EUS FNA in intraductal papillary mucinous tumors of the pancreas

BACKGROUND/AIMS: There is little information concerning the potential role of fine-needle aspiration guided by endoscopic ultrasonography in the pathologic diagnosis of intraductal papillary mucinous tumors of the pancreas. METHODOLOGY: Patients with an intraductal papillary mucinous tumor of the pancreas suggested by endoscopic ultrasonography underwent fine-needle aspiration guided by endoscopic ultrasonography in order to investigate the presence of mucin and/or cytologic changes consistent with this diagnosis. A group of 111 patients with other pancreatic lesions explored during the same period of time was used as a control group. RESULTS: Fine-needle aspiration guided by endoscopic ultrasonography was safely performed in 19 patients and supported the diagnosis in 17 of them. Nine out of the 17 patients with suspicion of intraductal papillary mucinous tumors of the pancreas went to surgery and this diagnosis was confirmed in the resected specimen in all of them. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS FNA in the diagnosis of IPMT were 82%, 100%, 100%, 92% and 94% respectively. CONCLUSIONS: Fine-needle aspiration guided by endoscopic ultrasonography is a good technique to support the diagnosis of intraductal papillary mucinous tumors of the pancreas and should be considered in this group of patients if pathologic confirmation is judged to be necessary.     

Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas

Recently, attention has been drawn to papillary neoplasm of the pancreatobiliary systems. In the pancreas, the disease entity of intraductal papillary mucinous neoplasm (IPMN-P) is widely recognized. In contrast, the pathological characteristics of biliary papillary tumors, such as biliary papilloma(tosis) and papillary cholangiocarcinoma, have not yet been well documented. In this study, we compared the pathological features and post-operative prognosis among biliary papillary tumors (10 cases of biliary papilloma(tosis) and 22 cases of papillary cholangiocarcinoma), conventional non-papillary cholangiocarcinoma (15 cases), and IPMN-P (31 cases). Macroscopically, all biliary papillary tumors were characterized by the prominent intraductal papillary proliferation, and macroscopic mucin-hypersecretion was seen in 9 of 32 cases (28%). Histologically, biliary papillary tumors consisted of three types of tumor cells (pancreaticobiliary, intestinal and gastric types), whereas only the pancreaticobiliary type was observed in non-papillary cholangiocarcinoma. Immunohistochemically, biliary papillary tumors were characterized by the common expression of MUC2, CDX2 and cytokeratin 20. In addition, biliary papillary tumors could be associated with two types of invasive lesions: tubular adenocarcinoma (9 cases) and mucinous carcinoma (5 cases). Patients with tubular adenocarcinoma had a poor prognosis compared to non-invasive papillary tumor or papillary tumor with mucinous carcinoma. These pathological characteristics and the survival status of biliary papillary tumors were different from those of non-papillary cholangiocarcinoma, and rather closely resembled those of IPMN-P. In conclusion, biliary papillary tumors may be the biliary counterpart (intraductal papillary neoplasm of the bile duct) of IPMN-P.     

Long-term follow up results of intraductal papillary mucinous tumors of pancreas

BACKGROUND AND AIM: Intraductal papillary mucinous tumor (IPMT) of the pancreas can be divided into three clinically distinct subtypes: main duct type, branch duct type and mixed type. Although it has been reported that the branch duct type IPMT is less invasive than the main duct type IPMT, we experienced a number of branch duct type IPMT having a poor prognosis. In the present study we surveyed the survival and recurrence rates according to the subtypes. METHODS: Sixty-seven IPMT cases were studied to investigate clinical behavior according to the duct types. Diagnostic findings and late results of treatment were reviewed in 27 cases of the main duct type IPMT and in 35 cases of the branch duct type IPMT. RESULTS: There was no statistically significant difference in the survival analysis between the main duct type IPMT and the branch duct type IPMT (P = 0.93). Seven patients (25.9%) died among the main duct type IPMT while six patients (17.1%) died among the branch duct type IPMT (P = 0.36). Tumor recurrence was noticed in four patients (18.1%) among 22 operated main duct type IPMT and in two patients (6.9%) among 29 operated branch duct type IPMT (P = 0.35). CONCLUSION: The long-term follow up result of the branch duct type IPMT is similar to that of the main duct type IPMT. Therefore, it is not safe just to monitor the branch duct type IPMT without operation. Surgery, whenever possible, is clearly the gold standard for treatment of IPMT, regardless of duct type.     

Invasive cancer and survival of intraductal papillary mucinous tumors of the pancreas

OBJECTIVES: Intraductal papillary mucinous tumor (IPMT) is frequently associated with pancreatic cancer. We hypothesized that IPMT progresses to invasive cancer with K-ras mutations as an early event, and that invasive cancer affects survival. We compared survival after resection and determined whether K-ras mutations predicted survival in IPMT patients without or with invasive cancer. METHODS: Records of 47 patients with IPMT who were seen between 1983 and 1998 were reviewed retrospectively in 15 cases and prospectively in 32. All histological material was reviewed to confirm the diagnosis of IPMT and to assess invasion. Kaplan-Meier survival curves were analyzed by the log-rank test. The chi2 test was used for differences in K-ras between groups. RESULTS: There were 30 men and 17 women, with a mean age of 65 yr (range 36-90 yr). Of the patients, 26 had IPMT without invasive cancer and 19 had IPMT with invasion. Tissue diagnosis was available in 45 patients. K-ras was analyzed in 40 patients. Mutations were present in 15 of 23 patients (65%) without invasive cancer and in 14 of 17 patients (82%) with invasive cancer (p = ns). At 2.5 yr, the overall cumulative survival of IPMT patients without invasive cancer was 94% compared to 24% of patients with invasive cancer (p < 0.001). The 5-yr survival of IPMT patients without invasive cancer was 94%. K-ras mutations did not correlate with survival. CONCLUSIONS: Invasive cancer in IPMT reduces the 2.5-yr survival after surgery from 93% to 24%. K-ras mutations occur before invasive cancer, and do not predict postoperative survival.     

Familial intraductal papillary mucinous neoplasms of the pancreas

The prevalence of intraductal papillary mucinous neoplasms in patients with a high risk of pancreatic adenocarcinoma was estimated to be 15%. However, a familial form of intraductal papillary mucinous neoplasms was never described.MethodsThree families (8 patients) with intraductal papillary mucinous neoplasms familial forms were described. Diagnosis was made according to radiological criteria and was confirmed by pathological data. Genetic predisposing factors of pancreatic cancer were searched for.ResultsSymptoms related to intraductal papillary mucinous neoplasms were recurrent acute pancreatitis (n = 3) or fortuitous discovery (n = 5). Number of cystic lesions was ≤3 (n = 4) or >3 (n = 4). Intraductal papillary mucinous neoplasms involved branch ducts (n = 7) or both main pancreatic duct and branch duct (n = 1). Severe and moderate dysplasia was found on surgical specimens. No genetic alteration was found (BRCA2, p16 or CDKN2A genes).ConclusionA familial form of intraductal papillary mucinous neoplasms was found in three families. No pancreatic cancer was found in relatives but an attentive survey has to be proposed.     

Outcome after surgical resection of intraductal papillary and mucinous tumors of the pancreas

OBJECTIVE: Treatment of intraductal papillary and mucinous tumors of pancreas (IPMT) usually requires surgery. The objective of this study was to evaluate the risk of recurrence in patients after surgery according to the histological nature of the neoplasm and the type of surgery. METHODS: The outcome of 45 patients who underwent partial pancreatectomy (n = 35) or total pancreatectomy (n = 10) for IPMT was studied according to the nature of the neoplasm (invasive carcinoma or noninvasive neoplasm), type of surgery (partial or total pancreatectomy), and lymph nodes status. RESULTS: The overall 3-yr actuarial survival rate was 83%. Death occurred in seven of 20 (35%) patients with invasive carcinoma and in one of 26 (4%) patients with noninvasive tumors (p<0.05). There were two recurrences in the seven patients with noninvasive neoplasm who underwent partial pancreatectomy with involved resection margins, and none in the 13 patients with disease-free margins. In patients with invasive carcinoma, there was one recurrence after total pancreatectomy, six after partial pancreatectomy with disease-free margins and six after partial pancreatectomy with involved margins. In patients with invasive carcinoma, total pancreatectomy and the absence of lymph nodes involvement were independently associated with a low risk of recurrence. CONCLUSIONS: IPMT may be managed as follows: 1) in patients with noninvasive neoplasms, partial pancreatic resection should be guided by frozen section examination until disease-free margins are obtained; and 2) in patients with invasive carcinoma, total pancreatectomy seems most likely to cure the patient, but should be discussed according to the general status and the age.     

Management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts. IPMNs have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. IPMNs are classified into main duct and branch duct types, based on the site of tumor involvement. IPMN patients have a favorable prognosis if appropriately treated. The postoperative 5-year survival rate is nearly 100% for benign tumors and noninvasive carcinoma, and approximately 60% for invasive carcinoma. A main duct type IPMN should be resected. Surgical treatment is indicated for a branch duct IPMN with suspected malignancy (tumor diameter ≥ 30 mm, mural nodules, dilated main pancreatic duct, or positive cytology) or positive symptoms. Malignant IPMNs necessitate lymph node dissection (D1). IPMNs are associated with a high incidence of extrapancreatic malignancies and pancreatic ductal carcinoma.     

不同病理类型的胰腺导管内乳头状黏液性肿瘤的临床特征

目的 总结不同病理类型胰腺导管内黏液性乳头状瘤(IPMT)的临床表现,提高对IPMT的诊治水平.方法 回顾分析1996年3月至2008年9月间经手术切除且病理证实的49例IPMT患者的临床表现、影像学特点及病理学特征,比较分析良性、交界性、恶性IPMT的临床表现.结果 49例IPMT患者中男27例,女22例,平均年龄(58±11)岁.良性19例,交界性9例,恶性21例.3类IPMT患者在性别、发病年龄、烟酒史、胰腺炎发作史、糖尿病病史,是否存在腹痛、腰背部放射痛、腹胀、腹泻、消瘦等症状,血CEA、AST、ALT水平,肿瘤位置及肿瘤分型上的差异均无明显统计学意义.但黄疸、术前CA19-9和碱性磷酸酶水平、肿瘤直径、主胰管直径、囊性肿瘤内是否存在隔膜、附壁结节的大小等方面的差异有统计学意义.恶性IPMT术后5年有1例病死,1例复发;交界性和良性IPMT有1例复发,1例因其他疾病病死.结论 不同病理类型的IPMT 临床特征存在一些差异,需综合判断进行鉴别.     

Clinical management of intraductal papillary mucinous tumors of the pancreas based on imaging findings

The aim of this study was to assess the imaging findings of pathologically proven intraductal papillary-mucinous tumors of the pancreas and the natural history of follow-up cases, and to optimize the therapeutic management of patients with these tumors according to their imaging findings. All nine patients with main duct type tumors were histologically diagnosed as having adenocarcinoma or adenoma, with no hyperplastic lesion. The images failed to discriminate between the two histologic types. In 26 patients with branch duct type tumors, all but one with intraductal mural nodules or tumors of > or = 30 mm had adenocarcinoma or adenoma, regardless of the caliber of the main duct. Of the nine patients with tumors < 30 mm and no mural nodules. three had adenoma, and six had hyperplasia. All of four patients had hyperplasia, with the additional caliber of the main duct being < 6 mm. In a series of 23 cases in which the patient was followed-up, no apparent progression was found in 17 patients who had no mural nodules and tumors of < 30 mm. Given these results, patients with main duct type tumors, and those with branch duct type tumors showing mural nodules or a tumor diameter of > or = 30 mm, are at high risk of developing neoplasms, including adenocarcinoma, for which surgical resection should be considered, whereas those patients with tumors < 30 mm and no mural nodules can be followed.     

Intraductal papillary mucinous tumors of the pancreas

Summary Methods. Literature is thoroughly reviewed and compared to our own experience. Results. Clinical history data do not appear to be useful in differentiating between benign and malignant cases. Usually IPMT patients are older than individuals suffering from chronic obstructive pancreatitis and tend to drink and smoke less. Malignant forms of IPMT are more frequently associated with diabetes, and pain seems to be more frequent in benign cases, although these findings are not confirmed in all reports. Also, laboratory tests are of little use, whereas imaging findings currently enable us to reach a correct diagnosis in about 70% of cases without differentiating in a reliable and definitive way the benign or malignant nature of the neoplasm. The WHO classification appears to be related to the different prognosis. Surgery, whenever possible, is the gold standard treatment. Conclusion. IPMT are a recent established clinical entity embracing a spectrum of lesions ranging from benign to malignant infiltrating cases. The only recognized radical treatment is surgery. Despite diagnostic capacity based on clinical presentation and imaging techniques has becoming increasingly refined we are still incapable of identifying the different degree of malignancy preoperatively, if any. The lengthy mean survival after resection confirm the high potential cure rate of IPMT of the pancreas.     

Intraductal papillary mucinous tumors of the pancreas

Cystic neoplasms of the exocrine pancreas are a small fraction of pancreatic tumors. Within that group of cystic neoplasms, intraductal papillary mucinous tumors (IPMTs) can be distinguished from mucinous cystic neoplasms, serous cystic neoplasms, and pseudopapillary cystic tumors. Awareness of IPMTs has increased since the World Health Organization classified these tumors as its own group in 1996. Because of their favorable prognosis, an extensive diagnostic workup for IPMTs should be performed in patients presenting with cystic lesions of the pancreas. This workup often leads to the diagnosis and the predominant tumor location and size, although the extent of the ductal changes can only be established by histopathology. Surgical resection is the therapy of choice for IPMTs. The type of resection depends upon the extent of the quantitative and qualitative ductal involvement. Total pancreatectomy is currently the treatment for an IPMT that comprises the entire main duct.     

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.     

Epigenetic alterations in intraductal papillary mucinous neoplasms of the pancreas

Intraductal papillary mucinous neoplasm (IPMN), an increasingly recognized cystic neoplasm of the pancreas with a broad spectrum of malignant potential, has been considered a precursor to infiltrating ductal adenocarcinoma. Because of its unique clinical, radiological, pathological, and molecular features, IPMN has attracted considerable interest among clinicians and researchers. Although some genetic alterations have been described in IPMNs, the molecular features that characterize the evolution and progression of these neoplasms are largely unknown. Recent studies have shown that aberrant methylation of the promoter cytosine-phospho-guanine (CpG) island is a common mechanism associated with the silencing of tumor-suppressor and cancer-related genes in IPMNs. Importantly, the prevalence of such methylation increases along with the grade of neoplasia, suggesting that these epigenetic events may contribute to the progression of IPMNs. Further studies of epigenetic alterations in IPMN will shed light on the molecular pathogenesis of this unique neoplasm and lead to the identification of epigenetic markers that can be applied in the clinical setting.     

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.