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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 -
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 -
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 -
Polski Przeglad Chirurgiczny Apr 2018The only way to cure the patient with adenocarcinoma of the pancreas (RT) is surgical excision of the tumor. The standard surgical treatment of resectable pancreatic... (Review)
Review
The only way to cure the patient with adenocarcinoma of the pancreas (RT) is surgical excision of the tumor. The standard surgical treatment of resectable pancreatic carcinoma is considered the classic pancreatoduodenectomy (PD) with the Kausch- Whipple procedure, or the pylorus-preserving PD with the Traverso-Longmire method. The most difficult technically and at the same time the most important PD stage from an oncological point of view is the separation of the head of the pancreas from the superior mesenteric artery. Over the last decades several PD modifications have been developed, focusing on this maneuver in the early phase of the operation, i.e. before the pancreas is cut (an irreversible stage of the procedure). These procedures in the English literature are called "artery-first approach" or "SMA-first approach". The term "mesopancreas" was created. Complete removal of the mesopancreas together with the proximal part of the jejunum is considered an R0 resection in the case of a tumor of the head of the pancreas with direct or indirect vascular invasion, or metastases to regional lymph nodes, and in English literature it is referred to as pancreatoduodenectomy with systematic mesopancreas dissection (SMDPD). Distal resection of the pancreas (DRT) due to cancer, is associated with a high percentage of positive margins, insufficient number of removed lymph nodes, low survival rates. A new technique was developed - a radical proximal-distal modular pancreatosplenectomy (RAMPS). In RAMPS, surgical operations proceed from the side of the pancreas head towards the tail, the pancreas is cut early, and the splenectomy is performed at the final stages of the procedure. Currently, following the PD model, attempts are made to further modify the original RAMPS technique, especially in the direction of SMA-first approach. In patients with borderline resectable pancreatic tumors or locally advanced tumors, after neoadjuvant treatment, a technique of radical resection with preservance of arterial vessels - "the TRIANGLE operation" has been elaborated. Despite the tremendous progress of surgical techniques, RT is still detected too late in the phase preventing effective resection.
Topics: Adenocarcinoma; Humans; Pancreatic Neoplasms; Pancreaticoduodenectomy
PubMed: 29773761
DOI: 10.5604/01.3001.0011.7493 -
Gastroenterology Clinics of North... Sep 2022Individuals at increased risk of developing pancreatic cancer, including those with a significant family history of the disease and those with pancreatic cancer... (Review)
Review
Individuals at increased risk of developing pancreatic cancer, including those with a significant family history of the disease and those with pancreatic cancer susceptibility gene variants, can benefit from pancreas surveillance. Most pancreatic cancers diagnosed during surveillance are early-stage and such patients can achieve long-term survival. Determining who should undergo pancreas surveillance is still a work-in-progress, but the main tools clinicians use to estimate an individual's risk of pancreatic cancer are patient's age, the extent of their family history of pancreatic cancer, and whether or not they have a pancreatic cancer susceptibility gene mutation.
Topics: Carcinoma; Early Detection of Cancer; Genetic Predisposition to Disease; Humans; Pancreatic Neoplasms; Risk Factors
PubMed: 36153110
DOI: 10.1016/j.gtc.2022.06.006 -
Deutsches Arzteblatt International May 2014Ductal adenocarcinoma of the pancreas is the fourth most common cause of death from cancer in men and women in Germany: about 15 000 persons die of this disease each... (Review)
Review
BACKGROUND
Ductal adenocarcinoma of the pancreas is the fourth most common cause of death from cancer in men and women in Germany: about 15 000 persons die of this disease each year.
METHOD
The S3 guideline on exocrine pancreatic carcinoma was updated with the aid of systematic literature reviews on the surgical, neoadjuvant, and adjuvant treatment of ductal pancreatic carcinoma, and on treatment in the metastatic stage. These reviews covered the periods 2002 to February 2012 (for radiotherapy) and 2006 to August 2011 (for all other topics).
RESULTS
The criteria for borderline resectable pancreatic tumors are the same as those of the guidelines of the National Comprehensive Cancer Network. Preoperative biliary drainage with a stent is recommended only if cholangitis is present or if a planned operation cannot be performed soon after the diagnosis is made. When a pancreatic carcinoma is resected, at least 10 regional lymph nodes should be excised, and the ratio of affected to excised nodes should be documented in the pathology report. Gemcitabine and 5-fluorouracil are recommended for adjuvant therapy. Neither of these drugs is preferred over the other; if the one initially given is poorly tolerated, the other one should be given instead. When gemcitabine and erlotinib are given for palliative treatment, erlotinib should be given for no longer than 8 weeks if no skin rash develops. In selected patients, the folfirinox protocol yields markedly better results than gemcitabin. Moreover, the new combination of nab-paclitaxel and gemcitabine can be used as first-line treatment. In the event of disease progression under first-line treatment, second-line treatment should be initiated.
CONCLUSION
In recent years, new chemotherapeutic protocols have brought about marked improvement in palliative care. Further trials are needed to determine whether the perioperative or adjuvant use of these protocols might also improve the outcome of surgical treatment with curative intent.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Germany; Humans; Laparoscopy; Medical Oncology; Palliative Care; Pancreatic Neoplasms
PubMed: 24980565
DOI: 10.3238/arztebl.2014.0396 -
Radiologia 2018Pancreatic carcinoma is becoming more common in our environment; the mortality rate for this tumor has barely changed over the last 20 years. Early diagnosis and... (Review)
Review
Pancreatic carcinoma is becoming more common in our environment; the mortality rate for this tumor has barely changed over the last 20 years. Early diagnosis and accurate staging are crucial to ensure an appropriate therapeutic approach, which should aim to improve survival in patients in whom complete resection is possible and to minimize surgical morbidity and mortality in those with a high risk of residual disease after the intervention. Various imaging techniques are used for tumor staging: multidetector computed tomography (CT), magnetic resonance imaging, positron emission tomography (PET)-CT, endoscopic ultrasound, and diagnostic laparoscopy. Currently, multidetector CT is the technique of choice for the study of pancreatic tumors; thus, this article aims to review the state of the art in staging adenocarcinoma of the pancreas, focusing mainly on the applications and limitations of this technique.
Topics: Humans; Neoplasm Metastasis; Neoplasm Staging; Pancreatic Neoplasms; Tomography, X-Ray Computed
PubMed: 29078990
DOI: 10.1016/j.rx.2017.08.004 -
Hematology/oncology Clinics of North... Aug 2015Familial pancreatic cancer (FPC) kindreds have at least 2 first-degree relatives with pancreatic ductal adenocarcinoma. Studies of FPC have focused on the discovery of... (Review)
Review
Familial pancreatic cancer (FPC) kindreds have at least 2 first-degree relatives with pancreatic ductal adenocarcinoma. Studies of FPC have focused on the discovery of genetic cause and on the management of those at genetically high risk. Research reveals that a half dozen known hereditary syndromes or genes are associated with increased risk of developing pancreatic cancer, the most prominent of which are BRCA2 and CDKN2A. Genetic risk assessment and testing is already available. Owing to limited experience worldwide, guidance is often based on expert opinion, although all agree that research is needed to improve the shaping of options.
Topics: Adenocarcinoma; Carcinoma; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; Humans; Pancreatic Neoplasms; Precision Medicine; Risk Factors
PubMed: 26226902
DOI: 10.1016/j.hoc.2015.04.007 -
World Journal of Gastroenterology Jun 2022Pancreatic carcinoma (PC) has one of the highest rates of cancer-related death worldwide. Except for surgery, adjuvant chemotherapy, chemoradiotherapy, and immunotherapy... (Review)
Review
Pancreatic carcinoma (PC) has one of the highest rates of cancer-related death worldwide. Except for surgery, adjuvant chemotherapy, chemoradiotherapy, and immunotherapy have shown various efficacies depending on the stage of the patient. We read the review "Current and emerging therapeutic strategies in pancreatic cancer: Challenges and opportunities" and offer some opinions that may improve its precision and completeness. This review presents a map of appropriate therapies for PC at different stages. Based on the clinical trial outcomes mentioned in the review, we evaluated the potential therapeutic options for PC and helped explain the contradictory efficacy between different programmed cell death protein 1/programmed cell death ligand 1 clinical trials, which may have resulted from the unique features of PC. Although R0 resection and adjuvant chemotherapy are still the gold standards for PC, new modalities, with or without clinical validation, are needed to establish more specific and precise treatments for PC.
Topics: Chemotherapy, Adjuvant; Humans; Neoadjuvant Therapy; Pancreatic Neoplasms; Precision Medicine
PubMed: 35979258
DOI: 10.3748/wjg.v28.i22.2523 -
World Journal of Gastroenterology Oct 2021Pancreatic carcinoma (PC) is one of the leading causes of cancer-related deaths worldwide. Despite early detection and advances in therapeutics, the prognosis remains... (Review)
Review
Pancreatic carcinoma (PC) is one of the leading causes of cancer-related deaths worldwide. Despite early detection and advances in therapeutics, the prognosis remains dismal. The outcome and therapeutic approach are dependent on the stage of PC at the time of diagnosis. The standard of care is surgery, followed by adjuvant chemotherapy. The advent of newer drugs has changed the landscape of adjuvant therapy. Moreover, recent trials have highlighted the role of neoadjuvant therapy and chemoradiotherapy for resectable and borderline resectable PC. As we progress towards a better understanding of tumor biology, genetics, and microenvironment, novel therapeutic strategies and targeted agents are now on the horizon. We have described the current and emerging therapeutic strategies in PC.
Topics: Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Chemotherapy, Adjuvant; Humans; Neoadjuvant Therapy; Pancreatectomy; Pancreatic Neoplasms; Tumor Microenvironment
PubMed: 34754153
DOI: 10.3748/wjg.v27.i39.6572