Publications by authors named "Rafal Pęksa"

50 Publications

Impact of chromosome 17 centromere copy number increase on patient survival and human epidermal growth factor receptor 2 expression in gastric adenocarcinoma.

Oncol Lett 2021 Feb 21;21(2):142. Epub 2020 Dec 21.

Department of Oncological Surgery, Gdynia Centre of Oncology, Pomeranian Hospitals, Gdynia, Pomeranian Voivodship 81-519, Poland.

The accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is essential for the appropriate use of targeted therapies. An increased number of chromosome 17 centromere enumeration probe (CEP17) signals may underrate fluorescence hybridization (FISH) outcomes, resulting in false-negative or a false-equivocal HER2 status assessment. The aim of the present study was to assess the frequency of CEP17 copy number increase (CNI), its effects on HER2 protein expression (and the subsequent effects on tumor cells), and the survival outcomes of patients with gastric cancer. Archival primary tumor samples from 244 patients that underwent gastric resection for adenocarcinoma were retrieved for both HER2 protein expression analysis (using immunochemistry) and gene amplification (using FISH). The associations between HER2 status, CEP17 CNI and multiple clinicopathological parameters (including survival outcome), were assessed. The relationship between CEP17 CNI and HER2 protein upregulation was also investigated. CEP17 CNI was detected in 17.2% of cases, and a strong association between CEP17 CNI and HER2 upregulation was revealed. The impact of CEP17 CNI on survival did not reach statistical significance. Consequently, CEP17 CNI was discovered to be strongly associated with HER2 upregulation in tumor cells, which may characterize a critical issue in HER2 testing. Therefore, the eligibility for HER2-targeted agents in CEP17 CNI-positive patients warrants further recognition.
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http://dx.doi.org/10.3892/ol.2020.12403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798021PMC
February 2021

Endoscopic ultrasound-guided ethanol ablation of insulinoma.

Endokrynol Pol 2020 30;71(6):585-586. Epub 2020 Oct 30.

Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.

Not required for Clinical Vignette.
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http://dx.doi.org/10.5603/EP.a2020.0070DOI Listing
October 2020

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers is Mainly Dependent on HER2 Status-A Pilot Study.

Diagnostics (Basel) 2020 Aug 20;10(9). Epub 2020 Aug 20.

Department of Oncology and Radiotherapy, Medical University of Gdansk, 80-214 Gdansk, Poland.

Estrogen (ER) and progesterone (PgR) receptors and HER2 are crucial in the assessment of breast cancer specimens due to their prognostic and predictive significance. Single hormone receptor-positive breast cancers are less common and their clinical course is less favorable than ER(+)/PgR(+) tumors. Their molecular features, especially microRNA (miRNA) profiles, have not been investigated to date. Tumor specimens from 36 chemonaive breast cancer patients with known ER and PgR status (18 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases) were enrolled to the study. The expression of 829 miRNAs was evaluated with nCounter Human v3 miRNA expression Assay (NanoString). miRNAs differentiating between ER/PgR/HER2 phenotypes were selected based on fold change (FC) calculated for the mean normalized counts of each probe in compared groups. The differences were estimated with Student's -test or Two-Way ANOVA (considering also the HER2 status). The results were validated using The Cancer Genome Atlas (TCGA) dataset. Following quality control of raw data, fourcases were excluded due to low sample quality, leaving 14 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases. After correction for multiple comparisons, we did not find miRNA signature differentiating between ER(-)/PgR(+) and ER(+)/PgR(-) breast cancers. However, a trend for differing expression (-value ≤ 0.05; FDR > 0.2; ANOVA) in eight miRNAs was observed. The ER(+)/PgR(-) group demonstrated elevated levels of four miRNAs-miR-30a-5p, miR-29c-3p, miR-141-3p and miR-423-5p-while the ER(-)/PgR(+) tumors were enriched in another four miRNAs-miR-514b-5p, miR-424-5p, miR-495-3p, and miR-92a-3p. For one of the miRNAs-miR-29c-3p-the association with the ER(+)/PgR(-) phenotype was confirmed in the TCGA cohort (-value = 0.024; -test). HER2 amplification/overexpression in the NanoString cohort was related to significant differences observed in 33 miRNA expression levels (FDR ≤ 0.2; ANOVA). The association with HER2 status was confirmed in the TCGA cohort for four miRNAs (miR-1180-3p, miR-223-3p, miR-30d-5p, and miR-195-5p). The main differences in miRNA expression amongst single hormone receptor-positive tumors were identified according to their HER2 status. However, ER(+)/PgR(-) cases tended to express higher levels of miRNAs associated with ER-positivity (miR-30a-5p, miR-29c-3p, miR-141-3p), whereas ER(-)/PgR(+) cancers showed elevated levels of miRNAs characteristic for double- and triple-negative tumors (miR-92a-3p, miR-424-5p). Further studies are necessary to comprehensively analyze miRNA signatures characteristic of ER(-)/PgR(+) and ER(+)/PgR(-) tumors.
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http://dx.doi.org/10.3390/diagnostics10090617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555149PMC
August 2020

Colorectal Adenocarcinomas Harboring ALK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 12 Cases and Review of the Literature.

Am J Surg Pathol 2020 09;44(9):1224-1234

Laboratory of Pathology, National Cancer Institute, Bethesda, MD.

This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody. These cancers harbored CAD-ALK (n=1), DIAPH2-ALK (n=2), EML4-ALK (n=2), LOC101929227-ALK (n=1), SLMAP-ALK (n=1), SPTBN1-ALK (n=4), and STRN-ALK (n=1) fusions, as detected by an RNA-based next-generation sequencing assay. ALK fusion carcinomas were diagnosed mostly in older patients with a 9:3 female predominance (median age: 72 y). All tumors, except a rectal one, occurred in the right colon. Most tumors were stage T3 (n=7) or T4 (n=3). Local lymph node and distant metastases were seen at presentation in 9 and 2 patients. These tumors showed moderate (n=6) or poor (n=3) glandular differentiation, solid medullary growth pattern (n=2), and pure mucinous morphology (n=1). DNA mismatch repair-deficient phenotype was identified in 10 cases. Tumor-infiltrating lymphocytes were prominent in 9 carcinomas. In 4 carcinomas, tumor cells showed strong, focal (n=3), or diffuse programmed death-ligand 1 immunoreactivity. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 tumors. Four patients died of disease within 3 years, and 7 were alive with follow-up ranging from 1 to 8 years. No mutations in BRAF, RAS, and in genes encoding components of PI3K-AKT/MTOR pathway were identified. However, 1 tumor had a loss-of-function PTEN mutation. Aberration of p53 signaling, TP53 mutations, and/or nuclear accumulation of p53 protein was seen in 9 cases. ALK fusion colorectal carcinomas are a distinct and rare subtype of colorectal cancers displaying some features of mismatch repair-deficient tumors.
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http://dx.doi.org/10.1097/PAS.0000000000001512DOI Listing
September 2020

Childhood longitudinal melanonychia: case series from Poland.

Postepy Dermatol Alergol 2020 Apr 10;37(2):195-201. Epub 2019 Sep 10.

Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Gdańsk, Poland.

Introduction: Longitudinal melanonychia (LM) is characterized by a tan, brown or black longitudinal streak within nail plate caused by the presence of melanin. LM is relatively common in dark-skinned population, infrequent in Caucasian population, and rare in children.

Aim: We report epidemiological, clinicopathological and dermoscopic analysis of 8 cases of childhood LM from Poland, which is the largest series in the Central and Eastern European population.

Material And Methods: Three hundred and forty-eight patients presenting with various nail pigmentation (in 2010-2016) were analysed. 72 cases of LM have been identified, including 8 cases of childhood LM (< 16 years of age), which were included in further analysis.

Results: Seven patients were boys and one girl, with mean age of 9 years (range: 6-13). More than a half ( = 5) presented skin phototype II. The most common location of melanonychia was the first left fingernail. Dermoscopy revealed heterogeneity of longitudinal lines colour in 5 cases. The irregularity of longitudinal line thickness in 5 cases and irregularity of parallelism in 5 cases was observed. Histopathological evaluation was performed in 4 patients, in 3 cases it revealed the presence of nail matrix nevus, in one case the presence of melanocytic proliferation of the lentiginous pattern along the dermoepidermal junction.

Conclusions: Despite the fact that melanoma was not recognised in any case, such a possibility should always be considered as the cause of LM, even in the paediatric population. Dermoscopy seems to be useful in patient follow-up and management.
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http://dx.doi.org/10.5114/ada.2019.87706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262813PMC
April 2020

Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.

Int J Mol Sci 2020 May 31;21(11). Epub 2020 May 31.

Department of General, Endocrine and Transplant Surgery, Faculty of Medicine, Medical University of Gdansk, Mariana Smoluchowskiego 17, 80-214 Gdansk, Poland.

HtrA proteases regulate cellular homeostasis and cell death. Their dysfunctions have been correlated with oncogenesis and response to therapeutic treatment. We investigated the relation between HtrA1-3 expression and clinicopathological, and survival data, as well as the microsatellite status of tumors. Sixty-five colorectal cancer patients were included in the study. The expression of was estimated at the mRNA and protein levels by quantitative PCR and immunoblotting. Microsatellite status was determined by high-resolution-melting PCR. We found that the mRNA level was higher in colorectal cancer tissue as compared to the unchanged mucosa, specifically in primary lesions of metastasizing cancer. The levels of HtrA1 and HtrA2 proteins were reduced in tumor tissue when compared to unchanged mucosa, specifically in primary lesions of metastasizing disease. Moreover, a decrease in and transcripts' levels in cancers with a high level of microsatellite instability compared to microsatellite stable ones has been observed. A low level of HtrA1 or/and HtrA2 in cancer tissue correlated with poorer patient survival. The expression of and changes during colorectal carcinogenesis and microsatellite instability may be, at least partially, associated with these changes. The alterations in the genes' expression are connected with metastatic potential of colorectal cancer and may affect patient survival.
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http://dx.doi.org/10.3390/ijms21113947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312515PMC
May 2020

Quantitative imaging of the receptor for advanced glycation end-products in prostate cancer.

Eur J Nucl Med Mol Imaging 2020 10 12;47(11):2562-2576. Epub 2020 Mar 12.

Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Purpose: Current screening and monitoring of prostate cancer (PCa) is insufficient, producing inaccurate diagnoses. Presence of the receptor for advanced glycation end-products (RAGE) is associated with signature characteristics of PCa development such as cell proliferation, anchorage-independent growth, angiogenesis, migration, invasion, and poor patient survival. Therefore, we developed a preclinical multimodal imaging strategy targeted at RAGE to diagnose and monitor PCa.

Methods: In this work, RAGE-targeted multimodal nanoparticles (64Cu-Cy5-G4-CML) were synthesized and rendered functional for nuclear and optical imaging using previously established methods. The probe's binding affinity and targeting specificity was assessed in androgen-dependent (LNCaP) and androgen-independent (DU145) prostate cancer cells using flow cytometry and confocal microscopy. In vivo PET-CT imaging was used to evaluate RAGE levels in DU145 and LNCaP xenograft models in mice. Then, tumors were excised post-imaging for histological staining and autoradiography to further assess RAGE levels and targeting efficiency of the tracer. Finally, RAGE levels from human PCa samples of varying Gleason Scores were evaluated using Western blot and immunohistochemical staining.

Results: PCa cell culture studies confirmed adequate RAGE-targeting with 64Cu-Cy5-G4-CML with K between 360 and 540 nM as measured by flow cytometry. In vivo PET-CT images of PCa xenografts revealed favorable kinetics, rapid blood clearance, and a non-homogenous, enhanced uptake in tumors, which varied based on cell type and tumor size with mean uptake between 0.5 and 1.4%ID/g. RAGE quantification of human samples confirmed increased RAGE uptake corresponding to increased Gleason scoring.

Conclusions: Our study has shown that RAGE-targeted cancer imaging is feasible and could significantly impact PCa management.
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http://dx.doi.org/10.1007/s00259-020-04721-1DOI Listing
October 2020

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer.

Sci Rep 2020 02 5;10(1):1871. Epub 2020 Feb 5.

Department of Oncology, Military Institute of Medicine, Warsaw, Poland.

Gallbladder cancer (GBC) is a highly malignant tumor with poorly understood etiology. An insight into phenotypic features of this malignancy may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. We assessed the expression of female sex hormone receptors (ERα, ERβ, PR), connective tissue growth factor (CTGF) and HER2 in GBC, and adjacent normal tissue (NT), and determined their prognostic impact. Immunohistochemical (IHC) expression of all biomarkers was performed in formalin-fixed, paraffin-embedded specimens in 60 Caucasian GBC patients (51 women and 9 men). ERβ, cytoPR and CTGF expression were found in 89%, 27%, 91% of GBC, and in 63%, 87%, 100% of NT, respectively. No ERα expression was found in GBC and NT. Strong (3+) HER2 expression by IHC or HER2 amplification was seen in five GBC (10.4%). A positive correlation was found between HER2 and CTGF and ERβ expression in GBC and matched NT. In the multivariate analysis, patient age >70 years, tumor size and ERβ expression in GBC was highly predictive for OS (p = 0.003). The correlation between HER2, CTGF and ERβ expression in GBC and NT may indicate the interaction of these pathways in physiological processes and gallbladder pathology.
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http://dx.doi.org/10.1038/s41598-020-58777-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002405PMC
February 2020

Liquid biopsy for minimally invasive heart transplant monitoring: a pilot study.

J Clin Pathol 2020 Aug 5;73(8):507-510. Epub 2019 Dec 5.

Department of Cardiac & Vascular Surgery, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.

Background: Heart transplantation allows for a long-term management of patients with end-stage heart failure. After the surgery, organ rejection is monitored with endomyocardial biopsy, which is an invasive, but not always informative procedure. Therefore, there is a pressing need for a new, safe, yet reliable, diagnostic method. Here, we present a pilot study confronting liquid biopsy based on donor-specific cell-free DNA with the protocol endomyocardial biopsy.

Methods: The study was performed on 21 blood samples matched with endomyocardial biopsy (graded according to acute cellular rejection scale) from nine patients after heart transplantation. Genotyping was performed on genomic DNA from donors and recipients for 10 single-nucleotide polymorphisms (SNPs). Cell-free DNA isolated from plasma was analysed with digital droplet PCR to detect donor-specific alleles.

Results: From 21 analysed endomyocardial biopsies, 4 were graded as 0R and 17 as 1R. Liquid biopsy was successfully performed in each sample for all informative SNPs (median of 3 per patient). We observed a high homogeneity of the results between SNPs in each sample (interclass correlation coefficient of >0.9).

Conclusions: There is a undeniable need for an alternative, non-invasive diagnostic procedure of early transplant rejection and investigation of donor-derived cell-free DNA seems to be the promising choice. The very high sensitivity is particularly enticing to consider liquid biopsy as a potential screening tool. Its minimal invasiveness may allow for more frequent examination and, thus, tighter monitoring. The reliable assessment of its clinical utility requires an adequately powered and properly designed multicentre study.
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http://dx.doi.org/10.1136/jclinpath-2019-205926DOI Listing
August 2020

The PD-L1/PD-1 axis expression on tumor-infiltrating immune cells and tumor cells in pediatric rhabdomyosarcoma.

Pathol Res Pract 2019 Dec 23;215(12):152700. Epub 2019 Oct 23.

Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland. Electronic address:

Background: Activation of immune checkpoints, e.g. PD-1/PD-L1 axis, in cancer microenvironment, enables evasion of host anti-cancer immune response and drives tumor progression. To date, there have been only a few studies analyzing PD-1/PD-L1 expression in pediatric malignancies.

Aim: In the current study, we aimed to assess PD-L1 and PD-1 expression in pediatric rhabdomyosarcoma (RMS) and to investigate their clinicopathological associations.

Materials And Methods: The study enrolled 31 children with RMS. Tissue microarrays with representative tumor tissue samples were stained with anti-PD-1 NAT105 clone (Ventana, Roche) and two different antibodies against PD-L1: SP142 (Ventana, Roche) and 22C3 (DAKO). Adequate positive controls were applied. Their expression was assessed in tumor-associated immune cells (TAICs) and in the tumor cells separately.

Results: We did not detect any positive PD-L1 staining in analyzed tumors using SP142 antibody; however, in 11 cases (35.48%) its expression was revealed by means of 22C3 clone. The staining was restricted to TAICs in all cases, which no reaction in tumor cells. The 5-year relapse free survival (RFS) rate was significantly higher in PD-L1 positive cases (61.5% vs 25.0%, p = 0.024), but it most likely results from more frequent PD-L1 expression in low-stage RMS. PD-1 expression on TAICs was detected in 7 cases and did not influence the prognosis.

Conclusions: We found that PD-L1 expression on TAICs, as detected with the use of 22C3 clone but not SP142 antibody, tends to be associated with low-stage RMS in children. PD-1 expression on TAICs in RMS is neither associated with distinct clinical course nor with clinicopathological features.
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http://dx.doi.org/10.1016/j.prp.2019.152700DOI Listing
December 2019

Expression of adiponectin receptors 1 and 2 and the leptin receptor in human adrenal tumors.

Arch Med Sci 2019 Sep 1;15(5):1254-1260. Epub 2018 Jun 1.

Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.

Introduction: The role of adipokines in neoplasms not related to obesity is unclear. The presence of adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) as well as the leptin receptor (Ob-R) has been recognized in human adrenal tumors. The authors of the present study were the first to compare the expression of these receptors in histopathologically distinct adrenal tumors.

Material And Methods: The study encompassed tissue specimens of 128 patients with adrenal tumors (28 adrenal cortical adenomas (CA), 35 cortical nodular hyperplasia tumors (CNH), 20 cortical carcinomas (CC), 40 pheochromocytomas (PHEO), 5 malignant pheochromocytomas (PHEOM)) operated on at a single clinical center. The expression of the adiponectin receptors AdipoR1 and AdipoR2 as well as the leptin receptor Ob-R was assessed by immunohistochemistry. The results were correlated with body mass index (BMI) and gender of the patients.

Results: AdipoR1 expression was significantly higher in cortical cancers ( < 0.001) and pheochromocytomas ( < 0.001) as compared to benign cortical tumors. AdipoR2 expression was significantly higher in cortical carcinomas as compared to cortical adenomas and hyperplasia tumors ( = 0.01), and also significantly higher in pheochromocytomas in comparison to adrenocortical cancers ( = 0.004). Leptin receptor expression was absent or minimal in half of nodular hyperplasia tumors and adrenal cortex adenomas. This receptor's expression was significantly higher in adrenocortical cancers ( = 0.038). In pheochromocytomas this receptor was expressed more abundantly than in adrenocortical cancers ( = 0.004).

Conclusions: These novel findings suggest that adiponectin and leptin receptors could play a regulatory role in human adrenal neoplasms.
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http://dx.doi.org/10.5114/aoms.2018.76142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764317PMC
September 2019

Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

Am J Surg Pathol 2020 02;44(2):162-173

Laboratory of Pathology, National Cancer Institute, Bethesda, MD.

This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity. ArcherDx assay detected TPM3-NTRK1 (n=9), LMNA-NTRK1 (n=3), TPR-NTRK1 (n=2) and EML4-NTRK3 (n=1) fusion transcripts in 15 cases with sufficient RNA quality. Patients were predominantly women (median age: 63 y). The tumors involved the right (n=12) and left colon unequally and were either stage T3 (n=12) or T4. Local lymph node and distant metastases were seen at presentation in 6 and 1 patients, respectively. Lymphovascular invasion was present in all cases. Histologically, tumors showed moderate to poor (n=11) differentiation with a partly or entirely solid pattern (n=5) and mucinous component (n=10), including 1 case with sheets of signet ring cells. DNA mismatch repair-deficient phenotype was seen in 13 cases. Tumor-infiltrating CD4/CD8 lymphocytes were prominent in 9 cases. Programmed death-ligand 1 positive tumor-infiltrating immune cells and focal tumor cell positivity were seen in the majority of cases. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 cases. No mutations in BRAF, RAS, and PIK3CA were identified. However, other genes of the PI3K-AKT/MTOR pathway were mutated. In several cases, components of Wnt/β-catenin (APC, AMER1, CTNNB1), p53, and TGFβ (ACVR2A, TGFBR2) pathways were mutated. However, no SMAD4 mutations were found. Two tumors harbored FBXW7 tumor suppressor gene mutations. NTRK fusion tumors constitute a distinct but rare subgroup of colorectal carcinomas.
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http://dx.doi.org/10.1097/PAS.0000000000001377DOI Listing
February 2020

Evaluation of Local Tissue Reaction After the Application of a 3D Printed Novel Holdfast Device for Left Atrial Appendage Exclusion.

Ann Biomed Eng 2020 Jan 15;48(1):133-143. Epub 2019 Jul 15.

Department of Cardiac and Vascular Surgery, Medical University of Gdansk, Gdańsk, Poland.

The left atrial appendage (LAA) is a small, finger-like extension of the left atrium and its exclusion is used as a treatment strategy to prevent ischemic stroke. Existing holdfast devices may damage the tissue, are unisized and not adjustable. A novel holdfast device for LAA exclusion devoid of these shortcomings was designed and 3D-printed using the Selective Laser Sintering (SLS) technology with polyamide powder and tested it on animal model. We selected the SLS 3D printing technology due to its wid14e availability and low production costs which could provide on-site 3D printing for specific patient. The purpose of this study was to evaluate the biocompatibility of the reported holdfast device and compare the histological results obtained for local tissue reactions to those obtained for an established grafting material. Thirty swine subdivided into two groups were examined. The LAA exclusion device was implanted and was either coated with a polyester vascular implant or not coated at all and the histological response to the device's presence was evaluated which is a standard approach to test the device biocompatibility. In all cases, complete occlusion was seen without any pathological findings during the incubation time. In both groups, the surface of the atrium under a holdfast device was smooth and shiny and had no clots. The foreign body reaction of the LAA holdfast device made of polyamide powder was insignificantly lower compared to the polyester graft. Thus, it fulfils the parameters of biocompatibility at the highest degree, and makes it suitable material for the manufacturing of LAA holdfast devices.
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http://dx.doi.org/10.1007/s10439-019-02320-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928093PMC
January 2020

A case report of melanoma metastasis to adrenal gland.

Pol Arch Intern Med 2019 09 10;129(9):636-637. Epub 2019 Jul 10.

Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland

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http://dx.doi.org/10.20452/pamw.14896DOI Listing
September 2019

Neuroendocrine tumour metastasis to the orbit.

Endokrynol Pol 2019 28;70(5):455-456. Epub 2019 May 28.

Medical University of Gdańsk, Gdańsk, Poland.

Neuroendocrine neoplasms are tumours that usually arise in the gastrointestinal tract and the bronchopulmonary system. The orbit is a rare anatomical site for their metastases. In the following article we present a case report of a 73-year-old man who was admitted to the Ophthalmology Department because of eye pain and high intraocular pressure in the right eye. There was also eye motility restriction, diplopia, oedema of the eyelid, and subconjunctival haemorrhage. Magnetic resonance imaging revealed a tumour in the right orbit, probably arising from the inferior rectus muscle. The patient was qualified for surgery, during which orbit decompression was conducted and a sample of the tumour tissue was collected. Based on the biopsy of the lesion, diagnosis of a metastatic neuroendocrine neoplasm, probably of gastrointestinal origin, was made. Further diagnostic procedures revealed metastases to other organs, and the patient was qualified for oncological treatment. In this case, orbital metastasis was the first diagnosed location of the neoplasm.
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http://dx.doi.org/10.5603/EP.a2019.0024DOI Listing
July 2020

Buschke-Löwenstein tumour associated with low-risk human papillomavirus genotypes successfully treated surgically.

Postepy Dermatol Alergol 2019 Feb 22;36(1):112-114. Epub 2019 Feb 22.

Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland.

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http://dx.doi.org/10.5114/ada.2019.82831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409871PMC
February 2019

Primarily resectable pancreatic adenocarcinoma - to operate or to refer the patient to an oncologist?

Crit Rev Oncol Hematol 2019 Mar 25;135:95-102. Epub 2019 Jan 25.

Department of Radiotherapy, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland.

The aim of this work is to investigate the optimal therapeutic sequence of resectable pancreatic cancer - primary surgery with adjuvant therapy or neoadjuvant followed by resection. Application of the neoadjuvant approach in routine treatment of pancreatic cancer is rapidly growing every year, despite the lack of final results from randomized trials. Recent advancements in the adjuvant therapy, due to the more effective chemotherapy regimens, favor the upfront surgery strategy. On the other hand, theoretical background and metaanalyses favor the neoadjuvant strategy. Currently, primary resection with adjuvant chemotherapy remains the standard approach in resectable pancreatic cancer, but the first recommendations considering the neoadjuvant approach as an option seem to arise among the scientific societies with a global impact. Preliminary results of Prodige 24 study and PREOPANC-1 trial demonstrates that both options are worth further evaluation in clinical trials. Their results should soon provide more answers to this important clinical questions.
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http://dx.doi.org/10.1016/j.critrevonc.2019.01.010DOI Listing
March 2019

Assessment of the usefulness of bacterial cellulose produced by Gluconacetobacter xylinus E as a new biological implant.

Mater Sci Eng C Mater Biol Appl 2019 Apr 14;97:302-312. Epub 2018 Dec 14.

Zbigniew Religa Foundation of Cardiac Surgery Development, ul. Wolności 345a, 41-800 Zabrze, Poland. Electronic address:

Bionanocellulose (BNC) is a clear polymer produced by the bacterium Gluconacetobacter xylinus. In our current study, "Research on the use of bacterial nanocellulose (BNC) in regenerative medicine as a function of the biological implants in cardiac and vascular surgery", we carried out material analysis, biochemical analysis, in vitro tests and in vivo animal model testing. In stage 1 of the project, we carried out physical and biological tests of BNC. This allowed us to modify subsequent samples of bacterial bionanocellulose. Finally, we obtained a sample that was accepted for testing on an animal model. That sample we define BNC1. Patches of BNC1 were then implanted into pigs' vessel walls. During the surgical procedures, we evaluated the technical aspects of sewing in the bioimplant, paying special attention to bleeding control and tightness of the suture line and the BNC1 bioimplant itself. We carried out studies evaluating the reaction of an animal body to an implantation of BNC1 into the circulatory system, including the general and local inflammatory reaction to the bioimplant. These studies allowed us to document the potential usefulness of BNC as a biological implant of the circulatory system and allowed for additional modifications of the BNC to improve the properties of this new implantable biological material.
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http://dx.doi.org/10.1016/j.msec.2018.12.016DOI Listing
April 2019

Aromatase inhibitor therapy for endometrial stromal sarcoma - two-centre experience.

Ginekol Pol 2018;89(11):607-610

Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland.

Objectives: Endocrine therapy is the recommended systemic treatment for steroid receptor positive endometrial stromal sarcoma (ESS). There is no current consensus on the optimal hormonal therapy for ESS. The literature offers several reports on advanced/recurrent/metastatic ESS patients treated with progestins, whereas data on the efficacy of aromatase inhibitors are scarce.

Material And Methods: We retrospectively identified cases treated for ESS with aromatase inhibitors at our institutions. There were five patients with advanced or unresectable recurrent estrogen, progesterone and androgen receptor-positive ESS, treated with aromatase inhibitors: letrozole or anastrozole (at a daily dose of 2.5 mg and 1 mg, respectively), as first-line endocrine therapy in all but one case treated following progression with megestrol acetate.

Results: Disease stabilization was achieved in four cases (80%), including two with long-term progression-free survival for up to 10 years attained under letrozole treatment, and one case after prior progestin treatment. During therapy, no substantial toxicity was observed.

Conclusions: Aromatase inhibitors as first- or second-line endocrine treatment achieve disease control in most steroid receptor positive ESS. Our series of cases is evidence of aromatase inhibitors efficacy as long-term endocrine treatment option for ESS patients.
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http://dx.doi.org/10.5603/GP.a2018.0104DOI Listing
February 2019

The relationship between HER2 overexpression and angiogenesis in gastric cancer.

Medicine (Baltimore) 2018 Oct;97(42):e12854

Department of Oncological Surgery, Gdynia Oncology Centre, Gdynia.

In gastric cancer, HER2 protein overexpression is considered to be conducive to the higher proliferation activity of the tumor cells. Tumor formation is associated with angiogenesis in order to secure an abundant supply of oxygen and glucose to cancer cells. The aim of the study was to assess if HER2 overexpression is related to higher microvessel density (MVD) in the tumor stroma.The archival samples of primary tumor from 144 consecutive patients that underwent gastric resection for cancer between August 1, 2006 and December 31, 2013 in the Department of Oncological Surgery of Medical University of Gdańsk were analyzed. CD34 was used as a marker of MVD in the tumor stroma. Both CD34 and HER2 protein expressions were tested by immunohistochemistry.The assays were unsuccessful to estimate HER2 in 10 cases and CD34 in 14 cases due to technical reasons. The results were obtained for 128 patients. HER2 0 and HER2 1+ were considered negative, while HER2+ and HER2 3+ were recognized as positive. Mean MVD (mean number of vessels in the visual field) was 32.4 (median 29.5). Microvessel density was insignificantly higher in HER2 positive tumors. The slight difference was also seen between IHC 2+ and 3+ groups. The differences did not reach the level of statistical significance.Statistical analysis performed in our study did not reveal the significant relationship between HER2 overexpression on the tumor cells and MVD in the tumor stroma.
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http://dx.doi.org/10.1097/MD.0000000000012854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211927PMC
October 2018

Cholecystectomy after endoscopic retrograde cholangiopancreatography - effect of time on treatment outcomes.

Prz Gastroenterol 2018 17;13(3):251-257. Epub 2018 Sep 17.

Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland.

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http://dx.doi.org/10.5114/pg.2018.78292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173079PMC
September 2018

The role of radiotherapy in the management of primary cardiac lymphoma a case report and the literature review.

Leuk Lymphoma 2019 03 6;60(3):812-816. Epub 2018 Sep 6.

a Department of Clinical Oncology and Radiotherapy , Medical University of Gdańsk , Gdańsk , Poland.

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http://dx.doi.org/10.1080/10428194.2018.1509321DOI Listing
March 2019

Liver metastasis of a neuroendocrine neoplasm of unknown primary origin in a female patient with a history of breast cancer.

Contemp Oncol (Pozn) 2018 29;22(2):124-128. Epub 2018 Jun 29.

Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.

We report on and discuss a case of a female patient diagnosed with breast cancer in 1996, which was histopathologically assessed as an invasive ductal carcinoma. The patient was admitted to our Department in 2017 with a liver metastasis of a neuroendocrine tumour. On admission she had no symptoms of an endo-crinopathy and was in a good general condition. Due to unknown primary site of the metastasis and given the patient's history of breast cancer, it was suspected that the breast cancer was in fact a neuroendocrine tumour. This hypothesis was confirmed by comparing histopathological specimens of the breast and liver tumours using advanced pathological methods.
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http://dx.doi.org/10.5114/wo.2018.76831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103232PMC
June 2018

Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases.

Nat Commun 2018 07 13;9(1):2705. Epub 2018 Jul 13.

Women's Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.

Brain metastases are devastating complications of cancer. The blood-brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood-tumor barrier (BTB) when brain metastases form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy by limiting drug uptake. Here, we report that experimental breast cancer brain metastases of low- and high permeability to a dextran dye exhibit distinct microenvironmental gene expression patterns. Astrocytic sphingosine-1 phosphate receptor 3 (S1P3) is upregulated in the neuroinflammatory response of the highly permeable lesions, and is expressed in patients' brain metastases. S1P3 inhibition functionally tightens the BTB in vitro and in vivo. S1P3 mediates its effects on BTB permeability through astrocytic secretion of IL-6 and CCL2, which relaxes endothelial cell adhesion. Tumor cell overexpression of S1P3 mimics this pathway, enhancing IL-6 and CCL-2 production and elevating BTB permeability. In conclusion, neuroinflammatory astrocytic S1P3 modulates BTB permeability.
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http://dx.doi.org/10.1038/s41467-018-05030-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045677PMC
July 2018

Expression of adiponectin and leptin receptors in adrenal incidentaloma patients with subclinical hormone secretion.

Cancer Biomark 2018 ;22(2):325-332

Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Poland.

Background: The role of adopokines in adrenal tumors' hormonal activity remains unclear. Obesity may induce arterial hypertension, disorders of carbohydrate metabolism, and is a risk factor of cardiovascular disease. In patients with subclinical hormone secretion by the adrenal cortex or medulla the risk of metabolic disease is increased.

Objective: Authors of this retrospective study selected 78 patients with subclinical hormone secretion out of all adrenal incidentaloma patients hospitalized in the Department of Endocrinology and Internal Medicine between 1995 and 2014.

Methods: The analyzed group comprised of 38 subclinical Cushing's syndrome (SCS), 40 incidentally discovered pheochromocytoma (PHEO) and 42 patients operated due to an adrenal tumor without pathological hormonal activity. Expression of adiponectin (AdipoR1, AdipoR2) and leptin (Ob-R) receptors in adrenal tumors was assessed in relation to body mass index (BMI) and hormonal activity.

Results: We found statistically significant negative correlations between BMI and expression of all examined receptors in SCS patients (AdipoR1: p= 0.032; AdipoR2: p< 0.001; leptin Ob-R: p= 0.001). In PHEOs, BMI correlated negatively only with AdipoR2 (p= 0.014).

Conclusions: Data obtained show that the most significant factor associated with the expression of AdipoR1, AdipoR2 and leptin Ob-R receptors in the adrenal tumor tissue is BMI, not their hormonal activity.
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http://dx.doi.org/10.3233/CBM-171049DOI Listing
October 2018

The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis.

Reumatologia 2017;55(5):230-236. Epub 2017 Oct 28.

Department and Clinic of Nephrology, Transplantology and Internal Diseases, Medical University of Gdansk, Poland.

Introduction: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated, systemic disease characterized by necrotizing small and medium vessel vasculitis of unknown etiology associated with granulomatous inflammation affecting the renal, pulmonary, upper airways, ocular systems and other tissues. Histological proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of clinically involved sites. The main purpose of this study was to examine histopathological changes in non-renal biopsies from patients with established diagnosis of GPA and evaluated the histological confirmation at diagnosis of this disease.

Material And Methods: A retrospective analysis was performed in patients with GPA diagnosed and treated in clinics of the University Clinical Center (UCK) in Gdansk in 1988-2009.

Results: In the analyzed group of GPA patients the histopathological examination of biopsies taken from involved tissues (except kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%) were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were non-specific. Considering all biopsies, the diagnosis was confirmed in 24 patients (57% of patients in whom biopsies were taken). Epitheloid cell granulomas were present in 33 biopsies (43%), characteristic necrosis in 27 biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while multinucleated giant cells were identified only in 9 biopsies (12%).

Conclusions: Histopathological examination of the affected tissues remains the gold standard of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative patients, in the initial phase of the disease, or in patients with atypical clinical presentation. In many cases, it is necessary to repeat biopsy to establish the diagnosis. The role of the histopathological examination seems to be particularly important when ANCA is negative or clinical symptoms are atypical of GPA.
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http://dx.doi.org/10.5114/reum.2017.71638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746633PMC
October 2017

PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients.

Oncotarget 2017 Oct 15;8(52):89903-89912. Epub 2017 Sep 15.

Department of Pathology, The Medical University, Gdańsk, Poland.

Background: Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies.

Aim: To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it's clinicopathological and prognostic significance.

Methods: Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells. PD-L1 positivity was defined as ≥5% of PD-L1-positive cells. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model.

Results: PD-L1 expression was detected on cancer and peritumoral immune cells. PD-L1-positivity of cancer nests (27/84, 32.1%) was correlated with higher infiltration of CD4+ (p=0.037), CD8+ (p=0.02), FOXP3+ (p=0.007), CD68+ (p=0.021) cells, while PD-L1 positivity of peritumoral immune cells (51/84, 60.7%) was correlated with higher infiltration of intraepithelial FOXP3+ cells only (p=0.037).PD-L1-positivity of cancer cells but not immune cells, was more frequently observed in p16-negative tumors (p=0.004). High-risk HPV-status did not correlate with the PD-L1 status of cancer and immune cells (p=1.000) and (p=1.000) respectively). Median follow up was 89.20 months (range 1.7-189.5). PD-L1 positivity of peritumoral immune cells was found to be an independent favorable prognostic factor for OS. Conclusion: This study highlights the importance of comprehensive PD-L1 assessment in both cancer and immune cells. PD-L1 expression on peritumoral immune cells seems to be an additional prognostic factor in vSCC patients and may influence the results by anti-PD-L1 treatment.
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http://dx.doi.org/10.18632/oncotarget.20911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685718PMC
October 2017

Diagnostic and prognostic role of SF1, IGF2, Ki67, p53, adiponectin, and leptin receptors in human adrenal cortical tumors.

J Surg Oncol 2017 Sep 3;116(3):427-433. Epub 2017 Jul 3.

Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.

Background: The authors have examined the immunohistochemical expression of several proteins and their relationship with adrenal cortical carcinoma (ACC) diagnosis and progression.

Materials And Methods: A total of 83 patients with benign and malignant adrenal cortex tumors operated on in a single center were included in the study. Expression of the following proteins was examined: steroidogenic factor 1 (SF1), insulin growth factor 2 (IGF2), Ki67, p53, as well as adiponectin (Adipo R1, Adipo R2), and leptin (Ob-R) receptors.

Results: Multivariate analysis revealed that the expression of SF1, IGF2, and Adipo R1 and R2 receptors was associated with ACC diagnosis. An acknowledged proliferation marker Ki67 was related with the size of ACC and was an independent ACC diagnosis marker. The authors also assessed the relationship between immunohistochemical parameters and overall survival (OS) and disease progression. Only high IGF2 expression was associated with longer OS (P = 0.025). The most significant one for the prognosis of ACC patients was tumor resectability of the primary tumor. More favorable prognosis was found for young men (P = 0.033).

Conclusions: The presented data indicate that immunohistochemical assessment (of IGF2, SF1, Adipo R1, and R2 receptors' expression) may be useful in making the diagnosis of uncertain ACC cases.
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http://dx.doi.org/10.1002/jso.24665DOI Listing
September 2017

SP174, NRAS Q61R Mutant-Specific Antibody, Cross-Reacts With KRAS Q61R Mutant Protein in Colorectal Carcinoma.

Arch Pathol Lab Med 2017 Apr 28;141(4):564-568. Epub 2017 Feb 28.

From the Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland (Drs Lasota, Felisiak-Golabek, Inaguma, Wang, and Miettinen); the Departments of Molecular Diagnostics (Dr Kowalik, Ms Pięciak, and Mr Zięba), Surgical Pathology (Dr Kopczynski), and Clinical Oncology (Dr Gozdz), Holycross Cancer Center, Kielce, Poland; the Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan (Dr Inaguma); the Department of Pathomorphology, Medical University of Gdansk, Poland (Drs Pęksa and Biernat); the Department of Pathomorphology, Jagiellonian University, Krakow, Poland (Dr Okoń); ZDUNOMED/Histopathology, Szczecin, Poland (Dr Waloszczyk); and Faculty of Health Sciences, The Jan Kochanowski University, Kielce, Poland (Dr Gozdz). Drs Lasota and Kowalik contributed equally to this work.

Context: - NRAS is a member of the RAS family oncoproteins implicated in cancer. Gain-of-function NRAS mutations were reported in a subset of colorectal cancers. These mutations occur at codons 12, 13, and 61 and are detected by molecular genetic testing. Recently, an antibody (clone SP174) became available to immunohistochemically pinpoint NRAS Q61R mutant protein. In malignant melanoma, NRAS Q61R mutant-specific immunohistochemistry was shown to be a valuable supplement to traditional genetic testing.

Objective: - To evaluate the significance of NRAS Q61R mutant-specific immunohistochemistry in a cohort of colorectal carcinomas.

Design: - A total of 1185 colorectal carcinomas were immunohistochemically evaluated with SP174 antibody. NRAS Q61R mutant-specific immunohistochemistry was validated by molecular genetic testing including Sanger sequencing, quantitative polymerase chain reaction (qPCR), and next-generation sequencing.

Results: - Twelve tumors showed strong SP174 immunoreactivity. Sanger sequencing detected an identical c.182A>G substitution, causing NRAS Q61R mutation at the protein level, only in 8 SP174-positive cases. These results were confirmed by qPCR study. Subsequently, NRAS wild-type tumors with strong SP174 staining were evaluated by next-generation sequencing and revealed KRAS c.182A>G substitutions predicted to cause KRAS Q61R mutation. Review of colorectal carcinomas with known KRAS and NRAS genotype revealed that none of 62 wild-type tumors or 47 mutants other than Q61R were SP174 positive.

Conclusion: - SP174 immunohistochemistry allows sensitive detection of NRAS and KRAS Q61R mutants. However, molecular genetic testing is necessary to determine specifically which RAS gene is mutated.
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http://dx.doi.org/10.5858/arpa.2016-0147-OADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888553PMC
April 2017

Self-diagnosis of hyperparathyroidism during pregnancy resulting in parathyroidectomy and uncomplicated delivery.

Gynecol Endocrinol 2017 Jun 6;33(6):425-428. Epub 2017 Mar 6.

a Department of Endocrinology and Internal Medicine.

Primary hyperparathyroidism is a condition with hypercalcemia and elevated parathyroid hormone (PTH). Typically, treating patients with such disease does not pose a problem for doctors, unless the patient is pregnant. Firstly, pregnancy may mask signs of hypercalcemia. Secondly, treatment should be applied with special care for immature fetus. If undiagnosed and untreated, it is life-threatening for the mother and the baby. The main cause of primary hyperparathyroidism is parathyroid adenoma, which should be removed surgically in second trimester. If the patient is monitored by a multidisciplinary team, the risk of mortality and pregnancy loss is reduced.
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http://dx.doi.org/10.1080/09513590.2017.1296946DOI Listing
June 2017