To block, or not to block is it still the question? Effectiveness of alpha- and beta-blockade in phaeochromocytoma surgery: an institutional analysis.

INTRODUCTION: Phaeochromocytomas/paraganglioma (PPGL) surgery was historically associated with significant risks of perioperative complications. The decreased mortality (<3.0%) had been attributed in part to optimal preoperative alpha-blockade. The value of alpha-blockade in decreasing morbidity is being challenged. The aim of our study is to present an institutional experience of preoperative alpha-blocking of PPGL and its effect on cardiovascular stability and postoperative morbidity. METHODS: A retrospective study using data from our institutional database was conducted. All patients undergoing adrenalectomy for PPGL from October 2011 to September 2020 were included. All patients were routinely alpha-blocked. Intraoperative cardiovascular instability (ICI) was assessed through number of systolic blood pressure (SBP) episodes >160mmHg, SBP <90mmHg, the need for vasoactive drugs and volume of intraoperative crystalloids administered. Morbidity was also evaluated. RESULTS: A total of 100 consecutive patients undergoing surgery were identified of whom 53 patients had complete anaesthetic records available for analysis. Thirty-two patients (60%) had at least one episode with an SBP >160mmHg. Nine (17%) cases had no intraoperative hypotensive episodes, while 3 (6%) patients had >10 intraoperative episodes of an SBP <90mmHg. Twenty-one (40%) patients received vasoactive drugs during surgery. The median volume of intraoperative crystalloids was 2 litres (1-4). Postoperatively, no patient experienced cardiovascular complications, including arrhythmia or myocardial ischaemia. Only two were admitted to an intensive care unit (ICU) and one 30-day readmission occurred. CONCLUSIONS: Cardiac instability remained significant in PPGL surgery despite optimal alpha- and beta-blockade. While omitting blockade would appear empirically questionable, a randomised controlled trial (RCT) of surgery with and without alpha-blockade will provide an answer.

To block, or not to block is it still the question? Effectiveness of alpha- and beta-blockade in phaeochromocytoma surgery: an institutional analysis.

INTRODUCTION: Phaeochromocytomas/paraganglioma (PPGL) surgery was historically associated with significant risks of perioperative complications. The decreased mortality (<3.0%) had been attributed in part to optimal preoperative alpha-blockade. The value of alpha-blockade in decreasing morbidity is being challenged. The aim of our study is to present an institutional experience of preoperative alpha-blocking of PPGL and its effect on cardiovascular stability and postoperative morbidity. METHODS: A retrospective study using data from our institutional database was conducted. All patients undergoing adrenalectomy for PPGL from October 2011 to September 2020 were included. All patients were routinely alpha-blocked. Intraoperative cardiovascular instability (ICI) was assessed through number of systolic blood pressure (SBP) episodes >160mmHg, SBP <90mmHg, the need for vasoactive drugs and volume of intraoperative crystalloids administered. Morbidity was also evaluated. RESULTS: A total of 100 consecutive patients undergoing surgery were identified of whom 53 patients had complete anaesthetic records available for analysis. Thirty-two patients (60%) had at least one episode with an SBP >160mmHg. Nine (17%) cases had no intraoperative hypotensive episodes, while 3 (6%) patients had >10 intraoperative episodes of an SBP <90mmHg. Twenty-one (40%) patients received vasoactive drugs during surgery. The median volume of intraoperative crystalloids was 2 litres (1-4). Postoperatively, no patient experienced cardiovascular complications, including arrhythmia or myocardial ischaemia. Only two were admitted to an intensive care unit (ICU) and one 30-day readmission occurred. CONCLUSIONS: Cardiac instability remained significant in PPGL surgery despite optimal alpha- and beta-blockade. While omitting blockade would appear empirically questionable, a randomised controlled trial (RCT) of surgery with and without alpha-blockade will provide an answer.

The PanSurg-PREDICT Study: Endocrine Surgery During the COVID-19 Pandemic.

BACKGROUND: In the midst of the COVID-19 pandemic, patients have continued to present with endocrine (surgical) pathology in an environment depleted of resources. This study investigated how the pandemic affected endocrine surgery practice. METHODS: PanSurg-PREDICT is an international, multicentre, prospective, observational cohort study of emergency and elective surgical patients in secondary/tertiary care during the pandemic. PREDICT-Endocrine collected endocrine-specific data alongside demographics, COVID-19 and outcome data from 11-3-2020 to 13-9-2020. RESULTS: A total of 380 endocrine surgery patients (19 centres, 12 countries) were analysed (224 thyroidectomies, 116 parathyroidectomies, 40 adrenalectomies). Ninety-seven percent were elective, and 63% needed surgery within 4 weeks. Eight percent were initially deferred but had surgery during the pandemic; less than 1% percent was deferred for more than 6 months. Decision-making was affected by capacity, COVID-19 status or the pandemic in 17%, 5% and 7% of cases. Indication was cancer/worrying lesion in 61% of thyroidectomies and 73% of adrenalectomies and calcium 2.80 mmol/l or greater in 50% of parathyroidectomies. COVID-19 status was unknown at presentation in 92% and remained unknown before surgery in 30%. Two-thirds were asked to self-isolate before surgery. There was one COVID-19-related ICU admission and no mortalities. Consultant-delivered care occurred in a majority (anaesthetist 96%, primary surgeon 76%). Post-operative vocal cord check was reported in only 14% of neck endocrine operations. Both of these observations are likely to reflect modification of practice due to the pandemic. CONCLUSION: The COVID-19 pandemic has affected endocrine surgical decision-making, case mix and personnel delivering care. Significant variation was seen in COVID-19 risk mitigation measures. COVID-19-related complications were uncommon. This analysis demonstrates the safety of endocrine surgery during this pandemic.

Post-thyroidectomy bleeding: analysis of risk factors from a national registry.

BACKGROUND: Post-thyroidectomy haemorrhage occurs in 1-2 per cent of patients, one-quarter requiring bedside clot evacuation. Owing to the risk of life-threatening haemorrhage, previous British Association of Endocrine and Thyroid Surgeons (BAETS) guidance has been that day-case thyroidectomy could not be endorsed. This study aimed to review the best currently available UK data to evaluate a recent change in this recommendation. METHODS: The UK Registry of Endocrine and Thyroid Surgery was analysed to determine the incidence of and risk factors for post-thyroidectomy haemorrhage from 2004 to 2018. RESULTS: Reoperation for bleeding occurred in 1.2 per cent (449 of 39 014) of all thyroidectomies. In multivariable analysis male sex, increasing age, redo surgery, retrosternal goitre and total thyroidectomy were significantly correlated with an increased risk of reoperation for bleeding, and surgeon monthly thyroidectomy rate correlated with a decreased risk. Estimation of variation in bleeding risk from these predictors gave low pseudo-R2 values, suggesting that bleeding is unpredictable. Reoperation for bleeding occurred in 0.9 per cent (217 of 24 700) of hemithyroidectomies, with male sex, increasing age, decreasing surgeon volume and redo surgery being risk factors. The mortality rate following thyroidectomy was 0.1 per cent (23 of 38 740). In a multivariable model including reoperation for bleeding node dissection and age were significant risk factors for mortality. CONCLUSION: The highest risk for bleeding occurred following total thyroidectomy in men, but overall bleeding was unpredictable. In hemithyroidectomy increasing surgeon thyroidectomy volume reduces bleeding risk. This analysis supports the revised BAETS recommendation to restrict day-case thyroid surgery to hemithyroidectomy performed by high-volume surgeons, with caution in the elderly, men, patients with retrosternal goitres, and those undergoing redo surgery.

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations.

INTRODUCTION: Reoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies. MATERIALS AND METHODS: Retrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B). RESULTS: From over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B. CONCLUSION: Optimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.

Video-assisted thoracoscopic surgery for ectopic mediastinal parathyroid adenoma.

Background: Primary hyperparathyroidism (PHPT), caused by an ectopic mediastinal parathyroid adenoma, is uncommon. In the past, when the adenoma was not accessible from the neck, median sternotomy was advocated for safe and successful parathyroidectomy. Video-assisted thoracoscopic surgical (VATS) parathyroidectomy represents a modern alternative approach to this problem. Methods: Information on patients undergoing VATS was obtained from a specific database, including clinical presentation, biochemistry, preoperative imaging, surgical approach and patient outcomes. A comprehensive literature review was undertaken to draw comparisons with other publications. Results: Over a 2-year period, nine patients underwent VATS parathyroidectomy for sporadic PHPT. Five patients had persistent PHPT following previous unsuccessful parathyroidectomy via cervicotomy, and four had had no previous parathyroid surgery. The median duration of surgery was 90 (range 60-160) min. Eight patients were cured biochemically, with no major complications. One patient required conversion to a median sternotomy for removal of a thymoma that had resulted in false-positive preoperative imaging. Conclusion: With appropriate preoperative imaging, multidisciplinary input and expertise, VATS parathyroidectomy is an effective, safe and well tolerated approach to ectopic mediastinal parathyroid adenoma.

Antecedentes: El hiperparatiroidismo primario (primary hyperparathyroidism, pHPT) causado por un adenoma paratiroideo ectópico mediastínico es infrecuente. Hace años, cuando un adenoma no era accesible por vía cervical se propugnaba una esternotomía media para efectuar una paratiroidectomía segura y con éxito. La paratiroidectomía por cirugía toracoscópica asistida por video (video­assisted thoracoscopic surgical, VATS) es una alternativa moderna para el abordaje de esta patología. Métodos: La información de los pacientes tratados con VATS se obtuvo de una base de datos específica, incluyendo presentación clínica, bioquímica, radiología preoperatoria, abordaje quirúrgico y resultados de los pacientes. Se efectuó una revisión extensa de la literatura para efectuar comparaciones con otras publicaciones. Resultados: Durante un periodo de 2 años, 9 pacientes fueron tratados mediante paratiroidectomía por VATS debido a un pHPT esporádico, de los cuales 5 presentaban pHPT persistente después del fracaso de una paratiroidectomía por cervicotomía, mientras que los 4 restantes no habían sido operados previamente de cirugía paratiroidea. El tiempo medio operatorio fue de 101 minutos (rango 60­160). Ocho pacientes se curaron bioquímicamente, sin ninguna complicación mayor. Un paciente precisó conversión a una esternotomía media para extirpar un timoma que había sido un falso positivo en la radiología preoperatoria. Conclusión: La paratiroidectomía por VATS es una intervención efectiva, segura y bien tolerada para la extirpación de un adenoma ectópico mediastínico, siempre y cuando se disponga de radiología preoperatoria adecuada, equipo multidisciplinar y experiencia.

Does fluoroscopy prevent inadvertent parathyroidectomy in thyroid surgery?

INTRODUCTION: Near-infrared imaging may facilitate intraoperative identification of parathyroid glands by causing autofluorescence but its clinical value has not been established. Inadvertent parathyroidectomy occurs in 5-22% of thyroidectomies and is associated with temporary and permanent hypoparathyroidism. The aim of this study was to determine whether near-infrared imaging prevents inadvertent parathyroidectomy and early hypocalcaemia as a surrogate for permanent hypoparathyroidism. MATERIALS AND METHODS: Near-infrared imaging was used in a prospective cohort of consecutive thyroidectomies. Thyroidectomies performed prior to the introduction of near-infrared imaging formed a control group. The thyroid bed and specimen were scanned with near-infrared imaging. Areas of autofluorescence on the specimen were examined and any parathyroid tissue found was autotransplanted. Inadvertent parathyroidectomy was therefore recorded as established intraoperatively by near-infrared imaging (allowing autotransplantation) or on subsequent histology (missed). Serum calcium and parathyroid hormone were measured on day one and at two weeks and six months postoperatively. RESULTS: A total of 269 patients were included: 106 near-infrared imaging and 163 controls. Inadvertent parathyroidectomy was detected by near-infrared imaging in two (and autotransplantation performed) and histologically (i.e. missed by near-infrared imaging in 13, 12.3% vs 17, 10.4% controls). Neither result was statistically significant (P = 0.08, 0.89). There was no significant difference in serum calcium or parathyroid hormone between near-infrared imaging and control groups at one day, two weeks or thereafter. DISCUSSION: Near-infrared imaging may detect inadvertent parathyroidectomy and may allow autotransplantation. It did not, however, reduce the incidence of missed inadvertent parathyroidectomy and no difference was seen in early hypocalcaemia or late hypoparathyroidism. Current near-infrared imaging technology does not appear to confer a clinical benefit sufficient to justify its use.

Patterns of disease in patients at a tertiary referral centre requiring reoperative parathyroidectomy.

INTRODUCTION: Reoperative parathyroidectomy is required when there is persistent or recurrent hyperparathyroidism following the initial surgery (at least 5% of parathyroidectomies nationally). By convention, 'persistent disease' is defined as the situation where the patient has not been cured by the first operation. The term 'recurrent hyperparathyroidism' is used when the patient was confirmed to be biochemically cured for six months from the first operation but has hyperparathyroidism after this date. Reoperative surgery is associated with higher rates of postoperative complications as well as a greater rate of failure to cure. The aim of our study was to review our departmental experience of reoperative parathyroidectomy, with a view to identify patterns of disease persistence and recurrence. METHODS: Using a departmental database, patients were identified who had undergone reoperative parathyroidectomy between 2006 and 2014. All the pre, intra and postoperative information was documented including the operative note so as to record the location of the abnormal parathyroid gland found at reoperation. RESULTS: Almost two-thirds (63%) of patients had negative, equivocal or discordant conventional imaging so secondary investigative tools were required frequently. The majority of abnormal glands were found in eutopic locations. The most common locations for ectopic glands were intrathyroidal, mediastinal and intrathymic. A third (33%) of the patients had multigland disease and over a quarter (28%) had coexisting thyroid disease. CONCLUSIONS: Persistent hyperparathyroidism represents a challenging patient subgroup for which access to all radiological modalities and intraoperative parathyroid hormone monitoring are required. Patient selection for reintervention is a key determinant in the reoperation cure rate.

Comparison of the utility of Cocaine- and Amphetamine-Regulated Transcript (CART), chromogranin A, and chromogranin B in neuroendocrine tumor diagnosis and assessment of disease progression.

CONTEXT: Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker. DESIGN AND PARTICIPANTS: Circulating levels of CART peptide and the established NET markers chromogranin A (CgA) and chromogranin B (CgB) were measured using RIA in 353 patients with NET (normal renal function) and in controls. Clinical data were collected retrospectively. MAIN OUTCOME MEASURE(S): The comparative and combined utility of CART, CgA, and CgB for diagnosis and assessment of disease progression was measured in different NET subtypes. RESULTS: CgA and CgB in combination improved diagnostic accuracy in patients with gut NETs, nongastroenteropancreatic NETs, and NETs with an unknown primary origin compared with each biomarker alone. Measuring CART did not further improve diagnosis in these NET subtypes. For pancreatic NETs, CgB was superior to CgA and CART in detecting stable disease (P < .007), whereas CgA and CART in combination were most effective in identifying progressive disease. In phaeochromocytomas/paragangliomas (PCC/PGL), CART was the most useful biomarker for identifying stable (P < .001) and progressive (P = .001) disease. Consistent with this, plasma CART decreased following PCC/PGL tumor resection, remaining low in all patients in remission, but increasing in those with progressive disease. CONCLUSIONS: CART is a useful marker for identifying progressive pancreatic NETs. CART is superior to CgA and CgB in detecting stable and progressive PCC/PGLs, and may have a role as a surveillance marker for PCC/PGL patients.

Do flow volume loops alter surgical management in patients with a goitre?

INTRODUCTION: Flow volume loops (FVLs) are considered part of the workup of patients with thyroid enlargement presenting to the endocrinology clinic. They are used to detect upper airway obstruction (UAO) secondary to tracheal compression (TC) from a goitre. Surgical assessment in contrast tends to focus on clinical evaluation supplemented when required by imaging. The aim of this study was to investigate whether FVLs influence the decision to operate in patients with a goitre. METHODS: We identified patients with a goitre referred by the department of endocrinology for FVLs between 2006 and 2011. The results of the FVL were collated, and their impact on patient management was assessed. RESULTS: Ninety-six patients were referred for FVL. In 38 patients, the indication was specifically to evaluate the effects of a goitre. Of these, 33 were reported as normal. Five FVLs were reported as abnormal (3 suggesting lung pathology and 2 TC). Both patients with TC on FVL presented no CT evidence of TC and underwent surgery due to abnormal cytology. Of the 33 normal FVLs, 7 underwent surgery: 2 for local compression, 4 for abnormal cytology and 1 for Graves' disease. None of the FVLs influenced the decision to operate. CONCLUSION: FVLs may detect subradiological TC, but rarely influence management in patients with a goitre. In view of this and the cost of £235 per investigation, FVL should be reserved for goitre patients with suspected primary lung pathology, where the distinction between large and small airway compression is likely to influence management.

(18)F-FDG uptake at initial staging of the adrenocortical cancers: a diagnostic tool but not of prognostic value.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. (18)F-FDG PET ((18)F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, (18)F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative (18)F-FDG PET based on SUVs assessments has a prognostic value in ACC patients. METHODS: A retrospective analysis was performed in patients who underwent (18)F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; (18)F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All (18)F-FDG PET/CT procedures were reinterpreted in a blind fashion. RESULTS: Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)(max) = 11 (range: 3-56) and a tumor/liver SUV(max) ratio = 4.2 (range: 1.3-15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. (18)F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis. CONCLUSIONS: At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.

Systematic review and meta-analysis of retroperitoneoscopic versus laparoscopic adrenalectomy.

BACKGROUND: Laparoscopic adrenalectomy (LA) has replaced open adrenalectomy as the standard operation for non-malignant adrenal tumours. Retroperitoneoscopic adrenalectomy (RA) is an increasingly popular alternative minimally invasive approach. Advocates of each technique claim its superiority, but the issue has yet to be resolved and conclusions are complicated by the existence of a lateral (LRA) and true posterior (PRA) RA. METHODS: A literature search was performed for all comparative studies of RA versus LA. Meta-analysis was performed according to PRISMA guidelines. Odds ratios and standardized mean differences (SMD) were used to compare dichotomous and continuous outcomes respectively. RESULTS: Twenty-two studies were included, reporting on 1257 LAs, 471 LRAs and 238 PRAs. Both PRA and LRA were associated with a reduced length of hospital stay: SMD - 1·45 (95 per cent confidence interval - 2·76 to - 0·14) and - 0·54 (-1·04 to - 0·03) days respectively compared with LA. Interstudy heterogeneity was present throughout the comparisons of hospital stay. When considering only the two randomized clinical trials (RCTs) there was no statistically significant difference in this outcome. One RCT, however, found a reduction in the median time to convalescence of 2·4 weeks in the LRA group. There were no differences in duration of operation, blood loss, time to ambulation and oral intake, or complication rates between techniques. CONCLUSION: RA overall has equivalent outcomes to LA but may be associated with a shorter hospital stay.

Serum phosphate predicts temporary hypocalcaemia following thyroidectomy.

BACKGROUND: Temporary hypocalcaemia occurs in up to 40% of patients following a total thyroidectomy. Serum calcium and parathyroid hormone (PTH) measurements are currently used to predict post-thyroidectomy hypocalcaemia. However, immediate access to PTH measurement is expensive and not widely available. Serum phosphate responds rapidly to changes in circulating PTH levels, and its measurement is readily available in all hospitals. We evaluated the use of serum phosphate to predict temporary hypocalcaemia post-thyroidectomy. METHODS: We retrospectively assessed 111 consecutive patients who had total or completion thyroidectomy. Patients had serum calcium and phosphate measured preoperatively, on the evening of surgery (day 0), on the morning of day 1 and over the following week as clinically indicated. Serum PTH was measured on the morning of day 1. Vitamin D levels were measured preoperatively. RESULTS: Seventy-six patients did not develop treatment-demanding hypocalcaemia. In these patients, the mean serum phosphate concentration was lower on the morning of day 1 compared to that on the evening of surgery. Seventeen patients with a vitamin D>25 nmol/l developed hypocalcaemia requiring treatment from day 1 onwards. All had an overnight rise in serum phosphate to >1.44 mmol/l (100% sensitivity and specificity for predicting hypocalcaemia). Twelve patients who had a vitamin D<25 nmol/l also developed hypocalcaemia but had an attenuated rise in serum phosphate. CONCLUSION: Serum phosphate is a reliable biochemical predictor of post-thyroidectomy hypocalcaemia in patients without vitamin D deficiency. The use of serum phosphate may facilitate safe day 1 discharge of patients undergoing thyroidectomy.

Comparison of [¹¹¹In]pentetreotide-SPECT and [¹8F]FDOPA-PET in the localization of extra-adrenal paragangliomas: the case for a patient-tailored use of nuclear imaging modalities.

AIMS AND METHODS: The aim of this prospective study was to compare the diagnostic value of [¹8F]FDOPA-PET and [¹¹¹In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [¹8F]FDOPA-PET. ¹³¹I-MIBG and [¹8F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [¹8F]FDOPA-PET. RESULTS: SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [¹8F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and ¹8F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [¹8F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [¹³¹I]MIBG and [¹8F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm (P = 0·002) and abdominal lesions (P = 0·031) were independently associated with "[¹8F]FDOPA-PET diagnosis only". In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size (P = 0·001). CONCLUSIONS: The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [¹8F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [¹8F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery).

Tumor protein p53-induced nuclear protein (TP53INP1) expression in medullary thyroid carcinoma: a molecular guide to the optimal extent of surgery?

BACKGROUND: Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent. METHODS: Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears. RESULTS: TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts. CONCLUSIONS: TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.

Limited value of 18F-F-DOPA PET to localize pancreatic insulin-secreting tumors in adults with hyperinsulinemic hypoglycemia.

CONTEXT: Fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-FDOPA PET) imaging is increasingly used in the workup of neuroendocrine tumors. It has been shown to be an accurate tool in the diagnosis of congenital hyperinsulinism, but limited information is available on its value in adult disease. OBJECTIVE, PATIENTS, AND DESIGN: The objective of this study was to review our experience with 18F-FDOPA PET imaging in six consecutive patients with hyperinsulinemic hypoglycemia (HH) (four solitary insulinomas, one diffuse beta-cell hyperplasia, one malignant insulinoma). 18F-FDOPA uptake was also evaluated in 37 patients (43 procedures) without HH or other pancreatic neuroendocrine tumors, which acted as a control group. RESULTS: Using visual analysis, 18F-FDOPA-PET proved positive in only one case (a multiple endocrine neoplasia type 1 related insulinoma). In diffuse beta-cell hyperplasia, the pancreatic uptake was similar to controls. In the patient with liver metastases, the extent of disease was underestimated. The pancreatic uptake was not statistically different between controls and hyperinsulinemic patients. The main limitation for identifying insulinomas or beta-cell hyperplasia in adults appears to be to the 18F-FDOPA uptake and retention in the whole pancreas. This drawback is potentially circumvented in focal hyperplasia in newborns due to a lower aromatic amino acid decarboxylase expression in the extralesional pancreatic parenchyma. CONCLUSIONS: 18F-FDOPA PET is of limited value in localizing pancreatic insulin secreting tumors in adult HH. Our results contrast with the referential study and require further analysis.

Adrenal incidentaloma in familial adenomatous polyposis: a long-term follow-up study and schema for management.

PURPOSE: Adrenal incidentaloma is often diagnosed in patients with familial adenomatous polyposis, because they frequently undergo abdominal imaging and have a raised incidence of adrenal incidentaloma. This study investigates the natural history of adrenal incidentaloma in familial adenomatous polyposis, and suggests a schema for management. METHODS: An original cohort of 14 familial adenomatous polyposis patients with adrenal incidentaloma, identified prospectively 12 years ago, was followed up clinically and radiologically. A further group of 16 patients was also identified. All had lesions >1 cm. For both cohorts, characteristics of patients (genotype, age at diagnosis, concomitant diagnoses) and incidentaloma (size, laterality, rate of growth, outcome) are described. RESULTS: Overall, 3 of 30 patients underwent adrenalectomy; one patient had pheochromocytoma and another had an adenoma of borderline malignancy. A further three lesions were radiologically suspicious for malignancy at the time of diagnosis; one was in a patient who was unfit for surgery but died of nonadrenal causes after nine years. None of the lesions radiologically benign at diagnosis showed an aggressive course, but one patient required referral for surgery after 12 years because of a slow increase in size of the lesion. There were no associations with genotype. CONCLUSIONS: Familial adenomatous polyposis-associated adrenal incidentaloma may warrant long-term follow-up. Although the natural history is similar to lesions occurring sporadically, these patients have concomitant familial adenomatous polyposis-associated manifestations under radiologic surveillance. In this rare condition, development of a robust protocol will require evidence from worldwide patient cohorts. However, a tailored schema is suggested as a consistent basis for future modification.

Does 18F-FDG PET/CT add diagnostic accuracy in incidentally identified non-secreting adrenal tumours?

PURPOSE: The widespread use of high-resolution cross-sectional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) for the investigation of the abdomen is associated with an increasing detection of incidental adrenal masses. We evaluated the ability of (18)F-fluorodeoxyglucose positron emission tomography to distinguish benign from malignant adrenal masses when CT or MRI results had been inconclusive. METHODS: We included only patients with no evidence of hormonal hypersecretion and no personal history of cancer or in whom previously diagnosed cancer was in prolonged remission. PET/CT scans were acquired after 90 min (mean, range 60-140 min) after FDG injection. The visual interpretation, maximum standardised uptake values (SUVmax) and adrenal compared to liver uptake ratio were correlated with the final histological diagnosis or clinico-radiological follow-up when surgery had not been performed. RESULTS: Thirty-seven patients with 41 adrenal masses were prospectively evaluated. The final diagnosis was 12 malignant, 17 benign tumours, and 12 tumours classified as benign on follow-up. The visual interpretation was more accurate than SUVmax alone, tumour diameter or unenhanced density, with a sensitivity of 100% (12/12), a specificity of 86% (25/29) and a negative predictive value of 100% (25/25). The use of 1.8 as the threshold for tumour/liver SUVmax ratio, retrospectively established, demonstrated 100% sensitivity and specificity. CONCLUSION: FDG PET/CT accurately characterises adrenal tumours, with an excellent sensitivity and negative predictive values. Thus, a negative PET may predict a benign tumour that would potentially prevent the need for surgery of adrenal tumours with inconclusive conventional imaging.