How fibrosis influences imaging and surgical decisions in pancreatic cancer

Erkan, Mert; Hausmann, Simone; Michalski, Christoph; Schlitter, Anna Melissa; Fingerle, Alexander A.; Dobritz, Martin; Frieß, Helmut; Kleeff, Jörg

doi:10.3389/fphys.2012.00389

Cited by 46 publications

(41 citation statements)

References 129 publications

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“…1) [7–9]. It is encountered as “stickiness” during surgery presenting technical challenges for achieving negative resection margins, which is currently the only chance of cure [10]. Only 20% of patients present at an operative stage in their disease, making effective chemotherapy crucial in the PDAC treatment armamentarium https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq.…”

Section: Introductionmentioning

confidence: 99%

The role of stromal cancer-associated fibroblasts in pancreatic cancer

et al. 2017

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6. The role of downstream signaling pathways including JAK/STAT, mTOR, sonic hedge hog (SHH), and NFkB have also been shown to play an important function in PDAC-CAF cross talk. The role of autophagy and other metabolic effects on each cell type within the tumor have also been proposed to play roles in facilitating CAF secretory function and enhancing tumor growth in a low-glucose microenvironment. Targeting the stroma has gained interest with multiple preclinical and clinical trials targeting SHH, JAK2, and methods of either exploiting the secretory capability of CAFs to enhance drug delivery or inhibiting it to prevent its influence on cancer cell chemoresistance. This review summarizes the most recent progress made in understanding stromal formation; its contribution to tumor proliferation, invasion, and metastasis; its role in chemoresistance; and potential therapeutic strategies on the horizon.

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Section: Introductionmentioning

confidence: 99%

The role of stromal cancer-associated fibroblasts in pancreatic cancer

et al. 2017

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“…Pancreatic fibrosis is often associated with chronic pancreatitis, pancreatic ductal cancer, or inflammatory pseudotumor. Since pancreatic fibrosis may affect decisions of surgical interventions and prognosis in such pathologies, it may be worthwhile to optimize the MRE technique to exploit information concerning pancreatic fibrosis reflected by its stiffness.…”

mentioning

confidence: 99%

Feasibility of magnetic resonance elastography for the pancreas at 3T

Itoh

Takehara

Kawase³

et al. 2015

Magnetic Resonance Imaging

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“…The intense non-neoplastic stromal reaction accounts for the scirrhous and fi rm macroscopic aspect, and is responsible for the low vascular density, which leads to the radiological detection as a hypovascular mass [ 15 ].…”

Section: Microscopymentioning

confidence: 99%

Ductal Adenocarcinoma

D’Onofrio¹,

Capelli²,

Robertis³

et al. 2014

Imaging and Pathology of Pancreatic Neoplasms

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PathologyDuctal adenocarcinoma is a malignant epithelial neoplasm with glandular (ductal) differentiation, without a predominant component of any other types of carcinoma [ 7 ].Sixty to seventy percent of ductal adenocarcinomas is located in the pancreatic head, 30 % in the body and tail, and 5 % involve the whole organ. Multifocal disease has been reported as well as synchronous or metachronous carcinomas.Carcinomas of the pancreatic head tend to cause symptoms such as painless jaundice, acute pancreatitis, and epigastric pain that radiates to the back.Carcinomas of the body-tail of the pancreas often present with unexplained weight loss, back pain, or distant metastases.Sudden onset of diabetes mellitus may be the fi rst sign of pancreatic cancer. 2Carcinomas of the pancreatic head are usually diagnosed earlier and are more often resectable than carcinomas that involve the body-tail.Surgically resected carcinomas of the pancreatic head are generally signifi cantly smaller than the tumors of the body and tail (2-3 cm versus 5-7 cm, respectively). MacroscopyOn the cut surface, the tumor usually appears as a solid fi rm mass with infi ltrative, indefi nable margins, whitish color, and hard consistency.The tumor is often surrounded by a phlogistic fi brous "cuff," derived from a focal peritumoral pancreatitis, making it sometimes hard to identify the actual dimensions of the tumor, both at imaging and macroscopically.Extensive areas of hemorrhage and necrosis with cystic cavitation are uncommon, but microscopic foci are not so uncommon.Carcinomas of the pancreatic head, with the exception of those arising in the uncinate process, almost always infi ltrate both the common bile duct and Wirsung's duct, leading to a variable degree of stenosis and upstream dilation (radiological "double-duct sign"). This causes jaundice and upstream obstructive pancreatitis, which could lead to chronic pancreatitis, characterized by the presence of fi brotic or fi bro-adipous components, associated with a variable degree of acinar cells atrophy, with duct dilatation and retention cysts formation.The involvement of duodenum and/or Vater's ampulla, frequently found in the carcinomas of the pancreatic head, causes retraction of the intestinal wall, and eventually mucosal ulceration.Invasion and thrombosis of large peripancreatic vessels, such as the splenic vein, are frequently observed in bodytail carcinomas.The pathological evaluation of the retroperitoneal resection margin provides the most important information about local recurrence and patient survival. This margin is defi ned as the peripancreatic adipose tissue behind the head of the pancreas, which is located ventral and lateral, in respect to the superior mesenteric artery [ 8 -11 ].When the tumor involves the celiac trunk or the superior mesenteric artery, it is considered unresectable; so, this involvement is rarely present in surgical pathology specimens. A focal and partial, noncircumferential, adhesion of the posterior pancreatic surface to the mesenteric vein may justify ...

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How fibrosis influences imaging and surgical decisions in pancreatic cancer

Cited by 46 publications

References 129 publications

The role of stromal cancer-associated fibroblasts in pancreatic cancer

The role of stromal cancer-associated fibroblasts in pancreatic cancer

Feasibility of magnetic resonance elastography for the pancreas at 3T

Ductal Adenocarcinoma

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