Although intracytoplasmic sperm injection (ICSI) is now a widely-used technique, it is still of interest to improve our knowledge as to which is the best spermatozoon to be selected for ICSI. Infertile men have increased risks of producing aneuploid spermatozoa. Using hyaluronic acid (HA)-binding sperm selection may reduce the genetic risks such as chromosomal aberrations of offspring. In the present study we examined the clinical success of ICSI with HA-selected sperm ('physiologic' ICSI, PICSI) compared to conventional ICSI, as well as the necessity to differentiate patients according to the initial HA-binding assay result (HBA score) and whether the sperm concentration or HBA score can provide additional information. We observed a significantly higher fertilization rate (FR) of the PICSI group with >60% HBA, implantation rate (IR) of the PICSI group with ≤ 60% HBA, and clinical pregnancy rate (CPR) in every PICSI group compared to the ICSI groups (p < 0.01). We also observed a significantly higher life birth rate (LBR) in the PICSI group with ≤ 60% HBA compared to ICSI patients with ≤ 60% HBA (p < 0.001). The pregnancy loss rate (PLR) was significantly lower in PICSI patients compared to the ICSI group (p < 0.0001). The FR, IR, CPR, and LBR of the PICSI group with <50% HBA were significantly higher and the PLR was lower than in the ICSI group with <50% HBA (p < 0.01). A statistically significant correlation was found between the sperm concentration and the HA-binding capacity (r = 0.62, p < 0.001). We found a closer relationship between HBA score and FR (r = 0.53, NS) than between sperm concentration and FR (r = 0.14, NS). HBA could be considered for sperm selection prior to ICSI because of its success and apparent ability to reduce genetic complications. However, this must be extended to a larger study.

Thyroid cancer (TC) coexisting with Hashimoto’s thyroiditis (HT) presents with several characteristic features including multifocality and lower clinical stages compared to de novo carcinomas but its exact biology is still not understood. We reexamined clinico-pathological and molecular correlations between Hashimoto’s thyroditis and papillary thyroid cancer. A total of 262 patients with TC was evaluated who underwent thyroidectomy at the Surgical Department of the University of Debrecen. Clinical data, histology and molecular data were evaluated. Our cohort included 43 patients (16.4%) with (5 male, 38 female) and 219 (83.6%) patients without coexisting HT (48 male, 171 female). Hashimoto’s thyroiditis related thyroid cancer presented predominantly (93.0% of the cases) with the papillary histological type. Multifocality was observed more frequently with coexisting HT (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%)(p = 0.034). In contrast, lymphatic metastasis (pN1) with a significantly reduced frequency in patients with HT (4/11; 36.4%) then without HT (34/41 pN1; 82.9%)(p = 0.002). BRAF V600E mutation could be demonstrated at significantly lower rates in cases of PTC + HT (32.1 vs 60.7%, p < 0.005). High incidence, multifocality and papillary morphology strongly support a causal relation between TC and preexisting Hashimoto’s thyroiditis, the latter to be considered as a preneoplastic condition promoting thyroid carcinogenesis.

Biliary tract cancer (BTC) is a rare malignancy with a long disease course and an overall poor prognosis. Despite multiple chemotherapy agents, there is no defined second-line treatment opportunity for advanced BTCs. In the era of precision oncology, NGS plays an important role in identifying mutations that may predict the molecular pathomechanism and manage the BTC therapy. The peripheral blood liquid biopsy (LB) of cancer patients represents variable amounts of cell-free DNA (cfDNA) released from tumor foci of any anatomical location. Our study aimed to identify somatic mutations and tumor variant burden (TVB) in cell-free and matched tumor DNA. We found a positive correlation between the estimated tumor volume and cfDNA yield (r = 0.9326, p < 0.0001). Comparing tissue and LB results, similar TVB was observed. SNVs were proven in 84% of the cases, while in two cases, only the LB sample was informative for molecular analysis. The most important aberrations in BTCs, such as FGFR2, IDH1, IDH2, KRAS, and TP53, could be detected in matched LB samples. Our prospective study demonstrates a minimally invasive testing approach to identify molecular genetic alterations in cholangiocarcinoma and gallbladder cancers. Clinical applications of cfDNA reflect by capturing the outstanding spatial tumor heterogeneity and guarantee novel aspects for the precision oncology treatment.

Approximately 15% of couples are unable to conceive after one year of unprotected intercourse. Because sperm can be accessed with ease, it is reasonable to search for non-invasive biomarkers in semen. MicroRNAs are a family of short single-stranded non-coding RNA molecules that are capable of regulating gene expression and causing mRNA degradation. We studied the most common 11 spermatogenesis-related microRNAs expression levels in sperm and seminal plasma from patients with oligozoospermic or asthenozoospermic ejaculates, and in men with normozoospermic ejaculates. Five of these miRNAs were significantly upregulated and three were downregulated in infertile males compared to men with normozoospermic ejaculates. A statistically significant negative correlation was found between the sperm concentration and several microRNA expression level (let-7a, miR-7-1-3p, miR-141, miR-200a, and miR-429, p < 0.0001) both in sperm and in seminal plasma. We also found positive correlation between sperm concentration and some miRNA expression levels (miR-15b, miR-34b, and miR-122, p < 0.001) in sperm and in seminal plasma. This is the first study to demonstrate differences between sperm and seminal plasma miRNA expression level and to identify a correlation between the sperm concentration and miRNAs expression level. Therefore, these MiRNAs could have the potential be used as non-invasive biomarkers to diagnose males with impaired sperm production.

The spectrum of lissencephaly ranges from absent (agyria) or decreased (pachygyria) convolutions to less severe malformation known as subcortical band heterotopia. Mutations involving LIS1 and TUBA1A result in the classic form of lissencephaly, whereas mutations of the DCX gene cause lissencephaly in males and subcortical band heterotopia in females. This report describes the clinical manifestations and imaging and genetic findings in 2 boys with lissencephaly and a girl with subcortical band heterotopia. An ovel mutation (c.83_84delAT, p.Tyr28Phefs*31) was identified in LIS1 in 1 of the boys with lissencephaly and another novel mutation (c.200delG, p.Ile68Leufs*87) was found in DCX in the girl with subcortical band heterotopia. The mutations appeared in the first half of the genes and are predicted to result in truncated proteins. A mutation was found in the TUBA1A gene (c.1205G>A, p.Arg402His) in the other boy. This mutation affects the folding of tubulin heterodimers, changing the interactions with proteins that bind microtubules.