Immunohistochemical profiling of the tumour microenvironment in borderline and malignant ovarian tumours in young women.

Ovarian cancer is a major cause of cancer-related deaths in women. Our previous study highlighted the interaction between cancer cells and the host immune response in solid cancers. The present study aimed to analyse the proportion, density and distribution of T and B lymphocytes within the tumour and surrounding stroma, and their prognostic significance in young women with borderline and malignant ovarian surface epithelial tumours. Full clinicopathological and outcome data were collected for 57 women aged <50 years diagnosed between January 2010 and December 2015. Representative tumour sections were stained for CD3 (T cells) and CD20 (B cells) and tumour-infiltrating lymphocytes (TILs) were scored following the TILs Working Group Recommendations and described as stromal, intra-tumoural, lymphoid aggregates and touching lymphocytes. Data were statistically analysed and the association with clinicopathological variables was assessed. The median age was 41 years and the most common histological type was serous carcinoma (n=21). The risk of malignancy index was a significant predictor of ovarian cancer diagnosis (P<0.05). A total of 15 out of 34 patients with cancer died. There was significantly greater stromal infiltration of CD3 and CD20 TILs (P=0.01 and P=0.03, respectively) and higher intratumoral CD20 expression in ovarian epithelial cancers compared with borderline tumours. The highest CD3 stroma count and density were observed in serous carcinoma, which also exhibited the highest numbers of CD3 and CD20 aggregates. There was no statistically significant difference between touching lymphocytes and tumour histological subtype. There was no significant association between TIL expression and patient survival. The count, distribution and density of T and B lymphocytes in ovarian tumours varied depending on tumour type and invasiveness. Their topographic distribution within the tumour and surrounding stroma did not impact prognosis in young women with ovarian cancer. TIL analysis in an older age group of women with ovarian tumours is ongoing to determine its potential prognostic significance.

Vulval extra-mammary Paget's disease: the master of disguise revealed.

Extra-mammary Paget's disease is a rare cancer affecting the anogenital region and can present with a myriad of symptoms. In women, the diagnosis of Paget's disease can be challenging as it mimics several other vulval conditions. It is important to promptly recognise this disease because of its potential association with synchronous tumours, such as colorectal adenocarcinoma. The mainstay of treatment is with immunomodulating therapies or surgery, but unfortunately the risk of recurrence is high and appears to be independent of treatment choice and tissue margin status. There is growing evidence to move away from traditional surgical excision to using topical therapy, such as imiquimod, as surgery can often be extensive and disfiguring with a prolonged recovery time. There is considerable psychosexual and physical morbidity associated with Paget's disease, largely owing to multiple surgical recurrences. As recurrences can occur several years after the initial presentation, long-term follow up of patients is recommended.

Aberrant activation of the Hedgehog signalling pathway in squamous cell carcinoma of the vulva as a potential target for cancer therapy.

In a previous study, we showed that the Hedgehog (Hh) signalling pathway is aberrantly activated in vulval squamous cell carcinoma (VSCC). In this study, we further validated our findings on a prospective cohort of primary VSCC cases, where immunohistochemical staining confirmed that key Hh pathway components were overexpressed in VSCC compared to normal vulval epithelium. We also undertook a series of in vitro studies to determine the extent of Hh pathway activation in VSCC-derived cell lines, and examine the consequences of pathway inhibition on the growth of these cells. We found that of six cell lines tested, four displayed elevated baseline Hh pathway activity that was dependent on SHH ligand, or in one case, a PTCH1 gene mutation. Hh signalling appeared necessary to sustain cell growth, as SHH ligand depletion with Robotikinin or SMO inhibition, either with chemical inhibitors (Itraconazole or LDE-225) or SMO-specific siRNA, attenuated GLI1 activity and cell proliferation in both monolayer and organotypic raft culture. Furthermore, treatment of Hh-dependent cell lines with SMO inhibitors sensitised cells to Cisplatin. Findings from our study offer us the opportunity to explore further the development of targeted chemotherapy for women with VSCC driven by aberrant Hh activation.

Impact of COVID-19 on Gynaecological oncology; a global perspective.

The coronavirus pandemic caused global devastation with over 2 million deaths and put unprecedented pressure on health care facilities world-wide. The response to the pandemic differed globally as countries faced different challenges. Within Gynaecological oncology, a multitude of guidance was published by various countries and organisations which demonstrated major themes. These consisted of implementations aimed at reducing transmission, managing limited resources, treatment prioritisation whilst continuing urgent oncological surgery where possible and the use of alternative therapies in the management of oncology patients to reduce hospital admission. Due to the novelty of this virus and its global effects, published guidance is currently limited to best practice and small-scale trials. This review aims to summarise the global response to coronavirus with respect to Gynaecological oncology and suggests potential interventions to limit the spread of the virus during resurgence or in the event of a future global pandemic. It also discusses the current trials recruiting relevant to the field of Gynaecological oncology to better inform the specialty on the management of cancer patients during COVID-19.

The impact on obstetric outcomes following complete amputation of the cervix uteri in fertility preservation surgery for cervical neoplasm.

OBJECTIVES: Radical trachelectomy is offered to women with early-stage cervical neoplasia who desire fertility. The presence of isthmic glands within histological specimens suggests complete cervical amputation and as such, we examined if the presence of these glands in surgical specimens adversely affects obstetric outcomes. STUDY DESIGN: The study cohort comprises 43 consecutive cases of early-stage cervical neoplasia. The presence of isthmic glands in pathological specimens was correlated with obstetric outcomes. Univariate and multivariate analyses were constructed to identify clinicopathological factors associated with adverse obstetric outcomes. RESULTS: 43 patients underwent fertility sparing surgery; radical (30; 69.8 %) or simple trachelectomy (13; 30.2 %). Of these, 26 (60.5 %) had isthmic glands within the surgical specimen. Isthmic gland presence was not influenced by surgery radicality, disease stage, histological diagnosis, or surgical approach. Obstetric outcomes were available for 36 patients, with 27 attempting conception post-trachelectomy and 15 (55.6 %) achieving at least one pregnancy. Of 21 total pregnancies, the miscarriage and live birth rates were 7.4 % and 85.0 %, respectively. The presence of isthmic glands did not influence the overall conception rate, with 53.8 % of women with complete cervical amputation conceiving compared to 57.1 % of those without (p = 0.8632). Complete removal of the cervix did not increase premature deliveries <37 weeks gestation (p = 0.2521). CONCLUSIONS: The presence of isthmic glands in trachelectomy specimens provides a reliable surrogate marker for complete cervical amputation. In cases where complete cervical amputation is required to achieve maximum oncological outcomes, patients may be assured that there is little evident impact on fertility and obstetric outcomes.

The role of preoperative computerized tomography (CT) scan of the pelvis and groin in the management of clinically early staged vulva squamous cell carcinoma.

INTRODUCTION: Vulvar squamous cell carcinoma (VSCC) commonly metastasises through groin lymphatics. However, the use of pre-operative imaging in detecting inguinal nodal metastasis before staging surgery or to triage patients for sentinel node biopsy remains unclear. Here, we investigated if pre-operative CT scan, the imaging choice in our cancer centre, influences the overall course of VSCC management in those patients without clinical evidence of groin lymphadenopathy. METHOD: The study comprised of a prospective cohort of 225 patients with VSCC who underwent staging surgery within a regional tertiary gynaecological cancer centre. Comprehensive information of the cohort's demography, clinicopathological variables and outcome data were collected and analysed. Findings of pre-operative imaging were compared with histological findings of inguinal lymph nodes following groin lymphadenectomy. Statistical analyses were performed using SPSS V24. RESULTS: Pre-operative CT scan was performed on 116 (56.6%) patients. The sensitivity and specificity of cross-sectional imaging in detecting groin lymphatic metastasis were 59.1% and 77.8%, respectively; while the positive (PPV) and negative predictive value (NPV) were 61.9% and 75.7%, respectively. In patients who had sentinel inguinal nodes biopsy, the sensitivity, specificity, PPV and NPV of CT scan in detecting inguinal node metastasis were 30.0%, 85.7%, 33.3% and 83.7%, respectively. There was no difference in disease-free and overall survival in those who received pre-operative imaging when compared to those who did not. CONCLUSION: Pre-operative CT scan may be omitted in early stage VSCC prior to surgical staging as it does not affect overall management and surgical outcomes.

A 5-year follow-up of vulval swelling due to extraskeletal myxoid chondrosarcoma: A rare case report.

Vulval extraskeletal myxoid chondrosarcoma (EMC) is a rare cause of vulval swelling, reported <10 times in the literature to date. EMC in this location is frequently misdiagnosed due to its rarity, and patients may incur delays in diagnosis and treatment. We herein present the diagnosis and management of the case of vulval EMC in a 42-year-old Caucasian female patient who presented in 2011 with a swelling on the right labium majus. The tumour was initially misdiagnosed as a Bartholin's cyst and managed conservatively. The tumour was ultimately diagnosed as EMC and treated by radical surgical excision and adjuvant radiotherapy. The aim of the present study was to report the results after a long-term follow-up period and review the available relevant literature.

The diagnostic conundrum of chronic ectopic pregnancy: A case report.

Chronic ectopic pregnancy (CEP) is a rare condition caused by implantation of trophoblastic tissue in the fallopian tube, which causes protracted tissue destruction at the site of attachment. The process of minor rupture and bleeding results in chronic inflammation, giving rise to a haematocele which often resembles a pelvic mass. Unlike ectopic pregnancy, the level of serum human chorionic gonadotropin (hCG) in patients with CEP is usually low or undetectable as chorionic villi are generally sparse. Therefore, CEP often poses a specific diagnostic challenge for clinicians, as both biochemical markers and imaging modalities are unreliable in its diagnosis. Nevertheless, in cases where serum bhCG is significantly elevated in the presence of a large pelvic mass, the possibility of a malignant ovarian germ cell tumour (MOGCT) must be considered and investigated appropriately. Here, we present a rare case of a young woman who was referred to a gynaecological cancer centre with an acute abdomen for the treatment of MOGCT but was subsequently diagnosed with CEP following laparotomy. In our case report, we highlight the diagnostic conundrum of CEP and MOGCT and discuss the surgical challenges both these conditions pose, especially as many of these women are young and desire fertility preservation.

Standing data disproves biomechanical mechanism for balance-based torso-weighting.

OBJECTIVE: To test a proposed mechanism for the effect of balance-based torso-weighting (BBTW) in people with multiple sclerosis (MS) and healthy controls. The mechanism to be tested is that application of light weights to the trunk may result in a biomechanical shift of postural sway in the direction of weighting, mechanically facilitating maintenance of the center of mass over the base of support. DESIGN: Nonrandomized controlled trial. SETTING: Motion analysis laboratory. PARTICIPANTS: Participants with MS (n=20; average Expanded Disability Status Scale score, 4.1) and controls matched for sex, age, height, and weight (n=18). INTERVENTION: Light weights strategically placed according to the BBTW protocol were applied to all participants after at least 3 walking trials and 10 seconds of quiet standing with feet together and eyes open and then eyes closed. Measures were repeated after weighting. MAIN OUTCOME MEASURE: Forceplate center of pressure (COP) changes >1 standard error of measurement. RESULTS: With BBTW, people with MS had larger maximum changes in COP than healthy controls in the left-right direction but not in the anterior-posterior direction. COP changes >1 standard error of measurement occurred in the same direction of weighting 20% of the time (95% confidence interval, 5-34), ranging from 10% to 28% across conditions and directions of postural sway. Direction of greatest weight placement did not match the direction of change in the average COP in most participants with MS or the healthy controls in eyes open or eyes closed conditions (P<.001). CONCLUSIONS: If BBTW worked via a biomechanical shift of the center of mass, COP changes should match the direction of greatest weighting with BBTW. Our data allowed us to reject this hypothesis. Future research may explore alternative mechanisms of action underlying this intervention.