الفهرس 
Pathology of pancreatic diseasesOnly 14 pages are availabe for public view
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Abstract
ROLE OF CONTRAST ENHANCED ENDOSCOPIC ULTRASOUND IN PANCREATIC DISEASES
The indications of contrast enhanced endoscopic ultrasound in pancreatic diseases are acute pancreatitis, pancreatic cysts, neoplasms e.g. benign pancreatic tumor & pancreatic cancer (Ravi Sharma et al., 2014).
Acute pancreatitis:-
In acute pancreatitis, contrast enhanced endoscopic ultrasound (CE-EUS) may help to identify and delineate necrotic areas, which do not enhance at the very early stage (Lopez et al., 2010). The lack of nephrotoxicity of CE-EUS contrast agents is of particular importance in patients with pancreatitis because of the fact that most severely ill patients develop renal failure. In those cases, CT contrast enhancers are contraindicated. Focal mass-forming pancreatitis (Zamboni et al., 2006) and autoimmune pancreatitis (Ignee et al., 2011) have similar or stronger enhancement to or than the normal pancreatic parenchyma which is of importance when it comes to a differential diagnosis for ductal adenocarcinoma. The homogenous increased contrast enhancing behavior of the pancreas can be a sign of diffuse autoimmune pancreatitis and might led the investigator into the right direction (Ignee et al., 2011).
The acute pancreatitis has an iso- or hypervascular appearance (Vilmann et al., 2012) and shows regular vascularization with the detection of venous vessels (Schulze et al., 2006).
Figure 16 : The contrast enhanced endoscopic ultrasound in (A) acute interstitial pancreatitis: shows diffusely increased echogenicity. (B) Necrotizing pancreatitis: shows multiple hypoechoic areas (arrows). (C) Necrotizing pancreatitis:shows multiple hyperechoic areas (bold arrows). Peripancreatic echogenicity suggestive of extrapancreatic necrosis also seen (open arrows). (D) Necrotizing pancreatitis: shows mixed hyperechoic (black arrows) and hypoechoic areas (white arrows) (Ravi Sharma et al., 2014).
Figure 17 : The contrast enhanced endoscopic ultrasound in necrotizing pancreatitis: mixed shows hyperechoic and hypoechoic areas (open arrows). Peripancreatic echogenicity, soft on EUS elastography, suggestive of extrapancreatic necrosis (EPN) also seen (bold arrows) (Ravi Sharma et al., 2014).
Pancreatic cysts:
CE-EUS improves the ultrasonographic differential diagnosis between pseudocysts and mucinous cystic neoplasia [mucinous cystadenoma, intraductal papillary mucinous neoplasms (IPMNs)] of the pancreas by accurately revealing microvascularization of intralesional septa and parietal nodules (Megibow et al., 2007). Pseudocysts typically contain non-vascularized material (debris), with the exception of transversing (large) vessels, which are frequently found in the early stages (Ignee et al., 2010).
Pseudocysts do not show any signal on CE-EUS and remain completely non-enhancing in all phases, even when they are heterogeneous on US. IPMNs are divided into main-duct and side branch-duct types with different prognosis depending on the age of patients and comorbidity (Megibow et al., 2007).
CE-EUS is helpful in differentiating perfused (nodules) from non-perfused (clots) regions. Serous oligo-and macrocystic cystadenomas are benign cystic lesions, typically with a lobulated appearance with thin walls and centrally orientated arteries. CE-EUS enables the investigators to discriminate pseudocysts from tumorous pancreatic lesions because of the vascularisation behaviour described above. However, the discrimination of different benign cystic lesions or even of benign from malignant cystic lesions is not so easy. If no typical cystic lesions (per example microcystic serous cystadenoma can already be safely diagnosed by the anatomic structure) have to be discriminated, every enhancing cystic lesion can be further discriminated by using endoscopic fine needle aspiration (FNA). Beside the cytology and the estimation of the carcinoembryonic antigen (CEA) level, the most important result is the analysis of the fluid. Mucinous cysts have a higher potential of malignancy and should be surgical treated if the patient’s condition allows (Ignee et al., 2010).
Serous microcystic neoplasia present typically as hyperenhancing masses in the arterial phase, owing to their abundant arterial vascularization and showed cystic wall and septae vascularization. Macrocystic mucinous cystadenoma showed a clear contrast enhancing effect in the thick cystic wall and included nodules (Ignee et al., 2008; Zamboni et al., 2009).
Figure 18 :The contrast enhanced endoscopic ultrasound shows macrocystic cystadenoma with contrast enhancing septae (Sharma et al., 2012).
Figure 19 :The contrast enhanced endoscopic ultrasound shows intraductal papillary mucinous neoplasm of the pancreas with perfused intraductular nodules (Dietrich et al., 2012).
Figure 20: The contrast enhanced endoscopic ultrasound shows series of different imaging methods of a macrocystic serous cystadenoma – diagnosis is based on the endoscopic fine-needle puncture with serous cystic fluid, low carcinoembryonic antigen level and benign cytology (Hocke et al., 2014).
Figure 21: The contrast-enhanced endoscopic ultrasound in low mechanical index shows mode in a patient with a pancreatic pseudocyst. Because of the echogenic material within the cyst a nodule cannot be excluded in B-mode ultrasound (Hocke et al., 2014).
Benign neoplasm of the pancreas:
Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) allows real-time perfusion imaging without Doppler-related artifacts, and visualizes not only parenchymal perfusion but also the microvasculature of the pancreas (Matsui et al., 2008). CEH-EUS is used in differentiating the pancreatic solid lesions from pancreatic cancer by imaging the microvasculature of the pancreas (Matsui et al., 2008).
The contrast enhanced endoscopic ultrasound (CE-EUS) has been reported to include differentiation of focal pancreatitis and carcinomas (Ignee et al., 2012), preoperative localization of pancreatic endocrine tumors (Ohno et al., 2010), differentiation of mural nodules in intraductal papillary mucinous neoplasms, and detection of malignant transformations (Ueda et al., 2013; Itoh et al., 2012).
Neuroendocrine tumors present typically as hyperenhancing masses in the arterial phase, owing to their abundant arterial vascularization (Ignee et al., 2008; Zamboni et al., 2009). It shows hyperintense signals in early phase and three of those maintained hyperintense signals in the late phase (Vilmann et al., 2012).
Figure 22: The CEH-EUS shows pancreatic neuroendocrine tumor. (A) The tumor shows a diffuse hyperintense echo signal in the early phase. (B) Hyperintensity was persistent in the late phase (Vilmann et al., 2012).
Figure 23: The contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) shows neuroendocrine tumour.
A. Conventional EUS demonstrates a hypoechoic lesion (arrowheads) with a round shape and a distinct margin in the body of the pancreas.
B. Contrast-enhanced harmonic EUS shows the lesion as a rather hypervascular heterogeneous mass with a clear margin and vessels protruding into the mass (arrows). In the arterial phase, the lesion was enhanced as a hypervascular homogeneous mass; this difference could enable the viewer to distinguish a neuroendocrine tumor from a ductal carcinoma in the pancreas (Itoh et al., 2012).
Figure 24: The contrast enhanced endoscopic ultrasound shows typically hyperenhancing neuroendocrine tumor of the pancreas (Zamboni et al., 2009).
Pancreatic cancer
The contrast enhanced endoscopic ultrasound (CE-EUS) evaluates vascularity using contrast agents to characterize the lesion(s) (Wallace et al., 2012; Brizzi et al., 2013; Lee et al., 2014). CE-EUS were reported by the sensitivity and the specificity of differentially diagnosing pancreatic adenocarcinoma to be 94% and 89%, respectively (Zhu et al., 2012). CE-EUS helps in visualizing the microvasculature of a pancreatic lesion to permit the characterization of intertumoral structures. This characterization can help in the diagnosis of pancreatic ductal adenocarcinoma in difficult cases by permitting the observation of hypovascularity, one of the signs of ductal adenocarcinoma (Ito et al., 2008; Napoleon et al., 2010).
CE-EUS, however, provided the possibility to analyze the macrovessels (arterioles and venoules) of the pancreas for neovascularization patterns. Contrast-Enhanced Doppler method reveals an irregular vessel system of the carcinoma without displaying venous vessels in adenocarcinomas in contrast to a netlike homogenous vessel system with both arterial and venous vessels in chronic pancreatitis (Ignee et al., 2011). The contrast-enhanced endoscopic ultrasound which was increased the sensitivity of endoscopic ultrasound in discriminating between focal pancreatitis and pancreatic cancer from 73 to 91% and the specificity from 83 to 93% (Hocke et al., 2006).
Ductal adenocarcinoma, the most common primary malignancy of the pancreas, is typically (about 90%) hypoenhancing in all phases because of the low mean vascular density (Kersting et al., 2009; Ignee et al., 2008). It showed irregular vascularization with only arterial and no venous vessels & shows to be a hypoperfused lesion, in comparison with the surrounding normal pancreatic parenchyma (Schulze et al., 2006).
Figure 25: The contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) shows pancreatic carcinoma.
A. Conventional EUS shows a hypoechoic lesion (arrowheads) with an indistinct margin in the head of the pancreas.
B. Contrast-enhanced harmonic EUS reveals the lesion as a hypovascular heterogeneous mass with the vessels (arrows) protruding into the cancer (Zhu et al., 2012).
Figure 26: The contrast enhanced endoscopic ultrasound shows typically hypoenhancing ductal adenocarcinoma of the pancreas (Ignee et al., 2011).
Figure 27: The contrast-enhanced endoscopic ultrasound shows a small hypoechoic mass in the pancreatic head without any color-Doppler signal, showing a notable early vascular flare after intravenous injection of an echo-contrast medium which suggests the neuroendocrine nature of the lesion (Hocke et al., 2006).
Figure 28: The contrast enhanced endoscopic ultrasound shows pancreatic adenocarcinoma. (A) The tumor shows a hypointense echo signal with fine branches in the early phase. (B) Persistent hypointensity was noted in the late phase (Mori et al., 2012).
SUMMARY AND CONCLUSION
Contrast enhancement involves the administration of an intravenous agent during the (endoscopic) ultrasound study. Contrast agents are microbubbles that respond to energy from sound waves in characteristic ways which aid in enhancing the distinctions between tissue types. They are categorized into first and second generation based on the capability for transpulmonary passage and the half-life in the human body.
Contrast-Enhanced endoscopic ultrasound (CE-EUS) is a newly established method which combines the advantage of high-resolution ultrasound (US) of internal organs with the administration of ultrasound contrast agents (UCAs).
The indications of contrast enhanced endoscopic ultrasound in pancreatic diseases are acute pancreatitis, pancreatic cysts, neoplasms e.g. benign pancreatic tumour and pancreatic cancer.
The lack of nephrotoxicity of CE-EUS contrast agents is of particular importance in patients with pancreatitis because of the fact that most severely ill patients develop renal failure. The contrast enhanced endoscopic ultrasound in acute pancreatitis appears as iso- or hypervascular and shows regular vascularization with the detection of venous vessels.
The use of contrast enhanced endoscopic ultrasound in pancreatic cancer is to evaluate vascularity using contrast agents to characterize the lesion(s). CE-EUS helps in visualizing the microvasculature of a pancreatic lesion to permit the characterization of intertumoral structures.
Further studies are needed to emphasize the role of contrast enhanced endoscopic ultrasound for the diagnosis of different pancreatic diseases.