Renal mucinous tubular and spindle cell carcinoma: a report of 8 cases and review of the literature

Background

Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a rare variant of renal tumor. The current data show most of MTSCCs are of low malignant potential and rare cases metastatic to lymph nodes have been reported; however, the recorded computed tomography (CT) and follow up data are limited.

Material and method

In the present study, we retrospectively analyzed CT and clinicopathological data of eight patients with renal MTSCC-K.

Results

A total of eight cases, including six females and two males, were included in this analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2 (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were slightly enhanced on both corticomedullary and nephrographic phase, which was different from many other renal cell carcinomas. Three of them were treated with open radical nephrectomy, three with laparoscopic radical nephrectomy and the other two with laparoscopic partial nephrectomy. No postoperative therapy was applied. Patients were followed up for 15 to 64 months and there was no evidence of recurrence and metastasis.

Conclusions

The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis. The diagnosis mainly depends on the histopathological examination and CT may help to differentiate with papillary renal cell carcinoma. Surgical treatment is recommended and additional therapies are not necessary.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249.

     

Histological subtypes and characteristic structures of HPV-associated oropharyngeal carcinoma; study with Japanese cases

Background

Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to determine the relationship between histological subtypes of OPC and HPV status for Japanese cases and to identify histological structures of HPV-OPC.

Methods

66 OPC cases were categorized into conventional squamous cell carcinoma (SCC) and the variants. Conventional SCC was subcategorized into keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). HPV status of all cases was determined using p16-immunohistochemistry and HPV-DNA ISH.

Results

Two histological subtypes, NKSCC and HSCC, tended to be HPV-OPC and KSCC tended to be nHPV-OPC with statistical significance. Two histological structures, abrupt keratinization, defined in the text, and comedo-necrosis among non-maturing tumor island, were observed for 58.1% and 38.7% of HPV-OPC, and tended to exist for HPV-OPC with statistical significance.

Conclusions

This study showed the association of NKSCC/HSCC with HPV-OPC in Japanese cases, and two histological structures, abrupt keratinization and comedo-necrosis among non-maturing island, were considered characteristic histological features of HPV-OPC.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1816432541113073.

     

Decreased P27 protein expression is correlated with the progression and poor prognosis of nasopharyngeal carcinoma

Background

To determine the correlation of cyclin-dependent kinase inhibitor 1B (p27) expression with clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient prognosis.

Methods

Real-time PCR and immunohistochemistry were used to examine the mRNA and protein expressions of p27 in NPC and nasopharyngeal tissues. The relationship of p27 expression levels with clinical features and prognosis of NPC patients was analyzed.

Results

The expression level of p27 mRNA was markedly lower in NPC tissues than that in the nasopharyngeal tissues (P?=?0.0006). Specific p27 protein staining by immunohistochemistry was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells but decreased expression was observed in NPC samples compared to normal epithelium samples (P?=?0.002). In addition, low levels of p27 protein were inversely correlated with the status of T classification (p?=?0.002) and clinical stage (p?=?0.019) of NPC patients. Patients with lower p27 expression had a significantly shorter overall survival time than did patients with high p27 expression. Multivariate analysis suggested that the level of p27 expression was not an independent prognostic indicator (p?=?0.682) for NPC survival.

Conclusion

Low level of p27 expression is a potential unfavorable prognostic factor for patients with NPC.

Virtual slides

The virtual slide (s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1915282782109343.

     

Accumulation of Fascin<Superscript>+</Superscript> cells during experimental autoimmune neuritis

Background

Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Fascin is an evolutionarily highly conserved cytoskeletal protein of 55 kDa containing two actin binding domains that cross-link filamentous actin to hexagonal bundles.

Methods

Here we have studied by immunohistochemistry the spatiotemporal accumulation of Fascin?+?cells in sciatic nerves of EAN rats.

Results

A robust accumulation of Fascin?+?cell was observed in the peripheral nervous system of EAN which was correlated with the severity of neurological signs in EAN.

Conclusion

Our results suggest a pathological role of Fascin in EAN.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticphatology.diagnomx.eu/vs/6734593451114811

     

Virtual slides in peer reviewed,open access medical publication

Background

Application of virtual slides (VS), the digitalization of complete glass slides, is in its infancy to be implemented in routine diagnostic surgical pathology and to issues that are related to tissue-based diagnosis, such as education and scientific publication.

Approach

Electronic publication in Pathology offers new features of scientific communication in pathology that cannot be obtained by conventional paper based journals. Most of these features are based upon completely open or partly directed interaction between the reader and the system that distributes the article. One of these interactions can be applied to microscopic images allowing the reader to navigate and magnify the presented images. VS and interactive Virtual Microscopy (VM) are a tool to increase the scientific value of microscopic images.

Technology and Performance

The open access journal Diagnostic Pathology http://www.diagnosticpathology.org has existed for about five years. It is a peer reviewed journal that publishes all types of scientific contributions, including original scientific work, case reports and review articles. In addition to digitized still images the authors of appropriate articles are requested to submit the underlying glass slides to an institution (DiagnomX.eu, and Leica.com) for digitalization and documentation. The images are stored in a separate image data bank which is adequately linked to the article. The normal review process is not involved. Both processes (peer review and VS acquisition) are performed contemporaneously in order to minimize a potential publication delay. VS are not provided with a DOI index (digital object identifier). The first articles that include VS were published in March 2011.

Results and Perspectives

Several logistic constraints had to be overcome until the first articles including VS could be published. Step by step an automated acquisition and distribution system had to be implemented to the corresponding article. The acceptance of VS by the reader is high as well as by the authors. Of specific value are the increased confidence to and reputation of authors as well as the presented information to the reader. Additional associated functions such as access to author-owned related image collections, reader-controlled automated image measurements and image transformations are in preparation.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1232133347629819.

     

Skin-impedance in Fabry Disease: A prospective,controlled, non-randomized clinical study

Background

We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system.

Methods

We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100^th repetitive reading, 2) rate of change, 3) average of 60–110^th reading and 4) overall average of all readings.

Results

All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions.

Conclusion

The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.

     

NMRProcFlow: a graphical and interactive tool dedicated to 1D spectra processing for NMR-based metabolomics

Introduction

Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.

Objectives

The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.

Methods

NMRProcFlow was developed to be a graphical and interactive 1D NMR (¹H & ¹³C) spectra processing tool.

Results

NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.

Conclusion

Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.

     

rDolphin: a GUI R package for proficient automatic profiling of 1D <Superscript>1</Superscript>H-NMR spectra of study datasets

Introduction

Adoption of automatic profiling tools for ¹H-NMR-based metabolomic studies still lags behind other approaches in the absence of the flexibility and interactivity necessary to adapt to the properties of study data sets of complex matrices.

Objectives

To provide an open source tool that fully integrates these needs and enables the reproducibility of the profiling process.

Methods

rDolphin incorporates novel techniques to optimize exploratory analysis, metabolite identification, and validation of profiling output quality.

Results

The information and quality achieved in two public datasets of complex matrices are maximized.

Conclusion

rDolphin is an open-source R package (http://github.com/danielcanueto/rDolphin) able to provide the best balance between accuracy, reproducibility and ease of use.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Characterization of ankylosing spondylitis and rheumatoid arthritis using <Superscript>1</Superscript>H NMR-based metabolomics of human fecal extracts

Introduction

The differences in fecal metabolome between ankylosing spondylitis (AS)/rheumatoid arthritis (RA) patients and healthy individuals could be the reason for an autoimmune disorder.

Objectives

The study explored the fecal metabolome difference between AS/RA patients and healthy controls to clarify human immune disturbance.

Methods

Fecal samples from 109 individuals (healthy controls 34, AS 40, and RA 35) were analyzed by ¹H NMR spectroscopy. Data were analyzed with principal component analysis (PCA) and orthogonal projection to latent structure discriminant (OPLS-DA) analysis.

Results

Significant differences in the fecal metabolic profiles could distinguish AS/RA patients from healthy controls but could not distinguish between AS and RA patients. The significantly decreased metabolites in AS/RA patients were butyrate, propionate, methionine, and hypoxanthine. Significantly increased metabolites in AS/RA patients were taurine, methanol, fumarate, and tryptophan.

Conclusion

The metabolome variations in feces indicated AS and RA were two homologous diseases that could not be distinguished by ¹H NMR metabolomics.

     

NMR-based metabolic characterization of chicken tissues and biofluids: a model for avian research

Introduction

Poultry is one of the most consumed meat in the world and its related industry is always looking for ways to improve animal welfare and productivity. It is therefore essential to understand the metabolic response of the chicken to new feed formulas, various supplements, infections and treatments.

Objectives

As a basis for future research investigating the impact of diet and infections on chicken’s metabolism, we established a high-resolution proton nuclear magnetic resonance (NMR)-based metabolic atlas of the healthy chicken (Gallus gallus).

Methods

Metabolic extractions were performed prior to ¹H-NMR and 2D NMR spectra acquisition on twelve biological matrices: liver, kidney, spleen, plasma, egg yolk and white, colon, caecum, faecal water, ileum, pectoral muscle and brain of 6 chickens. Metabolic profiles were then exhaustively characterized.

Results

Nearly 80 metabolites were identified. A cross-comparison of these matrices was performed to determine metabolic variations between and within each section and highlighted that only eight core metabolites were systematically found in every matrice.

Conclusion

This work constitutes a database for future NMR-based metabolomic investigations in relation to avian production and health.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

The role of bone marrow mononuclear cell-conditioned medium in the proliferation and migration of human dermal fibroblasts

Background

Several recent studies have demonstrated the great potential of bone marrow cells in regenerative medicine, not only for their ability to differentiate to match a damaged cell type, but also because they synthesize and release various growth factors and cytokines.We examined the effect of bone marrow cell-conditioned medium in the healing process, especially in terms of fibroblast proliferation and migration.

Methods

These in vitro studies consisted of co-culture (without direct contact) of dermal fibroblasts with mononuclear bone marrow cells and the use of conditioned medium obtained from these cultures in a scratch wound model.

Results

Mononuclear cells were found to increase the proliferation of fibroblasts, and the conditioned medium showed a stimulatory effect on the migration of fibroblasts.

Conclusion

When considered together with the observed increase in growth factor levels in conditioned medium, it appears that these cells act through a paracrine mechanism.

     

Expression and prognostic significance of Golgiglycoprotein73 (GP73) with Epithelial-mesenchymal transition (EMT) related molecules in Hepatocellular Carcinoma (HCC)

Background

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third cause of cancer-related deaths, worldwide. It is essential to develop an effective prognostic biomarker and determine the mechanisms underlying HCC invasion and metastasis.

Aims

This study aimed to investigate the expression of Golgi glycoprotein73 (GP73) and Epithelial-mesenchymal transition (EMT) molecules such as E-cadherin and Vimentin in HCC. We also evaluated the prognostic value of GP73 in HCC.

Methods

Immunohistochemistry (IHC) was used to determine the expression of GP73 and EMT molecules in 75 HCC specimens and the corresponding paracarcinomatous liver (PCL) tissues. Spearman’s correlation test was used to analyze the correlation of GP73 and EMT molecules. Clinicopathological features of the HCC patients were also analyzed. Univariate survival analysis was performed by the Kaplan–Meier method and differences among the groups were analyzed by the Log-rank test.

Results

GP73 expression in HCC was higher compared with PCL tissues (χ ² ?=?73.60, P?<?0.05). EMT molecules were also detected in HCC and PCL tissues. GP73 was negatively correlated with E-cadherin (r?=?? 0.49, P?<?0.05), but positively correlated with Vimentin (r?=?0.46, P?<?0.05) in HCC. GP73 was correlated with the clinicopathological features including Edmondson grade, vascular invasion and TNM stage (P?<?0.05), which was also associated with overall survival (OS) (P?<?0.05).

Conclusions

GP73 was negatively with E-cadherin and positively correlated with Vimentin. It might be associated with aggressive behavior of HCC and had influence on patients’ OS. Further research is needed to determine the potential of GP73.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/29 vs/1504046946108618; http://med.motic.com/MoticGallery/Slide?id=3b6a037e-f60e-4c68-9106-41e790de9431&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025; http://med.motic.com/MoticGallery/Slide?id=a25b5b32-b613-47b0-9f8b-e1e67a95d1bf&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025.

     

<Emphasis Type="Italic">massPix</Emphasis>: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics

Introduction

Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.

Objectives

We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.

Methods

massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.

Results

Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.

Conclusion

massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.

     

TarMet: a reactive GUI tool for efficient and confident quantification of MS based targeted metabolic and stable isotope tracer analysis

Introduction

Untargeted and targeted analyses are two classes of metabolic study. Both strategies have been advanced by high resolution mass spectrometers coupled with chromatography, which have the advantages of high mass sensitivity and accuracy. State-of-art methods for mass spectrometric data sets do not always quantify metabolites of interest in a targeted assay efficiently and accurately.

Objectives

TarMet can quantify targeted metabolites as well as their isotopologues through a reactive and user-friendly graphical user interface.

Methods

TarMet accepts vendor-neutral data files (NetCDF, mzXML and mzML) as inputs. Then it extracts ion chromatograms, detects peak position and bounds and confirms the metabolites via the isotope patterns. It can integrate peak areas for all isotopologues automatically.

Results

TarMet detects more isotopologues and quantify them better than state-of-art methods, and it can process isotope tracer assay well.

Conclusion

TarMet is a better tool for targeted metabolic and stable isotope tracer analyses.

     

Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

BACKGROUND

Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.

OBJECTIVE

The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.

METHODS

A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.

RESULTS

Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.

CONCLUSION

These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.