Aberrant p53 expression is associated with neoplastic progression in Barrett oesophagus diagnosed as indefinite for dysplasia.

The aim of this study was to investigate the role of immunohistochemical (IHC) expression of p53 and other potential clinical parameters as prognostic markers for predicting neoplastic progression in Barrett oesophagus (BE) patients diagnosed as indefinite for dysplasia (IND). The study included patients with established BE of any extent who had a diagnosis of IND accompanied by concurrent p53 immunohistochemistry (IHC) stain at the index endoscopic procedure and at least one follow-up examination between 2000 and 2021. Correlation between disease progression from IND to higher-grade dysplasia [low-grade dysplasia (LGD), high-grade dysplasia (HGD) and oesophageal adenocarcinoma (EAC)] and clinicopathological parameters were analysed. A total of 149 patients (99 males; mean age 63.3 ± 10.0 years, range = 35-89) were included in the final analysis. Median follow-up was 37.1 months [interquartile range (IQR) = 20.5-59.1 months]. Progression rates from IND to LGD and HGD were 12.1% (18 of 149) and 2.7% (four of 149), respectively. On multivariate analysis, the number of IND diagnoses was significantly associated with progression to both LGD and HGD (P = 0.016 and P < 0.001, respectively). Cox regression analysis showed that aberrant p53 expression was significantly associated with progression to LGD [hazard ratio (HR) = 4.87, 95% confidence interval (CI) = 1.91-12.45, P = 0.001] and HGD (HR = 21.81, 95% CI = 1.88-253.70, P = 0.014). Kaplan-Meier survival analysis also demonstrated that aberrant p53 expression was significantly associated with progression to LGD (P < 0.001) and HGD (P = 0.001). Our results suggest that frequency of IND diagnoses and status of p53 expression can help to stratify risk of neoplastic progression in BE patients with IND.

Colorectal carcinomas with mucinous differentiation are associated with high frequent mutation of KRAS or BRAF mutations, irrespective of quantity of mucinous component.

BACKGROUND: Mucinous adenocarcinoma (MAC) is a distinct type of colorectal cancer (CRC) associated with poor response to treatment and poorer prognosis. MAC is diagnosed by WHO definition when the extracellular mucin is more than 50% of the lesion. We aimed at assessing the gene expression profiles of the CRCs with any mucinous features (> 5%) in a retrospective study. METHODS: The data of a 50-gene next generation sequencing (NGS) panel of 166 CRCs was analyzed and the gene mutational profile with morphologic features was correlated. RESULTS: We identified the different genetic mutation profiles between CRCs with and without mucinous component, but noticed a similar genetic profile between MACs and CRCs with mucinous component, irrespective of the percentage (if mucinous component more than 5%). The different genetic mutation profile related to MSI status was also identified between two groups of tumors. The most frequent mutations in CRCs with mucinous component are KRAS (28/49, 57.1%) and BRAF (19/49, 38.7%), PIK3CA (16/49, 32.6%), followed by APC (12/49, 24.5%) and TP53 (11/49, 22.5%). The combined mutation frequency of the two key factors in the EGFR signaling pathway, KRAS and BRAF, in the CRCs with and without mucinous component is 95.9 and 52.1%, respectively. CONCLUSIONS: The dysregulation of EGFR pathway plays a critical role in the development of CRCs with mucinous component, irrespective of the percentage. The result suggested that the current cut off of 50% mucin component to define mucinous adenocarcinoma might be challengeable.

Impact of EUS-guided microforceps biopsy sampling and needle-based confocal laser endomicroscopy on the diagnostic yield and clinical management of pancreatic cystic lesions.

BACKGROUND AND AIMS: EUS-guided microforceps biopsy sampling (MFB) and needle-based confocal laser endomicroscopy (nCLE) are emerging diagnostic tools for pancreatic cystic lesions (PCLs). There is a paucity of data regarding their performance and impact. The aim of this study was to compare diagnostic outcomes and changes in clinical management resulting from MFB and nCLE use in PCLs. METHODS: This was a single-center retrospective study of patients with PCLs who underwent combined EUS-guided FNA, MFB, and nCLE. Primary outcomes included diagnostic yield (specific PCL type) and change in clinical management for each modality compared with the current "composite standard" (CS) obtained by combining clinical, morphologic, cyst fluid cytology, and chemical analysis. RESULTS: Forty-four cysts were studied in 44 patients. Technical success was 100% for EUS-FNA, 88.6% for MFB, and 97.7% for nCLE. Of 44 procedures, there was 1 adverse event (2.3%, an infected pseudocyst). Diagnostic yield for each individual modality was 34.1% for CS, 75.0% for MFB (P < .05 vs CS), and 84.1% for nCLE (P < .05 vs CS). Diagnostic yield for combined tests was 79.5% for CS/MFB, 88.6% for CS/nCLE, and 93.2% for CS/MFB/nCLE (P = not significant). Compared with the CS, the use of MFB, nCLE, and their combination led to overall change in clinical management in 38.6%, 43.2%, and 52.3% of cases, respectively. MFB and nCLE led to an overall increase in discontinuation of surveillance (MFB, 34.1% [P < .05]; nCLE, 31.8% [P < .05]), led by a reduction in the indication for follow-up radiologic or endoscopic studies (MFB, 34.1% [P < .05]; nCLE, 38.6% [P < .05]). Based on MFB and nCLE, 2 of 28 (7.1%) and 3 of 28 (10.7%) patients who would have undergone further surveillance were referred for surgery. CONCLUSIONS: In the evaluation of PCLs, the use of combined EUS-guided FNA, MFB, and nCLE is safe. MFB and nCLE led to significant improvements in specific PCL diagnosis, which in turn has major impacts in clinical management.

Green Tea Consumption and Esophageal Cancer Risk: A Meta-analysis.

Background: The protective role of green tea against cancer is still unknown.Objectives: To investigate the association between green tea consumption and esophageal cancer risk through meta-analysis.Methods: We searched MEDLINE, EMBASE, Web of Science and Cochrane Library for studies on the relationship between green tea and esophageal cancer risk. We assessed heterogeneity (I2) and publication bias (Begg's and Egger's tests). Pooled relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects models.Results: A total of 20 studies were included. The RRs for all studies was 0.65 (95% CI: 0.57-0.73), with I2 = 75.3% and P = 0. In the subgroup analysis, the following variables showed marked heterogeneity: Asian (RR: 0.64; 95% CI: 0.56-0.73) and non-Asian countries (RR: 0.74; 95% CI: 0.45-1.03), female (RR: 0.55; 95% CI: 0.39-0.71) and male + female (RR: 0.64; 95% CI: 0.54-0.75), case-control study (RR: 0.62; 95% CI: 0.52-0.71), impact factor >3 (RR: 0.65; 95% CI: 0.56-0.75), impact factor <3 (RR: 0.64; 95% CI: 0.48-0.80), Newcastle-Ottawa Scale >7 (RR: 0.82; 95% CI: 0.66-0.97) and Newcastle-Ottawa Scale ≤7 (RR: 0.59; 95% CI: 0.49-0.68).Conclusion: Green tea consumption could be a protective factor for esophageal cancer.

BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice.

T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naïve CD4+ T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential. Whether these BET proteins represent viable new epigenetic drug targets for inflammatory disorders has remained an unanswered question. In this study, we report that selective inhibition of the first bromodomain of BET proteins with our newly designed small molecule MS402 inhibits primarily Th17 cell differentiation with a little or almost no effect on Th1 or Th2 and Treg cells. MS402 preferentially renders Brd4 binding to Th17 signature gene loci over those of housekeeping genes and reduces Brd4 recruitment of p-TEFb to phosphorylate and activate RNA polymerase II for transcription elongation. We further show that MS402 prevents and ameliorates T-cell transfer-induced colitis in mice by blocking Th17 cell overdevelopment. Thus, selective pharmacological modulation of individual bromodomains likely represents a strategy for treatment of inflammatory bowel diseases.

Prediction of the histopathologic findings of intrahepatic cholangiocarcinoma: qualitative and quantitative assessment of diffusion-weighted imaging.

OBJECTIVE: To correlate qualitative and quantitative diffusion weighted imaging (DWI) characteristics of intrahepatic cholangiocarcinoma (ICC) with histopathologic tumour grade and fibrosis content. METHODS: Fifty-one patients (21M/30F; mean age 61y) with ICC and MRI including DWI were included in this IRB-approved multicentre retrospective study. Qualitative tumour features were assessed. Tumour apparent diffusion coefficient (ADC) mean, minimum, and normalized (nADCliver) values were computed. Tumour grade [well(G1), moderately(G2), or poorly differentiated(G3)] and tumour fibrosis content [minimal(1), moderate(2), or abundant(3)] were categorized pathologically. Imaging findings and ADC values were compared with pathologic measures. Utility of ADC values for predicting tumour grade was assessed using ROC analysis. RESULTS: 51 ICCs (mean size 6.5±1.1 cm) were assessed. 33/51(64%) of ICCs demonstrated diffuse hyperintensity and 15/51(29%) demonstrated target appearance on DWI. Infiltrative morphology (p=0.02) and tumour size (p=0.04) were associated with G3. ADCmean and nADCmean of G3 (1.32±0.47x10-3 mm2/sec and 0.97±0.95) were lower than G1+G2 (1.57±0.39x10-3 mm2/sec and 1.24±0.49; p=0.03 and p=0.04). ADCmean and nADCmean were inversely correlated with tumour grade (p<0.025). No correlation was found between ADC and tumour fibrosis content. AUROC, sensitivity and specificity of nADCmean for G3 versus G1+G2 were 0.71, 89.5% and 55.5%. CONCLUSION: ADC quantification has reasonable accuracy for predicting ICC grade. KEY POINTS: • ADC quantification was useful for predicting ICC tumour grade. • Infiltrative tumour morphology and size were associated with poorly differentiated ICCs. • ADC values depended more on ICC tumour grade than fibrosis content. • Ability to predict ICC tumour grade non-invasively could impact patient management.

Feasibility and reproducibility of BOLD and TOLD measurements in the liver with oxygen and carbogen gas challenge in healthy volunteers and patients with hepatocellular carcinoma.

PURPOSE: To quantify baseline relaxation rates R2* and R1 in the abdomen, their changes after respiratory challenges, and their reproducibility in healthy volunteers and patients with hepatocellular carcinoma (HCC) at 1.5T and 3.0T. MATERIALS AND METHODS: R2* measurements were acquired in the liver in 8 volunteers and 27 patients with 34 HCCs using multiecho T2* at baseline and after respiratory challenges with 100% oxygen (O2 ) and carbogen (CB = 95%O2 /5%CO2 ). R1 was measured at 1.5T in one volunteer and 21 patients with 23 HCCs. Test-retest coefficient of variation (CV) was assessed in 10 subjects. Intra- and interobserver variability of R2* and R1 measurements was assessed in 12 and 10 patients, respectively. Parameters for HCC, liver, and muscle were compared between baseline and after gas challenges. RESULTS: We observed that R2* and R1 imaging of HCCs with O2 and CB is feasible and reproducible (test-retest CV R2*<15%/R1 <5%; intra- and interobserver intraclass correlation coefficient R2*>0.88/R1 >0.7 and CV R2*<7%/R1 <3% at 1.5T). R2* measurements were observed to be less reproducible at 3.0T (CV<35%). There was a statistically significant decrease in R2* values in HCC before and after O2 (P = 0.02) and increase in R1 after O2 (P = 0.004). CB had no significant effect (P R2* = 0.47/R1 = 0.278). CONCLUSION: R2* measurements in HCC and liver parenchyma are more reproducible at 1.5T than at 3.0T, and with O2 than with CB challenge. We observed a decrease in R2* and an increase in R1 of HCCs from baseline in response to O2 challenge, as expected with increased tissue and blood oxygenation.

Intravoxel incoherent motion diffusion-weighted imaging of hepatocellular carcinoma: Is there a correlation with flow and perfusion metrics obtained with dynamic contrast-enhanced MRI?

PURPOSE: To assess the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) metrics in hepatocellular carcinoma (HCC) and liver parenchyma. MATERIALS AND METHODS: Twenty-five patients with HCC (M/F 23/2, mean age 58 years) underwent abdominal MRI at 1.5 or 3.0T, including IVIM-DWI (with 16 b-values) and DCE-MRI (3D FLASH sequence, mean temporal resolution of 2.3 sec). IVIM-DWI parameters (pseudodiffusion coefficient, D*, diffusion coefficient, D, and perfusion fraction, PF) were quantified in HCC lesions and liver parenchyma using a Bayesian fitting algorithm. DCE-MRI parameters (arterial flow, Fa , portal flow, Fp , total flow, Ft , mean transit time, MTT, distribution volume, DV, and arterial fraction, ART) were quantified using a dual-input single-compartment model. Correlations between IVIM-DWI and DCE-MRI parameters were assessed using a Spearman correlation test. RESULTS: Thirty-three HCC lesions (average size 5.0 ± 3.6 cm) were analyzed. D, D*, and PF were all significantly lower in HCC vs. liver (P < 0.05). Significantly higher Fa and ART and lower Fp were observed in HCC vs. liver (P < 0.001). Significant moderate to strong negative correlations were observed between ART and D* (r = -0.443, P = 0.028), ART and PF (r = -0.536, P = 0.006), ART and PFxD* (r = -0.655, P < 0.001), Fa and PF (r = 0.455, P = 0.023), and Fa and PFxD* (r = -0.475, P = 0.018) in liver parenchyma. There was no significant correlation between IVIM-DWI and DCE-MRI metrics in HCC lesions. CONCLUSION: IVIM-DWI and DCE-MRI provide nonredundant information in HCC, while they correlate in liver parenchyma. These findings may be secondary to predominant portal inflow in the liver and tortuous vasculature and tissue heterogeneity in tumors. J. MAGN. RESON. IMAGING 2016;44:856-864.

BRD4 inhibitor inhibits colorectal cancer growth and metastasis.

Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal.

Unusual Presentation of a Hepatic Neuroendocrine Tumor With Elevated CEA and CA 19-9: A Case Report.

Neuroendocrine tumors (NETs) of the gastrointestinal tract (GIT) are rare malignancies, which may have unique presentations. The diagnostic process predominantly relies on immunohistochemical analysis. While tumor markers are extensively utilized in diagnosing and monitoring GI malignancies, their specific role in NETs has not been fully explored. This case describes an 83-year-old male presenting with jaundice and general weakness. Diagnostic imaging through MRI and CT angiography (CTA) revealed a nodular texture on the liver's surface suggesting cirrhosis. The presence of elevated tumor markers, specifically carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), raised suspicions of malignancy. A subsequent liver biopsy confirmed the diagnosis of small-cell high-grade neuroendocrine carcinoma accompanied by reactive fibrosis. As per our knowledge, this case is the first recorded instance of a liver neuroendocrine tumor (NET) exhibiting elevated levels of both CEA and CA 19-9, with no abnormalities detected in the gallbladder, biliary tree, and bowel in the MRI with magnetic resonance cholangiopancreatography (MRCP) and CTA. This is an atypical presentation of a liver NET, mimicking cirrhotic liver morphology, and underscores the potential diagnostic relevance of tumor markers CEA and CA 19-9 in such cases.

A Novel Presentation of Autoimmune Hepatitis with IgG1 Elevation.

Autoimmune hepatitis (AIH) is a common and debilitating pathology that has acute, subacute, and chronic presentation, requiring prompt diagnosis and early intervention. Several serologic markers are found to be associated with the pathogenesis and progression of autoimmune hepatitis, most notably antinuclear antibodies and anti-smooth muscle antibodies [Front Immunol. 2018;9:609]. In addition, AIH is also characterized by the elevation of gamma globulin levels, mainly immunoglobulin G (IgG) [World J Gastroenterol. 2015;21(1):60-83]. Although the literature has well established the presence of increased IgG levels in AIH, few studies have evaluated the subtypes of IgG and their differential levels associated with AIH. Here, we present a rare case of AIH that lacks the common serologic markers but instead reveals an elevation in IgG1 level. Our patient was subsequently placed on corticosteroids, and her symptoms quickly resolved. We intend to introduce this case to the medical community in the hope of aiding in the proper diagnosis and timely intervention of subsequent cases with similar presentations.

Morphologic features of extrahepatic manifestations of hepatitis C virus infection.

Cirrhosis and hepatocellular carcinoma are the prototypic complications of chronic hepatitis C virus infection in the liver. However, hepatitis C virus also affects a variety of other organs that may lead to significant morbidity and mortality. Extrahepatic manifestations of hepatitis C infection include a multitude of disease processes affecting the small vessels, skin, kidneys, salivary gland, eyes, thyroid, and immunologic system. The majority of these conditions are thought to be immune mediated. The most documented of these entities is mixed cryoglobulinemia. Morphologically, immune complex depositions can be identified in small vessels and glomerular capillary walls, leading to leukoclastic vasculitis in the skin and membranoproliferative glomerulonephritis in the kidney. Other HCV-associated entities include porphyria cutanea tarda, lichen planus, necrolytic acral erythema, membranous glomerulonephritis, diabetic nephropathy, B-cell non-Hodgkin lymphomas, insulin resistance, sialadenitis, sicca syndrome, and autoimmune thyroiditis. This paper highlights the histomorphologic features of these processes, which are typically characterized by chronic inflammation, immune complex deposition, and immunoproliferative disease in the affected organ.

Electroacupuncture at Zusanli (ST36), Guanyuan (CV4), and Qihai (CV6) Acupoints Regulates Immune Function in Patients with Sepsis via the PD-1 Pathway.

Objective: The present study is aimed at investigating the biochemical and clinical effects of electroacupuncture in patients with sepsis. Methods: Patients with sepsis treated at Guangdong Provincial Hospital of Chinese Medicine from July 2019 to December 2020 were included. Patients were randomly assigned to treatment with routine Western medicine (WM group) or treatment with Western medicine plus electroacupuncture based on Western medicine (EA group). Indices associated with immune function and clinical efficacy were determined before and at 3 and 5 days after treatment. Indicators of immune function included the percentage of T lymphocyte subsets, natural killer (NK) cells, and soluble programmed death protein 1 (sPD-1) levels. Indicators of clinical efficacy included infection-related indicators in whole blood; levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interferon-γ (INF-γ); and assessments using acute physiology and chronic health evaluation-II (APACHE-II) and sequential organ failure assessment (SOFA) scores. Results: Baseline data were not different between WM (N = 30) and EA groups (N = 30). At day 5 following treatment, the level of sPD-1 in the EA group was lower than that in the WM group. Proportions of CD3 + T lymphocytes, CD4 + T lymphocytes, and NK cells, the percentage of lymphocytes, and INF-γ levels in the EA group were significantly higher than those in the WM group. Compared with the WM group, the white blood cell count (WBC), percentage and count of neutrophils, ratio of neutrophils to lymphocytes, and levels of CRP and TNF-α were significantly decreased in the EA group 5 days after treatment. The APACHE-II score of the EA group was significantly lower than that of the WM group 5 days after treatment. Conclusion: Electroacupuncture may regulate the immune function of patients with sepsis through the PD-1 pathway to achieve an anti-inflammatory state and improve clinical symptoms.

A case report on a large, peduncular intra-abdominal hepatocellular carcinoma extending into the retroperitoneum.

Here, we discuss a relatively uncommon presentation of a hepatocellular carcinoma and discuss its preoperative planning and surgical intervention required to reach complete resection.

Primary hepatic signet ring cell neuroendocrine tumor: a case report with literature review.

Primary hepatic signet ring cell neuroendocrine tumor is extremely rare and is characterized by distinct intracytoplasmic hyaline vacuoles that are mucin negative and cytokeratin positive. The unique histological features may cause difficulty in diagnosis and delay patient care. Here the authors report a 49-year-old man with an incidental finding of a 2.7 cm liver mass in the absence of chronic liver disease. The resected tumor was grossly unencapsulated but well demarcated with friable tissue texture. Microscopically, the entire tumor consisted of sheets of monotonous cells separated by delicate microvasculature. The tumor cells had granular chromatin, inconspicuous nucleoli, and eosinophilic cytoplasm. Many of the tumor cells had eccentric, pale intracytoplasmic vacuoles resembling signet ring cells in adenocarcinoma. Immunohistochemical studies showed that the tumor cells were positive for neuroendocrine markers and that the intracytoplasmic vacuoles were negative for mucin but strongly positive for cytokeratins. Careful systemic search including OctreoScan scintigraphy (Mallinckrodt Medical, Inc., St. Louis, MO) and capsule endoscopy failed to reveal any other tumors. A diagnosis of primary hepatic signet ring cell neuroendocrine tumor was established. Ten months after surgery, the patient is well without any other detectable tumor on radiology. Serological neuroendocrine markers are also within normal limits.

Polypoid Undifferentiated Carcinoma With Osteoclast-like Giant Cells Arising in the Distal Common Bile Duct: A Rare Case Report.

BACKGROUND: Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) in distal common bile duct (CBD) is a rare entity. CASE REPORT: This case report describes a 45-year-old male with a history of a choledochal cyst status post partial excision and cholecystectomy who presented with a mass in the remaining distal/intrapancreatic common bile duct. It was initially mistaken for post-surgery hematoma; however, the rapid growth raised concern for malignancy, and prompted a pancreaticoduodenectomy (Whipple) procedure. Macroscopic examination revealed a 5.5 cm polypoid mass grossly confined in the lumen of the distal CBD. Histology was consistent with UC-OGC, with minimal invasion into the polyp stalk and adjacent CBD wall. Immunohistochemistry demonstrated co-expression of CK7 and p40, normal/wild-type p53, and retained SMAD4 expression in tumor cells. Next-generation sequencing detected mutations at p.Q61H (c.183A>C) of KRAS and p.E545K (c.1633G>A) of PIK3CA, keeping in line with similarity to conventional cholangiocarcinoma. The patient remained disease-free after two years of follow-up without chemotherapy. CONCLUSION: To our knowledge, this is the first case report of UC-OGC presented as a polypoid mass in the distal CBD. It highlights the complex dynamism and controversial pathogenesis of this unique entity, which should be made aware to avoid diagnostic pitfalls.

Gastric Neuroendocrine Tumor and Duodenal Gastrinoma With Chronic Autoimmune Atrophic Gastritis.

Our group observed the first case of synchronous gastric neuroendocrine tumor (NET) and duodenal gastrinoma with autoimmune chronic atrophic gastritis (CAG), in the absence of Helicobacter pylori infection. Demographic, clinical, endoscopic, and pathologic data were abstracted from the electronic medical record at Mount Sinai Hospital from 2013 to 2015. The patient's anonymity was carefully protected, and informed consent was obtained for publication of protected health information. A 53-year-old woman with hypertension presented to Mount Sinai Hospital in June 2013 for a second opinion for management of gastric and duodenal NETs. After evaluation by gastroenterology and surgery, repeat upper endoscopy with ultrasound and fine-needle aspiration revealed multiple diminutive type I gastric NETs and 2 duodenal NETs, against a background of autoimmune CAG, with biopsy pathology negative for H. pylori. She subsequently underwent a transduodenal resection of the duodenal NETs, confirming low-grade, gastrin-positive, stage T2 duodenal NET. On routine follow-up over the next 2 years, clinical, radiographic, and endoscopic surveillance revealed no recurrent or metastatic gastric or duodenal disease. This first report of synchronous duodenal gastrinoma and gastric NET in the setting of autoimmune CAG can broaden our understanding of gastric NET pathophysiology.

Interobserver Agreement in the Diagnosis of Inflammatory Bowel Disease-Associated Neoplasia in China in Comparison to Subspecialized American Gastrointestinal Pathologists.

BACKGROUND: The aim of this study was to evaluate the interobserver variability in diagnosing inflammatory bowel disease (IBD)-associated neoplasia among practicing pathologists from China using telepathology, a practice of remote diagnostic consultation increasingly used nationally and internationally, and its comparison with the interpretation of subspecialized gastrointestinal (GI) pathologists from the United States (US). METHODS: Eight GI pathologists from the US and 4 pathologists from China with an interest in GI pathology participated in this study. A total of 50 colonic biopsies from patients with a clinical history of IBD from 8 medical centers in China were included. All microscopic slides in each case were digitized using an Aperio system. One pathologist (XL) reviewed the digitized full-slide images, and selected areas of interest were captured at low, medium, and high magnifications at a resolution of 1712 × 1072 pixels and saved as tagged image file format (TIFF) files on read-only DVD. Each pathologist evaluated the images and selected the most appropriate diagnostic category for each case (negative, indefinite, low-grade dysplasia [LGD], high-grade dysplasia [HGD], and carcinoma). A Fleiss' kappa coefficient (K) analysis was performed to determine interobserver agreement and the agreement of each pathologist from China with the consensus diagnosis (defined as diagnostic agreement by at least 4 participating US GI pathologists). RESULTS: There was substantial interobserver agreement among 4 pathologists from China on the interpretation of IBD-associated neoplasia (kappa value 0.68, 95% confidence interval: 0.56-0.78). A consensus diagnosis included negative (n = 22), LGD (n = 22), HGD (n = 3), carcinoma (n = 2), and indefinite for dysplasia (n = 1). Using consensus diagnoses as references, the agreement between each pathologist from China and the consensus diagnosis was substantial with kappa values ranging from 0.75 to 0.80. CONCLUSIONS: This study reveals substantial interobserver agreement for the interpretation of colonic neoplasia in IBD using digitized images among Chinese pathologists as well as between each Chinese pathologist and a consensus diagnosis generated by US GI pathologists.