Clinical and Experimental Medicine

Correction to: BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases The original version of this article unfortunately contained a mistake. First and last names of the authors were interchanged.

Systemic treatment of the metastatic renal cell carcinoma: usefulness of the apparent diffusion coefficient of diffusion-weighted MRI in prediction of early therapeutic response Abstract Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration—7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05–11.61), 7.40 ± 2.50 months (95% CI = 5.61–9.19) and 4.20 ± 1.99 months (95% CI = 2.78–5.62) accordingly (p < 0.05). There was no difference in change of main lesions’ longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35–25.87) and by 7.66 ± 6.72% (95% CI = 2.86–12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.

Dietary phytochemicals as the potential protectors against carcinogenesis and their role in cancer chemoprevention Abstract Health-threatening consequences of carcinogen exposure are mediated via occurrence of electrophiles or reactive oxygen species. As a result, the accumulation of biomolecular damage leads to the cancer initiation, promotion or progression. Accordingly, there is an association between lifestyle factors including inappropriate diet or carcinogen formation during food processing, mainstream, second or third-hand tobacco smoke and other environmental or occupational carcinogens and malignant transformation. Nevertheless, increasing evidence supports the protective effects of naturally occurring phytochemicals against carcinogen exposure as well as carcinogenesis in general. Isolated phytochemicals or their mixtures present in the whole plant food demonstrate efficacy against malignancy induced by carcinogens widely spread in our environment. Phytochemicals also minimize the generation of carcinogenic substances during the processing of meat and meat products. Based on numerous data, selected phytochemicals or plant foods should be highly recommended to become a stable and regular part of the diet as the protectors against carcinogenesis.

Correction to: Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis The original version of this article unfortunately contained a mistake. Camila Cataldi de Alcantara was not listed among the authors. The corrected author group should be:

Early fibrosis regression by shear wave elastography after successful direct-acting anti-HCV therapy Abstract Shear wave elastography (SWE) is a noninvasive ultrasound-based marker of hepatic fibrosis not requiring a special device. Successful direct-acting anti-HCV therapy was associated with hepatic fibrosis regression assessed by transient elastography (FibroScan). Data on the utility of SWE in these patients and how early fibrosis can regress after treatment are still lacking. To assess liver fibrosis by SWE before and after direct-acting antiviral treatment of chronic hepatitis C (CHC), we enrolled 165 CHC genotype 4 Egyptian patients treated with different Sofosbuvir-based regimens. Patients’ laboratory characteristics, fibrosis biomarkers, namely Fibrosis-4 (FIB-4) index and AST/platelet ratio index (APRI) and liver stiffness measurements (LSM) by SWE were evaluated at baseline, end of treatment (EOT at week 12), week 24 and week 36. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as FIB-4 and APRI indices decreased significantly at EOT, week 24 and week 36 in comparison to baseline (P value < 0.001). Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to week 24 and week 36 with a P value < 0.001. The mean LSM showed improvement at EOT (7.01 ± 3.59 kpa), week 24 (6.18 ± 3.39 kpa) and week 36 (5.74 ± 3.21 kpa) in comparison to baseline (8.49 ± 0.83 kpa) (P value < 0.001). There is early liver fibrosis regression at EOT and throughout the time after successful treatment with direct-acting antiviral agents (DAAs). SWE is a feasible, easily applicable noninvasive relatively inexpensive assessment method of liver fibrosis.

Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer Abstract One of the most common mechanisms of immune evasion in MSI colorectal cancers (CRCs) is loss of HLA class I expression due to mutations in B2M gene which can become a negative predictor for checkpoint blockade therapy. The aim of this study was the determination of prevalence of B2M somatic mutations in MSI CRC patients and relationship between B2M mutations and lymphocytes infiltration and other clinicopathological features as well as detection of methylation changes in B2M promoter region which can be another mechanism of immune escape. In our study, 37 MSI-H and 5 MSI-L patients were selected for screening of B2M mutational and methylation status. The characterization of patients was based on standard histopathological diagnosis and TNM classification; BRAF, KRAS mutations, tumor-infiltrating lymphocytes and peritumoral lymphoid reaction were also determined. MSI analysis was performed using fragment analysis. B2M mutations were identified by Sanger sequencing, and methylation of CpG islands in promoter region was detected by methylation-specific PCR. Heterozygous mutations in the B2M gene were detected in five MSI-H patients (13.5%), while the mutation c.45_48delTTCT was determined in four patients and mutation c.276delC was found in two patients. One of these five patients was compound heterozygote harboring both mutations. Methylation of the promoter region of the B2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic changes in B2M gene could be important in personalized therapy for CRC patients as these changes may be one of the mechanisms of secondary resistance of MSI positive tumors to immunotherapy.

PDCD1 and PDCD1LG1 polymorphisms affect the susceptibility to multiple myeloma Abstract Single-nucleotide polymorphisms (SNPs) of the programmed cell death protein-1 (PDCD1), programmed cell death protein-1 ligand-1 (PDCD1LG1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA4) genes are implicated in the pathogenesis of some cancers. We investigated the role of PDCD1, PDCD1LG1, and CTLA4 SNPs in MM pathogenesis and the susceptibility to and clinical features of multiple myeloma (MM). We obtained genomic DNA from 124 patients with MM and 211 healthy controls and detected PDCD1 (rs36084323, rs41386349, and rs2227982), PDCD1LG1 (rs2297136 and rs4143815), and CTLA4 (rs733618, rs11571316, rs231775, and rs3087243) genotypes using the polymerase chain reaction–restriction fragment length polymorphism method or the TaqMan allelic discrimination real-time PCR method. The patients with MM had a significantly higher frequency of the PDCD1 GCC/GCC haplotype (rs36084323/rs41386349/rs2227982) compared with the healthy controls. PDCD1 rs2227982 CC genotype was associated significantly with a higher frequency of bone lesions. Patients with PDCD1LG1 rs2297136 TT and TC types (high-expression types) showed lower albumin level than those with CC genotype. In addition, the PDCD1LG1 rs4143815 CC and CG types (high-expression types) were associated significantly with higher frequency of patients who were treated with thalidomide and/or bortezomib. However, there was no statistical significance between CTLA4 polymorphisms and clinical variables of patients with MM. There were no significant differences between all the polymorphisms and OS. Our study indicates that the PDCD1 haplotype is associated with a susceptibility to MM. The PDCD1 rs2227982 and PDCD1LG1 rs2297136 affect the clinical features of multiple myeloma patients.

Iron chelation therapy for myelodysplastic syndrome: a systematic review and meta-analysis Abstract Iron overload remains a concern in myelodysplastic syndrome (MDS) patients especially those requiring recurrent blood transfusions. Whether iron chelating therapy (ICT) is beneficial to the long-term survival of myelodysplastic syndrome is still a controversial issue. Therefore, we conducted a systematic review and meta-analysis to clarify the relationship between ICT and long-term survival in patients with MDS. A total of 14 studies involving 7242 participants were identified; the outcomes revealed that for patients with MDS, ICT resulted in a lower risk of mortality compared to those with no ICT (HR 0.57; 95% CI 0.44–0.70; P < 0.001); what is more, ICT led to a lower risk of leukemia transformation (HR 0.70; 95% CI 0.52–0.93; P = 0.016). Results of subgroup analyses based on adequate ICT or any ICT, low/int-1 IPSS or unclassified IPSS and study types indicated that the ICT had a beneficial role in all these groups of patients.

Correlation analysis of hepatitis C virus core antigen and low viral loads: Can core antigen replace nucleic acid test? Abstract Value of hepatitis C virus (HCV) core antigen (cAg) test has been controversy in patients with low HCV loads for its lower sensitivity. We assessed correlation between HCV-cAg and HCV RNA in serum samples with low viral loads and analyzed the performance of HCV-cAg assay in determining diagnosis and treatment outcomes in chronic hepatitis C patients. Both HCV RNA and HCV-cAg were detected for 2298 serum samples. Correlation analysis was performed between the two tests. Receiver operating characteristics (ROC) curve was used to assess value of HCV-cAg test in determining diagnosis and response outcomes at the different HCV RNA thresholds. The two tests were correlated very well, and moreover, correlation in the low viral load group was higher than that in the high viral load group (r value: 0.901 and 0.517). Positive agreement of HCV-cAg ≥ 3 fmol/L was as high as 97.0% for HCV RNA ≥ 1000 IU/mL, and its negative agreement for HCV RNA < 15 IU/mL was up to 98.9% in all samples. Area under ROCs ranged from 0.939 to 0.992, regardless of HCV RNA thresholds. When lower limit of detection of HCV RNA was 15, 100 or 1000 IU/mL, positive predictive value of HCV-cAg was 96.8%, 98.8% or 92.4%, and its negative predictive value was 87.0%, 89.9% or 98.3%, respectively, on the basis of different cutoff values. High-sensitivity HCV-cAg detection may likely replace HCV RNA to confirm the existence of HCV and to guide the treatment of chronic HCV infection.

Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis Abstract The objective of this study is to delineate the cellular adhesion molecule (CAM) profile and plasminogen activator inhibitor type 1 (PAI-1), and their association with metabolic syndrome (MetS) and carbohydrate metabolism biomarkers in psoriasis patients with mild and moderate severity. Sixty-seven patients with psoriasis as well as 102 healthy subjects were recruited. Insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), but not glucose, were significantly higher in psoriasis than in controls. Psoriasis was characterized by increased plasma levels of platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PAI-1 as compared with controls. Psoriasis diagnosis could explain 59.0% of CAM and PAI-1 variance, with a particularly strong impact on E-selectin (45.6%), VCAM-1 (32.7%), and PAI-1 (24.8%). Subjects with MetS showed significantly higher E-selectin and PAI-1 than those without MetS. Using VCAM-1, E-selectin, PAI-1 (all positively), and P-selectin (inversely) in a binary regression equation, it was found that 87.6% of all patients were correctly classified with a sensitivity of 92.5% and a specificity of 84.3%. CAM and PAI-1 were correlated with carbohydrate metabolism biomarkers (glucose, insulin, and HOMA-IR). In conclusion, CAM levels are associated with psoriasis diagnosis and MetS may influence E-selectin and PAI-1 concentrations. More studies are needed to verify the causality among these factors, as well as their relation to the different degrees of disease severity.