Charing Cross Hospital Research Articles

Can we replace adjuvant chemotherapy with surveillance for stage IA-C immature ovarian teratomas of any grade? an international multicenter analysis

BackgroundThe role of surveillance after surgery for stage IA-C grade 2 (G2) or grade 3 (G3) immature teratomas (ITs) is controversial with many guidelines advocating adjuvant chemotherapy. Here, we investigate the safety of surveillance in stage IA-C G1-3 ITs. MethodsClinicopathological data were analysed on postpubertal patients with stage I pure ITs in Multicenter Italian Trials in Ovarian Cancer centres and at Charing Cross Hospital, UK, between January 1985 and January 2018. ResultsOf 108 stage I patients, 66 (61.1%), 3 (2.8%) and 39 (36.1%) were International Federation of Gynecology and Obstetrics IA, IB, IC, respectively, with 31 (28.7%), 41 (38%) and 36 (33.3%) having grade 1 (G1), 2 and 3 disease, respectively. After surgery, 27 patients (25%) had adjuvant chemotherapy and 81 (75%) surveillance. There was no significant increase in the risk of malignant (G2-3 IT) relapse (9/81 vs 2/27; p = 0.72) or in disease-free survival (DFS) or overall survival in the surveillance vs chemotherapy groups. The median time to relapse was 17.8 months (range: 3–47) with no significant difference between surveillance or chemotherapy groups. The median follow-up was 64.3 months (Interquartile range (IQR) 22.2–101.7). Chemotherapy induced cures in all except for one patient who did not follow the surveillance protocol due to pregnancy and died of disease. Univariate and multivariate analyses revealed that only tumour grade (hazard ratio [HR] = 3.11; p = 0.02) and complete surgical staging (HR = 0.2; p = 0.01) were independent prognostic factors for decreased DFS. ConclusionThe present study suggests that in the adult setting careful surveillance appears to be an acceptable alternative to adjuvant chemotherapy for stage IA-C ITs of any grade, properly staged and with negative postoperative tumour markers.

Uterine artery pulsatility index and serum BMP-9 predict resistance to methotrexate therapy in gestational trophoblastic neoplasia: A cohort study

Methotrexate is the most common first-line chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Uterine artery pulsatility index (UAPI) is an ultrasound marker for tumor vascularity that has been associated with an increased risk of methotrexate resistance. The combination of circulating angiogenic factor levels with UAPI data may improve the capacity of this model to predict chemoresistance. This was a single-center cohort study of women newly diagnosed between January 2008 and June 2012 with low-risk GTN during postmolar surveillance and treated with single-agent methotrexate at Charing Cross Hospital, a UK national center for treatment of gestational trophoblastic disease. Two hundred seventeen women underwent an ultrasound for UAPI measurement prior to initiation of chemotherapy. To examine serologic markers of methotrexate resistance among this cohort, we performed a case-control study using archived serum from 76 patients who could be matched based on prognostic risk score. Serum samples were examined by immunoassay to measure 8 different angiogenic factors (VEGF-A, FGF-basic, PLGF-1, PDGF-BB, EGF, ANGPT2, BMP-9, and ENG). Receiver-operator characteristic area under the curve (AUC) values were calculated for the ability of each analyte to correctly classify patients as methotrexate sensitive (MTX-S) or resistant (MTX-R). Total human chorionic gonadotropin levels were similar between the MTX-S and MTX-R groups. UAPI values were significantly higher in MTX-S (median 1.30 [interquartile range {IQR} = 0.80-1.90]) compared to MTX-R patients (median 0.875 [IQR = 0.60-1.30]; P < 0.0001) with AUC 0.68 (95% confidence interval 0.61-0.76; P < 0.0001). In univariate analysis, only BMP-9 concentrations were significantly different between groups, lower among MTX-S (median of 225 ng/L, IQR = 170-287) compared to MTX-R patients (median 280 ng/L [IQR = 200-339]; P= 0.03). Combining UAPI with BMP-9 concentration improved prediction for chemoresistance with AUC 0.77 (95% confidence interval 0.66-0.88; P < 0.0001). Circulating levels of BMP-9 are elevated in newly diagnosed women with low-risk GTN destined to fail primary methotrexate therapy. A combined test using serum BMP-9 plus UAPI might improve prediction of MTX-R in low-risk GTN.

Roy William Lamb

From 1962 to 1993, Roy William Lamb (“Larry”) was a GP and anaesthetist in Stroud, Gloucestershire. He grew up in the East End of London during the war years and...

Christopher John Richard Newbegin

Christopher John Richard Newbegin (“Chris”) was educated at Harrow County School for Boys and St Mary’s Hospital Medical School. He initially planned to become an orthopaedic surgeon, but his friendship...

Invited Commentary: Changing Landscape of Imaging in Recurrent Prostate Cancer.

Invited Commentary: Changing Landscape of Imaging in Recurrent Prostate Cancer.

Spotlight in Plastic Surgery: April 2020

Spotlight in Plastic Surgery: April 2020

Expediting the management of cauda equina syndrome in the emergency department through clinical pathway design

IntroductionCauda equina syndrome (CES) is a neurosurgical emergency. Early diagnosis with MRI and subsequent surgical decompression surgery can prevent permanent neurological dysfunction. Charing Cross Hospital (CXH) is a tertiary neurosurgical...

GestaTIonal TrophoblAstic NeoplasIa Ultrasound assessMent: TITANIUM study

BackgroundThere are limited data on ultrasound morphologic features of gestational trophoblastic neoplasia. A predictive model to determine predictors of response to therapy would be ideal in the management of patients...

David Barrington Shaw

We readily forget travel problems once posed to rural patients with complex cardiac problems. David Barrington Shaw, who died on 15 March 2019, brought specialist cardiology to those who lived...

P108 Acetazolamide for obstructive hydrocephalus in the pregnant female: a case report and literature review.

ObjectivesThis study presents a case report and literature review of acetazolamide use in the pregnant patient to further delineate its role and controversies in the treatment of symptomatic hydrocephalus. Here we present a case from our neurosurgical service which demonstrated safe use and efficacy of acetazolamide in refractory hydrocephalus secondary to a space-occupying lesion.DesignCase report and literature review.Subjects33-year-old, primigravid female treated at Charing Cross Hospital, London.MethodsAdaptation of the PRISMA guideline to facilitate an initial PubMed database search for all available full-text, peer-reviewed publications in English. Papers were screened for relevance to pregnant patients with hydrocephalus receiving acetazolamide therapy, as well as relevant papers describing related disorders of cerebrospinal fluid flow.ResultsThere exist no prospective, randomised-controlled trials for the use of acetazolamide to treat hydrocephalus in pregnancy. Retrospective data in patients with related conditions suggest no significant link between acetazolamide use and teratogenicity in humans.ConclusionsAcetazolamide can be a safe and efficacious therapy in the pregnant patient with refractory hydrocephalus as a bridge to delivery. We agree with the consensus and its appropriate use in the pregnant neurosurgical patient.

P50 The role of care of the elderly in neurosurgery

ObjectivesAssess the volume of frailty in a neurosurgical centre and role of geriatric liaison.DesignRetrospective Review.SubjectsAll patients admitted to Charing Cross Hospital in Jan 2018.MethodsWe reviewed patient notes to assess frailty score using the Clinical Frailty Scale (Dalhousie University) and differences with emergency vs elective admissions and length of stay (LoS).ResultsMore than 50% of patients admitted to the unit were above 65 years old. 30% of all admissions met the criteria for mild to moderate frailty moreover 34% were classed as severely frail. These findings are comparable to acute medical wards. Two third of patients had an average LoS above 10 days, of these 50% were severely frail. Emergency admissions demonstrated a greater burden of frailty and expectedly LoS in severely frail patients was significantly higher 15 vs 40 days in elective and emergency admissions.ConclusionsNeurosurgery units would benefit from a geriatric liaison service given the burden of frailty is equivalent to medical wards in-order to improve patient care, experience, turnover and LoS.

Arthur Robertson Makey

Arthur Robertson Makey was born in Dover and was awarded a Kitchener’s scholarship to study medicine. After preregistration jobs he did his national service with the Royal Air Force as...

Association between spectral characteristics of paraspinal muscles and functional disability in patients with low back pain: a cohort study

ObjectivesCharacteristics of muscle activity, represented by surface electromyography (EMG), have revealed differences between patients with low back pain (LBP) and healthy adults; how they relate to functional and clinical parameters...

What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients

ObjectiveTo quantify the risk of developing post-molar gestational trophoblastic neoplasia (pGTN) beyond the first normal human chorionic gonadotrophin (hCG) in women who have had a complete (CHM) or partial molar pregnancy (PHM) and to re-evaluate the current UK Hydatidiform mole hCG surveillance guidelines. MethodsThe Charing Cross Hospital Trophoblast Disease Centre database was screened to identify all registered cases of hydatidiform mole (HM) between 1980 and 2009. ResultsWe identified 20,144 cases of HM, comprising 8400 CHM, 9586 PHM, and 2158 cases of unclassified hydatidiform mole (UHM). Twenty-nine cases (20 CHM, 3 PHM and 6 UHM) developed pGTN after the first normal hCG. For CHM the risk of pGTN at the point of hCG normalisation was 1 in 406, and fell rapidly in the first six months of monitoring. For PHM the risk of pGTN at the point of hCG normalisation was 1 in 3195. Women with CHM where hCG normalisation occurred beyond 56days after uterine evacuation of molar tissue were found to have a 3.8-fold higher risk of pGTN. ConclusionsOur results show that pGTN can occur after hCG normalisation following PHM but the risk is extremely low. Women with CHM have a comparatively higher risk of pGTN after hCG normalisation. Those with CHM where hCG normalises within 56days have a lower risk of pGTN. We have revised the current UK hCG surveillance protocol for PHM to a single additional confirmatory normal urine hCG measurement one month after first normalisation. The protocol for CHM remains unchanged.

Derivation and validation of a novel risk score for safe discharge after acute lower gastrointestinal bleeding: a modelling study

Acute lower gastrointestinal bleeding is a common reason for emergency hospital admission, and identification of patients at low risk of harm, who are therefore suitable for outpatient investigation, is a clinical and research priority. We aimed to develop and externally validate a simple risk score to identify patients with lower gastrointestinal bleeding who could safely avoid hospital admission. We undertook model development with data from the National Comparative Audit of Lower Gastrointestinal Bleeding from 143 hospitals in the UK in 2015. Multivariable logistic regression modelling was used to identify predictors of safe discharge, defined as the absence of rebleeding, blood transfusion, therapeutic intervention, 28 day readmission, or death. The model was converted into a simplified risk scoring system and was externally validated in 288 patients admitted with lower gastrointestinal bleeding (184 safely discharged) from two UK hospitals (Charing Cross Hospital, London, and Hammersmith Hospital, London) that had not contributed data to the development cohort. We calculated C statistics for the new model and did a comparative assessment with six previously developed risk scores. Of 2336 prospectively identified admissions in the development cohort, 1599 (68%) were safely discharged. Age, sex, previous admission for lower gastrointestinal bleeding, rectal examination findings, heart rate, systolic blood pressure, and haemoglobin concentration strongly discriminated safe discharge in the development cohort (C statistic 0·84, 95% CI 0·82-0·86) and in the validation cohort (0·79, 0·73-0·84). Calibration plots showed the new risk score to have good calibration in the validation cohort. The score was better than the Rockall, Blatchford, Strate, BLEED, AIMS65, and NOBLADS scores in predicting safe discharge. A score of 8 or less predicts a 95% probability of safe discharge. We developed and validated a novel clinical prediction model with good discriminative performance to identify patients with lower gastrointestinal bleeding who are suitable for safe outpatient management, which has important economic and resource implications. Bowel Disease Research Foundation and National Health Service Blood and Transplant.

PROSTATE CANCER;

Background: Androgen deprivation therapy (ADT) with luteinizing hormonereleasing hormone agonists (LHRHa) is a major treatment modality for prostate cancer (PC),particularly advanced disease. LHRHa induced hypogonadism promotes bone loss, leading toosteoporosis and heightened fracture risk. Most previous studies on skeletal impact of LHRHaemployed bone mineral density (BMD) testing. Serum bone-specific alkaline phosphatase(BSAP), an established bone biomarker, is reflective of changes in skeletal metabolism whichprecede BMD changes. In postmenopausal women, serum BSAP has been associated withfracture risk irrespective of BMD. Setting: Charing Cross Hospital, London, United Kingdom.Methods: We assessed early changes in serum BSAP levels of patients with non-metastaticPC (n=9) undergoing LHRHa therapy. Serum testosterone and estradiol concentrations werealso measured. Samples were taken at baseline before the start of treatment and three monthsafterward. Comparisons were made with blood samples taken at similar time points for agematchedcontrols without PC (n=9). Results: No significant difference in BSAP levels wasseen between groups (p=0.242). Testosterone and estradiol levels were significantly reducedfollowing treatment (p=0.000). No correlation was observed between serum BSAP and serumtestosterone (R=0.187, p=0.276) or serum estradiol (R=0.055, p=0.75). Conclusions:Changes in serum BSAP levels may not be evident as early as 3 months following ADT withLHRHa. The study was limited by the small sample size and use of serum BSAP only whichis one of the many bone markers. A larger study using multiple bone markers is warranted todetermine early effects of LHRHa treatment on bone metabolism.

John Armstrong (1944–2017)

John Armstrong, who died on 12 February at Charing Cross Hospital, Hammersmith, London was a widely acknowledged expert on the British coasting trade.A graduate of the London School of Economics an...

Reuben Frederick Payne

Reuben Frederick Payne (“Freddie”) was born in Lavenham, Suffolk, where his father was a general practitioner. He attended Asgarth Prep School and then Gresham’s School in Holt. During the second...

Tony R Bull

Tony R Bull was born in 1934, the son of a dentist. He trained at the London Hospital, and after working in Jamaica he was appointed as a consultant surgeon...

Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière's disease: a randomised, double-blind, comparative effectiveness trial

Ménière's disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin, the standard treatment for refractory Ménière's disease, reduces vertigo, but damages vestibular function and can worsen hearing. We aimed to assess whether intratympanic administration of the corticosteroid methylprednisolone reduces vertigo compared with gentamicin. In this double-blind comparative effectiveness trial, patients aged 18-70 years with refractory unilateral Ménière's disease were enrolled at Charing Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK). Patients were randomly assigned (1:1) by a block design to two intratympanic methylprednisolone (62·5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks apart, and were followed up for 2 years. All investigators and patients were masked to treatment allocation. The primary outcome was vertigo frequency over the final 6 months (18-24 months after injection) compared with the 6 months before the first injection. Analyses were done in the intention-to-treat population, and then per protocol. This trial is registered with ClinicalTrials.gov, number NCT00802529. Between June 19, 2009, and April 15, 2013, 256 patients with Ménière's disease were screened, 60 of whom were enrolled and randomly assigned: 30 to gentamicin and 30 to methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the mean number of vertigo attacks in the final 6 months compared with the 6 months before the first injection (primary outcome) decreased from 19·9 (SD 16·7) to 2·5 (5·8) in the gentamicin group (87% reduction) and from 16·4 (12·5) to 1·6 (3·4) in the methylprednisolone group (90% reduction; mean difference -0·9, 95% CI -3·4 to 1·6). Patients whose vertigo did not improve after injection (ie, non-responders) after being assessed by an unmasked clinician were eligible for additional injections given by a masked clinician (eight patients in the gentamicin group vs 15 in the methylprednisolone group). Two non-responders switched from methylprednisolone to gentamicin. Both drugs were well tolerated with no safety concerns. Six patients reported one adverse event each: three in the gentamicin group and three in the methylprednisolone group. The most common adverse event was minor ear infections, which was experienced by one patient in the gentamicin group and two in the methylprednisolone group. Methylprednisolone injections are a non-ablative, effective treatment for refractory Ménière's disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances. Ménière's Society and National Institute for Health Research Imperial Biomedical Research Centre.