Impact of adrenal surgeon volume on outcome: analysis of 4464 operations from the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS).

BACKGROUND: There is a surgeon volume-outcome effect in adrenal surgery but the threshold for high-volume surgeon remains controversial. This study aimed to determine predictors of high-risk adrenal operations and to explore whether these should be restricted to high-volume surgeons. METHODS: Patients undergoing adrenal surgery and registered in the United Kingdom Registry of Endocrine and Thyroid Surgery between 2004 and 2021 were analysed. Outcomes included postoperative complications, duration of hospital stay, and mortality. Factors included in multivariable analysis were age, sex, diagnosis, surgical approach, laterality, and surgeon volume. Patients with missing data were excluded. RESULTS: A total of 4464 of 6174 patients (72.3%) were analysed. Postoperative complications occurred in 418 patients (9.4%) and 14 (0.3%) died. Median duration of hospital stay was 3 (i.q.r. 2-5) days. Co-variables significantly associated with an increase or decrease in postoperative complications (P < 0.050) were age (OR 1.02, 95% c.i. 1.01 to 1.03), adrenal cancer (OR 1.64, 1.14 to 2.36), minimally invasive approach (OR 0.317, 0.248 to 0.405), bilateral surgery (OR 1.66, 1.03 to 2.69), and surgeon volume (OR 0.98, 0.96 to 0.99). An increase or decrease in mortality was associated with patient age (OR 1.08, 1.03 to 1.13), minimally invasive approach (OR 0.08, 0.02 to 0.27), and bilateral surgery (OR 6.93, 1.40 to 34.34). The incidence of postoperative complications was significantly lower above a threshold of 12 operations per year (P = 0.034) and 20 per year (P < 0.001), but not six per year (P = 0.540). Median duration of hospital stay was 2 days for surgeons doing over 20 operations per year, compared with 3 days for those undertaking fewer than 20, fewer than 12 or fewer than 6 operations per year. CONCLUSION: Increasing surgical volume is associated with shorter hospital stay and fewer complications. This analysis supports the case for centralization of surgery for adrenal cancer and bilateral tumours to higher-volume surgeons performing a minimum of 12 operations per year.

The adrenal glands are found in the fatty tissue at the back of the abdomen above each kidney, and produce steroid and adrenaline hormones. Surgery on tumours of the adrenal gland is uncommon compared with surgery for other tumours such as those of the breast, bowel, kidney, and lung. Research has shown that the more adrenal operations a surgeon undertakes per year, the better the overall outcomes for patients undergoing that type of surgery. In this study, the outcomes from adrenal operations recorded over 18 years in the national adrenal surgical registry by members of the British Association of Endocrine and Thyroid Surgeons were analysed. The results confirmed previous findings showing that postoperative complications and length of hospital stay were reduced for patients operated by surgeons who did more adrenal operations per year. Operations done by keyhole surgery had better outcomes. Operations done either in older patients, or for the rare adrenal cancer tumours had worse outcomes, as did operations in which both adrenal glands were removed. The authors recommended that all surgeons performing adrenal surgery should monitor the outcomes of their operations, ideally in a national registry, and discuss these with patients before surgery; and undertake a minimum of 6 adrenal operations per year, but a minimum of 12 per year if doing surgery for adrenal cancer or surgery to remove both adrenal glands.

Risk factors for postoperative complications after adrenalectomy for phaeochromocytoma: multicentre cohort study.

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.

Consensus statement on the management of incidentally discovered FDG avid thyroid nodules in patients being investigated for other cancers.

With the widespread use of 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) in the investigation and staging of cancers, incidental discovery of FDG-avid thyroid nodules is becoming increasingly common, with a reported incidence in the range 1%-4% of FDG PET/CT scans. The risk of malignancy in an incidentally discovered FDG avid thyroid nodule is not clear due to selection bias in reported retrospective series but is likely to be less than 15%. Even in cases where the nodule is found to be malignant, the majority will be differentiated thyroid cancers with an excellent prognosis even without treatment. If, due to index cancer diagnosis, age and co-morbidities, it is unlikely that the patient will survive 5 years, further investigation of an incidental FDG avid thyroid nodule is unlikely to be warranted. We provide a consensus statement on the circumstances in which further investigation of FDG avid thyroid nodules with ultrasound and fine needle aspiration might be appropriate.

Risk factors for postoperative hypotension after adrenalectomy for phaeochromocytoma: derivation of the PACS risk score.

BACKGROUND: Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring. METHODS: Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score. RESULTS: PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p < 0.001), preoperative catecholamine level (p < 0.001), open surgery (p < 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CI95%, 1.09-3.13, p = 0.02), preoperative catecholamine level (OR: 3.11, CI95%, 1.74-5.55, p < 0.001), open surgery (OR: 3.31, CI95%, 1.57-6.97, p = 0.002) and preoperative mean arterial blood pressure (OR: 0.59, CI95%, 0.48-1.02, p = 0.08) were independently associated with PH, and were incorporated into a clinical risk score (AUROC 0.69, C-statistic 0.69). The risk of PH was 25% and 68% in low and high risk patients, respectively. CONCLUSION: The derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

Systematic review of incidence, risk factors, prevention and treatment of post-laryngectomy hypoparathyroidism.

PURPOSE: Post-laryngectomy hypoparathyroidism is associated with significant short- and long-term morbidities. This systematic review aimed to determine incidence, risk factors, prevention and treatment of post-laryngectomy hypoparathyroidism. METHODS: Medline, EMBASE and the Cochrane library were searched for relevant articles on hypocalcaemia and/or hypoparathyroidism after laryngectomy or pharyngectomy. Two authors independently screened titles and abstracts from the search. Data from individual studies were collated and presented (without meta-analysis). Quality assessment of included studies was undertaken. The review protocol was registered in the PROSPERO database (CRD42019133879). RESULTS: Twenty-three observational studies were included. The rates of transient and long-term hypoparathyroidism following laryngectomy with concomitant hemi- or total thyroidectomy ranged from 5.6 to 57.1% (n = 13 studies) and 0 to 12.8% (n = 5 studies), respectively. Higher transient (62.1-100%) and long-term (12.5-91.6%) rates were reported in patients who had concomitant oesophagectomy and total thyroidectomy (n = 4 studies). Other risk factors included bilateral selective lateral neck dissection, salvage laryngectomy and total pharyngectomy. There is a lack of data on prevention and management. CONCLUSION: Hypoparathyroidism occurs in a significant number of patients after laryngectomy. Patients who underwent laryngectomy with concomitant hemithyroidectomy may still develop hypoparathyroidism. Research on prevention and treatment is lacking and needs to be encouraged.

Serum Magnesium Measurements After Parathyroidectomy for Primary Hyperparathyroidism: Should It be Routine?

BACKGROUND: Parathyroidectomy is the treatment of choice in primary hyperparathyroidism (PHPT). Following surgery, significant changes in bone and mineral metabolism may follow, but routine magnesium monitoring is not standard practice. The occurrence of significant clinical events linked to hypomagnesaemia in 3 patients after parathyroidectomy led to our evaluation of magnesium levels after surgery for PHPT. METHODS: Serum magnesium levels before and after parathyroidectomy for PHPT were prospectively evaluated in a single centre over a year. The incidence and severity of hypomagnesaemia and its correlation with other biochemical variables were assessed. RESULTS: A total of 138 patients underwent parathyroidectomy for PHPT. Pre-operative and day 1 post-operative serum magnesium levels were available in 57/138 (41.3%) and 99/138 (71.7%) patients, respectively. Serum magnesium decreased significantly after surgery (mean ± SD of 0.85 ± 0.08 and 0.75 ± 0.11 mmol/L, respectively, p < 0.001). On the day after parathyroidectomy, 31/99 (31.3%) patients had hypomagnesaemia (<0.70 mmol/L); in 3 of whom it was severe (<0.50 mmol/L). Patients with hypomagnesaemia had lower pre-operative magnesium (mean ± SD of 0.78 ± 0.06 and 0.87 ± 0.07 mmol/L, p < 0.001), higher pre-operative calcium [median (IQR) of 2.83 (2.71-2.99) and 2.71 (2.63-2.80) mmol/L, p = 0.001] and higher post-operative calcium [median (IQR) of 2.41 (2.30-2.51) and 2.35 (2.28-2.43) mmol/L, p = 0.046] compared to those with normomagnesaemia. In addition, these patients demonstrated higher drop in calcium levels after surgery (0.44 ± 0.20 and 0.35 ± 0.18 mmol/L, p = 0.033). Magnesium levels after surgery correlated positively with pre-operative magnesium (r = 0.561, p < 0.001) and post-operative PTH (r = 0.210, p = 0.037) and negatively with pre-operative adjusted calcium (r = - 0.389, p < 0.001). CONCLUSIONS: Serum magnesium decreased significantly following parathyroidectomy for PHPT and nearly a third of patients developed post-operative, mostly mild hypomagnesaemia. Whilst routine serum magnesium measurements could facilitate prompt recognition and treatment of this electrolyte disturbance, further research needs to establish the clinical importance of mild hypomagnesaemia in these clinical settings and, if indicated, to devise optimal treatment strategies.

Simultaneous presentation of parathyroid carcinoma, papillary thyroid cancer and ACTH-independent hypercortisolism due to benign cortical adenoma.

A 46-year-old woman presented with hypertension and renal disease. Investigations showed severe hypercalcaemia due to primary hyperparathyroidism. Imaging demonstrated renal calculi and an incidental left adrenal lesion. Additional biochemistry confirmed adrenocorticotropic hormone-independent hypercortisolism. Ultrasound and sestamibi scan found an enlarged right-sided parathyroid gland and a suspicious right thyroid nodule, biopsy of which suggested papillary carcinoma. The right parathyroid mass, right thyroid lobe and right central compartment tissue along with a segment of the right recurrent laryngeal nerve was resected en-bloc Completion thyroidectomy and left adrenalectomy were performed 6 months later. Histology showed parathyroid cancer, multifocal papillary thyroid cancer and adrenal clear cell cortical adenoma. Genetic tests were normal. There was no evidence of recurrence at 12 months follow-up. Parathyroid cancer should be suspected in the presence of significant hypercalcaemia, very high parathyroid hormone and end organ damage. Suspicious thyroid nodules on imaging should be appropriately investigated.

Outcomes After Urgent Thyroidectomy Following Rapid Control of Thyrotoxicosis in Graves' Disease are Similar to Those After Elective Surgery in Well-Controlled Disease.

BACKGROUND: Surgery for Graves' disease (GD) is usually performed after adequate control with medical treatment. Occasionally, rapid pre-operative optimization is required. The primary objective was to compare the outcomes of patients undergoing elective surgery for well-controlled GD with those undergoing rapid pre-operative treatment. We also propose a formal treatment protocol for future use. METHODS: A retrospective cohort study in a tertiary referral centre included 247 patients with well-controlled GD undergoing elective surgery and 19 patients with poorly controlled disease undergoing surgery after rapid optimization. The latter group did not respond well to thionamides (carbimazole and/or propylthiouracil) or had intolerance or side effects to thionamides and were treated with a range of non-thionamide drugs, including Lugol's iodine, cholestyramine, beta blockers and steroids (with or without thionamides), and closely monitored for 1-2 weeks before surgery. Outcome measures included thyroid storm, hypoparathyroidism and recurrent laryngeal nerve palsy. RESULTS: In total, 266 patients with male-to-female ratio of 1:6 and median (interquartile range) age of 39 (31-51) were included. Overall, long-term recurrent laryngeal palsy and hypoparathyroidism occurred in 1 (0.38%) and 13 (4.9%) patients, respectively. No patient had thyroid storm. There was no significant difference in hypoparathyroidism (p = 1), vocal cord palsy (p = 0.803) and post-operative bleeding (p = 0.362), between elective surgery and rapid optimization groups. CONCLUSION: Rapid pre-operative treatment is effective, safe and is associated with similar outcomes compared to usual treatment. A rapid pre-operative optimization protocol is proposed.

Evaluation of malpractice litigation in thyroid disease in the National Health Service.

Objectives: Thyroid disease is managed by primary and a range of secondary care specialties. Interventions for common thyroid conditions are effective, but delays in diagnosis, ineffective or inappropriate treatment may affect outcomes and be subject to litigation. This study aimed to analyze trends in thyroid malpractice litigation in the UK over a 14-year period.Methods: This retrospective cohort study analyzed negligence claims recorded by the NHS Litigation Authority from 2002 to 2016. Data on incident details, outcomes, time to settlement, costs, and specialties involved were collected and analyzed.Results: Out of 189 cases reviewed, an outcome was decided in 134 cases; of which, 67.9% were successful for the claimant, resulting in compensation being paid. The most common reasons for successful claims were treatment complications (47 cases) and delay or failure of diagnosis (22 cases). Nerve and/or vocal cord damage and hypoparathyroidism were cited in 12 and 3 cases, respectively. Common specialties involved in successful claims were general surgery, ENT and endocrinology. The median (range) costs paid for compensation were £50,701.35 (£189.00 to £4.5 million). The median (interquartile range) time from incident to settlement was 1254 (992-1756) days. The number of claims (overall and successful) has reduced over the 14-year period, but there has been no change in the total cost per successful claim from 2002 to 2014 (p = 0.151).Conclusion: This overview demonstrates common causes and identifies trends in thyroid malpractice litigation in the UK, highlighting the significant costs incurred. The outcomes of the study will provide a basis to enable clinicians to avoid potential pitfalls and formulate guidelines to minimize risk.

Two cases of spontaneous remission of primary hyperparathyroidism due to auto-infarction: different management and their outcomes.

Spontaneous remission of primary hyperparathyroidism (PHPT) due to necrosis and haemorrhage of parathyroid adenoma, the so-called 'parathyroid auto-infarction' is a very rare, but previously described phenomenon. Patients usually undergo parathyroidectomy or remain under close clinical and biochemical surveillance. We report two cases of parathyroid auto-infarction diagnosed in the same tertiary centre; one managed surgically and the other conservatively up to the present time. Case #1 was a 51-year old man with PHPT (adjusted (adj.) calcium: 3.11 mmol/L (reference range (RR): 2.20-2.60 mmol/L), parathyroid hormone (PTH) 26.9 pmol/L (RR: 1.6-6.9 pmol/L) and urine calcium excretion consistent with PHPT) referred for parathyroidectomy. Repeat biochemistry 4 weeks later at the surgical clinic showed normal adj. calcium (2.43 mmol/L) and reduced PTH. Serial ultrasound imaging demonstrated reduction in size of the parathyroid lesion from 33 to 17 mm. Twenty months later, following recurrence of hypercalcaemia, he underwent neck exploration and resection of an enlarged right inferior parathyroid gland. Histology revealed increased fibrosis and haemosiderin deposits in the parathyroid lesion in keeping with auto-infarction. Case #2 was a 54-year-old lady admitted with severe hypercalcaemia (adj. calcium: 4.58 mmol/L, PTH 51.6 pmol/L (RR: 1.6-6.9 pmol/L)) and severe vitamin D deficiency. She was treated with intravenous fluids and pamidronate and 8 days later developed symptomatic hypocalcaemia (1.88 mmol/L) with dramatic decrease of PTH (17.6 pmol/L). MRI of the neck showed a 44 mm large cystic parathyroid lesion. To date, (18 months later), she has remained normocalcaemic. Learning points: Primary hyperparathyroidism (PHPT) is characterised by excess parathyroid hormone (PTH) secretion arising mostly from one or more autonomously functioning parathyroid adenomas (up to 85%), diffuse parathyroid hyperplasia (<15%) and in 1-2% of cases from parathyroid carcinoma. PHPT and hypercalcaemia of malignancy, account for the majority of clinical presentations of hypercalcaemia. Spontaneous remission of PHPT due to necrosis, haemorrhage and infarction of parathyroid adenoma, the so-called 'parathyroid auto-infarction', 'auto-parathyroidectomy' or 'parathyroid apoplexy' is a very rare in clinical practice but has been previously reported in the literature. In most cases, patients with parathyroid auto-infarction undergo parathyroidectomy. Those who are managed conservatively need to remain under close clinical and biochemical surveillance long-term as in most cases PHPT recurs, sometimes several years after auto-infarction.

Tuberculosis as a differential for bilateral adrenal masses in the UK.

Primary adrenal insufficiency (PAI) is a potentially fatal disease. Adrenal tuberculosis(TB) causing PAI is rare in the developed world. We present a seemingly well, 78-year-old Caucasianwoman in the UK who developed adrenal crisis following elective hip surgery. Biochemical tests confirmed PAI and steroid replacement was initiated. Imaging of the abdomen demonstrated bilateral adrenal masses and a fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed increased uptake in both adrenals suggestive of malignancy. Following a retroperitoneoscopic left adrenalectomy, histology showed caseating necrosis with xanthogranulomatous inflammation favouring a diagnosis of TB. She was commenced on anti-TB treatment. Diagnosing adrenal TB in the west can be challenging especially in the absence of extra-adrenal TB. FDG-PET scans can be falsely positive in presence of chronic active inflammatory conditions, such as TB, and a tissue diagnosis is required. It is important that clinicians remain vigilant of this important disease, which can masquerade as malignancy.

Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism.

BACKGROUND: Post-surgical hypoparathyroidism is a common complication after thyroid surgery. The incidence is likely to increase given the rising trend in the annual number of thyroid operations being performed. Measures to prevent post-thyroidectomy hypoparathyroidism including different surgical techniques and prophylactic calcium and vitamin D supplements have been extensively studied. The management of post-thyroidectomy hypoparathyroidism however has not been extensively evaluated. Routine use of calcium and vitamin D supplements in the postoperative period may reduce the risk of symptoms, temporary hypocalcaemia and hospital stay. However, this may lead to overtreatment and has no effect on long-term hypoparathyroidism. Current recommendations on the management of post-thyroidectomy hypoparathyroidism is based on low-quality evidence. Existing guidelines do not often distinguish between surgical and non-surgical hypoparathyroidism, and transient and long-term disease.The aim of this systematic review was to summarise evidence on the use of calcium, vitamin D and recombinant parathyroid hormone in the management of post-thyroidectomy hypoparathyroidism. In addition, we aimed to highlight deficiencies in the current literature and stimulate further work in this field. OBJECTIVES: The objective of this systematic review was to assess the effects of calcium, vitamin D and recombinant parathyroid hormone in managing post-thyroidectomy hypoparathyroidism. SEARCH METHODS: We searched CENTRAL, MEDLINE, PubMed, Embase as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 17 December 2018 (except Embase, which was last searched on 21 December 2017). No language restrictions were applied. SELECTION CRITERIA: We planned to include randomised control trials (RCTs) or controlled clinical trials (CCTs) examining the effects of calcium, vitamin D or recombinant parathyroid hormone in people with temporary and long-term post-thyroidectomy hypoparathyroidism. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full texts for relevance. MAIN RESULTS: Database searches yielded a total of 1751 records. We retrieved potentially relevant full texts and excluded articles on the following basis: not a RCT or CCT; intervention, comparator or both did not match prespecified criteria; non-surgical causes of hypoparathyroidism, and studies on prevention. None of the articles was eligible for inclusion in the systematic review. AUTHORS' CONCLUSIONS: This systematic review highlights a gap in the current literature and the lack of high-quality evidence in the management of post-thyroidectomy temporary and long-term hypoparathyroidism. Further research focusing on clinically relevant outcomes is needed to examine the effects of current treatments in the management of temporary and long-term post-thyroidectomy hypocalcaemia.

Is there a role for routine laryngoscopy before and after parathyroid surgery?

INTRODUCTION: Recurrent laryngeal nerve (RLN) palsy is a potential complication of parathyroid surgery with significant morbidity and a cause of medico-legal litigation. Peri-operative laryngoscopy to assess RLN function helps identify a vocal cord palsy and guide management. The value of its routine use in asymptomatic patients is however unclear. The low risk of permanent palsy, rarity of true asymptomatic palsy and costs, discomfort and inconvenience to patients are arguments against routine laryngoscopy. This study assessed the results of routine laryngoscopy in patients having parathyroid surgery for primary hyperparathyroidism (PHPT). METHODS: All patients having parathyroid surgery for PHPT (exclusion: re-do surgery and concurrent thyroidectomy) over a 3-year period were included from a tertiary endocrine surgical unit. Data on voice-related outcomes and pre- and post-operative laryngoscopy, including its local cost, were collected and analysed. RESULTS: Of 189 patients who underwent parathyroid surgery, 66 had a unilateral neck exploration. The incidence of vocal cord palsy was 0.5% (1 in 186 patients) and 1.7% (3 in 179 patients) for pre- and post-operative laryngoscopy respectively. The single patient with pre-operative cord palsy was asymptomatic. Of the three with post-operative cord palsy, two were temporary and symptomatic and one was asymptomatic. In the region, the clinical commissioning group was charged £127.00 per laryngoscopy, amounting to £46,736.00 for the whole cohort. CONCLUSIONS: The rare nature of vocal cord palsy suggests laryngoscopy is not necessary for patients having surgery for PHPT. It may be reserved for patients with voice change and those having re-operative or concomitant thyroid surgery.

Use of methylene blue and near-infrared fluorescence in thyroid and parathyroid surgery.

PURPOSE: Intraoperative localisation and preservation of parathyroid glands improves outcomes following thyroid and parathyroid surgery. This can be facilitated by fluorescent imaging and methylene blue; a fluorophore is thought to be taken up avidly by parathyroid glands. This preliminary study aims to identify the optimum dose of methylene blue (MB), fluorescent patterns of thyroid and parathyroid glands and develop a protocol for the use of intravenous MB emitted fluorescence to enable parathyroid identification. METHODS: This is a phase 1b, interventional study (NCT02089542) involving 41 patients undergoing thyroid and/or parathyroid surgery. After exposure of the thyroid and/or parathyroid gland(s), intravenous boluses of between 0.05 and 0.5 mg/kg of MB were injected. Fluobeam® (a hand held fluorescence real-time imager) was used to record fluorescence from the operating field prior and up to 10 min following administration. RESULTS: The optimum dose of MB to visualise thyroid and parathyroid glands was 0.4 mg/kg body weight. The median time to onset of fluorescence was 23 and 22 s and the median time to peak fluorescence was 41.5 and 40 s, respectively. The peak fluorescence for thyroid and parathyroid glands compared to muscle were 2.6 and 4.3, respectively. Parathyroid auto-fluorescence prior to methylene blue injection was commonly observed. CONCLUSIONS: A clinical protocol for detection of fluorescence from MB during thyroid and parathyroid surgery is presented. Parathyroids (especially enlarged glands) fluoresce more intensely than thyroid glands. Auto-fluorescence may aid parathyroid detection, but MB fluorescence is needed to demonstrate viability.

Optimal Management of a Synchronous Diagnosis of Phaeochromocytoma and Colorectal Neoplasia.

The incidence rates of phaeochromocytoma and colorectal cancer (CRC) are approximately 1 and 65 per 100,000 per year, respectively. Simultaneous presentation of these conditions is rare and poses unique management challenges. We report on treatment strategies and clinical outcomes in a series of patients with colorectal neoplasia and phaeochromocytoma. Demographic and clinical details of four patients over a 4-year period were reviewed. The median (range) age at first presentation was 66 (52-70) years. Phaeochromocytoma (2.5-12.5 cm) was confirmed on biochemistry after incidental detection of an adrenal mass on CT scan-three had CT for staging of CRC and one had CT scan for weight loss. Adrenalectomy (three retroperitoneoscopic and one open procedure) was first performed after maximally tolerated alpha blockade; no significant complications were observed. Normalisation of biochemistry was confirmed and the patients then underwent colorectal surgery-laparoscopic right hemicolectomy, open right hemicolectomy (with further extensive surgery) for locally advanced cancer, laparoscopic low anterior resection and open high anterior resection. One respiratory infection and a seroma were the post-operative complications seen. In patients with a simultaneous diagnosis of phaeochromocytoma and CRC, surgical interventions should be staged. Adrenalectomy should first be performed to avoid haemodynamic instability during colorectal resection. A retroperitoneoscopic approach to the adrenal in patients with ipsilateral colonic tumours avoids transgressing the planes for colorectal resection. The synchronous diagnosis of these two rare conditions and the reported stimulatory effect of catecholamines on colorectal epithelia raise the possibility of an increased incidence of colorectal neoplasia in patients with phaeochromocytoma.

Effects of prolonged exposure to low dose metformin in thyroid cancer cell lines.

Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment. Some sub-types however have a poor prognosis. Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer). The proposed mechanisms include activation of the Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway and inhibition of the mTOR pathway (which promotes growth and proliferation). By inhibiting hepatic gluconeogenesis and increasing glucose uptake by muscles, metformin decreases blood glucose and circulating Insulin levels. Aims: Explore the effect of metformin on the growth and proliferation of thyroid cancer cell lines. Methods: The effects of metformin on thyroid cancer cell lines (FTC-133, K1E7, RO82-W-1, 8305C and TT) and normal thyroid follicular cells (Nthy-ori 3-1) were investigated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay for cell proliferation; clonogenic assays; FACS analysis for apoptosis and cell cycle, H2A.X phosphorylation (γH2AX) assay for DNA repair and scratch assay for cell migration. Results: Metformin inhibited cell proliferation and colony formation at 0.03 mM and above and inhibited cell migration at 0.3 mM. At concentrations of 0.1 mM and above metformin increased the percentage of apoptotic cells and induced cell cycle arrest in G0/G1 phase at minimum concentration of 0.3 mM. Unlike previous reports, no effect on DNA repair response was demonstrated. Conclusion: Metformin suppressed growth of all thyroid cancer cell lines, at concentrations considered to be within in the therapeutic range for diabetic patients on metformin (<0.3 mM).