胰腺导管内乳头状黏液性肿瘤的研究进展

胰腺导管内乳头状黏液性肿瘤（IPMNs）是一类以胰腺导管上皮乳头样增生和分泌大量黏液为特点的一,类肿瘤,大量黏液堵塞主胰管或分支胰管并使之扩张。近年对IPMNs的流行病学、病理特征与肿瘤基因表达、诊断处理原则方面均有了新的认识。本文就IPMN8的研究进展作一综述。     

胰腺导管内乳头状黏液性肿瘤研究进展

胰腺导管内乳头状黏液性肿瘤(pancreatic intraepithelial neoplasias,IPMNs)是新近被认识的一种胰腺囊性肿瘤.在不同类型胰腺肿瘤中,IPMNs预后相对较好,具有与一般胰腺肿瘤不同的分子及临床病理特征:按照乳头状结构及黏蛋白的表达又可将其分为多个亚型,不同亚型又具有不同的病理特点.病理学家提出IPMNs是胰腺癌发生过程中的重要阶段,深入研究IPMNs及其不同亚型的病理特点及其所蕴含的分子变化,将能更好的揭示IPMNs的发病机制及生物学特征.本文回顾相关文献,从分子特征、病理特征、诊断治疗及预后判断等不同角度对目前IPMNs的研究进展作一综述.     

胰管内乳头状黏液瘤七例并文献复习

胰管内乳头状黏液瘤(intraductai papillary mucinousneoplasms,IPMNs)是一临床比较少见的胰腺外分泌肿瘤,具有独特的临床表现和病理特征.我院自2005年3月至2007年12月共收治7例IPMNs患者,现报道如下.     

胰腺导管内乳头状黏液瘤

胰腺导管内乳头状黏液瘤（intraductal papillary mucinous neoplasm,IPMN）是胰管内来源的肿瘤,由日本Ohhashi等于1982年首先报道,随后陆续有一些文献出现,但命名上未统一,较常用的有导管内乳头状肿瘤、导管高分泌黏液肿瘤、导管产黏液肿瘤、导管扩展型黏液性囊腺瘤等。1996年WHO将胰腺囊性产粘蛋白肿瘤分为两类：胰腺导管内乳头状黏液瘤（intraductal papillary mucinous tumor,IPMT）和黏液性囊腺瘤（mucinous cystic tumor）。2000年,WHO将IPMT修正为IPMN。     

APC蛋白在胰腺癌及其癌前病变中的表达差异分析

背景：APC基因突变致Wnt／β-catenin信号通路异常活化可促进肿瘤发生。目的：分析APC蛋白在胰腺导管腺癌（PDAC）和胰腺癌前病变中的表达差异,探讨APC在PDAC发生中的作用。方法：以免疫组化方法检测APC蛋白在正常胰腺、胰腺上皮内瘤变（PanINs）、胰腺导管内乳头状黏液性肿瘤（IPMNs）、PDAC中的表达,分析其在PanIN-1、-2、-3、IPMN腺瘤（IPMA）、IPMN交界性肿瘤（IPMB）、IPMN腺癌（IPMC）、PDAC中的表达差异,以及APC蛋白表达与PDAC临床病理特征和患者预后的关系。结果：正常胰腺导管上皮APC表达阴性。由PanIN-1、PanIN-2至PanIN-3,APC免疫组化评分（IHCS）逐渐增高（P〈0．05）,PanIN-1APC阳性表达率显著低于PanIN-2、PanIN-3（P〈0．05）;IPMA、IPMB、IPMC间APCIHCS和APC阳性表达率均无明显差异。APC在PDAC和IPMNs中的表达具有明显不均一性,PDAC的APCIHCS和APC阳性表达率均显著低于各级别PanINs（P〈0．05）,与各级别IPMNs无明显差异。APC阳性表达与PDAC患者术后生存期短显著相关（P=0．003）。结论：APC蛋白表达异常是PDAC发生过程中的早期事件,其表达阳性提示患者预后不良。APC在胰腺癌中的具体作用机制有待进一步研究。     

胰腺导管内乳头状黏液性肿瘤七例分析

胰腺导管内乳头状黏液性肿瘤(intraductal papillary mutinous neoplasm,IPMN)是一种新近被逐渐认识的胰腺少见肿瘤,来源于胰腺导管黏液分泌上皮细胞,在胰腺肿瘤中预后较好.现回顾性分析我院收治的7例胰腺IPMN患者的临床资料,以提高临床医师对该病的诊治水平.     

胰腺导管内乳头状黏液瘤

胰腺导管内乳头状黏液瘤(intraductal papillary mucinous neoplasm,IPMN)是胰管内来源的肿瘤,由日本Ohhashi等[1]于1982年首先报道,随后陆续有一些文献出现,但命名上未统一,较常用的有导管内乳头状肿瘤、导管高分泌黏液肿瘤、导管产黏液肿瘤、导管扩展型黏液性囊腺瘤等.     

胰腺导管内乳头状黏液性肿瘤诊治进展

胰腺最常见的恶性肿瘤是胰腺导管腺癌,其预后很差。然而,胰腺导管上皮发生的另一类肿瘤,胰腺导管内乳头状黏液性肿瘤(intraductal papillary mucinous tumors,IPMT) 却有着较好的预后,以前临床及病理医师对其尚不熟悉,直至近几年才逐渐被认识。Kimura等曾以以下特点作了报道:(1)胰腺导管内大量的黏液产生和潴留;(2)乏特乳头部开口由于黏液流过而扩大;(3)主要在主胰管内发展和播散;     

胰腺导管内乳头状黏液性肿瘤诊治进展

胰腺最常见的恶性肿瘤是胰腺导管腺癌,其预后很差.然而,胰腺导管上皮发生的另一类肿瘤,胰腺导管内乳头状黏液性肿瘤(intraductal papillary mucinous tumors,IPMT)却有着较好的预后,以前临床及病理医师对其尚不熟悉,直至近几年才逐渐被认识.Kimura等[1]曾以以下特点作了报道:(1)胰腺导管内大量的黏液产生和潴留;(2)乏特乳头部开口由于黏液流过而扩大;(3)主要在主胰管内发展和播散;(4)很少有浸润性的倾向;(5)手术切除率高及预后良好.以前往往把IPMT归类于一般的胰腺囊性肿瘤,事实上两者之间无论在发病机制、病理形态、治疗方式及预后等方面都有着质的区别.为提高IPMT的认识及诊治水平,本文重点对IPMT患者的诊断和治疗,良恶性的判定以及与其他囊性肿瘤的鉴别诊断等方面进行了综述.     

胰腺导管内乳头状黏液性肿瘤的研究进展

胰腺导管内乳头状黏液性肿瘤（IPMN）是指起源于主胰管或分支胰管内上皮细胞,形成大体可见的乳头状（偶见扁平状）、产黏液的,并伴有不同程度胰管扩张的一类肿瘤,是最常见的胰腺囊性肿瘤.1982年由Ohashi等首先报道,并命名为产黏液胰腺癌;IPMN曾被称为绒毛状腺瘤、乳头状肿瘤、乳头状癌、胰腺黏液导管扩张症及胰腺产黏液性肿瘤等[1].2000年,WHO将胰腺产黏液性肿瘤分成IPMN及黏液性囊性肿瘤（MCN）.根据细胞及组织异型程度,IPMN又被分成非浸润性IPMN（包括低级别、中等级别及高级别异型增生）和浸润性IPMN;根据累及胰管的范围,IPMN又被分为主胰管型（20％）、分支胰管型（40％）及混合型（40％）[2].     

Intraductal papillary mucinous neoplasms of the pancreas--a surgical disease

Cystic pancreatic neoplasms are increasingly recognized, with intraductal papillary mucinous neoplasms of the pancreas (IPMNs) being the most frequently observed type. IPMNs are characterized by mucin production and epithelial growth within the pancreatic ducts, and are generally differentiated according to location: main pancreatic duct, its major side branches, or both (mixed type). IPMNs vary from benign to malignant and are considered precursor lesions of pancreatic adenocarcinoma. However, the exact time to neoplastic transformation and whether all IPMNs progress to malignant tumors is unclear. Surgical resection is warranted for all main-duct and mixed-type IPMNs (they harbor a high risk of malignancy of ~70%). By contrast, branch-duct IPMNs progress to cancer in only ~30% of cases. Thus, according to current guidelines (Sendai criteria), asymptomatic side-branch IPMNs <3 cm in size without suspicious radiological features (such as size progression) can be treated conservatively. Lately, even this approach has become controversial, owing to a number of Sendai-negative IPMNs showing malignant transformation. Although most IPMNs should be resected by standard oncological procedures (including lymphadenectomy), small Sendai-negative IPMNs can be treated with limited resections. This Review summarizes current knowledge of the treatment of IPMNs, with a particular focus on surgical approaches to this disease.     

Resektion zystischer Pankreastumoren

Cystic tumors of the pancreas are diagnosed increasingly more due to increasing life expectancy and the moderate use of modern radiological diagnostics. Intraductal papillary mucinous neoplasms of the pancreas (IPMN), mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and serous cystic neoplasms (SCN) represent over 90?% of all cystic neoplasms of the pancreas. Although serous cystic lesions have a low or even no potential for malignant transformation, they are mostly resected when symptomatic. In contrast, mucinous lesions have an increased malignant potential and should therefore be resected in almost all cases. While this is true for all cases of MCNs and SPNs this is controversial for all IPMNs as they show a wide spectrum of morphological variants. The IPMNs may arise in the main pancreatic duct, major side branches or in both (mixed type). Although all IPMNs are considered to be precursor lesions to pancreatic adenocarcinomas it is not clear what the time course of such potential neoplastic transformation might be and whether all lesions progress to malignant tumors. As no currently used diagnostic test can reliably differentiate between benign and malignant tumors, the majority of newly diagnosed IPMNs should undergo surgical resection. According to current treatment guidelines (Sendai criteria), asymptomatic side branch IPMNs of less than 3 cm in diameter without suspicious radiological features, such as nodules, thickness of the cystic wall or size progression can be treated conservatively without the need for surgical resection. Recently, this approach has become controversial due to a relevant number of IPMNs reported as Sendai negative that showed malignant transformation on final histological examination.     

Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways

More than 2% of adults harbor a pancreatic cyst, a subset of which progresses to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and solid pseudopapillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10 ± 4.6, 27 ± 12, 16 ± 7.6, and 2.9 ± 2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of the von Hippel-Lindau gene (VHL), a key component of the VHL ubiquitin ligase complex that has previously been associated with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.     

Endoscopic ultrasound in the diagnosis of pancreatic intraductal papillary mucinous neoplasms

Pancreatic cystic lesions are increasingly recognised due to the widespread use of different imaging modalities.Intraductal papillary mucinous neoplasms(IPMNs)of the pancreas represent a common,but also heterogeneous group of cystic tumors with a significant malignant potential.These neoplasms must be differentiated from other cystic tumors and properly classified into their different types,main-duct IPMNs vs branchduct IPMNs.These types have a different malignant potential and therefore,different treatment strategies need to be implemented.Endoscopic ultrasound(EUS)offers the highest resolution of the pancreas and can aid in the differential diagnosis,classification and differentiation between benign and malignant tumors.The addition of EUS fine-needle aspiration can supply further information by obtaining fluid for cytology,measurement of tumor markers and perhaps DNA analysis.Novel techniques,such as the use of contrast and sophisticated equipment,like intraductal probes can provide information regarding malignant features and extent of these neoplasms.Thus,EUS is a valuable tool in the diagnosis and appropriate management of these tumors.     

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.     

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.     

Analysis of clinicopathological features and predictors of malignancy in intraductal papillary mucinous neoplasms of the pancreas

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are increasingly recognized, but it is very difficult to evaluate accurately the malignancy of these neoplasms by modern imaging. We reviewed our experience in order to elucidate predictors of tumor malignancy, invasiveness, and outcome. METHODOLOGY: The clinicopathological features and surgical outcomes of 57 patients with IPMNs who underwent surgery in Nagoya University Hospital were analyzed. RESULTS: The histological diagnosis was adenoma in 40, borderline in 1, carcinoma in situ (CIS) in 7, and invasive carcinoma in 9 patients. Patients with invasive carcinomas had significantly shorter survival rates than patients with benign IPMNs or CIS (p < 0.0001). Multivariate analyses revealed that the main duct or the combined type was significantly predictive of malignancy, and both main duct or combined type and diabetes mellitus were associated significantly with invasive carcinoma. CONCLUSIONS: IPMNs generally grow slowly, but have a malignant potential that warrants radical surgical treatment when the tumor component invades the parenchyma. Our results suggest that the above factors should be considered in surgical management. The main duct type of IPMN or IPMN with mural nodules is potentially malignant or invasive. Therefore, radical operative management is indicated in these IPMNs.     

Molecular pathogenesis of intraductal papillary mucinous neoplasms of the pancreas

Over the last 3 decades, there have been substantial improvements in diagnostic imaging and sampling techniques to evaluate pancreatic diseases. The modern technology has helped us to recognize premalignant conditions of pancreas including mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMNs). Differentiation between benign and malignant lesions and early detection of any malignant transformation in premalignant lesion are extremely important for further management decisions. Diagnostic cytology has limited sensitivity to further differentiate between benign, premalignant, and malignant lesions of the pancreas. There is limited information about the epidemiological risk factors and molecular mechanisms leading to development and further progression to malignancy of IPMNs. Several studies have shown that pancreatic juice and pancreatic tissue from the lesion can be tested for molecular markers including K-ras, p53, and p16 to differentiate between cancer and chronic inflammatory process. We review cellular signaling pathways that contribute to pathogenesis of IPMNs of the pancreas to further identify potential biomarkers and molecular targets.