Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

OBJECTIVE: Preoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual-isotope subtraction scintigraphy with 99m Tc-MIBI/123 Iodide using SPECT/CT and planar pinhole imaging (Di-SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11 C-Choline PET/CT (faster with a lower radiation dose) is non-inferior to Di-SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies. DESIGN: This is a prospective, GCP-controlled cohort study. PATIENTS AND MEASUREMENTS: One hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard. RESULTS: Among the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%-88%) and 87% (95% CI: 79%-92%) for Choline PET and Di-SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases. CONCLUSION: Choline PET and Di-SPECT performed equally well and are both appropriate as first-line imaging modalities for preoperative imaging of PHPT. When the first-line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

Locating hyperfunctioning parathyroid glands using 11C-Choline PET/CT: an inter- and intra-observer variation study.

BACKGROUND: Use of 11C-Choline PET/CT is gaining ground in detecting hyperfunctioning parathyroid glands in primary hyperparathyroidism. The purpose of this study was to evaluate the robustness of 11C-Choline PET/CT by assessing intra- and inter-observer agreement to determine whether the method was reader sensitive and therefore should only be performed at highly specialised sites with a high number of cases. PET/CT images of 40 patients diagnosed with primary hyperparathyroidism were anonymised and evaluated three times by three readers: an expert reader and two non-experts (non-experts were experienced in PET/CT imaging, but not in 11C-Choline PET/CT in the setting of primary hyperparathyroidism). Number of hyperfunctioning parathyroid glands, location relative to the thyroid gland and confidence of each assessment (low, moderate or high) were noted, and intra- and inter-observer agreement calculated using Fleiss' kappa method. Sensitivities and specificities of the non-experts were calculated using the expert reader as gold standard. RESULTS: Intra-observer agreement was 'good' to 'near perfect' for all readers. Inter-observer agreement was good between non-experts and the expert, with kappa values ≥ 0.74. Sensitivities between non-experts and the expert were high, > 81%, when assessing which side and 75% when assessing thyroid quadrant. All specificities were > 94%. Reader certainties were 'high' in > 80% of cases for the expert and > 70% and > 65%, respectively for the two non-experts. CONCLUSION: 11C-Choline PET/CT is not reader sensitive for the localisation of hyperfunctioning parathyroid glands and may therefore be safely implemented at sites that have a moderate number of cases. Access to a cyclotron laboratory is, however, a necessity for the production of 11C-Choline. The study was conducted in accordance with the Helsinki 2 declaration and The International Council for Harmonisation Guideline for Good Clinical Practice (ICH_GCP) clinical trial, approved by the Research Ethics Committee of the Capital Region of Denmark (Journal-nr.:H-18012490, date of approval: 18 June 2018) and the Danish Medicines Agency (EudraCT no. 2018-000726-63, date of approval: 6 June 2018). The GCP unit in Eastern Denmark has carried out regular monitoring of the trial according to GCP (ID: 2018-1050).

[Treatment for tongue-tie].

Ankyloglossia, or tongue-tie, is a congenital malformation, in which a short, lingual frenulum or a tight genioglossus muscle restricts tongue movement. In newborns, the reported prevalence is 2-11%. However, only 18% of newborns, in whom clinical findings suggest ankyloglossia, develop symptoms. Several randomised clinical trials report a significant reduction in maternal nipple pain after frenotomy. Frenotomy is a low-procedure surgery, but the benefits are sparsely documented. Parents should be presented with risk and benefits, before a frenotomy is offered.

[Tracheotomy].

The number of tracheotomies in Denmark has roughly tripled over the past 15 years. During this period, percutaneous dilatational tracheotomy has become still more common because of its easier accessibility, and it accounted for 66% of all tracheotomies in 2015 vs. 9% in 2000. However, due to the risk of fatal complications the method is only applicable when anatomical and medical conditions are favourable. Surgical tracheotomy is a safer method in some patients, and it is preferred if the patient has had a tracheostomy previously or presents with a difficult anatomy, coagulopathy or previous neck irradiation.

Long-term results using LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum.

The purpose of the present study was to evaluate the long-term results and patient's satisfaction of a new approach using the LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum (ZD) and to compare with other long-term results using traditional treatment modalities. Between December 2011 and August 2013, a total of 23 patients with ZD underwent endoscopic surgery using the LigaSure™ technique in our department. A retrospective evaluation of the surgery was based on medical records and additionally a long-term follow-up was performed using a standardized questionnaire that was send to all patients. The questions dealt with complaints according to a visual analog scale (VAS) and were sent a minimum of one year after the surgery (mean time 22 months, range 12-32 month). The overall response rate was 91%. The mean age of the patients was 69 years (range 37-89 years). The patients reported nine for overall satisfaction on the VAS (range 0-10: 10 being very content and 0 very uncontent, 25 and 75% quartiles: 7 and 10) regarding the final outcome of their surgery, although several of the patients had continuous symptoms within the first postoperative year. Eight patients (38%) reported no symptoms at all. Our results suggest that endoscopic management of ZD with the LigaSure™ 5 mm instrument is a minimally invasive, fast and safe method with solid long-term outcome with relief of symptoms and patient satisfaction. This new operative instrument was not found inferior to traditional endoscopic techniques and is now the standard treatment method for ZD in our departments.

A Prospective Comparative Study of Parathyroid Dual-Phase Scintigraphy, Dual-Isotope Subtraction Scintigraphy, 4D-CT, and Ultrasonography in Primary Hyperparathyroidism.

PURPOSE: Preoperative localization of the diseased parathyroid gland(s) in primary hyperparathyroidism allows for minimally invasive surgery. This study was designed to establish the optimal first-line preoperative imaging modality. PATIENTS AND METHODS: Ninety-one patients were studied consecutively in a prospective head-to-head comparison of dual isotope (Tc-MIBI vs I) subtraction parathyroid scintigraphy (PS), dual-phase PS, 4-dimensional (4D) CT, and ultrasonography (US). Surgery, histological confirmation, and postoperative normalization of Ca and parathyroid hormone were the reference standard. RESULTS: Ninety-seven hyperfunctioning parathyroid glands (HPGs) were identified by the reference standard. Sensitivity and specificity for subtraction PS, dual-phase PS, 4D-CT, and US were 93%, 65%, 58%, and 57% as well as 99%, 99.6%, 86%, and 95%, respectively. Interrater agreement was excellent for subtraction PS (κ = 0.96) while only fair for 4D-CT (κ = 0.34). Pinhole imaging and subtraction of delayed images (the latter especially in case of a nodular thyroid gland) increased the sensitivity of subtraction PS. SPECT/low-dose CT did not increase sensitivity but aided in the exact localization of the HPGs. Of 7 negative subtraction PS studies, 4D-CT and US were able to locate 3 and 1 additional HPGs, respectively. CONCLUSIONS: Dual isotope pinhole subtraction PS has higher diagnostic accuracy compared with dual-phase PS, 4D-CT, and US as a first-line imaging study in primary hyperparathyroidism. In case of a negative scintigraphy or suspicion of multiglandular disease, 4D-CT and/or US is recommended as a second-line modality. However, diagnostic algorithms should be adapted in accordance with local availability and expertise.

Preoperative localization of hyperfunctioning parathyroid glands with 4D-CT.

Primary hyperparathyroidism (pHPT) is almost exclusively the result of a solitary parathyroid adenoma. In most cases, the affected gland can be surgically removed, but precise preoperative imaging is essential for adenoma localization prior to surgical intervention. In this study, we evaluated the diagnostic value of four-dimensional computed tomography (4D-CT) as a preoperative imaging tool in relation to the localization of pathologic parathyroid glands in patients with pHPT and negative sestamibi scans. This study included 43 consecutive patients with pHPT referred for parathyroidectomy at the Department of Head and Neck Surgery of Copenhagen University Hospital Rigshospitalet in 2011 and 2012. All patients had a 4D-CT performed prior to parathyroidectomy. CT localization of the suspected adenoma was correlated to the actual surgical findings and subsequent histological diagnosis was also available as references for the accuracy of this imaging tool. Hyperfunctioning parathyroid glands were found in 40 patients. 4D-CT identified 32 solitary hyperfunctioning parathyroid glands located on the correct side of the neck (PPV 76 %) and 21 located within the correct quadrant (PPV 49 %). Unilateral resection was performed in 72 % of patients due to the localization findings of preoperative imaging. 4D-CT can, therefore, be considered an effective method for the preoperative localization of parathyroid adenomas and is an important tool in surgical intervention for patients referred to parathyroidectomy.

Harmonic focus in thyroidectomy for substernal goiter.

OBJECTIVES: No previous prospective study has evaluated harmonic scalpel in thyroidectomy for substernal goiter. The objective of this study was to evaluate the use of harmonic scalpel (FOCUS shear, Ethicon Endo-Surgery) in thyroidectomy for substernal goiter for blood loss, operative time, hospital stay and complications. MATERIALS AND METHODS: Prospective non-randomised study of 242 consecutive patients with substernal goiter out of 2258 patients (11%) who underwent thyroidectomy. A total of 121 patients had thyroidectomy performed with bipolar electrocoagulation and knot-tying techniques and 121 patients had harmonic scalpel thyroidectomy. RESULTS: The use of harmonic scalpel was associated with significant reduction in intraoperative blood loss (50 vs. 100mL, p=0.001), postoperative haemorrhage (4% vs. 12%, p=0.03) and length of hospital stay (2 vs. 3 days, p=0.001). The mean operative time was significantly longer in the harmonic group. CONCLUSION: Harmonic scalpel is a safe tool for thyroidectomy for substernal goiter. Its utilisation is associated with reduced blood loss, lower incidence of postoperative haemorrhage and shorter hospital stay.

New technique using LigaSure for endoscopic mucomyotomy of Zenker's diverticulum: diverticulotomy made easier.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to present a new approach for treatment of Zenker's diverticulum using the LigaSure (Covidien, Mansfield, MA) technique. STUDY DESIGN: A consecutive study with follow-up of 15 patients with Zenker's diverticulum endoscopically treated using the LigaSure. METHODS: All patients underwent an endoscopic division of the bridge between the esophagus and the diverticulum through a rigid diverticuloscope using the LigaSure. Variables such as demographics, symptoms, surgical details, complications, and outcome were collected during admission, and all patients were followed up 5 to 14 months after discharge. RESULTS: The median age of patients was 76 years. The diverticula measured between 2 and 7 cm. The median time of surgery was 33 minutes. All patients but one resumed oral intake within 24 hours. One patient experienced prolonged coughing and vomiting immediately postoperatively and was hours later diagnosed with a perforation. The patient was successfully treated with antibiotics. At follow-up this patient was on a normal diet. At follow-up after 2 to 8 weeks, all patients were relieved of their preoperative symptoms. At follow-up after 5 to 14 months, all but three had relief of all symptoms. Two patients had relapse of the diverticulum and one had relapse of a stricture known from before the diverticulotomy. CONCLUSIONS: Our results show that treating Zenker's diverticulum using the LigaSure instrument safely improves the patients condition. As a new operative instrument, the LigaSure technique constitutes in our opinion a valid and easy alternative for treatment of Zenker's diverticulum compared to other endoscopic techniques.

Risk factors for recurrent nerve palsy after thyroid surgery: a national study of patients treated at Danish departments of ENT Head and Neck Surgery.

Recurrent laryngeal nerve (RLN) injury is a well-known and serious complication to thyroid surgery. The objective was to estimate the frequency of post-thyroidectomy RLN palsy and to identify possible risk factors. Based on the Danish national thyroid surgery database, 6,859 patients treated with thyroid surgery from 1 January 2001 to the 31 December 2008 at the Danish departments of ENT-HNS were analyzed. Unilateral RLN palsy was found in 2.1 % and bilateral in 0.1 %. In benign histology, RLN palsies were registered in 1.3 %. Malignant histology and accordingly neck dissection were the most predominant risk factors with a relative risk (RR) of 5.4 and 5.8, respectively. In benign cases previous performed thyroid surgery had a RR of 10.4. High volume departments with more than 150 thyroid procedures per year seem to perform significantly better. Malignant histology, neck dissection and previous performed thyroid surgery are the strongest predictors for RLN palsy and patient information should be given accordingly. Incomplete resections should be reserved for isthmectomy only. Centralization of thyroid surgery in larger units might improve quality.

Papillary thyroid microcarcinoma in Denmark 1996-2008: a national study of epidemiology and clinical significance.

BACKGROUND: With an observed general rise in papillary thyroid carcinoma incidence, papillary microcarcinoma (PMC) is accordingly found more frequently and often incidentally by histological examination of surgical specimens from presumed benign thyroid disease. Only a few studies have specifically addressed the prognosis of incidentally found PMC, and they have been limited to retrospective single-center studies. METHODS: This was a national, unselected, prospective cohort study of 406 papillary thyroid microcarcinoma patients diagnosed in Denmark from 1996 to 2008. OBJECTIVE: The aim of this study was to evaluate incidence, outcome, and extent of necessary treatment, with special attention given to incidentally detected PMC. RESULTS: Age-standardized ratios were found to increase from 0.35 per 100,000 per year in 1996 to 0.74 per 100,000 per year in 2008. A total of 240 out of 406 cases were found incidentally, and a significant rise in incidence was only found for the incidental cases. Median follow-up was 7.6 years for the incidental cases, and in this time span, five cases of recurrence and no deaths from thyroid cancer occurred. The five-year recurrence-free survival was 98.1%, and only occurrence of lymph-node metastasis was found to affect the recurrence rate. A total of 160 incidental cases were initially treated with lobectomy, and the incidence of recurrence was not significantly different in the cases receiving completion thyroidectomy. CONCLUSION: The rising incidence of PMC in Denmark is explained by incidental cases. When the carcinoma is not the index tumor for surgery, this study implies that completion thyroidectomy does not improve prognosis.

[Treatment of peritonsillar abscess]. / Behandling af peritonsillær absces.

Peritonsillar abscess (PTA) is associated with high morbidity and can cause serious and life-threatening complications. In Denmark, the most commonly isolated bacteria are Fusobacterium necrophorum and Streptococcus pyogenes gr. A. The incidence of PTA in Denmark is 41/100,000/year, the highest incidence ever reported for PTA. There is no definite consensus on the treatment. We recommend most patients treated with puncture and antibiotics as outpatients, and if necessary acute tonsillectomy instead of interval tonsillectomy. Steroids may be of value.

[Minimally invasive surgery for hyperparathyroidism]. / Minimalt invasiv operation for hyperparathyroidisme.

INTRODUCTION: The traditional surgical approach for primary hyperparathyroidism (PHPT) involves a bilateral neck exploration to identify all parathyroid glands and remove the suspected pathological parathyroid gland(s). However, with improved preoperative imaging modalities and the use of perioperative measuring of PTH the unilateral minimal invasive approach has been introduced. The purpose of this study was to describe the results of minimal invasive parathyroidectomy. MATERIAL AND METHODS: A total of 116 consecutive patients underwent PHPT surgery (117 procedures) with a minimal invasive approach. RESULTS: A true positive sestamibi scintigraphy was found in 75 of 116 (65%) cases. A total of 80 patients (69%) underwent a unilateral surgical procedure and 56 patients (48%) minimally invasive surgery. In 113 of 117 procedures one or more pathological parathyroid glands were found. The median duration of the surgical procedure was 55 minutes and only 35 minutes for the minimal invasive approach. No permanent vocal cord paralysis was found. In two patients, persistent mild hypercalcaemia was encountered postoperatively and in a further patient recurrence was seen one year after. CONCLUSION: In our hands the success rate for focused minimal invasive surgery for the treatment of PHPT is equal to or better than results obtained by the traditional bilateral neck exploration. The minimally invasive approach is a less time-consuming and safe procedure with a low complication rate. Postoperative hypocalcaemia is rare and further advantages include improved cosmetic results and reduced surgical trauma.

Adenosquamous carcinoma of the larynx associated with necrotizing sialometaplasia--a diagnostic challenge.

Necrotizing sialometaplasia is a benign, self-limiting, inflammatory process involving salivary glands, commonly associated with tissue ischemia. Clinically, necrotizing sialometaplasia is most often found in the hard palate as a deep ulcer with raised, indurated edges that can be indolent. This, as well as the histopathologic findings of necrotizing sialometaplasia, can be confused with those of a malignant neoplasm. We report a rare case of necrotizing sialometaplasia in the larynx, probably initiated by an underlying malignant process. We suggest an aggressive diagnostic approach, when necrotizing sialometaplasia involves the larynx and no recent exposure to radiation, surgery or trauma has been recorded. Necrotizing sialometaplasia of the larynx should be regarded as secondary to malignancy until proven otherwise.