Clinical guidelines for managing menopausal symptoms in women with (a history of) breast cancer.

Background: One in eight women will be diagnosed with breast cancer. At the time of diagnosis, 75% of patients are postmenopausal. Many will receive anti-hormone therapy, which often induces menopausal symptoms. Premenopausal breast cancer patients frequently become postmenopausal as a result of the treatment and often experience menopausal symptoms. The increased incidence of breast cancer, combined with longer survival, has led to an increase in the number of women experiencing menopausal symptoms. Therefore, the management of menopausal symptoms in women with a history or current breast cancer is a relevant and common clinical problem. Objectives: To provide a clinically useful overview of the steps in the management of menopausal symptoms in women with (a history of) breast cancer. Materials and Methods: A comprehensive literature review was conducted by authors JS and WT using the PubMed and Medline databases. Abstracts were critically appraised and, where appropriate, the full text was analysed. Main Outcome Measures: Not applicable. Results: Depending on the condition, either meta-analyses, randomised controlled trials or retrospective cohorts were identified. No evidence was found for some proposed treatments. Conclusions: Menopausal symptoms in women with (a history of) breast cancer require a patient-tailored approach. Shared decision making is paramount and adequate up-to-date knowledge can help the breast cancer specialist to advise and guide patients accordingly. What is new?: A comprehensive, clinically-based overview of evidence-based treatment options for menopausal symptoms in women with (a history of) breast cancer.

Survey: acceptability of opportunistic bilateral salpingectomy in Flanders.

Background: The VVOG (Flemish Society of Obstetrics and Gynaecology) published a consensus statement promoting opportunistic bilateral salpingectomy (OBS). Objectives: The aim of the study was to obtain insight into the current opinion and general practice of Flemish gynaecologists to counsel and perform OBS. Materials and Methods: A questionnaire was distributed to Flemish gynaecologists three months following publication. Main outcome measures: The drawbacks and incentives to counsel and perform OBS were questioned. Results: Complete response rate was obtained from 99 gynaecologists (17%) and 37 trainees (19%). The majority of respondents (77%) always counselled for OBS in patients scheduled for hysterectomy without oophorectomy. Eighteen per cent counselled only above a certain age cut off and/or if patient was already menopausal. The most important incentive to counsel in cases of hysterectomy by the abdominal approach and vaginal hysterectomy (VH) was the opportunity to prevent ovarian cancer. The yet-undetermined risk of premature ovarian failure was mentioned as the most important barrier in counselling women for OBS in those undergoing hysterectomy by the abdominal approach. For VH, the respondents saw the risk of complications and increased surgical time as the most important barriers. Sixty-one percent of gynaecologists preferred to perform bilateral salpingectomy as sterilisation method. Conclusions: Our study suggests that the concept of OBS is already well known in Flanders. There is a positive attitude towards the routine implementation of OBS, although some barriers and doubts about an age cut-off still exist in practice.

European consensus statement on essential colposcopy.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.

A high neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with a worse outcome in inflammatory breast cancer.

INTRODUCTION: Inflammatory breast cancer (IBC) is an uncommon, but aggressive form of breast cancer that accounts for a disproportionally high fraction of breast cancer related mortality. The aim of this study was to explore the peripheral immune response and the prognostic value of blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), in a large IBC cohort. PATIENTS & METHODS: We retrospectively identified 127 IBC patients and collected lab results from in-hospital medical records. The differential count of leukocytes was determined at the moment of diagnosis, before any therapeutic intervention. A cohort of early stage (n = 108), locally advanced (n = 74) and metastatic breast cancer patients (n = 41) served as a control population. RESULTS: The NLR was significantly higher in IBC compared to an early stage breast cancer cohort, but no difference between IBC patients and locally advanced breast cancer patients was noted. In the metastatic setting, there was also no significant difference between IBC and nIBC. However, a high NLR (>4.0) remained a significant predictor of worse outcome in IBC patients (HR: 0.49; 95% CI: 0.24-1.00; P = .05) and a lower platelet-lymphocyte ratio (PLR) (≤210) correlated with a better disease-free survival (DFS) (HR: 0.51; 95% CI: 0.28-0.93; P = .03). CONCLUSION: Patients with a high NLR (>4.0) have a worse overall prognosis in IBC, while the PLR correlated with relapse free survival (RFS). Since NLR and PLR were not specifically associated with IBC disease, they can be seen as markers of more extensive disease.

The multidisciplinary approach to ovarian tumours in children and adolescents.

Ovarian tumours in children and adolescents are rare diseases. Although the majority of tumours are benign, the diagnosis and management present various challenges that require a wide range of expertise. The multidisciplinary team ensures not only accurate diagnosis and correct and minimally invasive management, but also minimal psychological impact and the preservation of fertility. This article outlines the multidisciplinary team approach to ovarian masses in children and adolescents. The team includes paediatric oncologists, gynaecological surgeons, pathologists, radiologists, fertility experts, geneticists and psycho-social services.

Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes (sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort. PATIENTS AND METHODS: Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings. RESULTS: Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27-0.81, P = 0.006) in a multivariate model. CONCLUSIONS: IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.

Breast cancer and fat grafting: efficacy, safety and complications-a systematic review.

Autologous fat grafting (AFG) or lipofilling is nowadays a popular technique for breast reconstruction after breast cancer surgery. There is debate regarding the oncological safety and risks of this procedure in breast cancer patients. A systematic review of the literature published between January first 1995 and October first 2016 was conducted regarding the efficacy, safety and complications of this technique in breast cancer patients after their cancer treatment. The databases PubMed, Science Direct and Thomson Reuters Web of Science were used to search for qualified articles. Inclusion criteria were women with a personal history of breast cancer and at least one lipofilling procedure. Only studies containing a minimum of 20 patients were included in this systematic review. The search yielded a total of 23 suitable articles: 18 case series, 4 retrospective cohort studies and one prospective cohort study. The systematic review encompassed a total of 2419 patients. Medical imaging was used in the majority of the studies to assess the follow-up. Mammography was the most popular technique (65.2%), followed by ultrasound (47.8%) and MRI (30.4%). The prevalence of complications was the following: fat necrosis in 5.31%, benign lesions, like cysts or calcifications in 8.78%, infections in 0.96% and local cancer recurrence in 1.69%. AFG or lipofilling appears to be an oncological safe technique with a low morbidity in women with a history of breast cancer. In order to have a better understanding and evidence of the oncological safety a randomised controlled trial is urgently needed. We further recommend that all AFG be registered in the cancer register.

The impact of conisation on pregnancy outcome.

AIM: The objective of present study was to investigate whether conisation is associated with adverse pregnancy outcomes in Flanders, Belgium. Therefore a retrospective cohort study was conducted at the Antwerp University Hospital. MATERIALS AND METHODS: The study was approved by the Ethical Committee and based on a questionnaire as well as on medical records. Confounders, like smoking, alcohol use, drug use, chronic illness, and gynaecological disorders during pregnancy were all taken into account. A multiple logistic regression was performed for an association between adverse pregnancy outcomes and confounders. RESULTS: The study showed that there was association between conisation, low birth weight, and caesarean section. After conisation there was a significantly higher risk of 3.275 on a low birth weight. The risk of a caesarean section after conisation was tripled. A gynaecological disorder during the pregnancy had a significantly higher risk of delivering a child with a low birth weight and a higher risk of a caesarean section. Smoking and a chronic illness gave a significant higher risk of caesarean section. DISCUSSION: Conisation is easy to perform and highly effective in the prevention of cervical cancer. Conisation has a high morbidity, as it is associated with severe adverse pregnancy outcome. A conisation should therefore only be performed on a true indication; otherwise it will be the victim of its own success.

Guide wire surgery in breast cancer and why to avoid scissors.

CASE: A 58-year old woman presented with microcalcifications in her left breast. A biopsy showed a low-grade ductal carcinoma in situ. A tumorectomy was performed using a harpoon-shaped guide wire to remove the entire lesion. No additional therapy was given. Six months later during follow-up the mammography revealed that the distal end of the guide wire was still present in the left breast. CONCLUSION: When performing a tumorectomy using a guide wire, the completeness of the wire should be checked during surgery. Additionally cutting of the wire can be prevented by using a scalpel instead of scissors during surgery.

A cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer in Belgium.

OBJECTIVE: Despite an advanced national cervical cancer screening and vaccination programme cervical cancer is still the third most frequent diagnosed gynaecological tumour in Belgium. The goal of this study is to present the Belgian data of a cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer (ICC) conducted in 12 European countries. MATERIAL AND METHODS: Centres in four major Belgian cities (Antwerp, Brussels, Ghent and Liège) participated in this study. Tissue samples from women with ICC were collected from the period 2001 - 2008. All slides were centrally reviewed and analysed for HPV. The total enrolled cohort included 278 subjects. RESULTS: The histologically eligible cohort comprised of 255 patients (mean age 51.3 ± 15.1 years) and 237 were confirmed HPV positive (mean age 50.6 ± 14.9 years). A single HPV infection was present in 95.8%. The five most frequent HPV types were HPV 16 (68.7%), HPV18 (12.3%), HPV 31 (6.2%), HPV 33 (5.3%) and HPV 45 (1.8%). Multiple HPV types were present in 3.4%, with two HPV types in 2.5% and three HPV types in 0.8%. In the various HPV type combinations observed in multiple infected women, HPV 31 (62.5%) and HPV 33 (50.0%) were the most frequent. The ratio of adenocarcinoma (ADC) versus squamous cell carcinoma (SCC) cases in the histologically eligible cohort was 1:8. Compared to the pooled European data the Belgium HPV 16 is 1.1, HPV 33 is 1.2 and HPV 31 is 1.7 higher and the HPV 18 is 0.8 and HPV 45 is 0.34 lower. CONCLUSION: The 5 most frequent HPV types in Belgium are the same as in the rest of Europe, but the distribution is different. Cervical cancer screening should therefore be HPV type specific and HPV prophylactic vaccination should also focus on other types then HPV 16 and HPV 18. A national registry is needed in order to follow the trends of HPV types in the society and to measure the impact of prevention, for which the data presented in this study can be an important basis.

The socio-economical impact of intravenous (IV) versus subcutaneous (SC) administration of trastuzumab: future prospectives.

Trastuzumab was the first targeted therapy for HER2 positive breast cancer. It has become the standard of care for HER2 positive metastatic breast cancer since 2000 and in the adjuvant setting since 2006. Adjuvant it is given for a year and in patients with metastatic disease until progression. The standard mode of administration is intravenous. Recently a subcutaneous form has become available. A phase III study showed that there is no difference between the intravenous and subcutaneous form in terms of safety and efficacy. The patient's preference however significantly favoured the subcutaneous form. It is estimated that the use of the SC form could contribute to a cost saving between 758 and 2576 euro per annual course. For Belgium alone this could mean an estimated saving of 1.4 to 4.6 million euros per year. The potential benefit of the SC administration for healthcare facilities could be further increased when applied in a LEAN working day-care chemotherapy unit. After reviewing the existing literature we suggest to further validate the potential financial impact of SC trastuzumab compared to the traditional IV form and to introduce a scientific proposal incorporating the benefits of this formulation in a LEAN working healthcare unit.

Reimbursement for bone loss prevention is different between women with breast cancer and men with prostate cancer: time for a revision.

The hormone dependent breast and prostate cancers have in general a very good survival, due to the anti-hormonal treatment. A disadvantage of this treatment is the increased risk of osteoporosis and fractures. It is surprisingly to note that denosumab has the same impact on fracture reduction incidence for both sexes, but with different reimbursement criteria. Furthermore there is only reimbursement in case of osteoporosis and not for cancer patients who are at an increased risk of developing osteoporosis. The clinician detects the accelerated bone loss during follow-up, but has to wait until there is osteoporosis. The impact of osteoporosis on the quality of life is severe and underestimated. Management of cancer should not only focus on survival, therefore it is time to reconsider the reimbursement criteria, discuss the willingness of society to pay for bone health and make choices regarding the advice we give to our patients.

Safety of converting a radical vaginal trachelectomy to a radical hysterectomy during pregnancy.

Almost 1% of all cervical cancers occur in pregnant women. The recommended management during the first 20 weeks is to sacrifice the pregnancy and to perform standard therapy, which means the loss of future fertility. A trachelectomy during pregnancy could preserve the ongoing pregnancy and future fertility. The author reports a radical vaginal trachelectomy (RVT) during 18 weeks of pregnancy. Definitive pathology of the trachelectomy specimen showed a tumor of 48 millimeters. Subsequently a radical hysterectomy was performed. At present, eight years and six months later the patient is well with no signs of recurrence. RVT is feasible in the first and second trimester of pregnancy. Clinical examination and MRI however are less accurate in the evaluation of stage and the extent of the tumor during pregnancy. Converting a RVT to a radical hysterectomy in a second time is safe in a pregnant woman.

Abdominal intrauterine vacuum aspiration.

Evaluating and "cleaning" of the uterine cavity is probably the most performed operation in women. It is done for several reasons: abortion, evaluation of irregular bleeding in premenopausal period, and postmenopausal bleeding. Abortion is undoubtedly the number one procedure with more than 44 million pregnancies terminated every year. This procedure should not be underestimated and a careful preoperative evaluation is needed. Ideally a sensitive pregnancy test should be done together with an ultrasound in order to confirm a uterine pregnancy, excluding extra-uterine pregnancy, and to detect genital and/or uterine malformations. Three out of four abortions are performed by surgical methods. Surgical methods include a sharp, blunt, and suction curettage. Suction curettage or vacuum aspiration is the preferred method. Despite the fact that it is a relative safe procedure with major complications in less than one percent of cases, it is still responsible for 13% of all maternal deaths. All the figures have not declined in the last decade. Trauma, perforation, and bleeding are a danger triage. When there is a perforation, a laparoscopy should be performed immediately, in order to detect intra-abdominal lacerations and bleeding. The bleeding should be stopped as soon as possible in order to not destabilize the patient. When there is a perforation in the uterus, this "entrance" can be used to perform the curettage. This is particularly useful if there is trauma of the isthmus and uterine wall, and it is difficult to identify the uterine canal. A curettage is a frequent performed procedure, which should not be underestimated. If there is a perforation in the uterus, then this opening can safely be used for vacuum aspiration.

The ideal cervical cancer screening recommendation for Belgium, an industrialized country in Europe.

Cervical cancer should be a historical disease, why are we not succeeding! The prophylactic vaccination will reduce cervical cancer by almost 80% in Belgium. Cervical cancer screening should therefore remain in order to prevent the remaining 20%. The current used Pap cytology test misses 50% of all clinically significant precancers and cancers at the time of testing. The test should remain but the analysis should be altered. The screening should be modified based on our knowledge of human papillomavirus (HPV) as causal factor. Instead of looking for a cell abnormality, one should look for the presence of HPV. Then depending on the test, only two to ten percent of all relevant lesions are missed. The introduction of the vaccination should lead to the re-introduction of the screening based on HPV. This will not only lead to a considerable reduction in morbidity and mortality, allow longer screening intervals, but it will also be more cost-effective. More for less should be the driving force in cervical cancer screening if we want to be successful.

The effect of non-surgical weight loss interventions on urinary incontinence in overweight women: a systematic review and meta-analysis.

Although the aetiology of urinary incontinence can be multifactorial, in some cases weight loss could be considered as a part of the therapeutic approach for urinary incontinence in people who are overweight. The objective of this study was to review and meta-analyse the effect of non-surgical weight loss interventions on urinary incontinence in overweight women. Web of Science, PubMed, Pedro, SPORTDiscus and Cochrane were systematically searched for clinical trials that met the a priori set criteria. Data of women who participated in non-surgical weight loss interventions (diet, exercise, medication or a combination) were included in the meta-analysis. After removing duplicates, 62 articles remained for screening on title, abstract and full text. Six articles (totalling 2,352 subjects in the intervention groups) were included for meta-analysis. The mean change in urinary incontinence (reported as frequency or quantity, depending on the study) after a non-surgical weight loss intervention, expressed as standardized effect size and corrected for small sample sizes (Hedges' g), was -0.30 (95%CI = -0.47 to -0.12). This systematic review and meta-analysis shows evidence that a non-surgical weight loss intervention has the potential to improve urinary incontinence and should be considered part of standard practice in the management of urinary incontinence in overweight women.