Microanatomical study of arachnoid granulations and meningeal architecture around Meckel's cave.

Although the microanatomy of Meckel's cave (MC) has been well studied, there are still controversies regarding the meningeal architecture of the space. Moreover, there are only general mentions of the arachnoid granulations near MC in just a few sources. This study is aimed at determining the frequency, location, and anatomical variability of the main clusters of arachnoid granulations around MC. The dissection involved 26 isolated specimens of MC fixed in formalin (neutral buffered, 10%). This number included five freshly harvested specimens examined histologically. Additional paraffin block with MC horizontal section was taken from our neuroanatomical collection. Carefully selected anatomical and histological techniques were applied to assess the complex relationships between the arachnoid granulations and adjacent structures. Arachnoid granulations were found around MC in all specimens with different anatomical variations. The main clusters of arachnoid granulations were close to the trigeminal ganglion and its divisions. The dorsolateral wall of MC was a thick layer formed by interweaving bundles of collagen fibers arranged in various directions. The entire MC was surrounded by a dural sleeve (envelope). This sleeve separated MC from the lateral sellar compartment. At its anterior (rostral) end, it formed a cribriform area pierced by individual fascicles of the trigeminal nerve's primary divisions. The connective tissue forming the sleeve was not only continuous with the epineurium but also shifted to the perineuria surrounding individual nerve fascicles. The meningeal architecture around MC has a complex and multilayer arrangement with a collagenous sleeve closely related to the trigeminal ganglion. Arachnoid granulations are typically found around MC.

Uncommon reasons of the digestive tract-related paraneoplastic syndromes in children with neuroblastic tumors: three case reports.

AIM OF THE STUDY: presentation of the uncommon paraneoplastic syndromes related to the gastrointestinal tract that may occur in children with neuroblastic tumors and their impact on the disease course. MATERIAL AND METHODS: Retrospective analysis of three cases of patients mainly with digestive tract-related symptoms, who were originally admitted to the gastroenterology department from 2013 to 2016 and were finally diagnosed with neuroblastic tumors. RESULTS: The clinical data analysis showed that the symptoms from gastrointestinal tract were dominant in analyzed subjects. The first case is a girl with weight loss, bloating and severe diarrhea, admitted to the hospital in a state of dehydration. The laboratory tests revealed severe hypokalemia. Finally, vasoactive intestinal peptide (VIP) secreting ganglioneuroblastoma was diagnosed and effective surgery was performed. The second case was also a girl who suffered from the incidents of watery diarrhea and flatulence. The tumor was detected by computerized tomography scan. The 3rd stage of ganglioneuroblastoma was diagnosed. The patient required chemotherapy, radiotherapy and surgery treatment. The third child was a boy, hospitalized due to abdominal pain, constipation and weakness. During the diagnostic process, the 4th stage of neuroblastoma was recognized. The chemotherapy, surgery, radiotherapy and immunotherapy were applied. CONCLUSIONS: In children with common abdominal symptoms as chronic flatulence, diarrhea or severe constipation of unknown etiology, the neuroblastic tumors should be considered.

A case of intraparotid schwannoma in a juvenile: Clinical, pathological, ultrastructural, and immunohistopathological study, including an examination of Ki-67 and MCM-3 expressions.

Pleomorphic adenoma, the most common benign nonvascular tumor of the parotid gland in juveniles, should be differentiated from other extremely rare tumors, including schwannoma. In this article, we present a rare case of an intraparotid schwannoma in a juvenile, along with the patient history, a description of pathological features, and the results of ultrastructural and immunohistochemical examination. The respective labeling indexes of Ki-67 and MCM-3, i.e., the mean proportions of positive tumor cells out of 1000 tumoral cells counted in 10 microscopic fields at ×400 magnification, given as a percentage, were found to be 0.82% and 0.4%, respectively.

Comparison between immunohistochemical expression of Ki-67 and MCM-3 in major salivary gland epithelial tumors in children and adolescents. Preliminary study.

While Ki-67 expression is frequently used as an indicator of tumor cell proliferation, alternative markers have also been proposed. Possible alternative indicators of proliferation are the minichromosome maintenance (MCM) proteins, whose levels are inversely associated with tumor cell differentiation. The aim of this preliminary study was to compare the levels of Ki-67 and MCM-3 expression in major salivary gland epithelial tumors in all children and adolescents who underwent surgery in our department in the years 2009-2014. The histopathological diagnosis of the subjects was reviewed, as well as the expression of Ki-67 and MCM-3 in post-op specimens of the tumors. The normality of data was checked with the Shapiro-Wilk test. The t test for independent variables or the U test was used as appropriate to determine statistically significant differences in the expression of Ki-67 and MCM-3. Five cases of pleomorphic adenoma, one of myoepithelioma, one of basal cell adenoma and one of mucoepidermoid carcinoma were identified. Significantly greater MCM-3 than Ki-67 expression was observed in every case. The results of our preliminary study emphasize the need for future research on MCM-3 as a sensitive proliferation marker, providing an alternative to Ki-67, in cases of various major salivary gland epithelial tumors in children and adolescents.

Evaluation of potential prognostic value of Bmi-1 gene product and selected markers of proliferation (Ki-67) and apoptosis (p53) in the neuroblastoma group of tumors.

INTRODUCTION: Cancer in children is a very important issue in pediatrics. The least satisfactory treatment outcome occurs among patients with clinically advanced neuroblastomas. Despite much research, the biology of this tumor still remains unclear, and new prognostic factors are sought. The Bmi-1 gene product is a currently highly investigated protein which belongs to the Polycomb group (PcG) and has been identified as a regulator of primary neural crest cells. It is believed that Bmi­1 and N-myc act together and are both involved in the pathogenesis of neuroblastoma. The aim of the study was to assess the potential prognostic value of Bmi-1 protein and its relations with mechanisms of proliferation and apoptosis in the neuroblastoma group of tumors. MATERIAL/METHODS: 29 formalin-fixed and paraffin-embedded neuroblastoma tissue sections were examined using mouse monoclonal antibodies anti-Bmi-1, anti-p53 and anti-Ki-67 according to the manufacturer's instructions. RESULTS: There were found statistically significant correlations between Bmi-1 expression and tumor histology and age of patients. CONCLUSIONS: Bmi-1 seems to be a promising marker in the neuroblastoma group of tumors whose expression correlates with widely accepted prognostic parameters. The pattern of BMI-1 expression may indicate that the examined protein is also involved in maturation processes in tumor tissue.

Hepatoblastoma Biology Using Isotope Ratio Mass Spectrometry: Utility of a Unique Technique for the Analysis of Oncological Specimens.

INTRODUCTION: Hepatoblastoma is the most common primary liver tumor in children. However, it occurs rarely, with an incidence of 0.5-1.5 cases per million children. There is no clear explanation of the relationship between clinicopathologic features, therapy, and outcome in hepatoblastoma cases, so far. One of the most widely accepted prognostic factors in hepatoblastoma is histology of the tumor. The aim of the study was to determine the potential differences in biology of hepatoblastoma histological subtypes at the atomic level using the unique method of isotope ratio mass spectrometry, which is especially valuable in examination of small groups of biological samples. MATERIAL/METHODS: Twenty-four measurements of nitrogen stable isotope ratio, carbon stable isotope ratio and total carbon to nitrogen mass ratio in fetal and embryonal hepatoblastoma tissue were performed using a Sercon 20-22 Continuous Flow Isotope Ratio Mass Spectrometer (CF-IRMS) coupled with a Sercon SL elemental analyzer for simultaneous carbon-nitrogen-sulfur (NCS) analysis. RESULTS: A difference of about 1.781‰ in stable nitrogen isotope 15N/14N ratio was found between examined hepatoblastoma histological subtypes. CONCLUSIONS: The prognosis in liver tumors cases in children may be challenging particularly because of the lack of versatile methods of its evaluation. Isotope ratio mass spectrometry allows one to determine the difference between hepatoblastoma histological subtypes and clearly indicates the cases with the best outcome.

Rhabdomyosarcoma in children in the light of isotope ratio mass spectrometry.

Rhabdomyosarcoma is the third most common solid tumor in children and the most common soft tissue sarcoma in this age group. However, 5-year survival is only observed in approximately 70% of cases, and the prognosis for patients with progressive disease is still poor. The authors hypothesize that the still unidentified differences in embryonal and alveolar tumor biology reflect the complex chemical reactions occurring during cell growth and metabolism and may be pursued in isotopic fractionation processes. Presented herein is the first evaluation of the nitrogen and carbon isotope ratio using isotope ratio mass spectrometry in the two major rhabdomyosarcoma histologic types. 15N enrichment was found in tumor tissues of embryonal histological type. The obtained result may indicate that individual patient considerations such as isotope ratio, in addition to widely accepted prognostic factors, may facilitate patient classification in terms of risk groups.

The first protocol of stable isotope ratio assessment in tumor tissues based on original research.

Thanks to proteomics and metabolomics, for the past several years there has been a real explosion of information on the biology of cancer, which has been achieved by spectroscopic methods, including mass spectrometry. These modern techniques can provide answers to key questions about tissue structure and mechanisms of its pathological changes. However, despite the thousands of spectroscopic studies in medicine, there is no consensus on issues ranging from the choice of research tools, acquisition and preparation of test material to the interpretation and validation of the results, which greatly reduces the possibility of transforming the achieved knowledge to progress in the treatment of individual patients. The aim of this study was to verify the utility of isotope ratio mass spectrometry in the evaluation of tumor tissues. Based on experimentation on animal tissues and human neoplasms, the first protocol of stable isotope ratio assessment of carbon and nitrogen isotopes in tumor tissues was established.

[Evaluation of the expression of selected pro- and anti-apoptotic factors in syncytiotrophoblasts of human placenta and changes observed after vitamin supplementation]. / Ocena ekspresji wybranych czynników pro- i antyapoptotycznych w syncytiotrofoblascie lozysk ludzkich oraz ich zmian pod wplywem suplementacji witaminowej.

AIM: The main aim of the study was to estimate expression of Bcl-2 and Bax proteins in syncytiotrophoblast in placenta obtained from pregnancies complicated by hypertension and to compare results with group supplemented by antioxidants. MATERIAL AND METHOD: The study was performed in High Risk Department of Medical University Lodz. 3 groups of pregnant women were compared: I-pregnancy complicated by hypertension, II pregnancy complicated by hypertension treated by oral administration of antioxidants--vitamin C and vitamin E.III-rd group consisted of healthy women. After delivery incision from central part of placenta was taken on obtained slides due to immunohistochemical reactions the character intensity surface affected by reaction and expression of two proteins involved into process of apoptosis was measured- anti-apoptotic Bcl-2 and pro-apoptotic Bax. In every slide ten of random choosen fields were evaluated in 200x zoom using semi-quantative method. RESULTS: Highest value of Bcl-2 character was found in I-st group, the lowest in III-rd group- healthy women. The lowest intensity surface affected and expression of the reaction was found in II group- treated by antioxidants. The highest value of Bax reaction character and intensity was found in III group comparing to others. The lowest mean surface of syncytiotrophoblast affected by Bax reaction was found in II group. In III-rd group expression of reaction was higher than in both other groups. CONCLUSIONS: In the base of Bcl-2 reaction in syncytiotrophoblast no influence of antioxidants supplementation on apoptosis process that occurs by this path was found. Antioxidants supplementation decrease Bax activity in syncytiotrophoblast, that suggests restriction of apoptosis process despite of changes connected to hypertension.

The role of human papillomavirus infection in the head and neck region and methods for its detection.

Human papillomaviruses (HPV) are the etiological factors of many benign and malignant lesions localized in the skin and mucous membranes in the region of the urogenital organs and head and neck. Currently, most assays for the detection of HPV are based on detecting the presence of viral nucleic acids, mostly viral DNA. These molecular techniques can be divided into: 1) methods based on a targeted, selective amplification of nucleic acids, 2) signal amplification methods, 3) nucleic acid hybridization assays. This paper presents and explains a number of different HPV detection methods and provides examples of some commonly available commercial tests.

[Evaluation of cyclin E expression in endometrial hyperplasia and cancer in postmenopausal women]. / Ocena ekspresji cykliny E w rozrostach i raku blony sluzowej trzonu macicy u kobiet po menopauzie.

OBJECTIVES: The aim of present study was to determine expression of cyclin E in endometrial hyperplasia without atypia, atypical endometrial hyperplasia and endometrial cancers in comparison with expression of cyclin E in atrophic endometrium of postmenopausal women. We have also estimated relationship between cyclin E expression and prognostic factors for endometrial cancer such as: histological type, cancer stage and histological grade. MATERIAL AND METHODS: 154 women were enrolled into study Women were divided into 4 groups. The first group consist of 38 women with endometrial hyperplasia without atypia, the second group consist of 18 women with atypical endometrial hyperplasia. The third group comprise 62 women with endometrial cancer and the forth 36 women with atrophic endometrium. Cyclin E expression was estimated in formalin-fixed, paraffin-embedded tissues obtained from enrolled women with the use of immunohistochemical techniques. We estimated labelling index (LI) - the number of cells that stained for cyclin E in relation to all cells at the certain field of view. RESULTS: Medians of labelling indices of cyclin E in atrophic endometrium, endometrial hyperplasia with atypia, atypical endometrial hyperplasia end endometrial cancer were 13.7%, 34.7%, 62%, 72.2% respectively These differences were statistically significant. In our study we haven't found relationship between cyclin E expression and histological type of tumour (p = 0.186), cancer stage (p = 0.186) and histological grade (p = 0.539) CONCLUSIONS: In the carcinogenesis of endometrial tumours in postmenopausal women there is a progressive disorder in mechanisms regulating cell cycle. It seems impossible to use cyclin E as prognostic factor for endometrial cancer.

[Evaluation of COX-2 protein expression in melanocytic nevi in children]. / Ocena odczynów z COX-2 w znamionach melanocytarnych u dzieci.

UNLABELLED: Melanocytic skin tumors can be divided into benign nevi and malignant which take the form of melanoma. Melanocytic nevi are common in both adults and children. It is widely acknowledged that they are one of the risk factors of the formation of melanoma. However, melanoma among children is rare. In addition, differentiation of benign and malignant melanocytic tumors is often challenging. Recent studies suggest that COX-2 protein maybe useful in excluding malignant transformation of melanocytic lesion. The aim of the study was to evaluate the occurrence and differences of reactions with COX-2 in groups of nevi in children and melanoma adults. MATERIAL AND METHODS: The study included 75 common nevi and 43 atypical nevi incised in children and 15 cases of melanoma removed in adults. Paraffin blocks were used to make a preparations with routine hematoxylin and eosin staining (H + E) and immunohistochemistry. The results were statistically analyzed. RESULTS: Positive reactions were observed in both melanocytic nevi and melanoma. Differences between benign and malignant melanocytic tumors were statistically significant. Differences within melanocytic nevi were not statistically significant. CONCLUSIONS: The reactions of COX-2 are present in all nevi and do not allow to differentiate between their various types. COX-2 has potential utility in the differentiation of benign and malignant melanocytic tumors.

Oral Cavity Cancer Tissues Differ in Isotopic Composition Depending on Location and Staging.

The aim of this paper was to characterise the isotopic composition of oral squamous cell carcinoma (OSCC) specimens of different areas of the oral cavity. Secondly, we assessed whether there was a correlation between clinical stages of OSCC and isotopic abundance. The IRMS procedure was performed on 124 samples derived from 31 patients with OSCC of 15 N and 13 C to assess the isotopic composition. From each individual, four samples from the tumour, two from the margins, and two samples of healthy oral mucous membranes were derived. The two samples from the tumour and two samples from the margin were additionally subjected to histopathological assessment. Then, statistical analysis was conducted. Tumour infiltration tissues of the lower lip were characterised by higher mean δ13C values compared to samples derived from cancers of the other oral cavity regions (-23.82 ± 1.21 vs. -22.67 ± 1.35); (p = 0.04). The mean percentage of nitrogen content in tumour tissues was statistically higher in patients with the most advanced cancers (11.89 ± 0.03%) versus the group of patients with II and III stage cancers (11.12 ± 0.02%); (p = 0.04). In patients at stage IV, the mean δ13C value in the cancer samples equalled -22.69 ± 1.42 and was lower than that in patients at less severe clinical stages (p = 0.04). Lower lip cancer tissues differed in the isotopic abundance of carbon in comparison with tissues derived from the group of combined samples from other locations. Values of δ13C observed in specimens derived from lower lip cancers were similar to those observed in healthy oral mucous membranes. Cancer tissues obtained from patients in the last stage of OSCC had a different isotopic composition in comparison with those obtained from earlier stages. To confirm these observations, further research on larger groups of patients is needed.

Polyorchidism: An Up-to-Date Systematic Review.

Polyorchidism is a rare male urogenital tract anomaly characterized by at least one supernumerary testis in the scrotum or ectopically. According to data based on our systematic review, 76% of the supernumerary testes (SNTs) were located in the scrotum, and 24% were extra-scrotal (p < 0.001). Among testes located outside the scrotum, 87% were found in the inguinal canal and 13% in the abdominal cavity. In 80% of cases, the diagnosis of SNT was made based on imaging tests, and the remaining 20% of cases were detected incidentally during surgery. The imaging tests performed (US or MRI) resulted in a significantly higher rate of patients who qualified for observation vs. surgical treatment (45% vs. 35%, p < 0.001). The most common conditions associated with SNT were ipsilateral inguinal hernia (15% of cases) and cryptorchidism (15% of cases). Surgery (orchidopexy/orchidectomy) was performed on 54% of patients with SNT, and the decision to observe the SNT was made in a total of 46% of patients (p = 0.001). The therapeutic approach depends on the location of the SNT and the presence of factors that raise suspicion of neoplastic proliferation.

An Asymptomatic, Ectopic Mass as a Presentation of Adrenocortical Carcinoma Due to a Novel Germline TP53 p.Phe338Leu Tetramerisation Domain Variant.

Adrenocortical carcinoma (ACC) is a rare cancer in childhood. ACC is frequently associated with germline TP53 variants, with founder effects especially due to the p.Arg337His mutation. ACC leads to the secretion of adrenocortical hormones, resulting in endocrine syndromes, which is the usual trigger for establishing the diagnosis. We present a surprising ACC pathology in a non-secreting, ectopic retroperitoneal tumour in a 4-year-old boy, successfully controlled with chemotherapy and mitotane after microscopically incomplete tumour resection with spillage. Genomic analysis (gene panel sequencing and copy-number microarray) demonstrated a novel p.Phe338Leu tetramerisation domain (TD) TP53 variant in the proband and his cancer-free mother and a monoallelic deletion encompassing the TP53 locus in cancer tissue, consistent with cancer-predisposition syndrome. While the recurrent p.Arg337His variant translates into high ACC risk, residue 338 and, in general, TD domain variants drive heterogeneous clinical scenarios, despite generally being considered less disruptive than TP53 DNA-binding domain mutations.

[Expression of metalloproteinase MMP-9 and tissue inhibitor of metalloproteinase TIMP-2 in placenta of pregnant women with intrauterine growth restriction]. / Ekspresja metaloproteinazy MMP-9 oraz tkankowego inhibitora metaloproteinazy TIMP-2 w lozyskach u ciezarnych z wewnatrzmacicznym ograniczeniem wzrastania plodu.

INTRODUCTION: The development of pregnancy depends on many factors, among other the implantation and the development of the placenta and placental vascularity The correct course of these processes depends on the proper activity of the enzymes degradating elements of extracellular matrix and basal membrane - metalloproteinases. OBJECTIVES: Assessment of the expression of MMP-9 and TIMP-2 in the placenta of women with intrauterine fetal growth restriction. MATERIAL AND METHODS: Two study groups were distinguished - with untreated IUGR and with IUGR treated with the acetylsalicylic acid and L-arginine and the control group with correct fetal growth and course of pregnancy Marked microscope preparations from placental samples were made with specific antibodies for MMP-9 and TIMP-2. RESULTS: The greatest intensity of the reaction and the villous TIMP-2 expression was characteristic of the group with untreated IUGR. Strongest expression MMP-9 was observed in the control group. The smallest surface of the trophoblast with positive MMP-9 reaction appeared in the group with untreated IUGR. CONCLUSIONS: High MMP-9 activity in the placenta correlates with its correct structure and function. Application of IUGR treatment reduces the expression of TIMP-2 in the placental villi.

Evaluation of the psychological state of patients with advanced cancer and the impact of support on their emotional condition.

AIM OF THE STUDY: The aim of the study was to evaluate the patient's psychological state in the advanced stage of cancerous disease and to assess the effect of sustenance provided by the nursing personnel upon the emotional state of the patient. MATERIAL AND METHODS: The study group comprised 46 subjects treated in palliative care medical wards in Lódz. The data were collected in accordance with the HADS-M questionnaire as well as a self-developed survey. The information obtained was analysed by means of Pearson χ(2) test. RESULTS: The results obtained indicate that most subjects undergo mood aggravation. 76.2% of patients were diagnosed with depressive states. Only 19.6% of the population under investigation showed no signs of anxiety states. The study demonstrates irritation to be yet another unfavourable emotional state coupled with the advanced stage of cancerous disease with as few as 4.4% (4.2%) respondents claiming not to suffer any such symptoms. The patients highly prize the support they receive and it notably improved their well-being. Social support is essential in the advanced stage of the disease. Less severe mental disorders were noted in people who have received all kinds of support.

13C Natural Isotope Abundance in Urothelium as a New Marker in the Follow-Up of Patients with Bladder Cancer.

Bladder cancer (BC) is the most common urological malignancy and has a high incidence of recurrence. BC cells alter their nutrient uptake and metabolic pathways in order to continue the production of sufficient levels of ATP and metabolic intermediates for proliferation and survival. Changes in metabolic pathways regarding the rate of the enzymatic reaction and transport lead to differences in the content of natural isotopes (13C, 15N, 34S) between normal and cancerous tissues. The assessment of the stable isotopes of carbon, nitrogen, and sulfur in normal urothelium and bladder cancer samples was performed using Isotope Ratio Mass Spectrometry (IRMS). The natural abundance of 15N and 13C was decreased in bladder cancer samples when compared to normal urothelium. No significant correlation was observed in BC specimens depending on the tumor grade and stage. Samples derived from bladder tumors and normal urothelium had a different pattern of 15N and 13C isotope abundance. Decreased 13C natural isotopes in the normal urothelium of BC patients were significantly associated with a shorter DFS. Our results suggest that isotopic analysis of normal urothelium of BC patients can be used to predict bladder cancer recurrence.

G870A Polymorphic Variants of CCND1 Gene and Cyclin D1 Protein Expression as Prognostic Markers in Laryngeal Lesions.

CCND1 gene encodes Cyclin D1 protein, the alternations and overexpression of which are commonly observed in human cancers. Cyclin D1 controls G1-S transition in the cell cycle. The aim of the study was to assess utility of the genotyping and protein expression in predicting the susceptibility of transformation from normal tissue to precancerous laryngeal lesions (PLLs) and finally to laryngeal cancer (LC). Four hundred and thirty-five patients (101 with LC, 100 with PLLs and 234 healthy volunteers) were enrolled in the study. Cyclin D1 expression was examined by immunohistochemistry and G870A polymorphism of gene CCND1 by PCR-RFLP technique. We confirmed association between the A allele and risk of developing LC from healthy mucosa (p = 0.006). Significantly higher expression of Cyclin D1 was observed in LC compering with PLLs (p < 0.0001) and we found that it could be a predictive marker of shorter survival time. To sum up, in the study population CCND1 gene polymorphism A870G and Cyclin D1 expression have a significant impact on the risk of developing PLLs and LC, and, therefore, Cyclin D1 could be a useful marker for the prediction of survival time in LC, whereas CCND1 gene polymorphism does not have a direct impact on patients' outcome.

The use of computer image analyses in the assessment of chosen histoclinical features of nephroblastoma cells in children.

The goal of the research was to assess the nuclear morphometric discriminant function (MV(f)) in the analyzed group of nephroblastomas and to evaluate its potential prognostic value. We found a statistically important correlation between favourable histology of Wilms' tumours (according to SIOP 93-01 and SIOP 2001 classifications of kidney tumours of childhood) and low values of MV(f) discriminant function, which was also associated with the best prognosis for the patients. We believe that MV(f) assessment may be a helpful tool in making prognosis in doubtful cases of nephroblastomas in children.