Samira Mercedes Sadowski

Context Hyperparathyroidism is associated with hypercalcemia and the excess of parathyroid hormone secretion; however, the alterations in molecular pattern of functional genes during parathyroid tumorigenesis have not been unraveled. We aimed at establishing transcriptional patterns of normal and pathological parathyroid glands (PGs) in sporadic primary (HPT1) and secondary hyperparathyroidism (HPT2). Objective To evaluate dynamic alterations in molecular patterns as a function of the type of PG pathology, a comparative transcript analysis was conducted in subgroups of healthy samples, sporadic HPT1 adenoma and hyperplasia, and HPT2. Design Normal, adenomatous, HPT1, and HPT2 hyperplastic PG formalin-fixed paraffin-embedded samples were subjected to NanoString analysis. In silico microRNA (miRNA) analyses and messenger RNA–miRNA network in PG pathologies were conducted. Individual messenger RNA and miRNA levels were assessed in snap-frozen PG samples. Results The expression levels of c-MET, MYC, TIMP1, and clock genes NFIL3 and PER1 were significantly altered in HPT1 adenoma compared with normal PG tissue when assessed by NanoString and quantitative reverse transcription polymerase chain reaction. RET was affected in HPT1 hyperplasia, whereas CaSR and VDR transcripts were downregulated in HPT2 hyperplastic PG tissue. CDH1, c-MET, MYC, and CaSR were altered in adenoma compared with hyperplasia. Correlation analyses suggest that c-MET, MYC, and NFIL3 exhibit collective expression level changes associated with HPT1 adenoma development. miRNAs, predicted in silico to target these genes, did not exhibit a clear tendency upon experimental validation. Conclusions The presented gene expression analysis provides a differential molecular characterization of PG adenoma and hyperplasia pathologies, advancing our understanding of their etiology.

Adrenal oncocytoma (AO) is an extremely rare adrenocortical neoplasm and little is known about its malignant potential, secretory properties, and hereditary origin. We present the case of a benign AO with concomitant incidentally found papillary thyroid cancer (PTC) and review similar cases in the literature. Immunohistochemistry and next-generation sequencing (NGS) were performed. A 66-year-old women was incidentally found to have a large, androgen-secreting right adrenal mass. ¹⁸F-Fluorodeoxyglucose positron emission tomography showed intense uptake (SUV_max 88.7) of this mass and found a hypermetabolic right thyroid mass. Open adrenalectomy was performed for this highly suspicious adrenal mass. Histopathology revealed benign AO that was BRAF^V600E negative, with low Ki-67, and no somatic mutation found on NGS. Thyroidectomy revealed invasive, BRAF^V600E-positive PTC. At 6 months follow-up, androgen levels returned to normal, and no recurrence was seen on imaging. To our knowledge, this is the first report of an androgen-secreting AO with concomitant PTC. Possibly the simultaneous discovery of two independent neoplasms was observed. In conclusion, this case highlights that care should be given to exclude concomitant neoplasms. Long-term and regular imaging with biochemical follow-up is warranted, since the outcome and clinical behavior of AO remains uncertain.

Background and aim: To analyze the management and outcome of patients with primary typical (TC) and atypical lung carcinoids (AC) in Switzerland. Methods: Retrospective analysis of patients selected from a neuroendocrine tumor (NET) registry. Patients were divided into TC and AC according to pathology reports, and surgical procedures were grouped as wedge/segmentectomy, lobectomy/bilobectomy and pneumectomy. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Results: Over 7 years, 113 pulmonary carcinoids (61.9% females, mean age 59.4 years) were included from 19 hospitals, with pathology data on Ki67 and necrosis incomplete in 16 cases. Eighty-three TC and 14 AC underwent surgical resection with a primary tumor size of median 14.5 (range 1–80) mm and diagnosis was established in 55.8% at surgery. Mean follow-up was 30.2 ± 23.1 months. Lobectomy was performed in 54.2% and wedge resection in 17.7% of cases. Six patients received additional systemic therapy. There was a trend for larger primary lesion size and a significantly higher rate of N2–N3 status in AC. Mean survival tended to be increased in patients with TC compared to AC (86.1 vs 48.4 months, P = 0.06) and mean disease-free interval after surgical resection was 74.1 and 48.3 months for TC and AC, respectively (P = 0.74). Conclusion: AC of the lung has a more malignant behavior and a trend to a worse outcome. The results of this registry reinforce the need for standardized histological diagnosis and inter-disciplinary therapeutic decision making to improve the quality of care of patients with TC and AC.

Identification of the parathyroid glands (PGs) during thyroid surgery may prevent their inadvertent surgical removal and prevent postoperative hypoparathyroidism. However, identification of the PGs does not guarantee their function, and their vascular supply needs to be preserved as well. The recent introduction of intraoperative indocyanine green (ICG) fluorescent angiography of the PGs during thyroid surgery allows for the appraisal of the vascular anatomy and evaluation of PG function. The use of this tool could lead to a significant reduction in the rate of postoperative hypoparathyroidism, as it allows surgeons to adapt their surgical technique for the preservation of the PGs. ICG fluorescent angiography is currently the only available real-time tool to assess the vascular blood supply of each individual PG intraoperatively and can thus assist surgeons in their decision-making. Herein, we review the relevant literature.

Background: The aim of this study was to describe first experiences and changes in management using continuous intraoperative neuromonitoring (C‐IONM) in thyroid and parathyroid surgery.Method: Retrospective analysis of patients who underwent surgery with C‐IONM since 2012. Surgical maneuvers were modified when electrophysiologic events occurred. Patients with persistent loss of signal (LOS) underwent postoperative laryngoscopy.Results: One hundred and one patients (of 1586 neck surgeries) were included and 19 had events: In 13 these were temporary (resolved before end of surgery) and led to intraoperative modifications in surgical approach; in all cases traction was released, and in 8, recurrent laryngeal nerve (RLN) approach was changed [superior approach (2), inferior approach (2), both (4)]. Six patients had persistent LOS (5.9%, present at end of procedure), with RLN palsy (RLNP) on postoperative day 1: In three, LOS occurred at electrode placement on the vagus nerve, leading to distal placement of the electrode allowing ipsilateral dissection under continuous monitoring; all three had complete recovery at 6 months. In the three other patients, LOS occurred on the RLN: one probable thermal, one traction lesion and one accidental section of the anterior RLN branch. The RLN recovered within 6 months in two patients, and in the third, RLNP persisted after 6 months (1/101 = 1%).Conclusion: C‐IONM provides real‐time evaluation of the RLN function, allowing for adaptation of surgical maneuvers to prevent RLNP. It seems particularly useful in difficult cases like redo neck surgery, invasive thyroid cancer and intrathoracic or large goiter. Care should be given at electrode placement on the vagus nerve.

Background: Patients with neuroendocrine tumors (NETs) have divergent survival, even when having the same site of primary tumor, and tumor stage and grade. 68Gallium (68Ga)-DOTATATE positron emission tomography (PET)/computed tomography (CT) is a sensitive imaging modality for detecting NETs. The purpose of this study was to determine whether 68Ga-DOTATATE PET/CT imaging has any prognostic utility in patients with NETs. Methods: One hundred and eighty-four patients with NETs were enrolled in a prospective study of 68Ga-DOTATATE PET/CT imaging and comprehensive biochemical analysis. Total 68Ga-DOTATATE-Avid Tumor Volume (68Ga-DOTATATE TV) was measured in all participants. The primary outcome measures were progression-free survival (PFS) and disease-specific mortality (DSM). PFS and DSM rates were compared according to 68Ga-DOTATATE TV quartiles of the current cohort. Then, specific 68Ga-DOTATATE TV cut-offs were set using a receiver operating characteristic (ROC) curve analysis, and the risks for DSM and PFS were validated with Kaplan-Meyer and Cox regression analyses. Results: Patients were followed for a median of 18 months (range 4–35 months). 68Ga-DOTATATE TV quartiles had inverse correlation with PFS (P=0.001) and survival rates (P=0.002). Using cut-offs derived from ROC curve analysis, 68Ga-DOTATATE TV ≥7.0 was associated with a lower PFS (HR=2.0, P=0.03), and 68Ga-DOTATATE TV ≥35.8 ml was associated with increased (HR=10.7) disease-specific mortality in multivariate analysis (P=0.03), as well as in subgroup analysis of patients with pancreatic NETs. Conclusions: We show for the first time the prognostic utility of 68Ga-DOTATATE TV in a large cohort of patients with NETs, enabling clinicians to determine the need for intervention using this non-invasive tool.

Background: About 8–20% of patients with von Hippel-Lindau disease (vHLd) develop pancreatic neuroendocrine tumors (PNETs). However, prognostic markers for these tumors are lacking. The VHL gene mutation type is associated with the clinical phenotype of vHLd. Hence, we aimed to determine whether VHL mutation characteristics may be associated with PNETs phenotype in patients with vHLd. Methods: A prospective study of patients with vHLd and PNETs with follow-up imaging. VHL mutation type and position were defined using Sanger sequencing of germline DNA. Results: 182 patients (476 PNETs) were followed for a median of 52 months (range 3–84). The VHL gene was sequenced in 154 patients: 75 patients (48.7%) had a missense mutation [MisM], 51 (33.1%) - deletion, 12 (7.8%) - nonsense, one (0.6%) - rearrangement, and 15 (9.7%) had frameshift mutations. Patients with a largest lesion diameter 3 cm had higher risk for metastases compared with other patients (Log Rank test, P=0.007). Patients with MisM had a higher risk of requiring an intervention (Log-Rank test P=0.01) and for developing metastases during follow-up (P=0.007) compared to those with other mutation types. Among patients with a largest lesion diameter between 1.2 and 3 cm, those with MisM had higher risk for metastases (Log-Rank test, P=0.048) compared to other mutation types, and patients with mutation positioned in exon 3 of the VHL gene had higher risk for requiring intervention both in univariate (P=0.03) and multivariate analysis (Hazard ratio 2.9, 95% confidence interval 1.2–7.2, P=0.02). Conclusion: Lesion diameter should be the pivot factor in directing PNETs management in vHLd. Among patients with a largest PNET diameter >1.2 and VHL genotyping may be useful for risk stratification.

To report the association between thoracic duct ligation and acute pancreatitis. The association between sudden stop of lymphatic flow and pancreatitis has been established in experimental models. A 57-year-old woman operated for thymoma presented a iatrogenic chylothorax. After thoracic duct ligation, she presented an acute pancreatitis which resolved after conservative treatment. The chylothorax disappeared within 4 days of thoracic duct ligation. This is the first report of acute pancreatitis following thoracic duct ligation. The pancreas and digestive tract should be assessed in symptomatic patients after thoracic duct ligation.

We describe the case of a rare anatomical variant of the inferior thyroid artery (ITA) taking its origin directly from the common carotid artery (CCA) instead of the thyrocervical trunk (TCT). This anatomical feature exposes to risks of perioperative bleeding and nerve injuries when it is unrecognized by the surgeons. Knowledge of its existence may be helpful to reduce risks for the patient.