John Hart

• M.D.
• The University of Chicago Medical Center

The distinction of hepatocellular carcinoma (HCC) from metastatic tumor in the liver often presents a diagnostic challenge that carries significant impact on prognostication and therapy. The number of diagnostically useful immunohistochemical markers of hepatocytes is limited to hepatocyte paraffin antigen (HepPar-1), polyclonal carcinoembryonic an...

Angiogenesis has an important role in the carcinogenesis of esophageal adenocarcinoma, however, the diagnostic and prognostic utility of microvascular density counts have not been clinically established. The aim of this study is to assess the correlation between microvascular density and disease progression of non-dysplastic Barrett's esophagus, lo...

The 2011 American Gastroenterological Association diagnostic criteria for Barrett's esophagus (BE) require the presence of goblet cells in biopsy specimens of columnar mucosa within the esophagus. In other countries, patients can be diagnosed with BE based on evidence of columnar epithelium, regardless of the presence of goblet cells. We examined t...

4178 Background: The incidence of early-onset (age <50) gastrointestinal cancers, including early onset Appendiceal Adenocarcinoma (EOAA) is on the rise, however reported data on etiology, treatment, and outcomes is scarce. Here we present outcomes for EOAA patients treated at a single high-volume center. Methods: Records of patients (pts) with EOA...

4179 Background: Data regarding predictive biomarkers in Appendiceal Adenocarcinoma (AA) is scarce. GNAS mutations, frequent in mucinous AA, have been linked with poor objective response (OR) to chemotherapy. We hypothesize that activating GNAS mutations are associated with differential outcomes for metastatic AA treated with chemotherapy. Methods:...

Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification...

Abstract The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including non�invasive and tissue monitoring, immunosuppression...

Validated nonbiopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma. Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The reliability of such surrogates to predict mucosal rec...

A whole exome sequencing (WES)‐driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastr...

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with high mortality. Liver involvement is common (based on elevated liver function tests) with most patients demonstrating acute hepatitis. Liver biopsies are frequently obtained in the setting of suspected HLH for the purpose of identification of erythrophagocytosis, and if present, this f...

63 Background: Appendiceal cancers (AC) are a group of rare tumors that lack well-established guidelines. Care for ACs need multi-disciplinary teams. Excellence in hyperthermic intraperitoneal chemotherapy (HIPEC) and complete cytoreductive surgeries (CRS) is needed. This is challenging in community settings. Here we share our experience in establi...

Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma...

Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD) and histologic disease activity is evolving as a similarly important endpoint for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation...

Lymphocytic colitis is a microscopic colitis characterized endoscopically by nearly normal-appearing colonic mucosa and histology demonstrating intraepithelial lymphocytosis. Microscopic colitis that is refractory to conventional therapies, including budesonide, is rare but challenging and with scarce evidence. Upadacitinib is a novel Janus kinase...

Nonalcoholic fatty liver disease (NAFLD) is multifactorial in nature, affecting over a billion people worldwide. The gut microbiome has emerged as an associative factor in NAFLD, yet mechanistic contributions are unclear. Here, we show fast food (FF) diets containing high fat, added cholesterol, and fructose/glucose drinking water differentially im...

Abstract The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including non-invasive and tissue monitoring, immunosuppression opt...

Aims: Olmesartan, an angiotensin receptor blocker (ARB) used for hypertension management, is known to cause a sprue-like enteropathy in a subset of patients. Rare cases of gastritis occurring with ARB use have also been reported, but the histologic features of ARB-induced gastritis and the response to drug cessation have not been examined in a ded...

Background The endoscopic appearance in patients with “pouchitis” after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) can be quite heterogenous. Patients with an endoscopic phenotype resembling Crohn’s disease (CD) are at high risk of pouch loss. Aims We aimed to assess how the histopathology of colectomy specimens predicts endos...

Background Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immu...

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of metabolic syndrome and major indications for liver transplantation. Western diet contributes to disease pathogenesis, partially mediated through the gut microbiome, yet mechanisms remain elusive. Human epidemiological studies identified hi...

Introduction Treatment of ulcerative colitis (UC) now includes mucosal healing. Adoption of histologic end points is hindered by a lack of evidence guiding optimal sampling, interpretation, and reproducibility of results. Methods We analyzed biopsy fragments from colonoscopies in 92 patients with UC. Fragments were scored using 6-point histologic...

Context.— Endoscopic mucosal resection (EMR) has made it possible for Barrett esophagus patients with superficial cancers to be treated without esophagectomy. Recent guidelines recommend measuring depth of invasion (DOI) in submucosal cancers based on reports that in low-risk cancers, submucosal invasion 500 μm or less is associated with low nodal...

Background and study aimsEndoscopic submucosal dissection (ESD) is commonly used in Asia for resection of large non-pedunculated colorectal polyps (LNPCPs) and early (T1) colorectal cancers. It allows for en bloc removal and is often curative. We describe outcomes of colorectal ESD from a United States (US) academic medical center and compare this...

Dysregulation of epigenetic mechanisms, reflected by loss of expression of 5-hydroxymethylcytosine (5-hmC) is being increasingly recognized as a marker of aggressive behavior in several neoplasms; however, the role of such epigenetic modifiers in pancreatic neuroendocrine tumors (PanNETs) has not been studied. Annotated cohort of 60 PanNETs was eva...

Risk stratification of gastrointestinal stromal tumors (GISTs) is based on experience with tumors of the stomach, small bowel, and rectum, which are far more common than GISTs of other sites. In this study from 47 institutions, we analyzed GISTs of the esophagus (n = 102), colon (n = 136), and appendix (n = 27) for their size, mitotic rate, morphol...

The diagnosis of inflammatory bowel disease (IBD)–associated dysplasia is challenging, and past studies have demonstrated considerable interobserver variability in such diagnoses. This study aimed to assess interobserver agreement in IBD dysplasia diagnoses among subspecialty GI pathologists and to explore the impact of mentorship on diagnostic var...

Autopsies of patients who have died from COVID-19 have been crucial in delineating patterns of injury associated with SARS-CoV-2 infection. Despite their utility, comprehensive autopsy studies are somewhat lacking relative to the global burden of disease, and very few comprehensive studies contextualize the findings to other fatal viral infections....

The diagnosis of invasive adenocarcinoma of the gallbladder can sometimes be challenging. The presence of true desmoplastic reaction facilitates the diagnosis of invasion. However, desmoplasia-like changes can be observed in benign gallbladder conditions, and recognition of desmoplasia may be challenging based on morphology. In this study, we teste...

Objectives Metastases are common in non-cirrhotic livers but are considered unlikely in the setting of cirrhosis. However, the degree of fibrosis in cirrhosis may vary; thus metastases may still access the liver vasculature and present as a mass in cirrhotic livers. This possibility may affect pathologists’ diagnostic algorithms when faced with a l...

Historic and current pathology society guidelines recommend using visual gestalt to identify substantial inflammatory cell infiltrate in Helicobacter pylori gastritis, but these scales were subjectively designed. This study aims to objectively investigate the density of inflammation that justifies additional workup for H. pylori infection. We retro...

Mitophagy formed the basis of the original description of autophagy by Christian de Duve when he demonstrated that GCG (glucagon) induced macroautophagic/autophagic turnover of mitochondria in the liver. However, the molecular basis of liver-specific activation of mitophagy by GCG, or its significance for metabolic stress responses in the liver is...

Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted...

The one-year and median overall survival (mOS) rates of advanced gastroesophageal adenocarcinomas (GEA) are ∼50% and <12 months, respectively. Baseline spatial and temporal molecular heterogeneity of targetable alterations may be a cause of failure of targeted/immunooncologic therapies. This heterogeneity, coupled with infrequent incidence of some...

In 2008 Westermark et al. postulated that amyloid depositions found in allotransplanted islets derived from either islet overstimulation due to insulin production (as in type 2 diabetes), toxicity of immunosuppression, or perhaps both.¹ Amyloid depositions may promote a gradual decline in islet mass, progressive dysfunction, and ultimate failure. 2...

Background Evidence suggests that early‐onset gastric cancers are distinct from traditional gastric cancers; however, detailed genomic and morphologic characterization of these cancers has not been performed. Methods Genomic analysis was performed for 81 patients with gastric cancer who were 50 years old or younger; pathology slides were available...

Background and Aims ORISE Gel is a recently introduced, FDA-approved submucosal lifting agent used in endoscopic resection of GI lesions. Histologically evident gel deposits in resected specimens may pose a potential diagnostic pitfall. In order to aid in recognition of this procedure-related artifact, we report the largest histologic series of ORI...

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of appendiceal neoplasms specifically related to the management of peritoneal surface malignancies. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliati...

The Chicago Consensus Working Group provides the following multidisciplinary recommendations for the care of patients with peritoneal surface malignancies. This article focuses on the standards of a peritoneal surface malignancy center, standards of billing and coding, standards of operative reports for cytoreductive surgery and hyperthermic intrap...

4561 Background: Targeted therapies (tx) have had limited benefit in advanced (aGEA) due to baseline spatial (primary vs metastatic tumor PT/MT) & temporal molecular heterogeneity (BMH/TMH). We previously reported PANGEA methods & results: 35% BMH rate & 1 ⁰ OS results achieving 1yr OS of 66% & mOS of 16.4 months (m) using the personalized tx strat...

4547 Background: The incidence of early-onset gastroesophageal adenocarcinomas (EO-GEA) is increasing, and these tumors now constitute > 30% of all gastroesophageal cancers. Besides hereditary gastric cancer syndromes, which form ~3% of EO-GEA, the morphologic and molecular spectrum of these tumors is not well-studied. Methods: Next-generation sequ...

Background and aims: Complete histologic normalisation and reduction of inflammation severity in patients with ulcerative colitis are associated with improved clinical outcomes, but the clinical significance of normalisation of only segments of previously affected bowel is not known. We examined the prevalence, pattern, predictors and clinical out...

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoint molecules. ICIs are a novel immunotherapy for the treatment of many advanced malignancies. The advent of ICIs has been a major breakthrough in the field of oncology, a fact recognized by the 2018 Nobel Prize in Physiology or Medicine being awarded for the disc...

Background Chronic inflammation in ulcerative colitis (UC) is associated with the development of colorectal neoplasia (CRN). A group at St. Mark’s Hospital reported a novel cumulative inflammatory index that predicted the development of CRN in UC patients that we validated with an independent, well-described, matched, case-controlled cohort from th...

MFAP5, a 25-kD microfibril-associated glycoprotein that is involved in elastic microfibril assembly, has been demonstrated to be significantly downregulated in tumor stroma by previous gene expression study. The aim of this study was to confirm the reduced expression of MFAP5 in colonic tumor stroma using immunohistochemistry and to explore the uti...

Importance Patients with locally advanced gastroesophageal adenocarcinoma (ie, stage ≥T3 and/or node positive) have high rates of recurrence despite surgery and adjunctive perioperative therapies, which also have high toxicity profiles. Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT...

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic feat...

356 Background: 1-yr OS is ~40% for HER2- & ~55% for HER2+ advanced (aGEA). Targeted therapies (tx) have had limited benefit due to molecular heterogeneity. Methods: This phase 2a study of a personalized tx strategy (PTS) enrolled newly diagnosed aGEA pts who then received up to 3 cytotoxic (cx) lines: first line (1L) 5FU + oxaliplatin, 2L 5FU + ir...

Lymphoepithelioma‐like carcinomas (LELCs) are malignancies that appear histologically as undifferentiated epithelial cells accompanied by lymphoid response (1). LELCs have been described in a variety of organs including the liver, can present with hepatocellular or cholangiocarcinoma features, and have been reported to have a strong association wit...

Background & Aims Deep remission, based on clinical remission and evidence of healing during endoscopic evaluation, are goals of medical treatments for Crohn’s disease (CD). We investigated whether histologic healing is associated with outcomes of patients with CD ileitis. Methods We performed a retrospective study of 101 patients with CD (52% mal...

Histologic subtyping of ampulla of Vater carcinoma (ampullary carcinoma, AC) may guide choice of adjuvant chemotherapy for advanced disease, as intestinal (INT) subtype may have a better treatment response and survival as compared to the pancreatobiliary (PB) and mixed (MIX) subtypes. However, ambiguous morphologic features can result in inconsiste...

The molecular alterations identified among pyloric glands adenomas (PGAs) in the published literature are based on polymerase chain reaction of targeted genes and next-generation sequencing (NGS) has not been performed. In this study, we performed NGS and correlated the molecular alterations with the histologic grade of dysplasia and immunohistoche...

Background: There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease (NAFLD) are operationalised. Aim: To develop a consensus-based framework for standardising histologic assessment of liver biopsies in clinical trials of NAFLD. Methods: An expert panel of 14 liver pathologists and t...

Background: Nivolumab and pembrolizumab-two monoclonal antibodies that block human programmed cell death-1 (PD-1)-have been successfully used to treat patients with multiple advanced malignancies. The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them. Me...

The prevailing view that cirrhosis is irreversible has been challenged. It has been proposed that varying degrees of fibrosis regression can be achieved if the injurious agent is removed. In the normal liver, glutamine synthetase immunostaining is present around central veins. In regressed cirrhosis, although fibrous bands between portal tracts and...

Most patients with Cowden syndrome have lesions in the gastrointestinal tract, characterized by multiple polyps of various histologic types in the large bowel, polyps in the upper gastrointestinal tract, and esophageal glycogenic acanthosis. However, pathologists are often unaware of the distinctive polyposis phenotype of Cowden syndrome. In this m...

4050 Background: Complete resection (R0) and pathologic response grade (PRG) correlate with long-term GEA outcome. FOLFIRINOX demonstrated efficacy in advanced GEA; gFOLFIRINOX improved tolerability. We evaluated R0, PRG and tolerability in this pilot P study. Methods: Gastric body (GB) + esophagogastric (EGJ) GEA patients (pts) with ≥T3Nx or TxN+...

Colorectal cancer is a leading cause of cancer deaths. The renin-angiotensin system (RAS) is upregulated in colorectal cancer, and epidemiologic studies suggest RAS inhibitors reduce cancer risk. Because vitamin D (VD) receptor negatively regulates renin, we examined anticancer efficacy of VD and losartan (L), an angiotensin receptor blocker. Contr...

Inflammatory bowel disease-associated colorectal carcinomas (IBD-CRCs) develop in a background of chronic inflammation, and thus, the molecular landscape of these tumors likely differs from that of sporadic colorectal cancer. To add to emerging data on molecular alterations present in these tumors, we analyzed our institution's cohort of IBD-CRCs....

Although valuable insights into colon cancer biology have been garnered from human colon cancer cell lines and primary colonic tissues, and animal studies using human colon cancer xenografts, immunocompetent mouse models of spontaneous or chemically-induced colon cancer better phenocopy human disease. As most sporadic human colon tumors present ade...

Background Chronic inflammation in ulcerative colitis (UC) is associated with the development of subsequent colorectal neoplasia (CRN). The group at St. Mark's Hospital (London) previously reported a novel ‘cumulative inflammatory index’ that predicted development of CRN in patients with UC.¹ In this analysis, we sought to validate these findings.²...

Background: The present study aimed to investigate the role of blood supply in early tumorigenesis in colorectal cancer. We leveraged the renin angiotensin system (RAS) to alter colonic blood supply and determine the effect on tumor initiation and progression. Methods: To test the effect of blood supply on tumorigenesis, 53 male A/J mice were ra...

[This corrects the article DOI: 10.1371/journal.pone.0194234.].

The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines1-3 suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous co...

Identification of biological markers predicting the onset of neoplasia in patients with long-standing ulcerative colitis (UC) could allow for risk stratification in this population. In this study, we retrospectively identified subjects with chronic UC who developed colon neoplasia (n = 16) matched to UC patients who never developed neoplasia. RNA w...

Introduction In prior studies, we showed that EGFR is required for tumor promotion by Western diet in the azoxymethane (AOM) model of sporadic colon cancer and the AOM/DSS model of inflammation‐associated colon cancer. We also demonstrated that ADAM17, the metalloprotease responsible for shedding membrane‐bound EGFR ligands, controls tumor developm...

Background Intensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported. Materials and methods 52 patients with anal SCC w...

Previous anti-EGFR trials in unselected patients with gastroesophageal adenocarcinoma (GEA) were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven patients received ≥1 dose of tre...

Context: - Isolated loss of PMS2 staining is an uncommon immunophenotype in colorectal carcinomas, accounting for approximately 4% of tumors with microsatellite instability. Limited information regarding these tumors is available in the literature. Objective: - To compare the clinicopathologic features of colorectal carcinomas with isolated PMS2...

Background The impact of histological remission is currently investigated in patients with Crohn’s disease (CD). In this study, we aimed to assess the relationships between histological activity and (1) clinical activity, (2) endoscopic activity or (3) faecal calprotectin (Fcal), which are still unknown in CD. Methods From a prospectively maintain...

Background: When colon polyps are removed in the setting of inflammatory bowel disease (IBD) involving the large intestine, biopsies of the flat mucosa surrounding such polyps have been recommended, but there are no data to support this practice. Methods: We reviewed endoscopic and pathologic findings in IBD patients who had dysplastic polyps re...

Every year many new medications are approved for clinical use, several of which can cause clinically significant gastrointestinal tract toxicity. This article emphasizes the histologic features and differential diagnosis of drug-induced injury to the gastrointestinal mucosa. Ultimately, clinical correlation and cessation of a drug with resolution o...

Background and aims: Due to previous manipulation or submucosal invasion, GI lesions referred for endoscopic mucosal resection (EMR) frequently have flat areas of visible tissue that cannot be snared. Current methods for treating residual tissue may lead to incomplete eradication or not allow complete tissue sampling for histologic evaluation. Our...