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.

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.

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.

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.

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.

Cervical atypical glandular cells and false negative HPV testing: a dramatic reality of the wrong test at the right place.

BACKGROUND: Due to cervical cancer screening the number of squamous cancer have declined. The number of adenocarcinomas (ADCs) does appear to be rising. ADCs are often missed and human papillomavirus (HPV) testing could be helpful in detecting these abnormalities earlier. CASE: A 36-year-old woman, who had a normal smear three years earlier, had a pap smear with atypical glandular cells. The L1 HPV test showed that there was no HPV infection. Other HPV tests which looked at E6 and E7 showed an infection with HPV 16. Due to unknown reasons, no action was taken regarding the atypical glandular cells. Two years later the patient was diagnosed with a FIGO Stage IVb ADC of the cervix. The L1 HPV test was still negative and the E6/E7 HPV test was still positive. Despite several multiple treatment modalities she succumbed of her disease two years later leaving behind a young family. CONCLUSION: HPV test looking only at L1 can give false negative results if the virus is integrated in the human genome.

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.

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.

Desmoplastic small round cell tumor (DSRCT) arising in the ovary: report of a case diagnosed at an early stage and review of the literature.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma tumor affecting mainly young adult males. It rarely has an ovarian involvement. CASE: A 29-year-old woman presented to her gynecologist for amenorrhoea. The laboratory results demonstrated a menopausal status and the ultrasound revealed a large mass of the right ovary. The right ovary was completely removed by laparoscopy. Pathology, cytology and immunochemistry revealed a DSRCT. In January 2009 a left salpingo-oophorectomy and a right salpingectomy were performed via laparoscopy. After 35 months from diagnosis there was no clinical evidence of disease recurrence. CONCLUSION: DSRCT is a rare ovarian tumor in adolescence with a general poor outcome. Every ovarian mass regardless of age should be approached with caution.

Fibula metastasis as the presenting feature of vaginal cancer.

BACKGROUND: Metastatic bone involvement in vaginal carcinoma has not been reported in the literature. CASE: A 74-year-old woman was referred for a painful fibula to the orthopedic surgeon. A work-up revealed an isolated metastatic bone lesion in the right fibula of a primary squamous carcinoma of the vagina. Rather surprisingly this lesion had been missed during all previously regular clinical gynecological examinations. Palliative therapy including bone resection and radiotherapy of the metastatic lesion were given. CONCLUSION: This case highlights: (1) the unique presentation of a vaginal cancer by pain in the lower leg secondary to a metastasis in the fibula; (2) that a speculum examination can mask a mid-vaginal lesion; (3) the importance of aggressive treatment of a solitary bone metastasis in order to provide effective palliation.

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 VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer.

Vascular endothelial growth factor (VEGF)-A inhibitors exhibit unseen high responses and toxicity in recurrent epithelial ovarian cancer suggesting an important role for the VEGF/VEGFR pathway. We studied the correlation of VEGF signalling and AKT/mTOR signalling. Using a tissue microarray of clinical samples (N=86), tumour cell immunohistochemical staining of AKT/mTOR downstream targets, pS6 and p4E-BP1, together with tumour cell staining of VEGF-A and pVEGFR2 were semi-quantified. A correlation was found between the marker for VEGFR2 activation (pVEGFR2) and a downstream target of AKT/mTOR signalling (pS6) (R=0.29; P=0.002). Additional gene expression analysis in an independent cDNA microarray dataset (N=24) showed a negative correlation (R=-0.73, P<0.0001) between the RPS6 and the VEGFR2 gene, which is consistent as the gene expression and phosphorylation of S6 is inversely regulated. An activated tumour cell VEGFR2/AKT/mTOR pathway was associated with increased incidence of ascites (chi(2), P=0.002) and reduced overall survival of cisplatin-taxane-based patients with serous histology (N=32, log-rank test, P=0.04). These data propose that VEGF-A signalling acts on tumour cells as a stimulator of the AKT/mTOR pathway. Although VEGF-A inhibitors are classified as anti-angiogenic drugs, these data suggest that the working mechanism has an important additional modality of targeting the tumour cells directly.

Screening for human papillomavirus: is urine useful?

Persistent infection with high-risk Human papillomavirus (hr-HPV 16, 18, 31, 33, and 45) is the main risk factor for developing malignant genital lesions. Screening methods and follow-up schedules for cervical cancer are well known. A golden standard to screen and monitor men does not exist yet, because HPV-related, life threatening malignancies in men are rare. The importance of male HPV screening lies mainly in HPV vaccination. Young females are the target group for HPV, but men are considered to be the reservoir for HPV and to have a role in the perpetuation of the infection in the general population. We looked at the usefulness of urine as a tool for HPV screening. Pubmed was searched with the words ''HPV'', ''Urine,'' and ''HPV-DNA''. The chance of finding HPV-DNA in urine is higher in men with lesions in the urethra than outside the urethra, and in women with abnormal cervical cytology. In general, the results of testing urine for HPV-DNA are better for women than for men, probably because of the anatomical position of the urethra to the vagina, vulva, and cervix. In both genders, urine HPV prevalence is higher in HIV pos patients and in high-risk populations. Urine, to screen asymptomatic low-risk-profile (wo)men seems less useful because their urine samples are often inadequate. If urine proves to be the best medium to screen, a low-risk population remains controversial.

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.

Primary retroperitoneal mucinous cystadenocarcinomas are a distinct entity.

Primary retroperitoneal mucinous cystadenocarcinomas are rare tumors with a controversial pathogenesis. Present report describes a 74-year-old woman with a retroperitoneal cystic pelvic mass. Her past medical history included appendectomy, bilateral salpingo-oophorectomy, and a hysterectomy. An explorative laparotomy was performed and the mass was completely excised. Definitive pathology revealed a primary retroperitoneal mucinous cystadenocarcinoma of the ovarian type. Further management consisted of four cycles carboplatin. She had a recurrence after 8 months and died 31 months after the initial diagnosis. Primary retroperitoneal mucinous cystadenocarcinomas are distinct entity, with the same poor prognosis as their ovarian counterpart.

Sentinel node biopsy for ipsilateral breast cancer recurrence: a review.

The aim of this study was to review published reports on the feasability, results, and reliability of sentinel node biopsy in cases of ipsilateral recurrent breast cancer. A Medline search on publications from January 1999 to December 2007 and cross-references in published articles were looked for. We identified 16 reports on sentinel node biopsy in recurrent breast cancer, including a total of 287 patients. In 210/287 (73.2%) a sentinel node was identified, 77/210 (37.7%) had had previous axillary lymph node dissection and 131 (62.3%) a previous sentinel node procedure. Aberrant lymphatic drainage, other than the ipsilateral axilla was noted in 68/210 (32.4%). Of these 16/68 (23.6%) were located in the contralateral axilla. Of the removed contralateral axillary sentinel nodes 8/17 (47.1%) were invaded by cancer. We conclude that sentinel node biopsy in cases of recurrent ipsilateral breast cancer is feasible. In about one out of three cases drainage to the contralateral axilla with invasion in almost half the cases takes place. The therapeutical consequences of these findings need further study.