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Diagnosis of lymph node metastases in pelvic lymph node dissection (PLND) is important for staging and treatment. Standard practice is to submit visible or palpable lymph nodes for histology. We assessed the added value of embedding all residual fatty tissue.Patients (n = 85) who underwent PLND for cervical (n = 50) or bladder cancer (n = 35) between 2017 and 2019 were included. Study approval was obtained (MEC-2022-0156, 18.03.2022, retrospectively registered).The median lymph node yield with conventional pathological dissection was 21 nodes (Interquartile range (IQR) 18–28). This led to discovery of positive lymph nodes in 17 (20%) patients. Extended pathological assessment found 7 (IQR 3-12) additional nodes, but did not result in identification of more node metastases.Histopathological analysis of residual fatty tissue harvested at PLND resulted in an increased lymph node yield, but not in the detection of additional lymph node metastases.

Objective: In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC)

Introduction/Background* High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers opting for surgery to prevent ovarian cancer, and identified factors associated with high cancer worry. Methodology Cancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose between the standard risk-reducing salpingo-oophorectomy or a novel strategy, risk-reducing salpingectomy with delayed oophorectomy. The Cancer Worry Scale was obtained before and three and twelve months after surgery. Cancer worry patterns were analysed using latent class growth analysis and factors associated with cancer worry were identified with regression analysis. Result(s)* Of all 577 BRCA1/2-PV carriers, 320 (55.5%) had high (≥14) cancer worry pre-surgery and 70.2% had higher cancer worry pre-surgery than post-surgery. Based on the course of cancer worry, BRCA1/2-PV carriers could be classified into three groups: persistently low cancer worry (56.4%), persistently high cancer worry (6.3%), and fluctuating cancer worry that mainly declined over time (37.3%). Factors associated with persistently high cancer concerns were: age below 35 (BRCA1) or 40 (BRCA2) years, unemployment, previous breast cancer diagnosis, lower education and more recent diagnosis with the BRCA-PV. Conclusion* High cancer worry is common among BRCA1/2-PV carriers and mainly declines after risk-reducing surgery. However, cancer worry remains high in 6% of the women and they should be identified and offered support. It should be realized that in this group, surgery does not reduce cancer concerns.

Introduction: BRCA1/2 mutation carriers are at increased risk of developing breast cancer (BC) and ovarian cancer (OC). However, for BRCA1/2 mutation carriers previously affected with OC, primary BC (PBC) and contralateral BC (CBC) risks might be lowered due to OC treatment, but data hereon are limited. Accurate BC risk estimates are essential for counseling and optimal decision making on BC surveillance and risk-reducing mastectomy (RRM) after diagnosis of BRCA1/2-associated OC. Methods: From the national HEBON cohort study, we selected female BRCA1/2 mutation carriers born from 1940 and at risk of PBC (n=2019; 1194 BRCA1, 825 BRCA2) or at risk of CBC (n=1276; 839 BRCA1, 437 BRCA2). Eligibility criteria for the PBC risk analyses included no history of PBC and both breasts in situ at DNA testing. For the CBC risk analyses, CBC before DNA testing was not allowed and the contralateral breast had to be unaffected at DNA testing. To estimate the association between OC and BC risk, we used the Fine and Gray regression model, with OC as a time-dependent variable and death as competing risk event. The observation started at the age of DNA testing, age 35, or – for the CBC risk analyses – age at PBC diagnosis, whichever came last. Censoring events were RRM, study closing date (i.e. 2014-12-31), and – for the CBC risk analyses – ipsilateral BC recurrence. All analyses were performed separately for BRCA1 and BRCA2 mutation carriers. Results: For the PBC analyses, we selected 236 BRCA1/2 mutation carriers with OC and 1783 BRCA1/2 mutation carriers without OC (median age at start study 53 and 41 years, respectively). During a mean follow-up (FU) of 5.2 years, 15 (6%) OC patients developed PBC after OC, while PBC was diagnosed in 262 (15%) women without OC. OC diagnosis was associated with a lower PBC risk in BRCA1 mutation carriers (HR, 0.27; 95% CI, 0.14–0.53) but not in BRCA2 mutation carriers (HR, 0.88; 95% CI, 0.34–2.27). The cumulative PBC incidence at age 70 in BRCA1 mutation carriers was 25% for OC patients and 66% for women without OC, and in BRCA2 mutation carriers 49% for OC patients and 53% for women without OC. For the CBC analyses, we selected 99 BRCA1/2 mutation carriers affected with PBC and OC, and 1177 BRCA1/2-associated PBC patients without OC (median age at start study 54 and 46 years, respectively). During a mean FU of 3.5 years, 8 (8%) PBC/OC patients developed CBC after OC, while CBC was diagnosed in 131 (11%) PBC patients without OC. In BRCA1 mutation carriers, OC diagnosis was non-significantly associated with a lower CBC risk (HR, 0.44; 95% CI, 0.19–1.03). For BRCA2 mutation carriers the HR was 1.65 (95% CI, 0.34–8.04). The cumulative CBC incidence at age 70 in BRCA1 mutation carriers was 40% for OC patients and 68% for patients without OC; for BRCA2 mutation carriers the number of CBCs was too small to obtain meaningful estimates. Conclusion:­ For BRCA1 mutation carriers affected with OC the risk of developing subsequent BC is lower than for BRCA1 mutation carriers without OC. Our data suggest that the current BC prevention strategies should be reconsidered for OC patients carrying a BRCA1 mutation, possibly including less intensive BC surveillance, and RRM being indicated only for a subgroup of OC patients. Citation Format: Heemskerk-Gerritsen BAM, Hooning MJ, van Doorn HC, Collée MJ, Koppert LB, Jager A, van den Ouweland AMW, Netherlands H, Seynaeve C, Kriege M. Risk of primary and contralateral breast cancer in BRCA1/2 mutation carriers previously affected with ovarian cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-04.

Purpose Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. Methods Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). Results Twenty participants were 26–71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. Conclusions According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial. Electronic supplementary material The online version of this article (doi:10.1007/s00520-016-3453-2) contains supplementary material, which is available to authorized users.

Objective. In 2008 GROINSS-V-I, the largest validation trial on the sentinel node (SN) procedure in vulvar cancer, showed that application of the SN-procedure in patients with early-stage vulvar cancer is safe. The current study aimed to evaluate long-term follow-up of these patients regarding recurrences and survival. Methods. From2000 until 2006 GROINSS-V-I included 377 patientswith unifocal squamous cell carcinoma of the vulva (T1

Objective. To describe clinical characteristics of Lynch syndrome associated ovarian cancer and the efficacy of surveillance in the early detection of these ovarian cancers.Methods. All Lynch syndrome associated ovarian cancer cases identified in either the Dutch Lynch syndrome registry (DLSR) between 1987 and 2016, and/or the cohort at the University Medical Center Groningen (UMCG) between 1993 and 2016 were included. Clinical data on age at diagnosis, mutation type, histological type, FIGO stage, treatment, follow-up and gynecological surveillance were collected.Results. A total of 46/798 (6%) women in the DLSR and 7/80 (9%) in the UMCG cohort were identified as LS associated ovarian cancer patients. The median age at ovarian cancer diagnosis was 46.0 years (range 20-75 years). The most frequently reported histological type was endometrioid adenocarcinoma (40%; n = 21) and serous carcinoma (36%; n = 19). Most tumors (87%; n = 46) were detected at an early stage (FIGO I/II). Forty-one of 53 (77%) patients were diagnosed with ovarian cancer before LS was diagnosed. In the other 12/53 (23%) women, ovarian cancer developed after starting annual gynecological surveillance for LS; three ovarian cancers were screen-detected in asymptomatic women. Overall survival was 83%.Conclusion. Ovarian cancer in women with LS has a wide age-range of onset, is usually diagnosed at an early stage with predominantly endometrioid type histology and a good overall survival. The early stage at diagnosis could not be attributed to annual gynecological surveillance. (C) 2018 Published by Elsevier Inc.

The risk of recurrent postmenopausal bleeding in women whose endometrial thickness after a first episode was 4 mm or less could have major implications for management. If the recurrence rate is low, follow-up by transvaginal ultrasonography (TVU) would suffice. In contrast, a high recurrence rate (or the diagnosis of malignancy at follow-up) would call for immediate endometrial sampling. The investigators, from 7 university-affiliated teaching hospitals in The Netherlands, practiced expectant management for consecutive patients not on hormone replacement therapy who presented with a first episode of postmenopausal bleeding and were found to have a thin endometrium. Of 607 women with a first episode of postmenopausal bleeding, 249 had an endometrial thickness of 4 mm or less. During a median follow-up of approximately 3.25 years, 25 of these 249 women (10%) had recurrent bleeding. The median interval before bleeding recurred was 49 weeks. Two patients with recurrent bleeding proved to have endometrial carcinoma and another had malignant melanoma. Recurrent bleeding appeared not to correlate with age, time since menopause, body mass index, hypertension, diabetes, or anticoagulant therapy. Whether or not endometrial sampling was carried out in the office at initial presentation did not influence the findings. There was, however, a significant difference in recurrent bleeding between patients who underwent hysteroscopy and/or dilatation and curettage at initial workup (5/21) and those who did not (20/208). The hazard rate ratio was 2.8, with a 95% confidence interval of 1.05 to 7.5. These findings endorse the use of TVU as an initial measure in women with postmenopausal bleeding. It is, however, vital that patients who are managed expectantly be reevaluated and have endometrial sampling should bleeding recur.

Objective.To determine whether structured assessment of outpatient endometrial biopsies decreases the number of inconclusive samples.Design.Retrospective cohort study.Setting.Single hospital pathology laboratory.Population.Endometrial biopsy samples of 66 women with postmenopausal bleeding, collected during the usual diagnostic work-up and assessed as insufficient for a reliable histological diagnosis.Methods.Endometrial biopsy samples were requested from the pathology laboratories. The retrieved samples were systematically reassessed by a single pathologist specialized in gynecology.Main Outcome Measure.Disagreement between initial assessment and conclusion after structured reassessment.Results.We retrieved 36 of 66 endometrial biopsy samples from six different pathology laboratories. Structured reassessment of the retrieved samples by a single pathologist specialized in gynecology did not change the conclusion in 35 of the 36 samples. The remaining sample contained a large amount of endometrial tissue and the diagnosis at reassessment was endometrial hyperplasia without atypia. All other samples contained insufficient material for a reliable diagnosis.Conclusion.A structured reassessment of endometrial biopsies samples, which were classified as inconclusive due to insufficient material, did not change the conclusion. Although it might be helpful for pathologists to have diagnostic criteria for adequacy and/or inadequacy of an endometrial biopsy sample, the gain in efficiency is likely to be small.

The objective is to assess among women with postmenopausal bleeding the relationship of age and time since menopause on one hand and the presence of endometrial cancer and atypical hyperplasia on the other hand. In a multicenter prospective cohort study, 614 women presenting with postmenopausal bleeding were included. Women underwent transvaginal sonography and, in cases where the endometrial thickness was >4 mm, endometrial sampling. Splines were used to assess the association between each of the continuous variables and (pre)malignancy of the endometrium. Subsequently, univariate and multivariate analysis were performed. The average age for women without (pre)malignancy was 61.7 years (SD 9.8). As malignant and premalignant cases were found to have similar age, these subgroups were merged in the analyses. Age was an independent predictor of (pre)malignancy. In women younger than 55 years, the odds ratio was 1.9 (95% CI: 1.1–3.3) for each year under 55 years of age and 1.03 (95% CI: 1.00–1.06) for each year over 55 years of age. The risk of (pre)malignancy of the endometrium was 4.9% in women less than 3 years postmenopausal versus 19.7% in women more than 20 years postmenopausal. However, in a multivariate analysis only age contributed to the prediction of risk. This study demonstrates that, in postmenopausal women with vaginal bleeding, the risk of (pre)malignancy of the endometrium is low in women under 50 years of age, increases considerably until 55 years of age, and rises only modestly with further advancing age. Future studies should explore whether these findings can be incorporated in the diagnostic work-up of women with postmenopausal bleeding.

Item does not contain fulltext BACKGROUND: Previous studies have reported a breast cancer (BC) risk reduction of approximately 50% after risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation carriers, but may have been subject to several types of bias. The purpose of this nationwide cohort study was to assess potential bias in the estimated BC risk reduction after RRSO. METHODS: We selected BRCA1/2 mutation carriers from an ongoing nationwide cohort study on Hereditary Breast and Ovarian Cancer in the Netherlands (HEBON). First, we replicated the analytical methods as previously applied in four major studies on BC risk after RRSO. Cox proportional hazards models were used to calculate hazard ratios and conditional logistic regression to calculate odds ratios. Secondly, we analyzed the data in a revised design in order to further minimize bias using an extended Cox model with RRSO as a time-dependent variable to calculate the hazard ratio. The most important differences between our approach and those of previous studies were the requirement of no history of cancer at the date of DNA diagnosis and the inclusion of person-time preceding RRSO. RESULTS: Applying the four previously described analytical methods and the data of 551 to 934 BRCA1/2 mutation carriers with a median follow-up of 2.7 to 4.6 years, the odds ratio was 0.61 (95% confidence interval [CI] = 0.35 to 1.08), and the hazard ratios were 0.36 (95% CI = 0.25 to 0.53), 0.62 (95% CI = 0.39 to 0.99), and 0.49 (95% CI = 0.33 to 0.71), being similar to earlier findings. For the revised analysis, we included 822 BRCA1/2 mutation carriers. After a median follow-up period of 3.2 years, we obtained a hazard ratio of 1.09 (95% CI = 0.67 to 1.77). CONCLUSION: In previous studies, BC risk reduction after RRSO in BRCA1/2 mutation carriers may have been overestimated because of bias. Using a design that maximally eliminated bias, we found no evidence for a protective effect.

The goal of this study was to determine diagnostic accuracy of preoperative transvaginal sonography (TVS) to assess myometrial infiltration in patients with endometrial cancer and to determine the possibility of preoperatively selecting low-stage endometrial cancer patients at high risk of lymph node metastases. The depth of myometrial infiltration of endometrial cancer was assessed using TVS before or after curettage. Infiltration was classified as superficial if less than half of the myometrium was involved, otherwise it was classified as deep infiltration. Results were compared with the histology results of the definitive specimens. Patients were classified as high risk when they satisfied two of the following three criteria: 60 years of age or older; deep myometrial infiltration; and poorly differentiated or undifferentiated tumor. A total of 93 patients from 11 clinics were analyzed. The mean age was 66.1 years (SD +/- 11.4). The sonography and histology findings were in agreement in 69 of 93 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of "deep infiltration" by preoperative TVS were 79% (95% CI 0.65-0.93), 72% (95% CI 0.61-0.83), 61% (95% CI 0.46-0.75), and 86% (95% CI 0.76-0.96), respectively. Combining tumor grade and myometrial infiltration in the hysterectomy specimen and age, 30 of 81 patients were classified as high-risk patients. Sensitivity and PPV, specificity, and NPV for preoperative diagnosis of high risk were 80% (95% CI 0.65-0.94) and 88% (95% CI 0.79-0.97), respectively. Preoperative assessment of myometrial tumor infiltration using just TVS is only moderately reliable in endometrial cancer patients. If the results of TVS, however, are combined with the patient's age and the degree of tumor differentiation in curettings, it is possible to preoperatively select endometrial cancer patients with a high risk of pelvic lymph node metastases with sufficient reliability.

Aim—To investigate the correlation between immunohistochemical and biochemical steroid receptor analyses by measurement of oestrogen, progesterone, and androgen receptor status in ovarian neoplasia. Methods—Tissue samples were obtained from 27 ovarian neoplasms, including two borderline tumours. Immunohistochemical staining of the tissue slides was scored semiquantitatively, incorporating the intensity and percentage of positive staining (histoscore). Tumours with a histoscore of 10 or more were considered steroid receptor positive. The epithelial and stromal fractions of the tumours were analysed separately. To study the uniformity of receptor expression throughout a tumour, up to four samples were analysed. Results—Immunohistochemical histoscores of the oestrogen receptor in the epithelial fractions were significantly correlated with the biochemical oestrogen receptor values (r = 0.408). Androgen receptor status in the epithelial fraction was correlated with that in the stromal fraction (r = 0.741), while androgen receptor histoscores in the epithelial fraction correlated with the biochemical assay values (r = 0.463). On biochemical analysis, 17 of the 27 ovarian tumours were oestrogen receptor positive and seven were progesterone receptor positive. On immunohistochemical analysis, eight tumours were oestrogen receptor positive and two were progesterone receptor positive. Biochemical analysis showed that 14 of the 26 tumours were slightly androgen receptor positive (10–50 fmol/mg protein), while all the others were negative. On immunohistochemical analysis, seven of the 26 tumours were androgen receptor positive. When two or more specimens from one tumour were analysed, marked differences in steroid status were found, especially in progesterone receptor and androgen receptor expression. Some parts of a tumour were steroid receptor positive, while other parts were negative owing to heterogeneity of expression. Conclusions—Immunohistochemical and biochemical analysis of steroid receptors in ovarian tumours correlated weakly or not at all. Heterogeneity of expression within a tumour and the presence of progesterone and androgen receptors in the stromal fraction partly accounted for this observation. Biochemical and immunohistochemical androgen receptor status was much lower than in previous reports. Key Words: steroid receptors • ovarian neoplasia • immunohistochemical analysis • biochemical analysis

This paper covers an overview of the literature on the management of advanced endometrial cancer, concentrating on patients with histopathologic endometrioid type of tumors. The different treatment modalities are described and management recommendations are proposed.The standard surgical procedure includes an extrafacial total hysterectomy with bilateral salpingo-oophorectomy, collection of peritoneal washings for cytology, and exploration of the intraabdominal contents. In cases of extensive disease in the abdomen, an optimal surgical cytoreduction is associated with improved survival. Further treatment with radiotherapy may be indicated based on the pathological staging information to improve loco-regional control. Primary radiotherapy is indicated in cases where surgery is contraindicated. Systemic treatment can either be hormone therapy or chemotherapy. Progesterons are the cornerstone of hormone therapy. Prognostic factors for response are the presence of high levels of progesterone and estrogen receptors and low grade histology. Paclitaxel is the most active single agent drug. The combination therapy with paclitaxel and carboplatin is adopted as first choice in patients with endometrial cancer because of the efficacy and low toxicity, although not proven in a randomized trial.The literature on the management of patients with advanced endometrial cancer is discussed in detail. Each stage of advanced disease is presented separately, and management recommendations are proposed, and alternative approaches are given.Ongoing clinical trials are described, and the focuses of ongoing research are mentioned.

The introduction of paclitaxel/platinum combination chemotherapy and (interval) debulking surgery has significantly improved the prognosis of patients with ovarian cancer. Yet, many patients die of drug-resistant disease. Second-line chemotherapy may result in prolonged secondary remissions with alleviation of symptoms and improvement of quality of life. The response to second-line chemotherapy is strongly related to platinum sensitivity. More than 60% of platinum-sensitive patients respond to a re-challenge with platinum-containing chemotherapy. In platinum-resistant patients, on the contrary, the response rate to a re-challenge with 3-weekly platinum or any nonplatinum chemotherapy is less than 20%. The response to dose-dense weekly platinum-based regimens ranged from 48% to 64% in platinum-resistant patients. Moreover, the majority of the patients responded within 8 weeks after the start of the treatment. The progression-free survival ranged from a median of 5 months in a study using cisplatin/etoposide, to 11 months in a study with paclitaxel/carboplatin. The median survival was 11-15 months. The outpatient weekly paclitaxel/carboplatin regimen, with paclitaxel at a dose of 90 mg/m(2) and carboplatin at area under the curve 4, seems similarly effective and is better tolerated. Dose-dense weekly paclitaxel/carboplatin is an effective and well-tolerated therapy for platinum-sensitive, as well as platinum-resistant tumors. Responses to therapy are observed within 8 weeks in the majority of the patients. Whether a weekly regimen indeed is more effective than 3-weekly paclitaxel/carboplatin needs to be answered in a randomized study.