Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues.

This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.

siRNA-Mediated MELK Knockdown Induces Accelerated Wound Healing with Increased Collagen Deposition.

Skin wounds remain a significant problem for the healthcare system, affecting the clinical outcome, patients' quality of life, and financial costs. Reduced wound healing times would improve clinical, economic, and social aspects for both patients and the healthcare system. Skin wound healing has been studied for years, but effective therapy that leads to accelerated wound healing remains to be discovered. This study aimed to evaluate the potential of MELK silencing to accelerate wound healing. A vectorless, transient knockdown of the MELK gene using siRNA was performed in a murine skin wound model. The wound size, total collagen, type 3 collagen, vessel size, vessel number, cell proliferation, cell apoptosis, number of mast cells, and immune infiltration by CD45, CD11b, CD45, and CD8a cells were evaluated. We observed that treatment with MELK siRNA leads to significantly faster wound closing associated with increased collagen deposition.

Occurrence of IL-1, IL-10, CD25, CD40, and CD69 in the tissue of palatine tonsils.

Introduction: Palatine tonsil disease often coexists with dermatological diseases. Correct diagnosis of inflammation of the palatine tonsil tissue and removal of the diseased palatine tonsils results in remission of the disease. Aim: To determine similarities and differences in the immunohistochemistry profile of the palatine tonsil tissue between tonsillitis and hypertrophy, including location of the immunohistochemistry reactions in specific histological sites. Material and methods: A prospective analysis of 50 palatine tonsils that had undergone tonsillectomy due to tonsillitis (30 cases) and hypertrophy (20 cases) was performed. The collected material underwent immunohistochemistry staining for: IL-1, IL-10, CD25, CD40, and CD69, and subsequently phenotypic expression of the obtained results was performed including their histological location. Results: Statistically significant differences (p < 0.05) between the tonsillitis and hypertrophy groups were found for almost all IHC reactions in the epithelium covering the tonsils for CD-25, CD-69, IL-1, IL-10. Furthermore, significant differences between these groups were found for IL-10 reaction in the subepithelial inflammatory infiltrate and follicular centres of lymphatic follicles as well as for CD-69 reaction between the follicles. When all the locations were summarized, significant (p < 0.05) differences were found for all IHC reactions except for CD-40. Conclusions: The investigated markers and cytokines: CD25 and CD69, and IL-1 and IL-10 are more abundant in tonsillitis than in hypertrophy of the palatine tonsils.

Effect of Different Wavelengths of Laser Irradiation on the Skin Cells.

The invention of systems enabling the emission of waves of a certain length and intensity has revolutionized many areas of life, including medicine. Currently, the use of devices emitting laser light is not only an indispensable but also a necessary element of many diagnostic procedures. It also contributed to the development of new techniques for the treatment of diseases that are difficult to heal. The use of lasers in industry and medicine may be associated with a higher incidence of excessive radiation exposure, which can lead to injury to the body. The most exposed to laser irradiation is the skin tissue. The low dose laser irradiation is currently used for the treatment of various skin diseases. Therefore appropriate knowledge of the effects of lasers irradiation on the dermal cells' metabolism is necessary. Here we present current knowledge on the clinical and molecular effects of irradiation of different wavelengths of light (ultraviolet (UV), blue, green, red, and infrared (IR) on the dermal cells. .

Functional Assessment of Synoptic Pathology Reporting for Ovarian Cancer.

BACKGROUND: Ovarian cancer has one of the highest death/incidence rates and is commonly diagnosed at an advanced stage. In the recent WHO classification, new histotypes were classified which respond differently to chemotherapy. The e-standardized synoptic cancer pathology reports offer the clinicians essential and reliable information. The aim of our project was to develop an e-template for the standardized synoptic pathology reporting of ovarian carcinoma [based on the checklist of the College of American Pathologists (CAP) and the recent WHO/FIGO classification] to introduce a uniform and improved quality of cancer pathology reports. A functional and qualitative evaluation of the synoptic reporting was performed. METHODS: An indispensable module for e-synoptic reporting was developed and integrated into the Hospital Information System (HIS). The electronic pathology system used a standardized structure with drop-down lists of defined elements to ensure completeness and consistency of reporting practices with the required guidelines. All ovarian cancer pathology reports (partial and final) with the corresponding glass slides selected from a 1-year current workflow were revised for the standard structured reports, and 42 tumors [13 borderline tumors and 29 carcinomas (mainly serous)] were included in the study. RESULTS: Analysis of the reports for completeness against the CAP checklist standard showed a lack of pTNM staging in 80% of the partial or final unstructured reports; ICD-O coding was missing in 83%. Much less frequently missed or unstated data were: ovarian capsule infiltration, angioinvasion and implant evaluation. The e-records of ovarian tumors were supplemented with digital macro- and micro-images and whole-slide images. CONCLUSIONS: The e-module developed for synoptic ovarian cancer pathology reporting was easily incorporated into HIS.CGM CliniNet and facilitated comprehensive reporting; it also provided open access to the database for concerned recipients. The e-synoptic pathology reports appeared more accurate, clear and conclusive than traditional narrative reports. Standardizing structured reporting and electronic tools allows open access and downstream utilization of pathology data for clinicians and tumor registries.

Survivin expression as a prognostic factor in patients with epithelial ovarian cancer or primary peritoneal cancer treated with neoadjuvant chemotherapy.

BACKGROUND: The aim of this study was to evaluate association of expression of survivin and p53 with the effects of neoadjuvant chemotherapy (NAC) in patients with advanced ovarian cancer (AOC). METHODS: We retrospectively evaluated 60 consecutive patients with AOC (International Federation of Gynecology and Obstetrics stage IIIC-IV) treated with NAC. The expression of p53 and survivin was assessed immunohistochemically. The median of expression total score survivin equals 2 was adopted to dichotomize the group. The positive and negative expression of p53 was used to dichotomize the group. RESULTS: The expression of survivin in tumor tissue taken before and after NAC was a significant difference in the percentage of stained nuclei (P = 0.0002), the intensity of staining (P = 0.0003), and total score (P = 0.0001). There was a significant difference in p53 expression in tumor tissue before and after NAC in the percentage of stained nuclei (P = 0.0424). Survivin expression, in contrast to p53 expression, was a prognostic factor in patients with AOC treated with NAC (P = 0.0484). The expression of survivin and p53 was not a predictive factor. Independent adverse predictor factors were as follows: lack of optimal interval debulking surgery and the lack of an objective response (the respective hazard ratio was 3.93 [95% confidence interval, 2.07-7.46; P < 0.0001] and 2.36 [95% confidence interval,1.25-4.47; P = 0.0080]). The suboptimal range of interval debulking surgery, resistance to platinum, and the lack of paclitaxel in the NAC were adverse prognostic factors (the respective hazard ratio was 2.61 [95% confidence interval, 1.17-5.83], 2.72 [95% confidence interval, 1.07-6.89], and 2.56 [95% confidence interval, 1.06-6.18]; P < 0.05]). CONCLUSIONS: High expression of survivin could be a prognostic factor in patients treated with NAC for AOC.

Selected Immunohistochemical Assessment and Clinical Examinations in the Diagnosis of Palatine Tonsil Diseases.

INTRODUCTION: The palatine tonsils are secondary lymphoid organs where immune processes occur, influencing the development of a targeted cellular and humoral response. The diseased tonsils are subject to immunological imbalances, including the activity of pro-inflammatory and anti-inflammatory factors. This leads to the development of palatine tonsil diseases, such as palatine tonsillitis and palatine tonsillar hypertrophy. AIM: The main aim of the study was to evaluate the similarities and differences in the clinical and pathomorphological pictures of patients qualified for surgical treatment due to hypertrophy or inflammation of the palatine tonsils. The aim was achieved by demonstrating the relationship between the patient's medical history and physical examination and histopathological diagnosis of a given tonsillar disease, evaluating the usefulness of basic blood tests (leukocytosis, ASO, ESR, and CRP) in differential diagnosis, and assessing the immunohistochemical assessment of palatine tonsil tissue. MATERIAL AND METHODS: The tonsils were stained with the following antibodies: IL-1, IL-2, IL-6, IL-8 IL-10, and IL-37 and CD25, CD40, and CD69, taking into account the histological division of the studied lymphatic tissue (epithelial, subepithelial, follicular, follicular center, and interfollicular). Patients aged between 19 and 70 years with tonsillitis or clinical signs of tonsillar hypertrophy were qualified for tonsillectomy/UPPP. Seventy-two males (68.6%) and thirty-three females (31.4%) were enrolled in the study. Histopathological and immunohistochemical assessment was performed on 105 palatine tonsils. RESULTS: The diagnostic value of blood tests, including determination of ASO, ESR, CRP, and leukocyte level, proved to be a significant predictor of tonsil disease. In the pathomorphological assessment, 75% of the subjects who had simultaneously elevated ESR (>4.73) and leukocytosis (>6.96) and reduced ASO (<161.03) and CRP (<0.31) belonged to the tonsillitis group. The immunohistochemical assessment revealed a diverse profile of the markers tested depending on the diagnosed disease of the tonsils. The follicular center proved to be the region of palatine tonsil tissue for which the most statistically significant differences between the markers were found. Responses to CD-40 and IL-1 were observed in this region. The tissue of epithelial, follicular, and interfollicular regions each showed one statistically significant value for the studied chemokines and lymphokines. However, the lack of significant statistical differences for p < 0.05 between the study groups was only noted in the subepithelial region. It should be emphasized that for the data as a whole (calculated on the basis of the data for all regions together), no statistically significant differences were observed. CONCLUSION: In conclusion, the results obtained are indicative of the presence of a specific immunohistochemical profile for palatine tonsil diseases. Significant discrepancies have been found in the clinical and pathomorphological assessment of tonsils qualified for tonsillectomy. Therefore, these methods should be considered complementary. The patient's medical history and physical examination, depending on the adopted clinical or histopathological classification, show a variation in the distribution of features that are the basis for allocation to a particular group.

Clinical, Dermoscopic, and Histological Characteristics of Melanoma Patients According to the Age Groups: A Retrospective Observational Study.

BACKGROUND: Although the role of melanoma risk factors is well documented, their correlation with patients' age is less frequently analyzed. METHOD: The analysis was performed among 189 melanoma patients in different age groups, including <30 years, 31-60 years, and >60 years, to investigate the risk factors, topography, and coexistence of morphological features of 209 melanomas (dermoscopic and histopathological). RESULTS: Among the youngest age group, no correlation with the presence of estimated risk factors was found. The most common dermoscopic pattern was spitzoid and multicomponent asymmetric. The group of middle-aged patients was the most diverse in terms of the occurrence of risk factors, solar lentiginosis, dermoscopic patterns, topography, histological subtypes, and invasiveness of melanomas. The oldest group characterized a strong correlation between solar lentiginosis, NMSC comorbidity, the prevalence of facial melanomas, the dermoscopic pattern of melanoma arising on chronic sun-damaged skin, and regression. CONCLUSION: The findings regarding the presence of age-specific features in melanoma patients, especially in the youngest and middle-aged groups, might be helpful for clinicians and to target secondary prevention efforts.

Prognostic value of ALK overexpression and molecular abnormalities in high-grade serous ovarian carcinoma.

BACKGROUND: ALK receptor tyrosine kinase (ALK) aberrations have an established role in pathogenesis of many neoplasms, but their clinical significance in high grade serous ovarian carcinoma (HGSOC) is unclear. OBJECTIVE: To analyse the frequency of ALK overexpression, molecular abnormalities of ALK, and their impact on the progression-free survival (PFS) and overall survival (OS) in HGSOC. METHODS: Protein expression was examined by immunohistochemistry (IHC) using three different clones of anti-ALK antibody. The presence of translocations was analysed using fluorescent in situ hybridization. Next-generation sequencing was used for studying the copy number variation, as well as point mutation and translocations involving other commonly rearranged genes. RESULTS: ALK overexpression was demonstrated in up to 52% of tumours, whereas ALK copy gains in 8.2%, with no clear impact on survival. ALK point mutations were identified in 13 tumours (8.9%), with 3 belonging to the class IV showing significantly better OS. A trend suggesting better PFS was also noticed in these cases. Additionally, three gene fusions were found: ERBB2-GRB7, PRKCA-BRCA1 and SND1-BRAF, none of which has been previously described in HGSOC. CONCLUSIONS: HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.

Delay in Diagnosis of Autoimmune Polyendocrine Syndrome Type 2 as a Consequence of Misinterpretation of Gastrointestinal Symptoms.

Background: Type 2 autoimmune polyendocrine syndrome (APS-2) is characterized by the presence of at least two of three endocrinopathies: Addison's disease, autoimmune thyroiditis, and diabetes type 1. The prevalence of APS-2 is estimated to be 1 : 1000 to 1 : 20.000 in the general population. Diagnosis of APS-2 often is delayed due to its rarity and wide spectrum of clinical symptoms. Case Presentation. A 27-year-old presented with a 6-month history of abdominal pain, vomiting, diarrhea, weakness, fatigue, and 15 kg of weight loss. The patient was diagnosed with Crohn's disease in a local hospital and referred to our institution because of treatment failure. Colonoscopy performed in this hospital identified irregular mucosal erosions in terminal ileum, and the microscopy of biopsy specimens demonstrated nonspecific inflammation. On physical examination, the patient appeared cachectic. Blood pressure was 90/60 mmHg. Laboratory results were significant for severe hyponatremia and mild hyperkalemia. Morning cortisol was low, and adrenocorticotropic hormone (ACTH) concentration was high. An ACTH stimulation test did not present any increase in serum cortisol, which confirmed primary adrenal insufficiency. Antithyroid peroxidase antibody (anti-TPO) as well as both anti-21-hydroxylase antibodies and antiglutamic acid decarboxylase antibodies (GAD65) were positive. So, the diagnosis of APS-2 was made, and the replacement doses of hydrocortisone and fludrocortisone has brought a rapid improvement in all clinical symptoms; colonoscopy showed normal. Conclusion: The case presented herein highlights rapidly progressive nature of untreated APS-2 and that the diagnosis of APS-2 may be challenging.

Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration.

New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. These materials should be: stable, nontoxic, and biodegrade slowly and steadily, allowing the stable release of biodegradable and biologically active substances. We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. The release factor (Q) varied depending on both the peptide and the structure of the polysaccharide matrix. LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine.

Tonsillectomy in own material.

<b>Introduction:</b> Tonsillectomy belongs to the most frequently performed surgical treatments; however, the necessity of its performance is questioned. Therefore, there are many attempts to unify and define the indications for the procedure. <br><b>Aim:</b> The main objective of the current dissertation was an analysis of the clinical symptoms occurring in patients qualified for tonsillectomy, as well as a comparison of those with a histopathological image of the removed tonsils in a repeatedly carried out, unified pathomorphological examination. The secondary objective was the designation of the demographic profile, existing comorbidities, and complications in the form of postoperative bleeding in patients after tonsillectomy in own material. <br><b>Material and method:</b> A retrospective analysis of 301 procedures of palatine tonsil removal was performed, which were completed in the years 2017-2019 at the Department of Otolaryngology with Division of Cranio-Maxillo-Facial Surgery of the Military Institute of Medicine, Warsaw, Poland. The indications were defined on the grounds of data from the anamnesis. Based on unified criteria, the removed material was divided into 2 groups: with the signs of Chronic Tonsillitis (CT) as well as Tonsillar Hyperthrophy (TH). <br><b>Results:</b> The average size of tonsils was the greatest in a group of patients under 35 years of age, and smallest in the group over 51 years of age. As patients aged, the reduction in size of the palatal tonsils was observed. In the examined group, the histopathological diagnosis in the form of HT was found in 165 patients (54.8%), while CT in 136 (45.2%). It was proven that the larger the tonsils in the clinical picture, the more often the histopathological image responded to HT. Among clinical symptoms reported by patients qualified for tonsillectomy, the following were observed: recurring tonsil inflammation in 211 (70.1%), snoring and sleep apnea in 47 (15.6%), as well as sleep apnea in 33 (11%) patients. Primary bleeding occurred in 10 patients (3.34%), and secondary in 8 patients (2.66%). The most common comorbidities were cardiovascular burdens. <br><b>Conclusions:</b> For most cases, clinical symptoms were confirmed by adequate features of removed material in histopathological examination. The most common histopathological diagnosis was tonsillar hyperthrophy.

Selected protein expression in a new prognostic model for patients with non-muscle-invasive bladder cancer.

INTRODUCTION: After transurethral resection of a bladder tumor, patients frequently have a recurrence of the disease, thereby requiring adjuvant therapy. PURPOSE: The study aimed to determine the prognostic value of expression levels of p53, Ki-67, and survivin, and to develop a new prognostic model for patients with non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of a bladder tumor. METHODS: The study group consisted of 101 patients with primary NMIBC. Univariate followed by multivariate Cox proportional hazard regression analysis was performed to obtain a model including the smallest possible number of descriptive variables with the highest statistical significance and impact on risk. RESULTS: The RECINT model (RECurrence In Not Treated) including factors independently associated with cancer recurrence (tumor size [HR 1.148; p = 0.034], intensity of the color reaction for p53 [HR 1.716; p = 0.008], Ki-67 [HR 3.001; p = 0.022], and survivin [HR 1.461; p = 0.021]) adequately stratified recurrence free-survival (R2 = 0.341, p < 0.001) in patients with primary NMIBC. Patients with the lowest RECINT score (0-6) had the lowest probability of cancer recurrence (1- and 5-year recurrence of 16%) in comparison with other groups (p < 0.001). CONCLUSIONS: The RECINT model may be useful for stratifying the risk of recurrence in patients with non-muscle-invasive bladder cancer and may allow for identification of those who may benefit the most from adjuvant BCG immunotherapy.

Intensity of Nuclear Staining for Ki-67, p53 and Survivin as a New Prognostic Factor in Non-muscle Invasive Bladder Cancer.

The aim of the study was to determine the prognostic value of expression levels of biomarkers selected on the basis of the literature: p53, Ki-67, survivin, ß-catenin, E-cadherin and N-cadherin in patients with non-muscle invasive bladder cancer. Immunohistochemistry was performed on sections of primary papillary carcinoma of the bladder removed during transurethral resection of the tumor in 134 patients. The expression of ß-catenin and E-cadherin was found in all analyzed cases and N-cadherin expression was demonstrated in 3.73% of the tissues examined. The expression of the p53 protein was confirmed in 96.27% of tissues examined. The expression of the Ki-67 protein was demonstrated in all analyzed cases. Survivin expression was found in 95.52% of the study group. Multivariate analysis confirmed the relationship between the recurrence-free survival (RFS) and the intensity of the nuclear reaction for p53 (HR 1417, 95% CI 1.001-2.007, p = 0.049) and survivin (HR 1.451; 95% CI 1.078-1.955; p = 0.014), the expression level of the Ki-67 protein expressed by the TS index (HR 1.146, 95% CI 1.116-1.823, p = 0.005) and the use of adjuvant BCG therapy (HR 0.218, 95% CI 0.097-0.489, p = 0.0002). The evaluation of Ki-67 expression and the intensity of nuclear staining for survivin and p53 may provide additional information that will allow more accurate stratification of the risk of NMIBC recurrence after TURBT.

Convolutional neural networks can accurately distinguish four histologic growth patterns of lung adenocarcinoma in digital slides.

During the diagnostic workup of lung adenocarcinomas (LAC), pathologists evaluate distinct histological tumor growth patterns. The percentage of each pattern on multiple slides bears prognostic significance. To assist with the quantification of growth patterns, we constructed a pipeline equipped with a convolutional neural network (CNN) and soft-voting as the decision function to recognize solid, micropapillary, acinar, and cribriform growth patterns, and non-tumor areas. Slides of primary LAC were obtained from Cedars-Sinai Medical Center (CSMC), the Military Institute of Medicine in Warsaw and the TCGA portal. Several CNN models trained with 19,924 image tiles extracted from 78 slides (MIMW and CSMC) were evaluated on 128 test slides from the three sites by F1-score and accuracy using manual tumor annotations by pathologist. The best CNN yielded F1-scores of 0.91 (solid), 0.76 (micropapillary), 0.74 (acinar), 0.6 (cribriform), and 0.96 (non-tumor) respectively. The overall accuracy of distinguishing the five tissue classes was 89.24%. Slide-based accuracy in the CSMC set (88.5%) was significantly better (p < 2.3E-4) than the accuracy in the MIMW (84.2%) and TCGA (84%) sets due to superior slide quality. Our model can work side-by-side with a pathologist to accurately quantify the percentages of growth patterns in tumors with mixed LAC patterns.

Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma.

Tumor-driven immune suppression is a major barrier to successful immunotherapy in ovarian carcinomas (OvCa). Among various mechanisms responsible for immune suppression, arginase-1 (ARG1)-carrying small extracellular vesicles (EVs) emerge as important contributors to tumor growth and tumor escape from the host immune system. Here, we report that small EVs found in the ascites and plasma of OvCa patients contain ARG1. EVs suppress proliferation of CD4+ and CD8+ T-cells in vitro and in vivo in OvCa mouse models. In mice, ARG1-containing EVs are transported to draining lymph nodes, taken up by dendritic cells and inhibit antigen-specific T-cell proliferation. Increased expression of ARG1 in mouse OvCa cells is associated with accelerated tumor progression that can be blocked by an arginase inhibitor. Altogether, our studies show that tumor cells use EVs as vehicles to carry over long distances and deliver to immune cells a metabolic checkpoint molecule - ARG1, mitigating anti-tumor immune responses.

Image processing methods for the structural detection and gradation of placental villi.

The context-based examination of stained tissue specimens is one of the most important procedures in histopathological practice. The development of image processing methods allows for the automation of this process. We propose a method of automatic segmentation of placental structures and assessment of edema present in placental structures from a spontaneous miscarriage. The presented method is based on texture analysis, mathematical morphology, and region growing operations that are applicable to the heterogeneous microscopic images representing histological slides of the placenta. The results presented in this study were obtained using a set of 50 images of single villi originating from 13 histological slides and was compared with the manual evaluation of the pathologist. In the presented experiments, various structures, such as villi, villous mesenchyme, trophoblast, collagen, and vessels have been recognized. Moreover, the gradation of villous edema for three classes (no villous edema, moderate villous edema, and massive villous edema) has been conducted. Villi images were correctly identified in 98.21%, villous mesenchyme was correctly identified in 83.95%, and the villi evaluation was correct in 74% for the edema degree and 86% for the number of vessels. The presented segmentation method may serve as a support for current manual diagnosis methods and reduce the bias related to individual, subjective assessment of experts.

Role of WNT/ß-Catenin Pathway as Potential Prognostic and Predictive Factors in Renal Cell Cancer Patients Treated With Everolimus in the Second and Subsequent Lines.

BACKGROUND: The aim of the present study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of the WNT/ß-catenin pathway. PATIENTS AND METHODS: In a prospective, single-arm, phase II study, patients with mRCC received everolimus (10 mg/d) in a 30-day cycle. We performed a prospectively planned evaluation of the potential biomarkers of the WNT/ß-catenin pathway. RESULTS: The serum level of soluble E-cadherin (sE-cadherin) in patients with RCC was significantly greater than that in the controls (71.62 ± 22.28 pg/mL vs. 54.26 ± 10.317 pg/mL; P = .0069). After 2 cycles of everolimus therapy, we observed a significance increase in sE-cadherin (from 71.81 ± 21.18 pg/mL to 77.50 ± 28.212 pg/mL; P = .0151). The Dickkopf-1 protein levels in the study and control groups were not significantly different (P = .2135). The favorable independent predictors for everolimus therapy were normal lactate dehydrogenase level before treatment (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28-0.98; P = .0443) and low sE-cadherin level (HR, 0.54; 95% CI, 0.29-0.98; P = .0422). On multivariate analysis, we observed that worse overall survival was seen in patients with a lower regression coefficient of sE-cadherin after 2 cycles of treatment (HR, 2.60; 95% CI, 1.23-5.52; P = .0128), an increased corrected calcium level (HR, 3.09; 95% CI, 1.21-7.88; P = .0180), and an increased lactate dehydrogenase level before treatment (HR, 1.98; 95% CI, 1.02-3.83; P = .0426). CONCLUSION: WNT/ß-catenin component expression in patients with mRCC had no effect on progression-free survival or overall survival. However, we found that the sE-cadherin level might interact with response to everolimus therapy, although confirmation in future studies is needed.

Cystatin C as a predictor factor in patients with renal cell carcinoma treated by everolimus.

BACKGROUND: We evaluated the influence of serum cystatin C (CysC) with respect to other glomerular filtration rate (GFR) markers on the treatment effect of everolimus in a phase II study in patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Outcomes were from the study's primary analysis. GFR was calculated according to CKD-EPI-sCr equation, CKD-EPI-CysC equation and CKD-EPI-sCr-CysC equation, Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault (CG) equation, serum levels of creatinine (sCr) and CysC before the treatment. RESULTS: We observed in 56 patients analysed patients high correlation (R Spearman from ±0.69 to ±1.00; P < 0.0001) between CysC level and GFR markers: sCr, CKD-EPI-sCr, CKD-EPI-CysC, CKD-EPI-sCr-CysC, MDRD, GFR (CG) before everolimus therapy. We observed that the adverse independent predictors for everolimus therapy were increased CysC level [HR: 2.85 (95 % CI 1.34-6.05), P = 0.0065], histologic grade G1/2 [HR: 3.38 (95 % CI 1.59-7.20), P = 0.0016] and increased LDH level [HR: 5.59 (95 % CI 2.52-12.40), P < 0.0001]. Worse OS was seen in multivariate analysis in patients with increased cystatin C level before treatment [HR: 2.60 (1.03-2.60), P = 0.0428], increased corrected calcium level [HR: 2.78 (95 % CI 1.03-7.54), P = 0.0441] and increased LDH level before treatment [HR: 2.34 (95 % CI 1.11-4.97), P = 0.0262]. CONCLUSION: Increased serum CysC level in contrast to other studied GFR markers had predictive significance in patients with mRCC.

Minimally invasive transnasal approach for primary ectopic meningioma of the paranasal sinuses.

Endoscopic sinus surgery is a standard procedure in the treatment of various pathologies such as chronic sinusitis or some types of neoplasms. The transnasal approach to tumours of paranasal sinuses is favourable due to functional and aesthetic reasons. We report a rare case of a large primary ectopic meningioma of the paranasal sinuses in a 48-year-old woman referred to the Otolaryngology Clinic due to the incidental finding of a pathologic mass visualised on the orthopantomography picture. After diagnosis, the patient was successfully treated with radical transnasal surgery performed under endoscopic vision. In a 1-year follow-up there were no signs of tumour recurrence.