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Cancer Science Dec 2023Pancreatic neuroendocrine neoplasms (panNENs) are rare pancreatic neoplasms, and descriptions of treatment remain limited. Autotaxin (ATX) is a secreted autocrine...
Pancreatic neuroendocrine neoplasms (panNENs) are rare pancreatic neoplasms, and descriptions of treatment remain limited. Autotaxin (ATX) is a secreted autocrine motility factor involved in the production of lysophosphatidic acid (LPA), a lipid mediator that promotes the progression of various cancers. The aim of this study was to clarify the importance of the ATX-LPA axis in panNENs and to confirm its contribution to panNEN progression using clinical data, cell lines, and a mouse model. Serum ATX level was higher in patients with panNEN than in patients with other pancreatic diseases (chronic pancreatitis, pancreatic ductal adenocarcinoma [PDAC], intraductal papillary mucinous neoplasm, autoimmune pancreatitis) and healthy controls, and 61% of clinical specimens stained strongly for ATX. In a case we encountered, serum ATX level fluctuated with disease progression. An in vitro study showed higher ATX mRNA expression in panNEN cell lines than in PDAC cell lines. Cell proliferation and migration in panNEN cell lines were stimulated via the ATX-LPA axis and suppressed by RNA interference or inhibitors. An in vivo study showed that intraperitoneal injection of GLPG1690, an ATX inhibitor, suppressed tumor progression in a xenograft model. These findings revealed that ATX expression is significantly elevated in panNEN and is related to the progression of panNEN. We showed the potential of ATX as a novel biomarker and therapeutic target.
Topics: Animals; Humans; Mice; Biomarkers; Cell Line; Disease Models, Animal; Neuroendocrine Tumors; Pancreatic Neoplasms; Phosphoric Diester Hydrolases; RNA Interference
PubMed: 37770812
DOI: 10.1111/cas.15980 -
BMC Cancer Nov 2022Preoperative prediction of pancreatic cystic neoplasm (PCN) differentiation has significant value for the implementation of personalized diagnosis and treatment plans....
BACKGROUND
Preoperative prediction of pancreatic cystic neoplasm (PCN) differentiation has significant value for the implementation of personalized diagnosis and treatment plans. This study aimed to build radiomics deep learning (DL) models using computed tomography (CT) data for the preoperative differential diagnosis of common cystic tumors of the pancreas.
METHODS
Clinical and CT data of 193 patients with PCN were collected for this study. Among these patients, 99 were pathologically diagnosed with pancreatic serous cystadenoma (SCA), 55 were diagnosed with mucinous cystadenoma (MCA) and 39 were diagnosed with intraductal papillary mucinous neoplasm (IPMN). The regions of interest (ROIs) were obtained based on manual image segmentation of CT slices. The radiomics and radiomics-DL models were constructed using support vector machines (SVMs). Moreover, based on the fusion of clinical and radiological features, the best combined feature set was obtained according to the Akaike information criterion (AIC) analysis. Then the fused model was constructed using logistic regression.
RESULTS
For the SCA differential diagnosis, the fused model performed the best and obtained an average area under the curve (AUC) of 0.916. It had a best feature set including position, polycystic features (≥6), cystic wall calcification, pancreatic duct dilatation and radiomics-DL score. For the MCA and IPMN differential diagnosis, the fused model with AUC of 0.973 had a best feature set including age, communication with the pancreatic duct and radiomics score.
CONCLUSIONS
The radiomics, radiomics-DL and fused models based on CT images have a favorable differential diagnostic performance for SCA, MCA and IPMN. These findings may be beneficial for the exploration of individualized management strategies.
Topics: Humans; Cystadenoma, Mucinous; Deep Learning; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 36447168
DOI: 10.1186/s12885-022-10273-4 -
Archives of Pathology & Laboratory... Nov 2019According to the 2017 World Health Organization classification, pancreatic neuroendocrine neoplasms (PanNENs) include a new category of pancreatic neuroendocrine tumor,... (Review)
Review
CONTEXT.—
According to the 2017 World Health Organization classification, pancreatic neuroendocrine neoplasms (PanNENs) include a new category of pancreatic neuroendocrine tumor, grade 3, which is often difficult to differentiate from pancreatic neuroendocrine carcinoma. However, pancreatic neuroendocrine tumor grade 3 and pancreatic neuroendocrine carcinoma are distinct entities with very different clinical presentation, prognosis, and therapeutic strategies. Recent discoveries on the molecular characteristics of pancreatic neuroendocrine tumors also play an essential role in the pathologic differential diagnosis of PanNENs. In addition, the histopathologic varieties of PanNENs bring in many differential diagnoses with other pancreatic neoplasms, especially acinar cell carcinoma, solid pseudopapillary neoplasm, and ductal adenocarcinoma.
OBJECTIVE.—
To provide a brief update of the World Health Organization classification; the clinical, histopathologic, immunohistochemical, and molecular characteristics; and the differential diagnoses and biological behavior of PanNENs.
DATA SOURCES.—
Analysis of the pertinent literature (PubMed) and authors' clinical practice experience based on institutional and consultation materials.
CONCLUSIONS.—
The evolving clinical, histopathologic, immunohistochemical, and molecular features of PanNENs are reviewed. Important differential diagnoses with other neoplasms of the pancreas are discussed.
Topics: Diagnosis, Differential; Humans; Immunohistochemistry; Neoplasm Grading; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Prognosis; World Health Organization
PubMed: 31509453
DOI: 10.5858/arpa.2019-0338-RA -
World Journal of Gastroenterology Jun 2022We described the case of a peripancreatic paraganglioma (PGL) misdiagnosed as pancreatic lesion. Surgical exploration revealed an unremarkable pancreas and a large...
We described the case of a peripancreatic paraganglioma (PGL) misdiagnosed as pancreatic lesion. Surgical exploration revealed an unremarkable pancreas and a large well-defined cystic mass originating at the mesocolon root. Radical enucleation of the mass was performed, preserving the pancreatic tail. Histologically, a diagnosis of PGL was rendered. Interestingly, two previously unreported mutations, one affecting the gene in exon 7 and another on the gene in exon 4 were detected. Both mutations are known to be pathogenetic. Imaging and cytologic findings were blindly reviewed by an expert panel of clinicians, radiologists, and pathologists to identify possible causes of the misdiagnosis. The major issue was lack of evidence of a cleavage plane from the pancreas at imaging, which prompted radiologists to establish an intra-parenchymal origin. The blinded revision shifted the diagnosis towards an extra-pancreatic lesion, as the pancreatic parenchyma showed no structural alterations and no dislocation of the Wirsung duct. , the identified biases were the emergency setting of the radiologic examination and the very thin mesocolon sheet, which hindered clear definition of the lesion borders. Original endoscopic ultrasonography diagnosis was confirmed, emphasizing the intrinsic limit of this technique in detecting large masses. Finally, pathologic review favored a diagnosis of PGL due to the morphological features and immonohistochemical profile. Eighteen months after tumor excision, the patient is asymptomatic with no disease relapse evident by either radiology or laboratory tests. Our report strongly highlights the difficulties in rendering an accurate pre-operative diagnosis of PGL.
Topics: Endosonography; Female; Humans; Neoplasm Recurrence, Local; Pancreas; Pancreatic Neoplasms; Paraganglioma; Young Adult
PubMed: 35800185
DOI: 10.3748/wjg.v28.i21.2396 -
Cancer Medicine Mar 2021Current the surveillance and management are controversial for patients with IPMN. We aimed to develop an alternative nomogram to individualize IPMN prognosis and LNM.
BACKGROUND
Current the surveillance and management are controversial for patients with IPMN. We aimed to develop an alternative nomogram to individualize IPMN prognosis and LNM.
METHODS
Based on the data from SEER database of patients diagnosed with IPMN between 2004 and 2015, a nomogram predicting the survival and LNM of IPMN based on univariate and multivariate and Lasso regression analysis was performed, internally and externally validated, and measured by C-index, and decision curve analysis (DCA), and compared to the 7 TNM stage.
RESULTS
A total of 941 patients were included. Age, T stage examined nodes, tumor size, and pathology grade were identified as an independent factor for predicting LNM. The nomogram we established to predict LNM had a high predicting value with a C-index value of 0.735 and an AUC value of 0.753. Interestingly, including T1 stage, we found an inverse correlation was between age and LNM. In addition, nomogram for predicting CSS also performed better than TNM stage both in the internal validation group (1-year AUC:0.753 vs. 0.693, 3-year AUC: 0.801 vs. 0.731, 5-year AUC: 0.803 vs. 0.733) and external validation group (1-year AUC: 0.761 vs. 0.701, 3-year AUC: 0.772 vs. 0.713, 5-year AUC:0.811 vs. 0.735). DCA analysis showed the nomogram showed a greater benefit across the period of follow-up compared to 7 TNM stage.
CONCLUSION
A nomogram based on multivariate and Lasso regression analysis showed great clinical usability compared with current criteria. Also, for LNM of IPMN, younger age patients with IPMN should be attached more importance.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Area Under Curve; Black People; Decision Support Techniques; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Nomograms; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Regression Analysis; Risk Factors; SEER Program; Tumor Burden; White People; Young Adult
PubMed: 33641255
DOI: 10.1002/cam4.3632 -
Cancer Oct 2021
Topics: Bias; Humans; Pancreatic Neoplasms
PubMed: 34228811
DOI: 10.1002/cncr.33663 -
International Journal of Molecular... Nov 2022The advancement in molecular techniques has been attributed to the quality and significance of cancer research. Pancreatic cancer (PC) is one of the rare cancers with... (Review)
Review
The advancement in molecular techniques has been attributed to the quality and significance of cancer research. Pancreatic cancer (PC) is one of the rare cancers with aggressive behavior and a high mortality rate. The asymptomatic nature of the disease until its advanced stage has resulted in late diagnosis as well as poor prognosis. The heterogeneous character of PC has complicated cancer development and progression studies. The analysis of bulk tissues of the disease was insufficient to understand the disease, hence, the introduction of the single-cell separating technique aided researchers to decipher more about the specific cell population of tumors. This review gives an overview of the Laser Capture Microdissection (LCM) technique, one of the single-cell separation methods used in PC research.
Topics: Humans; Laser Capture Microdissection; Pancreatic Neoplasms; Pancreas; Carcinoma, Pancreatic Ductal
PubMed: 36498893
DOI: 10.3390/ijms232314566 -
Modern Pathology : An Official Journal... Mar 2020We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We...
We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age was 43 years (range: 26-75). Five occurred in the head/neck of the pancreas. All patients were treated surgically; none received neoadjuvant/adjuvant therapy. All patients are free of disease after 53 months of median follow-up (range: 8-94). The tumors were well-circumscribed, and the median size was 1.8 cm (range: 1.3-5.8). Microscopically, the unencapsulated tumors had a geographic pattern of epithelioid cell nests alternating with spindle cell fascicles. Some areas showed dense fibrosis, in which enmeshed tumor cells imparted a slit-like pattern. The predominant epithelioid cells had scant cytoplasm and round-oval nuclei with open chromatin. The spindle cells displayed irregular, hyperchromatic nuclei. Mitoses were rare. No lymph node metastases were identified. All tumors were positive for vimentin, CD99 and cytokeratin (patchy), while negative for markers of solid pseudopapillary neoplasm, neuroendocrine, acinar, myogenic/rhabdoid, vascular, melanocytic, or lymphoid differentiation, gastrointestinal stromal tumor as well as MUC4. Whole-exome sequencing revealed no recurrent somatic mutations or amplifications/homozygous deletions in any known oncogenes or tumor suppressor genes. RNA-sequencing and the Archer FusionPlex assay did not detect any recurrent likely pathogenic gene fusions. Single sample gene set enrichment analysis revealed that these tumors display a likely mesenchymal transcriptomic program. Unsupervised analysis (t-SNE) of their methylation profiles against a set of different mesenchymal neoplasms demonstrated a distinct methylation pattern. Here, we describe pancreatic neoplasms with unique morphologic/immunophenotypic features and a distinct methylation pattern, along with a lack of abnormalities in any of key genetic drivers, supporting that these neoplasms represent a novel entity with an indolent clinical course. Given their mesenchymal transcriptomic features, we propose the designation of "sclerosing epithelioid mesenchymal neoplasm" of the pancreas.
Topics: Adult; Aged; Biomarkers, Tumor; Epithelioid Cells; Europe; Female; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Japan; Male; Middle Aged; Molecular Diagnostic Techniques; Pancreatic Neoplasms; Phenotype; Retrospective Studies; Sclerosis; Stromal Cells; Terminology as Topic; Treatment Outcome; United States
PubMed: 31383964
DOI: 10.1038/s41379-019-0334-5 -
Seminars in Immunology Feb 2020Pancreatic cancer (PC) is a highly lethal malignancy with a dismal five-year survival rate. This is due to its asymptomatic nature, lack of reliable biomarkers, poor... (Review)
Review
Pancreatic cancer (PC) is a highly lethal malignancy with a dismal five-year survival rate. This is due to its asymptomatic nature, lack of reliable biomarkers, poor resectability, early metastasis, and high recurrence rate. Limited efficacies of current treatment modalities treatment-associated toxicity underscore the need for the development of immunotherapy-based approaches. For non-resectable, locally advanced metastatic PC, immunotherapy-based approaches including vaccines, antibody-targeted, immune checkpoint inhibition, CAR-T-cells, and adoptive T-cell transfer could be valuable additions to existing treatment modalities. Thus far, the vaccine candidates in PC have demonstrated modest immunological responses in different treatment modalities. The identification of tumor-associated antigens (TAA) and their successful implication in PC treatment is still a challenge. MUC4, a high molecular weight glycoprotein that functionally contributes to PC pathogenesis, is an attractive TAA. It is not detected in the normal pancreas; however, it is overexpressed in mouse and human pancreatic tumors. The recombinant MUC4 domain, as well as predicted immunogenic T-cell epitopes, elicited cellular and humoral anti-MUC4 response, suggesting its ulility as a vaccine candidate for PC therapy. Existence of PC-associated MUC4 splice variants, autoantibodies against overexpressed and aberrantly glycosylated MUC4 and presence of T-cell clones against the mutations present in MUC4 further reinforce its significance as a tumor antigen for vaccine development. Herein, we review the significance of MUC4 as a tumor antigen in PC immunotherapy and discuss both, the development and challenges associated with MUC4 based immunotherapy. Lastly, we will present our perspective on MUC4 antigenicity for the future development of MUC4-based PC immunotherapy.
Topics: Animals; Antigens, Neoplasm; Cancer Vaccines; Computational Biology; Epitopes; Humans; Immunotherapy; Mucin-4; Mutation; Pancreatic Neoplasms; T-Lymphocytes
PubMed: 31952903
DOI: 10.1016/j.smim.2020.101391 -
Journal of Hematology & Oncology Sep 2021Pancreatic cancer has the worst prognosis among common tumors which is attributed to its aggressive phenotype, diagnosis at advanced, inoperable stages, and resistance... (Review)
Review
Pancreatic cancer has the worst prognosis among common tumors which is attributed to its aggressive phenotype, diagnosis at advanced, inoperable stages, and resistance to systemic therapy. Non-coding RNAs (ncRNAs) such as microRNAs, long non-coding RNAs, and circular RNAs have been established as important regulators of gene expression and their deregulation has been implicated in multiple diseases and foremost cancer. In the tumor microenvironment, non-coding RNAs can be distributed among cancer cells, stromal cells, and immune cells via small extracellular vesicles (sEVs), thereby facilitating intercellular communication and influencing major cancer hallmarks such as angiogenesis, evasion of the immune system, and metastatic dissemination. Furthermore, sEV-ncRNAs have shown promising potential as liquid biopsies with diagnostic and prognostic significance. In this review, we summarize the role of sEVs as carriers of ncRNAs and underlying molecular mechanisms in pancreatic cancer. Moreover, we review the potential of sEV-ncRNAs as biomarkers and highlight the suitability of sEVs as delivery vehicles for ncRNA-based cancer therapy.
Topics: Animals; Biomarkers, Tumor; Extracellular Vesicles; Gene Expression Regulation, Neoplastic; Humans; Pancreatic Neoplasms; Prognosis; RNA, Untranslated; Tumor Microenvironment
PubMed: 34496946
DOI: 10.1186/s13045-021-01149-4