian cancer and concurrent endometriosis should be explained the role of endometriosis in ovarian cancer survival.

Mortality of midlife women with surgically verified endometriosis-a cohort study including 2.5 million person-years of observation.

STUDY QUESTION: Is all-cause and cause-specific mortality increased among women with surgically verified endometriosis? SUMMARY ANSWER: The all-cause and cause-specific mortality in midlife was lower throughout the follow-up among women with surgically verified endometriosis compared to the reference cohort. WHAT IS KNOWN ALREADY: Endometriosis has been associated with an increased risk of comorbidities such as certain cancers and cardiovascular diseases. These diseases are also common causes of death; however, little is known about the mortality of women with endometriosis. STUDY DESIGN, SIZE, DURATION: A nationwide retrospective cohort study of women with surgically verified diagnosis of endometriosis was compared to the reference cohort in Finland (1987-2012). Follow-up ended at death or 31 December 2014. During the median follow-up of 17 years, 2.5 million person-years accumulated. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty-nine thousand nine hundred and fifty-six women with at least one record of surgically verified diagnosis of endometriosis in the Finnish Hospital Discharge Register between 1987 and 2012 were compared to a reference cohort of 98 824 age- and municipality-matched women. The age (mean ± standard deviation) of the endometriosis cohort was 36.4 ± 9.0 and 53.6 ± 12.1 years at the beginning and at the end of the follow-up, respectively. By using the Poisson regression models the crude and adjusted all-cause and cause-specific mortality rate ratios (MRR) and 95% confidence intervals (CI) were assessed. Calendar time, age, time since the start of follow-up, educational level, and parity adjusted were considered in the multivariate analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1656 and 4291 deaths occurred in the endometriosis and reference cohorts, respectively. A lower all-cause mortality was observed for the endometriosis cohort (adjusted MRR, 0.73 [95% CI 0.69 to 0.77])-there were four deaths less per 1000 women over 10 years. A lower cause-specific mortality contributed to this: the adjusted MRR was 0.88 (95% CI 0.81 to 0.96) for any cancer and 0.55 (95% CI 0.47 to 0.65) for cardiovascular diseases, including 0.52 (95% CI 0.42 to 0.64) for ischemic heart disease and 0.60 (95% CI 0.47 to 0.76) for cerebrovascular disease. Mortality due to alcohol, accidents and violence, respiratory, and digestive disease-related causes was also decreased. LIMITATIONS, REASONS FOR CAUSATION: These results are limited to women with endometriosis diagnosed by surgery. In addition, the study does not extend into the oldest age groups. The results might be explained by the characteristics and factors related to women's lifestyle, and/or increased medical attention and care received, rather than the disease itself. WIDER IMPLICATIONS OF THE FINDINGS: These reassuring data are valuable to women with endometriosis and to their health care providers. Nonetheless, more studies are needed to address the causality. STUDY FUNDING/COMPETING INTEREST: This research was funded by the Hospital District of Helsinki and Uusimaa and The Finnish Medical Foundation. None of the authors report any competing interest in relation to the present work; all the authors have completed the disclosure form.

Immunohistochemistry expression of targeted therapies biomarkers in ovarian clear cell and endometrioid carcinomas (type I) and endometriosis.

Ovarian clear cell and endometrioid carcinomas (type I) are thought to develop from endometriosis. ARID1A loss of expression is known to be related to the promotion of the endometriosis carcinogenesis. Despite the diverse origins and prognosis of type I and type II carcinomas, surgery followed by platinum-based chemotherapy is the mainstay of treatment for both. Limited knowledge about the expression of targeted therapies' biomarkers prevents the use of such markers as potential guides for tailored treatment. This study aimed to evaluate the expression of ARID1A gene and target therapies biomarkers (VEGF, PD-L1, and PARP-1) in ovarian clear cell and endometrioid carcinomas and endometriosis, and its relationship with prognosis. Forty-six ovarian clear cell and endometrioid carcinomas, and 24 endometriosis foci samples retrieved from the same surgical specimens were studied. ARID1A, VEGF, PD-L1, and PARP-1 immunohistochemistry expression was compared in carcinomas and endometriosis with regard to the clinicopathological features and prognosis. We found that endometriosis was associated with increased rates of diagnosis of cancer in the initial stages (P = .008). Different levels of expression of all biomarkers were detected in clear cell and endometrioid carcinomas and endometriosis. However, only the VEGF expression level showed a significant increase in the carcinoma group when compared with endometriosis (P = .0002). PARP-1 overexpression correlated with worse progression-free survival (P = .03) and overall survival (P = .01). In conclusion, endometriosis and ovarian clear cell and endometrioid carcinomas exhibited ARID1A loss of expression, and VEGF, PD-L1, and PARP-1 expression. PARP-1 overexpression in clear cell and endometrioid carcinomas was associated with early recurrence and worse overall survival.

Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status.

OBJECTIVES: Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status. METHODS: Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. RESULTS: Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29-5.02], in the multivariate analysis. CONCLUSIONS: Age at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.

Endometriosis-associated Ovarian Cancer: A Distinct Clinical Entity?

AIM: The aim of the study was to evaluate the incidence of endometriosis-associated ovarian cancer (EAOC) and compare clinicopathological characteristics and overall survival (OS) between patients with EAOC and those with ovarian cancer not associated with endometriosis. PATIENTS AND METHODS: We identified EAOC among 203 patients with invasive epithelial ovarian cancer who underwent complete surgery at our Institution from January 2004 to March 2014. RESULTS: EAOC was present in 45 patients. EAOC was significantly more frequently diagnosed at an earlier stage of disease (p=0.038). At a median follow-up time of 32 months, OS among patients with EAOC was significantly longer (p=0.039). However, stratifying by stage, the OS advantage of EAOC was not significant. At multivariate analysis, only stage was an independent prognostic factor for OS (hazard ratio=5.7; 95% confidence interval=1.8-18.6; p=0.003). CONCLUSION: EAOC incidence was 22.2%. EAOC appears to be diagnosed at an earlier stage and confers a better OS. However, stratifying by stage, the advantage in survival of EAOC disappears.

Does the Presence of Endometriosis Affect Prognosis of Ovarian Cancer?

Ovarian cancers diagnosed between 2000 and 2013 were examined and cases with and without endometriosis compared. Among 139 epithelial ovarian, there were 49 (35%) with endometriosis and 90 (65%) without endometriosis. Endometriosis associated ovarian cancers were more likely to be confined to the pelvis (54% vs. 9%, p < 0.0001) and lower grade (51% vs. 29%, p = 0.014). Younger age and earlier stage independently predicted the presence of endometriosis (p = 0.0011 and p < 0.0001, respectively). Ovarian cancer patients with endometriosis had improved PFS and OS [(HR = 0.20; 95% CI, 0.09-0.43), (HR = 0.18; 95% CI, 0.04-0.81)], compared to patients without endometriosis; however, endometriosis had no independent prognostic significance.

Effect of Endometriosis on the Prognosis of Ovarian Clear Cell Carcinoma: A Two-Center Cohort Study and Meta-analysis.

BACKGROUND: Whether endometriosis affects the prognosis of ovarian clear cell carcinoma (OCCC) remains controversial despite the relationship between OCCC and endometriosis. A two-center cohort study and meta-analysis were performed to investigate the effect of endometriosis on the prognosis of OCCC. METHODS: The study reviewed the clinicopathologic data of 109 patients with OCCC arising (n = 47) or not arising (n = 62) in endometriosis between 1997 and 2012 at two tertiary medical centers. Tumor response and survival were compared between the two groups. For further evaluation, PubMed, EmBase, and the Cochrane Library were searched, and a meta-analysis was conducted using 10 cohort studies published from March 1996 to May 2014, including the current cohort study. RESULTS: Complete response did not differ between the patients with OCCC arising in endometriosis and those without endometriosis (77.5 vs. 87.3 %; P = 0.444). Early-stage disease and optimal debulking surgery were the only independent factors that reduced the risk of noncomplete response (adjusted odds ratios 0.203 and 0.038; 95 % confidence intervals [CIs] 0.045-0.920 and 0.006-0.226, respectively). Progression-free survival (PFS) and overall survival (OS) did not differ between the two groups. Early-stage disease and optimal debulking surgery were the only favorable factors that improved PFS (adjusted hazard ratios [HRs] 0.216 and 0.332; 95 % CIs 0.099-0.469 and 0.150-0.732, respectively) and OS (adjusted HRs 0.099 and 0.339; 95 % CIs 0.039-0.252 and 0.141-0.815, respectively). Furthermore, crude and subgroup meta-analyses showed no effect of endometriosis on PFS or OS in OCCC patients. CONCLUSION: Endometriosis may not affect the tumor response or the prognosis of OCCC patients.

Revisión: Modelos animales en el estudio etiopatogénico, el diagnóstico y el tratamiento de la endometriosis / Review: Animal models in the study of the etiopathogeny, diagnostic, and treatment of the endometriosis

La endometriosis es una enfermedad ginecológica común caracterizada por la presencia de tejido endometrial en el exterior de la cavidad uterina. Dicha patología cursa con diversos síntomas como dismenorrea, dolor pélvico crónico e infertilidad y presenta una elevada prevalencia, afectando a aproximadamente un 10% de la población femenina en edad reproductiva. Pese a todo, actualmente poco se conoce sobre los mecanismos que actúan en el establecimiento y desarrollo de esta enfermedad. Además, no se dispone de un tratamiento satisfactorio. Los modelos animales nos permiten el estudio de la secuencia temporal de eventos involucrados en el establecimiento y el desarrollo de la endometriosis, así como la evaluación de nuevos fármacos y/o tratamientos. En esta revisión se describen los modelos animales que han sido utilizados hasta la fecha, haciendo hincapié en su importancia en la investigación de los mecanismos de la enfermedad así como en su tratamiento (AU)

Endometriosis is a condition characterized by the presence of endometrial–like tissue outside the uterine cavity. It has a high prevalence (10% of the female population), and causes several symptoms like pelvic pain and infertility. Nevertheless, nowadays, little is known about the mechanisms underlying the development and establishment of this condition and the treatments available, which consists in surgery and medical therapies, are not satisfactory. The use of animal models allows us to study the temporal sequence of events involved in the establishment and progression of the disease. This review describes the animal models for endometriosis that have been used, highlighting their importance for the investigation of disease mechanisms and to test new drugs and/or treatments (AU)

Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis.

Clear cell adenocarcinoma of the ovary (OCC) is a chemo-resistant tumor with a relatively poor prognosis and is frequently associated with endometriosis. Although it is assumed that oxidative stress plays some role in the malignant transformation of this tumor, the characteristic molecular events leading to carcinogenesis remain unknown. In this study, an array-based comparative genomic hybridization (CGH) analysis revealed Met gene amplification in 4/13 OCC primary tumors and 2/8 OCC cell lines. Amplification of the AKT2 gene, which is a downstream component of the Met/PI3K signaling pathway, was also observed in 5/21 samples by array-based CGH analysis. In one patient, both the Met and AKT2 genes were amplified. These findings were confirmed using fluorescence in situ hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemistry. In total, 73 OCC cases were evaluated using real-time quantitative PCR; 37.0% demonstrated Met gene amplification (>4 copies), and 8.2% had AKT2 amplification. Furthermore, stage 1 and 2 patients with Met gene amplification had significantly worse survival than patients without Met gene amplification (p<0.05). Met knockdown by shRNA resulted in reduced viability of OCC cells with Met amplification due to increased apoptosis and cellular senescence, suggesting that the Met signaling pathway plays an important role in OCC carcinogenesis. Thus, we believe that targeted inhibition of the Met pathway may be a promising treatment for OCC.

Long term survival of ovarian endometriosis associated clear cell and endometrioid ovarian cancers.

OBJECTIVE: This study aimed to analyze long-term survival of clear cells (CCs) and endometrioid (E) ovarian cancer cases according to presence of endometriosis in the pathologic report. METHODS: This is a retrospective analysis of 47 CC and 66 E ovarian cancer cases observed consecutively at our center between 1990 and 2010.All cases had first surgery at our center or were referred to it for treatment and follow-up.Cases were identified according to the original diagnosis reported in clinical records.All pathologic reports were reviewed, and cases were classified with or without pathologic evidence of endometriosis on the basis of the pathologic report.Follow-up was updated in March 2011. The follow-up median was 147 months (range, 116-171). RESULTS: Endometriosis-associated ovarian cancer cases were more frequently diagnosed at stage I to II than cases without endometriosis: among the 36 endometriosis-associated ovarian cancer cases, 25 (69%) were at stage I or II, and the corresponding value was 35 (46%) of 77 among cases without endometriosis (P = 0.0173).The presence of endometriosis tended to be associated with a higher 10-year survival rate: after taking the potential confounding effect of stage into account, the finding was not statistically significant (hazards ratio, 0.7; 95% confidence interval, 0.3-1.5). CONCLUSIONS: This analysis shows that EA CCs and E ovarian cases are diagnosed at an earlier stage than cases without endometriosis. No clear association emerged between presence of endometriosis and survival.

Prognostic analysis of ovarian cancer associated with endometriosis.

OBJECTIVE: The objective of the study was to evaluate the prognosis of ovarian cancer arising in endometriosis. STUDY DESIGN: We retrospectively compared 42 cases of endometriosis-associated ovarian cancer (EAOC) with 184 cases of ovarian carcinoma without endometriosis (OC). RESULTS: The median age in the EAOC group was 52 vs 59 years in OC (P < .05). In comparison with OC, the EAOC patients were more likely to have low-grade (21% vs 8%; P = .04) and early-stage tumors (International Federation of Gynecology and Obstetrics I and II combined) (49% vs 24%; P = .002). Clear cell (21% vs 2%) and endometrioid (14% vs 3%) tumors were more frequent in EAOC, whereas mucinous tumors were more prevalent in OC (P = .001). The median survival (199 vs 62 months) and the 5 year survival (62% vs 51%) were better for EAOC when compared with OC (P = .038). After controlling for age, stage, grade, and treatment, association with endometriosis was not an independent predictor of better survival in ovarian cancer. CONCLUSION: As such, EAOC has a much better survival rate than OC. This could be explained by the higher prevalence of early-stage and low-grade tumors in EAOC when compared with OC.

Endometriosis as a prognostic factor for cancer survival.

Studies have shown an increased risk of malignancies in women with endometriosis. Little is known about the impact of endometriosis on cancer survival. We investigated whether the survival after a diagnosis of a malignancy differs in women with a previously diagnosed endometriosis compared to other women. Women with a first time diagnosis of a malignancy in 1969-2005, were identified using the National Swedish Cancer Register (NSCR). By use of the National Swedish Patient Register (NSPR) we identified all women with a diagnosis of endometriosis during the same period and linked these patients with the data from the NSCR. The cohort comprised 4,278 women with endometriosis and a malignancy, and 41,831 randomly selected matched women without endometriosis. Cox regression was used for all calculations to obtain crude and adjusted cause specific mortality rates, measured as hazard ratios (HR) with 95% confidence intervals (CI). A total of 46,109 women entered the study. There was a statistically significant better survival for women with endometriosis for all malignancies combined (HR=0.92) and for breast cancer (HR=0.86) and ovarian cancer (HR=0.81) specifically. For breast cancer the survival enhancing effect in women with endometriosis decreased with increasing parity. There was poorer survival in malignant melanoma for women with endometriosis (HR=1.52). The survival in a malignancy is better in women with a previously diagnosed endometriosis compared to women without endometriosis especially for breast and ovarian cancers. The prognosis of malignant melanoma is poorer in women with endometriosis.

Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery.

OBJECTIVE: To investigate the need for further surgery after laparoscopic excision of endometriosis or hysterectomy. METHODS: In this retrospective study, women who had surgery for endometriosis-associated pain at the Cleveland Clinic were assessed for requirement for subsequent surgery. One hundred twenty patients who underwent hysterectomy with or without oophorectomy for endometriosis and 120 patients who had laparoscopic excision of their endometriotic lesions only (local excision group) formed the study population. Estimates of reoperation-free survival at 2, 5, and 7 years were calculated using Kaplan-Meier methods, and estimates of risk (hazard ratios) were computed using Cox proportional hazards models. A significance level of .05 was assumed for all tests. RESULTS: In women who underwent local excision with ovarian preservation, the surgery-free percentages were 79.4%, 53.3%, and 44.6%, respectively, at 2, 5, and 7 years. In women who underwent hysterectomy with ovarian preservation, the 2-, 5-, and 7-year reoperation-free percentages were 95.7%, 86.6%, and 77.0%, respectively. In women who underwent hysterectomy without ovarian preservation, the percentages were 96.0%, 91.7%, and 91.7%, respectively. However, in women between 30 and 39 years of age, removal of the ovaries did not significantly improve the surgery-free time. CONCLUSION: Local excision of endometriosis is associated with good short-term outcomes but, on long-term follow-up, has a high reoperation rate. Hysterectomy is associated with a low reoperation rate. Preservation of the ovaries at the time of hysterectomy remains a viable option. LEVEL OF EVIDENCE: II.

Long-term follow-up after conservative surgery for rectovaginal endometriosis.

OBJECTIVE: The purpose of this study was to evaluate long-term results in patients who received conservative surgical treatment for rectovaginal endometriosis. STUDY DESIGN: We analyzed the follow-up data for 83 women who underwent surgery for rectovaginal endometriosis. The inclusion criteria were age 20 to 42 years, moderate-to-severe pain symptoms, conservative treatment with retention of the uterus, and at least 1 ovary; the follow-up period was > or =12 months. Kaplan-Meier analysis and Cox regression were used to calculate recurrence rates. RESULTS: The cumulative rates of pain recurrence, clinical or sonographic recurrence, and new treatment were 28%, 34%, and 27%, respectively. The younger patients had the higher risk of recurrence. Pregnancy had protective effects against the recurrence of symptoms and a need for a new treatment. Patients who underwent bowel resection had fewer recurrences. CONCLUSION: Segmental resection and anastomosis of the bowel, when necessary, improves the outcome without affecting chances of conception. Higher recurrence rates in younger patients seems to justify a more radical treatment in this group of women.

Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the cynomolgus monkey.

An increase in the incidence and severity of endometriosis following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was a serendipitous finding in a reproductive toxicology study in rhesus monkeys. The purpose of this study was to investigate the effects of subchronic exposure to TCDD on the survival and growth of surgically implanted endometrial fragments. Endometrial fragments of equal size (4 x 1 mm(2)) were auto-transplanted to the pelvic cavity of nulliparous cynomolgus monkeys (Macaca fascicularis, n = 23), who were divided into 4 treatment groups and dosed 5 days a week with gelatin capsules containing 0, 1, 5, or 25 ng/kg body weight of TCDD mixed with glucose. Endometrial implant survival was monitored by laparoscopy at intervals of 1, 3, and 6 months. Animals were euthanized at 12 months of treatment in the early to mid luteal phase and the maximal and minimal endometrial implant diameter was measured. Both the maximal and minimal diameters were significantly reduced in the 0.71-ng/kg/day-TCDD dose group, compared to controls, whereas the survival rate was unaffected (20 vs. 16%, respectively). In contrast, exposure to 3.57 and 17.86 ng/kg/day TCDD for 1 year resulted in a significantly higher survival rate of implants (26.7% and 33.3% respectively vs. 16.0%) and significantly larger diameter implants in the 17.86-ng/kg/day dose group only, compared to the control group. Treatment had no effect on circulating gonadal steroid levels or menstrual cycle characteristics. It is concluded that TCDD facilitates the survival of endometrial implants and exerts a bimodal effect on endometrial implant growth.

Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation.

OBJECTIVE: To assess the efficacy of two laparoscopic methods for the management of endometriomas with regard to pain relief, pregnancy rate, and disease recurrence. DESIGN: Prospective, randomized clinical trial. SETTING: Tertiary care hospital. PATIENT(S): Sixty-four patients with advanced stages of endometriosis. INTERVENTION(S): Patients were randomly allocated at the time of laparoscopy to undergo either cystectomy of the endometrioma (group 1) or drainage of the endometrioma and bipolar coagulation of the inner lining (group 2). MAIN OUTCOME MEASURE(S): Pain relief and pregnancy rate. RESULT(S): Thirty-two patients were enrolled in each group. The 24-month cumulative recurrence rates of dysmenorrhea, deep dyspareunia, and nonmenstrual pelvic pain were lower in group 1 than in group 2 (dysmenorrhea: 15.8% versus 52.9%; deep dyspareunia: 20% versus 75%; nonmenstrual pelvic pain: 10% versus 52.9%). The median interval between the operation and the recurrence of moderate to severe pelvic pain was longer in group 1 than in group 2 (19 months [range, 13.5-24 months] versus 9.5 months [range, 3-20 months]). The 24-month cumulative pregnancy rate was higher in group 1 than in group 2 (66.7% versus 23.5%). CONCLUSION(S): For the treatment of ovarian endometriomas, a better outcome with a similar rate of complications is achieved with laparoscopic cystectomy than with drainage and coagulation.

Primary squamous cell carcinoma of the ovary. Report of 37 cases.

A total of 37 cases of ovarian primary squamous cell carcinoma (SCC)-19 associated with a dermoid cyst (SCCD), seven associated with endometriosis (SCCE), and 11 pure (SCCP)-are described. The last 18 cases belong within the new World Health Organization category of SCC in the surface epithelial-stromal category. The 19 patients with SCCD were 21-75 (mean, 52) years old; three of the carcinomas were in situ and seven, six, and three tumors were stages I, II, and III, respectively. The tumors and associated dermoid cysts were 6-35 cm in greatest dimension, usually forming mural nodules with intracavitary protrusion and focal necrosis and hemorrhage; two, seven, and seven tumors were grades 1, 2, and 3, respectively. SCCD was focally associated with a columnar epithelial cyst lining in 13 cases, suggesting an origin therein. One patient with stage I, grade 1 SCCD also had squamous cell carcinoma in situ (CIS) of the cervix. The seven patients with SCCE were 29-70 (mean, 49) years old, and one, three, one, and two tumors were stages I, II, III, and IV, respectively; all of the tumors were grade 3. One was associated with squamous cell carcinoma in situ of the cervix. The 11 patients with SCCP were 27-73 (mean, 56) years old, and one, four, five, and one tumors were stages I, II, III, and IV, respectively. The tumors were 6-26 cm in greatest diameter, usually solid with focal necrosis; one and 10 tumors were grades 2 and 3, respectively. Three patients with SCCP also had cervical squamous cell carcinoma in situ. The patients with SCCE had a poorer overall survival than those with SCCD. Five of the six patients with SCCE for whom adequate follow-up information was available died of their disease (mean survival, 5 months); also, in all five cases of SCCE reported in the literature, the patients died of their disease (mean survival, 4 months). The stage of the tumor and its grade correlated best with overall survival for all three types of SCC.

Endometrioid adenocarcinoma of the ovary and its relationship to endometriosis.

In order to better understand the clinical presentation and biologic behavior of ovarian carcinomas arising in endometriosis, we performed a historical cohort study of all women with endometrioid adenocarcinoma of the ovary (ECO) diagnosed between 1979 and 1991 at our institutions. A review of pathology reports determined the presence or absence of coexisting endometriosis. Cancers adjacent to endometriosis on the same ovary or arising within endometriosis were labeled endometriosis-associated endometrioid adenocarcinoma (EAEA), while all others were considered typical endometrioid adenocarcinoma (TEA). Associations between tumor type and clinicopathologic variables were analyzed by chi 2 and Fisher's exact tests as indicated. Disease-free interval (DFI) and overall survival were estimated using the Kaplan-Meier method. The independent prognostic significance of clinicopathologic variables was determined by multivariate analysis using the Cox proportional hazards regression model. Of 91 ECO patients identified, 63 (69%) had TEA and 28 (31%) had EAEA. Significant differences between TEA and EAEA existed for age at diagnosis (greater than 55 years; 56 vs 32%, P = 0.039), nulliparity (19 vs 46%, P = 0.007), stage (I and II combined; 37 vs 70%, P = 0.004), and disease status at completion of primary surgery (complete tumor resection; 47 vs 70%, P = 0.04). Synchronous atypical endometrial hyperplasia or uterine carcinoma was found in 7/63 (11%) TEA versus 7/28 (25%) EAEA cases (P = 0.054). Estimated 5-year DFI by life table analysis was significantly longer in the EAEA than in the TEA cohorts (57 vs 25%, P = 0.02); however, the 5-year survival difference was not significant (59 vs 45%, P = 0.18). Multivariate analysis identified only stage as an independent prognostic factor in predicting both DFI and survival. In conclusion, women with EAEA are significantly younger, present with earlier stage disease, and have a longer disease-free survival than those with TEA. These factors may reflect a more favorable biologic behavior of ECO when arising in association with endometriosis.

Clinical remission criteria for epithelial carcinoma of the ovary.

After primary cytoreductive surgery 188 patients with epithelial ovarian cancer were treated with combination chemotherapy between 1986 and 1989 in the Tokai Ovarian Tumor Study Group. Clinical remission criteria were set in this study and patients were examined to determine if they were in remission or not. Forty-seven cases (25%) had no remission and 85.9% of them died within 20 months after primary surgery. Fifty-seven cases (30.3%) had a remission and a subsequent recurrence. Eighty-four cases (44.7%) had no recurrence and all are currently alive. Independent remission factors by multivariate analysis were higher stage (P = 0.018), clear-cell carcinoma (P = 0.0048), larger maximum residual tumor (P = 0.0023), and PVB therapy (P = 0.026). Independent recurrence factors were higher stage (P = 0.0012), serous cystadenocarcinoma (P = 0.0001), clear-cell carcinoma (P = 0.00409), and PVB therapy (P = 0.0499). A significantly high remission rate and low recurrence rate was achieved using PVB therapy. This criteria has value for the treatment of epithelial ovarian carcinoma. The disease-free survival rate after clinical remission was the same as that after a negative second-look laparotomy, which implies that a second-look laparotomy may be unnecessary in the management of epithelial carcinoma of the ovary.