Conservative Lymph Node Sampling Is Clinically Appropriate in Intestinal Resections Related to Nonneoplastic Inflammatory Bowel Disease.

CONTEXT.­: In this era of health care challenges, efficient resource use is crucial. Patients with inflammatory bowel disease (IBD) may undergo surgery owing to treatment-refractory disease or strictures. Unlike colorectal cancer resections, there are no guidelines for lymph node retrieval in nonmalignant IBD resections. OBJECTIVE.­: To assess the usefulness and cost-effectiveness of extensive lymph node examination in nonmalignant IBD resections. DESIGN.­: A retrospective analysis of 354 cases from 2011 to 2018 was conducted. Resections for suspected malignancy or lesions grossly suggestive of carcinoma were excluded. Patient data, resection type, lymph node count, and follow-up information were collected. RESULTS.­: Results showed 51% (180) of cases had 12 or more examined lymph nodes. Only 1 case (0.3%) revealed microscopic invasive carcinoma associated with stricture without metastasis to 26 examined lymph nodes. No metastatic disease was found among the 4972 evaluated lymph nodes. Estimated total savings were at least $19 812, with approximately 10.4 minutes saved on microscopic evaluation. During a mean 5.7-year follow-up, no patients developed metastatic disease from an intestinal primary tumor. Among the 20 deceased patients, cause of death was available for 14 patients (70%), of whom 11 (55%) died of nonneoplastic causes and 3 (15%) of nonintestinal malignancies. CONCLUSIONS.­: While lymph node assessment is crucial in IBD-associated colorectal carcinoma, a colorectal cancer protocol-type lymph node search is unnecessary without clinical or gross pathologic suspicion. A conservative approach to lymph node sampling optimizes resources without compromising patient care.

Deployment of an Artificial Intelligence Histology Tool to Aid Qualitative Assessment of Histopathology Using the Nancy Histopathology Index in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by increased stool frequency, rectal bleeding, and urgency. To streamline the quantitative assessment of histopathology using the Nancy Index in UC patients, we developed a novel artificial intelligence (AI) tool based on deep learning and tested it in a proof-of-concept trial. In this study, we report the performance of a modified version of the AI tool. METHODS: Nine sites from 6 countries were included. Patients were aged ≥18 years and had UC. Slides were prepared with hematoxylin and eosin staining. A total of 791 images were divided into 2 groups: 630 for training the tool and 161 for testing vs expert histopathologist assessment. The refined AI histology tool utilized a 4-neural network structure to characterize images into a series of cell and tissue type combinations and locations, and then 1 classifier module assigned a Nancy Index score. RESULTS: In comparison with the proof-of-concept tool, each feature demonstrated an improvement in accuracy. Confusion matrix analysis demonstrated an 80% correlation between predicted and true labels for Nancy scores of 0 or 4; a 96% correlation for a true score of 0 being predicted as 0 or 1; and a 100% correlation for a true score of 2 being predicted as 2 or 3. The Nancy metric (which evaluated Nancy Index prediction) was 74.9% compared with 72.3% for the proof-of-concept model. CONCLUSIONS: We have developed a modified AI histology tool in UC that correlates highly with histopathologists' assessments and suggests promising potential for its clinical application.

This multicenter study deployed an artificial intelligence tool based on machine learning to scan histopathology slides from ulcerative colitis biopsies and assign a Nancy Histopathology Index. The performance of the tool was similar to that of a panel of expert histopathologists.

A spatial expression atlas of the adult human proximal small intestine.

The mouse small intestine shows profound variability in gene expression along the crypt-villus axis1,2. Whether similar spatial heterogeneity exists in the adult human gut remains unclear. Here we use spatial transcriptomics, spatial proteomics and single-molecule fluorescence in situ hybridization to reconstruct a comprehensive spatial expression atlas of the adult human proximal small intestine. We describe zonated expression and cell type representation for epithelial, mesenchymal and immune cell types. We find that migrating enterocytes switch from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip. Villus tip cells are pro-immunogenic, recruiting γδ T cells and macrophages to the tip, in contrast to their immunosuppressive roles in mouse. We also show that the human small intestine contains abundant serrated and branched villi that are enriched at the tops of circular folds. Our study presents a detailed resource for understanding the biology of the adult human small intestine.

Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis.

OBJECTIVES: Autoimmune gastritis (AIG) is a rare chronic inflammatory disorder with potential long-term sequelae including gastric neoplasia. There is limited data on the natural history of pediatric AIG. We aimed to characterize the clinical course and outcomes of children with AIG. METHODS: This was a multicenter retrospective study that included pediatric patients diagnosed with AIG between January 1, 2000 and December 31, 2021. Diagnosis of AIG was based on the demonstration of histological corpus-predominant atrophic gastritis, with or without positive antiparietal cell (APCA) or anti-intrinsic factor (IF) antibodies. Demographic, clinical, laboratory, endoscopic, and histologic data were retrieved, along with follow-up data. RESULTS: Thirty-three patients, (23 females, [69.7%], median age 12.0 [interquartile range 7.0-15.0] years at diagnosis) were identified. Twenty-two patients (66.7%) had positive APCA and/or anti-IF serology. The most common presenting manifestation was iron deficiency anemia (75%), and accompanying autoimmune disorders were significantly more common in patients with positive serology (62% vs. 18%, p < 0.05). Pseudo-pyloric or intestinal-type metaplasia was present at diagnosis in eight patients (24%), and 11 additional patients (33%) developed metaplasia during a median follow-up time of 27 (17.5-48.3) months. One patient developed a type 1 gastric neuroendocrine tumor. Helicobacter pylori was identified in only one patient, while two patients had prior eradication. Endoscopic and histologic improvements weren't identified in any patients. CONCLUSIONS: AIG should be considered in patients with autoimmunity and resistant iron-deficiency anemia. H. pylori infection may not be associated with pediatric AIG. The development of neuroendocrine tumor in one patient, and the high rates of metaplasia, highlight the importance of surveillance.

[IDIOPATHIC MYOINTIMAL HYPERPLASIA OF THE MESENTERIC VEINS: A CASE REPORT].

INTRODUCTION: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a rare disease of unknown etiology characterized by ischemia of intestinal segments, occuring due to intimal proliferation of the mesenteric veins and partial blockage of blood drainage. Diagnosis is performed pathologically and definitive treatment is surgical, where involved segments of the intestine are resected. Here we describe a case in which the patient underwent a comprehensive medical evaluation, finally diagnosed with IMHMV after bowel resection. The purpose of this case report is to present the diagnostic challenge to clinicians and raise awareness to this condition.

Mucosal transcriptomics highlight lncRNAs implicated in ulcerative colitis, Crohn's disease, and celiac disease.

Ulcerative colitis (UC), Crohn's disease (CD), and celiac disease are prevalent intestinal inflammatory disorders with nonsatisfactory therapeutic interventions. Analyzing patient data-driven cohorts can highlight disease pathways and new targets for interventions. Long noncoding RNAs (lncRNAs) are attractive candidates, since they are readily targetable by RNA therapeutics, show relative cell-specific expression, and play key cellular functions. Uniformly analyzing gut mucosal transcriptomics from 696 subjects, we have highlighted lncRNA expression along the gastrointestinal (GI) tract, demonstrating that, in control samples, lncRNAs have a more location-specific expression in comparison with protein-coding genes. We defined dysregulation of lncRNAs in treatment-naive UC, CD, and celiac diseases using independent test and validation cohorts. Using the Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) inception UC cohort, we defined and prioritized lncRNA linked with UC severity and prospective outcomes, and we highlighted lncRNAs linked with gut microbes previously implicated in mucosal homeostasis. HNF1A-AS1 lncRNA was reduced in all 3 conditions and was further reduced in more severe UC form. Similarly, the reduction of HNF1A-AS1 ortholog in mice gut epithelia showed higher sensitivity to dextran sodium sulfate-induced colitis, which was coupled with alteration in the gut microbial community. These analyses highlight prioritized dysregulated lncRNAs that can guide future preclinical studies for testing them as potential targets.

Müller's Muscle as a Sensory Proprioceptive Organ: Histological and Histochemical Analysis.

Purpose: The purpose of this study was to determine whether proprioceptive nerves are present in Müller's muscle. Methods: This was a prospective cohort study in which histologic and immunofluorescence analyses of excised Müller's muscle specimens were performed. Twenty fresh Müller's muscle's specimens from patients undergoing posterior approach ptosis surgery in one center between 2017 and 2018 were evaluated by histologic and immunofluorescent analysis. Axonal types were determined by measuring axon diameter in methylene blue stained plastic sections and by immunofluorescence of frozen sections. Results: We identified large (greater than 10 microns) and small myelinated fibers in the Müller's muscle, with 6.4% of these fibers being large. Immunofluorescent labeling with choline acetyltransferase showed no evidence of skeletal motor axons in the samples, indicating large axons are likely to be sensory and proprioceptive. In addition, we identified C-fibers using double labeling with peripherin and neural cell adhesion molecules. Conclusions: Overall, large myelinated sensory fibers are present in the Müller's muscle, likely serving proprioceptive innervation. This suggests that proprioception signals from Müller's muscle may have a role in eyelid spatial positioning and retracting, in addition to visual deprivation. This finding sheds new light on our understanding of this complex mechanism.

Direct identification of ALK and ROS1 fusions in non-small cell lung cancer from hematoxylin and eosin-stained slides using deep learning algorithms.

Anaplastic lymphoma kinase (ALK) and ROS oncogene 1 (ROS1) gene fusions are well-established key players in non-small cell lung cancer (NSCLC). Although their frequency is relatively low, their detection is important for patient care and guides therapeutic decisions. The accepted methods used for their detection are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assay, as well as DNA and RNA-based sequencing methodologies. These assays are expensive, time-consuming, and require technical expertise and specialized equipment as well as biological specimens that are not always available. Here we present an alternative detection method using a computer vision deep learning approach. An advanced convolutional neural network (CNN) was used to generate classifier models to detect ALK and ROS1-fusions directly from scanned hematoxylin and eosin (H&E) whole slide images prepared from NSCLC tumors of patients. A two-step training approach was applied, with an initial unsupervised training step performed on a pan-cancer sample cohort followed by a semi-supervised fine-tuning step, which supported the development of a classifier with performances equal to those accepted for diagnostic tests. Validation of the ALK/ROS1 classifier on a cohort of 72 lung cancer cases who underwent ALK and ROS1-fusion testing at the pathology department at Sheba Medical Center displayed sensitivities of 100% for both genes (six ALK-positive and two ROS1-positive cases) and specificities of 100% and 98.6% respectively for ALK and ROS1, with only one false-positive result for ROS1-alteration. These results demonstrate the potential advantages that machine learning solutions may have in the molecular pathology domain, by allowing fast, standardized, accurate, and robust biomarker detection overcoming many limitations encountered when using current techniques. The integration of such novel solutions into the routine pathology workflow can support and improve the current clinical pipeline.

Diagnosing Oncocytoma by Core Needle Biopsy: A Single-Center Experience.

Background: Oncocytoma is one of the most common benign kidney tumors, accounting for 3-7% of all solid renal masses. Diagnosing oncocytomas using renal biopsy remains a controversy in the uro-pathologic community. With the increasing use of biopsies for assessment of renal lesions, reaching this pathologically benign diagnosis may prevent further surgical measures and have significant clinical benefit. Objective: To demonstrate our center's results using renal biopsy to diagnose oncocytomas and to suggest that this diagnosis can be made with high success rates. Design: , Setting, and Participants. From our center's database, we retrospectively identified and retrieved all cases of oncocytoma diagnosed between the years 2011 and 2020 by renal biopsy. Medical records of those patients were then reviewed to view follow-up meetings and imaging of the lesions biopsied. Outcome Measurements and Statistical Analysis. In 21 biopsies performed on 19 patients, diagnosis was supported by subsequent follow-up averaging at 3.44 years per patient. Results and Limitations. The lesions exhibited benign behavior during follow-up after biopsy, consistent with the diagnosis of oncocytoma. Conclusions: Our study demonstrates that with good patient selection and proficient cooperation between urologists, radiologists and dedicated uro-pathologists, correctly diagnosing oncocytomas using RCB is a viable task. Patient Summary. Oncocytomas are benign lesions of the kidney. In our study, we reviewed all cases of oncocytomas pathologically diagnosed using renal biopsy from our center's database. We found that in subsequent follow-up later to biopsy, the lesions displayed benign behavior consistent with oncocytoma. The use of percutaneous biopsies to reach this diagnosis could save patients more extensive surgeries.

Host transcriptome signatures in human faecal-washes predict histological remission in patients with IBD.

BACKGROUND: Colonoscopy is the gold standard for evaluation of inflammation in inflammatory bowel diseases (IBDs), yet entails cumbersome preparations and risks of injury. Existing non-invasive prognostic tools are limited in their diagnostic power. Moreover, transcriptomics of colonic biopsies have been inconclusive in their association with clinical features. AIMS: To assess the utility of host transcriptomics of faecal wash samples of patients with IBD compared with controls. METHODS: In this prospective cohort study, we obtained biopsies and faecal-wash samples from patients with IBD and controls undergoing lower endoscopy. We performed RNAseq of biopsies and matching faecal-washes, and associated them with endoscopic and histological inflammation status. We also performed faecal mass-spectrometry proteomics on a subset of samples. We inferred cell compositions using computational deconvolution and used classification algorithms to identify informative genes. RESULTS: We analysed biopsies and faecal washes from 39 patients (20 IBD, 19 controls). Host faecal-transcriptome carried information that was distinct from biopsy RNAseq and faecal proteomics. Transcriptomics of faecal washes, yet not of biopsies, from patients with histological inflammation were significantly correlated to one another (p=5.3×10-12). Faecal-transcriptome had significantly higher statistical power in identifying histological inflammation compared with transctiptome of intestinal biopsies (150 genes with area under the curve >0.9 in faecal samples vs 10 genes in biopsy RNAseq). These results were replicated in a validation cohort of 22 patients (10 IBD, 12 controls). Faecal samples were enriched in inflammatory monocytes, regulatory T cells, natural killer-cells and innate lymphoid cells. CONCLUSIONS: Faecal wash host transcriptome is a statistically powerful biomarker reflecting histological inflammation. Furthermore, it opens the way to identifying important correlates and therapeutic targets that may be obscured using biopsy transcriptomics.

Giant leiomyosarcoma of the inferior vena cava necessitating extended liver resection: A case report and review of the literature.

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumour of smooth muscle origin. It commonly presents with non-specific symptoms including abdominal pain, distention, and lower extremity edema. Surgical resection with macroscopically clear margins is the only potential curative treatment for the disease. Here we present the case of a previously healthy 38-year-old woman with a subacute one-month increase of a four-year slowly progressive right sided abdominal pain and back pain. Imaging revealed a 14.5x12x15cm mass in the right hepatic lobe causing mass effect on adjacent abdominal and retroperitoneal organs, and involving the retrohepatic IVC. En-bloc resection of the right hemi-liver, most of segment four, the caudate lobe, and approximately a 10 cm section of the retrohepatic IVC, along with IVC reconstruction, was performed. Histologic examination revealed the diagnosis of a high grade leiomyosarcoma.

The concordance of treatment decision guided by OncotypeDX and the PREDICT tool in real-world early-stage breast cancer.

BACKGROUND: Decision-making regarding adjuvant chemotherapy for early-stage breast cancer can be guided by genomic assays such as OncotypeDX. The concordance of expected clinical decisions guided by OncotypeDX and prognostication online tools such as PREDICT is unknown. METHODS: We performed a retrospective single-center cohort study comprising all women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, node negative disease, whose tumors were sent for OncotypeDX analysis. Expected decision on adjuvant chemotherapy was evaluated using OncotypeDX and using PREDICT. The concordance between these two tools was calculated. The impact on concordance of prespecified features was assessed, including age, tumor size, intensity of ER and progesterone receptor (PR), grade, Ki67 and perineural and lymphovascular invasion. RESULTS: A total of 445 women were included. Overall concordance was 75% (K = 0.284). The concordance was significantly higher for grade 1 disease compared to grade 2-3 (93% vs 72%, P < .001), tumor ≤ 1 cm compared to >1 cm (85% vs 72%, P = .009), PR positive compared to PR negative (78% vs 58%, P < .001) and ki67 < 10% compared to ≥10% (92% vs 63%, P < .001). The intensity of ER and the presence of perineural or lymphovascular invasion had no significant impact on concordance. CONCLUSIONS: Compared to PREDICT, using OncotypeDx in node negative, ER positive disease is expected to change the clinical decision in a quarter of patients. The concordance between OncotypeDx and PREDICT is influenced by pathological features. In patients with very low risk, treatment decisions may be made based solely on clinical risk assessment.

Posterolateral capsular release for correction of valgus deformity.

Achieving coronal balance during arthroplasty of a valgus knee presents a challenge for the surgeon. Various techniques for lateral release had been described with no consensus among surgeons. We retrospectively reviewed 42 consecutive patients (38 women, mean age 72.7 years, follow-up 42 ± 23 months) with a valgus deformity who were operated while using a posterolateral capsular release as the sole method of lateral release. All knees were successfully balanced, without the need for further release of other structures. Valgus angles improved from 17.5 ± 4.6 degrees (range 11 to 31) to 6.3 ± 2.2 degrees (range 2 to 11) (p < 0.0001), and the knee and functional scores improved from 5.4 ± 17.7 and 24.8 ± 24.7 to 88.2 ± 15.8 and 70 ± 30, respectively (p < 0.0001) at last follow-up. One patient developed transient peroneal palsy after correction of severe deformity. The posterolateral capsule release, which is similar to that of the "inside-out" technique, provides a simple and safe solution for balancing a valgus knee.