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Virchows Archiv : An International... Feb 2024Neoplasias of the hepatopancreatobiliary tract are growing in numbers, have the poorest prognosis of all major cancer entities, and thus represent a rising clinical... (Review)
Review
Neoplasias of the hepatopancreatobiliary tract are growing in numbers, have the poorest prognosis of all major cancer entities, and thus represent a rising clinical problem. Their molecular diagnostic has dramatically improved, contributing to tumor subtyping, definition of malignancy, and uncovering cases with hereditary predisposition. Most of all, predictive molecular testing allows to identify cases amenable to treatment with the rising number of approved targeted drugs, immune-oncological treatment, and clinical trials. In this review, the current state of molecular testing and its contribution to clinical decision-making are outlined.
Topics: Humans; Pathology, Molecular; Pancreatic Neoplasms; Genetic Predisposition to Disease; Molecular Diagnostic Techniques; Medical Oncology
PubMed: 38429607
DOI: 10.1007/s00428-024-03744-5 -
Modern Pathology : An Official Journal... Dec 2022Pancreatic intraductal tubulopapillary neoplasm (ITPN) is a recently recognized intraductal neoplasm. This study aimed to clarify the clinicopathologic and molecular...
Pancreatic intraductal tubulopapillary neoplasm (ITPN) is a recently recognized intraductal neoplasm. This study aimed to clarify the clinicopathologic and molecular features of this entity, based on a multi-institutional cohort of 16 pancreatic ITPNs and associated adenocarcinomas. The genomic profiles were analyzed using histology-driven multi-regional sequencing to provide insight on tumor heterogeneity and evolution. Furthermore, an exploratory transcriptomic characterization was performed on eight invasive adenocarcinomas. The clinicopathologic parameters and molecular alterations were further analyzed based on survival indices. The main findings were as follows: 1) the concomitant adenocarcinomas, present in 75% of cases, were always molecularly associated with the intraductal components. These data definitively establish ITPN as origin of invasive pancreatic adenocarcinoma; 2) alterations restricted to infiltrative components included mutations in chromatin remodeling genes ARID2, ASXL1, and PBRM1, and ERBB2-P3H4 fusion; 3) pancreatic ITPN can arise in the context of genetic syndromes, such as BRCA-germline and Peutz-Jeghers syndrome; 4) mutational profile: mutations in the classical PDAC drivers are present, but less frequently, in pancreatic ITPN; 5) novel genomic alterations were observed, including amplification of the Cyclin and NOTCH family genes and ERBB2, fusions involving RET and ERBB2, and RB1 disruptive variation; 6) chromosomal alterations: the most common was 1q gain (75% of cases); 7) by transcriptome analysis, ITPN-associated adenocarcinomas clustered into three subtypes that correlate with the activation of signaling mechanism pathways and tumor microenvironment, displaying squamous features in their majority; and 8) TP53 mutational status is a marker for adverse prognosis. ITPNs are precursor lesions of pancreatic cancer with a high malignant transformation risk. A personalized approach for patients with ITPN should recognize that such neoplasms could arise in the context of genetic syndromes. BRCA alterations, ERBB2 and RET fusions, and ERBB2 amplification are novel targets in precision oncology. The TP53 mutation status can be used as a prognostic biomarker.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Adenocarcinoma; Syndrome; Precision Medicine; Pancreas; Tumor Microenvironment
PubMed: 36056133
DOI: 10.1038/s41379-022-01143-2 -
Pancreas Mar 2020Radiologic characterization of pancreatic lesions is currently limited. Computed tomography is insensitive in detecting and characterizing small pancreatic lesions.... (Review)
Review
Radiologic characterization of pancreatic lesions is currently limited. Computed tomography is insensitive in detecting and characterizing small pancreatic lesions. Moreover, heterogeneity of many pancreatic lesions makes determination of malignancy challenging. As a result, invasive diagnostic testing is frequently used to characterize pancreatic lesions but often yields indeterminate results. Computed tomography texture analysis (CTTA) is an emerging noninvasive computational tool that quantifies gray-scale pixels/voxels and their spatial relationships within a region of interest. In nonpancreatic lesions, CTTA has shown promise in diagnosis, lesion characterization, and risk stratification, and more recently, pancreatic applications of CTTA have been explored. This review outlines the emerging role of CTTA in identifying, characterizing, and risk stratifying pancreatic lesions. Although recent studies show the clinical potential of CTTA of the pancreas, a clear understanding of which specific texture features correlate with high-grade dysplasia and predict survival has not yet been achieved. Further multidisciplinary investigations using strong radiologic-pathologic correlation are needed to establish a role for this noninvasive diagnostic tool.
Topics: Disease-Free Survival; Humans; Neoplasm Grading; Pancreatic Neoplasms; Predictive Value of Tests; Radiographic Image Interpretation, Computer-Assisted; Risk Assessment; Risk Factors; Tomography, X-Ray Computed
PubMed: 32168248
DOI: 10.1097/MPA.0000000000001495 -
Frontiers in Immunology 2023The mutation of the crucial genes such as tumor suppressors or oncogenes plays an important role in the initiation and development of tumors. The non-synonymous... (Review)
Review
The mutation of the crucial genes such as tumor suppressors or oncogenes plays an important role in the initiation and development of tumors. The non-synonymous mutations in the tumor cell genome will produce non-autologous proteins (neoantigen) to activate the immune system by activating CD4+ and CD8+ T cells. Neoantigen-based peptide vaccines have exhibited exciting therapeutic effects in treating various cancers alone or in combination with other therapeutic strategies. Furthermore, antigen-loaded DC vaccines are more powerful in inducing stronger immune responses than vaccines generated by antigens and adjuvants. Therefore, neoantigen-based dendritic cell (DC) vaccines could achieve promising effects in combating some malignant tumors. In this review, we summarized and discussed the recent research progresses of the neoantigen, neoantigen-based vaccines, and DC-based vaccine in pancreatic cancers (PCs). The combination of the neoantigen and DC-based vaccine in PC was also highlighted. Therefore, our work will provide more detailed evidence and novel opinions to promote the development of a personalized neoantigen-based DC vaccine for PC.
Topics: Humans; Antigens, Neoplasm; Pancreatic Neoplasms; CD8-Positive T-Lymphocytes; Dendritic Cells
PubMed: 36761724
DOI: 10.3389/fimmu.2023.1104860 -
BMJ Case Reports Jan 2021Intraductal papillary mucinous neoplasms (IPMNs) are mucin-secreting cystic neoplasm of pancreas. They have a malignant potential. They are usually localised to the...
Intraductal papillary mucinous neoplasms (IPMNs) are mucin-secreting cystic neoplasm of pancreas. They have a malignant potential. They are usually localised to the pancreas but occasionally can involve surrounding structures (1.9%-6.6%), like bile duct and duodenum, and are labelled as IPMN with invasion. Jaundice as a manifestation of IPMN is not common (4.5%). It can present as jaundice as a result of invasion of common bile duct (CBD) resulting in stricture formation or uncommonly as a result of fistulising to CBD with resultant obstruction of CBD by thick mucin secreted by this tumour. As only few cases (around 23) of mucin-filled CBD are reported in the literature. We are presenting our experience in dealing a rare case of obstructive jaundice caused by IPMN fistulising into CBD, highlighting the difficulties faced in managing such case, especially with regards to biliary drainage and what can be the optimum management in such cases.
Topics: Adenocarcinoma, Mucinous; Anti-Bacterial Agents; Biliary Fistula; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Common Bile Duct; Drainage; Female; Humans; Jaundice, Obstructive; Middle Aged; Mucins; Neoplasm Invasiveness; Pancreas; Pancreatic Fistula; Pancreatic Neoplasms; Stents; Treatment Outcome
PubMed: 33431462
DOI: 10.1136/bcr-2020-238363 -
Diagnostic Pathology Dec 2020Pancreatic Solid Pseudopapillary Neoplasms (SPNs) are rare low-grade malignant tumors with a marked preponderance for young females. Objective was to describe the... (Review)
Review
Clinicopathological and immunohistochemical study of 29 cases of solid-pseudopapillary neoplasms of the pancreas in patients under 20 years of age along with detailed review of literature.
BACKGROUND
Pancreatic Solid Pseudopapillary Neoplasms (SPNs) are rare low-grade malignant tumors with a marked preponderance for young females. Objective was to describe the morphology, differential diagnosis, and prognosis of SPNs in patients under 20 years of age and present a detailed review of literature.
METHODS
A total of 29 cases in patients under 20 years of age reported as SPN during the period January 2014 to December 2019, were included in the study. These included 19 resection specimens, 4 incision biopsies and 6 cases received as blocks for second opinion. Hematoxylin and eosin (H&E) slides as well as immunohistochemistry (IHC) slides of all cases were retrieved and reviewed by the authors. TFE3 and Progesterone Receptor were performed retrospectively.
RESULTS
Twenty-eight of the 29 patients were females. Ages of patients ranged from 12 to 19 years. Nineteen cases were resections. Tail was the commonest location. Mean tumor size was 9.5 cm. In 89.5% cases, tumor was confined to the pancreas. In 2 cases, distant metastasis was present. In 2 cases, extension beyond pancreas was seen. Solid and pseudopapillary areas were seen in all cases while other features were variable. Beta catenin and Cyclin D1 were positive in most cases while TFE3 was positive in 57% cases. Progesterone Receptor (PR) was positive in all 13 cases in which it was performed. Follow up was available in 14 patients. Follow up period ranged from 3 to 70 months. Twelve were alive and well without recurrence or metastasis while 2 were alive with recurrence and metastasis to liver and omentum respectively.
CONCLUSIONS
Although many studies on SPNs have been published, surgeons, oncologists and even pathologists in this part of the world are often not aware of these rare tumors leading to inaccuracies and delays in diagnosis. In addition, this paper focusses on the interesting observation that the majority of SPNs diagnosed in our department during study period occurred in patients under 20 years of age (29 versus 21 in patients over 20). However, clinico-epidemiological, morphologic and prognostic features were similar in both age groups. Possibility of SPNs should always be considered in case of pancreatic neoplasms occurring in patients under 20 years of age as well. We believe that this is a very interesting and helpful study for the clinicians as well as the pathologists.
Topics: Adolescent; Age of Onset; Child; Female; Humans; Immunohistochemistry; Male; Pancreatic Neoplasms; Young Adult
PubMed: 33298094
DOI: 10.1186/s13000-020-01058-z -
IUBMB Life May 2020Pancreatic cancer (PC) is one of the most lethal cancers and 12th most common cancer in the world. Due to the inaccessible anatomical position of the pancreas and... (Review)
Review
Pancreatic cancer (PC) is one of the most lethal cancers and 12th most common cancer in the world. Due to the inaccessible anatomical position of the pancreas and asymptomatic early stages of this disease, PC has a high mortality rate. Therefore, providing reliable diagnostic and therapeutic tools are the keys to increase the PC survival rate. Nanotechnology is an inchoate field of science that previously scientists' tendency to enhance the efficacy of current preventive, diagnostic, and therapeutic methods has oriented them to build a bridge between this science and medicine. In the case of PC, nanotechnology suggests using drug delivery devices for a more effective and targeted therapy. Chitosan is a natural polymer that recently has attracted a lot of attention for being renewable, nontoxic, and bioabsorbable. In this article, we tend to look for the answer to this question: has nanotechnology been successful in using chitosan-based nanoformulations as carriers for preventing more individuals from suffering or at least increasing the 5-year survival of the PC patients?
Topics: Antineoplastic Agents; Chitosan; Drug Compounding; Drug Delivery Systems; Gene Expression Regulation, Neoplastic; Glycoconjugates; Humans; Molecular Targeted Therapy; Nanoparticles; Nanotechnology; Neoplasm Proteins; Nuclear Pore Complex Proteins; Pancreatic Neoplasms; Photochemotherapy; Photosensitizing Agents; Survival Analysis; TOR Serine-Threonine Kinases
PubMed: 32057169
DOI: 10.1002/iub.2252 -
World Journal of Surgical Oncology Aug 2023Invasive pancreatic cystic neoplasms (iPCNs) are an uncommon and biologically heterogeneous group of malignant neoplasms. We aimed to investigate the clinicopathological...
PURPOSES
Invasive pancreatic cystic neoplasms (iPCNs) are an uncommon and biologically heterogeneous group of malignant neoplasms. We aimed to investigate the clinicopathological characteristics of iPCN patients and to develop nomograms for individual survival prediction after radical surgery.
METHODS
Data of patients diagnosed with iPCN and pancreatic ductal adenocarcinoma (PDAC) between 2000 and 2018 from the SEER database were retrieved. The differences in clinical outcomes were evaluated using the Kaplan-Meier analysis. Nomograms were proposed based on the Cox regression model and internally validated by C-index, area under the curve (AUC) value, and calibration plot.
RESULTS
A total of 7777 iPCN patients and 154,336 PDAC patients were enrolled. Most neoplasms were advanced, with 63.1% at stage IV. The 3-year overall survival (OS) and cancer-specific survival (CSS) rates in surgical patients were as follows: 45.7% and 50.1% for invasive intraductal papillary mucinous neoplasm (IPMN), 54.8% and 59.3% for invasive mucinous cystic neoplasm (MCN), 97.8% and 98.2% for invasive solid pseudopapillary neoplasm (SPN), 88.9% and 88.9% for invasive serous cystic neoplasm (SCN), and 27.3% and 30.5% for PDAC. Subgroup analyses showed no clinical benefit from chemotherapy or radiotherapy in lymph node-negative iPCN patients who underwent surgery. The following variables associated with OS and CSS were identified: age, race, chemotherapy, radiotherapy, histologic type, pathological grade, regional nodes examined, and T, N, and M stage. The nomograms had good discrimination and calibration by internal validation, with an AUC value of 0.800 for 3-year OS and 0.814 for 3-year CSS.
CONCLUSION
Our study showed that the prognosis of iPCN patients was significantly better than PDAC patients. The proposed nomograms demonstrated substantially better discrimination and calibration.
Topics: Humans; Retrospective Studies; Pancreas; Pancreatic Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Carcinoma, Pancreatic Ductal
PubMed: 37612715
DOI: 10.1186/s12957-023-03145-z -
Molecular and Cellular Biochemistry Jun 2021Pancreatic cancer (PC) is the third lethal disease for cancer-related mortalities globally. This is mainly because of the aggressive nature and heterogeneity of the... (Review)
Review
Pancreatic cancer (PC) is the third lethal disease for cancer-related mortalities globally. This is mainly because of the aggressive nature and heterogeneity of the disease that is diagnosed only in their advanced stages. Thus, it is challenging for researchers and clinicians to study the molecular mechanism involved in the development of this aggressive disease. The single-cell sequencing technology enables researchers to study each and every individual cell in a single tumor. It can be used to detect genome, transcriptome, and multi-omics of single cells. The current single-cell sequencing technology is now becoming an important tool for the biological analysis of cells, to find evolutionary relationship between multiple cells and unmask the heterogeneity present in the tumor cells. Moreover, its sensitivity nature is found progressive enabling to detect rare cancer cells, circulating tumor cells, metastatic cells, and analyze the intratumor heterogeneity. Furthermore, these single-cell sequencing technologies also promoted personalized treatment strategies and next-generation sequencing to predict the disease. In this review, we have focused on the applications of single-cell sequencing technology in identifying cancer-associated cells like cancer-associated fibroblast via detecting circulating tumor cells. We also included advanced technologies involved in single-cell sequencing and their advantages. The future research indeed brings the single-cell sequencing into the clinical arena and thus could be beneficial for diagnosis and therapy of PC patients.
Topics: Humans; Pancreatic Neoplasms; Sequence Analysis; Single-Cell Analysis; Transcriptome
PubMed: 33599893
DOI: 10.1007/s11010-021-04095-4 -
Endocrine-related Cancer Aug 2023High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an...
Expert Consensus Practice Recommendations of the North American Neuroendocrine Tumor Society for the management of high grade gastroenteropancreatic and gynecologic neuroendocrine neoplasms.
High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.
Topics: Humans; Female; Neuroendocrine Tumors; Consensus; Neoplasm Grading; Carcinoma, Neuroendocrine; North America; Pancreatic Neoplasms
PubMed: 37184955
DOI: 10.1530/ERC-22-0206