Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism.

PURPOSE: CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT). METHODS: During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples. RESULTS: DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3. CONCLUSION: Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge.

Site and size of bleeding peptic ulcer. Is there any relation to the efficacy of hemostatic sclerotherapy?

In 78 patients with high-risk bleeding peptic ulcers (either with active bleeding or non-bleeding visible vessel) endoscopic hemostasis by injection of adrenaline and polidocanol was attempted. Sclerotherapy was performed in 70 (90%) patients. Initial hemostasis was achieved in 35 (94.5%) patients with active bleeding, and permanent hemostasis in 61 (87%). Efficacy of injection therapy was significantly lower in ulcers larger than 2 cm (p = 0.001), and in those located on the posteroinferior duodenal wall (p = 0.03). It was not possible to perform endoscopic injection in 8 (10%) patients due to difficulty of access, lesions located mainly high on the lesser gastric curvature and on the posteroinferior duodenal wall. From these results we conclude that endoscopic injection is a very useful technique for the initial treatment of high-risk bleeding peptic ulcer, although the size and anatomical location of the lesions may be a limitation of its use.