Precursor Lesions for Sporadic Pancreatic Cancer: PanIN, IPMN, and MCN

Distler, Marius; Aust, Daniela E.; Weitz, Jürgen; Pilarsky, Christian; Grützmann, Robert

doi:10.1155/2014/474905

Cited by 164 publications

(139 citation statements)

References 88 publications

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“…These precursor lesions are referred to as pancreatic intraepithelial neoplasia (PanIN). PanINs are lesions composed of mucin-producing epithelia with varying degrees of cytologic and architectural atypia that involve the small ducts of the pancreas [33]. PanINs can be flat (PanIN-1A), papillary without atypia (PanIN-1B), papillary with atypia (PanIN-2), or may even meet histopathologic criteria for carcinoma in situ (PanIN-3) [33].…”

Section: Solid Epithelial Tumorsmentioning

confidence: 99%

“…PanINs are lesions composed of mucin-producing epithelia with varying degrees of cytologic and architectural atypia that involve the small ducts of the pancreas [33]. PanINs can be flat (PanIN-1A), papillary without atypia (PanIN-1B), papillary with atypia (PanIN-2), or may even meet histopathologic criteria for carcinoma in situ (PanIN-3) [33]. PanIN-3 is associated with severe architectural and cytonuclear abnormalities, but invasion through the basement membrane is absent.…”

Section: Solid Epithelial Tumorsmentioning

confidence: 99%

“…Although much less common than PanINs, MCNs can also be precursors of infiltrating ductal adenocarcinoma of the pancreas [33]. As with PanINs, MCNs progress through stages of increasing dysplasia, from mucinous cystadenoma to borderline mucinous cystic neoplasm to mucinous cystic neoplasm with in situ carcinoma, finally to reach the stage of invasive adenocarcinoma.…”

Section: Mucinous Cystic Neoplasms (Mcns)mentioning

confidence: 99%

See 2 more Smart Citations

The Pathogenesis, Diagnosis, and Management of Pancreatic Cancer

Malhotra¹,

Ahn²,

Bloomston

2015

J Gastrointest Dig Syst

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Pancreatic cancer is an aggressive and devastating disease accounting for 44,000 new cases per year in US. It is characterized by invasiveness, rapid progression and profound resistance to treatment. The majority of cases are diagnosed above age 65 with about 60% of cases at an advanced stage and 5 year survival less than 10%. Advances in molecular biology have greatly improved our understanding of pathogenesis of pancreatic cancer. Many patients have mutations of K-ras oncogene and various tumor suppressor genes are also investigated. Radical surgery remains the only curative treatment option for pancreatic cancer in early stages. For locally advanced, unresectable and metastatic disease, treatment is palliative, in form of adjuvant or neoadjuvant chemotherapy with or without radiotherapy. Gemcitabine based combinations have essentially failed to provide a substantial prolongation of survival and constitute treatment option only in patients with a good performance status. This article provides an overview of epidemiology; risks factors, molecular genetics, biomarkers, diagnostic modality and evidence based therapeutic options for resectable and palliative options for unresectable disease. Keywords: Pancreatic cancer; Diagnosis EpidemiologyPancreatic cancer is one of the most lethal human cancers and is the fourth leading cause of cancer-related deaths in the United States [1,2]. It is estimated that 38,460 of 45,220 people diagnosed with pancreatic cancer in the United States in 2013 will die of their disease, representing approximately 6% of total U.S. cancer deaths [1]. Typically a cancer of the elderly, only 13% of cases occur in patients younger than 55 years, whereas 69% of cases occur in those older than 65. There is a slight predilection for men over women in most countries. Furthermore the incidence of pancreatic cancer in the United States increased from 1999 to 2008, possibly because of the increasing prevalence of obesity and other unknown factors [1,[3][4][5]. Mortality rates have remained largely unchanged [6].The etiology of pancreatic cancer remains unclear, thus making specific risk factors allusive. Still, accepted associated risk factors include smoking, family history of chronic pancreatitis, advancing age, male gender, diabetes mellitus, obesity, non-O blood group, occupational exposures (to chlorinated hydrocarbon solvents and nickel), African American ethnic origin, a high-fat diet, diets high in meat and low in vegetables and folate, and possibly Helicobacter pylori infection and periodontal disease [7]. Findings of preliminary studies suggest that metformin could protect against development of pancreatic cancer [8,9]. A retrospective analysis of 302 patients with pancreatic cancer and diabetes found that metformin use was associated with increased survival at 2 years (30.1% vs. 15.4%; P=0.004) and increased overall survival (OS) (15.2 months vs. 11.1; P=0.009). The OS difference was significant only in patients without distant metastases and remained significant when insulin user...

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Section: Solid Epithelial Tumorsmentioning

confidence: 99%

Section: Solid Epithelial Tumorsmentioning

confidence: 99%

Section: Mucinous Cystic Neoplasms (Mcns)mentioning

confidence: 99%

See 1 more Smart Citation

The Pathogenesis, Diagnosis, and Management of Pancreatic Cancer

Malhotra¹,

Ahn²,

Bloomston

2015

J Gastrointest Dig Syst

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“…[5][6][7] Three precursors have been characterized, namely, pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms.…”

Section: Pancreatic Cancermentioning

confidence: 99%

Pancreatic cancer vaccine: a unique potential therapy

Cappello¹,

Principe²,

Novelli³

2015

GICTT

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Pancreatic ductal adenocarcinoma (PDA) is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological checkpoints. Keywords: pancreatic cancer, vaccines, T-cells, antibody, immunotherapy Pancreatic cancerAlthough lung, breast, prostate, and colorectal cancers are considered to be the "big four" cancer types in the USA, pancreas and liver cancers are expected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related deaths by 2030, respectively.1 Pancreatic ductal adenocarcinomas (PDAs) arise from the exocrine pancreas and account for 95% of pancreatic cancers. In the USA, there were an estimated 48,960 cases of new-onset pancreatic cancer in 2015, which led to 40,560 deaths, with a 5-year survival rate of ∼7%.3 PDA is nearly universally lethal; ,20% of patients are suitable candidates for surgery at the time of diagnosis, and the median survival rate is 3.5 months and 12.6 months for nonresected patients and resected patients, respectively.2,4 PDA evolves from noninvasive precursor lesions that do not invade the basement membrane. [5][6][7] Three precursors have been characterized, namely, pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms.

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“…There are two primary types of precancerous pancreatic cystic lesions, intraductal papillary mucinous neoplasms (IPMN), and mucinous cystic neoplasms (MCN) 8,9 , that could be treated surgically, achieving a high cure rate. However, the majority of cystic pancreatic lesions have no malignant potential and do not require surgery.…”

mentioning

confidence: 99%

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy

et al. 2017

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Pancreatic cancers are usually detected at an advanced stage and have poor prognosis. About one fifth of these arise from pancreatic cystic lesions. Yet not all lesions are precancerous, and imaging tools lack adequate accuracy for distinguishing precancerous from benign cysts. Therefore, decisions on surgical resection usually rely on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Unfortunately, cyst fluid often contains few cells, and fluid chemical analysis lacks accuracy, resulting in dire consequences, including unnecessary pancreatic surgery for benign cysts and the development of cancer. Here, we report an optical spectroscopic technique, based on a spatial gating fibre-optic probe, that predicts the malignant potential of pancreatic cystic lesions during routine diagnostic EUS-FNA procedures. In a double-blind prospective study in 25 patients, with 14 cysts measured in vivo and 13 postoperatively, the technique achieved an overall accuracy of 95%, with a 95%confidence interval of 78–99%, in cysts with definitive diagnosis.

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Precursor Lesions for Sporadic Pancreatic Cancer: PanIN, IPMN, and MCN

Cited by 164 publications

References 88 publications

The Pathogenesis, Diagnosis, and Management of Pancreatic Cancer

The Pathogenesis, Diagnosis, and Management of Pancreatic Cancer

Pancreatic cancer vaccine: a unique potential therapy

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy

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