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Nature Reviews. Gastroenterology &... Jul 2021Pancreatic cancer is a leading cause of cancer death worldwide and its global burden has more than doubled over the past 25 years. The highest incidence regions for... (Review)
Review
Pancreatic cancer is a leading cause of cancer death worldwide and its global burden has more than doubled over the past 25 years. The highest incidence regions for pancreatic cancer include North America, Europe and Australia, and although much of this increase is due to ageing worldwide populations, there are key modifiable risk factors for pancreatic cancer such as cigarette smoking, obesity, diabetes and alcohol intake. The prevalence of these risk factors is increasing in many global regions, resulting in increasing age-adjusted incidence rates for pancreatic cancer, but the relative contribution from these risk factors varies globally due to variation in the underlying prevalence and prevention strategies. Inherited genetic factors, although not directly modifiable, are an important component of pancreatic cancer risk, and include pathogenic variants in hereditary cancer genes, genes associated with hereditary pancreatitis, as well as common variants identified in genome-wide association studies. Identification of the genetic changes that underlie pancreatic cancer not only provides insight into the aetiology of this cancer but also provides an opportunity to guide early detection strategies. The goal of this Review is to provide an up-to-date overview of the established modifiable and inherited risk factors for pancreatic cancer.
Topics: Comorbidity; Early Detection of Cancer; Genetic Predisposition to Disease; Humans; Life Style; Pancreatic Neoplasms; Risk Factors
PubMed: 34002083
DOI: 10.1038/s41575-021-00457-x -
Pancreatology : Official Journal of the... Mar 2024This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and... (Review)
Review
This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.
Topics: Humans; Pancreatic Intraductal Neoplasms; Pancreas; Pancreatic Neoplasms; Endosonography; Carcinoma, Pancreatic Ductal
PubMed: 38182527
DOI: 10.1016/j.pan.2023.12.009 -
Cell Apr 2023Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant efforts have largely defined major genetic factors driving PDAC pathogenesis... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant efforts have largely defined major genetic factors driving PDAC pathogenesis and progression. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this review, we highlight the foundational studies that have driven our understanding of these processes. We further discuss the recent technological advances that continue to expand our understanding of PDAC complexity. We posit that the clinical translation of these research endeavors will enhance the currently dismal survival rate of this recalcitrant disease.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Tumor Microenvironment; Early Diagnosis; Prognosis
PubMed: 37059070
DOI: 10.1016/j.cell.2023.02.014 -
CA: a Cancer Journal For Clinicians Sep 2020Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed... (Review)
Review
Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis-free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor-specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under-addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.
Topics: Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Clinical Decision-Making; Clinical Trials as Topic; Early Detection of Cancer; Genetic Predisposition to Disease; Humans; Neoplasm Staging; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Patient Care Team; Radiotherapy, Adjuvant; Risk Factors; Standard of Care
PubMed: 32683683
DOI: 10.3322/caac.21626 -
Gastroenterology Apr 2023Pancreatic cancer usually results in poor survival with limited options for treatment, as most affected individuals present with advanced disease. Early detection of...
Pancreatic cancer usually results in poor survival with limited options for treatment, as most affected individuals present with advanced disease. Early detection of preinvasive pancreatic neoplasia and identifying molecular therapeutic targets provide opportunities for extending survival. Although screening for pancreatic cancer is currently not recommended for the general population, emerging evidence indicates that pancreatic surveillance can improve outcomes for individuals in certain high-risk groups. Changes in the epidemiology of pancreatic cancer, experience from pancreatic surveillance, and discovery of novel biomarkers provide a roadmap for new strategies for pancreatic cancer risk assessment, early detection, and prevention.
Topics: Humans; Early Detection of Cancer; Pancreatic Neoplasms; Risk Assessment; Pancreas; Risk Factors
PubMed: 36804602
DOI: 10.1053/j.gastro.2023.02.012 -
Digestive Surgery 2020The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological... (Review)
Review
BACKGROUND
The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance.
METHODS
We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery.
RESULTS
The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies.
CONCLUSIONS
Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need.
Topics: Humans; Pancreas; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Practice Guidelines as Topic; Precancerous Conditions
PubMed: 30636253
DOI: 10.1159/000496509 -
Neuroendocrinology 2020The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear... (Review)
Review
The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeutic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.
Topics: Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms
PubMed: 31557758
DOI: 10.1159/000503721 -
World Journal of Gastroenterology May 2020Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging,... (Review)
Review
Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.
Topics: Ablation Techniques; Antineoplastic Agents; Biomarkers, Tumor; Chemotherapy, Adjuvant; Combined Modality Therapy; Cytoreduction Surgical Procedures; Disease-Free Survival; Humans; Lymph Node Excision; Molecular Targeted Therapy; Neoplasm Grading; Neoplasm Staging; Neuroendocrine Tumors; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Patient Care Team; Prognosis; Progression-Free Survival; Somatostatin; Treatment Outcome
PubMed: 32476795
DOI: 10.3748/wjg.v26.i19.2305 -
Acta Cytologica 2023The World Health Organization (WHO), the International Academy of Cytology, and the International Agency for Research on Cancer, with expert contributors from around the... (Review)
Review
The World Health Organization (WHO), the International Academy of Cytology, and the International Agency for Research on Cancer, with expert contributors from around the world, present an international approach to standardized reporting of pancreaticobiliary cytopathology. This reporting system is one of the first in a series from various body sites that mirror the WHO Classification of Tumours series and provides an evidence-based terminology system with associated risk of malignancy and diagnostic management recommendation per diagnostic category. The WHO Reporting System for Pancreaticobiliary Cytopathology (WHO system) revises the Papanicolaou Society of Cytopathology (PSC) system for Reporting Pancreaticobiliary Cytology published in 2015 and replaces the six-tiered system with a seven-tiered system: "insufficient/inadequate/nondiagnostic"; "benign (negative for malignancy)," "atypical," "pancreaticobiliary neoplasm of low risk/low grade," "pancreatic neoplasm of high risk/high grade," "suspicious for malignancy," and "malignant." The principal differences between the WHO and the PSC systems revolve around the classification of neoplasia. In the PSC system, there was a single category for "neoplastic" lesions that includes two groups, one for "benign neoplasms" [primarily serous cystadenoma] and one named "other," dominated by premalignant intraductal neoplasms (primarily intraductal papillary mucinous neoplasms) and low-grade malignant neoplasms [pancreatic neuroendocrine tumors (PanNETs) and solid pseudopapillary neoplasms (SPNs)]. In the WHO system, benign neoplasms with virtually no risk of malignancy are included in the "benign" category and low-grade malignancies (PanNET and SPN) are included in the "malignant" category, as per the WHO Classification of Digestive System Tumours, thus leaving in the "neoplasm" category primarily those noninvasive premalignant lesions of the ductal system. These neoplasms are divided by the cytomorphological grade of the epithelium into low risk/low-grade and high risk/high-grade, with distinctly different risks of malignancy. As with the PSC system, the WHO system advocates close correlation with imaging and encourages incorporation of ancillary testing into the final diagnosis, such as biochemical (CEA and amylase) and molecular testing of cyst fluid and bile duct brushings. Key diagnostic cytopathological features of specific lesions or neoplasms, ancillary studies for diagnostic and prognostic evaluation, and implications of diagnosis for patient care and management are discussed. In addition, the WHO system includes reporting and diagnostic management options that recognize the variations in the availability of diagnostic and prognostic ancillary testing modalities in low- and middle-income countries, where cytopathology is particularly useful and is increasingly available in the absence of histopathological services.
Topics: Humans; Societies, Medical; Pancreatic Neoplasms; Precancerous Conditions; Cytodiagnosis
PubMed: 36516741
DOI: 10.1159/000527912 -
Nature Communications Jan 2021Ferroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Transcription factors play multiple roles in...
Ferroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Transcription factors play multiple roles in ferroptosis, although the key regulator for ferroptosis in iron metabolism remains elusive. Using NanoString technology, we identify NUPR1, a stress-inducible transcription factor, as a driver of ferroptosis resistance. Mechanistically, NUPR1-mediated LCN2 expression blocks ferroptotic cell death through diminishing iron accumulation and subsequent oxidative damage. Consequently, LCN2 depletion mimics NUPR1 deficiency with respect to ferroptosis induction, whereas transfection-enforced re-expression of LCN2 restores resistance to ferroptosis in NUPR1-deficient cells. Pharmacological or genetic blockade of the NUPR1-LCN2 pathway (using NUPR1 shRNA, LCN2 shRNA, pancreas-specific Lcn2 conditional knockout mice, or the small molecule ZZW-115) increases the activity of the ferroptosis inducer erastin and worsens pancreatitis, in suitable mouse models. These findings suggest a link between NUPR1-regulated iron metabolism and ferroptosis susceptibility.
Topics: Animals; Cell Line, Tumor; DNA-Binding Proteins; Ferroptosis; Gene Expression Regulation, Neoplastic; Humans; Iron; Kaplan-Meier Estimate; Lipocalin-2; Mice, Knockout; Mice, Nude; Mice, Transgenic; Neoplasm Proteins; Pancreatic Neoplasms; Piperazines; RNAi Therapeutics; Signal Transduction; Thiazines; Xenograft Model Antitumor Assays; Mice
PubMed: 33510144
DOI: 10.1038/s41467-021-20904-2