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Mesenteric Pathologic Conditions: Interactive Case-based Approach

Kernizan, Amelia L; Revels, Jonathan; Hajdu, Cristina; Manning, Maria; Taffel, Myles T
PMID: 37917539
ISSN: 1527-1323
CID: 5610552

Author Correction: Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment

Werba, Gregor; Weissinger, Daniel; Kawaler, Emily A; Zhao, Ende; Kalfakakou, Despoina; Dhara, Surajit; Wang, Lidong; Lim, Heather B; Oh, Grace; Jing, Xiaohong; Beri, Nina; Khanna, Lauren; Gonda, Tamas; Oberstein, Paul; Hajdu, Cristina; Loomis, Cynthia; Heguy, Adriana; Sherman, Mara H; Lund, Amanda W; Welling, Theodore H; Dolgalev, Igor; Tsirigos, Aristotelis; Simeone, Diane M
PMID: 37400453
ISSN: 2041-1723
CID: 5539082

Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment

Werba, Gregor; Weissinger, Daniel; Kawaler, Emily A; Zhao, Ende; Kalfakakou, Despoina; Dhara, Surajit; Wang, Lidong; Lim, Heather B; Oh, Grace; Jing, Xiaohong; Beri, Nina; Khanna, Lauren; Gonda, Tamas; Oberstein, Paul; Hajdu, Cristina; Loomis, Cynthia; Heguy, Adriana; Sherman, Mara H; Lund, Amanda W; Welling, Theodore H; Dolgalev, Igor; Tsirigos, Aristotelis; Simeone, Diane M
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression; however, in-depth single cell characterization of the PDAC TME and its role in response to therapy is lacking. Here, we perform single-cell RNA sequencing on freshly collected human PDAC samples either before or after chemotherapy. Overall, we find a heterogeneous mixture of basal and classical cancer cell subtypes, along with distinct cancer-associated fibroblast and macrophage subpopulations. Strikingly, classical and basal-like cancer cells exhibit similar transcriptional responses to chemotherapy and do not demonstrate a shift towards a basal-like transcriptional program among treated samples. We observe decreased ligand-receptor interactions in treated samples, particularly between TIGIT on CD8 + T cells and its receptor on cancer cells, and identify TIGIT as the major inhibitory checkpoint molecule of CD8 + T cells. Our results suggest that chemotherapy profoundly impacts the PDAC TME and may promote resistance to immunotherapy.
PMID: 36781852
ISSN: 2041-1723
CID: 5427092

Multi-Center Follow-up Study to Develop a Classification System Which Differentiates Mucinous Cystic Neoplasm of the Liver and Benign Hepatic Cyst Using Machine Learning

Hardie, Andrew D; Chamberlin, Jordan H; Boyum, James H; Sharbidre, Kedar G; Petrocelli, Robert; Flemming, Brian P; Zahid, Mohd; Venkatesh, Sudhakar K; Mruthyunjayappa, Smitha; Hajdu, Cristina H; Kovacs, Mark D
RATIONALE AND OBJECTIVES/OBJECTIVE:To date, no clinically useful classification system has been developed for reliably differentiating mucinous cystic neoplasm (MCN) from a benign hepatic cyst (BHC) in the liver. The objective was to use machine learning and a multi-center study design to develop and assess the performance of a novel classification system for predicting whether a hepatic cystic lesion represents MCN or BHC. MATERIALS AND METHODS/METHODS:A multi-center cohort study identified 154 surgically resected hepatic cystic lesions in 154 subjects which were pathologic confirmed as MCN (43) or BHC (111). Readers at each institution recorded seven pre-determined imaging features previously identified as potential differentiating features from prior publications. The contribution of each of these features to differentiating MCN from BHC was assessed by machine learning to develop an optimal classification system. RESULTS:Although several of the assessed imaging features demonstrated statistical significance, only 3 imaging features were found by machine learning to significantly contribute to a potential classification system: (1) solid enhancing nodule (2) all septations arising from an external macro-lobulation (3) whether the lesion was solitary or one of multiple cystic liver lesions. The optimal classification system had only four categories and correctly identified 144/154 lesion (93.5%). CONCLUSION/CONCLUSIONS:This multi-center follow-up study was able to use machine learning to develop a highly accurate classification system for differentiation of hepatic MCN from BHC, which could be readily applied to clinical practice.
PMID: 34598868
ISSN: 1878-4046
CID: 5067612

Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment

Barkley, Dalia; Moncada, Reuben; Pour, Maayan; Liberman, Deborah A; Dryg, Ian; Werba, Gregor; Wang, Wei; Baron, Maayan; Rao, Anjali; Xia, Bo; França, Gustavo S; Weil, Alejandro; Delair, Deborah F; Hajdu, Cristina; Lund, Amanda W; Osman, Iman; Yanai, Itai
Transcriptional heterogeneity among malignant cells of a tumor has been studied in individual cancer types and shown to be organized into cancer cell states; however, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Here, we perform a pan-cancer single-cell RNA-sequencing analysis across 15 cancer types and identify a catalog of gene modules whose expression defines recurrent cancer cell states including 'stress', 'interferon response', 'epithelial-mesenchymal transition', 'metal response', 'basal' and 'ciliated'. Spatial transcriptomic analysis linked the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment. Using mouse models, we further found that induction of the interferon response module varies by tumor location and is diminished upon elimination of lymphocytes. Our work provides a framework for studying how cancer cell states interact with the tumor microenvironment to form organized systems capable of immune evasion, drug resistance and metastasis.
PMID: 35931863
ISSN: 1546-1718
CID: 5286422

Anastomosing hemangioma: a current update on clinical, pathological and imaging features

Shanbhogue, Krishna; Khandelwal, Ashish; Hajdu, Cristina; Cao, Wenqing; Surabhi, Venkateswar R; Prasad, Srinivasa R
Anastomosing hemangioma (AH) is a rare, benign vascular neoplasm with distinctive histopathology and characteristic tumor distribution. AHs show marked proclivity to involve the kidneys, gonads and the retroperitoneal soft tissues; kidney is the most common target site often in the context of end stage renal disease. Recent studies have identified activating mutations of GNA genes that drive the molecular pathogenesis of AHs. AH appears as a solitary, well-circumscribed, hypervascular tumor that charters a benign course with an excellent prognosis. The purpose of this article is to provide a current update on clinical, pathological and imaging features of anastomotic hemangioma.
PMID: 35678844
ISSN: 2366-0058
CID: 5248512

Utility of EZH2 Immunostaining for Atypical Bile Duct Brush Cytology [Meeting Abstract]

Chen, F; Wang, Q; Hajdu, C; Szeto, O; Simsir, A; Brandler, T
Background: Bile duct brush cytology (B
ISSN: 1530-0285
CID: 5252112

Gain-of-function p53R172H mutation drives accumulation of neutrophils in pancreatic tumors, promoting resistance to immunotherapy

Siolas, Despina; Vucic, Emily; Kurz, Emma; Hajdu, Cristina; Bar-Sagi, Dafna
Tumor genotype can influence the immune microenvironment, which plays a critical role in cancer development and therapy resistance. However, the immune effects of gain-of-function Trp53 mutations have not been defined in pancreatic cancer. We compare the immune profiles generated by KrasG12D-mutated mouse pancreatic ductal epithelial cells (PDECs) engineered genetically to express the Trp53R172H mutation with their p53 wild-type control. KrasG12D/+;Trp53R172H/+ tumors have a distinct immune profile characterized by an influx of CD11b+Ly6G+ neutrophils and concomitant decreases in CD3+ T cells, CD8+ T cells, and CD4+ T helper 1 cells. Knockdown of CXCL2, a neutrophil chemokine, in the tumor epithelial compartment of CRISPR KrasG12D/+;Trp53R172H/+ PDEC tumors reverses the neutrophil phenotype. Neutrophil depletion of mice bearing CRISPR KrasG12D/+;Trp53R172H/+ tumors augments sensitivity to combined CD40 immunotherapy and chemotherapy. These data link Trp53R172H to the presence of intratumoral neutrophils in pancreatic cancer and suggest that tumor genotypes could inform selection of affected individuals for immunotherapy.
PMID: 34433022
ISSN: 2211-1247
CID: 5011142

Author Correction: The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H; Torres-Hernandez, Alejandro; Pergamo, Matthew; Ochi, Atsuo; Zambirinis, Constantinos P; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Engle, Dannielle; Miller, George
PMID: 33707632
ISSN: 1476-4687
CID: 4809512

The histopathologic characteristics of the gastrointestinal system in SARS-COV-2 infected patients who underwent biopsy or resection [Meeting Abstract]

Ahmed, S; Hoskoppal, D; Lin, L; Suarez, Y; Liu, W; Cho, M; Thomas, K; Guzzetta, M; Hajdu, C; Theise, N; Jour, G; Sarkar, S; Cao, W
Background: In addition to respiratory distress, GI symptoms have been reported in COVID-19 patients at various stages of the disease. Among the GI symptoms that have been reported, diarrhea, nausea, vomiting, abdominal pain and GI bleeding were often seen. Age and comorbid conditions such as obesity, HTN, DM and/or CAD have been considered as risk factors for COVID-19 patients for severe disease. GI manifestations in COVID-19 patients appeared to act as a sign for a serious condition. The virus has been identified in the stool and in rectal swabs of some infected patients, even after a negative nasopharyngeal test. There is a lack of reports on pathological alterations of the GI tract in COVID-19 infected patients.
Design(s): 16 PCR confirmed COVID-19 patients (11 males and 5 females) were included in the study. Biopsy or resection specimens were taken from the esophagus (4), stomach (6), small intestine (5), appendix (3), colon (5) and gallbladder (3). Clinical information including demographics, comorbidities, GI symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): The age of the patients ranged from 10 to 84 years old, with an average of 47 years. Eight (50%) patients had at least one comorbid condition, two patients (12.5%) had prior history of cancer, and six patients had no significant medical history. Abdominal pain and GI bleeding were the most common presenting symptoms. Histologically, acute and chronic inflammation was seen in 14 of 16, and 15 of 16 cases, respectively. Eight cases showed severe acute inflammation with ulceration. The mucosal changes included nonspecific reactive change, hypermucinous, atrophic/ischemic changes, and necrosis, were indiscriminately noticed in these cases. Four cases showed intraepithelial lymphocytosis. Viral like inclusions were found in four cases. Microthrombi were identified in 5 cases with an average patient age of 60 years. Notably, microthrombi were seen in about 5 out of 8 (62%) patients with comorbidities. The patients with microthrombi had a higher D dimer test value than those without thrombus. Three patients died shortly after operation, and two of them showed microthrombi in the tissue specimens.
Conclusion(s): Acute and chronic inflammation were indiscriminately seen in these cases. Microthrombi were dominantly found in aging patients with comorbidities, suggesting microthrombi in the GI tract may be a histologic indication for severe COVID-19 patients with GI symptoms
ISSN: 1530-0307
CID: 4857062