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Gastroenterology Aug 2022Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer, due to both its late stage at diagnosis and its resistance to chemotherapy. However, recent... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer, due to both its late stage at diagnosis and its resistance to chemotherapy. However, recent advances in our understanding of the biology of PDAC have revealed new opportunities for early detection and targeted therapy of PDAC. In this review, we discuss the pathogenesis of PDAC, including molecular alterations in tumor cells, cellular alterations in the tumor microenvironment, and population-level risk factors. We review the current status of surveillance and early detection of PDAC, including populations at high risk and screening approaches. We outline the diagnostic approach to PDAC and highlight key treatment considerations, including how therapeutic approaches change with disease stage and targetable subtypes of PDAC. Recent years have seen significant improvements in our approaches to detect and treat PDAC, but large-scale, coordinated efforts will be needed to maximize the clinical impact for patients and improve overall survival.
Topics: Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Humans; Pancreatic Neoplasms; Tumor Microenvironment
PubMed: 35398344
DOI: 10.1053/j.gastro.2022.03.056 -
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 -
JAMA Sep 2021Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is... (Review)
Review
IMPORTANCE
Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030.
OBSERVATIONS
Effective screening is not available for PDAC, and most patients present with locally advanced (30%-35%) or metastatic (50%-55%) disease at diagnosis. A multidisciplinary management approach is recommended. Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels. For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months, compared with 35 months for single-agent gemcitabine (stratified hazard ratio for death, 0.64 [95% CI, 0.48-0.86]; P = .003). Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease. For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiation is an option for definitive locoregional disease control. For patients with advanced (locally advanced and metastatic) PDAC, multiagent chemotherapy regimens, including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil, all have a survival benefit of 2 to 6 months compared with a single-agent gemcitabine. For the 5% to 7% of patients with a BRCA pathogenic germline variant and metastatic PDAC, olaparib, a poly (adenosine diphosphate [ADB]-ribose) polymerase inhibitor, is a maintenance option that improves progression-free survival following initial platinum-based therapy.
CONCLUSIONS AND RELEVANCE
Approximately 60 000 new cases of PDAC are diagnosed per year, and approximately 50% of patients have advanced disease at diagnosis. The incidence of PDAC is increasing. Currently available cytotoxic therapies for advanced disease are modestly effective. For all patients, multidisciplinary management, comprehensive germline testing, and integrated supportive care are recommended.
Topics: Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Combined Modality Therapy; Early Detection of Cancer; Humans; Incidence; Neoadjuvant Therapy; Pancreatectomy; Pancreatic Neoplasms
PubMed: 34547082
DOI: 10.1001/jama.2021.13027 -
Annual Review of Pathology Jan 2023Pancreatic ductal adenocarcinoma (PDAC) features a prominent stromal microenvironment with remarkable cellular and spatial heterogeneity that meaningfully impacts... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) features a prominent stromal microenvironment with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology and treatment resistance. Recent advances in tissue imaging capabilities, single-cell analytics, and disease modeling have shed light on organizing principles that shape the stromal complexity of PDAC tumors. These insights into the functional and spatial dependencies that coordinate cancer cell biology and the relationships that exist between cells and extracellular matrix components present in tumors are expected to unveil therapeutic vulnerabilities. We review recent advances in the field and discuss current understandings of mechanisms by which the tumor microenvironment shapes PDAC pathogenesis and therapy resistance.
Topics: Humans; Drug Resistance, Neoplasm; Tumor Microenvironment; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 36130070
DOI: 10.1146/annurev-pathmechdis-031621-024600 -
Best Practice & Research. Clinical... 2022Pancreatic cancer is one of the deadliest malignancies. Therefore, there is an urgent need to detect pancreatic cancer in an earlier stage to improve outcomes. A variety... (Review)
Review
Pancreatic cancer is one of the deadliest malignancies. Therefore, there is an urgent need to detect pancreatic cancer in an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance programs. Surveillance programs have shown potential to improve outcomes, but have important risks such as overtreatment. In this review we will discuss the definitions and epidemiology of hereditary pancreatic cancer, recommendations for genetic testing and participation in surveillance. Important aspects are differences in surveillance strategies, target lesions, and potential benefits and harms of surveillance. Lastly we will highlight future directions for research and improvement of care for individuals at high-risk of pancreatic cancer.
Topics: Carcinoma; Genetic Predisposition to Disease; Humans; Neoplastic Syndromes, Hereditary; Pancreatic Neoplasms; Risk Factors
PubMed: 35988957
DOI: 10.1016/j.bpg.2021.101783 -
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 -
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 -
World Journal of Gastroenterology Oct 2022Acinar cell carcinoma (ACC) is a rare pancreatic malignancy with distinctive clinical, molecular, and morphological features. The long-term survival of ACC patients is... (Review)
Review
Acinar cell carcinoma (ACC) is a rare pancreatic malignancy with distinctive clinical, molecular, and morphological features. The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients. As there are no significant patient series about ACCs, our understanding of this illness is mainly based on case reports and limited patient series. Surgical resection is the treatment of choice for patients with the disease restricted to one organ; however, with recent breakthroughs in precision medicine, medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon. There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible. As a result of shared genetic alterations, ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas. The role of neoadjuvant or adjuvant chemoradiotherapy has not been established. This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer.
Topics: Humans; Carcinoma, Acinar Cell; Pancreatic Neoplasms; Immunohistochemistry; Mutation
PubMed: 36353206
DOI: 10.3748/wjg.v28.i40.5827 -
Updates in Surgery Feb 2022Multimodal treatment including surgery and chemotherapy is considered the gold standard treatment of pancreatic cancer by most guidelines. Neoadjuvant therapy (NAT) has... (Review)
Review
Multimodal treatment including surgery and chemotherapy is considered the gold standard treatment of pancreatic cancer by most guidelines. Neoadjuvant therapy (NAT) has been seen as a possible treatment option for resectable, borderline resectable and locally advanced PaC. The aim of this paper is to offer a state-of-the-art review on neoadjuvant treatments in the setting of pancreatic ductal adenocarcinoma. A systematic literature search was performed using PubMed, Cochrane, Web of Science and Embase databases, in order to identify relevant studies published up to and including July 2021 that reported and analyzed the role of neoadjuvant therapy in the setting of pancreatic carcinoma. Most authors are concordant on the strong role of neoadjuvant therapy in the setting of borderline resectable pancreatic cancers. Recent randomized trials demonstrated improvement of R0 rate and survival after NAT in this setting. Patients with locally advanced cancers may become resectable after NAT, with better results than those obtained with palliative therapies. Even in the setting of resectable cancers, NAT is being evaluated by ongoing randomized trials. Chemotherapy regimens in the setting of NAT and response to NAT are discussed. NAT has an important role in the multimodal treatment of patients with borderline resectable pancreatic cancer. It has a role in patients with locally advanced tumors as it can allow surgical resection in a relevant proportion of patients. For resectable pancreatic cancers, the role of NAT is under evaluation by several randomized trials.
Topics: Carcinoma, Pancreatic Ductal; Combined Modality Therapy; Humans; Neoadjuvant Therapy; Pancreatic Neoplasms
PubMed: 34628591
DOI: 10.1007/s13304-021-01186-1 -
Pancreas Mar 2021Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are... (Review)
Review
Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.
Topics: Artificial Intelligence; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Genomics; Humans; Interdisciplinary Communication; Pancreatic Neoplasms; Prognosis; Survival Analysis
PubMed: 33835956
DOI: 10.1097/MPA.0000000000001762