stabilized-window-for-intravital-imaging-of-the-murine-pancreas

Stabilized Window for Intravital Imaging of the Murine Pancreas

The physiology and pathophysiology of the pancreas are complex. Diseases of the pancreas, such as pancreatitis and pancreatic adenocarcinoma (PDAC) have ...

Einstein College of Medicine / Montefiore Medical Center

Esophagitis results from diverse causes, including gastroesophageal reflux, immune-mediated or allergic reactions, therapeutic complications, and infections. The appropriate clinical management differs in each of these situations and is often guided by pathologic interpretation of endoscopic mucosal biopsy specimens. This review summarizes the diagnostic features of unusual forms of esophagitis, including eosinophilic esophagitis, lymphocytic esophagitis, esophagitis dissecans superficialis, drug-induced esophageal injury, and bullous disorders. Differential diagnoses and distinguishing features are emphasized.

Other Forms of Esophagitis: It Is Not Gastroesophageal Reflux Disease, So Now What Do I Do?

Immune compromise may result from genetic abnormalities, HIV/AIDS, or consequences of therapy for neoplastic and autoimmune diseases. Many immunocompromised patients develop severe gastrointestinal symptoms, particularly diarrhea, accompanied by non-specific or mild endoscopic abnormalities; mucosal biopsy with pathologic interpretation has a major role in the diagnosis and management of these patients. Immunocompromised individuals are at risk for all the diseases that affect those with a healthy immune system, but they are also prone to other illnesses that rarely affect immunocompetent patients. This review discusses the gastrointestinal manifestations of primary and acquired immunodeficiency, chemotherapy-related injury, and infections that show a predilection for immunocompromised patients. Key histologic features and relevant differential diagnoses are emphasized.

Inflammatory and infectious manifestations of immunodeficiency in the gastrointestinal tract.

Pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are grave illnesses with high levels of morbidity and mortality. Intravital imaging (IVI) is a powerful technique for visualizing physiological processes in both health and disease. However, the application of IVI to the murine pancreas presents significant challenges, as it is a deep, compliant, visceral organ that is difficult to access, easily damaged and susceptible to motion artefacts. Existing imaging windows for stabilizing the pancreas during IVI have unfortunately shown poor stability for time-lapsed imaging on the minutes to hours scale, or are unable to accommodate both the healthy and tumour-bearing pancreata. To address these issues, we developed an improved stabilized window for intravital imaging of the pancreas (SWIP), which can be applied to not only the healthy pancreas but also to solid tumours like PDAC. Here, we validate the SWIP and use it to visualize a variety of processes for the first time, including (1) single-cell dynamics within the healthy pancreas, (2) transformation from healthy pancreas to acute pancreatitis induced by cerulein, and (3) the physiology of PDAC in both autochthonous and orthotopically injected models. SWIP can not only improve the imaging stability but also expand the application of IVI in both benign and malignant pancreas diseases.

SWIP-a stabilized window for intravital imaging of the murine pancreas.

Neoplastic and nonneoplastic mast cell disorders can cause diarrhea, nausea, and abdominal pain that result from heightened release of mast cell mediators. Systemic mastocytosis is characterized by neoplastic mast cell aggregates in the bone marrow and other sites, particularly the skin and gastrointestinal tract. In this situation, extramedullary mast cell aggregates display atypical morphology, with aberrant immunostaining for CD25 in addition to staining for other mast cell markers, such as mast cell tryptase and CD117. Morphologically normal mast cells have also been implicated in nonneoplastic conditions. For example, increased mast cell numbers have been reported in the mucosal biopsy samples from patients with irritable bowel syndrome and hereditary alpha-tryptasemia. Patients with mast cell activation syndrome presumably experience symptoms related to the aberrant elaboration of histamine and other mediators from normal-appearing mast cells present in normal numbers. Unfortunately, similarities in terminology among these biologically distinct clinical conditions have caused considerable diagnostic confusion among clinical colleagues, resulting in frequent requests for pathologists to quantify and characterize mast cells in normal gastrointestinal biopsy samples from patients with diarrheal symptoms. The purpose of this review is to summarize the available data related to mast cell assessment in the gastrointestinal tract and provide pathologists with practical information so that they can help their clinical colleagues manage patients with presumed mast cell disorders.

What Is the Value of Counting Mast Cells in Gastrointestinal Mucosal Biopsies?

Distinguishing inflammatory bowel disease (IBD) from its mimics remains a diagnostic challenge for surgical pathologists. Several gastrointestinal infections produce inflammatory patterns that overlap with typical findings of IBD. Although stool culture, PCR, and other clinical assays may identify infectious enterocolitides, these tests may not be performed or the results may be unavailable at the time of histologic evaluation. Furthermore, some clinical tests, including stool PCR, may reflect past exposure rather than an ongoing infection. It is important for surgical pathologists to be knowledgeable about infections that simulate IBD to generate an accurate differential diagnosis, perform appropriate ancillary studies, and prompt clinical follow-up. This review covers bacterial, fungal, and protozoal infections in the differential diagnosis of IBD.

Article	Year
Other Forms of Esophagitis: It Is Not Gastroesophageal Reflux Disease, So Now What Do I Do? Surgical pathology clinics\| PubMed ID: 29103532	2017
Inflammatory and infectious manifestations of immunodeficiency in the gastrointestinal tract. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc\| PubMed ID: 29403083	2018
SWIP-a stabilized window for intravital imaging of the murine pancreas. Open biology\| PubMed ID: 35702996	2022
What Is the Value of Counting Mast Cells in Gastrointestinal Mucosal Biopsies? Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc\| PubMed ID: 36853780	2023
Infectious Mimics of Inflammatory Bowel Disease. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc\| PubMed ID: 37172904	2023

Nicole C. Panarelli

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