Molecular biomarkers have the potential to improve the diagnostic work-up of pancreatic cystic lesions

Pancreatic cysts are increasingly diagnosed due to the widespread use of cross-sectional imaging, and some of these lesions harbor malignant potential. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are the major premalignant cystic neoplasms of the pancreas. A variety of diagnostic tools are used to predict the malignant potential of these cysts, but specificity and sensitivity are limited. Thus, many patients undergo unnecessary operations for benign cysts. Balancing the risks of watchful waiting with those of operative management is key in managing these lesions. During the last decade, genetic changes of pancreatic cysts have been examined extensively to estimate their malignant potential. In this review, we provide an overview of the latest molecular and genetic aspects of pancreatic cysts and how they may contribute to the differential diagnosis in patients with pancreatic cystic neoplasms.     

Management of the rare entity of primary pancreatic cystic neoplasms

Primary cystic neoplasms of the pancreas constitute a rare entity and are composed of a variety of neoplasms with a wide range of malignant potential. Approximately 90% of these lesions are serous cystic neoplasms or mucin-producing neoplasms. In contrast to serous cystadenomas which are nearly always benign, the mucinous cystic neoplasms represent a more diverse, heterogenous spectrum of related neoplasms. Intraductal papillary mucinous neoplasms manifest a much greater latent or overt malignant potential than other cystic neoplasms of the pancreas. The various subgroups of cystic neoplasms of the pancreas are evaluated and compared through a review of current literature. No symptoms or signs are pathognomonic for the cystic pancreatic neoplasms. While identification of a cystic tumor is relatively easy, the identification of the specific tumor type may be difficult. Most investigators agree that accurate differentiation of benign from malignant neoplasms can be made only at histopathologic examination of the entire resected segment of the pancreas. Because of the low mortality and low postoperative morbidity, surgical resection is indicated in all patients with cystic tumors.     

Multifocal intraductal papillary mucinous neoplasm of the pancreas-A case report

Cystic neoplasms of the pancreas are relatively rare, comprising 10 percent of pancreatic cysts and only 1 percent of pancreatic cancers. Cystic neoplasms include mucinous cystic neoplasms, serous cystadenomas, papillary cystic tumors, cystic islet cell tumors and intraductal papillary mucinous neoplasms of the pancreas （IPMNs）. IPMN was first described in 1982. It has been most commonly described in 60 to 70 years old males, and represents a relatively ＂new＂ but increasingly recognized disease. The improvement and widespread use of modern imaging equipments and heightened awareness of physicians contribute to the increasing incidence of IPMN. The majority of IPMNs are located in the pancreatic head （75%） while the rest involves the body/tail regions. Multifocal IPMNs have been hypothesized, but the true presence of multifocality is unknown. Here we present a 72-year- old male diagnosed with IPMN （carcinoma in situ） in the pancreatic head and a branch duct type IPMN （duct atypia） in the pancreatic body and tail. The patient underwent a Whipple intervention and a distal pancreatectomy. A three-year disease-free survival has been observed so far.     

胰腺癌的不典型64排螺旋CT影像表现

目的 分析胰腺癌的64排螺旋CT的不典型表现,以提高对该肿瘤的CT征象的认识水平.方法 回顾性分析经手术病理证实的缺乏典型CT征象的12例胰腺导管腺癌的64排螺旋CT资料.结果 12例均为胰腺导管腺癌.其中,中分化导管腺癌7例,中高分化导管腺癌1例;黏液腺癌1例;腺鳞癌3例.8例导管腺癌病灶中位于胰头及(或)钩突部7例,胰颈部1例,表现为等、低密度或囊实性肿块,增强后无明显强化;5例肿瘤呈明显外生性或有外生倾向;5例肿瘤远端胰管无扩张,2例出现胆总管和肝内胆管扩张,仅1例出现肿瘤远端胰腺萎缩.1例黏液腺癌CT平扫示胰头部5 cm囊性病灶,增强后仅囊性病灶下方少许实性部分轻度强化,体尾部胰管中度扩张(7 mmn),胆总管及邻近血管未受侵犯.3例腺鳞癌病灶中位于胰头2例,胰体部1例,肿块最大径3.0～4.5 cm,CT增强扫描胰腺实质期示3例病灶内均见液化坏死区,病灶远端胰管均轻度扩张(4～5 mm),胆总管和肝内胆管均未见扩张.结论 胰腺癌可出现不典型的CT影像表现,要注意与易混淆疾病进行鉴别诊断.     

Endosonography in the diagnosis and management of pancreatic cysts

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.     

Cystic tumors of the pancreas: Opportunities and risks

Pancreatic cystic neoplasms(PCNs) are a high prevalence disease. It is estimated that about 20% of the general population is affected by PCNs. Some of those lesions can progress till cancer, while others behave in a benign fashion. In particular intraductal papillary mucinousneoplasms of the pancreas can be considered as the pancreatic analogon to colonic polyps. Treatment of these precursor lesions at an early stage can potentially reduce pancreas cancer mortality and introduce a new "era" of preemptive pancreatic surgery. However, only few of those lesions have an aggressive behavior. The accuracy of preoperative diagnosis, i.e., the distinction between the various PCNs is around 60%, and the ability to predict the future outcome is also less accurate. For this reason, a significant number of patients are currently over-treated with an unnecessary, high-risk surgery. Furthermore, the majority of patients with PCN are on life-long follow-up with imaging modality, which has huge cost implications for the Health Care System for limited benefits considering that a significant proportion of PCNs are or behave like benign lesions. The current guidelines for the diagnosis and management of PCNs are more based on expert opinion than on evidence. For all those reasons, the management of cystic tumors of the pancreas remains a controversial area of pancreatology. On one hand, the detection of PCNs and the surgical treatment of pre-cancerous neoplasms can be considered a big opportunity to reduce pancreatic cancer related mortality. On the other hand, PCNs are associated with a considerable risk of under- or over- treatment of patients and incur high costs for the Health Care System.     

Mucinous cystic neoplasm of the pancreas during pregnancy: the importance of proper management

We describe a case of huge mucinous cystic tumor of the pancreas in a 26-year-old woman during pregnancy. Ultrasonography demonstrated a well-delimited cystic mass in the left upper abdominal quadrant, suggestive of benignity. Magnetic resonance imaging showed a large cystic mass resembling a mucinous cystic tumor of the pancreas. After this assessment the patient underwent surgical exploration and a huge cystic tumor of the pancreas was discovered. The tumor was enucleated and distal pancreatectomy was performed. The resected margin of the specimen was free of tumor. In this case report we discuss the management of mucinous pancreatic tumors during pregnancy and we briefly review the previously reported cases of mucinous pancreatic tumors in pregnant patients. We conclude that surgical resection of these tumors should be strongly considered in pregnancy. Removal of the tumor appears to be a safe procedure without harmful effects to the fetus.     

内镜诊治胰腺导管内乳头状粘液性肿瘤的应用

目的探讨胰腺导管内乳头状粘液性肿瘤(IPMN)的诊断、内镜下治疗,以提高对该疾病的认识及内镜对其诊断及治疗的意义。方法回顾性分析经内镜诊治的IPMN患者12例,总结并分析他们的一般情况、临床症状、影像学检查、实验室检查、内镜下治疗等方面资料。结果 12例IPMN患者以老年男性为主,无特异性临床表现,主要发生部位为胰头或钩突部,CT主要表现为囊实性低密度影,其内可有壁结节,胰管扩张伴或不伴胆管扩张,2例侵及胰腺实质。磁共振胰胆管造影(MRCP)主要表现为胰管扩张,胰腺萎缩,胰头部圆形高信号影。内镜下逆行胰胆管造影(ERCP)显示十二指肠乳头膨大,开口扩张,可见胶冻样粘液流出,胰管造影显示胰管全程扩张或胰头部囊状扩张,3例伴胆总管、肝内胆管扩张。9例行ERCP治疗,清除粘液栓并置入胰管支架,3例同时置入胆管支架。结论 IPMN是一种特殊类型的胰腺囊性疾病,影像学检查有其独特的表现,ERCP对其诊断及治疗有重要意义。     

Cystic pancreatic lesions: Current evidence for diagnosis and treatment

Abstract

Pancreatic cystic neoplasms are detected at an increasing frequency due to an increased use and quality of abdominal imaging. There are well known differential diagnostic difficulties concerning these lesions. The aim is to review current literature on the diagnostic options and the following treatment for cystic lesions in the pancreas focusing on serous cystadenomas, primary mucinous neoplasm of the pancreas and mucinous cystadenocarcinomas, as well as intraductal papillary mucinous neoplasms, starting with excluding pseudocysts. A conservative approach is feasible in patients with a clinical presentation suggestive of an asymptomatic serous cystadenoma. Surgical management, as well as follow-up, is discussed for each of the types of neoplastic lesions, including an uncharacterized cyst, based on patient data, symptoms, serum analysis, cyst fluid analysis and morphological features. Aspects for future diagnostics and management of these neoplasia are commented upon.     

Diagnosis and management of relapsing pancreatitis associated with cystic neoplasms of the pancreas

One of the most important causes of relapsing pancreatitis is a cystic neoplasm of the pancreas. These low grade malignancies may cause pancreatitis by obstructing or communicating with a pancreatic duct. Patients with relapsing pancreatitis and a focal fluid fluid collection should be investigated for the possibility of a mucinous cystic neoplasm. Cross sectional imaging can provide a diagnosis with the imaging findings of a low attenuation cystic lesion containing mural calcification （CT scanning） or a lobular T2 enhancing lesion （MRCP）. Endoscopic ultrasound can provide more detailed imaging with the ability to guide fine needle aspiration of the cyst fluid. Cyst fluid analysis can provide a diagnosis of a mucinous cystic lesion with the combination of cytology （mucinous epithelium）, elevated carcinoembryonic antigen （CEA）, and the presence of DNA mutations. Management of these patients consists of surgical resection and monitoring in patients not able to withstand surgery.     

Magnetic resonance imaging in the detection of pancreatic neoplasms

Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi-imaging protocol, which includes MR cross-sectional imaging, MR cholangiopancreatography and dynamic contrast-enhanced MR angiography, integrates the advantages of various special imaging techniques. The non-invasive all-in-one MR multi-imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low-grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non-functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well-defined margins.     

Prevalence,Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions

Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. This review discusses the different cystic neoplasms of the pancreas and reports diagnostic strategies based on clinical features and imaging data. Surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines, is also discussed, with special reference to intraductal papillary mucinous neoplasm (IPMN; particularly the branch duct variant), which is the lesion most frequently identified incidentally. IPMN pathology, its risk for development into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk are discussed. Finally, surgical treatment, strategies for surveillance of pancreatic cysts, and possible future directions are discussed.     

Intraductal mucinous tumors occurring simultaneously in the liver and pancreas

A case of simultaneous intraductal mucinous tumors of the liver and pancreas in a 67-year-old man is described. Abdominal ultrasonography and computed tomography (CT) revealed the presence of cystic lesions with intraluminal septae both in the caudate lobe of the liver and in the uncinate process of the pancreas; these cystic lesions communicated with the hepatic duct and pancreatic duct, respectively. Mucin retention was observed in the cysts, and cholestasis was induced by mucin secretion into the common bile duct. The lesions were resected by left hepatic lobectomy with caudate lobectomy, and segmental pancreatectomy. Both lesions were multilocular cystic tumors with no papillary projections or focal mass effect in their walls. Histologically, both cystic lesions were a mixture of hyperplasia and adenoma lined by low papillary columnar epithelium. There were no cellular or histological features to suggest malignant change. The fibrous intratumor interstitium lacked any mesenchymal or ovarian-like stroma. The hepatic lesion was considered to be of a similar nature to intraductal papillary mucinous tumor (IPMT) of the pancreas. However, the two lesions occurred simultaneously in the liver and pancreas. This case is of interest in regard to the diagnosis and management of mucinous hepatopancreatobiliary lesions. Received: March 16, 2001 / Accepted: September 14, 2001     

Endoscopic ultrasound characteristics of mucinous cystic neoplasms of the pancreas

OBJECTIVE: Mucinous cystic neoplasms of the pancreas have a more favorable prognosis than ductal adenocarcinoma. Management of a subgroup, intraductal papillary-mucinous neoplasms, is controversial. Endoscopic ultrasound (EUS) with fine-needle aspiration biopsy may emerge as the imaging modality of choice. There are few studies describing the EUS features of these tumors. METHODS: A total of 35 consecutive cases of cystic tumors of the pancreas with an established pathological diagnosis were analyzed for characteristic EUS features. RESULTS: Mucinous cystadenocarcinomas (n = 14) were more likely to be characterized by hypoechoic cystic/solid mass or complex cyst and were frequently associated with a dilated main pancreatic duct. Benign mucinous duct ectasia (n = 6) were characterized by a dilated main pancreatic duct in conjunction with hyperechoic thickening of the duct wall. The two cases of intraductal mucinous hyperplasia additionally showed a hypoechoic mass. Intraductal papillary carcinoma (n = 11) had features in common with mucinous cystadenocarcinoma but also had echogenic foci in the mass and intraductal hyperechoic lesions. The two cases of microcystic cystadenoma showed either a mixed hypoechoic solid/cystic mass or a complex cyst without the additional features seen in mucinous cystadenocarcinoma. CONCLUSIONS: EUS features seem to exist that may help to differentiate cystic neoplasms from adenocarcinoma of the pancreas and, thus, to establish the preoperative diagnosis of cystic tumors of the pancreas.     

Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is a spectrum of neoplasia in the pancreatic duct epithelium characterized by cystic dilation of the main and/or branch pancreatic duct. According to the site of involvement IPMNs are classified into three categories, i.e., main duct type, branch duct type, and combined type. Most branch duct IPMNs are benign, whereas the other two types are often malignant. A large size of branch duct IPMN and marked dilation of the main pancreatic duct indicate the presence of adenoma at least. The additional existence of large mural nodules increases the possibility of malignancy in all types. Of recent interest is the relatively high prevalence of synchronous and/or metachronous malignancy in various organs, including the pancreas. The prognosis is favorable after complete resection of benign and noninvasive malignant IPMNs. Malignant IPMNs acquiring aggressiveness after parenchymal invasion necessitate adequate lymph node dissection. On the other hand, asymptomatic branch duct IPMNs without mural nodules can be observed without resection for a considerably long time. This review addresses available data, current understanding, controversy, and future directions.     

Multicentric pancreatic intraepithelial neoplasias (PanINs) presenting with the clinical features of chronic pancreatitis

A 46-year-old woman was readmitted to our hospital in August 2005 because of severe abdominal pain and nausea. Computed tomography demonstrated a huge cystic lesion in the retroperitoneal space behind the hepatoduodenal ligament and lesser peritoneal cavity. Endoscopic retrograde pancreatography revealed communication between the dilated main pancreatic duct and a pseudocyst. The condition was preoperatively diagnosed as chronic pancreatitis associated with a pseudocyst or an intraductal papillary mucinous neoplasm without mucin hypersecretion. The patient underwent a distal pancreatectomy with splenectomy. The pathologic diagnosis was multicentric pancreatic intraepithelial neoplasia (PanIN), and histological examination revealed a positive surgical margin around the remnant pancreas. Four months after the surgery, the patient underwent a total pancreatectomy. Macroscopic observation revealed diffuse fibrosis of the pancreatic parenchyma compatible with chronic pancreatitis. Histological examination revealed a constellation of noninvasive intraductal neoplasias with high-grade atypia, diffusely distributed in the small pancreatic ducts of the resected pancreas. Localized fibrosis and cystic dilation of the small ducts were detected in a lobule of exocrine glands draining into a ductule involved by PanIN lesions in the head of the pancreas. In summary, multicentric PanIN lesions are associated with lobular atrophy of the pancreatic parenchyma and chronic pancreatitis-like changes that follow. Total pancreatectomy may be recommended for patients with multicentric precursor lesions throughout the entire pancreas.     

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging (MRI)/magnetic resonance cholangio pancreatography (MRCP) and computer tomography (CT) scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms (IPMN). While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging （MRI）/magnetic resonance cholangio pancreatography （MRCP） and computer tomography （CT） scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms （IPMN）. While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

Cystic precursors to invasive pancreatic cancer

Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not.