Towards the Point of Care and Noninvasive Classification of Bladder Cancer from Urine Sediment Infrared Spectroscopy. Spectral differentiation of normal, abnormal and cancer patients

Bladder cancer (BC) is the 9th cancer cause of death and one of most cost-intensive in the world. The diagnostic tools are still not at all satisfactory. Herein we evaluated the potential of infrared spectroscopy to detect molecular changes that precede and accompany the carcinogenesis in voided urine sediment. We collected 165 samples from patients being diagnosed for BC and measured them with attenuated total reflectance Fourier transformed infrared spectroscopy (ATR FTIR). Samples were primarily divided into three groups according to cytology that indicated the presence of normal, abnormal and cancer cells. ATR FTIR spectra of sediments were analyzed with the use of partial least square discriminant analysis (PLSDA). The 1800–750 cm− 1 region discriminated the three groups with selectivity and sensitivity values around 68% using cytology as a reference method. These cross-validation values (which were found significant according to a permutation test) were comparable to the sensitivity and specificity values of cytology versus the gold standard (histology). The average spectra of each class and the regression vectors of the PLS-DA indicated that an increased content of carbohydrates and nucleic acids as well as transformations of protein secondary structures were the main discriminators of healthy patients from abnormal and cancer groups. Additionally, we revised the obtained classification according to diagnosis made on histopathological assessment of bladder sections. We finally discuss the potential of the technique to be used as a Point of Care (PoC) testing tool

The terminal branch of the posterior interosseous nerve : an anatomic and histologic study

Background: The aim of this study was to evaluate the terminal branch of the posterior interosseous nerve (PIN) by anatomically and histologically assessing the number, dimension, and area of its individual fascicles, by determining the dimension and area of the whole nerve itself, and by calculating the nerve density ratio (ratio of the sum of the areas of individual fascicles to the area of the whole nerve) of the terminal branch of the PIN. Materials and methods: Twenty-eight terminal branches of the PIN nerve samples were collected from patients undergoing partial denervation of the wrist. The nerve samples were fixed in 10% buffered formalin and stained with haematoxylin and eosin to visualise their nerve bundles. Quantitative analysis of individual fascicles and the whole nerve itself were carried out. Results: Ten nerve samples (35.7%) had one single fascicle (group 1) while the remaining 18 nerve samples (64.3%) contained 2-9 fascicles (group 2). The difference in the sum of the areas of individual fascicles between the two groups did not constitute a statistical difference. Statistically significant between-group differences (p < 0.05) were seen in the area of whole nerve, the ratio of fascicle area to the nerve cross-sectional area and the cross-section maximum nerve length and width. Conclusions: The number of nerve fascicles in the terminal branch of the PIN does not affect the overall size of the nerve. The majority of the volume of multi-fascicle nerves, therefore, primarily consists of the internal perineurium. However, due to the low number of nerves, this question cannot be clearly answered. This sets a further direction for further research on a larger group

Tracking extracellular matrix remodeling in lungs induced by breast cancer metastasis : Fourier transform infrared spectroscopic studies

This work focused on a detailed assessment of lung tissue affected by metastasis of breast cancer. We used large-area chemical scanning implemented in Fourier transform infrared (FTIR) spectroscopic imaging supported with classical histological and morphological characterization. For the first time, we differentiated and defined biochemical changes due to metastasis observed in the lung parenchyma, atelectasis, fibrous, and muscle cells, as well as bronchi ciliate cells, in a qualitative and semi-quantitative manner based on spectral features. The results suggested that systematic extracellular matrix remodeling with the progress of the metastasis process evoked a decrease in the fraction of the total protein in atelectasis, fibrous, and muscle cells, as well as an increase of fibrillar proteins in the parenchyma. We also detected alterations in the secondary conformations of proteins in parenchyma and atelectasis and changes in the level of hydroxyproline residues and carbohydrate moieties in the parenchyma. The results indicate the usability of FTIR spectroscopy as a tool for the detection of extracellular matrix remodeling, thereby enabling the prediction of pre-metastatic niche formation

Fourier transform infrared polarization contrast imaging recognizes proteins degradation in lungs upon metastasis from breast cancer

The current understanding of mechanisms underlying the formation of metastatic tumors has required multi-parametric methods. The tissue micro-environment in secondary organs is not easily evaluated due to complex interpretation with existing tools. Here, we demonstrate the detection of structural modifications in proteins using emerging Fourier Transform Infrared (FTIR) imaging combined with light polarization. We investigated lungs affected by breast cancer metastasis in the orthotopic murine model from the pre-metastatic phase, through early micro-metastasis, up to an advanced phase, in which solid tumors are developed in lung parenchyma. The two IR-light polarization techniques revealed, for the first time, the orientational ordering of proteins upon the progression of pulmonary metastasis of breast cancer. Their distribution was complemented by detailed histological examination. Polarized contrast imaging recognised tissue structures of lungs and showed deformations in protein scaffolds induced by inflammatory infiltration, fibrosis, and tumor growth. This effect was recognised by not only changes in absorbance of the spectral bands but also by the band shifts and the appearance of new signals. Therefore, we proposed this approach as a useful tool for evaluation of progressive and irreversible molecular changes that occur sequentially in the metastatic process

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

BackgroundFollicular cell-derived thyroid carcinoma represents the vast majority of paediatric thyroid cancers (TCs). Papillary thyroid carcinoma (PTC) accounts for over 90% of all childhood TC cases, and its incidence in paediatric patients is increasing. The objective of this follow-up study was to present the outcome of ultrasound (US) and laboratory monitoring of paediatric patients with autoimmune thyroiditis (AIT) prior to the development of PTC.Patients and methodsThis prospective study included 180 children and adolescents (132 females; 73.3%) with a suspicion of thyroid disorder referred to the Outpatient Endocrine Department. The patients were divided into four groups: 1) 28 patients with a mean age of 10.7 [standard deviation (SD), 3.1] y, in whom PTC was detected during the active surveillance of AIT [AIT(+), PTC(+) follow up (F)]; 2) 18 patients with a mean age of 12.8 (SD, 3.4) y, in whom PTC and AIT were detected upon admission (A) [AIT(+), PTC(+) A]; 3) 45 patients with a mean age of 13.0 (SD, 3.4) y, in whom PTC was detected upon admission and AIT was excluded [AIT(-), PTC(+) A]; and 4) an age- and sex-matched control group of 89 patients with AIT and with a mean age of 9.4 (SD, 3.0) y. The analysis included clinical, US, and laboratory assessment results of children on admission (groups 1–4) and during follow-up (groups 1 and 4) in the Paediatric Endocrine Outpatient Department.ResultsUpon admission of those in group 1, the US evaluation revealed a hypoechogenic thyroid gland in 12 and an irregular normoechogenic gland in 16 patients. US monitoring revealed an increase in thyroid echogenicity and an increased irregularity of the thyroid structure during the follow-up period of all of the patients from group 1. Such changes were not noticed in group 4. PTC was diagnosed at the mean time of 3.6 y (3 mo–9 y) since AIT confirmation in group 1. The mean maximum PTC diameter as per the US was significantly smaller in group 1 than in groups 2 and 3 [13.2 (10.8) mm vs. 22.2 (12.8) and 22.05 (15.4) mm]. Fewer patients in group 1 were referred to 131I than in groups 2 and 3 (71.4% vs. 94.4 and 93.3%). Interestingly, significant differences were observed in the thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) ratio between groups 2 and 3, as opposed to group 4, at the beginning of observation [15.3 (27.6) and 3.5 (8.8] vs. 0.77 (1.9)]. In group 1, after the follow-up, an increase in the TgAb/TPOAb ratio was observed [1.2 (9.8) to 5.2 (13.5)]. There were no significant differences between groups 1–3 in labeling index Ki67, lymph nodes metastasis, extrathyroidal extension, and angioinvasion. There were no associations between thyroid-stimulating hormone, TgAb, and the extent of the disease.ConclusionThe use of thyroid US focused on the search for developing tumours in the routine follow-up of patients with AIT may not only help in the early detection of thyroid malignancies that are not clinically apparent but may also influence the invasiveness of oncological therapy and reduce the future side effects of 131I therapy. We propose that the repeat evaluation of TPOAb and TgAb warrants further exploration as a strategy to determine TC susceptibility in paediatric patients with AIT in larger multicentre studies

In Vitro Spectroscopy-Based Profiling of Urothelial Carcinoma: A Fourier Transform Infrared and Raman Imaging Study

Markers of bladder cancer cells remain elusive, which is a major cause of the low recognition of this malignant neoplasm and its recurrence. This implies an urgent need for additional diagnostic tools which are based on the identification of the chemism of bladder cancer. In this study, we employed label-free techniques of molecular imaging&mdash;Fourier Transform Infrared and Raman spectroscopic imaging&mdash;to investigate bladder cancer cell lines of various invasiveness (T24a, T24p, HT-1376, and J82). The urothelial HCV-29 cell line was the healthy control. Specific biomolecules discriminated spatial distribution of the nucleus and cytoplasm and indicated the presence of lipid bodies and graininess in some cell lines. The most prominent discriminators are the total content of lipids and sugar moieties as well as the presence of glycogen and other carbohydrates, un/saturated lipids, cytochromes, and a level of S-S bridges in proteins. The combination of the obtained hyperspectral database and chemometric methods showed a clear differentiation of each cell line at the level of the nuclei and cytoplasm and pointed out spectral signals which differentiated bladder cancer cells. Registered spectral markers correlated with biochemical composition changes can be associated with pathogenesis and potentially used for the diagnosis of bladder cancer and response to experimental therapies