Incidence of ovarian cancer after bilateral salpingo-oophorectomy in women with histologically proven endometriosis.

OBJECTIVE: To assess the incidence of ovarian cancer in women with histologically proven endometriosis after bilateral salpingo-oophorectomy (BSO). DESIGN: Retrospective nationwide cohort study. SETTING: Dutch pathology database. PATIENT(S): Women with histologically proven endometriosis who had undergone BSO between 1990 and 2015 (n = 7,984). This study consists of 2 control cohorts: women with histologically proven endometriosis without BSO (n = 42,633) and women with a benign dermal nevus (n = 132,535). INTERVENTION(S): Observational study. MAIN OUTCOME MEASURE(S): Number of histologic diagnoses of (extra-)ovarian cancers. Incidence rate ratios (IRR) were estimated for (extra-)ovarian cancer. The number needed to treat was calculated. RESULT(S): We identified 9 (0.1%) (extra-)ovarian cancers in the BSO cohort and 170 (0.4%) and 444 (0.3%) ovarian cancers in the endometriosis and nevus control cohorts, respectively. We found an age-adjusted IRR of 0.34 (95% confidence interval [CI], 0.15-0.76) when the BSO cohort was compared with the endometriosis cohort. Comparing the BSO cohort with the nevus control cohort resulted in an age-adjusted IRR of 0.38 (95% CI, 0.17-0.85). The number needed to treat when the BSO cohort was compared with the endometriosis control cohort was 351 (95% CI, 272-591). CONCLUSION(S): In this nationwide study, we found that the (extra-)ovarian cancer incidence in women with histologically proven endometriosis decreased to less than the background population risk after BSO. Additionally, we found a significant reduction of the incidence of ovarian cancer when compared with women with histologically proven endometriosis without BSO. Endometriosis surgery could in the future be a preventive strategy in women with endometriosis and a high-risk profile for ovarian cancer.

Endometrial cancer prognosis in women with endometriosis and adenomyosis: A retrospective nationwide cohort study of 40 840 women.

We aim to compare endometrial cancer survival in women with or without histological proven endometriosis or adenomyosis. We identified all women with endometrial cancer between 1990 and 2015 from the Netherlands Cancer Registry (NCR). Data were linked to the Dutch pathology database (PALGA) to select all women with histological proven endometriosis/adenomyosis. Overall survival was compared between women with endometrial cancer with or without endometriosis/adenomyosis. We used multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs). We included 1701 women with endometrial cancer and endometriosis/adenomyosis, of whom 1236 (72.7%) women had adenomyosis, 320 (18.8%) had endometriosis and 145 (8.5%) had both. We compared these women to 39 139 women with endometrial cancer without endometriosis/adenomyosis. Women in the combined endometriosis/adenomyosis cohort were younger at endometrial cancer diagnosis, had earlier disease stage, more often had endometrioid endometrial cancer and low grade tumors. The 5-year survival rate in the combined endometriosis/adenomyosis cohort was 84.8% (95% CI 84.6-88.1) and 71.6% (95% CI 71.1-72.0) in the nonendometriosis/adenomyosis cohort. Univariable analysis resulted in a crude HR of 0.63 (95% CI 0.59-0.69). Significant confounding factors were age, stage, cancer subtype, histological grading, surgery and chemotherapy rate. Correction for these confounders resulted in a HR of 0.98 (95% CI 0.90-1.06). Including endometriosis/adenomyosis status as a categorical factor resulted in similar HRs. In conclusion, women with endometrial cancer and histologically proven endometriosis/adenomyosis have a better overall survival when compared to women with endometrial cancer without endometriosis/adenomyosis. This better survival was correlated to stage, grade, age and histological subtype, but not to the presence of endometriosis/adenomyosis.

Endometrial Cancer Incidence in Endometriosis and Adenomyosis.

Women with histologically proven endometriosis/adenomyosis have an increased risk of ovarian cancer. Small studies show conflicting results on the endometrial cancer risk in women with endometriosis/adenomyosis. Therefore, we assessed the incidence of endometrial cancer in women with histologically proven endometriosis or adenomyosis. We performed a population-based retrospective cohort study of 129,862 women with histologically proven endometriosis/adenomyosis, matched with 132,700 women with a nevus selected from the Dutch pathology registry between 1990 and 2015. Histology results for endometrial cancer were retrieved. Crude and age-adjusted odds ratios for endometrial cancer were estimated. In the endometriosis/adenomyosis group, 1827 (1.4%) women had a histological report on endometrial cancer, and in the nevus group, 771 (0.6%) women. The age-adjusted OR for endometrial cancer was 2.58 (95%CI 2.37-2.81). After excluding the first year of follow-up, the age-adjusted OR was 0.76 (95%CI 0.63-0.92), indicating that endometrial cancer is most often found at time of histological diagnosis of endometriosis/adenomyosis. In around 20% of the endometrial cancer cases, the endometrial cancer was not recognized until after hysterectomy. Of these women, 35% had no prior (micro)curettage or biopsy. This study shows an increased incidence of endometrial cancer in women with histologically proven endometriosis and adenomyosis.

Increased incidence of ovarian cancer in both endometriosis and adenomyosis.

OBJECTIVE: Assessing the association between endometriosis and/or adenomyosis and ovarian cancer. METHODS: We identified all women with histological proven endometriosis (51,544 women) and/or adenomyosis (85,015 women) from the Dutch pathology database (1990-2015) and matched with women with a benign dermal nevus (132,654 women). Histology results for ovarian cancer were retrieved. We estimated crude and age-adjusted incidence rate ratios (IRR) for ovarian cancer. RESULTS: We found 1017 (2.0%), 1284 (1.5%) and 471 (0.4%) ovarian cancer cases in the endometriosis, adenomyosis and nevus cohort, respectively. The age-adjusted IRRs were 19.75 (95% CI 16.70-23.35) in the endometriosis cohort and 5.93 (95% CI 4.91-7.16) in the adenomyosis cohort. The highest IRRs were found for endometrioid and clear cell ovarian cancer subtypes. Excluding the first year of follow-up did not result in a significant IRR for ovarian cancer overall but resulted in a statistically significant age-adjusted IRR of 3.92 (95% CI 2.19-7.01) for clear cell ovarian cancer and 2.39 (95% CI 1.28-4.45) for endometrioid ovarian cancer in the endometriosis cohort. Additionally, we found a statistically significant age-adjusted IRR of 2.51 (95% CI 1.29-4.90) for endometrioid ovarian cancer in the adenomyosis cohort. CONCLUSION: We found an increased ovarian cancer incidence in both histological proven endometriosis and adenomyosis. This increased incidence was largest for endometriosis. Excluding the first year of follow-up resulted in an increased incidence for endometrioid ovarian cancer in both cohorts and clear cell ovarian cancer in the endometriosis cohort. This study shows that gynecologist should also be aware of an increased ovarian cancer incidence in women with adenomyosis.

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.

Increased association of ovarian cancer in women with histological proven endosalpingiosis.

BACKGROUND: Few studies have investigated the possible association between endosalpingiosis and ovarian cancer, therefore we assessed whether there is an association between histological confirmed endosalpingiosis and ovarian cancer. METHODS: We identified all women with a histological diagnosis of endosalpingiosis between 1990 and 2015 from the Dutch nationwide registry of histopathology and cytopathology (PALGA). We used women with a benign dermal nevus as controls. Histology results for cancer of the ovaries, fallopian tubes and peritoneum between January 1990 and July 2017 were retrieved. Incidence rate ratios (IRR) were estimated for ovarian cancer and its subtypes. RESULTS: We found 2490 women with a histological diagnosis of endosalpingiosis, of which 1005 women 40.4 %) had concurrent endometriosis. The age-adjusted IRR for ovarian cancer in endosalpingiosis patients (including endometriosis) was 43.7 (95 %CI 35.1-54.3). Excluding cases with concurrent endometriosis, resulted in an age-adjusted IRR of 38.8 (95 %CI 29.3-50.4). IRRs were 2.4 (95 %CI 1.4-3.9) and 1.8 (95 %CI 0.8-4.0) respectively when excluding synchronously diagnosed cases. The increased IRRs seem to be caused by an increased risk of clear cell and endometrioid ovarian cancer subtypes. CONCLUSIONS: This study shows an association between histological diagnosed endosalpingiosis and ovarian cancer. The association with endometrioid and clear cell subtypes seems most outspoken. Additionally, this study shows that this association is independent of histological endometriosis diagnosis, making it important for pathologists to report endosalpingiosis accurately and for gynaecologists to be more aware of the increased association of ovarian cancer in women with endosalpingiosis.

Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study.

BACKGROUND: Several studies have suggested that endometriosis is associated with an increased risk of ovarian cancer, especially for the clear-cell and endometrioid subtypes. However, previous studies lack sufficient power or diagnostic certainty. OBJECTIVE: The objective of the study was to assess the association between histologically proven endometriosis and ovarian cancer in a large population-based cohort study. STUDY DESIGN: We identified 131,450 women with a histological diagnosis of endometriosis between 1990 and 2015 from the Dutch nationwide registry of histopathology and cytopathology (PALGA). For the control cohort 132,654 women with a benign dermal nevus were matched on age and inclusion year with the endometriosis cases. Histological diagnoses of ovarian, fallopian tubes, and peritoneal cancers between January 1990 and July 2017 were retrieved. Incidence rate ratios were estimated for ovarian cancer and its subtypes for the whole follow-up period as well as for women with more than 1 person-year at risk. RESULTS: We found a crude incidence rate ratio of 4.79 (95% confidence interval, 4.33-5.31) and an age-adjusted incidence rate ratio of 7.18 (95% confidence interval, 6.17-8.36) for ovarian cancer overall. Endometrioid and clear-cell ovarian cancer had the highest age-adjusted incidence rate ratio of 29.06 (95% confidence interval, 20.66-40.87) and 21.34 (95% confidence interval, 14.01-32.51), respectively. Median age at ovarian cancer diagnosis was 56 years (interquartile range, 49-63) for the endometriosis cohort and 60 years (interquartile range, 53-67) for the nevus cohort, (P < .05). After excluding women with less than 1 person-year at risk following an endometriosis diagnosis, we found a crude incidence rate ratio of 1.04 (95% confidence interval, 0.91-1.19) and an age-adjusted incidence rate ratio of 1.08 (95% confidence interval, 0.87-1.35) for ovarian cancer overall. However, statistically significant age-adjusted incidence rate ratios of 2.29 (95% confidence interval, 1.24-4.20) for clear-cell ovarian cancer and 2.56 (95% confidence interval, 1.47-4.47) for endometrioid ovarian cancer were found. CONCLUSION: A significantly higher incidence of clear-cell and endometrioid ovarian cancer was found in women with histologically proven endometriosis. Additionally, we found an increased incidence of all ovarian cancer subtypes in histologically proven endometriosis; however, in many of these women, endometriosis and ovarian cancer were diagnosed synchronously after the average menopausal age, which may suggest that the risk of ovarian cancer in endometriosis patients remains, even when clinical endometriosis symptoms are no longer present.

A brother and sister with intellectual disability and characteristic neuroimaging findings.

Leukoencephalopathy with brain calcifications and cysts (LCC) is a genetic white matter disorder, which involves the brain small blood vessels. In the absence of extra-neurological symptoms, LCC has a pathognomonic radiological phenotype. Recently, biallelic mutations in the SNORD118 gene, which is a non-protein coding gene, were discovered to cause LCC. We present here two siblings with developmental delay and a typical MRI pattern, who were diagnosed with LCC. The mutations in the SNORD118 gene were initially missed with whole exome sequencing (WES), but recognition of the MRI patterns of both children raised the suspicion of LCC and led to a genetically proven diagnosis after re-evaluation of the WES data.

Multimodal Hyperspectroscopic Imaging for Detection of High-Grade Cervical Intraepithelial Neoplasia.

OBJECTIVE: Numerous new alternative digital colposcopy techniques have been developed, of which multimodal hyperspectroscopy (MHS) showed a high sensitivity in previous studies. The objective of this prospective single-center cohort study was to evaluate the clinical value of MHS for detecting high-grade cervical intraepithelial neoplasia in a colposcopy referral population and colposcopy follow-up population, to assess whether MHS could be safely used to improve care for women at risk for high-grade cervical intraepithelial neoplasia. MATERIALS AND METHODS: A total of 125 women from a colposcopy referral population and colposcopy follow-up population were evaluated with MHS and tested for the presence of high-risk human papillomavirus (HPV) with HPV-16/18 genotyping. Spectroscopic measurements of the cervix were taken and compared with an end point based on histology, high-risk HPV, and cytology. Evaluable data for analysis were collected from 102 of the subjects. Sensitivity, specificity, and predictive values were calculated for MHS and colposcopic impression based on conventional colposcopic examination. RESULTS: From the total study population of the 102 patients, 47 were enrolled in the colposcopy referral group and 55 in the colposcopy follow-up group. The MHS yielded a sensitivity of 93.6% (95% CI = 78.6-99.2), with a corresponding specificity of 42.3% (95% CI = 30.6-54.6) in the group with a composite end point. No adverse effects occurred, and patient acceptability was high. CONCLUSIONS: Multimodal hyperspectroscopy is a digital colposcopy technique that offers an easy, rapid, well-tolerated point-of-care assessment with a high sensitivity for the presence of high-grade cervical intraepithelial lesions, however, with a low specificity, resulting in limited clinical value.

Alternative Colposcopy Techniques: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the diagnostic value of alternative (digital) colposcopy techniques for detection of cervical intraepithelial neoplasia (CIN) 2 or worse in a colposcopy population. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Library were searched from inception up to January 11, 2016, for studies that evaluated the diagnostic value of alternative (digital) colposcopy techniques. METHODS OF STUDY SELECTION: Inclusion criteria were: 1) an alternative (digital) colposcopy technique was used in a colposcopy population; 2) a histologic outcome was reported, classified as CIN, differentiating between mild dysplasia or less (CIN 1 or less), and moderate dysplasia or worse (CIN 2 or greater); 3) the entire cervix was scanned at once or a per-woman analysis was performed; 4) no other topical application than acetic acid and Lugol's solution was used; 5) at least three eligible studies had to be available within a single technique; and 6) studies obtained research ethics approval. Language was restricted to English. TABULATION, INTEGRATION, AND RESULTS: Two reviewers assessed the eligibility of the identified articles. Disagreements were resolved by a third reviewer. Thirteen studies met the inclusion criteria. We found six studies on fluorescence and reflectance spectroscopy, including 2,530 women, with a pooled sensitivity of 93% (95% confidence interval [CI] 89-95%) and specificity of 62% (95% CI 47-76%). Four studies on dynamic spectral imaging were found including 1,173 women with a pooled sensitivity of 69% (95% CI 48-85%) and specificity of 83% (95% CI 76-88%). We found three studies on optical coherence tomography including 693 women with a pooled sensitivity of 48% (95% CI 32-64%) and specificity of 77% (95% CI 52-91%). Previously published conventional colposcopy results showed a sensitivity of 61% (95% CI 58-63%) and a specificity of 85% (95% CI 83-86%). CONCLUSION: Alternative (digital) colposcopy techniques may result in increased sensitivity and specificity, but no recommendation for introduction in clinical practice can be made yet.