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BACKGROUND The guidelines published by the Papanicolaou Society of Cytopathology (PSC) intend to unify the reporting language in pancreaticobiliary specimens and improve communication between cytopathologists and clinicians. The six categories in the system will determine the best management for patients. However, there is limited evidence regarding the risk of malignancy (ROM) associated with each category. METHODS A retrospective search was performed for pancreaticobiliary fine-needle aspiration (FNA) reports with corresponding surgical follow-up. Cases were reclassified according to the PSC. The ROM, sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each category. RESULTS A total of 297 cases were identified and reclassified as: 30 nondiagnostic (category I), 45 negative for malignancy (II), 20 atypical (III), 42 neoplastic: other (IVB), 19 suspicious for malignancy (V), and 141 malignant (VI). The absolute ROM was 10% for category I, 8.9% for category II, 60% for category III, 4.8% for category IV when the neoplasms were not characterized as malignant, and 100% when categorized as malignant; 100% for category V, and 95.7% for category VI. Sensitivity, specificity, positive predictive value, and negative predictive value for neoplasia and malignancy, including categories IV to VI, were 96.6%, 88.4%, 97.5%, and 84.4%, respectively. CONCLUSIONS The categories developed by the PSC stratify the ROM. Aspirates designated as categories V and VI had the highest ROM. Our rate of atypical category complies with the recommended rate of

Background H. pylori infection is the main risk factor for gastric cancer. In this study, we investigated H. pylori-mediated activation of STAT3 and NF-κB in gastric cancer, using in vitro and in vivo models. Methods To investigate the activation of NF-κB and STAT3 by H. pylori strains we used in vitro and in vivo mouse models, western blots, immunofluorescence, ChIP Assay, luciferase and quantitative real-time PCR assays. Results Following infection with H. pylori in vitro, we found an earlier phosphorylation of NF-kB-p65 (S536), followed by STAT3 (Y705). Immunofluorescence, using in vitro and in vivo models, demonstrated nuclear localization of NF-kB and STAT3, following H. pylori infection. NF-kB and STAT3 luciferase reporter assays confirmed earlier activation of NF-kB followed by STAT3. In vitro and in vivo models demonstrated induction of mRNA expression of IL-6 (p VEGF-α (p IL-17 (p IL-23 (p IL6 promoter. The reconstitution of Trefoil Factor 1 (TFF1) suppressed activation of NF-kB with reduction in IL6 levels and STAT3 activity, in response to H. pylori infection. Using pharmacologic (BAY11-7082) and genetic (IκB super repressor (IκBSR)) inhibitors of NF-kB-p65, we confirmed the requirement of NF-kB-p65 for activation of STAT3, as measured by phosphorylation, transcription activity, and nuclear localization of STAT3 in in vitro and in vivo models. Conclusion Our findings suggest the presence of an early autocrine NF-kB-dependent activation of STAT3 in response to H. pylori infection. TFF1 acts as an anti-inflammatory guard against H. pylori-mediated activation of pro-inflammatory networks.

Context.— The gastrointestinal (GI) tract is the most common site of extranodal non-Hodgkin lymphoma, accounting for 20% to 40% of all extranodal lymphomas. The majority of these are systemic processes secondarily involving the GI tract. Primary GI lymphomas are less common, accounting for approximately 10% to 15% of all non-Hodgkin lymphomas. Most non-Hodgkin lymphomas involving the GI tract are of B-cell lineage, of which diffuse large B-cell lymphoma is the most common subtype, irrespective of location. Objective.— To review the lymphoproliferative neoplasms of B-cell and T-cell lineage involving the luminal GI tract according to the most prevalent subtypes at each anatomic site. Data Source.— Systematic search of the PubMed database for updated literature on GI lymphoma epidemiology, subtypes, clinical, endoscopic, and genetic findings. Histologic images are derived from our collection of clinical cases. Conclusions.— The GI tract is the most common site of extranodal lymphoproliferative neoplasms. Recognition of the most frequently encountered GI lymphomas is imperative for patient management and treatment.

OBJECTIVES Colloid carcinoma (CC) of the pancreas is associated with an improved prognosis compared with pancreatic ductal adenocarcinoma (PDAC), yet studies on the optimal management of these rare lesions are lacking. METHODS Patients with CC or PDAC treated from 2004 to 2014 were identified in the National Cancer Database. Clinicopathologic characteristics were compared between groups and stratified by disease stage. Survival analysis evaluating the role of perioperative chemotherapy was performed. RESULTS A total of 1295 CC patients (11%) and 10,855 PDAC patients (89%) were identified. Pancreatic ductal adenocarcinoma was associated with a higher likelihood of mortality compared with CC (hazard ratio, 1.35; 95% confidence interval, 1.25-1.45; P < 0.001). When stratifying by stage, perioperative chemoradiation improved overall survival in early stage (I/IIA) PDAC but had no effect in CC patients. However, for node-positive disease (stage IIB), median overall survival was improved with adjuvant chemoradiation for both CC patients (22 vs 13 months; P < 0.001) and PDAC patients (20 vs 11 months; P < 0.001) compared with surgery alone. CONCLUSIONS Surgery alone may be sufficient for the management of node-negative (I/IIA) CC lesions in contrast to conventional PDAC, whereas CC patients with stage IIB disease have a survival benefit from perioperative chemoradiation.

Gastric polyps can be truly neoplastic but most polypoid dysplastic lesions are manifestations of gastritis-associated dysplasia that happens to form a polypoid lesion rather than true adenomas arising in normal background mucosa as is typically observed in the colon. However, the term adenoma has been used over the years to describe polyps with intestinal and pyloric gland differentiation, and this terminology is entrenched in our lexicon. In this review, we briefly discuss the issue of terminology, gastritis, and the following polyp types: intestinal type adenoma, pyloric gland adenoma, foveolar adenoma, and oxyntic gland adenoma (also termed oxyntic gland neoplasm and adenocarcinoma of fundic gland type.

The prevalence of benign mass-forming liver lesions has significantly increased in recent years due to advances in diagnostic imaging. In general, these lesions can be either neoplastic or nonneoplastic and carry a different prognosis and management. Among benign mass-forming lesions of the liver, hemangiomas are the most common, followed by focal nodular hyperplasia, which is encountered ten times more frequently than adenomas. Hepatocellular adenomas are the third most common benign tumor of the liver. Their classification was revised in 2016 based on histomorphology and molecular signatures and includes hepatocyte nuclear factor-1 alpha (HNF1A)-mutated hepatocellular adenomas, beta-catenin 1 (CTNNB1) gene–mutated hepatocellular adenomas, interleukin-6 signal transducer gene–mutated or inflammatory/telangiectatic hepatocellular adenomas, and unclassified hepatocellular adenomas. Since then, a new subtype has been discovered, decreasing the proportion of unclassified cases. Hepatocellular adenomas have different molecular characteristics, behavior, and management, depending on the subtype. The telangiectatic subtype tends to bleed and may cause hemoperitoneum whereas the beta-catenin mutated subtype can progress to malignancy and is surgically resected independent of the size or symptoms. Other hepatic lesions include nodular regenerative hyperplasia, which occurs in the setting of blood flow alterations; and focal fatty change or benign steatotic nodules. Lastly, epithelioid angiomyolipomas are very uncommon benign mesenchymal liver tumors that belong to a family of tumor arising from perivascular epithelioid cells (PEComas) either sporadically or in the setting of tuberous sclerosis. Herein, we review these benign hepatic lesions and neoplasms and discuss the histomorphology and immunohistochemistry that allow us to render a specific diagnosis.

The Paris System (TPS) for reporting urine cytology was developed for standardization of diagnosis focusing on the detection of high-grade urothelial carcinoma (HGUC). Probably the most challenging task for TPS is to provide criteria for the atypical urothelial cell (AUC) category. The TPS criteria for AUC include increased nuclear/cytoplasmic (N/C) ratio (0.5) and 1 of the 3 minor criteria including nuclear hyperchromasia (NH), coarse chromatin (CC) and irregular nuclear membrane (INM). We evaluated TPS-AUC diagnostic value and investigated whether other morphologic parameters can improve its criteria.Urine samples with diagnoses of AUC collected during a 6-month period were re-reviewed. Data captured included N/C ratio0.5, NH, CC, INM, and 2 additional criteria including enlarged nuclear size (ENS) and the presence of nucleolus (N). ENS was considered when the nucleus was 2 times larger than the urothelial cell or 3 times larger than lymphocyte.By applying the TPS-AUC criteria, the rate of atypia diagnosis reduced in comparison to Pre-TPS (9% versus 13%, P = 0.02). Among the AUC minor criteria, NH was the best criterion with the highest interobserver agreement (IOA) and correlation with HGUC (k = 0.342, r = 0.61, P0.001) and strong PPV (93.6%). ENS had the highest PPV (95.8%) and, after NH, had the highest IOA and correlation with HGUC (k = 0.29, r = 0.52, P0.001).TPS improves the diagnostic value of urine cytology, particularly in cases with atypia. ENS is a strong criterion for increasing the diagnostic value of AUC and potentially can improve TPS performance as a minor criterion.

Colorectal carcinoma (CRC) is one of the most common type of cancers and a leading cause of cancer-related deaths worldwide and in the United States. CRC is a heterogeneous disease with a well-characterized stepwise accumulation molecular alteration associated with adenoma formation and progression to carcinoma. We review the genomic and epigenomic pathways, including chromosomal instability, microsatellite instability, and epigenetic instability or CpG island methylator phenotype, their characteristics, and prognosis. We describe the four consensus molecular subtypes of CRC established by the international Colorectal Cancer Subtyping Consortium, their mechanisms to develop cancer, molecular characterization, clinical features, and prognosis. Finally, we review currently used predictive biomarkers.

Infection with Helicobacter pylori (H. pylori) is the main risk factor for gastric carcinogenesis. In this study, we investigated the expression, molecular functions, and downstream effectors of miR490-3p in gastric cancer. We used in vitro and in vivo models to investigate the role of H. pylori in regulating miR490-3p, DARPP-32-dependent functions, and therapeutic resistance. Human and mouse neoplastic gastric lesions demonstrated a negative correlation between DARPP-32 and miR490-3p expression (R = -0.58, P 0.01). This was also detected following infection with H. pylori (R = -0.66, P 0.01). Molecular assays confirmed DARPP-32 as a direct target of miR490-3p. CHRM2, the host gene of miR490-3p, was hypermethylated and downregulated in neoplastic gastric tissues (P 0.05). H. pylori induced methylation and downregulation of CHRM2 and miR490-3p. Functionally, the reconstitution of miR490-3p sensitized cancer cells to gefitinib by inactivating DRAPP-32-dependent AKT and STAT3 pathways. Patients with low miR490-3p or high DARPP-32 expression had decreased overall survival (P 0.05). Hypermethylation-mediated silencing of CHRM2 and miR490-3p by H. pylori increased DARPP-32 expression. Downregulation of miR490-3p in gastric cancer plays a role in gefitinib response by inducing DARPP-32-mediated activation of PI3K/AKT, STAT3 signaling pathways.

Introduction Liquid nitrogen-based cryoablation induces freezing evenly throughout the probe tip surface, resulting in larger ablation volumes and faster treatment times. The purpose of this preliminary investigation is to determine the efficacy of the liquid nitrogen-based Visica2 Cryoablation System (Sanarus Technologies, Pleasanton, CA) in in vivo porcine kidney, liver, and fibro-fatty tissue. Methods Ablations were performed under ultrasound guidance in 4 Yorkshire pigs. The target lesion cross-section width (W) and depth (D) were 1 cm for liver (n=8), kidney (n=4), and head-neck (n=5) and 2 cm for kidney (n=4). Expected axial length (L) of the resulting lesion is approximately 4 cm. After three-day survival, the ablated tissue was harvested and histologically analysed. The mean width and depth were compared with the target diameter using a one-sample t-test. Results All animals survived the procedure. For the 1 cm target, mean dimensions (L x W x D) were 3.8±1.5 x 1.7±0.3 x 1.7±0.7 for liver, 3.0±0.5 x 2.0±0.4 x 1.7±0.6 for kidney, and 3.3±0.8 x 1.8±0.4 x 1.8±0.4 for head-neck. Mean width and depth were significantly greater than desired dimension. For the 2 cm target, mean dimensions were 3.2±0.5 x 3.1±0.8 x 1.9±0.7. Mean width and depth were not significantly different to desired target. Conclusion Our preliminary results show that the Visica2 liquid nitrogen-based cryoablation system can efficiently and reproducibly create ablation volumes in liver, kidney, and fibro-fatty tissue within 4 minutes and 12 minutes for 1cm and 2cm targeted diameters, respectively. Further investigation is necessary to determine the optimal freeze-thaw-freeze protocol for larger ablation volumes. .

Approximately half of the world's population is infected with the stomach pathogen Helicobacter pylori. Infection with H. pylori is the main risk factor for distal gastric cancer. Bacterial virulence factors, such as the oncoprotein CagA, augment cancer risk. Yet despite high infection rates, only a fraction of H. pylori-infected individuals develop gastric cancer. This raises the question of defining the specific host and bacterial factors responsible for gastric tumorigenesis. To investigate the tumorigenic determinants, we analyzed gastric tissues from human subjects and animals infected with H. pylori bacteria harboring different CagA status. For laboratory studies, well-defined H. pylori strain B128 and its cancerogenic derivative strain 7.13, as well as various bacterial isogenic mutants were employed. We found that H. pylori compromises key tumor suppressor mechanisms: the host stress and apoptotic responses. Our studies showed that CagA induces phosphorylation of XIAP E3 ubiquitin ligase, which enhances ubiquitination and proteasomal degradation of the host proapoptotic factor Siva1. This process is mediated by the PI3K/Akt pathway. Inhibition of Siva1 by H. pylori increases survival of human cells with damaged DNA. It occurs in a strain-specific manner and is associated with the ability to induce gastric tumor.

Increasing use of radiographic studies of the hepatobiliary system has led to a growing diagnostic rate of many asymptomatic polyps of the gallbladder which would have gone undiagnosed otherwise. Neoplastic polyps of the gallbladder are 5% of the total number of polyps of this organ. However, due to their malignant potential, the correct diagnosis and classification become of crucial importance. Lack of unified terminology and reporting criteria have led to a limited body of scientific evidence regarding their classification and management. Therefore in 2012 the novel and unified terminology, Intracholecystic papillary-tubular neoplasm was proposed for these lesions when they measure1 cm. Smaller lesions are usually of no adverse outcome. Intracholecystic papillary-tubular neoplasms show 5 histologic subcategories: (1) pyloric gland subtype which is the most commonly encountered neoplastic polyp in the gallbladder and has the lowest rate of harboring high-grade dysplasia and invasive carcinoma and it shows diffuse cytoplasmic positivity with MUC6, a specific pyloric marker; (2) biliary subtype which is diffusely positive for MUC1 and has the highest risk of concurrent adenocarcinoma; (3) gastric foveolar subtype which is MUC5AC positive in all the cases. Most of the cases in this category are associated with some extent of high-grade dysplasia; (4) intestinal subtype which is the easiest one to recognize as it mimics tubular adenomas of the gastrointestinal tract and show MUC2 and CDX2 positivity; and (5) oncocytic subtype which is the least common.

Introduction Endoscopic ultrasound (EUS)-guided fine-needle aspiration and biopsy (FNA/FNB) to obtain cytological aspirates and histological core samples, respectively, are the standard of care for diagnosing lesions in/adjacent to the upper/lower gastrointestinal tract. Due to the lack of standardization of tissue processing, it is unclear whether core samples should be sent only for histology (formalin) or cytology (CytoLyt), or both. The aim of this study was to investigate the diagnostic concordance rates between cytology and histology on EUS-FNB core samples. Methods A total of 227 patients underwent EUS-FNB between October-2017 and February-2019 by a single therapeutic endoscopist; 44 core-tissue samples (41 patients) were placed alternately in CytoLyt (cytology) and formalin (histology), with equal passes into each, to best achieve a proportionate sample amount. The patient's demographics, medical history, pertinent imaging, EUS indication/findings were reviewed. Main outcomes included concordance rates between cytology-histology and diagnostic accuracy for malignancy. Results Cytology and histology were discordant in five cases (11.5%); four with negative cytology but a definite diagnosis of malignancy achieved with histology. One case was suspected as neoplasm on cytology but further characterized as benign on histology. Cytology failed to sub-characterize an additional four mass-like pancreatic benign entities, due to inadequate tissue architecture assessment in the CytoLyt sample. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology for diagnosis of malignancy were 87.88% (95%CI: 71.8-96.6), 90.91% (95%CI: 58.7-99.7), 96.67% (95%CI: 81.6-99.4), and 71.43% (95%CI: 49.4-86.4). Discussion We observed 11.5% diagnostic discordance between cytology and histology on EUS-FNB core samples, with histology being superior. Future multicenter prospective randomized studies are needed to establish an accurate and cost-effective diagnostic process.

Gastric neuroendocrine tumors (gNETs) are a rare entity that is increasing in incidence. Different pathophysiological processes can lead to the development of these tumors, appropriate histological analysis is necessary to differentiate between grade 1 (G1) and grade 2 (G2) tumors as this will impact the management of these patients based on their increased risk of lymph node and distant metastases. To provide a comprehensive clinicopathologic review of multifocal gastric neuroendocrine tumors, with particular emphasis on G1 and G2 tumors and differentiating between types I, II and II and risk stratification based upon immunohistochemical profile. This review is based on peer-reviewed literature and the authors’ experience. gNETs are a heterogenous group of tumors that is rising in incidence. These lesions while arise from the same cell type, they have different etiologies. Identifying the type of gNETs is a collective effort of clinical and pathologic correlation. The correct grading and staging of these lesions are of paramount significance, due its impact on patient management and prognosis.

Neoplastic polypoid mucosal lesions of the gallbladder are increasingly being reported in cholecystectomy specimens. However, due to the absence of unified terminology and reporting criteria, the body of scientific evidence on their classification, prognosis, and management is scarce and sometimes controversial. While they have different histomorphologic features (gastric foveolar, gastric pyloric gland, biliary, and intestinal), a significant immunohistochemical overlap exists which highlights their mixed cell lineage with a dominant cell type in each, establishing the subcategory. Because of many shared attributes, intracholecystic papillary-tubular neoplasm (ICPN) has been introduced as an umbrella terminology. ICPNs of the pyloric subtype are lesions larger than 1 cm, as most of the smaller ones are clinically insignificant and represent polypoid hyperplasia rather than a true neoplasm. In this review, we will focus on the pyloric gland adenomas as the most frequent histologic subtype of ICPNs.

Yttrium-90 (Y-90) trans-arterial radioembolization (TARE) is used in the management of unresectable hepatocellular carcinoma (HCC). During the last 5 years, dosimetry software has been developed to allow for a more rigorous approach of dose prescription in Y-90 TARE. We present here a case study of a 77-year-old woman diagnosed with HCC, who underwent a Y-90 TARE as a bridge procedure to liver resection. This clinical scenario represents a unique opportunity to illustrate the predictive value of dosimetric findings correlating dosimetry with pathological findings. In this case, Y-90 TARE dosimetry was predictive of treatment response in which the tumor received a mean dose of 156 Gy and demonstrated a complete pathologic response.

Brunner's gland adenoma (hyperplasia) (BGA/H) is a benign gastrointestinal lesion, usually asymptomatic and frequently detected incidentally by endoscopy as a submucosal nodule. Most BGA/Hs are diagnosed by their typical cytological morphology and immunohistochemical features, characterized by monomorphic cells arranged as loosely clusters of epithelial cells with abundant, clear, and granular cytoplasm, eccentrically located nuclei, and immunoreactivity for MUC-6. The combination of the clinical and pathological features is essential for rendering a correct diagnosis. Herein, we report two cases of BGA/H, including their cytologic and histologic features, and a literature review of the clinicopathologic findings along with its differential diagnoses.

Dietary supplements are unregulated medications that can lead to serious liver injury. Despite this, many people take vitamin supplements believing they are safe because they do not require prescriptions. We are reporting a case of an African American man who took large doses of vitamin supplements leading to noncirrhotic portal hypertension. The case highlights the importance of detailed history taking to diagnose and treat patients properly.

When South Florida became a hotspot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists and administrators, who rapidly built a multi-platform, PCR- and serology-based detection program, established drive-thru facilities and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and to multiple diagnostic laboratory companies and government officials enabled us to implement both FDA authorized and laboratory developed testing (LDT)-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers, to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity, to testing hundreds of healthcare workers and patients daily, within three weeks. We believe our experience can inform the efforts of others, when faced with a crisis situation.

When South Florida became a hot spot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists, and administrators who rapidly built a multiplatform, polymerase chain reaction- and serology-based detection program, established drive-through facilities, and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and multiple diagnostic laboratory companies, and government officials enabled us to implement both Food and Drug Administration authorized and laboratory-developed testing-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity to testing hundreds of health care workers and patients daily, within 3 weeks. We believe our experience can inform the efforts of others when faced with a crisis situation.

Background. Epithelioid hemangioendothelioma (EHE) is an uncommon malignant endothelial neoplasm that most commonly arises in soft tissue, bone, lung, and liver. Crohn’s disease (CD) is an inflammatory bowel disease of unknown etiology that is frequently associated with complications including strictures, fistulas/fissures, and neoplasms. Case description. A 43-year-old woman with a 6-year history of severe CD presented with anal pain and bleeding. She had prior partial colectomy for a stricture and a diverting ileostomy for perianal fissures and stricture. Colonoscopy showed severe chronic active colitis, stricture at 30 cm of anal verge, and a perianal fistula. The patient underwent total proctocolectomy. The colonic mucosa exhibited segmental ulceration and irregular thickening of the colon wall. Beneath an ulcer of the anal canal within the muscularis propria was a 1.2-cm poorly circumscribed, firm, white-tan mass. The mass was composed of cords and groups of large epithelioid endothelial cells with intracytoplasmic vacuoles enmeshed in a myxohyaline stroma. Immunohistochemically, the tumor cells were positive for ERG, CD31, and CAMTA1 and focally positive for keratin and SMA. Next-generation sequencing revealed a WWTR1-CMATA1 fusion. The morphology, immunoprofile, and molecular genetics were diagnostic of EHE. Discussion. Long-standing inflammatory bowel disease is associated with significant risk for developing neoplasms, usually carcinomas, which can be indistinguishable radiologically and clinically from nonneoplastic complications. These tumors are often identified as an incidental finding in specimens resected for clinically severe disease. This is the first report of EHE arising in the bowel affected by CD, and it mimicked mural fibrosis and fissures.

Lipomas are uncommon tumors of the gastrointestinal tract; gastric lipomas account for1% of all gastric tumors encountered (Nickloes and Sutphin [1]). Giant gastric lipomas, defined as ≥10 cm, are exceedingly rare with only 6 cases reported since 1980 (Cappell et al., Termos et al., Singh et al., Ramaraj et al., Rao et al., Priyadarshi et al., Neto et al. [3-9]). We hereby present a case of a giant gastric lipoma that became symptomatic seven years after its initial identification and was excised preserving gastric continuity.Our patient is a 58-year-old African American male with a 3 cm gastric mass incidentally found on CT in 2010. In September of 2017, the patient presented with severe epigastric pain, nausea, and vomiting. Abdominal CT scan revealed an increase in size of the patient's gastric lesion to 7.2 × 10.3 × 7.3 cm. He underwent an exploratory laparotomy with transverse anterior gastrotomy and primary closure. Pathologic examination revealed a 12 cm submucosal, well-circumscribed, non-encapsulated mass comprised of mature adipose tissue without atypia or mitotic figures, consistent with lipoma.The majority of gastric lipomas are asymptomatic, identified on CT scan as round/ovoid masses with low attenuation and homogenous appearance, measuring -80 to -120 Hounsfield units. These findings are nearly pathognomonic. Due to the benign nature of gastric lipomas, circumferential excision with a clear margin of normal tissue is adequate for symptomatic resection. This is the second report of giant gastric lipoma excised with continuity preserving partial gastrectomy, avoiding gastrojejunostomy complications.Fatty tumors are rare in the gastrointestinal tract, yet lipomas must be on the differential when masses are found with Hounsfield units similar to peripheral fat.

Introduction: Hepatic granulomas are common in patients with sarcoidosis, but clinically significant liver disease is uncommon and poorly studied. We aimed to characterize the frequency and clinical course of hepatic sarcoidosis in an ethnically diverse population. Methods: This is a retrospective study including all cases of hepatic sarcoidosis in a single center. The median follow-up time was 49 months (4–121). Cases were identified based on ICD-9 and ICD-10 codes for granulomatous hepatitis, sarcoidosis, and hepatic sarcoidosis. The Chi-square and Wilcoxon-signed rank tests were used as indicated to assess for differences between groups. Results: Of 286 patients with sarcoidosis, 27 had hepatic involvement; 78% were female and 48% African American. The most common pattern of liver tests abnormalities was cholestatic. Ten patients had clinically significant hepatic involvement: cirrhosis in seven (25.9%), portal hypertension in nine (33%), and portal vein thrombosis in one (3.7%). Sex, race, and ethnicity were not associated with an increased risk of hepatic involvement or symptomatic hepatic sarcoidosis. Most patients received medical treatment, most commonly oral glucocorticoids. At the end of the follow-up period, all patients were alive but two had undergone liver transplantation due to complications of hepatic sarcoidosis. Three patients with hepatic sarcoidosis had initially been classified as AMA-negative PBC. Conclusions: Hepatic sarcoidosis was found in 9.4% of patients with sarcoidosis and was clinically significant in 37% of those. Identifying and monitoring hepatic sarcoidosis is crucial given its potential complications.

Esophageal adenocarcinoma (EAC) has one of the fastest rising incidence rates in the U.S. and many other Western countries. One of the unique risk factors for EAC is gastroesophageal reflux disease (GERD), a chronic digestive condition in which acidic contents from the stomach, frequently mixed with duodenal bile, enter the esophagus resulting in esophageal tissue injury. At the cellular level, progression to EAC is underlined by continuous DNA damage caused by reflux and chronic inflammatory factors that increase the mutation rate and promote genomic instability. Despite recent successes in cancer diagnostics and treatment, EAC remains a poorly treatable disease. Recent research has shed new light on molecular alterations underlying progression to EAC and revealed novel treatment options. This review focuses on the genetic and molecular studies of EAC. The molecular changes that occur during the transformation of normal Barrett's esophagus to esophageal adenocarcinoma are also discussed.

Background Checkpoint inhibitors have shown modest activity in patients with advanced hepatocellular carcinoma (HCC). Herein, the authors report a prospective single-institution clinical/translational phase 2 study of pembrolizumab in patients with advanced HCC and circulating biomarkers closely related to response. Methods Pembrolizumab was administered at a dose of 200 mg intravenously every 3 weeks among patients who may have developed disease progression while receiving, were intolerant of, or refused sorafenib. The circulating levels of cytokines, chemokines, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and PD-L2 were correlated with response, tumor PD-L1 expression, and other clinicopathological features. Results A total of 29 patients were treated and 28 patients were evaluable for response. The most common laboratory grade 3/4 adverse events were increases in aspartate aminotransferase and/or alanine aminotransferase and serum bilirubin, which for the most part were reversible. In terms of efficacy, one patient achieved a complete response and 8 patients achieved partial responses for an overall response rate of 32%. Four other patients had stable disease. The median progression-free survival was 4.5 months and the median overall survival was 13 months. Response did not correlate with prior sorafenib therapy, PD-L1 tumor staining, or a prior history of hepatitis. Correlative studies revealed that high baseline plasma TGF-β levels (≥200 pg/mL) significantly correlated with poor treatment outcomes after pembrolizumab. Tumor PD-L1 and plasma PD-L1/PD-1 levels were associated with plasma IFN-γ or IL-10. Conclusions Pembrolizumab was found to demonstrate activity in patients with advanced HCC. Toxicity generally was tolerable and reversible. A set of immunological markers in blood plasma as well as PD-L1 staining indicated that baseline TGF-β could be a predictive biomarker for response to pembrolizumab.

Biomarkers in the field of pathology and oncology may allow for the detection of disease, assessment of prognosis or to predict response to certain therapy. Molecular abnormalities in colorectal cancer genesis may occur due to chromosome instability, microsatellite instability and DNA methylation (CpG island methylator phenotype). These alterations are associated in some cases to sporadic carcinomas whereas in others are seen in syndrome-related tumors and are the basis for the use of different biomarkers in the clinical setting. These may include mismatched repair gene/proteins, RAS, BRAF, PIK3CA, which help to determine tumor prognosis and predict response to certain drugs.

A 48-year-old Egyptian woman presented with 8 months of sharp right upper chest pain and weight loss. She was discovered to have an enlarged cardiac silhouette on chest x-ray, and an echocardiogram revealed a large pericardial effusion with diastolic right atrial collapse. Pericardial window was done, and epithelial membrane antigen-positive neoplastic cells were identified in the pericardial fluid. Computed tomography showed a 6-cm hypermetabolic lesion on the liver segment IV, confirmed on biopsy to be a moderately differentiated adenocarcinoma consistent with intrahepatic cholangiocarcinoma.

Patients with irritable bowel syndrome (IBS) frequently have meal-related symptoms and can recognize specific trigger foods. Lactose intolerance is a well-established carbohydrate malabsorption syndrome that causes symptoms similar to IBS such as bloating, abdominal pain, and diarrhea. However, the prevalence of sucrase-isomaltase deficiency (SID) in this population is poorly defined. SID is a condition in which sucrase-isomaltase, an enzyme produced by brush border of small intestine to metabolize sucrose, is deficient. Just like lactase deficiency, SID causes symptoms of maldigestion syndromes including abdominal pain, bloating, gas, and diarrhea. In this study, we aim to determine the prevalence of SID in patients with presumed IBS-D/M and characterize its clinical presentation. Patients with a presumed diagnosis of IBS-D/M based on symptoms of abdominal pain, diarrhea, and/or bloating who underwent esophagogastroduodenoscopy with duodenal biopsies and testing for disaccharidase deficiency were included. Patients with a history of inflammatory bowel disease, gastrointestinal malignancy, or celiac disease were excluded. Odds ratio was calculated for abdominal pain, diarrhea, and bloating in patients with versus without SID. A total of 31 patients with clinical suspicion for IBS-D/M were included with a median age of 46 years (IQR 30.5–60) and with 61% females. SID was present in 35% of patients. Among patients with SID, 63.6% had diarrhea, 45.4% had abdominal pain, and 36.4% had bloating. Patients with SID were less likely than controls to have abdominal pain (OR 0.16, 95% CI 0.03–0.81, p = 0.04) although no difference in diarrhea or bloating was found. Only two patients with SID underwent sucrose breath testing of which only one had a positive result. However, this patient also had a positive glucose breath test and may have had small intestinal bacterial overgrowth as a confounder. SID was found in 35% of patients with presumed IBS-D/M and should be considered in the differential diagnosis of patients presenting with abdominal pain, diarrhea, or bloating. Further studies should better characterize the clinical features of SID and investigate the effects of dietary modification in this group of patients.

Summary Frozen section telepathology interpretation experience has been largely limited to practices with locations significantly distant from one another with sporadic need for frozen section diagnosis. In 2010, we established a real-time nonrobotic telepathology system in a very active cancer center for daily frozen section service. Herein, we evaluate its accuracy compared to direct microscopic interpretation performed in the main hospital by the same faculty and its cost-efficiency over a 1-year period. From 643 (1,416 parts) cases requiring intraoperative consultation, 333 cases (690 parts) were examined by telepathology and 310 cases (726 parts) by direct microscopy. Corresponding discrepancy rates were 2.6% (18 cases: 6 [0.9%] sampling and 12 [1.7%] diagnostic errors) and 3.2% (23 cases: 8 [1.1%] sampling and 15 [2.1%] diagnostic errors), P = .63. The sensitivity and specificity of intraoperative frozen diagnosis were 0.92 and 0.99, respectively, in telepathology and 0.90 and 0.99, respectively, in direct microscopy. There was no correlation of error incidence with postgraduate year level of residents involved in the telepathology service. Cost analysis indicated that the time saved by telepathology was $19,691.00 over 1 year of the study period, whereas the capital cost for establishing the system was $8,924.00. Thus, real-time nonrobotic telepathology is a reliable and easy-to-use tool for frozen section evaluation in busy clinical settings, especially when frozen section service involves more than one hospital, and it is cost-efficient when travel is a component of the service.

Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment-related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens.

Mucoepidermoid carcinoma of the bile duct is a rare entity. Only one mucoepidermoid carcinoma from the common bile duct has been reported in the Korean literature. Herein, we present the first in the English literature. The tumor arose in the intrapancreatic (distal) common bile duct in an 83-year-old woman who presented with obstructive jaundice and elevated liver enzymes. The tumor invaded the underlying pancreas and peripancreatic adipose tissue and showed pagetoid spread into the extrapancreatic common bile duct and cystic duct. The tumor exhibited nests of malignant cells with diffuse CK7 and MUC1 positivity. The basal cells were p63 and CK5/6 positive. The luminal cells were stained with carcinoembryonic antigen, MUC5, and mucicarmine and were focally positive for CK20. There was focal MUC4 staining on the apical luminal border. The neoplastic cells were negative for MUC2 and HER2-neu. We discuss the clinical presentation, diagnostic features, immunohistochemical profile, and prognosis of mucoepidermoid carcinoma of the common bile duct. The features of this neoplasm are further compared with mucoepidermoid carcinoma of the hepatobiliary system, adenosquamous carcinoma, and mucoepidermoid carcinoma of other organs.

Syndrome of inappropriate anti-diuretic hormone (SIADH) has been reported to be associated with systemic Strongyloides stercoralis. Here, we report a case of a stem cell transplant (SCT) recipient who developed severe SIADH secondary to systemic S Stercoralis. The SIADH resolved quickly after treating the systemic S Stercoralis with ivermectin. A systematic review of the literature was performed by PubMed, Scopus, and Cochrane database search. Only eight cases of S Stercoralis in allogeneic SCT recipients have been previously reported. To our knowledge, ours is the first reported case of SIADH secondary to S Stercoralis infection in an allogeneic SCT recipient. Prior to transplantation, even if asymptomatic, patients from endemic regions should be screened with strongyloides immunoglobulin (Ig)G serology. Pretransplantation eosinophilia should be evaluated by screening multiple stool samples for ova and parasites. Transplant candidates with positive serology or stool tests can be treated pretransplantation to eradicate infection. Patients at risk for S Stercoralis who develop nonspecific gastrointestinal complaints, rash, pulmonary infiltrates, or gram-negative bacteremia or meningitis may have S Stercoralis hyperinfection syndrome. Our case indicates that the development of SIADH may be an additional clue to this diagnosis. Appropriate diagnostic studies, including repeat stool and other body fluid sampling, should be expedited and ivermectin therapy initiated rapidly to prevent significant morbidity and mortality.

Which of the following is the most common differential diagnosis of autoimmune pancreatitis?

Pulmonary embolism (PE) is a critical complication related to multiple disorders and different medical or cosmetic procedures. This case report presents two patients who were admitted for respiratory symptoms in the setting of previously receiving silicone injections for cosmetic purposes and were diagnosed with silicone pulmonary embolism. The relevance of including questions about all cosmetic procedures as a part of a medical history is highlighted, in particular about silicone injections. The diagnosis is confirmed by histological means. Additionally, our review showed the change of most common sites of silicone injections and a significant increase in cosmetic procedures causing silicone embolism during the past twelve years.

Which of the following is released by the duodenum in response to the presence of acidic chyme?

All of the following are histologic characteristics of well-differentiated pancreatic neuroendocrine tumors (PNENs), except