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Japanese Journal of Clinical Oncology Aug 2023Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a... (Review)
Review
Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments.
Topics: Humans; Retrospective Studies; Pancreatic Neoplasms; Carcinoma; Pancreas
PubMed: 37325968
DOI: 10.1093/jjco/hyad062 -
Journal of Clinical Pathology Nov 2023Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is one of the most well-established precursors of pancreatic cancer. Its progression to acquire... (Review)
Review
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is one of the most well-established precursors of pancreatic cancer. Its progression to acquire invasiveness is a complex process, based on the accumulation of morphological and genetic alterations. Recent advances in DNA sequencing also showed that co-occurring IPMNs and pancreatic cancers could be totally independent, further complicating our understanding of this complex scenario. The distinction between IPMN and related pancreatic cancer vs IPMN and co-occurring-but not related-pancreatic cancer is a challenging task in routine diagnostic activity, but may have important implications for precision oncology. Of note, recent multiregional sequencing-based studies focused not only on IPMN multi-step tumourigenesis, but also on the divergent intratumoural heterogeneity of this neoplasm. Globally considered, there are three different situations in which co-occurring IPMNs and invasive carcinomas can be found in the same pancreata, indicated with different terminologies: (1) IPMN-associated carcinoma: this definition indicates a carcinoma arising from an IPMN and can be also defined as IPMN-derived carcinoma, sequential or likely related; (2) independent IPMN and invasive carcinoma: the two lesions are not related, and this situation is defined as concomitant, de novo or likely independent; (3) branch-off pathway, where an invasive carcinoma and an adjacent IPMN develop divergently in a forked fashion from a common ancestral clone. In this review, we aim at clarifying the most important nomenclature/definitions of these different situations, also providing an overview of the molecular state-of-the-art and of the clinical implications of this complex landscape.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Intraductal Neoplasms; Pathology, Molecular; Adenocarcinoma, Mucinous; Precision Medicine; Pancreatic Neoplasms; Retrospective Studies
PubMed: 37500498
DOI: 10.1136/jcp-2023-209012 -
Seminars in Cancer Biology Nov 2022Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or... (Review)
Review
Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases including various malignancies. Currently, understanding the mechanism of oncogenesis became a necessity for the development of targeted therapeutic strategy for different cancer types. It is evident that many TFs go awry in cancers of the pancreas such as pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PanNENs). These mutated or dysregulated TFs abnormally controls various signaling pathways in PDAC and PanNENs including RTK, PI3K-PTEN-AKT-mTOR, JNK, TGF-β/SMAD, WNT/β-catenin, SHH, NOTCH and VEGF which in turn regulate different hallmarks of cancer. Aberrant regulation of such pathways have been linked to the initiation, progression, metastasis, and resistance in pancreatic cancer. As of today, a number of TFs has been identified as crucial regulators of pancreatic cancer and a handful of them shown to have potential as therapeutic targets in pre-clinical and clinical settings. In this review, we have summarized the current knowledge on the role and therapeutic usefulness of TFs in PDAC and PanNENs.
Topics: Humans; Carcinoma, Pancreatic Ductal; Gene Expression Regulation, Neoplastic; Pancreas; Pancreatic Neoplasms; Transcription Factors
PubMed: 36058426
DOI: 10.1016/j.semcancer.2022.08.011 -
World Journal of Surgery Jul 2020Due to the rarity of malignant insulinoma, a lack of the literature describing factors affecting outcomes exists. Our aim was to review malignant insulinoma incidence,... (Review)
Review
INTRODUCTION
Due to the rarity of malignant insulinoma, a lack of the literature describing factors affecting outcomes exists. Our aim was to review malignant insulinoma incidence, characteristics and survival trends.
METHODS
We identified all patients with malignant insulinoma in the SEER registries from 1973 to 2015. Incidence, neoplasm characteristics and factors affecting cancer-specific survival (CSS) were described.
RESULTS
A total of 121 patients were identified. The crude annual overall incidence was low (range 0.0-0.27 cases per million person years). The largest proportion had localized disease (40%), while 16% had regional disease, 39% distant metastatic disease, and stage was unreported in 5%. Most neoplasms were in the body/tail of the pancreas, followed by the head of the pancreas. Grade was reported in 40% of patients; only a single patient reported as having grade IV with the remainder all grades I/II. Surgical resection was performed in 64% of patients. Within surgical patients, the median primary neoplasm size was 1.8 cm. Regional lymph nodes were examined in 57.1% of surgical patients, while 34% of examined nodes were positive. The median CSS was 183 months. On multivariable analysis, surgical resection, male sex and absence of metastatic disease were associated with superior survival.
CONCLUSION
While the greatest proportion of patients with malignant insulinoma present with localized disease, regional lymph node involvement was found in 34% of whose nodes were tested. Further studies are needed to assess the role of lymph node dissection in improving survival and preventing recurrence given the observed frequency of lymph node involvement.
Topics: Humans; Insulinoma; Lymph Node Excision; Lymphatic Metastasis; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; Survival Rate
PubMed: 32128613
DOI: 10.1007/s00268-020-05445-x -
World Journal of Gastroenterology Apr 2021Bile duct epithelial tumours showing papillary neoplasm in the bile duct lumen are present in the intrahepatic and extrahepatic bile ducts. Clinicopathological images of... (Review)
Review
Bile duct epithelial tumours showing papillary neoplasm in the bile duct lumen are present in the intrahepatic and extrahepatic bile ducts. Clinicopathological images of these tumours are distinctive and diverse, including histological images with a low to high grade dysplasia, infiltrating and noninfiltrating characteristics, excessive mucus production, and similarity to intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The World Health Organization Classification of Tumours of the Digestive System in 2010 named these features, intraductal papillary neoplasm of the bile duct (IPNB), as precancerous lesion of biliary carcinoma. IPNB is currently classified into type 1 that is similar to IPMN, and type 2 that is not similar to IPMN. Many of IPNB spreads superficially, and diagnosis with cholangioscopy is considered mandatory to identify accurate localization and progression. Prognosis of IPNB is said to be better than normal bile duct cancer.
Topics: Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Humans; Pancreatic Neoplasms
PubMed: 33958844
DOI: 10.3748/wjg.v27.i15.1569 -
Revista Espanola de Enfermedades... Aug 2022Zollinger Ellison syndrome is an unusual entity. This termn is used to describe the clinical manifestations of a gastrin-synthesizing neoplasm. Gastrinomas occur mainly...
Zollinger Ellison syndrome is an unusual entity. This termn is used to describe the clinical manifestations of a gastrin-synthesizing neoplasm. Gastrinomas occur mainly in the duodenum and pancreas. Primary gastrinomas are rarely found in other intra-abdominal sites, such as the ovary, bile ducts, spleen or kidney, or even more unusual in extra-abdominal locations. Several studies provide strong evidence that gastrinomas can also occur in the lymph nodes. However, the existence of primary lymph node gastrinomas is controversial.
Topics: Female; Gastrinoma; Gastrointestinal Stromal Tumors; Humans; Pancreas; Pancreatic Neoplasms; Zollinger-Ellison Syndrome
PubMed: 35255699
DOI: 10.17235/reed.2022.8753/2022 -
Expert Review of Anticancer Therapy Nov 2020Tumor control and survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) has improved with more effective polychemotherapies. The identification of... (Review)
Review
INTRODUCTION
Tumor control and survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) has improved with more effective polychemotherapies. The identification of novel therapeutic targets is strongly needed in order to propose maintenance therapies that improve quality of life while maintaining tumor control.
AREAS COVERED
PDAC with mutations in homologous recombination repair genes such as are particularly sensitive to platinum agents. Recently, the potential role of poly(ADP-ribose) polymerase (PARP) inhibitors was suggested. The POLO study has shown that olaparib was efficient and well-tolerated as maintenance therapy in patients with germline mutation and a metastatic PDAC controlled after a platinum-based induction chemotherapy.
EXPERT OPINION
The demonstration of olaparib efficacy in patients with metastatic PDAC and BRCA germline mutation has paved the way for maintenance with a targeted therapy. Further studies are needed to assess; the potential role for PARPI in earlier forms of PDAC, those with somatic or more rare BRACness signatures, to overcome primary or secondary resistances to PARPi, and to combine them with other antitumoral agents.
Topics: Animals; Carcinoma, Pancreatic Ductal; Drug Resistance, Neoplasm; Germ-Line Mutation; Humans; Molecular Targeted Therapy; Neoplasm Metastasis; Pancreatic Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Quality of Life; Survival Rate
PubMed: 32936674
DOI: 10.1080/14737140.2020.1820330 -
Nature Reviews. Gastroenterology &... Jul 2021Due to its poor prognosis and the late stage at which it is typically diagnosed, early detection of pancreatic cancer is a pressing clinical problem. Advances in genomic... (Review)
Review
Due to its poor prognosis and the late stage at which it is typically diagnosed, early detection of pancreatic cancer is a pressing clinical problem. Advances in genomic analysis of human pancreatic tissue and other biospecimens such as pancreatic cyst fluid, pancreatic juice and blood have opened the possibility of DNA-based molecular approaches for early detection of pancreatic cancer. In this Review, we discuss and focus on the pathological and molecular features of precancerous lesions of the pancreas, including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm and mucinous cystic neoplasm, which are target lesions of early detection approaches. We also discuss the most prevalent genetic alterations in these precancerous lesions, including somatic mutations in the oncogenes KRAS and GNAS as well as tumour suppressor genes CDKN2A, TP53 and SMAD4. We highlight the latest discoveries related to genetic heterogeneity and multifocal neoplasia in precancerous lesions. In addition, we review specific approaches, challenges and clinically available assays for early detection of pancreatic cancer using DNA-based molecular techniques. Although detection and risk stratification of precancerous pancreatic neoplasms are difficult problems, progress in this field highlights the promise of molecular approaches for improving survival of patients with this disease.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Early Detection of Cancer; Genetic Heterogeneity; Humans; Mutation; Pancreatic Neoplasms; Precancerous Conditions; Sequence Analysis, DNA
PubMed: 34099908
DOI: 10.1038/s41575-021-00470-0 -
Clinical Imaging Nov 2020Solid Pseudopapillary Neoplasms of the pancreas are rare pancreatic tumors with low-grade malignant potential, typically affecting young females. In this review, we... (Review)
Review
Solid Pseudopapillary Neoplasms of the pancreas are rare pancreatic tumors with low-grade malignant potential, typically affecting young females. In this review, we discuss the surgical anatomy; the imaging characteristics, and image reporting essentials for proper surgical planning along with the atypical features which should caution the physician regarding the risk of malignancy. We also discuss the common surgical procedures and organ preservation surgeries along with a comprehensive review of the literature.
Topics: Adult; Female; Humans; Neoplasms, Glandular and Epithelial; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Radiography
PubMed: 32559679
DOI: 10.1016/j.clinimag.2020.06.008 -
Cancer Science May 2023Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare pancreatic tumor in children. Its origin remains elusive, along with its pathogenesis. Heterogeneity...
Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare pancreatic tumor in children. Its origin remains elusive, along with its pathogenesis. Heterogeneity within SPN has not been previously described. In addition, low malignant but recurrent cases have occasionally been reported. To comprehensively unravel these profiles, single-cell RNA sequencing was performed using surgical specimens. We identified the cell types and suggested the origin of pancreatic endocrine progenitors. The Wnt/β-catenin pathway may be involved in tumorigenesis, while the epithelial-to-mesenchymal transition may be responsible for SPN recurrence. Furthermore, NOV, DCN were nominated as primary and S100A10, MGP as recurrent SPN marker genes, respectively. Our results provide insight into the pathogenesis of SPN.
Topics: Humans; Child; Pancreas; Pancreatic Neoplasms; Carcinoma, Papillary; Wnt Signaling Pathway; Sequence Analysis, RNA
PubMed: 36721980
DOI: 10.1111/cas.15744