Evaluating the impact of the COVID-19 pandemic on tertiary gynaecological cancer care delivery: a population based study.

During the COVID-19 pandemic, reports of delays and alterations in cancer treatment pathways have emerged. We aim to evaluate the proportional impact of the pandemic over time on standard care delivery in a large tertiary gynaecological cancer centre. Consecutive patient records from weekly multidisciplinary team meetings were collected prospectively between 6 March 2020 and 26 March 2021. In total, 1943 patient discussions were held in our multidisciplinary team meetings during the study period, with 2.1% standard management decisions being altered due to the pandemic, the majority of which occurred during the first wave. Amongst alterations, 87.5% were deferral of surgery, and, in 62.5% of cases, were due to reduced critical care capacity. The majority of patients were offered alternative treatment, and surgery once resources permitted. During subsequent waves of COVID-19, with similar reductions in critical care capacity, we demonstrate avoidance of a second major increase in standard care pathway alterations.IMPACT STATEMENTWhat is already known about the subject? Recent evidence has demonstrated significant delays to cancer surgery during the COVID-19 pandemic. However, few studies have objectively evaluated the quantity and nature of deviations from both surgical and non-surgical standard gynaecological cancer care pathways.What the results of this study add? We examined in detail the effects of the pandemic on tertiary gynaecological cancer service delivery in our centre. The main impact was in the ability to perform major surgery due to reduced critical care capacity. However, with the majority of standard care alterations clustered during the first wave of the pandemic, we demonstrate how the implementation of a COVID-19 mitigation plan minimised service disruption during subsequent waves.What the implications are of these findings for clinical practice and/or further research? This study reinforces the importance of protecting gynaecological cancer services during situations where resources are limited. Having identified several key factors affected by the pandemic, we hope that our results will support others in coordinating responses to similar scenarios in future. Having not examined the effects of the pandemic on primary and secondary level cancer services, further research will be needed to evaluate the overall impact on long term patient outcomes.

Prolonged interruption of chemotherapy in patients undergoing delayed debulking surgery for advanced high grade serous ovarian cancer is associated with a worse prognosis.

INTRODUCTION: The current standard of care for advanced high grade serous ovarian cancer (HGSC) comprises a combination of debulking surgery and platinum-based chemotherapy given in the neoadjuvant or adjuvant setting. In the neoadjuvant setting, patients usually undergo 3 cycles of chemotherapy followed by interval cytoreductive surgery (ICS), then 3 further cycles of chemotherapy. However, the optimum timeframe to administer chemotherapy before and after ICS remains unclear. We therefore examine the survival impact of the interval between pre- and post-operative chemotherapy in patients undergoing ICS in a well-established patient cohort. Factors leading to "delays" in recommencing post-operative chemotherapy were also examined. METHODS: The study comprises of a retrospective cohort of 205 cases with FIGO stage III and IV HGSC undergoing ICS. The duration of the interval between pre-operative and post-operative chemotherapy was correlated with progression-free (PFS) and overall survival (OS). Univariate and multivariate analyses were constructed to identify factors associated with survival and prolonged chemotherapy interruption. RESULTS: The median interval between pre-operative and post-operative chemotherapy was 63 days. Multivariate analyses revealed macroscopic residual disease (HR:2.280, 95% CI:1.635-3.177, p ≤ 0.001) and interruption of chemotherapy >10 weeks (HR:1.65, 95%CI:1.201-2.290, p = 0.002) were associated with poorer OS. Existing medical comorbidities and longer hospital stay were independent prognostic factors for prolonging the chemotherapy interruption. CONCLUSION: Our study recommends that interruption to chemotherapy to allow patients to undergo ICS should be ≤10 weeks; otherwise, OS is significantly impacted. Patients with pre-existing medical comorbidities should receive additional support pre- and post-operatively to keep the chemotherapy interruption to a minimum.

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.

Socioeconomic differences impact overall survival in advanced ovarian cancer (AOC) prior to achievement of standard therapy.

PURPOSE: Survival difference between socioeconomic groups with ovarian cancer has persisted in the United Kingdom despite efforts to reduce disparities in care. Our aim was to delineate critical episodes in the patient journey, where deprivation has most impact on survival. METHODS: A retrospective review of 834 patients with advanced ovarian cancer (AOC) between 16/8/07-16/2/17 at a large cancer centre serving one of the most deprived areas of the UK. Using the Index of Multiple Deprivation (IMD), patients were categorised into five groups. RESULTS: Surgery was more common in less deprived patients (p < 0.00001). Across IMD groups, there were no differences in complete (R0) cytoreduction rate (r = 0.18, p > 0.05), age, or comorbidity. The R0/total cohort rate increased with increasing IMD group (p < 0.0001). Patients refusing any intervention belonged exclusively to the three most deprived groups; 5/7 patients who refused surgery belonged to the most deprived IMD group. Overall survival in the total patient group was less in IMD group 1-2 compared to 9-10 (p = 0.002). On multivariate analysis, IMD group was not an independent predictor of survival (p > 0.05). CONCLUSIONS: Socioeconomic differences in survival manifest in patients not receiving surgical treatment for AOC and are not purely explained by comorbidity, age, stage, or histological factors.

Ulipristal acetate for uterine fibroids: 2 years of real world experience in a UK hospital.

Ulipristal acetate (UPA), is a selective progesterone-receptor modulator, it decreases fibroid size and reduces menstrual bleeding. We reviewed its use at the Heart of England Foundation Trust (HEFT), one of the largest prescribing trusts in the UK. The electronic records of patients treated with UPA from January 2013 to August 2015 were reviewed. One hundred and thirty four patients received UPA, 20 women (15%) received a second course. Eighty percent reported subjective global improvements in symptoms after the first course; 45.5% described amenorrhoea or light bleeding compared to 4.5% prior to treatment. Fewer patients were anaemic (Hb <11 g/dL) following treatment (8.2% versus 33.6%). The majority of fibroids (34%) reduced or remained the same size (25%). Two-thirds of women treated for symptom control avoided surgical intervention. UPA improves symptoms and modifies the use of surgery in treating fibroids. Correcting anaemia prior to major surgery reduces the risk of blood transfusion and optimises a patient's condition as part of an enhanced recovery pathway. Impact Statement What is already known on this subject: In women with heavy menstrual bleeding secondary to fibroids, UPA has been shown to reduce fibroid size and control uterine bleeding, inducing amenorrhoea in the majority. Initially, only licenced for pre-operative use, an expansion of the licence has included on-going intermittent use for symptomatic fibroids. What the results of this study add: Our review is the largest published cohort of women treated with UPA. It demonstrates symptomatic improvements and advantageous modifications in fibroid size in women of all ethnicities and ages. Our inclusion of women with a uterine size greater than 16 weeks and fibroid diameter larger than 10 cm demonstrates the benefits of UPA with increased fibroid dimensions. What the implications are of these findings for clinical practice and/or further research: These findings can allow clinicians to consider alternative surgical interventions or even avoid surgery completely in a proportion of patients with fibroids. Correcting anaemia and optimising a patient's pre-operative condition reduces post-operative complications and ongoing morbidity. However, 25% of fibroids failed to respond to UPA treatment, further research into the characteristics of women and fibroids that show favourable clinical outcomes will allow identification of those women who are likely to benefit from treatment and prevent futile use in others.

A survey on the use of topical steroids in patients treated for lichen sclerosus-associated vulval squamous cell carcinoma.

Evidence suggests that lichen sclerosus (LS) is the primary aetiological factor for local vulval recurrence (LVR) in vulval squamous cell carcinoma (VSCC). The long-term application of topical corticosteroids is believed to prevent LVR. Patients treated for LS-associated VSCC at a gynaecological cancer centre were invited to complete a questionnaire to evaluate whether they are receiving corticosteroids. 55 of the 95 eligible patients (58%) completed the questionnaire; LS was treated in 69%, with steroids given to 84.2%. Most received steroids >3 months, but discontinued treatment once asymptomatic. An online survey was distributed to 313 British Gynaecological Cancer Society members to determine whether gynaecological oncologists prescribe corticosteroids for LS following VSCC surgery. 41 consultants (13.1%) completed the survey; 70.7% prescribe topical corticosteroids (potent/very potent in 79.3%), and 58.6% treat >1 year. Our findings demonstrate that patients are more likely to be given topical corticosteroids if symptomatic of LS. Furthermore, although treatment regimens vary, the majority of respondents advocate the use of very potent steroids and would support a tertiary chemopreventative trial. Impact statement What is already known on this subject: Local vulval recurrence (LVR) affects approximately one in four women who have received surgery for vulval squamous cell carcinoma (VSCC). What the results of this study add: Lichen sclerosus (LS), an inflammatory dermatosis, is recognised as the likely primary aetiological factor for LVR. Although there is evidence to suggest that long-term topical corticosteroid use in patients with residual LS may prevent LVR, the extent to which women were given topical steroids following surgery remains unclear. Our patient questionnaire evaluates if these patients are already receiving topical steroids, along with the strength of such steroids and duration of treatment. The consultant survey determines whether clinicians currently prescribe topical steroids following VSCC surgery, as well as the strength and duration of steroid therapy. What the implications are of these findings for clinical practice and/or further research: We aim to establish whether the gynaecological oncology community believe that long-term steroids may prevent LVR in women with LS-associated VSCC and whether they would support and recruit to a multicentre tertiary chemopreventative trial. These findings could influence a future clinical trial and may alter the ongoing management of these women.

Predictive value of the age-adjusted Charlston co-morbidity index on peri-operative complications, adjuvant chemotherapy usage and survival in patients undergoing debulking surgery after neo-adjuvant chemotherapy for advanced epithelial ovarian cancer.

The aim of this study was to determine whether the age-adjusted Charlston co-morbidity index (ACCI) can predict post-operative complications, adjuvant chemotherapy usage and overall survival (OS) in patients with advanced epithelial ovarian cancer (AOC) treated with neoadjuvant chemotherapy (NACT). A review was performed of all cytoreductive surgeries performed between 16/8/07-3/2/14 for AOC at a UK Cancer Centre. All surgeries were stratified by ACCI into three groups: Low (0-1), Intermediate (2-3) and High (≥4). Of the 293 cases the ACCI distribution was: 74 (25.26%) low, 164 (55.97%) intermediate and 55 (18.77%) high. Patients with a high ACCI were less likely to receive adjuvant chemotherapy (p = .023), more likely to receive fewer adjuvant cycles (p = .0057) but no more likely to experience complications. Median OS for patients with a low, intermediate and high ACCI was 44.58 (95%CI 36.98-52.19), 34.65 (95%CI 29.48-39.82) and 33.37 (95%CI 17.47-49.27) months. ACCI was associated with OS (p < .01) confirmed on multivariate analysis (p = .03). The ACCI is, therefore, a marker of survival in these patients and predicts adjuvant chemotherapy usage. Impact statement The Age-Adjusted Charlston Co-morbidity Index has previously been identified as a predictor of survival in both medical and surgical conditions. Recently it has also been validated in patients undergoing primary cytoreductive surgery for advanced ovarian cancer. This study is the first to validate the Age-Adjusted Charlston Co-morbidity Index in patients undergoing cytoreductive surgery following neoadjuvant chemotherapy. Our findings demonstrate that it can be used to not only predict overall survival in women undergoing debulking surgery after neo-adjuvant chemotherapy but also predicts the uptake and commencement of adjuvant chemotherapy. Such findings are important considerations to enable an informed patient choice regarding interval surgery in the more co-morbid patients. More importantly, although the ACCI can be used as a marker of overall survival, even in the most co-morbid of patients there remains a significant survival advantage following surgery to the extent that it should not be contraindicated in this cohort. The ACCI is being increasingly incorporated into various clinical trials as a standard demographic measure and this study validates its inclusion in patients undergoing interval debulking surgery.

When is it safe to omit surgery in primary peritoneal cancer with small volume disease?

Primary peritoneal cancer (PPC) is considered a very rare condition, with mesotheliomas deemed the only true PPC when considering the cellular content and embryological derivation of the peritoneum. However, in women, PPC are seen in much greater abundance than that in men and the type of cancer detected is often that of a serous epithelial carcinoma, histologically similar to serous ovarian carcinomas. The management is also similar, i.e. surgery and platin-based chemotherapy. The definition clinically of PPC is that of widespread carcinomatosis with normal-sized ovaries. The carcinomatosis is often extensive, and the only bulk disease may be within the omentum and achieving complete clearance of all disease at primary surgery unlikely. Thus, the concept of using chemotherapy as the main strategy is a reasonable approach and may well be the best single therapeutic option in some patients. This paper reviews the data on PPC and how this approach could be assessed.

Vulval cancer in pregnancy: Two case reports.

Vulval cancer is rare in women of reproductive age. We report two cases of vulval squamous cell carcinoma (VSCC) in pregnancy. They presented with a solitary labial mass, at 20 and 21 weeks of gestation, diagnosed as stage 1B VSCC based on clinical examination and cross-sectional imaging. In the first case, the patient underwent close clinical surveillance whilst pregnant and had an elective caesarean section at 39 weeks of gestation. Two months post-partum she underwent a radical anterior vulvectomy and bilateral groin sentinel lymph node biopsy. In the second case, the patient underwent an anterior vulvectomy at 33 weeks of gestation followed by a vaginal delivery at 37 weeks of gestation. Six weeks post-natally she had bilateral groin sentinel lymph node biopsies. We conclude that surgical resection is safe during pregnancy under spinal anaesthesia but it can be deferred until the post-partum period if the cancer presents at early stage.

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.

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.

A graphic elicitation technique to represent patient rights.

BACKGROUND: A patient charter is an explicit declaration of the rights of patients within a particular health care setting. In early 2020 the Save the Children Emergency Health Unit deployed to Cox's Bazar Bangladesh to support the establishment of a severe acute respiratory infection isolation and treatment centre as part of the COVID-19 response. We developed a charter of patient rights and had it translated into Bangla and Burmese; however, the charter remained inaccessible to Rohingya and members of the host community with low literacy. METHODS: To both visualise and contextualise the patient charter we undertook a graphic elicitation method involving both the Rohingya and host communities. We carried out two focus group discussions during which we discussed the charter and agreed how best to illustrate the individual rights contained therein. RESULTS: Logistical constraints and infection prevention and control procedures limited our ability to follow up with the original focus group participants and to engage in back-translation as we had planned; however, we were able to elicit rich descriptions of each right. Reflecting on our method we were able to identify several key learnings relating to: 1) our technique for eliciting feedback on the charter verbatim versus a broader discussion of concepts referenced within each right, 2) our decision to include both men and women in the same focus group, 3) our decision to ask focus group participants to describe specific features of each illustration and how this benefited the inclusivity of our illustrations, and 4) the potential of the focus groups to act as a means to introduce the charter to communities. CONCLUSIONS: Though executing our method was operationally challenging we were able to create culturally appropriate illustrations to accompany our patient charter. In contexts of limited literacy it is possible to enable access to critical clinical governance and accountability tools.

En bloc resection of the external iliac vein along with broad ligament leiomyosarcoma: A case report.

Outcomes following the excision of the external iliac vein during gynaecological oncology surgery are poorly documented. This is because most gynaecological oncologists consider tumours with vascular involvement inoperable. We describe a patient whose right external iliac vein was transected during the removal of a large broad ligament leiomyosarcoma invading the right external iliac vein. The patient's recovery following surgery was uneventful, and she remained disease-free 6 months postoperatively, with minimal morbidity. In describing this case, we hope to educate and inform other gynaecological oncologists facing a similar surgical challenge. We also propose that resection of the external iliac vessels in such cases is safe and feasible, and summarise the anatomical course of venous collaterals, which develop when the external iliac veins are obstructed.

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.

Diaphragm disease in advanced ovarian cancer: Predictability of pre-operative imaging and safety of surgical intervention.

OBJECTIVES: To establish the positive predictive values of pre-operative identification with CT imaging of metastatic diaphragm disease in surgically managed cases of advanced ovarian cancer (AOC). Additionally, we have assessed the post-operative morbidity and survival following diaphragmatic surgical intervention in a large regional cancer centre in the United Kingdom. STUDY DESIGN: A retrospective review of all cases of AOC with metastatic diaphragm disease surgically treated at the Pan-Birmingham Gynaecological Cancer Centre, UK between 1st August 2007 and 29th February 2016. RESULTS: A total of 536 women underwent surgery for primary AOC. Diaphragm disease was evident intra-operatively in 215/536 (40.1%) and 85/536 women (15.9%) underwent a procedure involving their diaphragm. Of these 85 cases, 38 peritoneal strippings (38/85, 44.7%), 31 partial diaphragmatic resections (31/85, 35.6%) and 16 electro-surgical ablations (16/85, 18.9%) were performed. There were no significant differences in post-operative complications between the three different diaphragmatic surgical groups. Of those patients who underwent peritoneal stripping or partial diaphragm resection, 12% were upstaged to stage 4A by virtue of pleural invasion. The positive predictive value for pre-operative radiological identification of diaphragmatic disease was 78.6%. CT imaging failed to detect diaphragmatic involvement despite obvious diaphragm disease during surgery in 29.4% of cases, giving a low negative predictive value of 64.8%. The sensitivity and specificity for CT imaging in detecting diaphragm disease was 44.3% and 93.8%, respectively. CONCLUSIONS: Diaphragmatic disease is often discovered in AOC. However, pre-operative assessment with CT imaging is not reliable in accurately detecting diaphragm involvement. Therefore, all patients with AOC should be regarded as in potential need for diaphragm surgery and their operation undertaken in cancer centres with adequate expertise in upper abdominal surgery. If there is a suspicion of diaphragm muscle invasion during diaphragmatic peritonectomy, the muscle should be partially resected. This will lead to potential upstaging of disease to stage 4A and therefore, to suitability for targeted therapy. In our Centre, the surgical removal of diaphragmatic disease did not significantly increase surgical morbidity.

Under expression of the Sonic Hedgehog receptor, Patched1 (PTCH1), is associated with an increased risk of local recurrence in squamous cell carcinoma of the vulva arising on a background of Lichen Sclerosus.

OBJECTIVE: Dysregulation of the Hedgehog (Hh) pathway has been described in a variety of cancers, including cervical cancer, a disease which shares a common aetiology with vulval squamous cell carcinoma (VSCC). Here, we investigate a large number of primary VSCC cases for evidence of Hedgehog pathway activation and examine the implications of pathway activity on clinical outcomes in a cohort of patients with primary VSCC. METHODS: Archival histology blocks containing VSCC and histologically normal adjacent epithelium were retrieved from a cohort of 91 patients who underwent treatment for primary VSCC. Immunohistochemistry staining was undertaken to assess for the expression of key Hh pathway components (SHH, PTCH1, GLI1). A competing risks statistical model was used to evaluate the implications of the levels of key Hh pathway components on clinical outcomes. RESULTS: We show that 92% of primary VSCC cases over-expressed one or more components of the Hh signalling pathway when compared to the adjacent normal epithelium. While expression of SHH and GLI1 did not correlate with any clinicopathological criteria, over- or under-expression of PTCH1 was associated with a reduced or increased risk of developing a local disease recurrence, respectively. In VSCC arising on a background of Lichen Sclerosus, the risk of local recurrence was potentiated in cases where PTCH1 was under-expressed. CONCLUSIONS: Our findings reveal, for the first time, that the Hh pathway is activated in VSCC and that PTCH1 expression can be used as a biomarker to stratify patients and inform clinicians of the risk of their local recurrence, particularly in cases of VSCC associated with LS.

Repurposing itraconazole for the treatment of cancer.

The repurposing of drugs is becoming increasingly attractive as it avoids the lengthy process and cost implications associated with bringing a novel drug to market. Itraconazole is a broad-spectrum anti-fungal agent. An emerging body of in vivo, in vitro and clinical evidence have confirmed that it also possesses antineoplastic activities and has a synergistic action when combined with other chemotherapeutic agents. It acts via several mechanisms to prevent tumour growth, including inhibition of the Hedgehog pathway, prevention of angiogenesis, decreased endothelial cell proliferation, cell cycle arrest and induction of auto-phagocytosis. These allow itraconazole, either alone or in combination with other cytotoxic agents, to increase drug efficacy and overcome drug resistance. This study reviews the reported literature on the use of itraconazole in a variety of malignancies and highlights the recent insights into the critical pathways acted upon to prevent tumour growth.

Fetal Limb Ischaemia in Twin-to-Twin Transfusion Syndrome.

Objective. To describe the rare association between prenatal vascular limb occlusion and twin-to-twin transfusion syndrome. The Case. A woman with severe twin-to-twin transfusion syndrome was treated with fetoscopic laser ablation at 19-week gestation. At 27 weeks, the twins were delivered by an emergency caesarean section. The right arm of twin 1, the recipient twin, was noted to be "ischaemic" and was later amputated. Conclusion. This case is unusual in that it affected the upper limb and there was no evidence of polycythaemia, which is a suggested pathological mechanism. It was initially thought that the limb damage was due to the laser ablation, but after discussion with the fetal medicine team vascular limb occlusion in association with twin-to-twin transfusion syndrome was considered. Limb ischaemia is a serious complication of twin-to-twin transfusion syndrome and is unrelated to any form of fetal therapy. Implications. Neonatologists and paediatricians need to be aware of this association as it has medicolegal implications and parents should be counselled as to the possible, albeit rare, occurrence, especially when twin-to-twin transfusion syndrome is of advanced stage at presentation.