High incidence of extrapancreatic neoplasms in patients with intraductal papillary mucinous neoplasms

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are associated with a high incidence of extrapancreatic neoplasms. DESIGN: Retrospective study. SETTING: Tertiary care referral center. PATIENTS: Sixty-one patients underwent surgical resection for IPMN between January 1, 1993, and June 30, 2004. Thirty-eight patients with mucinous cystic neoplasms and 50 patients with pancreatic ductal adenocarcinoma also were examined for development of extrapancreatic neoplasms. MAIN OUTCOME MEASURES: The incidence and clinicopathological features of extrapancreatic neoplasms with IPMNs were compared with those with mucinous cystic neoplasm and pancreatic ductal adenocarcinoma. RESULTS: Of the 61 patients with IPMNs, 24 (39%) developed 26 extrapancreatic neoplasms, and 18 (30%) had extrapancreatic malignancies. Gastric adenocarcinoma (33%) and colorectal adenocarcinoma (17%) were the most common neoplasms in the 24 patients. During postoperative follow-up, 3 patients died of malignant IPMNs, 3 of associated malignancies, and 1 of a nonmalignancy-related cause. Comparisons of the clinicopathological features in patients with IPMNs with and without associated malignancies revealed no significant differences in age, sex, family history of malignancy, history of cigarette smoking or alcohol abuse, or type of IPMN. The incidence of extrapancreatic neoplasms in patients with IPMN was significantly higher than in those with other pancreatic diseases such as mucinous cystic neoplasm (8%) or pancreatic ductal adenocarcinoma (10%). CONCLUSIONS: Frequently, IPMNs are associated with the development of extrapancreatic neoplasms. Considerable attention should be paid to the possible occurrence of other associated malignancies in patients with IPMNs, either concurrently or postoperatively. Further molecular studies may be necessary to elucidate the unusual association between IPMN and other primary neoplasms.     

Presentation, treatment and prognosis of intraductal papillary mucinous neoplasm

Intraductal papillary mucinous neoplasms (IPMNs) are rare tumours rising from the pancreatic duct epithelium. They are characterized by intraductal papillary growth and thick mucin secretion; mucin fills the Wirsung and/or branch pancreatic ducts and may cause ductal dilatation. IPMNs are classified into three types, according to the site of involvement: main duct type, branch duct type, and combined type. Most branch type IPMNs are benign, while the other two types are frequently malignant. Recent advances in diagnostic imaging have led to an increased frequency of diagnosis of IPMNs, but the clinical features of them can range broadly from benign, borderline, and malignant non-invasive to invasive lesions, and their management has not yet been clearly defined. The most of patients are asymptomatic. The possibility of malignancy is increased in cases which large mural nodules are presented. Presence of a large branch type IPMN and marked dilatation of the main duct indicate the existence of adenoma. Not infrequently, synchronous or metachronous malignancies may be developed in various organs. Endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography (EUS), intraductal ultrasonography, and magnetic resonance cholangiopancreatography (MRCP) are the most valuable imaging techniques for diagnosis of these lesions. Prognosis is excellent after complete resection of benign and non-invasive malignant IPMNs. Total pancreatectomy should be reserved for patients with resectable but extensive IPMN involving the whole pancreas; its benefits must be balanced against perioperative risks.     

76例胰腺导管内乳头状黏液性肿瘤的外科治疗及预后分析

目的 分析胰腺导管内乳头状黏液性肿瘤患者的临床特征及手术疗效.方法 收集1999年1月至2008年12月复旦大学附属中山医院手术切除的76例胰腺导管内乳头状黏液性肿瘤的病史资料,并进行随访,分析其临床特征及手术疗效.结果 76例患者中,男性49例,女性27例;肿瘤位于胰头者63例,胰体尾10例,全胰3例;32例为非浸润性肿瘤(腺瘤16例,交界性肿瘤6例,原位癌10例),44例为浸润癌,两者在发病年龄及黄疸、消瘦、无症状患者、CA199升高等方面差异有统计学意义(P＜0.05);胰十二指肠切除59例,联合门静脉切除重建4例,胰体尾切除6例,局部切除2例,节段性胰腺切除2例,全胰切除3例;总体并发症发生率为28.9%,无手术相关死亡病例;非浸润性及浸润性肿瘤患者5年生存率分别为100%及35%;非浸润性肿瘤患者7例切缘阳性,其中1例术后67个月复发转移;多因素分析显示肿瘤直径及淋巴结状况是影响浸润性癌患者预后的独立因素.结论 非浸润性胰腺导管内乳头状黏液性肿瘤手术疗效极佳,而浸润癌患者的预后较差;及早手术是防止病变进展及改善预后的关键;术后必须进行长期随访.

Abstract：

Objective To investigate the outcome of intraductual papillary mucious neoplasms (IPMN) of the pancreas after surgical resection. Method Clinical data of 76 patients with intraductal papillary neoplasms of the pancreas undergoing surgical resection at Zhongshan Hospital, Fudan University between January 1999 and December 2008 were retrospectively analyzed. Results Among the 76 patients,49 were male, 37 were female. 32 had noninvasive IPMNs, including adenomas( n = 16), borderline tumors (n =6 ), carcinomas in situ (n = 10 ). 44 had invasive IPMNs. Lesions were present in the head in 63 cases, in the body or tail in 10, in the whole pancreas in 3. There were significant difference in age,jaundice, weight loss, asymptomatic cases and CA199 value between noninvasive and invasive IPMNs.Three patients underwent total pancreatectomy, 59 patients underwent pancreaticoduodenectomy, 4 patients underwent pancreaticoduodenectomy with portal vein resection and reconstruction, six patients underwent distal pancreatectomy, two patients each underwent central pancreatectomy or enucleation. The overall postoperative morbidity rate were 28.9%, there was no operative mortality. Positive pancreatic margin was identified in seven patients of noninvasive neoplasms, among thoee one developed recurrence after 67 months. The five-year survival rate for patients with noninvasive and invasive neolpasms was 100% and 35% ,respectively. Size and lymph node metastasis were significant prognostic factors after surgical resection of the invasive IPMNs. Conclusions Surgical resection provides a favorable outcome for patients with noninvasive IPMNs. In contrast, invasive IPMNs was associated with a poor survival. Early resection is essential for improving survival. Long-term follow-up is necessary for all patients with IPMNs after resection.     

76例胰腺导管内乳头状黏液性肿瘤的外科治疗及预后分析

目的 分析胰腺导管内乳头状黏液性肿瘤患者的临床特征及手术疗效.方法 收集1999年1月至2008年12月复旦大学附属中山医院手术切除的76例胰腺导管内乳头状黏液性肿瘤的病史资料,并进行随访,分析其临床特征及手术疗效.结果 76例患者中,男性49例,女性27例;肿瘤位于胰头者63例,胰体尾10例,全胰3例;32例为非浸润性肿瘤(腺瘤16例,交界性肿瘤6例,原位癌10例),44例为浸润癌,两者在发病年龄及黄疸、消瘦、无症状患者、CA199升高等方面差异有统计学意义(P＜0.05);胰十二指肠切除59例,联合门静脉切除重建4例,胰体尾切除6例,局部切除2例,节段性胰腺切除2例,全胰切除3例;总体并发症发生率为28.9%,无手术相关死亡病例;非浸润性及浸润性肿瘤患者5年生存率分别为100%及35%;非浸润性肿瘤患者7例切缘阳性,其中1例术后67个月复发转移;多因素分析显示肿瘤直径及淋巴结状况是影响浸润性癌患者预后的独立因素.结论 非浸润性胰腺导管内乳头状黏液性肿瘤手术疗效极佳,而浸润癌患者的预后较差;及早手术是防止病变进展及改善预后的关键;术后必须进行长期随访.     

76例胰腺导管内乳头状黏液性肿瘤的外科治疗及预后分析

目的 分析胰腺导管内乳头状黏液性肿瘤患者的临床特征及手术疗效.方法 收集1999年1月至2008年12月复旦大学附属中山医院手术切除的76例胰腺导管内乳头状黏液性肿瘤的病史资料,并进行随访,分析其临床特征及手术疗效.结果 76例患者中,男性49例,女性27例;肿瘤位于胰头者63例,胰体尾10例,全胰3例;32例为非浸润性肿瘤(腺瘤16例,交界性肿瘤6例,原位癌10例),44例为浸润癌,两者在发病年龄及黄疸、消瘦、无症状患者、CA199升高等方面差异有统计学意义(P＜0.05);胰十二指肠切除59例,联合门静脉切除重建4例,胰体尾切除6例,局部切除2例,节段性胰腺切除2例,全胰切除3例;总体并发症发生率为28.9%,无手术相关死亡病例;非浸润性及浸润性肿瘤患者5年生存率分别为100%及35%;非浸润性肿瘤患者7例切缘阳性,其中1例术后67个月复发转移;多因素分析显示肿瘤直径及淋巴结状况是影响浸润性癌患者预后的独立因素.结论 非浸润性胰腺导管内乳头状黏液性肿瘤手术疗效极佳,而浸润癌患者的预后较差;及早手术是防止病变进展及改善预后的关键;术后必须进行长期随访.     

Intraductal papillary mucinous neoplasms of the pancreas: an updated experience

OBJECTIVE: To update the authors' experience with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND DATA: IPMNs are intraductal mucin-producing cystic neoplasms of the pancreas with clear malignant potential. Since the authors' 2001 report, the number of IPMNs resected at our institution has more than doubled, providing an opportunity to define the clinical features of this distinct neoplasm. METHODS: All patients undergoing pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and March 2003 were evaluated. Noninvasive IPMNs were classified as "adenoma," "borderline," or "carcinoma-in situ" (CIS) depending on the degree of dysplasia within the specimen. Invasive cancers were classified as tubular, colloid, mixed, or anaplastic types. Pathology was retrospectively reviewed to identify main-duct or branch-duct origin of the tumors. Long-term overall survival for patients having IPMNs with invasive cancer was compared with those patients having IPMNs without an invasive component. RESULTS: Between January 1987 and March 2003, inclusive, 136 pancreatic resections were performed for patients with IPMNs, with 78 resections performed since January 2001. The mean age of the patients was 66.8 +/- 1.1 years, with 57% being male and 89% white. Pancreaticoduodenectomy was performed in 71% of patients, total pancreatectomy in 15%, distal pancreatectomy in 12%, and central pancreatic resection in 2%. IPMNs without evidence of invasive cancer were identified in 62% (n = 84) of patients (17% adenoma, 28% borderline, or 55% CIS). The remaining 38% (n = 52) of patients had IPMNs with associated invasive cancer (60% tubular, 27% colloid, 7% mixed, and 6% anaplastic). The mean age of patients with IPMN adenoma was 63.2 years, 66.7 years for those with borderline/CIS IPMNs, and 68.1 years for those with invasive cancer (P = 0.08, adenomas vs. invasive cancer). In those patients with invasive cancers, 15% had invasive cancer at the final surgical margin, 23% had IPMN without invasive cancer at the margin, and 54% had lymph node metastases. Residual IPMN was identified at the neck or uncinate margin in 24% of patients with noninvasive IPMNs. The overall 5-year survival for patients having IPMNs without invasive cancer was 77% (several deaths secondary to metachronous invasive cancer), compared with 43% in those patients with an invasive component (P < 0.0001). There were no differences in survival when comparing adenomas, borderline neoplasms, and CIS. Similarly, there were no statistically significant differences in survival when comparing branch-duct, main-duct, and combined variants; however, the branch-duct variants were more often noninvasive. For those patients with invasive IPMNs, 2-year survival was 40% when margins were positive for invasive cancer or for IPMN without invasive cancer, and 60% when margins were tumor-free (P = 0.15). Those patients with colloid carcinomas (n = 14) had improved survival compared with those with tubular carcinomas (n = 31), with 5-year survival rates of 83% and 24%, respectively. IPMN recurrences and deaths from cancer occurred in patients with both invasive and noninvasive IPMNs at initial resection. CONCLUSIONS: IPMNs continue to be recognized with increasing frequency. Five-year survival for those patients following resection of IPMNs with invasive cancer (43%) is improved compared with those patients with resected pancreatic ductal adenocarcinoma in the absence of IPMN (averages 15%-25%). Survival following resection of IPMNs without invasive cancer (regardless of degree of dyplasia) is good, but recurrent disease in the residual pancreas suggests that long-term surveillance is critical. Based on the age at resection data, there appears to be a 5-year lag time from IPMN adenoma (63.2 years) to invasive cancer (68.1 years).     

Extent of surgical resections for intraductal papillary mucinous neoplasms

Intraductal papillary mucinous neoplasms (IPMNs) can involve the main pancreatic duct (MD-IPMNs) or its secondary branches (BD-IPMNs) in a segmental of multifocal/diffuse fashion. Growing evidence indicates that BD-IPMNs are less likely to harbour cancer and in selected cases these lesions can be managed non operatively. For surgery, clarification is required on: (1) when to resect an IPMN; (2) which type of resection should be performed; and (3) how much pancreas should be resected. In recent years parenchyma-sparing resections as well as laparoscopic procedures have being performed more frequently by pancreatic surgeons in order to decrease the rate of postoperative pancreatic insufficiency and to minimize the surgical impact of these operations. However, oncological radicality is of paramount importance, and extended resections up to total pancreatectomy may be necessary in the setting of IPMNs. In this article the type and extension of surgical resections in patients with MD-IPMNs and BD-IPMNs are analyzed, evaluating perioperative and long-term outcomes. The role of standard and parenchyma-sparing resections is discussed as well as different strategies in the case of multifocal neoplasms.     

Laparoscopic distal pancreatectomy for intraductal papillary mucinous neoplasm-associated pancreatic cancer: A case report

Introduction and importanceIntraductal papillary mucinous neoplasm (IPMN) of the pancreas is often found incidentally during examination for other diseases. In addition to the risk of malignant transformation, patients with IPMN are at risk of developing pancreatic cancer. We report a case of pancreatic tail cancer that developed separately from a preexisting IPMN after minimally invasive esophagectomy for cancer of the esophagogastric junction and was resected successfully by laparoscopic distal pancreatectomy.Case presentationA 72-year-old man underwent thoracoscopic and laparoscopic esophagectomy for esophagogastric junction cancer. He had undergone surgery for ascending colon cancer 20 years ago. At that time, IPMN was confirmed in the pancreatic body by a preoperative examination. Computed tomography was regularly performed for postoperative work-up and follow-up of the IPMN, and a solid lesion with cystic components was detected in the pancreatic tail 9 months after the operation. On detailed examination, pancreatic ductal adenocarcinoma concomitant with IPMN, accompanied by a retention cyst, was considered. Laparoscopic distal pancreatectomy was successfully performed after neoadjuvant chemotherapy. Pathological diagnosis of the lesion in the pancreatic tail was of an invasive intraductal papillary mucinous carcinoma (ypT3ypN0yM0 ypStageIIA).Clinical discussionIf an IPMN is detected during preoperative examination for malignancies of other organs, careful follow-up is necessary due to the high risk of pancreatic cancer development. Furthermore, initial operation with minimally invasive surgery may reduce adhesion and facilitate subsequent surgeries.ConclusionWe have provided evidence that supports the importance of a careful follow-up of IPMNs, even if they are low risk.     

Intraductal papillary mucinous neoplasms of the pancreas: an analysis of clinicopathologic features and outcome

OBJECTIVE: To define the natural history of resected intraductal papillary mucinous neoplasms (IPMN) of the pancreas and to identify clinical and pathologic prognostic features. SUMMARY BACKGROUND DATA: IPMN of the pancreas is a recently described pancreatic tumor. Because of a limited number of cases, prognostic factors and the natural history of resected cases have not been well defined. MATERIALS AND METHODS: A prospective pancreatic database was reviewed to identify patients with IPMN who were surgically managed. Pathologic re-review of each case was performed, and the clinicopathologic features were examined. Log rank and chi2 analysis were used to identify factors predictive of survival and recurrence. RESULTS: Over a 17-year period, 63 patients were identified. One patient was unresectable, 6 (10%) underwent a total pancreatectomy, and 56 (89%) had a partial pancreatectomy. Invasive carcinoma was present in 30 patients (48%). Transection margins were involved with atypia or carcinoma in 32 patients (51%). The median follow-up for survivors was 38 months. Disease-specific 5- and 10-year survival were 75% and 60%, respectively. Significant predictors of poor outcome included presentation with elevated bilirubin, presence of invasive carcinoma, increasing size and percentage of invasive carcinoma, histologic type of invasive carcinoma, positive lymph nodes, and vascular invasion. The presence of atypia or carcinoma in situ at the ductal resection margin was not associated with a poor outcome. CONCLUSIONS: Overall, IPMN has a favorable prognosis. Poor outcome in a subset of patients is largely the result of the presence, extent, and type of an invasive component, lymph node metastases, and vascular invasion.     

A Resected Case of Intraductal Tubulopapillary Neoplasm of the Pancreas: Report of a Case

The patient was a 61-year-old male who was referred to our hospital after dilatation of the main pancreatic duct was detected by screening ultrasonography. Computed tomography revealed a protruding lesion measuring 15 mm in diameter within the main pancreatic duct in the head of the pancreas, and magnetic resonance cholangiopancreatography revealed interruption of the duct at the tumor site. We performed pancreaticoduodenectomy under a suspected diagnosis of invasive ductal carcinoma. Gross examination of the resected specimen showed that the tumor invaginated into the main pancreatic duct, and no mucin was found. Histological examination revealed proliferation of high-grade dysplastic cells in a tubulopapillary growth pattern. Immunohistochemically, cytokeratin 7 expression was detected, but not trypsin expression. Based on these morphological features, we diagnosed the tumor as intraductal tubulopapillary neoplasm (ITPN). We report the case with bibliographic consideration, together with a review of intraductal neoplasms of the pancreas encountered at our institution.Key words: Intraductal tubulopapillary neoplasm (ITPN), Intraductal neoplasms of the pancreas, PancreaticoduodenectomyIntraductal tubulopapillary neoplasms (ITPN) were first reported in 2009 by Yamaguchi et al¹ and were adopted by the WHO classification revised in 2010, as a subclass of intraductal neoplasms of the pancreas, along with intraductal papillary mucinous neoplasm (IPMN). Intraductal tubulopapillary neoplasms are rare, accounting for less than 1% of all pancreatic exocrine neoplasms, and are considered to have a better prognosis than conventional pancreatic cancer.¹ Clinicopathologically, ITPNs have features distinct from those of other intraductal neoplasms of the pancreas. Here, we report on a case of ITPN encountered by us who was treated by resection, along with some bibliographic consideration, as well as present a comprehensive review of intraductal neoplasms of the pancreas encountered at our hospital.     

Intraductal papillary mucinous neoplasms of the pancreas: an analysis of protein expression and clinical features

Background/Purpose The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of associated invasive carcinoma in patients with IPMNs. We investigated the clinicopathologic characteristics of 37 IPMNs and the immunohistochemical findings of these tumors to investigate the malignancy of IPMNs. Methods Between May 1992 and September 2003, 37 patients with IPMNs, 24 with adenoma and 13 with carcinoma, underwent pancreatic resections at Sapporo Medical University Hospital, Japan. In tumor specimens from these patients, we immunohistochemically analyzed the expression of p53 protein, proliferating-cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP-7), and E-cadherin. Clinical features and follow-up after resection were recorded. Results Aberrant expression of the proteins examined was frequently observed. Namely, there were significant differences in the expression of MMP-7 according to clinicopathological characteristics. Positive expression of MMP-7 was found in all of nine patients with infiltrating ductal pancreatic adenocarcinoma (IDC) and in all of seven patients with invasive intraductal papillary mucinous adenocarcinoma (IC-IPMC); however, 33.3% of patients with noninvasive IPMA, 58.3% of patients with intraductal papillary mucinous adenoma (IPMA), and all normal pancreatic tissues were negative for MMP-7; differences which were statistically significant (P < 0.05). Conclusions Our current results indicate that MMP-7 may play a significant role in the progression of noninvasive to invasive IPMC.     

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胰腺导管内乳头状黏液性肿瘤(intraductal papil-lary mucinous neoplasm,IPMN)分主胰管型、混合型和分支胰管型。主胰管型、混合型和有症状的分支胰管型IPMN建议行手术切除,对恶性IPMN,需行规则性胰腺切除。对良性和交界性IPMN,可行功能保留性胰腺手术。对暂时不行手术切除的IPMN病人,应定期随访。IPMN的治疗决策需综合考虑各方面因素,包括病人的预期寿命、身体状况、治疗意愿、依从性、随访的条件等加以综合评估,最后形成个体化的治疗方案。     

Repeating regional acute pancreatitis in the head of the pancreas caused by intraductal papillary mucinous neoplasms in the tail: report of a case

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucin production and cystic dilatation of the pancreatic ducts. The clinical presentation often involves recurrent episodes of pancreatitis associated with the temporal obstruction of the main pancreatic duct caused by the hypersecretion of mucin. We herein describe a case in which the patient repeatedly experienced the occurrence of idiopathic acute pancreatitis in the head of the pancreas over a 9-year period, and who was ultimately was cured by distal pancreatectomy for IPMNs in the pancreatic tail. This case illustrates the potential pitfalls in the diagnosis of IPMNs owing to a discrepancy between the site of pancreatitis and that of the IPMN. The possible mechanisms linking acute pancreatitis with the formation of IPMNs are also reviewed.     

Multifocal branch-duct pancreatic intraductal papillary mucinous neoplasms

The appropriate management for patients with multifocal branch-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas involving the entire pancreatic gland remains unclear. We present a 66-year-old woman who underwent pylorus-preserving pancreaticoduodenectomy for a branch-duct intraductal papillary mucinous carcinoma demonstrating a grape-like multilocular cyst, 35 mm in diameter, in the head of the pancreas along with numerous number of small branch-duct IPMNs in the whole pancreas. Histologically, the multifocal cystic lesions were lined by a single row of columnar mucin-containing epithelial cells without atypia. The patient has been doing well without any recurrence during 9-year follow-up after surgery. Surgical removal of the prominent lesions suspicious of malignancy and a close observation of the remaining lesions in the remnant pancreas may be a reasonable treatment plan for patients with multifocal branch-duct IPMNs involving the entire pancreatic gland.     

Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas include a spectrum of dysplasia ranging from minimal mucinous hyperplasia to invasive carcinoma and are extensive tumors that often spread along the ductal tree. Several studies have demonstrated that preoperative imaging is not accurate enough to adapt the extent of pancreatectomy and have suggested routinely using frozen sectioning (FS) to evaluate the completeness of resection and also to check if ductal dilatation is active or passive, in order to avoid an excessive pancreatic resection. Separate main duct and branch duct analysis is needed due to the difference in the natural history of the disease. FS accuracy averages 95%. Eroded epithelium on the main duct, severe ductal inflammation mimicking dysplasia and reactive epithelial changes secondary to obstruction can lead to inappropriate FS results. FS results change the planned extent of resection in up to 30% of cases. The optimal cut-off leading to extend pancreatectomy is not consensual and our standard option is to extend pancreatectomy if FS reveals: (1) at least IPMN adenoma on the main duct; or (2) at least borderline IPMN on branch ducts; or (3) invasive carcinoma. However, the decision to extend resection must be taken after a multidisciplinary discussion since it does not exclusively depend on the FS result but also on age, general condition and expected prognosis after resection. The main limitation of using FS is the existence of discontinuous ("skip") lesions which account for approximately 10% of IPMN in surgical series and can lead to reoperation in up to 8% of cases.     

Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current Perspectives

In this article, we aimed to review the literature on the clinics and management of intraductal papillary mucinous neoplasm (IPMN). Intraductal papillary mucinous neoplasm of the pancreas is a mucin-producing cystic mass originating from the pancreatic ductal system. Approximately 25% of the pancreatic neoplasms resected surgically and 50% of pancreatic cysts detected incidentally are IPMNs. They can be benign or malignant in character, while malignant transformation of benign forms can be encountered. It is important to determine IPMNs in the early stages, implementation of appropriate treatment approaches, and follow-up to provide better prognosis. We reviewed the studies published in the English medical literature through PubMed and summarized the clinical features and current approaches to the treatment and follow-up of the IPMN. Due to the recent advances and widespread implementation of radiological imaging techniques, the incidental detection rate of IPMNs has increased significantly. The effective treatment of the disease is possible via the detailed diagnosis of the disease, determination of the prognostic factors, and a multidisciplinary approach. Recent literature also emphasized the molecular profile determination approaches for assessment of prognosis of patients with IPMN. Current knowledge on IPMN, a clinically important epidemiologic problem, shows that the treatment should be personalized considering the prognostic features and life expectancy of the patient.Key words: Intraductal papillary mucinous neoplasm, Pancreas, Treatment optionsIntraductal papillary mucinous neoplasm (IPMN) of the pancreas is a mucin-producing cystic mass originating from the pancreatic ductal system.^1,2 It was first defined by Ohashi et al³ in 1982 following the detection of four patients with puffiness in the Vater ampulla, dilated pancreatic ducts, and mucin secretion. In the following years, lesions with similar characteristics were reported under different names. Finally, the World Health Organization (WHO) classified the mucin-producing cystic masses of the pancreas into 2 groups: mucinous cystic neoplasm and IPMN.^4,5 Recent advances and widespread implementation of radiological imaging techniques, as well as the identification and classification of the disease, has led to an increased detection rate and incidence of IPMNs. They can be benign or malignant in character, while malignant transformation of benign forms can be encountered. In general, compared with sporadic pancreatic adenocarcinomas, invasive IPMNs have a better prognosis. The overall survival 5 years after resection is reported to be 22% for invasive IPMNs and 11% for sporadic pancreatic adenocarcinomas.^6,7 It is important to determine IPMNs, which are clinically important epidemiologic problems, in the early stages, for implementation of appropriate treatment approaches, and follow-up to provide better prognosis.     

胰腺导管内乳头状黏液性肿瘤的诊治策略

胰腺导管内乳头状黏液性肿瘤（intraductal papillary mucinous neoplasm,IPMN）分主胰管型、混合型和分支胰管型。主胰管型、混合型和有症状的分支胰管型IPMN建议行手术切除,对恶性IPMN,需行规则性胰腺切除。对良性和交界性IPMN,可行功能保留性胰腺手术。对暂时不行手术切除的IPMN病人,应定期随访。IPMN的治疗决策需综合考虑各方面因素,包括病人的预期寿命、身体状况、治疗意愿、依从性、随访的条件等加以综合评估,最后形成个体化的治疗方案。     

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.     

Frozen sectioning of the pancreatic cut surface during resection of intraductal papillary mucinous neoplasms of the pancreas is useful and reliable: a prospective evaluation

OBJECTIVE: To prospectively evaluate the accuracy of frozen sectioning (FS) of the pancreatic transection margin and its influence on surgery during resection of intraductal papillary and mucinous neoplasms (IPMNs). SUMMARY BACKGROUND DATA: Preoperative assessment of IPMN extension is difficult and transection margin is frequently tumoral on the surgical specimen. PATIENTS AND METHODS: FS was performed in 127 patients who underwent partial pancreatectomy for IPMN from 1996 to 2004, corresponding to 90 pancreaticoduodenectomies (1-4 successive FS; total = 132), 25 distal pancreatectomies (1-2 FS; total = 27), and 12 medial pancreatectomies (2-4 FS; total = 29). Dysplasia was graded in both main (MD) and branch ducts (BD), and pancreatectomy was extended if FS revealed at least IPMN adenoma on the MD or borderline IPMN on BD (defined as "significant" lesions). RESULTS: The 188 FS revealed that MD and BD epithelium comprised significant noninvasive lesions in 49 and 13 cases, respectively, and infiltrating carcinoma in 4 other ones. Definitive examination corroborated FS in 176 of 188 cases (94%). Altogether, 54 of 188 (29%) FS comprised significant lesions that resulted in 46 additional resections in 38 patients (30%). Eight patients did not have additional resection because of either high operative risk or preoperative diagnosis of noncurable infiltrating carcinoma. The 134 FS without significant lesions were associated with 7 additional resections mainly because of macroscopic suspicion of another tumor location. Conflicting results between FS and definitive examination resulted in inadequate extent of pancreatectomy in 4 patients (3%). CONCLUSIONS: Results of FS of the transection margin are confirmed by definitive examination in 94% of cases. According to our protocol, FS changes the extent of resection in 30% of patients and allows adequate resection in 97% of patients.