Registered multi-device/staining histology image dataset for domain-agnostic machine learning models.

Variations in color and texture of histopathology images are caused by differences in staining conditions and imaging devices between hospitals. These biases decrease the robustness of machine learning models exposed to out-of-domain data. To address this issue, we introduce a comprehensive histopathology image dataset named PathoLogy Images of Scanners and Mobile phones (PLISM). The dataset consisted of 46 human tissue types stained using 13 hematoxylin and eosin conditions and captured using 13 imaging devices. Precisely aligned image patches from different domains allowed for an accurate evaluation of color and texture properties in each domain. Variation in PLISM was assessed and found to be significantly diverse across various domains, particularly between whole-slide images and smartphones. Furthermore, we assessed the improvement in domain shift using a convolutional neural network pre-trained on PLISM. PLISM is a valuable resource that facilitates the precise evaluation of domain shifts in digital pathology and makes significant contributions towards the development of robust machine learning models that can effectively address challenges of domain shift in histological image analysis.

Transfer of learning in histology: Insights from a longitudinal study.

All anatomical educators hope that students apply past training to both similar and new tasks. This two-group longitudinal study investigated the development of such transfer of learning in a histology course. After 0, 10, and 20 sessions of the 10-week-long course, medical students completed theoretical tasks, examined histological slides trained in the course (retention task), and unfamiliar histological slides (transfer task). The results showed that students in the histology group gradually outperformed the control group in all tasks, especially in the second half of the course, η2 = 0.268 (p < 0.001). The best predictor of final transfer performance was students' retention performance after 10 sessions, ß = 0.32 (p = 0.028), and theoretical knowledge after 20 sessions, ß = 0.46 (p = 0.003). Results of eye tracking methodology further revealed that the histology group engaged in greater "visual activity" when solving transfer tasks, as indicated by an increase in the total fixation count, η2 = 0.103 (p = 0.014). This longitudinal study provides evidence that medical students can use what they learn in histology courses to solve unfamiliar problems but cautions that positive transfer effects develop relatively late in the course. Thus, course time and the complex relationship between theory, retention, and transfer holds critical implications for anatomical curricula seeking to foster the transfer of learning.

Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics of disease recurrence or metastatic spread, which go along with a particularly dismal outcome, are currently unclear. Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison with matched primary tumor samples. Microscopically, AT/RT recurrences demonstrated a loss of architecture and significantly enhanced mitotic activity as compared to their related primary tumors. Based on DNA methylation profiling, primary tumor and related recurrence were grossly similar, but three out of 26 tumors belonged to a different molecular type or subtype after second surgery compared to related primary lesions. Copy number variations (CNVs) differed in six cases, showing novel gains on chromosome 1q or losses of chromosome 10 in recurrences as the most frequent alterations. To consolidate these observations, our cohort was combined with a data set of unmatched primary and recurrent AT/RT, which demonstrated chromosome 1q gain and 10 loss in 18% (n = 7) and 11% (n = 4) of the recurrences (n = 38) as compared to 7% (n = 3) and 0% (n = 0) in the primary tumors (n = 44), respectively. Similar to the observations made by DNA methylation profiling, RNA sequencing of our cohort revealed AT/RT primary tumors and matched recurrences clustering closely together. However, a number of genes showed significantly altered expression in AT/RT-SHH recurrences. Many of them are known tumor driving growth factors, involved in embryonal development and tumorigenesis, or are cell-cycle-associated. Overall, our work identifies subtle molecular changes that occur in the course of the disease and that may help define novel therapeutic targets for AT/RT recurrences.

High-Order Correlation-Guided Slide-Level Histology Retrieval With Self-Supervised Hashing.

Histopathological Whole Slide Images (WSIs) play a crucial role in cancer diagnosis. It is of significant importance for pathologists to search for images sharing similar content with the query WSI, especially in the case-based diagnosis. While slide-level retrieval could be more intuitive and practical in clinical applications, most methods are designed for patch-level retrieval. A few recently unsupervised slide-level methods only focus on integrating patch features directly, without perceiving slide-level information, and thus severely limits the performance of WSI retrieval. To tackle the issue, we propose a High-Order Correlation-Guided Self-Supervised Hashing-Encoding Retrieval (HSHR) method. Specifically, we train an attention-based hash encoder with slide-level representation in a self-supervised manner, enabling it to generate more representative slide-level hash codes of cluster centers and assign weights for each. These optimized and weighted codes are leveraged to establish a similarity-based hypergraph, in which a hypergraph-guided retrieval module is adopted to explore high-order correlations in the multi-pairwise manifold to conduct WSI retrieval. Extensive experiments on multiple TCGA datasets with over 24,000 WSIs spanning 30 cancer subtypes demonstrate that HSHR achieves state-of-the-art performance compared with other unsupervised histology WSI retrieval methods.

Handcrafted Histological Transformer (H2T): Unsupervised representation of whole slide images.

Diagnostic, prognostic and therapeutic decision-making of cancer in pathology clinics can now be carried out based on analysis of multi-gigapixel tissue images, also known as whole-slide images (WSIs). Recently, deep convolutional neural networks (CNNs) have been proposed to derive unsupervised WSI representations; these are attractive as they rely less on expert annotation which is cumbersome. However, a major trade-off is that higher predictive power generally comes at the cost of interpretability, posing a challenge to their clinical use where transparency in decision-making is generally expected. To address this challenge, we present a handcrafted framework based on deep CNN for constructing holistic WSI-level representations. Building on recent findings about the internal working of the Transformer in the domain of natural language processing, we break down its processes and handcraft them into a more transparent framework that we term as the Handcrafted Histological Transformer or H2T. Based on our experiments involving various datasets consisting of a total of 10,042 WSIs, the results demonstrate that H2T based holistic WSI-level representations offer competitive performance compared to recent state-of-the-art methods and can be readily utilized for various downstream analysis tasks. Finally, our results demonstrate that the H2T framework can be up to 14 times faster than the Transformer models.

Perceptions of medical students towards the role of histology and embryology during curricular review.

BACKGROUND: The continuous changes in the medical education to prepare medical doctors for the future requires updates in medical curriculum. However, the perspectives of the medical students are not frequently considered during the revision of the medical curriculum. In parallel with the process of defining and adjusting the medical curriculum, a large survey was performed to inquire the perspectives of the medical students at the Faculty of Medicine of the University of Porto (FMUP), Portugal, about the role of Histology and of Embryology. METHODS: Medical students at FMUP (Portugal) completed a structured and anonymous online questionnaire about the subjects Histology and Embryology. The questionnaire was prepared using questions of previous surveys performed in Europe, including another Portuguese medical school, and additional questions that were specifically prepared to this study. The questions referred to teaching methods, clinical relevance, use of virtual (digital) microscopes and association of Histology and Embryology with other subjects of the medical curriculum. RESULTS: Four hundred and sixty-two students participated in the study. The students in clinical years were more likely to recognise the clinical relevance of Histology (p = 0.016) and Embryology (p < 0.001). Students agree that teaching of these subjects would benefit from a clinical orientation (89% for Histology; 90% for Embryology). Students highlighted that Histology is crucial to understand Biopathology and agree (75%) that an integration of Histology with Biopathology could be considered in the medical curriculum. Most students (55%) agree that slide microscopes are more useful than virtual microscopes. CONCLUSIONS: Our study contributes to the debate about the evolution of medical curriculum. Gathering the medical students' perceptions using large surveys such as that performed in the present study may be useful to adapt the methods of teaching which may increase the motivation of the students. In the case of Histology and Embryology at the FMUP (Portugal) providing more clinically oriented teaching may be useful to motivate the students. Students of clinical years have strong clinical perspectives of Histology and Embryology and their enrolment in teaching of Histology and Embryology can also contribute to increase motivation of younger students. Consulting and involving medical students in the development of the medical curriculum can be positive and students should be more responsible and engaged in building their own education.

Integration of virtual microscopy podcasts in the histology discipline in osteopathic medical school: Learning outcomes.

Virtual microscopy podcasts (VMPs) are narrative recordings of digital histology images. This study evaluated the outcomes of integrating the VMPs into teaching histology to osteopathic medical students. The hypothesis was that incorporating virtual microscopy podcasts as supplementary histology resources to the curriculum would have a positive impact on student performance and satisfaction. Sixty-one podcasts of dynamic microscopic images were created using screen recordings of the digital slides. The VMPs were integrated as supplementary histology resources in multiple courses during the first and second years of the medical curriculum for three classes, a total of 477 osteopathic medical students. A voluntary and anonymous survey was obtained from the students using a questionnaire that included two open-ended questions. The overall performance of the three classes on the histology content of the preclinical course examinations was compared to historical controls of the previous two classes that did not have access to the VMPs. Most students indicated that the podcasts enabled more efficient study time and improved their confidence in the histology content on examinations. The findings indicated a positive association between podcast viewing and efficient study time utilization and class performance. The class average scores of the three consecutive cohorts that used the VMPs progressively increased by 7.69%, 14.88%, and 14.91% compared to the controls. A summary of students' feedback and academic performance supported that integration of the VMPs into Histology teaching improved the learning experience. The findings align with previous studies on the effectiveness of multimedia-based teaching in histology laboratory modules.

Evaluation of the usage of YouTube videos about Histology and Embryology as an educational material.

The use of YouTube videos for educational purposes has been increasingly popular. The quality and accuracy of the information level of these videos should be checked by expert trainers. This study aims to evaluate the content, quality and functionality of YouTube videos on Histology and Embryology and to measure their educational usefulness. In the study, searches were performed using the keywords "Histology" and "Embryology" in the YouTube search tab. Quality and content were evaluated using the Video Power Index (VPI), modified DISCERN scale, JAMA and the Global Quality Scale (GQS). Videos were categorized by educational usefulness. SPSS software was used for statistical analysis. A statistically significant high correlation was observed between modified DISCERN scores and JAMA scores (r = 0.757, p < 0.001) and between modified DISCERN scores and GQS scores (r = 0.743, p < 0.001). A statistically significant high correlation was also determined between JAMA and GQS scores (r = 0.632, p < 0.001). GQS scores were weakly, negatively and significantly correlated with the number of comments (r = -0.302, p < 0.05) and dislikes (r = -0.325, p < 0.05). Based on GQS, the useful and non-useful videos differed significantly in terms of views, likes, dislikes, comments counts and days since upload (p < 0.05). Modified DISCERN and JAMA scores also differed significantly between the useful and non-useful videos (p < 0.001). Educational videos published for Histology and Embryology education on the internet will be more beneficial if they are prepared by expert educators from reliable information sources, by the current literature, and by scoring systems such as DISCERN, JAMA and GQS.

Protein arginine methyltransferase 3 promotes glycolysis and hepatocellular carcinoma growth by enhancing arginine methylation of lactate dehydrogenase A.

BACKGROUND: Protein arginine methylation has emerged a pivotal role in cancer progression. However, the role of protein arginine methyltransferase 3 (PRMT3) in hepatocellular carcinoma (HCC) remains unknown. METHODS: The expression pattern of PRMT3 in HCC was analysed using quantitative real-time-polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry assays. Loss- and gain-of-function experiments were carried out to determine the oncogenic role of PRMT3 in HCC. Glucose consumption and lactate production assays, seahorse bioscience, mass spectrometry, co-immunoprecipitation, metabonomic analysis and site-specific mutation experiments were used to explore the underlying molecular mechanisms. Furthermore, a xenograft mouse model was established to investigate the effects of PRMT3 and its inhibitor, SGC707, treatment on tumour growth in vivo. RESULTS: The expression of PRMT3 was significantly upregulated in HCC, with high expression of which correlated with poor prognosis. PRMT3 knockdown led to the decrease in proliferation, glycolysis of HCC cells and tumour growth, whilst its overexpression showed opposite results. The catalytic activity of PRMT3 was important in mediating these biological processes. Mechanistically, our data showed that PRMT3 interacted with and mediated asymmetric dimethylarginine (ADMA) modification of lactate dehydrogenase A (LDHA) at arginine 112 (R112). Compared with LDHA-wild-type (LDHA-WT) cells, LDHA-R112K-mutant-expressing HCC cells exhibited a decrease in lactate dehydrogenase (LDH) activity, HCC cell glycolysis and proliferation. Furthermore, the administration of SGC707, a selective inhibitor of PRMT3, disrupted the PRMT3-mediated LDHA methylation and abolished PRMT3-induced HCC glycolysis and tumour growth. CONCLUSIONS: Our results suggested a novel oncogenic role of PRMT3 in HCC, and it could be a promising therapeutic target for HCC by linking post-translational modification and cancer metabolism.

Clinicopathological and histopathological review of dedifferentiated liposarcoma: a comprehensive study of 123 primary tumours.

AIMS: Dedifferentiated liposarcoma (DDLS) has varying histopathological features, but their significance for the biological behaviour of this disease has not been fully clarified. The aim of this study was to elucidate the prognostic factors for DDLS by clinicopathologically reviewing a large case series. METHODS AND RESULTS: We clinicopathologically reviewed 123 cases of primary de-novo DDLS without preoperative treatment, including 81 in the internal trunk (internal DDLS) and 42 in peripheral sites (peripheral DDLS). Univariate and multivariate analyses of their features were also performed for all cases, the internal DDLS group, and the peripheral DDLS group. The results showed that, in all three groups, distant metastasis was significantly associated with shorter overall survival (OS) (univariate analysis, P < 0.0001, P = 0.0011, and P = 0.0101, respectively), whereas local recurrence showed no significant effect on prognosis. Histopathologically, a high mitotic count and the presence of round tumour cells were significantly associated with shorter OS in multivariate analysis of the internal DDLS group [respectively: P = 0.0022, hazard ratio (HR) 4.39, 95% confidence interval (CI) 1.71-11.28; and P = 0.0014, HR 7.19, 95% CI 2.14-24.16]. In the peripheral DDLS group, necrosis and high-grade histological components were significantly associated with shorter OS (univariate analysis, P = 0.0068 and P = 0.0174, respectively). CONCLUSIONS: The presence of round tumour cells may be one of the histological factors associated with a worse prognosis of DDLS patients, as previous studies indicated. This study also suggests that distant metastasis may be predictive of prognosis for both internal and peripheral DDLS, rather than local recurrence.

Adverse Histological Features of Differentiated Thyroid Cancer Are Commonly Found in Autopsy Studies: Implications for Treatment Guidelines.

Background: While the popularity of lobectomy for differentiated thyroid cancer (DTC) has increased since the 2015 ATA (American Thyroid Association) guidelines, recent studies reported that adverse histological features (minimal extrathyroidal extension [mETE], multifocality, vascular invasion, and lymph node [LN] metastases) may be found in 30-60% of lobectomy specimens, questioning the validity of this approach. Aim: To assess the prevalence adverse histological features in occult DTC detected in autopsy studies. Methods: Meta-analysis of autopsy studies of the thyroid in subjects without known history of thyroid cancer. Results: Twenty-nine studies including 8750 subjects fulfilled the inclusion criteria, with incidentally discovered DTC in 740 autopsies (8.5%). Age was reported in 17 studies, with a median age of 61 years (range 41-68 years). Multifocality was reported in 27 studies with a calculated event rate of 28.2% ([CI 23.1-33.8], I2 = 46.3%), with bilateral involvement in 18% [CI 12.6-25.1]. mETE was reported in 5 studies, with an event rate of 24.5% ([CI 9.3-50.7], I2 = 88.5%), and the presence of LN metastases were reported in 13 studies with an event rate of 11% ([CI 6.1-19.1], I2 = 69.5%). Vascular invasion was reported in seven studies with an event rate of 16% ([CI 4-47], I2 = 86.8%). Of 25 studies with whole body autopsies (722 subjects), 3 cases of distant metastases were reported, of which 2 had fatal metastatic disease (where thyroid origin was not diagnosed before death), and 1 had occult disease. Conclusions: Adverse histological features including mETE, LN metastases, multifocality, and vascular invasion are common in occult DTC. When minimal in size, these adverse histological features do not seem to be markers of aggressive disease and may not be an indication for completion thyroidectomy or radioiodine therapy.

Gut lumen formation defect can cause intestinal atresia: evidence from histological studies of human embryos and intestinal atresia septum.

Intestinal atresia (IA), a common cause of neonatal intestinal obstruction, is a developmental defect, which disrupts the luminal continuity of the intestine. Here, we investigated (i) the process of lumen formation in human embryos; and (ii) how a defective lumen formation led to IA. We performed histological and histochemical study on 6-10 gestation week human embryos and on IA septal regions. To investigate the topology of embryonic intestine development, we conducted 3D reconstruction. We showed that a 6-7th gestation week embryonic gut has no lumen, but filled with mesenchyme cells and vacuoles of a monolayer of epithelial cells. A narrow gut lumen was formed by gestation week-9, the gut was filled with numerous vacuoles of different sizes, some vacuoles were merging with the developing embryonic gut wall. At gestation week-10, a prominent lumen was developed, only few vacuoles were present and were merging with the intestine wall. At IA septal regions, vacuoles were located in the submucous layer, covered by a single layer of epithelium without glandular structure, and surrounded with fibrous tissue. The mucosal epithelium was developed with lamina propria and basement membrane, but the submucosa and the longitudinal smooth muscle layers were not properly developed. Hence, the vacuoles in IA septum could represent a remnant of vacuoles of embryonic gut. In conclusion, the fusion of vacuoles with the developing intestine wall associates with the disappearance of vacuoles and gut lumen formation in human embryos, and perturbation of these developmental events could lead to IA.

Automated Annotator: Capturing Expert Knowledge for Free.

Deep learning enabled medical image analysis is heavily reliant on expert annotations which is costly. We present a simple yet effective automated annotation pipeline that uses autoencoder based heatmaps to exploit high level information that can be extracted from a histology viewer in an unobtrusive fashion. By predicting heatmaps on unseen images the model effectively acts like a robot annotator. The method is demonstrated in the context of coeliac disease histology images in this initial work, but the approach is task agnostic and may be used for other medical image annotation applications. The results are evaluated by a pathologist and also empirically using a deep network for coeliac disease classification. Initial results using this simple but effective approach are encouraging and merit further investigation, specially considering the possibility of scaling this up to a large number of users.

Resolution-based distillation for efficient histology image classification.

Developing deep learning models to analyze histology images has been computationally challenging, as the massive size of the images causes excessive strain on all parts of the computing pipeline. This paper proposes a novel deep learning-based methodology for improving the computational efficiency of histology image classification. The proposed approach is robust when used with images that have reduced input resolution, and it can be trained effectively with limited labeled data. Moreover, our approach operates at either the tissue- or slide-level, removing the need for laborious patch-level labeling. Our method uses knowledge distillation to transfer knowledge from a teacher model pre-trained at high resolution to a student model trained on the same images at a considerably lower resolution. Also, to address the lack of large-scale labeled histology image datasets, we perform the knowledge distillation in a self-supervised fashion. We evaluate our approach on three distinct histology image datasets associated with celiac disease, lung adenocarcinoma, and renal cell carcinoma. Our results on these datasets demonstrate that a combination of knowledge distillation and self-supervision allows the student model to approach and, in some cases, surpass the teacher model's classification accuracy while being much more computationally efficient. Additionally, we observe an increase in student classification performance as the size of the unlabeled dataset increases, indicating that there is potential for this method to scale further with additional unlabeled data. Our model outperforms the high-resolution teacher model for celiac disease in accuracy, F1-score, precision, and recall while requiring 4 times fewer computations. For lung adenocarcinoma, our results at 1.25× magnification are within 1.5% of the results for the teacher model at 10× magnification, with a reduction in computational cost by a factor of 64. Our model on renal cell carcinoma at 1.25× magnification performs within 1% of the teacher model at 5× magnification while requiring 16 times fewer computations. Furthermore, our celiac disease outcomes benefit from additional performance scaling with the use of more unlabeled data. In the case of 0.625× magnification, using unlabeled data improves accuracy by 4% over the tissue-level baseline. Therefore, our approach can improve the feasibility of deep learning solutions for digital pathology on standard computational hardware and infrastructures.

The differential expression of perilipin-2 in hepatoblastoma and its association with prognosis.

Perilipin-2, a lipid droplet (LD) coating protein, has been found to be involved in cancer progression. However, its role in hepatoblastoma (HB) is undefined. We collected 87 HB samples and the corresponding clinical data. Immunohistochemistry (IHC) staining was performed to detect perilipin-2 and the association of the perilipin-2 expression with clinical characteristics and prognosis was analyzed. The expression of perilipin-2 was increased in fetal HB components in comparison to embryonal HB components. The predominant staining pattern was vesicular in fetal HB cells, while it was granular in embryonal HB cells. Furthermore, strong expression of perilipin-2 was associated with the histopathological type of fetal predominant HB. Although event-free survival (EFS) did not differ to a statistically significant extent between the strong and weak expression groups in a univariate survival analysis, a multivariate survival analysis revealed that EFS was significantly improved in the strong perilipin-2 expression group. In conclusion, perilipin-2 is differentially expressed in HB and the strong expression of perilipin-2 predicts a better prognosis.

The usefulness of histopathology examples in teaching practical histology for medical students: A CONSORT-compliant randomized crossover trial.

BACKGROUND: Teaching histology as an image-intensive discipline is a major challenge to medical teachers. We compared knowledge retention and student preference after performing comparison-based and traditional methods of teaching practical histology. METHODS: We performed a crossover randomized controlled trial. Eighty nine first-year and 37 second-year medical students were randomly assigned to comparison-based or traditional classes in which PowerPoint slides were used. Each teaching approach was then switched to another group for a second tissue set. Quantitative assessment was performed using multiple-choice questions and a questionnaire. RESULTS: The first-year students' overall examination scores were significantly higher in the comparison-based approach compared to the traditional approach for both tissue sets, with a large effect size. Interestingly, even for the second-year students, a significantly higher overall score for one set of tissue samples was observed in the comparison-based approach compared to the traditional approach. The students' responses to all the elements in the questionnaire were significantly in favor of the comparison-based approach. CONCLUSION: Our findings indicate that the simple implementation of a few histopathology examples can yield a tremendous improvement in first-year medical students' understanding, enjoyment, and engagement in practical histology classes.

DNA methylation patterns at and beyond the histological margin of early-stage invasive lung adenocarcinoma radiologically manifested as pure ground-glass opacity.

BACKGROUND: Early-stage lung cancers radiologically manifested as ground-glass opacities (GGOs) have been increasingly identified, among which pure GGO (pGGO) has a good prognosis after local resection. However, the optimal surgical margin is still under debate. Precancerous lesions exist in tumor-adjacent tissues beyond the histological margin. However, potential precancerous epigenetic variation patterns beyond the histological margin of pGGO are yet to be discovered and described. RESULTS: A genome-wide high-resolution DNA methylation analysis was performed on samples collected from 15 pGGO at tumor core (TC), tumor edge (TE), para-tumor tissues at the 5 mm, 10 mm, 15 mm, 20 mm beyond the tumor, and peripheral normal (PN) tissue. TC and TE were tested with the same genetic alterations, which were also observed in histologically normal tissue at 5 mm in two patients with lower mutation allele frequency. According to the difference of methylation profiles between PN samples, 2284 methylation haplotype blocks (MHBs), 1657 differentially methylated CpG sites (DMCs), and 713 differentially methylated regions (DMRs) were identified using reduced representation bisulfite sequencing (RRBS). Two different patterns of methylation markers were observed: Steep (S) markers sharply changed at 5 mm beyond the histological margin, and Gradual (G) markers changed gradually from TC to PN. S markers composed 86.2% of the tumor-related methylation markers, and G markers composed the other 13.8%. S-marker-associated genes enriched in GO terms that were related to the hallmarks of cancer, and G-markers-associated genes enriched in pathways of stem cell pluripotency and transcriptional misregulation in cancer. Significant difference in DNA methylation score was observed between peripheral normal tissue and tumor-adjacent tissues 5 mm further from the histological margin (p < 0.001 in MHB markers). DNA methylation score at and beyond 10 mm from histological margin is not significantly different from peripheral normal tissues (p > 0.05 in all markers). CONCLUSIONS: According to the methylation pattern observed in our study, it was implied that methylation alterations were not significantly different between tissues at or beyond P10 and distal normal tissues. This finding explained for the excellent prognosis from radical resections with surgical margins of more than 15 mm. The inclusion of epigenetic characteristics into surgical margin analysis may yield a more sensitive and accurate assessment of remnant cancerous and precancerous cells in the surgical margins.

Kiwifruit (Actinidia deliciosa), compared with cellulose and psyllium, influences the histology and mucus layer of the gastrointestinal tract in the growing pig.

Kiwifruit (KF) fiber, a mixture of soluble and insoluble fibers, elicits mucosal changes in the gastrointestinal tract (GIT). This study aimed to define the nature of these changes in mucosal features throughout the GIT of the growing pig in response to semi-synthetic iso-fiber diets containing cellulose (CEL, low GIT luminal functionality) as the sole fiber source (4.5%), or diets where half of the CEL was replaced by either PSY fiber (PSY husk, high GIT luminal functionality) or KF fiber (consumed as intact fruit). Entire male growing pigs (n = 24, 21 kg bodyweight) received the three diets (n = 8) for 42 d. GIT tissues, digesta, and feces were sampled. The partial replacement of CEL increased (P≤ 0.05) the ileal (KF 22% and PSY 33%) and colonic (PSY 86%) mucus layer thickness, whereas it decreased the rectal crypt depth (KF -26%), and small intestinal (duodenum to ileum) villus length (PSY -17%). The number of duodenal goblet cells was 77% higher (P≤ 0.05) for KF than CEL. Pigs fed the KF-containing diet had greater (P≤ 0.05) apparent ileal organic matter digestibility and apparent total tract organic matter digestibility compared with CEL, but the lowest amount of fermented organic matter in the large intestine. In conclusion, partial substitution of CEL with PSY or KF at a constant, practically-relevant dietary fiber intake, affected several measures of GIT functionality with effects being specific to the added fiber.

Routine histopathology of septal myectomy for hypertrophic obstructive cardiomyopathy in a greek cohort.

Hypertrophic cardiomyopathy (HCM) is a diverse inherited disease affecting 1 in 500 individuals irrespective of gender and ethnicity. A fraction of HCM patients will eventually develop drug refractory dynamic obstruction of the left ventricular outflow tract. For such patients, septal myectomy is the procedure of choice to alleviate their symptoms and improve their quality of life. The current histopathological study, the first from the Greek region, aims to examine the hallmark histopathological characteristics of Hypertrophic Obstructive Cardiomyopathy in a population of patients undergoing septal myectomy at a single center over a ten year period. Medical records and histopathology specimens of thirty nine (n=39) patients were evaluated. The sample comprised 22 males (56.4%) and 17 females (43.6%). Mean patient age at myectomy was 53.9±16.7 years, ranging from 12 to 79 years. Maximal IVS thickness on echocardiography was available for 35 patients with a median value of 2.08cm. Peak resting LVOT Pressure Gradient was available for 33 patients with a mean value of 104.88±44.20 mmHg. Central tendency of each histopathological attribute expressed as the median value was: moderate for myocyte hypertrophy, mild for cytoplasmic vacuolization, moderate for subendocardial fibrosis, moderate for interstitial fibrosis, mild for replacement fibrosis, moderate for myofibrillar disarray and mild for capillary stenosis. Myocyte hypertrophy, present in all specimens, was positively correlated with maximal IVS thickness (tau-b=0.43, p=0.002). Replacement fibrosis was positively correlated with the grade of microvascular stenosis (tau-b=0.45, p=0.004). LVEF was negatively correlated with the grade of interstitial fibrosis (tau-b=-0.43, p=0.035) and with the extent of myocardial fiber disarray (tau-b=-0.42, p=0.034). Histopathological attributes were not correlated with patient gender or age thus proving that HCM has a histological phenotype unique to each patient, mainly depending on each specific sarcomeric mutation.