Gastrointestinal Biopsies Research Articles

Association Between Inflammatory Bowel Disease and Spondyloarthritis: Findings from a Nationwide Study in Sweden.

Inflammatory bowel disease [IBD] has been associated with spondyloarthritis [SpA], but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD with the general population, overall and by IBD subtype and age. We used a nationwide register-based cohort study of 39 203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390 490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios [ORs] for a prior [prevalent] SpA diagnosis and conditional Cox regression to calculate hazard ratios [HRs] for a subsequent [incident] SpA diagnosis in IBD patients. IBD patients were more likely to have prevalent SpA at IBD diagnosis [2.5%] compared with reference individuals [0.7%] with an OR of 3.48 [95% CI: 3.23, 3.75]. They also more often received an incident diagnosis of SpA; during 23 341 934 person-years of follow-up in IBD patients, there were 1030 SpA events [5.0/1000 person-years] compared with 1524 SpA events in the reference group [0.72/1000 person-years], corresponding to an HR of 7.15 [95% CI: 6.60, 7.75]. In subgroup analyses, associations were most pronounced among patients with Crohn's disease ([OR = 5.20; 95% CI: 4.59, 5.89], and [HR = 10.55; 95% CI: 9.16, 12.15]) and paediatric onset IBD ([OR = 3.63; 95% CI: 2.35, 5.59] and [HR = 15.03; 95% CI: 11.01, 20.53]). IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared with the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity, across IBD subtypes and age groups, calls for targeted approaches to facilitate timely diagnosis and intervention.

Increased tryptase expression in HαT is associated with upregulation of epithelia-derived MRGPRX2 agonists and MRGPRX2+ MCs in the GI mucosa

Abstract Hereditary α-tryptasemia (HαT) is a genetic trait characterized by elevated serum tryptase and increased copy number of the TPSAB1 gene. It is associated with flushing, itching, GI symptoms and anaphylaxis. HαT gut epithelia undergo increased rates of pyroptosis, and HαT gut mast cells (MCs) are increased in number with highly expressed FCER1 and CD203C. Gut MCs express Mas-related G protein–coupled receptor-X2 (MRGPRX2). Studies have clearly shown that this receptor contributes to host defense, mediates pseudo-allergy, and is involved in a number of atopic skin conditions. Herein, we sought to evaluate the impact of MRGPRX2 in individuals with HαT and GI symptoms. We observed increased numbers of MRGPRX2+ mast cells in HαT versus non-HαT gastrointestinal (GI) biopsies (colon->duodenum->stomach->Ileum). mRNA expression of tryptase and MRGPRX2 in intestine of HαT increased ~6-fold and 3-fold respectively over non-HαT biopsies. Epithelial derived agonists of MGPRX2 including human beta defensin (HBD) 2 and adrenomedullin (PAMP12) mRNA expression were also found to be upregulated ~2-fold and ~3-folds in HαT over non-HαT biopsies. MC protease carboxydeptidase-3 was also increased. Taken together, this data suggests that in addition to upregulation of MRGPRX2 in MCs, increased tryptase expression in HαT leads to upregulation of MRGPRX2 agonists and modifiers in gut epithelial cells, nociceptors and MCs, and results in GI symptoms. This work was supported by National Institutes of Health grants R01-AI124182, R01-AI143185 and R01-AI149487 to Hydar Ali.

Gastrointestinal Biopsy Obtained During Cancer Screening, a Biological Marker for α-Synucleinopathy?

The hallmark alteration in α-synucleinopathies, α-synuclein, is observed not only in the brain but also in the peripheral tissues, particularly in the intestine. This suggests that endoscopic biopsies performed for colon cancer screening could facilitate the assessment of α-synuclein in the gastrointestinal (GI) tract. Using immunohistochemistry for α-synuclein, we assessed whether GI biopsies could be used to confirm an ongoing α-synucleinopathy. Seventy-four subjects with cerebral α-synucleinopathy in various Braak stages with concomitant GI biopsies were available for study. In 81% of the subjects, α-synuclein was seen in the mucosal/submucosal GI biopsies. Two subjects with severe cerebral α-synucleinopathy and a long delay between biopsy and death displayed no α-synuclein pathology in the gut, and 11 subjects with sparse cerebral α-synucleinopathy displayed GI α-synuclein up to 36 years prior to death. The finding that there was no GI α-synuclein in 19% of the subjects with cerebral α-synucleinopathy, and α-synuclein was observed in the gut of 11 subjects (15%) with sparse cerebral α-synucleinopathy even many years prior to death is unexpected and jeopardizes the use of assessment of α-synuclein in the peripheral tissue for confirmation of an ongoing cerebral α-synucleinopathy.

Gastrointestinal biopsy in the horse: overview of collection, interpretation, and applications.

Evaluation of gastrointestinal (GI) biopsies is a multistep process that includes reviewing an appropriate history, determining sample quality, and evaluating histologic sections. Selected diagnostic parameters that, in combination with intestinal histopathology, can be useful to localize disease to the intestinal tract in the horse include hypoproteinemia and hypoalbuminemia, ultrasound evidence of increased thickness of the small intestinal wall, and alterations in glucose or D-xylose absorption tests. Biopsies may be acquired either endoscopically, or via laparoscopy or standing flank incisional approaches. GI sections should be evaluated using a systematic approach that includes both architectural changes and inflammatory cell infiltrates. Although strategies have been developed for assessment of GI biopsies from the dog and cat, a standardized approach to interpretation of the equine GI biopsy has yet to be developed. GI biopsies pose several challenges to the pathologist, especially for endoscopic biopsies in which the quality of the specimen and its orientation may vary greatly. Architectural changes are arguably the most critical changes to evaluate. In a horse with chronic GI inflammation, such as occurs in idiopathic inflammatory bowel disease (IBD), the cell types encountered frequently are macrophages, eosinophils, lymphocytes, and plasma cells. Increased numbers of these cell types are categorized loosely as mild, moderate, and severe. Specific forms of idiopathic IBD have been further classified by this infiltrate as granulomatous enteritis, eosinophilic enteritis, and lymphoplasmacytic enteritis; there is limited information on microscopic changes with each. Unfortunately, microscopic GI lesions are usually nonspecific, and determination of etiology requires further investigation.

Individuals With Eosinophilic Esophagitis Are at Greater Risk of Later Psychiatric Disorder.

Several gastrointestinal and allergic diseases have been linked to psychiatric disease, but there are limited data on psychiatric disease in eosinophilic esophagitis (EoE). Our aim was to study the association between EoE and later psychiatric disorders. This was a population-based nationwide cohort study. Individuals with EoE diagnosed during 1989-2017 in Sweden (n = 1,458) were identified through the ESPRESSO histopathology cohort that represents all gastrointestinal biopsy reports in Sweden's 28 pathology departments. Individuals with EoE were matched with up to 5 reference individuals on sex, age, county, and calendar year (n = 6,436). Cox proportional hazard modeling estimated adjusted hazard ratios (HRs). In a secondary analysis, we compared individuals with EoE with their siblings to adjust for intrafamilial confounding. The median age at EoE diagnosis was 39 years, and 76% of the enrolled individuals with EoE were male. During a median follow-up of 4 years, 106 individuals with EoE (15.96/1,000 person-years) developed a psychiatric disorder compared with 331 reference individuals (10.93/1,000 person-years), corresponding to an HR of 1.50 (95% confidence interval = 1.20-1.87). The increased risk was seen in the first 5 years of follow-up, but not thereafter. The highest relative risks were seen in individuals diagnosed with EoE in childhood. Compared with siblings, individuals with EoE were at an increased risk of psychiatric disease (HR = 1.62; 95% confidence interval = 1.14-2.31). EoE was linked to mood disorders, anxiety disorder, and attention-deficit hyperactivity disorder. Individuals with EoE may be at greater risk of psychiatric disease than their siblings and the general population. This risk needs to be considered in clinical care to detect, prevent, and treat comorbidity.

Feasibility of combined upper and lower gastrointestinal endoscopic biopsy in the common marmoset (Callithrix jacchus) to evaluate gastrointestinal diseases.

Chronic gastroenteropathies, including gluten sensitivity and marmoset wasting syndrome, frequently occur in captive colonies of common marmosets (Callithrix jacchus). Early identification and diagnosis of affected animals are desirable. Endoscopic examination of the colon in marmosets is described, but the small intestine can harbor significant mucosal lesions not representing those in the colon. Evaluating the small intestine currently requires invasive surgical biopsies due to the small patient size, carrying a risk of severe complications. Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum are demonstrated in 10 marmosets under general anesthesia. Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets with chronic gastrointestinal signs. This minimally invasive technique is feasible in marmosets. Future investigations into the pathogenesis of chronic gastroenteropathies will benefit from these data, leading to improved animal welfare and better individual and colony health management.

Prevalence of inflammatory versus neoplastic lesions in dogs with chronic gastrointestinal signs undergoing gastroduodenoscopy: 195 cases (2007–2015)

ObjectivesPrevalence of inflammatory enteropathy versus lymphoma in dogs undergoing gastroduodenoscopy has not been evaluated. This retrospective study assessed outcome from 195 client-owned dogs scheduled to undergo upper gastrointestinal endoscopy as the next diagnostic step. Material and methodsCases were grouped into the following diagnoses according to WSAVA guidelines: lymphoplasmacytic enteritis (LPE), eosinophilic enteritis (EE), mixed-cell enteritis (ME), histologically normal biopsies (N), and lymphoma (L). Clinical signs, and preendoscopic results from laboratory and ultrasonography examinations, were compared among groups. ResultsLPE was diagnosed in 133 (68%), EE in 17 (9%), ME in 9 (5%), 32 (16%) dogs had histologically normal biopsies. Four (2%) dogs were diagnosed with lymphoma. Vomiting was the most frequent clinical sign (61%), followed by weight loss (43%), and diarrhea (39%). Vomiting also predominated when looking at individual histological disease categories, however clinical signs did not differ significantly between groups. Dogs with lymphoma were more likely to have ultrasonographic abnormalities, had significantly lower haematocrit, albumin and total protein concentrations compared to dogs with LPE and histologically normal biopsies. Clinical significanceLymphoma was rarely found in this group of dogs with nonspecific results of pre-endoscopic work-up. Our results provide first reference for clinicians when discussing the possibility of a step-up therapeutic approach (such as multiple dietary trials) with owners before pursuing endoscopy. Understanding the likelihood of finding lymphoma is important in that histologic documentation of inflammatory enteropathy alone has limited therapeutic consequences. Future studies are needed to validate these findings in dogs undergoing combined upper and lower gastrointestinal endoscopy and biopsies.

Divergent Impact of Enzyme Replacement Therapy on Human Cardiomyocytes and Enterocytes Affected by Fabry Disease: Correlation with Mannose-6-phosphate Receptor Expression.

Background: The impact of enzyme replacement therapy (ERT) on cardiomyocytes and intestinal cells, affected by Fabry disease (FD), is still unclear. Methods: Six patients with FD, including five family members with GLA mutation c.666delC and one with GLA mutation c.658C > T, manifesting cardiomyopathy and intestinal symptoms (abdominal pain, diarrhea and malabsorption) were included in the study. Clinical outcome, cardiac magnetic resonance (CMR), endomyocardial and gastro-intestinal biopsies were evaluated before and after 2 years of treatment with agalsidase-α (0.2 mg/kg every other week). Immunohistochemistry and Western blot assessments of mannose-6-phosphate receptors (IGF-II-R) on intestinal and myocardial frozen tissue were obtained at diagnosis and after 2 years of ERT. Results: After ERT left ventricular maximal wall thickness, ranging from pre (<10.5 mm) to mild (<15 mm) and moderate hypertrophy (16 mm), was not associated with significant changes at CMR. Degree of dyspnea, mean cardiomyocyte diameter and % vacuolated areas of cardiomyocytes, representing intracellular GL3, remained unmodified. In contrast, intestinal symptoms improved with disappearance of diarrhea, recovery of anemia and weight gain, correlating with near complete clearance of the enterocytes from GL3 inclusions. IGF-II-R expression was remarkably higher even at histochemistry in intestinal tissue compared with myocardium (p < 0.001) either at baseline and after ERT, thus justifying intestinal recovery. Conclusions: Human cells affected by FD may respond differently to ERT: while cardiomyocytes retain their GL3 content after 2 years of treatment, gastro-intestinal cells show GL3 removal with recovery of function. This divergent response may be related to differences in cellular turnover, as well as tissue IGF-II-R expression.

Very Early Onset-IBD: evidence for the need of a multidisciplinary approach.

SummaryVery early onset inflammatory bowel disease (VEO-IBD) represents approximately 25% of cases of IBD-like colitis occurring during childhood and, by definition, it is characterized by an onset prior to 6 years of age. This subgroup of patients presents significant differences from IBD occurring in older children and in adults, including a more severe clinical course, a reduced responsiveness to conventional IBD therapy, and a greater proportion of cases featuring an underlying monogenic disorder. Histological findings from gastro-intestinal (GI) biopsies are characterized by an IBD-like, apoptotic or enterocolitis-like pattern, complicating the differential diagnosis with other pediatric diseases involving GI tract. Moreover, individuals with monogenic disorders may develop significant comorbidities, such as primary immunodeficiency (PID), impacting treatment options. Without an appropriate diagnosis, the clinical course of VEO-IBD has greater potential for escalated treatment regimens involving extensive surgery, more intensive medical therapies and, even more important, inadequate recognition of underlying monogenic defect that may lead to inappropriate (sometimes fatal) therapy. For these reasons, an adequate context leading to an appropriate diagnosis is imperative, calling for a close collaboration between pediatricians, pathologists, geneticists, and immunologists.

Pathologist’s approach to paediatric and neonatal eosinophilic gastrointestinal disorders

SummaryChildren are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach.Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist’s ability in identifying an abnormal number of eosinophils in this setting of patients.When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis.Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like “with eosinophilic pattern” should be favoured over a specific diagnosis of “eosinophilic disorder” in order to avoid potential confusion between different entities.

Diagnosis and treatment of sliding hiatal hernia and false gastric diverticulum in a British shorthair cat

AbstractA 7‐year 9‐month‐old, neutered, male British shorthair cat was referred for chronic regurgitation and vomiting. Previous symptomatic medical management did not improve these clinical signs. Survey radiographs and abdominal ultrasound revealed no significant abnormalities of the gastrointestinal tract. Exploratory laparotomy was performed to obtain gastrointestinal biopsies. Sliding hiatal hernia and an abnormal gastric outpouching at the fundus, measuring 15 × 15 × 15 mm, were identified. Surgical treatment of the hiatal hernia included phrenoplasty, oesophagopexy and left‐sided gastropexy. Additionally, the gastric outpouching was resected. Histopathologic examination of the excised fundic tissue revealed findings consistent with those indicative of a false gastric diverticulum. Postoperative examinations on Days 5 and 10 and telephone follow‐up on Days 30 and 120 revealed a marked reduction in clinical signs. The combination of surgical techniques—phrenoplasty, left‐sided gastropexy, oesophagopexy and gastric diverticulum resection—was found to effectively improve the cat's clinical signs.

Cytomegalovirus cell tropism and clinicopathological characteristics in gastrointestinal tract of patients with HIV/AIDS

BackgroundCytomegalovirus (CMV) has been recognized as one of the frequently occurring opportunistic infections (OIs) reported in the patients having human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In addition, it has been identified as the factor leading to gastrointestinal (GI) tract disorder among HIV/AIDS population. CMV exhibits broad cell tropism in different organs. This study evaluated the CMV cell tropism and clinicopathological characteristics of CMV infection in the different GI regions in HIV/AIDS cases.MethodsUsing nucleic acid in situ hybridization (ISH), CMV was detected in the gastrointestinal mucosal biopsy samples. The paraffin-embedded samples were stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC), respectively.ResultsA total of 32 HIV/AIDS patients were enrolled in this study. Fourteen of these patients underwent gastroscopy, while the remaining eighteen received colonoscopy. CMV-infected cells were observed at 46 GI sites. Among them, the colon was the region with the highest susceptibility to GI CMV infection (n = 12, 26.1%). The CMV giant cell inclusion bodies were detected in epithelial cells and mesenchymal cells, including histiocytes, smooth muscle cells, fibroblasts, and endothelial cells. In the duodenum, there were markedly more positive epithelial cells than mesenchymal cells (p = 0.033). In contrast, in the esophagus (p = 0.030), cardia (p = 0.003), rectum (p = 0.019), colon (p < 0.001), and cecum (p < 0.001), there were notably less positive epithelial cells than mesenchymal cells. The expression levels of PDGFRα and Nrp2 in the mesenchymal cells were higher than the epithelial cells in cardia, cecum, colon, sigmoid, and rectum, especially in the areas with ulcers. However, Nrp2 in the epithelial cells was higher than that in the duodenum. Moreover, the positive CMV DNA in peripheral blood was related to the CMV-positive cell count, as well as the ulceration in GI tract (p = 0.035 and 0.036, respectively).ConclusionsThe colon has been identified as the GI site with the highest susceptibility to CMV infection. There are different CMV-infected cells in the different sites of the GI that relate to the expression level of PDGFRα and Nrp2. CMV DNA positive in the blood is related to the positive CMV cell count, as well as ulceration in the GI tract.

Severe Acute Respiratory Syndrome Coronavirus 2 Is Detected in the Gastrointestinal Tract of Asymptomatic Endoscopy Patients but Is Unlikely to Pose a Significant Risk to Healthcare Personnel.

Background and AimsRecent evidence suggests that the gut is an additional target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, whether SARS-CoV-2 spreads via gastrointestinal secretions remains unclear. To determine the prevalence of gastrointestinal SARS-CoV-2 infection in asymptomatic subjects, we analyzed gastrointestinal biopsy and liquid samples from endoscopy patients for the presence of SARS-CoV-2.MethodsWe enrolled 100 endoscopic patients without known SARS-CoV-2 infection (cohort A) and 12 patients with a previous COVID-19 diagnosis (cohort B) in a cohort study performed at a regional hospital. Gastrointestinal biopsies and fluids were screened for SARS-CoV-2 by polymerase chain reaction (PCR), immunohistochemistry, and virus isolation assay, and the stability of SARS-CoV-2 in gastrointestinal liquids in vitro was analyzed.ResultsSARS-CoV-2 ribonucleic acid was detected by PCR in the colonic tissue of 1/100 patients in cohort A. In cohort B, 3 colonic liquid samples tested positive for SARS-CoV-2 by PCR and viral nucleocapsid protein was detected in the epithelium of the respective biopsy samples. However, no infectious virions were recovered from any samples. In vitro exposure of SARS-CoV-2 to colonic liquid led to a 4-log–fold reduction of infectious SARS-CoV-2 within 1 hour (P ≤ .05).ConclusionOverall, the persistent detection of SARS-CoV-2 in endoscopy samples after resolution of COVID-19 points to the gut as a long-term reservoir for SARS-CoV-2. Since no infectious virions were recovered and SARS-CoV-2 was rapidly inactivated in the presence of colon liquids, it is unlikely that performing endoscopic procedures is associated with a significant infection risk due to undiagnosed asymptomatic or persistent gastrointestinal SARS-CoV-2 infections.

Metastatic Gastric Carcinoma with Gastric Outlet Obstruction Extirpated by Palliative Gastrojejunostomy

Gastric cancer, third most common cause of death due to cancer and the fifth most common cancer across the world, present with symp-toms like early satiety, nausea, vomiting, abdominal pain and loss of weight. The common age of presentation lies between 50 to 70 years. Here, we discuss about a case of a 50years old patient presented with chief complaints of pain in the epigastric region, insidious in onset, gradually progressive, burning in nature and associated with early satiety and bloodstained vomiting. Upper Gastrointestinal Endoscopy (UGIE), Endoscopic biopsy and Contrast Enhanced Computed Tomography (CECT) were in favor of Metastatic Gastric Adenocarcinoma obstructing Gastric Outlet. Considering Gastric outlet obstruction, the patient underwent Palliative Gastrojejunostomy and Postoperative Radio chemotherapy. This case emphasizes the significance about considering palliative surgical care in improving the patient compliance and quality of life.

HIV-negative plasmablastic lymphoma sustaining long-term response after autologous peripheral blood stem cell transplantation

The patient is a 34-year-old HIV antibody-negative female with normal immunocompetence. The patient was referred to the hospital of the current study due to diarrhea and abdominal pain, which developed in May 2014. On conducting computed tomography (CT), remarkable wall thickening was noted in the terminal ilium over the ascending colon, suggesting a malignant tumor. However, making a definite diagnosis by lower gastrointestinal endoscopic biopsy and left hemicolectomy was not possible. The dense proliferation of plasma cell-like cells and plasmablasts was noted; CD20, CD19, CD79a, CD3, CD4, and Epstein-Barr virus-encoded miRNAs (EBER) were negative and CD138 was positive on immunostaining. Based on the aforementioned data, the patient was diagnosed with plasmablastic lymphoma (PBL). High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (PBSCT) was performed in the first remission period after the completion of four cycles of hyper CVAD/MTX-AraC alternating therapy. Remission was confirmed by FDG-PET/CT 3 months after autologous PBSCT. No signs of recurrence have been observed in 6 years after the transplantation. Although no standard treatment for PBL has been established, autologous peripheral blood stem cell transplantation combined with high-dose chemotherapy during the first remission period may be a beneficial treatment option.

Histopathological spectrum with clinical correlation of lower gastrointestinal tract endoscopic biopsies

Histopathological spectrum with clinical correlation of lower gastrointestinal tract endoscopic biopsies

Histopathological Spectrum of Endoscopic Gastrointestinal Biopsies: An Experience from a Tertiary Care Centre, Uttarakhand, India

Introduction: The Gastrointestinal Tract (GIT) is the site of numerous pathological lesions from inflammatory to malignant. Endoscopic biopsy plays an important role in detection of early- stage cancers and precursor lesions. It also aids in determining the extent of disease, monitoring response to therapy and for early detection of complications. However, histopathological evaluation serves as gold standard for diagnosis and aids the clinician in deciding further management. Aim: To determine the histopathological spectrum of gastrointestinal lesions and assess the frequency of benign and malignant tumours in GIT in a tertiary care center in North India. Materials and Methods: It was a retrospective study in which all endoscopic gastrointestinal biopsies received in Department of Pathology at Shri Guru Ram Rai Institute of Medical and Health Sciences from January 2015 to December 2017 were retrieved. The lesions from oropharynx, oesophagus, stomach, small intestine, large intestine, rectum and anal canal were categorised as neoplastic (further divided as benign and malignant) and non neoplastic. The results were tabulated and expressed as frequencies and percentages. Results: Of the 867 cases, 582 were males and 285 were females with a male to female ratio of 2.1:1. The most common age group was sixth decade with a mean age of 53.8 years. Out of a total of 7782 specimens received, 867 (11.1%) were endoscopic gastrointestinal biopsies. Among all the biopsies evaluated, 116 (13.4%) were from oropharynx, 55 (6.3%) oesophageal, 97 (11.2%) from stomach and Gastro-Oesophageal (GE) junction, 138 (15.9%) small intestinal and 461 (53.2%) from colorectum and anal canal. Out of 867 biopsies, 670 (77.3%) were classified as non neoplastic and 197 (22.7%) were neoplastic. Incidence of malignancy was highest in gastric (29%) and oropharyngeal (28.4%) biopsies while it was least in small intestinal biopsies (4.3%). Conclusion: In the current study, squamous cell carcinoma and ulcerative colitis were the most prevalent neoplastic and non neoplastic lesions, respectively. It is advisable to interpret and correlate endoscopic findings with histopathology to arrive at a final diagnosis and aid the clinician for further management.

Quantification of Mucosal Eosinophils for the Histopathologic Diagnosis of Eosinophilic Gastritis and Duodenitis: A Primer for Practicing Pathologists.

Eosinophilic gastrointestinal diseases, specifically eosinophilic gastritis and duodenitis, are chronic inflammatory conditions characterized by persistent gastrointestinal (GI) symptoms and elevated levels of activated eosinophils in the GI tract. Both clinical and endoscopic findings are nonspecific, no clinical or histopathologic diagnostic guidelines are published, and disease awareness is low, both among clinicians and amongst pathologists, who tend to overlook mild or moderate increases in the density of eosinophils in GI biopsy specimens. Yet, evaluating and, at times, counting eosinophils in GI biopsies may have important clinical implications: the numbers of tissue eosinophils correlate with clinical manifestations, can be used as determinants of effective management, and are used to assess the effects of treatment. A most persuasive argument for providing a count rather than a value judgment is that patients read reports, understand numbers, and use them to help to understand the course of their disease. The objective of this primer is to provide pathologists with the tools to incorporate a quantitative assessment of eosinophilia in the diagnosis of gastric and duodenal biopsy specimens and to develop a systematic approach to their evaluation, counting, and reporting. To achieve this aim, we present our general approach to the biopsy (where to count), followed by details on the characteristics of a countable eosinophil (what to count), and provide with a set of suggestions on the counting methods (how to count). We conclude with suggestions on how to report GI tissue eosinophilia in a manner that alerts clinicians and prompts pertinent management steps.

Gastrointestinal mucosal biopsies in Parkinson's disease: beyond alpha-synuclein detection.

Alpha-synuclein deposits, the pathological hallmarks of Parkinson's disease, are consistently found in the gastrointestinal tract of parkinsonian subjects. These observations have raised the potential that endoscopically obtainable mucosal biopsies can aid to a molecular diagnosis of the disease. The possible usefulness of mucosal biopsies is, however, not limited to the detection of alpha-synuclein, but also extends to other essential aspects underlying pathophysiological mechanisms of gastrointestinal manifestations in Parkinson's disease. The aim of the current review is to provide an appraisal of the existing studies showing that gastrointestinal biopsies can be used for the analysis of enteric neuronal and glial cell morphology, intestinal epithelial barrier function, and gastrointestinal inflammation in Parkinson's disease. A perspective on the generation of organoids with GI biopsies and the potential use of single-cell and spatial transcriptomic technologies will be also addressed.

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics.

Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR43) and at the onset of GvHD (p 0.000 for GPR109A, p=0.006 for GPR43) and correlated strongly with FOXP3 and NLRP3 expression. The use of broad-spectrum antibiotics (Abx) drastically suppressed GPR expression as well as FOXP3 expression in patients’ gut biopsies (p=0.000 for GPRs, FOXP3 mRNA and FOXP3+ cellular infiltrates). Logistic regression analysis revealed treatment with Abx as an independent factor associated with GPR and FOXP3 loss. The upregulation of GPRs was evident only in the absence of Abx (p=0.001 for GPR109A, p=0.014 for GPR43) at GvHD onset. Thus, GPR expression seems to be upregulated in the presence of commensal bacteria and associates with infiltration of FOXP3+ T regs, suggesting a protective, regenerative immunomodulatory response. However, Abx, which has been shown to induce dysbiosis, interferes with this protective response.