RARE COLORECTAL MALFORMATIONS IN NEWBORNS. LITERATURE REVIEW AND OWN OBSERVATIONS

The article presents literature data andown observations of some rare congenital malformationsof the colorectal area in newborns that require surgicaltreatment. These are defects such as congenital pouch colonand congenital segmental dilatation of the colon. Thereare isolated cases of birth of children with these defectsin European countries and North America. They are morecommon in Asian countries, especially in India. Diagnosisand surgical correction of such congenital malformationscause difficulties associated with insufficient awarenessof pediatric surgeons, neonatologists, pediatricians aboutthis pathology. Data is presented on clinical manifestations,antenatal and postnatal diagnosis and treatment tactics, aswell as the histopathological structure of the affected colonin these defects.The analysis of literature data and the presented clinicalobservations of congenital pouch colon and congenitalsegmental dilatation of the colon in newborns indicate thepossibility of their antenatal and preoperative diagnosis.It is concluded that children with anorectal malformationsand Hirschsprung's disease require a thorough differentialdiagnosis with congenital pouch colon and segmentaldilatation of the colon, as the tactics of their surgicalcorrection significantly differ from the treatment tacticsof common anorectal malformations and Hirschsprung'sdisease surgical management.

A deep learning based graph-transformer for whole slide image classification

Deep learning is a powerful tool for assessing pathology data obtained from digitized biopsy slides. In the context of supervised learning, most methods typically divide a whole slide image (WSI) into patches, aggregate convolutional neural network outcomes on them and estimate overall disease grade. However, patch-based methods introduce label noise in training by assuming that each patch is independent with the same label as the WSI and neglect the important contextual information that is significant in disease grading. Here we present a Graph-Transformer (GT) based framework for processing pathology data, called GTP, that interprets morphological and spatial information at the WSI-level to predict disease grade. To demonstrate the applicability of our approach, we selected 3,024 hematoxylin and eosin WSIs of lung tumors and with normal histology from the Clinical Proteomic Tumor Analysis Consortium, the National Lung Screening Trial, and The Cancer Genome Atlas, and used GTP to distinguish adenocarcinoma (LUAD) and squamous cell carcinoma (LSCC) from those that have normal histology. Our model achieved consistently high performance on binary (tumor versus normal: mean overall accuracy = 0.975+/-0.013) as well as three-label (normal versus LUAD versus LSCC: mean accuracy = 0.932+/-0.019) classification on held-out test data, underscoring the power of GT-based deep learning for WSI-level classification. We also introduced a graph-based saliency mapping technique, called GraphCAM, that captures regional as well as contextual information and allows our model to highlight WSI regions that are highly associated with the class label. Taken together, our findings demonstrate GTP as a novel interpretable and effective deep learning framework for WSI-level classification.

Folate-Receptor Positive Circulating Tumor Cell Is a Potential Diagnostic Marker of Prostate Cancer

Folate-receptor positive circulating tumor cells (FR+CTCs) shows an important role in the diagnosis and dynamic monitoring for many solid tumors; however, the application of FR+CTCs in prostate cancer remains unclear. We explored the potential application of FR+CTCs in this retrospective study. The levels of FR+CTCs were detected in 30 prostate cancer patients and 7 bladder cancer patients in Peking University Cancer Hospital from August 2017 to August 2021. Clinical and pathology data were collected. One-way ANOVA was used to compare the difference in FR+CTCs levels in patients with prostate cancer, bladder cancer, and benign disease. The area under the receiver operating curve (AUROC) was used to compare the accuracy of FR+CTCs and tPSA in the diagnosis of prostate cancer. We found that levels of FR+CTCs were significantly higher in cancer patients (both prostate and bladder cancer) than in patients with benign urinary disease (p < 0.001). Besides, FR+CTCs level was consistently high in the prostate cancer patients with different tPSA levels (p < 0.001), and it was significantly higher in the patients with f/tPSA levels <0.16 than in those patients with f/tPSA levels >0.16 (12.20 ± 1.31 vs. 8.73 ± 0.92 FU/3 ml, p = 0.043). The diagnosis efficiency of FR+CTCs is better than the tPSA in prostate cancer patients with tPSA <10 ng/ml (0.871 vs. 0.857). In the prostate cancer patients with tPSA <10 ng/ml and f/tPSA <0.16, a combination of FR+CTCs and tPSA (AUROC, 0.934) further increased the diagnosis efficiency of each of these biomarkers alone (FR+CTCs, 0.912; tPSA, 0.857). Therefore, FR+CTCs could serve as an early diagnosis marker in the prostate cancer patients with uncertain tPSA levels.

Recognition Rate Advancement and Data Error Improvement of Pathology Cutting with H-DenseUNet for Hepatocellular Carcinoma Image

Due to the fact that previous studies have rarely investigated the recognition rate discrepancy and pathology data error when applied to different databases, the purpose of this study is to investigate the improvement of recognition rate via deep learning-based liver lesion segmentation with the incorporation of hospital data. The recognition model used in this study is H-DenseUNet, which is applied to the segmentation of the liver and lesions, and a mixture of 2D/3D Hybrid-DenseUNet is used to reduce the recognition time and system memory requirements. Differences in recognition results were determined by comparing the training files of the standard LiTS competition data set with the training set after mixing in an additional 30 patients. The average error value of 9.6% was obtained by comparing the data discrepancy between the actual pathology data and the pathology data after the analysis of the identified images imported from Kaohsiung Chang Gung Memorial Hospital. The average error rate of the recognition output after mixing the LiTS database with hospital data for training was 1%. In the recognition part, the Dice coefficient was 0.52 after training 50 epochs using the standard LiTS database, while the Dice coefficient was increased to 0.61 after adding 30 hospital data to the training. After importing 3D Slice and ITK-Snap software, a 3D image of the lesion and liver segmentation can be developed. It is hoped that this method could be used to stimulate more research in addition to the general public standard database in the future, as well as to study the applicability of hospital data and improve the generality of the database.

Brief Synopsis: “Instruction Manual for Juvenile Clinical Pathology”

This symposium synopsis summarizes key points discussed related to clinical pathology data interpretation for reproduction and juvenile toxicology studies. In pregnant and growing animals, several changes in clinical pathology parameters linked to growth/maturation of organ and physiological functions can occur, and understanding these changes is important to enable accurate interpretation of clinical pathology data. A brief overview of the general approach to clinical pathology data analysis according to contemporary practices is provided, followed by a discussion focused specifically on reproductive and juvenile clinical pathology. In this context, the approach to recognize and differentiate changes that may be related to pregnancy and growth as opposed to those that may be related to test article effects is highlighted.

The Society of Toxicologic Pathology: Advances and Adventures in the First 50 Years

The Society of Toxicologic Pathology (STP, https://www.toxpath.org /) was founded in North America in 1971 as a nonprofit scientific and educational association to promote the professional practice of pathology as applied to pharmaceutical and environmental safety assessment. In the ensuing 50 years, the STP has become a principal global leader in the field. Society membership has expanded to include toxicologic pathologists and allied scientists (eg, toxicologists, regulatory reviewers) from many nations. In addition to serving membership needs for professional development and networking, major STP outreach activities include production of articles and presentations designed to optimize toxicologic pathology procedures (“best practice” recommendations), communicate core principles of pathology evaluation and interpretation (“points to consider” and “opinion” pieces), and participation in international efforts to harmonize diagnostic nomenclature. The STP has evolved into an essential resource for academic, government, and industrial organizations that employ and educate toxicologic pathologists as well as use toxicologic pathology data across a range of applications from assessing product safety (therapies, foods, etc) to monitoring and maintaining environmental and occupational health. This article recapitulates the important milestones and accomplishments of the STP during its first 50 years.

Immunosuppressive niche engineering at the onset of human colorectal cancer

The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells and the immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique opportunity to study the transition to malignancy as pre-cancers (adenomas) and early stage cancers are frequently detected and surgically removed. Here, we demonstrate a key role for the immune response in tumor initiation by studying tumor-immune eco-evolutionary dynamics from pre-cancer to carcinoma using a computational model, ecological analysis of digital pathology data, and multi-region exome sequencing and neoantigen prediction in a total of 62 patient samples. Modelling indicates there are several potential routes to malignancy, each of which uniquely sculpts tumor ecology and intra-tumor antigenic heterogeneity (aITH). In patient samples, the immune microenvironment was characterized using the spatial distribution of 17 markers across registered whole-slide images, and patterns of intra-lesion aITH measured using multi-region exome sequencing and neoantigen prediction. The patient data were best described by a model whereby immunogenic adenomas do not progress to CRC because they are under immune control, and progression initially proceeds in adenomas with low immunogenicity followed by the gradual construction of an immunosuppressive niche depleted in CD8+ cytotoxic T cells. There was little evidence for immune blockade (PD-L1 expression) in tumor initiation or progression. These results suggest that re-engineering the immunosuppressive niche may prove to be an effective immunotherapy in CRC.

Sleep and Covid-19: neurophysiological and biochemical issues

Functional disorders of the nervous system against the background of Covid-19 are reviewed with the emphasis on sleep and circadian clock disorders during the pandemic. The pandemic is regarded as the strong stress factor that affects sleep and the clock. A large risk group consists of elderly people and people with concomitant somatic pathology. Data on the effect of SARS-CoV-2 on other organs and systems, on the functioning of the immune system, are presented.

Porcine teschovirus, sapelovirus, and enterovirus in Swiss pigs: multiplex RT-PCR investigation of viral frequencies and disease association

Porcine teschovirus (PTV), sapelovirus (PSV-A), and enterovirus (EV-G) are enteric viruses that can infect pigs and wild boars worldwide. The viruses have been associated with several diseases, primarily gastrointestinal, neurologic, reproductive, and respiratory disorders, but also with subclinical infections. However, for most serotypes, proof of a causal relationship between viral infection and clinical signs is still lacking. In Switzerland, there has been limited investigation of the occurrence of the 3 viruses. We used a modified multiplex reverse-transcription PCR protocol to study the distribution of the viruses in Swiss pigs by testing 363 fecal, brain, and placental or abortion samples from 282 healthy and diseased animals. We did not detect the 3 viruses in 94 placental or abortion samples or in 31 brain samples from healthy pigs. In brain tissue of 81 diseased pigs, we detected 5 PSV-A and 4 EV-G positive samples. In contrast, all 3 viruses were detected at high frequencies in fecal samples of both healthy and diseased pigs. In healthy animals, PTV was detected in 47%, PSV-A in 51%, and EV-G in 70% of the 76 samples; in diseased animals, frequencies in the 81 samples were 54%, 64%, and 68%, respectively. The viruses were detected more frequently in fecal samples from weaned and fattening pigs compared to suckling piglets and sows. Co-detections of all 3 viruses were the most common finding. Based on clinical and pathology data, statistical analysis yielded no evidence for an association of virus detection and disease. Further research is required to determine if pathogenicity is linked to specific serotypes of these viruses.

Vaginismus: Degrees of Expression, Clinical Forms, Family Parental Environment, Characteristics of Patients and Their Sexual Partners, Reactions to the Pathology, Data of Paraclinical Studies

The article deals with and characterizes degrees of vaginismus expression, present in a number of classifications, and contains characteristics of the phobic and hysteric (conversion) forms of vaginismus. It presents a clinical case, which contains a detailed description of psychotraumatic circumstances that resulted in phobic vaginismus and supported its existence, as well as a case of penis captivus in a female patient supervised by the author of this article. Self-perception of the women, suffering from vaginismus, and their family and parental environment are described. In particular it is informed that in many women with vaginismus their fathers were extremely critical, imperious, moralistic and threatening. At the same time, they were sexually seductive with their daughters to an excessive degree. It seemed that in some specific way the daughter substituted for her mother. The fathers behaved like jealous lovers, when their daughters went around with men. On the one hand, they were moralists, but on the other one they extremely concerned themselves with sexuality of their daughters. Also the article points out that half of the patients with vaginismus have alexithymia and discusses the issue of causal relationships between these two conditions. Data about a high rate of comorbid psychic disorders in patients with vaginismus, characteristics of sex partners of women with the above pathology, their responses to the existing disorder as well as information about their sexual dysfunctions are presented. Besides, findings of instrumental physiological examinations (electromyography – EMG) are presented; these demonstrate that women with vaginismus reveal an increased activity of muscles in their pelvic floor both at rest and during induction of vaginismus. The article also contains data, according to which vaginismus is associated with hystrionic-hysterical character traits and sexual distress.