Publications by authors named "Anju Sahdev"

59 Publications

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1.

Endocrinol Diabetes Metab Case Rep 2021 Jun 1;2021. Epub 2021 Jun 1.

Department of Endocrinology, Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.

Summary: A male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare.

Learning Points: It is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1). Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis. Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients.
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http://dx.doi.org/10.1530/EDM-20-0208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240703PMC
June 2021

Performance evaluation of scoring systems for predicting post-operative hypertension cure in primary aldosteronism.

Clin Endocrinol (Oxf) 2021 May 27. Epub 2021 May 27.

Department of Endocrinology, St Bartholomew's Hospital, London, UK.

Objective: Hypertension cure following adrenalectomy in unilateral primary aldosteronism is not guaranteed. Its likelihood is associated with pre-operative parameters, which have been variably combined in six different predictive scoring systems. The relative performance of these systems is currently unknown. The objective of this work was to identify the best performing scoring system for predicting hypertension cure following adrenalectomy for primary aldosteronism.

Design: Retrospective analysis in a single tertiary referral centre.

Patients: Eighty-seven adult patients with unilateral primary aldosteronism who had undergone adrenalectomy between 2004 and 2018 for whom complete data sets were available to calculate all scoring systems.

Measurements: Prediction of hypertension cure by each of the six scoring systems.

Results: Hypertension cure was achieved in 36/87 (41.4%) patients within the first post-operative year, which fell to 18/71 (25.4%) patients at final follow-up (median 53 months, P = .002). Analysis of receiver operating characteristic area under the curves for the different scoring systems identified a difference in performance at early, but not late, follow-up. For all systems, the area under the curve was lower at early compared with late follow-up and compared to performance in the cohorts in which they were originally defined.

Conclusions: No single scoring system performed significantly better than all others when applied in our cohort, although two did display particular advantages. It remains to be determined how best such scoring systems can be incorporated into the routine clinical care of patients with PA.
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http://dx.doi.org/10.1111/cen.14534DOI Listing
May 2021

Radiomics for Renal Cell Carcinoma: Predicting Outcomes from Immunotherapy and Targeted Therapies-A Narrative Review.

Eur Urol Focus 2021 May 11. Epub 2021 May 11.

Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UK.

T-cell immunotherapy and molecular targeted therapies have become standard-of-care treatments for renal cell carcinoma (RCC). There is a need to develop robust biomarkers that predict patient outcomes to targeted therapies to personalise treatment. In recent years, quantitative analysis of imaging features, termed radiomics, has been used to extract tumour features. This narrative mini review summarises the evidence for radiomics prediction of immunotherapy and molecular targeted therapy outcomes in RCC. Radiomics may predict survival, treatment response, and disease progression in RCC treated with tyrosine kinase inhibitors (eg, sunitinib) and immune checkpoint inhibitors (eg, nivolumab). Further validation is necessary in large-scale studies. PATIENT SUMMARY: We summarise evidence on the ability of features extracted from CT (computed tomography) scans to predict patient outcomes from new treatments for kidney cancer. Although these features can predict treatment outcomes for patients, including survival, treatment response, and cancer progression, further research is necessary before this technology can be applied clinically.
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http://dx.doi.org/10.1016/j.euf.2021.04.024DOI Listing
May 2021

Single-agent carboplatin AUC10 in metastatic seminoma: A multi-centre UK study of 216 patients.

Eur J Cancer 2020 Oct 8. Epub 2020 Oct 8.

Department of Medical Oncology, St Bartholomew's Hospital, London, EC1A 7BE, UK. Electronic address:

Background: Radiotherapy and cisplatin-based combination chemotherapy are accepted standard-of-care treatments for metastatic seminoma with excellent survival outcomes but with established short- and long-term morbidity. Carboplatin monotherapy may be a less toxic alternative; however early historic studies at AUC7 showed inferior outcomes.

Objectives: To evaluate multi-institutional data on and toxicity and longer-term survival for metastatic seminoma patients treated with the single-agent carboplatin AUC10.

Methods: We undertook a multi-institutional analysis incorporating all men with the International Germ Cell Cancer Collaborative Group good-prognosis metastatic seminoma treated until 2018. Carboplatin AUC10 was given every 21 days. Toxicity, progression-free survival (PFS), disease-specific survival (DSS) and overall survival were noted. Variables predictive of progression were identified.

Results And Limitations: 216 patients were treated. The three-year PFS rate was 96.5%, and five-year DSS was 98.3%. There were seven relapses, of which 5 were successfully salvaged with further chemotherapy ± surgery, and three non-seminoma-related deaths. There were no treatment-related deaths. Of 148/216 evaluable patients for toxicity, 37% and 27% suffered >/ = grade III neutropenia and thrombocytopenia, respectively. Twelve percent of patients needed a platelet or blood transfusion (or both). The incidence of febrile neutropenia was 5%.

Conclusion: For metastatic seminoma, carboplatin AUC10 harbours a similar oncological efficacy to established therapies, with a low failure risk. The major acute toxicity was myelosuppression. Our study establishes carboplatin AUC10 as another standard-of-care treatment option for good-prognosis metastatic seminoma, with a potentially lower toxicity profile than other therapies.
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http://dx.doi.org/10.1016/j.ejca.2020.08.031DOI Listing
October 2020

The impact of a supranetwork multidisciplinary team (SMDT) on decision-making in testicular cancers: a 10-year overview of the Anglian Germ Cell Cancer Collaborative Group (AGCCCG).

Br J Cancer 2021 01 29;124(2):368-374. Epub 2020 Sep 29.

Barts Health NHS Trust, London, UK.

Background: The germ cell supranetwork multidisciplinary team (SMDT) for the Anglian Network covers a population of 7.5 million.

Methods: We reviewed 10 years of SMDT discussion and categorised them into five domains ((1) overall outcome, (2) chemotherapy regimens-untreated disease and salvage therapy, (3) radiology, (4) pathology and (5) complex cases) to assess the impact of the SMDT.

Results: A total of 2892 new cases were reviewed. In the first 5 years, patients with good prognosis disease had poorer survival in low-volume vs high-volume centres (87.8 vs 95.3, p = 0.02), but the difference was no longer significant in the last 5 years (93.3 vs 95.1, p = 0.30). Radiology review of 3206 scans led to rejection of the diagnosis of progression in 26 cases and a further 10 cases were down-staged. There were 790 pathology reviews by two specialised uropathologists, which lead to changes in 75 cases. F-fluorodeoxyglucose (FDG) PET-CT was undertaken during this time period but did not help to predict who would have viable cancer. A total of 26 patients with significant mental health issues who were unable to give informed consent were discussed.

Conclusion: SMDT working has led to an improvement in outcomes and refining of treatment in patients with germ cell tumours.
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http://dx.doi.org/10.1038/s41416-020-01075-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853071PMC
January 2021

Low-grade Cortisol Cosecretion Has Limited Impact on ACTH-stimulated AVS Parameters in Primary Aldosteronism.

J Clin Endocrinol Metab 2020 10;105(10)

Department of Endocrinology, St Bartholomew's Hospital, London, UK.

Context: In primary aldosteronism, cosecretion of cortisol may alter cortisol-derived adrenal venous sampling indices.

Objective: To identify whether cortisol cosecretion in primary aldosteronism alters adrenal venous sampling parameters and interpretation.

Design: Retrospective case-control study.

Setting: A tertiary referral center.

Patients: 144 adult patients with primary aldosteronism who had undergone both adrenocorticotropic hormone-stimulated adrenal venous sampling and dexamethasone suppression testing between 2004 and 2018.

Main Outcome Measures: Adrenal venous sampling indices including adrenal vein aldosterone/cortisol ratios and the selectivity, lateralization, and contralateral suppression indices.

Results: 21 (14.6%) patients had evidence of cortisol cosecretion (defined as a failure to suppress cortisol to ≤50 nmol/L post dexamethasone). Patients with evidence of cortisol cosecretion had a higher inferior vena cava cortisol concentration (P = .01) than those without. No difference was observed between the groups in terms of selectivity index, lateralization index, lateralization of aldosterone excess, or adrenal vein cannulation rate.

Conclusions: Cortisol cosecretion alters some parameters in adrenocorticotrophic hormone-stimulated adrenal venous sampling but does not result in alterations in patient management.
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http://dx.doi.org/10.1210/clinem/dgaa519DOI Listing
October 2020

Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial.

Lancet Diabetes Endocrinol 2020 04 25;8(4):278-291. Epub 2020 Feb 25.

Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address:

Background: An urgent need to reduce the metabolic side-effects of glucocorticoid overexposure has been recognised, as glucocorticoid excess can lead to Cushing's syndrome, which is associated with high morbidity. We aimed to evaluate the potential of metformin to reverse such effects while sparing the anti-inflammatory benefits of glucocorticoids.

Methods: We did a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial involving four hospitals in the UK. Patients without diabetes were eligible if they were between the ages of 18 and 75 years with an inflammatory disease treated with continuous prednisolone (≥20 mg/day for ≥4 weeks and remaining on ≥10 mg/day for the subsequent 12 weeks, or its cumulative dose-equivalent). Eligible patients were randomly allocated (1:1) to either the metformin or placebo groups, using a computer-generated randomisation table stratified according to age and BMI. Metformin and placebo were administered orally for 12 weeks in escalating doses: 850 mg/day for the first 5 days, 850 mg twice a day for the next 5 days, and 850 mg three times a day subsequently. The primary outcome was the between-group difference in visceral-to-subcutaneous fat area ratio over 12 weeks, assessed by CT. Secondary outcomes included changes in metabolic, bone, cardiovascular, and inflammatory parameters over 12 weeks. Our analysis followed a modified intention-to-treat principle for the primary outcome. This study is registered with ClinicalTrials.gov, NCT01319994.

Findings: Between July 17, 2012, and Jan 14, 2014, 849 patients were assessed for study eligibility, of which 53 were randomly assigned to receive either metformin (n=26) or placebo (n=27) for 12 weeks. 19 patients in the metformin group and 21 in the placebo group were eligible for the primary outcome analysis. Both groups received an equivalent cumulative dose of glucocorticoids (1860 mg prednisolone-equivalent [IQR 1060-2810] in the metformin group vs 1770 mg [1020-2356] in the placebo group); p=0·76). No change in the visceral-to-subcutaneous fat area ratio between the treatment groups was observed (0·11, 95% CI -0·02 to 0·24; p=0·09), but patients in the metformin group lost truncal subcutaneous fat compared with the placebo group (-3835 mm, 95% CI -6781 to -888; p=0·01). Improvements in markers of carbohydrate, lipid, liver, and bone metabolism were observed in the metformin group compared with the placebo group. Additionally, those in the metformin group had improved fibrinolysis, carotid intima-media thickness, inflammatory parameters, and clinical markers of disease activity. The frequency of pneumonia (one event in the metformin group vs seven in the placebo group; p=0·01), overall rate of moderate-to-severe infections (two vs 11; p=0·001), and all-cause hospital admissions due to adverse events (one vs nine; p=0·001) were lower in the metformin group than in the placebo group. Patients in the metformin group had more events of diarrhoea than the placebo group (18 events vs eight; p=0·01).

Interpretation: No significant changes in the visceral-to-subcutaneous fat area ratio between the treatment groups were observed; however, metformin administration did improve some of the metabolic profile and clinical outcomes for glucocorticoid-treated patients with inflammatory disease, which warrants further investigation.

Funding: Barts Charity and Merck Serono.
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http://dx.doi.org/10.1016/S2213-8587(20)30021-8DOI Listing
April 2020

Diffusion-weighted imaging (DWI) highlights SDHB-related tumours: A pilot study.

Clin Endocrinol (Oxf) 2019 07 11;91(1):104-109. Epub 2019 Apr 11.

Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.

Objective: There is consensus that asymptomatic carriers of SDHB mutations should undergo periodic surveillance imaging. MRI has the advantage of avoiding radiation exposure but its sensitivity and specificity for detecting phaeochromocytoma and paraganglioma (PPGL) are dependent on sequences performed and expertise of reporting radiologists. We aim to highlight the additional value of diffusion-weighted imaging (DWI) for MR based surveillance, demonstrating DWI's ability to identify small PPGLs at all body sites.

Design: We presented DWI sequences taken as part of SDHB surveillance to a radiologist, expert in reporting PPGL screening scans. Areas of high signal on DWI were interrogated using other standard MRI sequences.

Patients: We reviewed the MRI scans for 18 SDHB mutation carriers with a total of 18 histologically proven SDHB-related tumours and 12 presumed PGLs/metastatic deposits.

Results: The DWI sequences identified all 30 lesions. False-positive lesions were excluded by standard sequences. The tumours detected by DWI ranged in size from 5 to 52 mm. PPGLs were identified on DWI in the abdomen (n = 14), adrenal gland (n = 1), thorax (n = 3), neck (n = 2) and bladder (n = 2). Additionally, other SDHB-related tumours (GIST, RCC) were also highlighted by DWI, as were metastatic deposits in the liver and bone.

Conclusions: These preliminary data suggest that DWI has high sensitivity and can identify even small SDHB-related tumours. If these findings are confirmed in larger series, for all SDH subunits, it will provide reassurance about identifying small SDH-related tumours, without exposing patients to the consequences of radiation-based imaging and will secure the role of MRI for surveillance imaging.
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http://dx.doi.org/10.1111/cen.13980DOI Listing
July 2019

An analysis of surveillance screening for SDHB-related disease in childhood and adolescence.

Endocr Connect 2019 Mar;8(3):162-172

Centre for Endocrinology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Objective Phaeochromocytomas (PCC) and paragangliomas (PGL) are rare in children. A large proportion of these are now understood to be due to underlying germline mutations. Here we focus on succinate dehydrogenase subunit B (SDHB) gene mutation carriers as these tumours carry a high risk of malignant transformation. There remains no current consensus with respect to optimal surveillance for asymptomatic carriers and those in whom the presenting tumour has been resected. Method We undertook a retrospective analysis of longitudinal clinical data of all children and adolescents with SDHB mutations followed up in a single UK tertiary referral centre. This included index cases that pre-dated the introduction of surveillance screening and asymptomatic carriers identified through cascade genetic testing. We also conducted a literature review to inform a suggested surveillance protocol for children and adolescents harbouring SDHB mutations. Results Clinical outcomes of a total of 38 children are presented: 8 index cases and 30 mutation-positive asymptomatic carriers with 175 patient years of follow-up data. Three of the eight index cases developed metachronous disease and two developed metastatic disease. Of the 30 asymptomatic carriers, 3 were found to have PGLs on surveillance screening. Conclusions Surveillance screening was well tolerated in our paediatric cohort and asymptomatic paediatric subjects. Screening can identify tumours before they become secretory and/or symptomatic, thereby facilitating surgical resection and reducing the chance of distant spread. We propose a regular screening protocol commencing at age 5 years in this at-risk cohort of patients.
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http://dx.doi.org/10.1530/EC-18-0522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391899PMC
March 2019

Can subunit-specific phenotypes guide surveillance imaging decisions in asymptomatic SDH mutation carriers?

Clin Endocrinol (Oxf) 2019 01 28;90(1):31-46. Epub 2018 Nov 28.

Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.

Objective: With the discovery that familial phaeochromocytoma and paraganglioma syndrome can be caused by mutations in each subunit of the succinate dehydrogenase enzyme (SDH), has come the recognition that mutations in the individual subunits have their own distinct natural histories. Increased genetic screening is leading to the identification of increasing numbers of, mostly asymptomatic, gene mutation carriers and the implementation of screening strategies for these individuals. Yet there is, to date, no international consensus regarding screening strategies for asymptomatic carriers.

Design: A comprehensive PubMed search from 1/1/2000 to 28/2/2018 was undertaken using multiple search terms and subsequently a manual review of references in identified papers to identify all clinically relevant cases and cohorts. In this review, the accumulated, published experience of phenotype and malignancy risks of individual SDH subunits is analysed. Where possible screening results for asymptomatic SDH mutation carriers have been analysed separately to define the penetrance in asymptomatic carriers (asymptomatic penetrance).

Results: The combined data confirms that "asymptomatic penetrance" is highest for SDHD and when there is penetrance, the most likely site to develop a PGL is head and neck (SDHD) and extra-adrenal abdominal (SDHB). However, the risk in SDHB carriers of developing HNPGL is also high (35.5%) and a PCC is low (15.1%), and in SDHD carriers there is a high risk of developing a PCC (35.8%) or abdominal PGL (9.4%) and a small, but significant risk at other sympathetic sites. The data suggest that the risk of malignant transformation is the same for both PCC and extra-adrenal abdominal PGLs (30%-35%) in SDHB carriers. In SDHD carriers, the risk of malignant transformation was highest in HNPGLs (7.5%) and similar for sympathetic sites (3.8%-5.2%).

Conclusions: Using this data, we suggest surveillance screening of asymptomatic carriers can be tailored to the underlying SDH subunit and review possible surveillance programmes.
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http://dx.doi.org/10.1111/cen.13877DOI Listing
January 2019

Adverse effects and radiological manifestations of new immunotherapy agents.

Br J Radiol 2019 Jan 16;92(1093):20180164. Epub 2018 Oct 16.

St Bartholomew's Hospital West Smithfields London , London, UK.

Immunotherapy has had increasing use in Medical Oncology for a diverse range of primary malignancies. There are various types of immunotherapy which are grouped based on mechanism of action. In recent decades, the immune checkpoint inhibitors (ICI) immunotherapies have been at the forefront of Medical Oncology, sparked by very encouraging results. Some patients with metastatic cancer who were previously deemed palliative were seeing durable response rates and significant increased survival with ICIs. The mechanism of action of ICIs vary wildly compared to the conventional, cytotoxic chemotherapy, upon which traditional radiology response criteria were based and validated upon. Novel responses such as pseudo progression, disease response in the context of new metastases and prolonged stable disease were observed and correlated with improved patient survival with ICI. New radiology response criteria were proposed to better capture disease response to ICI; however, the criteria have been applied heterogeneously and there is continued work in this sector. In addition to the novel responses, ICIs have been linked to numerous, diverse immune-related adverse events (irAE) affecting multiple systems. A large majority of these are mild, but some irAEs are life threatening. Only some of the irAEs have radiological manifestations. It is important that the reporting radiologist recognises potential irAE so clinical teams can be alerted, ICI treatment paused or cessated and steroid treatment initiated. This review will discuss the evolution of the radiology response criteria in ICI and the varied radiological appearances of irAE.
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http://dx.doi.org/10.1259/bjr.20180164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435070PMC
January 2019

MRI versus laparoscopy to diagnose the main causes of chronic pelvic pain in women: a test-accuracy study and economic evaluation.

Health Technol Assess 2018 07;22(40):1-92

Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK.

Background: Chronic pelvic pain (CPP) symptoms in women are variable and non-specific; establishing a differential diagnosis can be hard. A diagnostic laparoscopy is often performed, although a prior magnetic resonance imaging (MRI) scan may beneficial.

Objectives: To estimate the accuracy and added value of MRI in making diagnoses of (1) idiopathic CPP and (2) the main gynaecological causes of CPP. To quantify the impact MRI can have on decision-making with respect to triaging for therapeutic laparoscopy and to conduct an economic evaluation.

Design: Comparative test-accuracy study with cost-effectiveness modelling.

Setting: Twenty-six UK-based hospitals.

Participants: A total of 291 women with CPP.

Methods: Pre-index information concerning the patient's medical history, previous pelvic examinations and ultrasound scans was collected. Women reported symptoms and quality of life at baseline and 6 months. MRI scans and diagnostic laparoscopy (undertaken and interpreted blind to each other) were the index tests. For each potential cause of CPP, gynaecologists indicated their level of certainty that the condition was causing the pelvic pain. The analysis considered both diagnostic laparoscopy as a reference standard for observing structural gynaecological causes and consensus from a two-stage expert independent panel for ascertaining the cause of CPP. The stage 1 consensus was based on pre-index, laparoscopy and follow-up data; for stage 2, the MRI scan report was also provided. The primary analysis involved calculations of sensitivity and specificity for the presence or absence of each structural gynaecological cause of pain. A decision-analytic model was developed, with a 6-month time horizon. Two strategies, laparoscopy or MRI, were considered and populated with study data.

Results: Using reference standards of laparoscopic and expert panel diagnoses, MRI scans had high specificity but poor sensitivity for observing deep-infiltrating endometriosis, endometrioma, adhesions and ovarian cysts. MRI scans correctly identified 56% [95% confidence interval (CI) 48% to 64%] of women judged to have idiopathic CPP, but missed 46% (95% CI 37% to 55%) of those considered to have a gynaecological structural cause of CPP. MRI added significant value, over and above the pre-index information, in identifying deep-infiltrating endometriosis ( = 0.006) and endometrioma ( = 0.02) as the cause of pain, but not for other gynaecological structural causes or for identifying idiopathic CPP ( = 0.08). Laparoscopy was significantly more accurate than MRI in diagnosing idiopathic CPP ( < 0.0001), superficial peritoneal endometriosis ( < 0.0001), deep-infiltrating endometriosis ( < 0.0001) and endometrioma of the ovary ( = 0.02) as the cause of pelvic pain. The accuracy of laparoscopy appeared to be able to rule in these diagnoses. Using MRI to identify women who require therapeutic laparoscopy would lead to 369 women in a cohort of 1000 receiving laparoscopy unnecessarily, and 136 women who required laparoscopy not receiving it. The economic analysis highlighted the importance of the time horizon, the prevalence of CPP and the cut-off values to inform the sensitivity and specificity of MRI and laparoscopy on the model results. MRI was not found to be a cost-effective diagnostic approach in any scenario.

Conclusions: MRI was dominated by laparoscopy in differential diagnosis of women presenting to gynaecology clinics with CPP. It did not add value to information already gained from history, examination and ultrasound about idiopathic CPP and various gynaecological conditions.

Trial Registration: Current Controlled Trials ISRCTN13028601.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 22, No. 40. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta22400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088265PMC
July 2018

Paediatric pancreatic neuroendocrine tumours in von Hippel-Lindau disease.

Endocr Relat Cancer 2018 09 11;25(9):L43-L47. Epub 2018 May 11.

Department of EndocrinologySt Bartholomew's Hospital, London, UK

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http://dx.doi.org/10.1530/ERC-18-0123DOI Listing
September 2018

Radiological Surveillance Screening in Asymptomatic Succinate Dehydrogenase Mutation Carriers.

J Endocr Soc 2017 Jul 6;1(7):897-907. Epub 2017 Jun 6.

Department of Endocrinology, St. Bartholomew's Hospital, Barts Health National Health Service Trust, West Smithfield, London EC1A 7BE, United Kingdom.

There has been a significant increase in the availability of testing for pheochromocytoma and paraganglioma (PPGL) germline susceptibility genes. As more patients with genetic mutations are identified, cascade genetic testing of family members is also increasing. This results in identifying genetic predispositions at a much earlier age. With our current understanding of familial PPGL syndromes, lifelong surveillance is required. This review focuses on carriers of succinate dehydrogenase () mutations. For genetic testing to be proven worthwhile, the results must be used for patient benefit. For mutations, this should equate to a surveillance program that is safe and removes as much uncertainty around diagnosis as possible. Early identification of these tumors is the goal of any surveillance program, as surgical resection is the mainstay of treatment with curative intent to prevent the morbidity and mortality consequences associated with catecholamine excess, in addition to the risk of malignancy. Modality and frequency of surveillance imaging and how to engage individuals in the process of surveillance remain controversial questions. The data reviewed here and the cumulative advice supports the avoidance of using radiation-exposing imaging in this group of individuals that require lifelong screening.
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http://dx.doi.org/10.1210/js.2017-00230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686572PMC
July 2017

Incidentally detected testicular lesions <10 mm in diameter: can orchidectomy be avoided?

BJU Int 2018 04 12;121(4):575-582. Epub 2017 Nov 12.

Barts Cancer Institute, Queen Mary University of London, London, UK.

Objective: To investigate the pathology of excised testicular lesions <10 mm in size.

Patients And Methods: The pathological reports of 2 681 patients with testicular lesions from Barts Health NHS Trust and Oxford University Hospitals NHS Foundation Trust were reviewed as part of a service evaluation audit from January 2003 to May 2016. Cases in which the lesion had a maximum diameter of <10 mm were selected. Clinical features were also accessed, where available, to examine patient demographics, prediagnostic levels of serum markers, ultrasonographic findings and clinical details.

Results: A total of 81 patients with a lesion size <10 mm on histology were identified and, of these, 16 (20%) had a lesion diameter <5 mm. Of the 81 patients, 56 (69%) had benign lesions. Of 16 patients with a benign lesion <5 mm in diameter, 15 underwent orchidectomy and just one underwent partial orchidectomy. Preoperative tumour markers were available in 47/81 patients. None of the 16 malignant tumours in these 47 patients were associated with raised tumour markers, while seven of 31 remaining patients with benign lesions had raised α-fetoprotein and lactate dehydrogenase levels. In total there were 25/81 malignant cases (31%), which were all germ cell tumours (GCTs): 15 seminomas (60%) and 10 non-seminomatous GCTs (40%). Only one GCT had a diameter of <5 mm, and this was a regressed tumour within an 18-mm area of granulomatous inflammation. Only one GCT relapsed: a clinical stage I, embryonal carcinoma of 6 mm in maximum diameter. The 56 'benign' cases included 34 sex cord stromal tumours, including 23 Leydig cell tumours (41%), eight Sertoli cell tumours (14%) and three mixed sex cord stromal tumours (5%). None showed any malignant features. The remaining 22/56 lesions (40%) were lesions with no further follow-up. Benign lesions seemed to be associated with a small diameter, and we found <5 mm to be the best threshold for predicting benign vs malignant lesions (P = 0.002).

Conclusion: The majority of testicular lesions <10 mm, identified by radiology, were benign, although approxmiately one-third were malignant. In the present study, 100% of lesions <5 mm in diameter were benign. Tumour markers appear to be unhelpful in the distinction of these small tumours. We suggest that regular ultrasound surveillance be more widely used for testicular lesions of this size. Testicular tumours now have a very high cure rate and changes in size of lesions may be monitored prospectively with minimal risk of increased morbidity. Patients who undergo an orchidectomy for lesions <5 mm are 'victims of modern imaging technology'. If surgery is undertaken in lesions 5-10 mm, patients should be counselled that two-thirds of cases are benign.
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http://dx.doi.org/10.1111/bju.14056DOI Listing
April 2018

The role of F-FDG PET CT in common gynaecological malignancies.

Br J Radiol 2017 Nov 22;90(1079):20170283. Epub 2017 Aug 22.

2 Department of Imaging, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.

[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (F-FDG PET CT) has increasing clinical applications supplementing conventional TVUS, CT and MRI imaging in assessing ovarian, cervical and endometrial cancer. The published literature on the applications of F-FDG PET CT shows its use can have significant impact on patient management by improving staging of the cancers, influencing patient selection for treatment and in detecting early recurrent disease. However, the increasing clinical use of PET CT does not always align with the guidelines, recommendations or expert opinion in the use of PET CT. This article summarizes the existing evidence base for the established clinical applications and the emerging roles for F-FDG PET CT in the common gynaecological malignancies.
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http://dx.doi.org/10.1259/bjr.20170283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963379PMC
November 2017

Recommendations for the management of adrenal incidentalomas: what is pertinent for radiologists?

Authors:
Anju Sahdev

Br J Radiol 2017 Apr 9;90(1072):20160627. Epub 2017 Feb 9.

Department of Imaging, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.

Adrenal incidentalomas are unsuspected, asymptomatic adrenal masses detected on imaging. Most are non-functioning benign adrenocortical adenomas but can represent other benign lesions or lesions requiring therapeutic intervention including adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis. This review summarizes and highlights radiological recommendations within the recently issued guidelines for the management of adrenal incidentalomas from the European Society of Endocrinology Clinical Practice in collaboration with the European Network for Study of Adrenal Tumours. Four pre-defined clinical questions were addressed in the guidelines and two have specific relevance and implications for radiologists: (1) how to assess risk of malignancy on imaging and (2) what follow-up is indicated if an adrenal incidentaloma is not surgically removed? The guidelines also include recommendations for frequently encountered special circumstances, including bilateral incidentalomas, incidentalomas in patients with extra-adrenal malignancy and in the young and elderly patients. This review highlights radiological recommendations within the guidelines and evidence used for formulating the guidelines.
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http://dx.doi.org/10.1259/bjr.20160627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605062PMC
April 2017

Preprocedural MRI and MRA in planning fibroid embolization.

Diagn Interv Radiol 2017 Mar-Apr;23(2):163-171

Department of Radiology, Centro Hospitalar São João, Porto, Portugal.

This pictorial review aims to discuss and illustrate the up-to-date use of preprocedural magnetic resonance imaging (MRI) in selecting patients and planning uterine artery embolization (UAE). The merits of magnetic resonance angiography (MRA) in demonstrating the pelvic vasculature to guide UAE are highlighted. MRI features of fibroids and their main differential diagnoses are presented. Fibroid characteristics, such as location, size, and enhancement, which may impact patient selection and outcome, are presented based on recent literature. Pelvic arterial anatomy relevant to UAE, including vascular variants are illustrated, with conventional angiography and MRA imaging correlation. MRA preprocedural determination of the optimal projection angles for uterine artery catheterization is straightforward and constitutes an important strategy to minimize ionizing radiation exposure during UAE. A reporting template for MRI/MRA preassessement of UAE for fibroid treatment is provided.
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http://dx.doi.org/10.5152/dir.2016.16623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338584PMC
September 2017

Heterogeneous response and progression patterns reveal phenotypic heterogeneity of tyrosine kinase inhibitor response in metastatic renal cell carcinoma.

BMC Med 2016 11 14;14(1):185. Epub 2016 Nov 14.

Centre for Evolution and Cancer, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.

Background: Molecular intratumour heterogeneity (ITH) is common in clear cell renal carcinomas (ccRCCs). However, it remains unknown whether this is mirrored by heterogeneity of drug responses between metastases in the same patient.

Methods: We performed a retrospective central radiological analysis of patients with treatment-naïve metastatic ccRCC receiving anti-angiogenic tyrosine kinase inhibitors (TKIs) (sunitinib or pazopanib) within three similar phase II trials. Treatment was briefly interrupted for cytoreductive nephrectomy. All patients had multiple metastases that were measured by regular computed tomography scans from baseline until Response Evaluation Criteria In Solid Tumours (RECIST)-defined progression. Each metastasis was categorised as responding, stable or progressing. Patients were classed as having a homogeneous response if all lesions were of the same response category and a heterogeneous response if they differed.

Results: A total of 115 metastases were assessed longitudinally in 27 patients. Of these patients, 56% had a heterogeneous response. Progression occurred through the appearance of new metastases in 67%, through progression of existing lesions in 11% and by both in 22% of patients. Despite RECIST-defined progression, 57% of existing metastases remained controlled. The sum of controlled lesions was greater than that of uncontrolled lesions in 47% of patients who progressed only with measurable new lesions.

Conclusions: We identified frequent ITH of anti-angiogenic TKI responses, with subsets of metastases responding and progressing within individual patients. This mirrors molecular ITH and may indicate that anti-angiogenic drug resistance is confined to subclones and not encoded on the trunk of the tumours' phylogenetic trees. This is clinically important, as patients with small-volume progression may benefit from drug continuation. Predominant progression with new rather than in existing metastases supports a change in disease biology through anti-angiogenics. The results highlight limitations of RECIST in heterogeneous cancers, which may influence clinical trial data validity. This analysis requires prospective confirmation.

Trial Registration: European Clinical Trials Database(EudraCT): 2009-016675-29 , registered 17 March 2010; EudraCT: 2006-004511-21 , registered 09 March 2007; EudraCT: 2006-006491-38 , registered 22 December 2006.
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http://dx.doi.org/10.1186/s12916-016-0729-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108081PMC
November 2016

Outcomes of annual surveillance imaging in an adult and paediatric cohort of succinate dehydrogenase B mutation carriers.

Clin Endocrinol (Oxf) 2017 Feb 24;86(2):286-296. Epub 2016 Oct 24.

Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.

Objective: For 'asymptomatic carriers' of the succinate dehydrogenase subunit B (SDHB) gene mutations, there is currently no consensus as to the appropriate modality or frequency of surveillance imaging. We present the results of a surveillance programme of SDHB mutation carriers.

Design: Review of clinical outcomes of a surveillance regimen in patients identified to have an SDHB gene mutation, based on annual MRI, in a single UK tertiary referral centre.

Patients: A total of 92 patients were identified with an SDHB gene mutation. a total of 27 index patients presented with symptoms, and 65 patients were identified as asymptomatic carriers.

Measurements: Annual MRI of the abdomen, with alternate year MRI of the neck, thorax and pelvis. Presence of an SDHB-related tumour included paraganglioma (PGL), phaeochromocytoma (PCC), renal cell carcinoma (RCC) and gastrointestinal stromal tumour (GIST).

Results: A total of 43 PGLs, eight PCCs and one RCC occurred in the 27 index patients (23 solitary, four synchronous, five metachronous). A further 15 SDHB-related tumours (11 PGLs, three RCCs, one GIST) were identified in the asymptomatic carriers on surveillance screening (25% of screened carriers): 10 on the first surveillance imaging and five on subsequent imaging 2-6 years later. A total of 11 patients had malignant disease.

Conclusions: SDHB-related tumours are picked up as early as 2 years after initial negative surveillance scan. We believe the high malignancy rate and early identification rate of tumours justifies the use of 1-2 yearly imaging protocols and MRI-based imaging could form the mainstay of surveillance in this patient group thereby minimizing radiation exposure.
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http://dx.doi.org/10.1111/cen.13246DOI Listing
February 2017

Succinate Dehydrogenase B (SDHB)-Associated Bladder Paragangliomas.

Clin Genitourin Cancer 2017 02 23;15(1):e131-e136. Epub 2016 Jun 23.

Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK.

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http://dx.doi.org/10.1016/j.clgc.2016.06.006DOI Listing
February 2017

CT in ovarian cancer staging: how to review and report with emphasis on abdominal and pelvic disease for surgical planning.

Authors:
Anju Sahdev

Cancer Imaging 2016 Aug 2;16(1):19. Epub 2016 Aug 2.

St Bartholomew's Hospital, Barts Health, West Smithfield, London, EC1A 7BE, UK.

CT of the abdomen and pelvis is the first line imaging modality for staging, selecting treatment options and assessing disease response in ovarian cancer. The staging CT provides disease distribution, disease burden and is the imaging surrogate for surgico-pathological FIGO staging. Optimal cyto-reductive surgery offers patients' the best chance for disease control or cure, but sub-optimal resection confers no advantage over chemotherapy and adversely increases the risk of post surgical complications. Although there is extensive literature comparing performance of CT against laparoscopy and surgery, for the staging abdominal and pelvic CT, there are currently no accepted guidelines for interpretation or routinely used minimum data set templates for reporting these complex CT scans often with extensive radiological findings. This review provides a systematic approach for identifying the important radiological findings and highlighting important sites of disease within the abdomen and pelvis, which may alter or preclude surgery at presentation or after adjuvant chemotherapy. The distribution of sites and volume of disease can be used to categorize patients as suitable, probably suitable or not suitable for optimal cyto-reductive surgery. This categorization can potentially assist oncological surgeons and oncologists as a semi objective assessment tool useful for selecting patient treatment, streamlining multi disciplinary discussion and improving the reproducibility and correlation of CT with surgical findings. The review also highlights sites of disease and complications of ovarian cancer which should be included as part of the radiological report as these may require additional surgical input from non gynaecological surgeons or influence treatment selection.
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http://dx.doi.org/10.1186/s40644-016-0076-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971689PMC
August 2016

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.

Eur J Endocrinol 2016 Aug;175(2):G1-G34

Departments of Clinical Epidemiology and Internal MedicineLeiden University Medical Centre, Leiden, The Netherlands Department of Clinical EpidemiologyAarhus University, Aarhus, Denmark.

: By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas.
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http://dx.doi.org/10.1530/EJE-16-0467DOI Listing
August 2016

MANAGEMENT OF ENDOCRINE DISEASE: Imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis.

Eur J Endocrinol 2016 Aug 2;175(2):R51-64. Epub 2016 Jun 2.

Institute of Metabolism and Systems ResearchUniversity of Birmingham, Birmingham, UK Centre for EndocrinologyDiabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

Objective: Adrenal masses are incidentally discovered in 5% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses.

Design: A systematic review and meta-analysis was conducted.

Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or (18)F-fluoro-deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard.

Results: We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n=16), MRI (n=15), and FDG-PET (n=9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with ≤10HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers.

Conclusions: Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis.
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http://dx.doi.org/10.1530/EJE-16-0461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065077PMC
August 2016

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer.

JAMA Oncol 2016 Oct;2(10):1303-1309

Cancer Sciences Unit, University of Southampton, Southampton, England.

Importance: The role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain.

Objective: To establish the safety and efficacy of upfront pazopanib therapy prior to cytoreductive nephrectomy in previously untreated patients with metastatic clear cell renal cancer.

Design, Setting, And Participants: Single-arm phase 2 study of 104 previously untreated patients with metastatic clear cell renal cancer recruited between June 2008 and October 2012 at cancer treatment centers with access to nephrectomy services. The minimum follow-up was 30 months.

Interventions: Patients received 12 to 14 weeks of preoperative pazopanib therapy prior to planned cytoreductive nephrectomy and continued pazopanib therapy after surgery. Treatment was stopped at disease progression.

Main Outcomes And Measures: The primary end point was clinical benefit (using Response Evaluation Criteria in Solid Tumors, version 1.1) prior to surgery (at 12-14 weeks). Secondary end points included surgical complications, progression-free survival (PFS), overall survival (OS), and biomarker analysis.

Results: Of 104 patients recruited, 100 patients were assessable for clinical benefit prior to planned nephrectomy; 80 of 104 (76.9%) were men; median [interquartile range] age, 64 [56-71] years). Overall, 84 of 100 (84% [95% CI, 75%-91%]) gained clinical benefit before planned nephrectomy. The median reduction in the size of the primary tumor was 14.4% (interquartile range, 1.4%-21.1%). No patients were unable to undergo surgery as a result of local progression of disease. Nephrectomy was performed in 63 (61%) of patients; 14 (22%) reported surgical complications. The 2 most common reasons for not undergoing surgery were progression of disease (n = 13) and patient choice (n = 9). There was 1 postoperative surgical death. The median PFS and OS for the whole cohort were 7.1 (95% CI, 6.0-9.2) and 22.7 (95% CI, 14.3-not estimable) months, respectively. Patients with MSKCC poor-risk disease or progressive disease prior to surgery had a poor outcome (median OS, 5.7 [95% CI, 2.6-10.8] and 3.9 [95% CI, 0.5-9.1] months, respectively). Surgical complications were observed in 14 (22%) of the nephrectomies. Biomarker analysis from sequential tissue samples revealed a decrease in CD8 expression (20.00 vs 13.75; P = .05) and significant reduction in expression of von Hippel-Lindau tumor suppressor (100 vs 40; P < .001) and C-MET (300 vs 100; P < .001) and increased programmed cell death ligand 1 expression (0 vs 1.5; P < .001) in the immune component. No on-treatment biomarker correlated with response.

Conclusions And Relevance: Nephrectomy after upfront pazopanib therapy could be performed safely and was associated with good outcomes in patients with intermediate-risk metastatic clear cell renal cancer.
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http://dx.doi.org/10.1001/jamaoncol.2016.1197DOI Listing
October 2016

Adrenal surgery in England: better outcomes in high-volume practices.

Clin Endocrinol (Oxf) 2016 07 15;85(1):17-20. Epub 2016 Feb 15.

Academic Unit of Diabetes, Endocrinology & Metabolism, University of Sheffield, Sheffield, UK.

Aims And Background: Adrenal surgery is performed by a variety of surgical specialities in differing environments and volumes. International data suggest that there is a correlation between adrenal surgery volume and outcomes but there are no UK data to support this or UK surgical guidelines. A multidisciplinary team representing the stakeholders in adrenal disease is preparing a national guidance on adrenal surgery. A review of the outcomes for adrenal surgery in England was performed to correlate outcomes with the volume of surgeon practice.

Methods: Hospital Episode Statistics (HES) data for the National Health Service (NHS) in England in the tax year 2013-2014 were examined for adrenal surgery. Length of hospital stay and rate of postoperative readmission were assessed as surrogate quality markers and a comparison made between 'high-' and 'low-' volume surgeons.

Results: A total of 795 adult adrenalectomies were performed by 222 different surgeons with a range of between 1 and 34 adrenalectomies performed per surgeon. Only thirty-six (16%) adrenal surgeons performed 6 or more adrenalectomies. A total of 186 surgeons (84%) performed a median of one adrenalectomy a year. Length of stay and readmission rate within thirty days of operation was 60% longer and 47% higher, respectively, when performed by low-volume surgeons.

Conclusion: The current provision of adrenal surgery in the UK is not in the best interests of patients and is not cost-effective for the NHS. Adrenal surgery is best performed by higher volume surgeons in centres with dedicated adrenal multidisciplinary teams expert in all aspects of care of the adrenal patient.
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http://dx.doi.org/10.1111/cen.13021DOI Listing
July 2016

MRI reporting standard for chronic pelvic pain: consensus development.

Br J Radiol 2016 ;89(1057):20140615

7 Department of Imaging, Ground Floor, KGV Wing, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London, UK.

Aim: To identify radiological parameters that should be reported on gynaecological MRI in order to create a standardized assessment pro forma for reporting CPP, which may be used in clinical practice.

Methods: Chronic pelvic pain (CPP) in females is a common problem presenting a major challenge to healthcare providers. The complex multifactorial aetiology requires a multidisciplinary approach and often necessitates diagnostic laparoscopy for assessment. MRI is emerging as a potential non-invasive alternative for evaluation of CPP; however, standardization of reporting is required for it to be used in routine clinical practice. A two-generational Delphi survey with an expert panel of 28 radiologists specializing in gynaecological MRI from across the UK was used to refine a proposed reporting template for CPP.

Results: 75% response rate for the first round and 79% for the second. Following the second round, agreement was reached on the structure of the pro forma and the way in which information was sought, with overall consistency of agreement between experts deemed as fair (intraclass correlation coefficient = 0.394). This was accepted as the final version by consensus.

Conclusion: The standardized pro forma developed in this study will form the basis for future prospective evaluation of MRI in CPP. This template could be modified for the assessment of other benign gynaecological conditions.

Advances In Knowledge: Female CPP is a significant problem presenting challenges for clinicians. MRI is often used for evaluation and standardization of techniques, and reporting is required. The pro forma developed in this study will form the basis for future prospective MRI evaluation.
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http://dx.doi.org/10.1259/bjr.20140615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985937PMC
May 2016

Diffusion-weighted imaging and dynamic contrast-enhanced MRI in assessing response and recurrent disease in gynaecological malignancies.

Cancer Imaging 2015 Mar 15;15. Epub 2015 Mar 15.

Imaging Department, St. Bartholomew's Hospital, Barts Health, West Smithfield, London, UK.

Magnetic resonance imaging (MRI) has an established role in imaging pelvic gynaecological malignancies. It is routinely used in staging endometrial and cervical cancer, characterizing adnexal masses, selecting optimal treatment, monitoring treatment and detecting recurrent disease. MRI has also been shown to have an excellent performance and an evolving role in surveillance of patients after chemoradiotherapy in cervical cancer, post-trachelectomy, detecting early recurrence and planning exenterative surgery in isolated central recurrences in both cervical and endometrial cancer and in young patients on surveillance for medically managed endometrial cancer. However, conventional MRI still has limitations when the morphological appearance of early recurrent or residual disease overlaps with normal pelvic anatomy or treatment effects in the pelvis. In particular, after chemoradiotherapy for cervical cancer, distinguishing between radiotherapy changes and residual or early recurrent disease within the cervix or the vaginal vault can be challenging on conventional MRI alone. Therefore, there is an emerging need for functional imaging to overcome these limitations. The purpose of this paper is to discuss the emerging functional MRI techniques and their applications in predicting treatment response, detecting residual disease and early recurrent disease to optimize the treatment options available using diffusion-weighted imaging and dynamic contrast enhancement particularly in cervical and endometrial cancer.
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http://dx.doi.org/10.1186/s40644-015-0037-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432943PMC
March 2015

A phase Ib study investigating the combination of everolimus and dovitinib in vascular endothelial growth factor refractory clear cell renal cancer.

Eur J Cancer 2014 Aug 4;50(12):2057-64. Epub 2014 Jun 4.

Department of Uro-oncology, Guys and St Thomas's Hospital, London, UK.

Background: Everolimus (mammalian target of rapmaycin (mTOR) inhibitor) and dovitinib (vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) inhibitor) demonstrate activity in metastatic clear cell renal cancer. The combination of these agents has a broad spectrum of relevant activity. The combination is explored in this phase Ib study.

Methods: Patients with metastatic clear cell renal cancer who have failed VEGF targeted therapy were eligible. Up to four cohorts of three to six patients (3+3 design) were treated with escalating doses of everolimus and dovitinib. Dose-limiting toxicities (DLTs) were assessed to determine the maximum tolerated dose (MTD). An expansion cohort (n=15) was investigated to obtain additional efficacy information. Sequential fluorodeoxyglucose positron emission tomography (FDG-PET) was used as a surrogate marker of response.

Results: Overall 18 patients were recruited into the study. Fifteen patients received the MTD, which was everolimus 5mg orally (PO) once daily (OD) and dovitinib 200mg PO day 1-5/7. The MTD was associated with toxicity, which included fatigue, mucositis and diarrhoea in 73%, 53% and 53% (Common Toxicity Criteria (CTC) grade 1-4) of patients, respectively. Frequent biochemical abnormalities occurred (such as hypertriglyceridaemia in 67%). Higher doses of the combination were not tolerable due to grade 3 fatigue in 2/3 patients and grade 3 nausea in 1/3 patients within 1 month of therapy. The response rate at the MDT was 1/15 (7%) while the progression free survival for the MTD was 7 months (95% confidence interval (CI) 2.2-11 months). Pharmacokinetic data at the MTD showed stable kinetics with time.

Conclusion: Dovitinib and everolimus had modest activity, but did not meet all of the planned efficacy end-points. Fatigue was the dose limiting toxicity.
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http://dx.doi.org/10.1016/j.ejca.2014.04.021DOI Listing
August 2014

Re: the prevalence of incidentally detected adrenal enlargement on CT. A reply.

Clin Radiol 2014 Jun 26;69(6):658-9. Epub 2014 Mar 26.

Barts and the London NHS Trust, Radiology Department St Bartholomew's Hospital, West Smithfield, London, UK.

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http://dx.doi.org/10.1016/j.crad.2014.02.002DOI Listing
June 2014