Rare Thyroid Diseases Mimicking or Concealing Primitive Thyroid Neoplasms: A Call for a "Check and Double-Check" Clinical Mindset.

Clinical endocrinologists encounter in their practice patients with thyroid diseases on a daily basis. Still, diagnosis of rare structural thyroid disorders can be quite challenging. In some instances, they do not only impersonate but can also conceal, other conditions such as thyroid carcinomas. We describe a series of patients with structural thyroid disorders including 1) anaplastic thyroid carcinoma initially presenting with features of thyroid abscess; 2) unicentric hyaline vascular Castleman's disease of the thyroid embedded in a stroma of papillary thyroid carcinoma; and 3) primary thyroid lymphoma with a rapid and fulminant evolution. The common challenge in the diagnosis of these cases lies in both their low incidence and their complex presentation. We use the presentation of these cases to raise the attention related to their identification. We highlight the need for precision diagnosis to enable a patient-tailored management approach and improve patient outcomes.

Phase II Trial Assessing the Repeatability and Tumor Uptake of [68Ga]Ga-HER2 Single-Domain Antibody PET/CT in Patients with Breast Carcinoma.

Human epidermal growth factor receptor 2 (HER2) status is used for decision-making in breast carcinoma treatment. The status is obtained through immunohistochemistry or in situ hybridization. These two methods have the disadvantage of necessitating tissue sampling, which is prone to error due to tumor heterogeneity or interobserver variability. Whole-body imaging might be a solution to map HER2 expression throughout the body. Methods: Twenty patients with locally advanced or metastatic breast carcinoma (5 HER2-positive and 15 HER2-negative patients) were included in this phase II trial to assess the repeatability of uptake quantification and the extended safety of the [68Ga]Ga-NOTA-anti-HER2 single-domain antibody (sdAb). The tracer was injected, followed by a PET/CT scan at 90 min. Within 8 d, the procedure was repeated. Blood samples were taken for antidrug antibody (ADA) assessment and liquid biopsies. On available tissues, immunohistochemistry, in situ hybridization, and mass spectrometry were performed to determine the correlation of HER2 status with uptake values measured on PET. If relevant preexisting [18F]FDG PET/CT images were available (performed as standard of care), a comparison was made. Results: With a repeatability coefficient of 21.8%, this imaging technique was repeatable. No clear correlation between PET/CT uptake values and pathology could be established, as even patients with low levels of HER2 expression showed moderate to high uptake. Comparison with [18F]FDG PET/CT in 16 patients demonstrated that in 7 patients, [68Ga]Ga-NOTA-anti-HER2 shows interlesional heterogeneity within the same patient, and [18F]FDG uptake did not show the same heterogeneous uptake in all patients. In some patients, the extent of disease was clearer with the [68Ga]Ga-NOTA-anti-HER2-sdAb. Sixteen adverse events were reported but all without a clear relationship to the tracer. Three patients with preexisting ADAs did not show adverse reactions. No new ADAs developed. Conclusion: [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT imaging shows similar repeatability to [18F]FDG. It is safe for clinical use. There is tracer uptake in cancer lesions, even in patients previously determined to be HER2-low or -negative. The tracer shows potential in the assessment of interlesional heterogeneity of HER2 expression. In a subset of patients, [68Ga]Ga-NOTA-anti-HER2-sdAb uptake was seen in lesions with no or low [18F]FDG uptake. These findings support further clinical development of [68Ga]Ga-NOTA-anti-HER2-sdAb as a PET/CT tracer in breast cancer patients.

Breast cancer preoperative 18FDG-PET, overall survival prognostic separation compared with the lymph node ratio.

PURPOSE: To evaluate the overall survival prognostic value of preoperative 18F-fluorodeoxyglucose positron emission tomography (PET) in breast cancer, as compared with the lymph node ratio (LNR). METHODS: Data were abstracted at a median follow-up 14.7 years from a retrospective cohort of 104 patients who underwent PET imaging before curative surgery. PET-Axillary|Sternal was classified as PET-positive if hypermetabolism was visualized in ipsilateral nodal axillary and/or sternal region, else as PET-negative. The differences of 15 years restricted mean survival time ∆RMST according to PET and LNR were computed from Kaplan-Meier overall survival. The effect of PET and other patients' characteristics was analyzed through rankit normalization, which provides with Cox regression the Royston-Sauerbrei D measure of separation to compare the characteristics (0 indicating no prognostic value). Multivariate analysis of the normalized characteristics used stepwise selection with the Akaike information criterion. RESULTS: In Kaplan-Meier analysis, LNR > 0.20 versus ≤ 0.20 showed ∆RMST = 3.4 years, P = 0.003. PET-Axillary|Sternal positivity versus PET-negative showed a ∆RMST = 2.6 years, P = 0.008. In Cox univariate analyses, LNR appeared as topmost prognostic separator, D = 1.50, P < 0.001. PET ranked below but was also highly significant, D = 1.02, P = 0.009. In multivariate analyses, LNR and PET-Axillary|Sternal were colinear and mutually exclusive. PET-Axillary|Sternal improved as prognosticator in a model excluding lymph nodes, yielding a normalized hazard ratio of 2.44, P = 0.062. CONCLUSION: Pathological lymph node assessment remains the gold standard of prognosis. However, PET appears as a valuable surrogate in univariate analysis at 15-year follow-up. There was a trend towards significance in multivariate analysis that warrants further investigation.

Percutaneous tracheostomy for long-term ventilated COVID-19-patients: rationale and first clinical-safe for all-experience.

INTRODUCTION: COVID-19 infection has resulted in thousands of critically ill patients admitted to ICUs and treated with mechanical ventilation. Percutaneous tracheostomy is a well-known technique utilised as a strategy to wean critically ill patients from mechanical ventilation. Worldwide differences exist in terms of methods, operators, and settings, and questions remain regarding timing and indications. If tracheostomy is to be performed in COVID-19 patients, a safe environment is needed for optimal care. MATERIAL AND METHODS: We present a guidewire dilating forceps tracheostomy procedure in COVID-19 patients that was optimised including apnoea-moments, protective clothing, checklists, and clear protocols. We performed a retrospective analysis of the outcome after tracheostomy in COVID-19 patients between March 2020 and May 2020. RESULTS: The follow-up of the first 16 patients, median age 62 years, revealed a median intubation time until tracheostomy of 18 days and median cannulation time of 20 days. The overall perioperative complication rate and complication rate while cannulated was 19%, mainly superficial bleeding. None of the healthcare providers involved in performing the procedure developed any symptoms of the disease. CONCLUSIONS: This COVID-19-centred strategy based on flexibility, preparation, and cooperation between healthcare providers with different backgrounds facilitated percutaneous tracheostomy in COVID-19 patients without an increase in the overall complication rate or evidence of risk to healthcare providers. Our findings provide initial evidence that tracheostomy can be performed safely as a standard of care for COVID-19 patients requiring prolonged mechanical ventilation as was standard practice in ICU patients prior to the COVID-19 pandemic to promote ventilator weaning and patient recovery.

Intrathyroidal parathyroid carcinoma presenting as an asymptomatic hypercalcemia: a case report.

INTRODUCTION: A 26-year-old female presented with severe hypercalcemia. She was asymptomatic. Blood analysis revealed high serum calcium (13 mg/dL = 3.25 mmol/L) and elevated intact parathyroid hormone (iPTH) levels (267.5 ng/L). RESULTS: Ultrasonography showed a mixed solid-cystic nodule of 30 mm in the left thyroid lower lobe and a nodular lesion of 14 mm posterior of the thyroid upper pole suggestive for parathyroid adenoma. Sestamibi scan and magnetic resonance imaging (MRI) revealed hyperfunctioning parathyroid tissue posterior of the left thyroid upper lobe. During surgery, a 15 mm nodule in the usual location of the left superior parathyroid was resected. Intraoperative frozen section revealed normal parathyroid tissue and intraoperative PTH levels did not decrease. Left thyroidectomy was performed due to the large solid-cystic nodule. Intraoperative PTH levels normalized 10 min later. Pathologic examination revealed a 28 mm nodule in the lower thyroid pole compatible with a parathyroid carcinoma (PC). Due to positive margins, a completion thyroidectomy was performed. 5-year follow-up showed no recurrence. CONCLUSIONS: PC is a rare entity comprising 0.5-2% of patients with primary hyperparathyroidism. Even more unusual is an intrathyroidal parathyroid gland (0.2%). Only a dozen cases of intrathyroidal PC have been reported. Our case is the second patient reported to be asymptomatic.

An air-containing mediastinal mass in a patient with a primary adenocarcinoma of the right lung.

Objective: The following case report elicits the treatment of a 55-year-old male who was diagnosed with a surinfected mediastinal chyloma as a complication of mediastinoscopy and radiotherapy for a primary adenocarcinoma of the right lung (cT2aN2M0). Methods: The patient was admitted to the hospital after radiographical imaging showed a surinfected mediastinal chyloma. CT-guided percutaneous drainage was performed and via gastroscopy a fistula was diagnosed for which a full covered stent was placed. Then, a right thoracotomy was performed to wash out the chylous cavity, to seal the thoracic duct and to cover the other end of the fistula with an intercostal muscle flap. Results: Postoperative imaging showed a clear reduction of the mediastinal mass with no residual air-fluid level. Realimention was possible three days after placement of the stent. The patient was discharged after 11 days. There was no recurrence of the chyloma. Fistulisation did recur after removal of the stent. Conclusion: Surinfected mediastinal chyloma due to oesopagho-mediastinal fistula is an extremely rare complication after cervical mediastinoscopy and radiotherapy. Open drainage of the chyloma and total coverage of the fistula can control infection and prevent recurrence on short term.

Thyroglossal duct cysts in children: a 30-year survey with emphasis on clinical presentation, surgical treatment, and outcome.

Background: Thyroglossal duct cysts (TGDC) are one of the most common congenital anomalies found in the anterior neck region of children. Sistrunk's procedure, described in 1920 already, is still considered as the gold standard. However, clinical reality shows that in a minority of patients, marsupialization and simple cyst excision are still performed as well. Cyst recurrence is the most feared complication. The main goal of this retrospective study is to determine risk factors of recurrence. Furthermore, data on presentation characteristics, management and outcome were collected as well. Methods: The data of 104 patients aged between 0 and 16 years who underwent surgery for TGDC at the University Hospital of Brussels between 1986 and 2016 were retrospectively analyzed. We focused on aspects of clinical presentation, intra- and postoperative treatment and long-term follow-up. Results: Overall recurrence of TGDC was seen in twelve of the 104 cases (11.5%). Eight out of these 12 showed a preoperative infection, 4 out of 12 had intra-operative cyst rupture. Five out of the 12 patients had not been treated by the Sistrunk procedure, but by cyst excision or marsupialization only. Non-adherence to the Sistrunk procedure appeared to be the only significant risk factor of TGDC recurrence. Conclusion: Our study shows that Sistrunk's operation for thyroglossal duct cyst in pediatric patients is significantly superior in reducing the risk of cyst recurrence compared to other surgical treatments. Preoperative infection and cyst rupture did not influence the recurrence rates.

The Impact of Combining a Low-Tube Voltage Acquisition with Iterative Reconstruction on Total Iodine Dose in Coronary CT Angiography.

OBJECTIVES: To assess the impact of combining low-tube voltage acquisition with iterative reconstruction (IR) techniques on the iodine dose in coronary CTA. METHODS: Three minipigs underwent CCTA to compare a standard of care protocol with two alternative study protocols combining low-tube voltage and low iodine dose with IR. Image quality was evaluated objectively by the CT value, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the main coronary arteries and aorta and subjectively by expert reading. Statistics were performed by Mann-Whitney U test and Chi-square analysis. RESULTS: Despite reduced iodine dose, both study protocols maintained CT values, SNR, and CNR compared to the standard of care protocol. Expert readings confirmed these findings; all scans were perceived to be of at least diagnostically acceptable quality on all evaluated parameters allowing image interpretation. No statistical differences were observed (all p values > 0.11), except for streak artifacts (p = 0.02) which were considered to be more severe, although acceptable, with the 80 kVp protocol. CONCLUSIONS: Reduced tube voltage in combination with IR allows a total iodine dose reduction between 37 and 50%, by using contrast media with low iodine concentrations of 200 and 160 mg I/mL, while maintaining image quality.

Contrast agent and radiation dose reduction in abdominal CT by a combination of low tube voltage and advanced image reconstruction algorithms.

OBJECTIVES: To assess image quality in abdominal CT at low tube voltage combined with two types of iterative reconstruction (IR) at four reduced contrast agent dose levels. METHODS: Minipigs were scanned with standard 320 mg I/mL contrast concentration at 120 kVp, and with reduced formulations of 120, 170, 220 and 270 mg I/mL at 80 kVp with IR. Image quality was assessed by CT value, dose normalized contrast and signal to noise ratio (CNRD and SNRD) in the arterial and venous phases. Qualitative analysis was included by expert reading. RESULTS: Protocols with 170 mg I/mL or higher showed equal or superior CT values: aorta (278-468 HU versus 314 HU); portal vein (205-273 HU versus 208 HU); liver parenchyma (122-146 HU versus 115 HU). In the aorta, all 170 mg I/mL protocols or higher yielded equal or superior CNRD (15.0-28.0 versus 13.7). In liver parenchyma, all study protocols resulted in higher SNRDs. Radiation dose could be reduced from standard CTDIvol = 7.8 mGy (6.2 mSv) to 7.6 mGy (5.2 mSv) with 170 mg I/mL. CONCLUSION: Combining 80 kVp with IR allows at least a 47 % contrast agent dose reduction and 16 % radiation dose reduction for images of comparable quality. KEY POINTS: • There is a balance between image quality, contrast dose and radiation dose. • Iterative reconstruction has a major, positive impact on this balance. • Both contrast dose and radiation dose can be reduced in abdominal CT. • The trade-off can be quantitatively described by a 3D model. • Contrast and radiation dose can be tailored according to specific safety concerns.

Diagnostic and prognostic correlates of preoperative FDG PET for breast cancer.

PURPOSE: To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. METHODS: In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. RESULTS: PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). CONCLUSION: Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients.

Therapeutic vaccination with an autologous mRNA electroporated dendritic cell vaccine in patients with advanced melanoma.

The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-α-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-α-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-α-2b.

Restoration of tumor equilibrium after immunotherapy for advanced melanoma: three illustrative cases.

Metastatic melanoma runs a predictable detrimental course in the vast majority of patients. New modalities of immunotherapy, such as melanoma antigen-specific therapeutic vaccination and cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor blockade by monoclonal antibodies (mAbs), have been associated with atypical kinetics of tumor response that differ from those observed during cytotoxic treatment. Recently, new tumor response criteria have been proposed based on the tumor response characteristics observed in clinical studies with ipilimumab (the so-called 'immune-related response criteria'). We report three illustrative cases of the American Joint Committee on Cancer stage IV-M1c melanoma patients who experienced atypical kinetics of tumor response to the treatment with the CTLA-4-blocking mAb, ipilimumab (case 1), or an autologous dendritic cell vaccine in combination with interferon α-2b (cases 2 and 3). These cases show that atypical response patterns not only relate to the outcome of CTLA-4-blocking mAb therapy but also to the treatment with therapeutic vaccines and interferon α-2b.

Hemorrhagic regression of melanoma metastases during therapeutic vaccination: a report of three cases.

Melanoma metastases are characterized by pronounced neo-angiogenesis and spontaneous bleeding frequently occurring within central nervous system metastases. Clinically apparent spontaneous hemorrhage within subcutaneous melanoma metastases, however, is a rare event that coincides with progression of such metastases. We report, to our knowledge the first observation, on regression of subcutaneous metastases with hemorrhage of the overlying skin in three patients with stage IV melanoma who participated in clinical trials on therapeutic vaccination. In two patients, loss of arterial flow on Doppler ultrasound imaging was documented in the metastasis at the time of hematoma formation. One patient suffered from an intracranial hemorrhage in a subcentimetric brain metastasis coincident with the hemorrhagic regression of some of his skin metastases.