Investigating age and ethnicity as novel high-risk phenotypes in mucinous ovarian cancer: retrospective study in a multi-ethnic population.

OBJECTIVES: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer. METHODS: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots. RESULTS: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38). CONCLUSION: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts.

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.

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.

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.

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.

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.

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.

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.

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.

Trends in Pediatric Intestinal Failure: A Multicenter, Multinational Study.

OBJECTIVES: To assess the natural history and outcomes of children with intestinal failure in a large, multicenter, geographically diverse contemporary cohort (2010-2015) from 6 pediatric intestinal failure programs. STUDY DESIGN: Retrospective analysis of a multicenter intestinal failure cohort (n = 443). Competing-risk analysis was used to obtain cumulative incidence rates for the primary outcome (enteral autonomy, transplantation, or death). The χ2 test and Cox proportional hazard regression were used for bivariate and multivariable analyses. RESULTS: The study cohort comprised 443 patients (61.2% male). Primary etiologies included short bowel syndrome (SBS), 84.9%; dysmotility disorder, 7.2%; and mucosal enteropathy, 7.9%. Cumulative incidences for enteral autonomy, transplantation, and death at 6 years of follow-up were 53.0%, 16.7%, and 10.5%, respectively. Enteral autonomy was associated with SBS, ≥50% of small bowel length, presence of an ileocecal valve (ICV), absence of portal hypertension, and follow-up in a non-high-volume transplantation center. The composite outcome of transplantation/death was associated with persistent advanced cholestasis and hypoalbuminemia; age <1 year at diagnosis, ICV, and intact colon were protective. CONCLUSIONS: The rates of death and transplantation in children with intestinal failure have decreased; however, the number of children achieving enteral autonomy has not changed significantly, and a larger proportion of patients remain parenteral nutrition dependent. New strategies to achieve enteral autonomy are needed to improve patient outcomes.

Maintaining surgical care delivery during the COVID-19 pandemic: A comparative cohort study at a tertiary gynecological cancer centre.

BACKGROUND: Surgery is the cornerstone of gynecological cancer management, but inpatient treatment may expose both patients and healthcare staff to COVID-19 infections. Plans to mitigate the impact of the COVID-19 pandemic have been implemented widely, but few studies have evaluated the effectiveness of these plans in maintaining safe surgical care delivery. AIM: To evaluate the effects of mitigating plans implemented on the delivery of gynecological cancer surgery during the COVID-19 pandemic. METHODS: A comparative cohort study of patients treated in a high-volume tertiary gyneoncological centre in the United Kingdom. Prospectively-recorded consecutive operations performed and early peri-operative outcomes during the same calendar periods (January-August) in 2019 and 2020 were compared. RESULTS: In total, 585 operations were performed (296 in 2019; 289 in 2020). There was no significant difference in patient demographics. Types of surgery performed were different (p = 0.034), with fewer cytoreductive surgeries for ovarian cancer and laparoscopic procedures (p = 0.002) in 2020. There was no difference in intra-operative complication rates, critical care admission rates or length of stay. One patient had confirmed COVID-19 infection (0.4%). The 30-day post-operative complication rates were significantly higher in 2020 than in 2019 (58 [20.1%] versus 32 [10.8%]; p = 0.002) for both minor and major complications. This increase, primarily from March 2020 onwards, coincided with the first peak of the COVID-19 pandemic in the UK. CONCLUSIONS: Maintaining surgical throughput with meticulous and timely planning is feasible during the COVID-19 pandemic but this was associated with an increase in post-operative complications due to a multitude of reasons.

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.

Deficits in Muscle Strength and Physical Performance Influence Physical Activity in Sarcopenic Children After Liver Transplantation.

Sarcopenia is a muscle disease characterized by reduced skeletal muscle mass (SMM), muscle strength, and physical performance. Reduced SMM has been identified in children after liver transplantation (LT), but no information related to muscle strength/physical performance or lifestyle factors contributing to sarcopenia is available. We hypothesized that sarcopenia, as determined by measures of SMM, muscle strength, and physical performance, is highly prevalent in children after LT and is related to poor diet quality (DQ) and physical inactivity. A cross-sectional study in post-LT children (n = 22) and age-matched healthy controls (n = 47) between the ages of 6 and 18 years examining body composition (dual energy X-ray absorptiometry and multiple skinfold), measures of muscle strength (handgrip, sit-to-stand, and push-ups), physical performance (6-minute walk test and stair climb test), diet (3-day food intake), and physical activity (accelerometer) was conducted. Low muscle strength/physical performance and SMM (SMM z scores ≤-1.5) were defined by values 2 standard deviations below the mean values for age- and sex-matched controls. Sarcopenia occurred in 36% of children who underwent LT, and they had significantly lower scores for muscle strength (sit-to-stand and push-up tests) and physical performance (stair climb test) than controls (P < 0.05). Deficits in physical performance in children with sarcopenia were predominantly revealed by longer stair climbing times (P = 0.03), with no differences in other muscle tests. Low SMM, muscle strength, and physical performance were associated with a lower amount of time spent in fairly and very active physical activity, but no associations with DQ were found. Sarcopenia is highly prevalent in children after LT and is related to lower moderate-to-vigorous physical activity. Development of effective rehabilitation strategies to treat sarcopenia are needed in post-LT children.

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.

Kindergarten-age neurocognitive, functional, and quality-of-life outcomes after liver transplantation at under 6 years of age.

BACKGROUND: We aimed to describe school-entry age neurocognitive, functional, and HRQL outcomes and their predictors after liver transplant done at age <6 years. METHODS: A prospective cohort of all (n = 69) children surviving liver transplant from 1999 to 2014 were assessed at age 55.4 (SD 7.2) months and 38.6 (12.4) months after transplant. Assessment included: the Wechsler Preschool and Primary Scales of Intelligence, Beery-Buktenica Developmental Test of VMI, Adaptive Behavior Assessment System caregiver-completed questionnaire, and PedsQL 4.0 Generic Core Scales. Univariate and multiple linear regression determined predictors of outcomes at P < .05. RESULTS: Neurocognitive and functional outcomes were on average within 1 SD of population norms, although shifted to the left (P ≤ .03), with more patients than expected having scores >2 (3.7-5.9 times more, P ≤ .007) SD below population norms. Total and Summary HRQL scores were statistically significantly lower than the healthy normative population (P ≤ .02) and a congenital heart disease group (P ≤ .02), but similar to children with other chronic health conditions; differences often exceeded the MCID and were lowest in the School functioning domain. There were few predictors on multiple linear regressions, and we could not confirm previous studies that suggested various inconsistent predictors of outcomes. Neurocognitive and functional outcomes scores were highly correlated with HRQL scores except for the School functioning domain, but did not fully explain them. CONCLUSIONS: Long-term follow-up of this vulnerable population is important in order to facilitate support for the patient and family, and early intervention for any difficulties identified.

Paediatric intestinal failure and transplantation.

Intestinal failure is a complex and debilitating condition characterised by inadequate small intestinal function requiring parenteral or intravenous nutrition to maintain health and, for children, to enable growth and development. Although parenteral nutrition can be prescribed in many hospitals, children with chronic intestinal failure have improved outcomes when managed at a paediatric centre by a multidisciplinary team with specialised expertise in the comprehensive management of intestinal failure. Recent advances in the medical, surgical and nutritional approach have been effective at optimising intestinal rehabilitation and achieving enteral autonomy while limiting complications of intestinal failure. The role of intestinal transplantation in the management of the child with intestinal failure continues to evolve as an option for children with life-threatening complications of intestinal failure. The aim of this review is to highlight key advances in the care of children with intestinal failure.

Healthy Body Weights With Corticosteroid-free Immunosuppression Is the Best Predictor of Cardiovascular Health in Children After Liver Transplantation.

INTRODUCTION: Cardiometabolic dysregulation (CMD) influences morbidity and mortality risk in adults post-liver transplantation (LTx). CMD is reported in 10% to 25% of pediatric LTx recipients, but no information regarding the longitudinal expression of CMD is available. The study objective was to examine the longitudinal expression of CMD and associations with body composition and growth in children post-LTx. METHODS: A retrospective review was conducted in youth (34 F/30 M) who underwent LTx between 1994 and 2015 at the Stollery Children's Hospital. Primary outcomes included serum markers of CMD (insulin, glucose, hemoglobin A1C [A1C], homeostasis model assessment for insulin resistance [abnormal >3], lipid panel triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol) and systolic/diastolic blood pressure (BP: absolute/z scores). RESULTS: Mean (±SD) age, weight z, height z, body mass index z was 9.7 ±â€Š3.4 years (3.5-17.9), 0.26 ±â€Š1.03, 0.017 ±â€Š1.2, and 0.41 ±â€Š1.05, respectively. The majority of children had percentage fat mass, percentage fat-free mass within normal reference ranges. Systolic/diastolic BP was within healthy references ranges in 83.1% and 93.5% of children, respectively. Serum insulin (83.4%) and high-density lipoprotein-cholesterol (43.9%) concentrations were low, with abnormal findings of other laboratory markers found in <5% of participants. Abnormal findings for metabolic parameters were independent of weight z, body mass index z, fat mass, and corticosteroids but were positively related to child's age (>9.7 years) and fat-free mass (total, arms). Insulin levels decreased significantly in the first 4 years post-LTx, but no changes in lipid panel, A1C and glucose were noted over 10 years. CONCLUSIONS: Pediatric LTx recipients with healthy body weights and corticosteroid-free immunosuppression have a low expression of CMD over 10 years.