Small and large bowel anatomy is associated with enteral autonomy in infants with short bowel syndrome: A retrospective cohort study.

BACKGROUND: Achievement of enteral autonomy (EA) is the ultimate treatment goal in pediatric intestinal failure (IF). We aimed to assess predictors of EA in pediatric short bowel syndrome (SBS) and explore the impact of residual small bowel (SB) and large bowel (LB) length on EA. METHODS: A retrospective cohort study was performed on infants aged <12 months (n = 367, six centers) with SBS referred between 2010 and 2015. The cohort was stratified based on the achievement of EA. Statistical testing was completed using t-test, chi-square, Cox proportional hazards regression model, and Kaplan-Meier analysis. RESULTS: EA was achieved in 229 patients. In the multivariable analysis, the percentage of residual LB (hazard ratio [HR] = 1.02; 95% CI = 1.01-1.02) and SB (HR = 1.01; 95% CI = 1.01-1.02) length, presence of the ileocecal valve (HR = 2.02; 95% CI=1.41-2.88), and not coming from a high-volume transplantation center (HR = 2.42; 95% CI = 1.68-3.49) were positively associated with EA, whereas a negative association was seen with the presence of stoma at the time when shortest remnant was documented (HR = 0.72; 95% CI = 0.52-1.00). EA achievement was significantly different between the anatomical subgroups (log-rank test P < 0.001) with an EA rate of 80.4% in infants with ≥50% SB and LB (median time 209 days); 62.5% with ≥50% SB and <50% LB (397 days); 58.3% with <50% SB and ≥50% LB (1192 days), and 25.9% with <50% SB and LB. Necrotizing enterocolitis (NEC) was not associated with a better achievement of EA (NEC vs other etiologies: log-rank test P = 0.33). CONCLUSIONS: Overall, 62% of infants with IF secondary to SBS achieved EA over a mean time of follow-up of 2.3 years. A colon length of >50% can compensate for the loss of small bowel (<50%) and account for similar EA rates as those in children with residual SB > 50%.

Completing a genomic characterisation of microscopic tumour samples with copy number.

BACKGROUND: Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples. RESULTS: Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy. CONCLUSIONS: PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available.

Identifying Key Themes of Care Coordination for Patients with Chronic Conditions in Singapore: A Scoping Review.

A projected rise in patients with complex health needs and a rapidly ageing population will place an increased burden on the healthcare system. Care coordination can bridge potential gaps during care transitions and across the care continuum to facilitate care integration and the delivery of personalised care. Despite having a national strategic vision of improving care integration across different levels of care and community partners, there is no consolidation of evidence specifically on the salient dimensions of care coordination in the Singapore healthcare context. Hence, this scoping review aims to uncover the key themes that facilitate care coordination for patients with chronic conditions in Singapore to be managed in the community while illuminating under-researched areas in care coordination requiring further exploration. The databases searched were PubMed, CINAHL, Scopus, Embase, and Cochrane Library. Results from Google Scholar were also included. Two independent reviewers screened articles in a two-stage screening process based on the Cochrane scoping review guidelines. Recommendation for inclusion was indicated on a three-point scale and rating conflicts were resolved through discussion. Of the 5792 articles identified, 28 were included in the final review. Key cross-cutting themes such as having standards and guidelines for care programmes, forging stronger partnerships across providers, an interoperable information system across care interfaces, strong programme leadership, financial and technical resource availabilities and patient and provider-specific factors emerged. This review also recommends leveraging these themes to align with Singapore's national healthcare vision to contain rising healthcare costs.

Sentinel lymph node biopsy based on anatomical landmarks and locoregional mapping of inguinofemoral sentinel lymph nodes in women with vulval cancer: an operative technique.

Inguinal lymph node involvement is the most robust predictor of mortality in vulval cancer and sentinel lymph node (SLN) biopsy is a safe diagnostic modality. We describe a technique based on anatomical landmarks. Our aims are (1) to describe the territorial mapping of SLNs, (2) to evaluate the associated complication rate vis-à-vis those reported in the literature, and (3) to assess its accuracy in detecting SLNs. Data from women who underwent groin SLN biopsies for vulval cancer at a single cancer centre were prospectively collected. All subjects met the GROINSS-V eligibility criteria. The location of the SLN relative to the saphenous vein was recorded. All women were followed up and early and late complications were recorded. The recurrence rate at the time of the census was calculated. A total of 71 groins in 44 women were included. The SLN was primarily located over Cloquet's node (85.2%). The incidence of early wound cellulitis and dehiscence were 2.8% and 11.3% while lymphocysts were present in 11.3% of groins. The negative nodal recurrence rate was 1.7%. Results showed that this reproducible technique allows access to 96.7% of SLNs, including both deep and superficial SLNs whilst minimising the need for extensive dissection and complications associated with overharvesting of lymph nodes.

What is already known on this subject? Inguinal sentinel lymph node (SLN) biopsy in women with vulval cancer is often construed as a challenging skill to master and the success rate of SLN detection is dependent on the experience and skill of the surgeon. A review of the literature has revealed that whilst studies have largely concentrated on the efficacy of different intraoperative detection modalities or histopathological protocols, the literature describing a standardised surgical technique remains deficient.What do the results of this study add? Our technique offers multiple advantages: our incision, albeit small, allows the operator to gain access to 96.7% of inguinal SLNs and facilitates access to both deep and superficial SLNs regardless of patients' body mass index, minimises the need for extensive dissection and hence reduces the incidence of complications associated with overharvesting of lymph nodes such as lymphoedema or lymphocysts, particularly in obese women. Our local figures also support the safety of this operative technique (negative nodal recurrence rate 1.7%) and compare favourably with those from the GROINSS-V study.What are the implications of these findings for clinical practice and/or further research? We describe a reproducible technique based on anatomical landmarks and an appreciation of the territorial mapping of inguinal SLN to optimise the chances of identifying the inguinal SLN in women with vulval cancer while circumventing the sequelae often attributed to this procedure.

Nonsquamous Malignancies of Vagina and Vulva: 23-Year Experience at a Tertiary Center in the United Kingdom.

Under 10% of gynaecological cancers are diagnosed in the vulva and vagina, mostly squamous cell carcinomas. Melanoma, Paget disease, basal cell carcinomas, and other cancers can present with vulval/vaginal symptoms. The pathology information system of a tertiary referral center for vulvo-vaginal cancers was searched for cancers of the vulva and vagina from 1996 to 2019. Squamous carcinomas were excluded, and the remaining entities were catalogued. A total of 221 nonsquamous cancers were found, including 135 vaginal and 86 vulval cases. One hundred eight cases of metastatic carcinomas from the endometrium, cervix, ovary, bowel, bladder, kidney, and breast formed the largest category. Basal cell carcinomas constituted the second largest category. Others included melanomas, Paget disease, and adenoid cystic carcinomas. Primary adenocarcinomas included porocarcinoma, mammary type carcinoma, enteric type carcinoma, clear cell carcinoma, Bartholin gland adenocarcinoma and malignant transformation of hidradenoma papilliferum. The vulva and vagina can harbor a wide range of nonsquamous malignancies. The most challenging of these are adenocarcinomas which can be metastatic from other sites. The dominance of metastatic carcinomas in this series is likely to reflect consultation practice of specialist pathologists.

Accuracy and Precision of Point-of-Care International Normalized Ratio in Patients With Liver Disease.

OBJECTIVE: To determine if the CoaguChek XS Pro Point-of-Care (POC) device can accurately and precisely measure the international normalized ratio (INR) compared with the gold standard laboratory INR in pediatric and adult patients with liver disease. METHODS: This prospective cohort study included 15 pediatric patients without liver disease, 13 pediatric patients with liver disease, and 17 adult patients with liver disease. The accuracy of the POC INR values was determined using the correlation and Bland-Altman limits of agreement. The accuracy of the coagulometer INR was assessed by calculating the proportion of POC INR measurements that were ≤15% of their corresponding laboratory INR. RESULTS: A comparison of INR measurements showed an excellent correlation in pediatric patients without liver disease ( r = 0.82), pediatric patients with liver disease ( r = 0.89), and adult patients with liver disease ( r = 0.96). Fourteen (93%) POC INR values were ≤15% in pediatric patients without liver disease from its paired laboratory INR. All 13 paired measurements were ≤15% in pediatric patients with liver disease. In adult patients with liver disease, 12 (71%) POC INR values were ≤15% of their paired laboratory INR. CONCLUSIONS: In patients with liver disease, the CoaguChek XS Pro provides an accurate measure of the INR compared to laboratory INR measurements.

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.

Comparison of Body Composition, Muscle Strength and Cardiometabolic Profile in Children with Prader-Willi Syndrome and Non-Alcoholic Fatty Liver Disease: A Pilot Study.

Syndromic and non-syndromic obesity conditions in children, such as Prader-Willi syndrome (PWS) and non-alcoholic fatty liver disease (NAFLD), both lower quality of life and increase risk for chronic health complications, which further increase health service utilization and cost. In a pilot observational study, we compared body composition and muscle strength in children aged 7−18 years with either PWS (n = 9), NAFLD (n = 14), or healthy controls (n = 16). Anthropometric and body composition measures (e.g., body weight, circumferences, skinfolds, total/segmental composition, and somatotype), handgrip strength, six minute-walk-test (6MWT), physical activity, and markers of liver and cardiometabolic dysfunction (e.g., ALT, AST, blood pressure, glucose, insulin, and lipid profile) were measured using standard procedures and validated tools. Genotyping was determined for children with PWS. Children with PWS had reduced lean body mass (total/lower limb mass), lower handgrip strength, 6MWT and increased sedentary activity compared to healthy children or those with NAFLD (p < 0.05). Children with PWS, including those of normal body weight, had somatotypes consistent with relative increased adiposity (endomorphic) and reduced skeletal muscle robustness (mesomorphic) when compared to healthy children and those with NAFLD. Somatotype characterizations were independent of serum markers of cardiometabolic dysregulation but were associated with increased prevalence of abnormal systolic and diastolic blood pressure Z-scores (p < 0.05). Reduced lean body mass and endomorphic somatotypes were associated with lower muscle strength/functionality and sedentary lifestyles, particularly in children with PWS. These findings are relevant as early detection of deficits in muscle strength and functionality can ensure effective targeted treatments that optimize physical activity and prevent complications into adulthood.

Australasian paediatric gastroenterologist practices of coeliac disease diagnosis before and during the COVID-19 pandemic.

AIM: To explore the perceptions and practices of Australasian paediatric gastroenterologists in diagnosing coeliac disease (CD) before and during the COVID-19 pandemic. METHODS: Paediatric gastroenterologists in Australasia were invited via email to complete an anonymous online questionnaire over a 2-week period in 2021. RESULTS: The questionnaire was completed by 39 respondents: 33 from Australia and six from New Zealand (NZ) equating to a 66% response rate. Thirty-four (87%) of the 39 respondents reported they currently practised non-biopsy diagnosis of CD in eligible children, while the rest diagnosed CD using biopsy confirmation only. All NZ respondents practised non-biopsy CD diagnosis. A majority of responders (76%) who practised non-biopsy CD diagnosis followed the 2020 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines. Twenty-two (56%) respondents reported that they started using a non-biopsy CD diagnosis protocol before the pandemic and did not change their practice during the pandemic, 10 (26%) started diagnosing non-biopsy CD during the pandemic, 5 (13%) stated their practices of CD were not impacted by the pandemic and 2 (5%) did not respond on whether the pandemic changed their practice. CONCLUSION: The majority of Australasian gastroenterologist respondents reported they routinely utilised the 2020 ESPGHAN diagnostic criteria in eligible children; half of them started prior to the pandemic and another quarter started this approach due to the pandemic. A minority of practitioners routinely rely only on biopsy confirmation to diagnose CD.

An international multicenter validation study of the Toronto listing criteria for pediatric intestinal transplantation.

Deciding which patients would benefit from intestinal transplantation (IT) remains an ethical/clinical dilemma. New criteria* were proposed in 2015: ≥2 intensive care unit (ICU) admissions, loss of ≥3 central venous catheter (CVC) sites, and persistently elevated conjugated bilirubin (CB ≥ 75 µmol/L) despite 6 weeks of lipid modification strategies. We performed a retrospective, international, multicenter validation study of 443 children (61% male, median gestational age 34 weeks [IQR 29-37]), diagnosed with IF between 2010 and 2015. Primary outcome measure was death or IT. Sensitivity, specificity, NPV, PPV, and probability of death/transplant (OR, 95% confidence intervals) were calculated for each criterion. Median age at IF diagnosis was 0.1 years (IQR 0.03-0.14) with median follow-up of 3.8 years (IQR 2.3-5.3). Forty of 443 (9%) patients died, 53 of 443 (12%) were transplanted; 11 died posttransplant. The validated criteria had a high predictive value of death/IT; ≥2 ICU admissions (p < .0001, OR 10.2, 95% CI 4.0-25.6), persistent CB ≥ 75 µmol/L (p < .0001, OR 8.2, 95% CI 4.8-13.9). and loss of ≥3 CVC sites (p = .0003, OR 5.7, 95% CI 2.2-14.7). This large, multicenter, international study in a contemporary cohort confirms the validity of the Toronto criteria. These validated criteria should guide listing decisions in pediatric IT.

Prevalence of computed tomography-based sarcopenia and the prognostic value of skeletal muscle index and muscle attenuation amongst women with epithelial ovarian malignancy: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia represents an index of frailty amongst cancer patients and it is associated with poor oncological outcomes and a higher risk of surgical complications in several types of malignancy. AIM: To further delineate the impact of sarcopenia assessed via computed tomography scan (CT) on oncological outcomes and post-operative complications amongst women with epithelial ovarian carcinoma (EOC). Our secondary objective was to quantify and understand the prevalence of sarcopenia in EOC. DESIGN: We systematically searched MEDLINE, SCOPUS, ClinicalTrials.gov, and Cochrane Database, from inception up to August 2021. Quality assessment was performed using the Newcastle-Ottawa scale (NOS). Outcomes consisted of prevalence, overall survival (OS), progression-free survival (PFS) and post-operative complications. Pooled analyses of proportion estimates, hazard ratios (HRs) and odds ratios (ORs) were performed with STATA and Review Manager 5.3. RESULTS: 21 studies were included in this meta-analysis. NOS scores ranged from six to nine. Pooled analysis yielded an overall sarcopenia prevalence of 41%. Pooled analysis of adjusted HRs demonstrated significant association between low muscle attenuation (MA) [aHR = 1.23, (95% CI 1.02-1.47), p-value = 0.03] and OS, whilst low skeletal muscle index (SMI) trended towards shorter OS [aHR = 1.37, (95% CI 0.99-1.90), p-value = 0.05. Low-SMI was also associated with higher risk of total post-operative complications [uOR = 1.56, (95% CI 1.16-2.11), p-value = 0.004]. CONCLUSION: Our findings suggest that CT-assessed skeletal mass and radiodensity represent rather accurate indices of nutritional status and could prospectively be incorporated into the decision-making process in women with EOC.

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.

Friend or foe? The prognostic role of endometriosis in women with clear cell ovarian carcinoma. A UK population-based cohort study.

PURPOSE: The prognostic role of endometriosis amongst women with ovarian clear cell carcinoma (OCCC) remains debatable. The aim of this study was to ascertain the effect of endometriosis on the prognosis of OCCC. METHODS: A retrospective review of the medical records of 94 women diagnosed and treated for OCCC at a tertiary gynaecological cancer centre in the UK, spanning the period 2010-2019. Women were divided into two groups according to the presence of endometriosis. Clinico-pathological characteristics, progression-free survival (PFS) and overall survival (OS) were collated between the two groups. RESULTS: Forty-six cases of endometriosis-free OCCC (Ef-OCCC) were collated with 48 cases of endometriosis-related OCCC (Er-OCCC). There was no significant difference between the two groups regarding age (p-value = 0.2), FIGO stage (p-value = 0.8), residual disease (RD) (p-value = 0.07), adjuvant chemotherapy agent (p-value = 0.4) or chemo-resistance (p-value = 0.9). The presence of endometriosis did not significantly affect either OS or PFS. The median OS in the Ef-OCCC and Er-OCCC was 55.00 (95% CI 32.00-189.00) and 71.00 (95% CI 47.00-97.00; log rank = 1.35, p-value = 0.2) months. The median PFS in the Ef-OCCC and Er-OCCC group was 39.00 (95% CI 19.00-143.00) and 39.00 (95% CI 19.00-62.00; log rank = 0.7, p-value = 0.4) months. Survival differences between the two groups were not significant after stratification analysis for independent prognosticators. CONCLUSION: Endometriosis was not independently associated with the prognosis of OCCC either in crude analysis or after stratification for stage and RD. Further larger, well-designed prospective studies are warranted to draw firmer conclusions on the intrinsic link between endometriosis and OCCC.

COVID-19 and the ageing workforce: global perspectives on needs and solutions across 15 countries.

BACKGROUND: COVID-19 has a direct impact on the employment of older people. This adds to the challenge of ageism. The World Health Organization has started a worldwide campaign to combat ageism and has called for more research and evidence-based strategies that have the potential to be scaled up. This study specifically aims to identify solutions to combat the adverse effects of COVID-19 on the global ageing workforce. METHODS: We present 15 case studies from different countries and report on what those countries are doing or not doing to address the impact of COVID-19 on ageing workers. RESULTS: We provide examples of how COVID-19 influences older people's ability to work and stay healthy, and offer case studies of what governments, organizations or individuals can do to help ensure older people can obtain, maintain and, potentially, expand their current work. Case studies come from Australia, Austria, Canada, China, Germany, Israel, Japan, Nigeria, Romania, Singapore, Sweden, South Korea, Thailand, United Kingdom (UK), and the United States (US). Across the countries, the impact of COVID-19 on older workers is shown as widening inequalities. A particular challenge has arisen because of a large proportion of older people, often with limited education and working in the informal sector within rural areas, e.g. in Nigeria, Thailand and China. Remedies to the particular disadvantage experienced by older workers in the context of COVID are presented. These range from funding support to encouraging business continuity, innovative product and service developments, community action, new business models and localized, national and international actions. The case studies can be seen as frequently fitting within strategies that have been proven to work in reducing ageism within the workplace. They include policy and laws that have increased benefits to workers during lockdowns (most countries); educational activities such as coaching seniorpreneurship (e,g, Australia); intergenerational contact interventions such as younger Thai people who moved back to rural areas and sharing their digital knowledge with older people and where older people reciprocate by teaching the younger people farming knowledge. CONCLUSION: Global sharing of this knowledge among international, national and local governments and organizations, businesses, policy makers and health and human resources experts will further understanding of the issues that are faced by older workers. This will facilitate the replication or scalability of solutions as called for in the WHO call to combat ageism in 2021. We suggest that policy makers, business owners, researchers and international organisations build on the case studies by investing in evidence-based strategies to create inclusive workplaces. Such action will thus help to challenge ageism, reduce inequity, improve business continuity and add to the quality of life of older workers.

A Multiethnic Asian Perspective of Presumed Consent for Organ Donation: A Population-Based Perception Study.

Background: Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations. Therefore, this study aimed to understand public sentiment and different barriers toward organ donation from the perspective of Singapore, a highly diverse and multiethnic Asian society. Methods: A cross-sectional community semi-structured interview was conducted in a public housing estate in Singapore. Pilot test was undertaken before participants were interviewed face-to-face by trained personnel. All statistical evaluations were conducted using Stata. The χ2-test compared subgroups based on patient characteristics while multivariable logistic regression identified predictors of willingness to donate/ assent. Effect estimates were quantified using odds ratio (OR). Findings: Out of 799 individuals, 85% were agreeable to organ donation after death and 81% were willing to assent to donations of family members' organs, which declined by 16% (p < 0.001) after a clinical scenario was presented. Demographic factors including ethnicity, education, marital, and employment status affected willingness to donate and assent. Knowledge correlated significantly with willingness to donate and assent. In particular, knowledge regarding brain death irreversibility had the strongest correlation (AOR 2.15; 95% CI 1.60-2.89). Conclusions: Organ donation rates remain low albeit presumed consent legislation, due to patient-level barriers, including but not limited to knowledge gaps, cultural values, religious backgrounds, and emotional impact at relatives' death. To effectively boost donor rates, it is crucial for policy makers to invest in public education and improve transplant provisions and family protocols.

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.