A Direct Comparison of Patients With Hereditary and Sporadic Pancreatic Neuroendocrine Tumors: Evaluation of Clinical Course, Prognostic Factors and Genotype-Phenotype Correlations.

Introduction: Pancreatic neuroendocrine tumors (PNETs) in hereditary syndromes pose a significant challenge to clinicians. The rarity of these syndromes and PNETs itself make it difficult to directly compare them with sporadic PNETs. Despite research suggesting differences between these two entities, the same approach is used in hereditary and sporadic PNETs. Methods: We included 63 patients with hereditary PNET (GpNET) and 145 with sporadic PNET (SpNET) in a retrospective observational study. Clinical and genetic data were collected in two Polish endocrine departments from January 2004 to February 2020. Only patients with confirmed germline mutations were included in the GpNET cohort. We attempted to establish prognostic factors of metastases and overall survival in both groups and genotype-phenotype correlations in the GpNET group. Results: Patients with GpNET were younger and diagnosed earlier, whereas their tumors were smaller and more frequently multifocal compared with patients with SpNET. Metastases occurred more frequently in the SpNET group, and their appearance was associated with tumor size in both groups. GpNET patients had longer overall survival (OS). OS was affected by age, age at diagnosis, sex, grade, stage, tumor diameter, occurrence and localization of metastases, type of treatment, and comorbidities. In the MEN1 group, carriers of frameshift with STOP codon, splice site, and missense mutations tended to have less advanced disease, while patients with mutations in exon 2 tended to have metastases more frequently. Conclusions: Direct comparisons of GpNET and SpNET demonstrate significant differences in the clinical courses of both entities, which should force different approaches. A larger group of patients with GpNET should be assessed to confirm genotype-phenotype correlations.

Multiple endocrine neoplasia type 1 in Poland: a two-centre experience.

INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) has been causing problems for clinicians since it was first described in 1954 by Wermer. Not only its rarity, but also its variable clinical manifestations and lack of genotype-phenotype correlation make it hard to establish evidence-based guidelines for the management of this syndrome. Nationwide registers and population-based research are the best means to improve knowledge about this rare disease. As yet, there is no example of such research in the Polish population of MEN1 patients. MATERIAL AND METHODS: We performed a retrospective analysis of clinical and genetic data of patients diagnosed with MEN1 syndrome and followed-up in two polish referral centres in the years 1994-2018. RESULTS: We analysed 79 patients, of whom the majority were women. The mean age of the patient population was 43 years, mean age at MEN1 diagnosis was 37.95 years, and mean interval from initial symptoms to MEN1 diagnosis was 6.93 years. Primary hyperparathyroidism (PHP), gastroenteropancreatic neuroendocrine tumour (GEP-NET), and pituitary adenoma (PA) developed in 90%, 52%, and 47% of patients, respectively. The dominance of insulinoma with low prevalence of gastrinoma is the most vivid difference, when compared to previously described populations. Moreover, we found 3.5-fold higher risk of developing a pituitary tumour in patients with a frameshift mutation with the STOP codon of the MEN1 gene. CONCLUSIONS: The Polish population of patients with MEN1 is different than previously described European and Asian populations, primarily in prevalence of functional NETs. A frameshift mutation with the STOP codon of the MEN1 gene significantly increases the risk of PA. Further studies with a larger cohort of patients are needed to fully describe the Polish population and improve diagnosis and management of the syndrome.

Atrial fibrillation in outpatients with stable coronary artery disease: results from the multicenter RECENT study.

INTRODUCTION: Atrial fibrillation (AF) frequently coexists with other cardiovascular diseases. OBJECTIVES: The aim of this study was to assess the prevalence of AF in outpatients with stable coronary artery disease (CAD) and to determine clinical and laboratory parameters associated with the higher prevalence of this arrhythmia. In addition, we compared the indications for antithrombotic treatment using the older CHADS2 and the currently used CHA2DS2-VASc scores. PATIENTS AND METHODS: We studied the clinical data of 2578 Polish patients with stable CAD participating in the multicenter RECENT study (age, 65 ±10 years; men, 55%; Canadian Cardiovascular Society class I/II/III+IV, 38%/48%/14%). RESULTS: AF was present in 19% of patients with CAD. Advanced age, longer history of CAD, and concomitant heart failure were independently associated with the higher prevalence of AF (all P <0.05). Among patients with CAD and AF, 73% of the patients required antithrombotic treatment according to the CHADS2 score (≥2), and 94%-according to the CHA2DS2-VASc score (≥2). A CHA2DS2-VASc score of 2 or higher was found in 47% of the patients with a CHADS2 score of 0 and 85% of those with a CHADS2 score of 1. Twenty-one percent of patients with CAD and AF did not have unequivocal indications for antithrombotic treatment according to the CHADS2 score (0-1), while they had strong indications for such treatment on the basis of the CHA2DS2-VASc score (≥2). CONCLUSIONS: AF affects every fifth ambulatory patient with CAD. According to the CHA2DS2-VASc score, almost all patients with CAD and AF require antithrombotic treatment, which may complicate coronary revascularization and related antiplatelet treatment.