Multiple Endocrine Neoplasia Type 1 and the Pancreas: Diagnosis and Treatment of Functioning and Non-Functioning Pancreatic and Duodenal Neuroendocrine Neoplasia within the MEN1 Syndrome - An International Consensus Statement.

The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.

Phaeochromocytoma presenting as Takotsubo cardiomyopathy.

We report a case of a 72-year-old woman who presented with ST-elevation myocardial infarction (STEMI). However, coronary angiography showed unobstructed arteries while echocardiography (ECHO) showed severe left ventricular (LV) apical hypokinesia with ejection fraction (EF) of 25-30%. Seven months later she presented with a transient ischaemic attack and a repeat ECHO showed a normal EF.A few months later, she was diagnosed with breast cancer and as part of staging procedure, an incidental left adrenal mass was identified. This was biochemically confirmed as phaeochromocytoma (PY) and she underwent laparoscopic adrenalectomy.PY is a rare catecholamine secreting tumour arising from adrenomedullary chromaffin cells. Excessive catecholamine-induced stimulation can present as transient, reversible cardiomyopathy similar to Takotsubo cardiomyopathy and cerebrovascular events. The diagnosis of PY is often delayed but it is important to recognize PY as a cause of reversible cardiomyopathy. Early intervention is essential to improve mortality from cardiovascular and cerebrovascular complications.

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents.

BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Impact of surgical volume and surgical outcome assessing registers on the quality of thyroid surgery.

The available evidence concerning the relationship between volume and outcome for thyroid surgery is assessed in this article. Morbidity forms the principal surrogate marker of thyroid surgery quality for which postoperative hypocalcaemia and recurrent laryngeal nerve injuries are most commonly reported upon. Whilst there is an abundance of published data for these outcomes, interpretation to recommend annual volume thresholds is challenging. This is due to a lack of consensus on definitions not only for outcomes but high and low volume surgeons. The evidence reviewed in this article supports the notion that high volume surgeons achieve superior outcomes in thyroid surgery quality though it is not possible to recommend minimal annual volumes on the basis of this evidence alone. Every thyroid surgeon should know their own outcomes and how they compare with their peers and engagement in thyroid surgery registries can facilitate this.

The surgical management of sporadic primary hyperparathyroidism.

Sporadic primary hyperparathyroidism (pHPT) is the commonest cause of hypercalcaemia in the ambulatory population. It has a female preponderance and its incidence is increasing. In 85% of cases it is caused by a single parathyroid adenoma, with four gland hyperplasia in up to 20%. Parathyroidectomy is the only cure and bilateral neck exploration remains the gold standard to achieve this. Several adjuncts have been developed to improve success rates or limit the extent of surgery. Pre-operative localisation permits planned targeted surgery. Ultrasound scanning and scintigraphy are the most commonly employed, although 4DCT has become a useful modality in complex cases. However, excellent rates of biochemical cure can be achieved in specialist centres when pre-operative imaging is negative. Pre-operative prediction models and intra-operative parathyroid hormone (ioPTH) assist, with high sensitivity, to predict single gland disease. Reoperations present a major challenge to the endocrine surgeon.

AHNS Series: Do you know your guidelines? Optimizing outcomes in reoperative parathyroid surgery: Definitive multidisciplinary joint consensus guidelines of the American Head and Neck Society and the British Association of Endocrine and Thyroid Surgeons.

BACKGROUND: Revision parathyroid is challenging due to possible diagnostic uncertainty as well as the technical challenges it can present. METHODS: A multidisciplinary panel of distinguished experts from the American Head and Neck Society (AHNS) Endocrine Section, the British Association of Endocrine and Thyroid Surgeons (BAETS), and other invited experts have reviewed this topic with the purpose of making recommendations based on current best evidence. The literature was also reviewed on May 12, 2017. PubMed (1946-2017), Cochrane SR (2005-2017), CT databases (1997-2017), and Web of Science (1945-2017) were searched with the following strategy: revision and reoperative parathyroidectomy to ensure completeness. RESULTS: Guideline recommendations were made in 3 domains: preoperative evaluation, surgical management, and alternatives to surgery. Eleven guideline recommendations are proposed. CONCLUSION: Reoperative parathyroid surgery is best avoided if possible. Our literature search and subsequent recommendations found that these cases are best managed by experienced surgeons using precision preoperative localization, intraoperative parathyroid hormone (PTH), and the team approach.

An InDel in Phospholipase-C-B-1 Is Linked with Euthyroid Multinodular Goiter.

BACKGROUND: Euthyroid multinodular goiter (MNG) is common, but little is known about the genetic variations conferring predisposition. Previously, a family with MNG of adolescent onset was reported in which some family members developed papillary thyroid carcinomas (PTC). METHODS: Genome-wide linkage analysis and next-generation sequencing were conducted to identify genetic variants that may confer disease predisposition. A multipoint nonparametric LOD score of 3.01 was obtained, covering 19 cM on chromosome 20p. Haplotype analysis reduced the region of interest to 10 cM. RESULTS: Analysis of copy number variation identified an intronic InDel (∼1000 bp) in the PLCB1 gene in all eight affected family members and carriers (an unaffected person who has inherited the genetic trait). This InDel is present in approximately 1% of "healthy" Caucasians. Next-generation sequencing of the region identified no additional disease-associated variant, suggesting a possible role of the InDel. Since PLCB1 contributes to thyrocyte growth regulation, the InDel was investigated in relevant Caucasian cohorts. It was detected in 0/70 PTC but 4/81 unrelated subjects with MNG (three females; age at thyroidectomy 27-59 years; no family history of MNG/PTC). The InDel frequency is significantly higher in MNG subjects compared to controls (χ2 = 5.076; p = 0.024. PLCB1 transcript levels were significantly higher in thyroids with the InDel than without (p < 0.02). CONCLUSIONS: The intronic PLCB1 InDel is the first variant found in familial multiple papilloid adenomata-type MNG and in a subset of patients with sporadic MNG. It may function through overexpression, and increased PLC activity has been reported in thyroid neoplasms. The potential role of the deletion as a biomarker to identify MNG patients more likely to progress to PTC merits exploration.

The Role of Thyrotropin Receptor Activation in Adipogenesis and Modulation of Fat Phenotype.

Evidence from clinical and experimental data suggests that thyrotropin receptor (TSHR) signaling is involved in energy expenditure through its impact on white adipose tissue (WAT) and brown adipose tissue (BAT). TSHR expression increases during mesenchymal stem cell (MSC) differentiation into fat. We hypothesize that TSHR activation [TSHR*, elevated thyroid-stimulating hormone, thyroid-stimulating antibodies (TSAB), or activating mutation] influences MSC differentiation, which contributes to body composition changes seen in hypothyroidism or Graves' disease (GD). The role of TSHR activation on adipogenesis was first investigated using ex vivo samples. Neck fat (all euthyroid at surgery) was obtained from GD (n = 11, TSAB positive), toxic multinodular goiter (TMNG, TSAB negative) (n = 6), and control patients with benign euthyroid disease (n = 11, TSAB negative). The effect of TSHR activation was then analyzed using human primary abdominal subcutaneous preadipocytes (n = 16). Cells were cultured in complete medium (CM) or adipogenic medium [ADM, containing thiazolidinedione (TZD), PPARγ agonist, which is able to induce BAT formation] with or without TSHR activation (gain-of-function mutant) for 3 weeks. Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, qPCR measurement of terminal differentiation marker (LPL). BAT [PGC-1α, uncoupling protein 1 (UCP1), and ZIC1], pre-BAT (PRDM16), BRITE- (CITED1), or WAT (LEPTIN) markers were analyzed by semiquantitative PCR or qPCR. In ex vivo analysis, there were no differences in the expression of UCP1, PGC-1α, and ZIC1. BRITE marker CITED1 levels were highest in GD followed by TMNG and control (p for trend = 0.009). This was associated with higher WAT marker LEPTIN level in GD than the other two groups (p < 0.001). In primary cell culture, TSHR activation substantially enhanced adipogenesis with 1.4 ± 0.07 (ORO), 8.6 ± 1.8 (foci), and 5.5 ± 1.6 (LPL) fold increases compared with controls. Surprisingly, TSHR activation in CM also significantly increased pre-BAT marker PRDM16; furthermore, TZD-ADM induced adipogenesis showed substantially increased BAT markers, PGC-1α and UCP1. Our study revealed that TSHR activation plays an important role in the adipogenesis process and BRITE/pre-BAT formation, which leads to WAT or BAT phenotype. It may contribute to weight loss as heat during hyperthyroidism and later transforms into WAT posttreatment of GD when patients gain excess weight.

Does elective parathyroidectomy for primary hyperparathyroidism affect renal function? A prospective cohort study.

INTRODUCTION: Major surgery is associated with acute kidney injury (AKI). This study examines associations between elective parathyroid surgery and post-operative renal impairment. METHODS: Consecutive patients undergoing elective parathyroidectomy were evaluated, and demographic data and relevant blood parameters collected. A renal risk score was calculated for each patient based on locally agreed criteria. RESULTS: 62 patients were evaluated. Mean ± standard deviation creatinine increased between pre-operative and day 1 post-operative (72 ± 19 vs. 76 ± 20 µmol/L; p < 0.010). Mean eGFR reduced between baseline and day 1 (78 ± 15 vs. 75 ± 16; p < 0.010) and baseline and follow-up (78 ± 15 vs. 73 ± 17; p < 0.050). 19 patients (30.7%) had a creatinine increase of ≥10% on day 1 post-operatively and 7 (11.3%) a rise of >20%. At follow-up, 14 (30.4% of 46 patients with follow up creatinine measurements) and 5 (10.9%) patients had a creatinine of >10% and >20% higher than pre-operative or day 1 values respectively. Those with an increase in serum creatinine of ≥10% (at any time point) had a greater renal risk score [median 2 (inter-quartile range, IQR 0-3) vs. 1 (0-2); p = 0.040]. CONCLUSION: A significant minority of patients undergoing elective parathyroid surgery demonstrate worsening renal function post-operatively. A pre-operative risk stratification tool may identify those at risk in the clinical setting.

Imaging of the parathyroid glands in primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine diseases worldwide. Surgery is the only potentially curable option for patients with this disorder, even though in asymptomatic patients 50 years of age or older without end organ complications, a conservative treatment may be a possible alternative. Bilateral neck exploration under general anaesthesia has been the standard for the definitive treatment. However, significant improvements in preoperative imaging, together with the implementation of rapid parathyroid hormone determination, have determined an increased implementation of focused, minimally invasive surgical approach. Surgeons prefer to have a localization study before an operation (both in the classical scenario and in the minimally invasive procedure). They are not satisfied by having been referred a patient with just a biochemical diagnosis of PHPT. Imaging studies must not be utilized to make the diagnosis of PHPT. They should be obtained to both assist in determining disease etiology and to guide operative procedures together with the nuclear medicine doctor and, most importantly, with the surgeon. On the contrary, apart from minimally invasive procedures in which localization procedures are an obligate choice, some surgeons believe that literature on parathyroidectomy over the past two decades reveals a bias towards localization. Therefore, surgical expertise is more important than the search for abnormal parathyroid glands.

Resistant hypertension with adrenal nodule: are we removing the right gland?

UNLABELLED: Resistant hypertension is often difficult to treat and may be associated with underlying primary aldosteronism (PA). We describe the case of an elderly gentleman who presented with severe and resistant hypertension and was found to have a left adrenal incidentaloma during evaluation but had aldosterone excess secondary to unilateral adrenal hyperplasia (UAH) of the contralateral gland, which needed surgical intervention. A 65-year-old gentleman was evaluated for uncontrolled high blood pressure (BP) in spite of taking four antihypertensive medications. The high BP was confirmed on a 24-h ambulatory reading, and further biochemical evaluation showed an elevated serum aldosterone renin ratio (ARR) (1577 pmol/l per ng per ml per h). Radiological evaluation showed an adrenal nodule (15 mm) in the left adrenal gland but an adrenal vein sampling demonstrated a lateralization towards the opposite site favouring the right adrenal to be the source of excess aldosterone. A laparoscopic right adrenalectomy was performed and the histology of the gland confirmed nodular hyperplasia. Following surgery, the patient's BP improved remarkably although he remained on antihypertensives and under regular endocrine follow-up. PA remains the most common form of secondary and difficult-to-treat hypertension. Investigations may reveal incidental adrenal lesions, which may not be the actual source of excess aldosterone, but UAH may be a contributor and may coexist and amenable to surgical treatment. An adrenal vein sampling should be undertaken for correct lateralization of the source, otherwise a correctable diagnosis may be missed and the incorrect adrenal gland may be removed. LEARNING POINTS: Severe and resistant hypertension can often be associated with underlying PA.ARR is an excellent screening tool in patients with suspected PA.Lateralization with adrenal venous sampling is essential to isolate the source and differentiate between unilateral and bilateral causes of hyperaldosteronism.Adrenal incidentalomas and UAH may coexist and the latter may often be the sole cause of excess aldosterone secretion.Decisions about adrenalectomy should be made only after integrating and interpreting radiological and biochemical test findings properly.

Surgical Approach to the Adrenal Glands.

Any surgeon treating a patient with adrenal disease should be a member of a multi-disciplinary team involving dedicated specialists, including an endocrinologist, anaesthetist, radiologist, intensivist and geneticist. In an era of epidemic numbers of adrenal incidentalomas, great care must be taken to determine not only the endocrine diagnosis, but also the benefits (if any) of adrenal surgery. Finally, the surgeon must be competent in both minimally invasive and gross resectional surgical techniques and know when to adopt these two very different surgical approaches.

Electrostatic precipitation is a novel way of maintaining visual field clarity during laparoscopic surgery: a prospective double-blind randomized controlled pilot study.

BACKGROUND: Ultravision™ is a new device that utilizes electrostatic precipitation to clear surgical smoke. The aim was to evaluate its performance during laparoscopic cholecystectomy. METHODS: Patients undergoing laparoscopic cholecystectomy were randomized into "active (device on)" or "control (device off)." Three operating surgeons scored the percentage effective visibility and three reviewers scored the percentage of the procedure where smoke was present. All assessors also used a 5-point scale (1 = imperceptible/excellent and 5 = very annoying/bad) to rate visual impairment. Secondary outcomes were the number of smoke-related pauses, camera cleaning, and pneumoperitoneum reductions. Mean results are presented with 95% confidence intervals (CI). RESULTS: In 30 patients (active 13, control 17), the effective visibility was 89.2% (83.3-95.0) for active cases and 71.2% (65.7-76.7) for controls. The proportion of the procedure where smoke was present was 41.1% (33.8-48.3) for active cases and 61.5% (49.0-74.1) for controls. Operating surgeons rated the visual impairment as 2.2 (1.7-2.6) for active cases and 3.2 (2.8-3.5) for controls. Reviewers rated the visual impairment as 2.3 (2.0-2.5) for active cases and 3.2 (2.8-3.7) for controls. In the active group, 23% of procedures were paused to allow smoke clearance compared to 94% of control cases. Camera cleaning was not needed in 85% of active procedures and 35% of controls. The pneumoperitoneum was reduced in 0% of active cases and 88% of controls. CONCLUSIONS: Ultravision™ improves visibility during laparoscopic surgery and reduces delays in surgery for smoke clearance and camera cleaning.

Assessment of resource use and costs associated with parathyroidectomy for secondary hyperparathyroidism in end stage renal disease in the UK.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a major complication of end stage renal disease (ESRD). For the National Health Service (NHS) to make appropriate choices between medical and surgical management, it needs to understand the cost implications of each. A recent pilot study suggested that the current NHS healthcare resource group tariff for parathyroidectomy (PTX) (£2071 and £1859 in patients with and without complications, respectively) is not representative of the true costs of surgery in patients with SHPT. OBJECTIVE: This study aims to provide an estimate of healthcare resources used to manage patients and estimate the cost of PTX in a UK tertiary care centre. METHODS: Resource use was identified by combining data from the Proton renal database and routine hospital data for adults undergoing PTX for SHPT at the University Hospital of Wales, Cardiff, from 2000-2008. Data were supplemented by a questionnaire, completed by clinicians in six centres across the UK. Costs were obtained from NHS reference costs, British National Formulary and published literature. Costs were applied for the pre-surgical, surgical, peri-surgical, and post-surgical periods so as to calculate the total cost associated with PTX. RESULTS: One hundred and twenty-four patients (mean age=51.0 years) were identified in the database and 79 from the questionnaires. The main costs identified in the database were the surgical stay (mean=£4066, SD=£,130), the first month post-discharge (£465, SD=£176), and 3 months prior to surgery (£399, SD=£188); the average total cost was £4932 (SD=£4129). From the questionnaires the total cost was £5459 (SD=£943). It is possible that the study was limited due to missing data within the database, as well as the possibility of recall bias associated with the clinicians completing the questionnaires. CONCLUSION: This analysis suggests that the costs associated with PTX in SHPT exceed the current NHS tariffs for PTX. The cost implications associated with PTX need to be considered in the context of clinical assessment and decision-making, but healthcare policy and planning may warrant review in the light of these results.

Adrenalectomy for solid tumor metastases: results of a multicenter European study.

BACKGROUND: We assessed the results of adrenalectomy for solid tumor metastases in 317 patients recruited from 30 European centers. METHODS: Patients with histologically proven adrenal metastatic disease and undergoing complete removal(s) of the affected gland(s) were eligible. RESULTS: Non-small cell lung cancer (NSCLC) was the most frequent tumor type followed by colorectal and renal cell carcinoma. Adrenal metastases were synchronous (≤6 months) in 73 (23%) patients and isolated in 213 (67%). The median disease-free interval was 18.5 months. Laparoscopic resection was used in 46% of patients. Surgery was limited to the adrenal gland in 73% of patients and R0 resection was achieved in 86% of cases. The median overall survival was 29 months (95% confidence interval, 24.69-33.30). The survival rates at 1, 2, 3, and 5 years were 80%, 61%, 42%, and 35%, respectively. Patients with renal cancer showed a median survival of 84 months, patients with NSCLC 26 months, and patients with colorectal cancer 29 months (P = .017). Differences in survival between metachronous and synchronous lesions were also significant (30 vs. 23 months; P = .038). CONCLUSION: Surgical removal of adrenal metastasis is associated with long-term survival in selected patients.

The value of intraoperative PTH measurements in patients with mild primary hyperparathyroidism.

PURPOSE: Intraoperative parathyroid hormone (ioPTH) measurement has facilitated a move to minimally invasive parathyroidectomy. Patients are referred for surgery earlier with milder hypercalcaemia and smaller tumours. Whilst previous research has shown that glands size can affect ioPTH kinetics in patients with multiple gland disease, the dynamics of ioPTH in patients with mild hyperparathyroidism (HPT) has not been studied. We therefore investigated the relationship between biochemical parameters and parathyroid adenoma weight, and determined the dynamics and accuracy of ioPTH assay in patients with milder hypercalcaemia undergoing parathyroidectomy. METHODS: Patients undergoing parathyroidectomy for single gland disease from January 2004 to March 2011 were divided prospectively into two groups according to preoperative serum calcium: patients with a preoperative calcium ≥ 2.85 mmol/L (11.4 mg/dL) and <2.85 mmol/L were grouped as severe and mild hypercalcaemia, respectively. Correlation coefficients were calculated to assess the relationship between biochemical markers of calcium homeostasis and ioPTH measurements with respect to parathyroid gland weight. RESULTS: There was a weak correlation of preoperative serum calcium (r = 0.248, r = 0.207), PTH (r = 0.392, r = 0.275), and baseline ioPTH (r = 0.516, r = 0.244) with parathyroid gland weight in severe (n = 113) and mild groups (n = 190), respectively. No correlation between the magnitude in ioPTH drop with parathyroid gland weight at 5 or 10 min post-excision for either group was observed. Success rates (post-operative normocalcaemia) were similar for each group (99.1 % severe, 98.9 % mild). CONCLUSION: This prospective study provides evidence that ioPTH assay is a valuable tool in predicting adequate tissue removal in patients with milder and more severe hypercalcaemia due to single gland primary HPT.

Use of intraoperative insulin assay for the localisation of insulinoma.

BACKGROUND: The curative treatment for patients with insulinoma is the surgical removal of the tumour; however, these tumours are small and therefore their preoperative localisation using ultrasound and CT scans may be difficult. METHODS: Intraoperative serum insulin measurements were used as an aid to the surgical management of seven unselected and consecutive presentations of insulinoma. RESULTS: In six of the seven cases we were able to demonstrate an increase in the peripheral serum insulin concentration between 3 and 5 min after manual examination of the tumour. In addition, there was a 50% decrease in concentration 10 min after removal of the tumour. CONCLUSIONS: We believe that intraoperative insulin measurements are of use in demonstrating the functionality of tumours localised by intraoperative ultrasound and surgical examination. In addition, they act as an indicator of the completeness of surgery post tumour excision.

Clinical utility of peri-operative C-reactive protein testing in general surgery.

INTRODUCTION: C-reactive protein (CRP) is an acute-phase protein used clinically to diagnose infectious and inflammatory disease and monitor response to treatment. CRP measurement in the peri-operative period was audited and patterns of change analysed for elective general surgical patients. PATIENTS AND METHODS: General surgical patients (201) admitted for elective general surgery over a 3-month period were considered for the study. CRP results pre- and postoperatively were recorded, and data on co-morbid conditions and surgical procedure were noted. RESULTS: CRP was requested pre-operatively on 84% of patients. A high CRP was more likely to be found in patients with co-morbidity. Postoperatively, CRP was requested during the first 3 days on 69% of patients. CRP peaked at postoperative days two or three, and then fell. In patients who had a high pre-operative CRP, the peak CRP was higher and occurred later, than those who had a normal pre-operative CRP. CONCLUSIONS: CRP requesting pre-operatively is common, but is not recommended in NICE guidelines. Postoperatively, CRP levels rise; as a result, its use as a tool to screen for infection is limited. CRP has a role in diagnosis of infection after the first three postoperative days and in monitoring response to treatment. Therefore, routine use of CRP measurements pre-operatively and in the first 2 or 3 days post-operatively is not recommended. A peri-operative CRP should only be requested if there is a clear clinical indication.