Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas.
TL;DR: The working group has revised the guidelines regarding prediction of invasive carcinoma and high-grade dysplasia, surveillance, and postoperative follow-up of IPMN and includes updated information and recommendations based on the current understanding.
About: This article is published in Pancreatology.The article was published on 2017-09-01. It has received 1104 citations till now.
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TL;DR: This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy.
Abstract: This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. Research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. Recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to bring breakthroughs seen for other cancer sites.
951 citations
TL;DR: A conservative approach is recommended for asymptomatic MCN and IPMN, and Lifelong follow-up of IPMN is recommended in patients who are fit for surgery.
Abstract: Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring 5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
712 citations
University of California, San Francisco1, University of South Florida2, University of Michigan3, University of Tennessee Health Science Center4, Northwestern University5, Vanderbilt University6, Seattle Cancer Care Alliance7, City of Hope National Medical Center8, Duke University9, University of Colorado Boulder10, Ohio State University11, University of California, Los Angeles12, Fox Chase Cancer Center13, Harvard University14, Roswell Park Cancer Institute15, Case Western Reserve University16, Washington University in St. Louis17, University of Nebraska Medical Center18, Yale Cancer Center19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Johns Hopkins University23, University of Texas Southwestern Medical Center24, University of Alabama at Birmingham25, Memorial Sloan Kettering Cancer Center26, University of Utah27, Stanford University28, University of Pennsylvania29, University of Texas MD Anderson Cancer Center30, Brigham and Women's Hospital31, National Comprehensive Cancer Network32
Abstract: Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.
402 citations
TL;DR: Current and emerging imaging modalities that are critical to identifying early, potentially curable PDAC in high-risk cohorts on surveillance are discussed.
370 citations
TL;DR: The ability to perform high-resolution profiling of the transcriptomic changes that occur during multistep progression of cystic PDAC precursors to cancer is demonstrated and might be a useful substrate to identify targets for cancer interception.
Abstract: Purpose: Early detection of pancreatic ductal adenocarcinoma (PDAC) remains elusive. Precursor lesions of PDAC, specifically intraductal papillary mucinous neoplasms (IPMNs), represent a bona fide pathway to invasive neoplasia, although the molecular correlates of progression remain to be fully elucidated. Single-cell transcriptomics provides a unique avenue for dissecting both the epithelial and microenvironmental heterogeneities that accompany multistep progression from noninvasive IPMNs to PDAC. Experimental Design: Single-cell RNA sequencing was performed through droplet-based sequencing on 5,403 cells from 2 low-grade IPMNs (LGD-IPMNs), 2 high-grade IPMNs (HGD-IPMN), and 2 PDACs (all surgically resected). Results: Analysis of single-cell transcriptomes revealed heterogeneous alterations within the epithelium and the tumor microenvironment during the progression of noninvasive dysplasia to invasive cancer. Although HGD-IPMNs expressed many core signaling pathways described in PDAC, LGD-IPMNs harbored subsets of single cells with a transcriptomic profile that overlapped with invasive cancer. Notably, a proinflammatory immune component was readily seen in low-grade IPMNs, composed of cytotoxic T cells, activated T-helper cells, and dendritic cells, which was progressively depleted during neoplastic progression, accompanied by infiltration of myeloid-derived suppressor cells. Finally, stromal myofibroblast populations were heterogeneous and acquired a previously described tumor-promoting and immune-evading phenotype during invasive carcinogenesis. Conclusions: This study demonstrates the ability to perform high-resolution profiling of the transcriptomic changes that occur during multistep progression of cystic PDAC precursors to cancer. Notably, single-cell analysis provides an unparalleled insight into both the epithelial and microenvironmental heterogeneities that accompany early cancer pathogenesis and might be a useful substrate to identify targets for cancer interception. See related commentary by Hernandez-Barco et al., p. 2027
223 citations
Cites background from "Revisions of international consensu..."
...To guide clinicians, several radiologic guidelines have been reported and progressively updated (3,42,43)....
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...1% (range, 1181%) and should be surgically treated (3)....
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...To guide clinicians with identifying IPMNs harboring HGD or PDAC, several radiological “high risk” or “worrisome features” (so-called Sendai and Fukuoka criteria) have been proposed (3)....
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References
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TL;DR: The present guidelines include recent information and recommendations based on the current understanding, and highlight issues that remain controversial and areas where further research is required.
2,053 citations
"Revisions of international consensu..." refers background in this paper
...Early on, the malignant potential of this entity led to surgical resection of most pancreatic cysts, and although in very few centers this continues to be the case, following the publication of the International Association of Pancreatology (IAP) Sendai guidelines in 2006 [1] and the subsequ ent Fukuoka guidelines in 2012 [2], a more conservative attitude is followed....
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...There are considerable differences in the proportio ns of each type and the risks of invasive carcinoma and HGD [1-19]....
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TL;DR: Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN, and some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases.
1,912 citations
"Revisions of international consensu..." refers background in this paper
...Early on, the malignant potential of this entity led to surgical resection of most pancreatic cysts, and although in very few centers this continues to be the case, following the publication of the International Association of Pancreatology (IAP) Sendai guidelines in 2006 [1] and the subsequ ent Fukuoka guidelines in 2012 [2], a more conservative attitude is followed....
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...There are considerable differences in the proportio ns of each type and the risks of invasive carcinoma and HGD [1-19]....
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TL;DR: Of tested markers, cyst fluid CEA is the most accurate test available for the diagnosis of mucinous cystic lesions of the pancreas.
1,253 citations
Johns Hopkins University1, Osaka Medical College2, Memorial Sloan Kettering Cancer Center3, Wayne State University4, LSU Health Sciences Center Shreveport5, McGill University6, Tohoku University7, Japanese Foundation for Cancer Research8, University of Kiel9, Dartmouth College10, University of Amsterdam11, Saitama Medical University12, Kagoshima University13
TL;DR: The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms.
Abstract: Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.
991 citations
"Revisions of international consensu..." refers background in this paper
...grade IPMNs of gastric type [191], it may be preferable to report that “no in-situ or invasive carcinoma is identified; intraductal/...
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TL;DR: It is suggested that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.
Abstract: The Peutz-Jeghers syndrome is an autosomal dominant hereditary disease characterized by hamartomatous polyps of the gastrointestinal tract and by mucocutaneous melanin deposits. The frequency of cancer in this syndrome has not been studied extensively. Therefore, we investigated 31 patients with the Peutz-Jeghers syndrome who were followed from 1973 to 1985. All cases of cancer were verified by histopathological review. Cancer developed in 15 of the 31 patients (48 percent)--gastrointestinal carcinomas in 4, nongastrointestinal carcinomas in 10, and multiple myeloma in 1. In addition, adenomatous polyps of the stomach and colon occurred in three other patients. The cancers were diagnosed when the patients were relatively young, but after the Peutz-Jeghers syndrome had been diagnosed (interval between diagnoses, 25 +/- 20 years; range, 1 to 64). According to relative-risk analysis, the observed development of cancer in the patients with the syndrome was 18 times greater than expected in the general population (P less than 0.0001). Our results suggest that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.
819 citations
"Revisions of international consensu..." refers background in this paper
...5e10-fold) [236,237], familial atypical mole malignant melanoma syndrome (relative risk, 9e47-fold) [238], and PeutzJeghers syndrome (relative risk, 132-fold) [239]....
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