Management of intraductal papillary-mucinous neoplasm of the pancreas: treatment strategy based on morphologic classification

GOALS: The aim of this study was to examine and clarify the preoperative markers that are useful for differentiating between benign and malignant lesions of intraductal papillary-mucinous neoplasms (IPMN) of the pancreas, grouped according to morphologic classification. BACKGROUND: There are various stages of pathology in IPMN, ranging from benign to malignant lesions. Although the determination of appropriate treatment guidelines to deal with IPMN is a critical issue, no such guidelines have been established. PATIENTS AND METHODS: One hundred twenty cases of IPMN were classified morphologically into either main or branch duct types. We compared the morphologic classification with histopathologic diagnosis using indicators of malignancy detected by imaging such as main duct diameter, the number and diameter of cysts, and the presence or absence of mural nodules. We also examined the usefulness of pancreatic juice cytology and measurement of telomerase activity as indicators of malignancy. Finally, we performed a survival analysis on the basis of morphologic classification to determine prognosis of IPMN. RESULTS: Whereas a high incidence (64%) of malignant lesions was seen in main duct type IPMN, benign lesions were dominant (80.5%) in branch duct type IPMN. Survival analysis showed that the prognosis was significantly worse in main duct type than in branch duct type IPMN. The lesions were aggravated in all patients with main duct type who did not undergo resection, resulting in death due to progression of the pancreatic lesion. The incidence of mural nodules was a useful indicator in main duct type, whereas main duct diameter and incidence of mural nodules were useful indicators in branch duct type. Although pancreatic juice cytology showed a high accuracy rate with low sensitivity for determining malignancy, measurement of telomerase activity in this juice was very effective for differentiating between benign and malignant lesions. CONCLUSIONS: The incidence of malignant lesions was extremely high in main duct type IPMN, indicating that surgery is required in all these patients. However, to determine whether surgery is indicated in branch duct type IPMN it is necessary to obtain an appropriate image diagnosis focusing on main duct diameter and mural nodules and also to carry out cytology and measurement of telomerase activity in samples of pancreatic juice.     

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.     

Clinicopathological features and medical management of intraductal papillary mucinous neoplasms

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are a clinicopathological entity that is being diagnosed with increasing frequency. However, the best approach to medical management of IPMN needs to be clarified. The aim of the present study was to identify preoperative features that may be predictors of malignant IPMN, and to define the medical management of IPMN of the pancreas. METHODS: A total of 23 patients who underwent surgical resection for IPMN of the pancreas at Kochi Medical School between 1982 and 2004 were examined. Multivariate Cox regression analysis was used to identify factors independently associated with IPM carcinoma. RESULTS: Among the 23 patients, 12 had IPMN adenoma, three had borderline IPMN, four had IPMN with carcinoma in situ, and four had IPMN with invasive carcinoma. In multivariate analysis, elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels were found to be preoperative predictors of malignant IPMN. These results suggest that the following IPMN of the pancreas should be resected: (i) IPMN of the pancreas situated in the main duct; (ii) IPMN located in the branch duct if the size of the cystic lesion is >30 mm and the mural nodules are >5 mm in height by endoscopic ultrasound (EUS); and (iii) the diameter of the main pancreatic duct is >10 mm by endoscopic retrograde pancreatography (ERP). Careful observation of patients with branch-type IPMN with small cysts and/or without mural nodules is recommended as a management strategy. CONCLUSION: The present study reinforces the need for immediate surgical resection of malignant IPMN and suggests indicators for IPMN that should assist physicians in making decisions on treatment options.     

胰腺导管内乳头状黏液瘤

胰腺导管内乳头状黏液瘤（IPMN）是由胰腺导管内产生黏液的上皮细胞呈乳头状增殖形成的肿瘤。与经典的胰腺癌相比,IPMN具有低度恶性、生长缓慢、少有侵犯周围组织、淋巴结转移率和再发率低的特点。IPMN根据肿瘤累及的部位可分为主胰管型、分支胰管型和混合型,病理组织特征涵盖从单纯腺瘤到浸润癌等多个亚型,临床表现多样,多种影像学检查手段可显示弥漫性或节段性扩张的主胰管和囊状扩张的分支胰管,ERCP经扩大的乳头获取黏液和胰液,取胰腺导管内皮组织和壁结节供活检均有助于诊断。IPMN确诊后应积极手术,手术切除率高,术后5年生存率高于一般的胰腺癌。本文就其临床表现、分类、病理特征、影像学诊断和治疗等方面做一综述。     

Size of mural nodule as an indicator of surgery for branch duct intraductal papillary mucinous neoplasm of the pancreas during follow-up

Background

A mural nodule is a strong predictive factor for malignancy in branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas, but the nodule size has hardly been considered. The aim of this study was to investigate whether a mural nodule of 10?mm was appropriate as an indicator of surgery for IPMN during follow-up.

Methods

The follow-up outcomes of 100 patients who had branch duct IPMN without mural nodules or who had branch duct IPMN with mural nodules of less than 9?mm in a tertiary care setting were investigated retrospectively. The patients underwent abdominal ultrasound (US) every 3?months and additional imaging examinations or cytologic examination of pancreatic juice when necessary. Surgery was recommended to them when a mural nodule developed or when a nodule enlarged and reached 10?mm.

Results

During an average follow-up period of 97?months, branch duct IPMNs developed mural nodules that reached 10?mm in 5 patients (0.62% per year). In one patient the IPMN was revealed to be non-invasive carcinoma by resection, 1 IPMN was shown to be malignant by further follow-up, and 3 were not resected because of refusal or the patient??s age. In 7 patients, mural nodules stayed within 9?mm. The remaining 88 patients lacked mural nodules in their branch duct IPMNs throughout the follow-up. The occurrence of invasive carcinoma around the IPMN was not indicated by imaging examinations in any patient. Univariate analysis showed that the size of the cyst at baseline significantly predicted the development of a mural nodule that reached 10?mm during follow-up (P?=?0.05).

Conclusions

A mural nodule of 10?mm is appropriate as an indicator of surgery in the follow-up of branch duct IPMN.     

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.     

Intraductal papillary mucinous neoplasm of the pancreas: diagnosis and treatment

Intraductal papillary mucinous neoplasm (IPMN) is characterized by cystic dilatation of the main and/or branch pancreatic duct. Only one-third of all patients are symptomatic, and others are diagnosed by chance. IPMNs are classified into 3 types: main duct, branch duct, and mixed IPMN. Most branch-type IPMNs are benign, while the other 2 types are frequently malignant. The presence of large mural nodules increases the possibility of malignancy in all types. Presence of a large branch-type IPMN and marked dilatation of the main duct indicate, at the very least, the existence of adenoma. Ultrasonography, endosonography, and intraductal ultrasonography clearly demonstrate ductal dilatation and mural nodules, and magnetic resonance pancreatography best visualizes the entire outline of IPMN. Not infrequently, synchronous or metachronous malignancy develops in various organs, including the pancreas. Prognosis is excellent after complete resection of benign and noninvasive malignant IPMNs. Asymptomatic branch-type IPMNs without mural nodules may be followed up without resection. Malignant IPMNs displaying acquired aggressiveness after parenchymal invasion require adequate lymph node dissection. Total pancreatectomy is needed for some IPMNs; its benefits, however, must be balanced against operative and postoperative risks because most IPMNs are slow growing and affect elderly people, and prognosis is favorable for IPMN patients with even malignant neoplasms.     

Pancreatic juice cytology as sensitive test for detecting pancreatic malignancy in intraductal papillary mucinous neoplasm of the pancreas without mural nodule

ObjectiveRecent studies reported that mural nodule (MN) was the most associated with malignant intraductal papillary mucinous neoplasms (IPMNs). However, IPMNs without MN cannot be diagnosed as malignant if only MN is determined to be indicator of malignancy. This study aimed to investigate role of pancreatic juice cytology for IPMNs without MN.MethodsMedical records of 50 patients with histologically proven malignant IPMNs were reviewed. Exclusively for non-invasive cancer, extent of high-grade dysplasia along the main pancreatic duct (MPD) was determined microscopically.ResultsThirty-six percent IPMNs had no MN. Cyst and main MPD diameter were significantly smaller in IPMN without MN compared to those in IPMN with MN (23 ± 14.1 vs 35 ± 13.2 mm, p = 0.010; 6.6 ± 4.3 vs 10.9 ± 6.1 mm, p = 0.006). Sensitivity of pancreatic juice cytology was higher in IPMN without MN compared to that in IPMN with MN (94% vs 53%, p = 0.004) although it could be affected by selection bias of study patients. Absence of MN was determined to be an independent factor associated with true positive cytology (OR = 24.3, p = 0.005). Extent of high-grade dysplasia was significantly longer in IPMN with true positive cytology compared to that in IPMN with false negative cytology (46.8 ± 20.5 vs 26.4 ± 11.0 mm, p = 0.005), and tended to be longer in IPMN without MN compared to that in IPMN with MN (47.0 ± 19.0 vs 36.0 ± 20.1 mm, p = 0.16).ConclusionsSensitivity of pancreatic juice cytology was excellent in IPMN without MN. Pancreatic juice cytology may be a sensitive test for detection of pancreatic malignancy in IPMN without MN compared to high-risk imaging features.     

A case of mixed adenoneuroendocrine carcinoma of the pancreas mimicking intraductal papillary mucinous carcinoma

A previously healthy 52-year-old man was referred to our hospital for further evaluation of main pancreatic duct dilatation. The preoperative work-up was consistent with intraductal papillary mucinous carcinoma (IPMC) derived from a mixed type intraductal papillary mucinous neoplasm (IPMN), because multilocular cysts with enhancing thickened pancreatic head walls and dilated pancreatic ducts lined with dysplastic mucinous epithelium, with papillary proliferation from the pancreatic body to the tail, were observed; in addition, the pancreatic juice cytology was class V, which is suggestive of adenocarcinoma. Total pancreatectomy was performed because a definite mass was not found before surgical resection and the tumors could have spread to the tail. The pathological diagnosis was mixed adenoneuroendocrine carcinoma of the pancreatic head. IPMN with high- or low-grade dysplasia was not observed anywhere in the pancreatic duct. The pancreatic ductal adenocarcinoma consisted of large caliber malignant glands with intraluminal flat or papillary structures; therefore, we were unable to recognize a definite pancreatic mass before surgical resection, and suspected an IPMC derived from a mixed type IPMN.     

Clinical Evaluation of Brushing Cytology and Biopsy of the Pancreatic Duct in Patients with Mucin Producing Tumor of the Pancreas

Abstract: A cytological study of pure pancreatic juice obtained endoscopically after brushing the lesion of the pancreatic duct urns performed in 10 patients with mucin producing tumors of the pancreas. In 6 of these 10 patients, biopsies from the lesion in the pancreatic duct were also carried out endoscopically. The brushing cytology in all 6 patients with mucin producing carcinoma of the pancreas, except for the sidebranch type, showed cellular atypism and the cytological diagnoses were Class IV or Class V. The results of the brushing cytology in the patients assumed clinically benign were Class I ? Class III. Biopsy results in 4 patients with mucin producing carcinoma of the pancreas indicated that one of them had adenocarcinoma, and the other 3 had atypical hyperplasia which suggests the existence of malignancy. In the patient with adenoma, diagnosis of the biopsy specimen revealed hyperplasia only. It was concluded that cytology and biopsy of lesions in the pancreatic duct are a valuable way of assessing mucin producing tumors of the pancreas before surgery.     

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.     

Cytological and Cyst Fluid Analysis of Small (≤3 cm) Branch Duct Intraductal Papillary Mucinous Neoplasms Adds Value to Patient Management Decisions

Background/Aim: Management of patients with small (1–3 cm) branch duct intraductal papillary mucinous neoplasms (IPMN) is a challenge. Symptoms, dilated duct, mural nodule or positive cytology have been proposed as parameters for resection. The aim of our study was to compare this proposed algorithm to one that incorporates cytology with less than malignant epithelial cells and cyst fluid carcinoembryonic antigen (CEA). Methods: A retrospective study was conducted. Results: There were 14 nonmalignant and 6 malignant cysts with 3 invasive IPMN. None were associated with a dilated duct and none had positive cytology. Only a mural nodule was significant by univariate analysis for the detection of malignancy (p = 0.01) and invasion (p = 0.009). The detection of atypical epithelial cells or a cyst fluid CEA of >2,500 ng/ml was more accurate for the detection of malignancy than using the recommended algorithm. Conclusions: The presence of a mural nodule in a small branch duct IPMN is a predictor of malignancy and invasion by univariate analysis. Recognition of an atypical epithelial cell component in contrast to positive cytology or a cyst fluid CEA of >2,500 ng/ml is more accurate than the recommended algorithm and adds value to the preoperative assessment of clinically diagnosed small branch duct IPMN.     

胰管内乳头状黏液性肿瘤的术前良、恶性与浸润性预测因子

目的 分析术前预测胰管内乳头状黏液性肿瘤(IPMN)良、恶性与浸润性的因子,及不同病理类型IPMN的手术后生存率.方法 回顾性分析长海医院1993年1月至2009年9月间手术切除的78例IPMN病例资料,采用单因素与多因素分析的方法分析病史、临床表现、肝功能、CEA、CA19-9、影像学征象等在术前判断IPMN良、恶性与浸润性的价值,分析患者术后生存率.结果 单因素分析结果显示,黄疸、急性胰腺炎、血CA19-9>37 U/ml、AKP、肿块边界不清为恶性及浸润性预测因子;主胰管扩张、分支胰管直径>30 mm、出现壁节结等为恶性预测因子;CEA>6 ng/ml为浸润性预测因子.多因素分析显示,肿块边界不清为恶性及浸润性预测因子;急性胰腺炎为浸润性预测因子.良性IPMN患者的5年生存率为100%;恶性IPMN的2年生存率为78.9%、5年生存率为68.5%,其中浸润性IPMN的2年生存率为64.6%、5年生存率为43.1%.结论 肿块边界不清为IPMN恶性预测因子,急性胰腺炎、肿块边界不清是IPMN的浸润性预测因子.     

COMPARISON OF THE HEIGHT OF PAPILLARY TUMOR IN INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS BETWEEN MEASURED PREOPERATIVE IMAGES AND RESECTED MATERIAL

The height of the mural nodules and papillary tumors in main pancreatic duct or dilated branch duct is the most important factor for diagnosis of intraductal papillary mucinous neoplasm (IPMN). In this study, the authors compared the height of the papillary lesions and mural nodules between the height of resected tissues and the height detected by the preoperative imaging tools (endoscopic ultrasonography [EUS] and intraductal ultrasonography [IDUS]) in 38 patients with IPMN. In 21 out of 23 cases of adenoma, and in cases with the non‐invasive cancer, the difference of the height of operative and preoperative analysis measured by EUS and IDUS was within 1–2 mm. EUS and IDUS are useful for diagnosis of degree of malignancy in IPMN.     

Magnetic resonance (MR) for mural nodule detection studying Intraductal papillary mucinous neoplasms (IPMN) of pancreas: Imaging-pathologic correlation

PurposeMagnetic Resonance (MR) is recommended to diagnose Intraductal Papillary Mucinous Neoplasms (IPMN) and in the follow-up of borderline lesions. The purpose of this work is to evaluate the diagnostic accuracy of dynamic MR with Diffusion Weighted Imaging (DWI) in the identification of mural nodules of pancreatic IPMN by using pathological analysis as gold standard.Materials and methodsNinety-one preoperative MR with histopathological diagnosis of IPMN were reviewed by two radiologists. Presence, number and size of mural nodule, signal intensity of the nodule on T1-weighted imaging (T1-WI) after contrast medium administration and on DWI. Inter-observer agreement was evaluated.ResultsSignificant correlation (p < 0.0001) were found for presence of nodules > 5 mm on MR and pathological specimen, size and number of mural nodules evaluated on pathological review and degree of dysplasia, size and number of mural nodules evaluated on MR and tumoral dysplasia, presence of nodule > 5 mm with enhancement after contrast medium administration and hyperintensity on DWI and degree of dysplasia. Interobserver agreement was moderate for the presence of mural nodule (K = 0.56), for the presence of high signal intensity on DWI (K = 0.57) and enhancement of mural nodule (K = 0.58). Apparent Diffusion Coefficient (ADC) map histogram analysis showed a correlation between Entropy of the entire cystic lesion and the degree of dysplasia (p < 0.034).ConclusionsMR with dynamic and DWI sequences was an accurate method for the identification of ≥ 5 mm solid nodules of the IPMNs and correlate with the lesion malignancy. Entropy, calculated from the histogram analysis of the IPMN ADC map, correlated with the lesion dysplasia.     

Intraductal papillary mucinous neoplasms of the pancreas: clinical surveillance and malignant progression, multifocality and implications of a field-defect

Intraductal papillary mucinous neoplasms (IPMNs) are a heterogeneous group of mucin producing cystic tumors that involve the main pancreatic duct and/or branch ducts and may be associated with invasive carcinoma. Predicting the risk of malignant transformation of an IPMN lesion can be challenging. The Sendai criteria, based in large part on radiographic imaging features, help guide surgical intervention based on the stratification of cysts into high and low risk lesions for malignancy. Invasive carcinoma may develop in the index IPMN lesion or in a separate site within the pancreas, supporting the concept of a field defect in IPMN tumorigenesis. This stresses the importance of evaluation of the entire pancreas upon diagnosis of IPMN and continued surveillance of the residual pancreas following resection. Herein, the authors summarize the data presented at the 2012 ASCO Gastrointestinal Cancers Symposium regarding prevalence and site of invasive carcinoma detected in patients undergoing surveillance for IPMN (Abstract #152).     

Clinicopathologic review of 41 cases of pancreatic mucinous cystic neoplasms]

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms are included in mucin-producing pancreatic tumors. The reports about IPMN are not uncommon but those about the mucinous cystic neoplasms are relatively few. The aims of this study were to define the natural history of resected mucinous cystic neoplasms of the pancreas and to identify the findings which suggest malignancy. METHODS: The authors retrospectively evaluated the clinical outcomes of 41 patients with mucinous cystic neoplasms who were surgically resected at Asan Medical Center between 1995 and 2004. RESULTS: Women (n=33) were more frequently affected than men (n=8). Thirty three patients (80.6%) had adenoma, 1 (2.4%) borderline malignancy, 1 (2.4%) carcinoma in situ, and 6 (14.6%) invasive mucinous cystadenocarcinoma. The most frequent symptom was abdominal pain (39%). About half of the enrolled patients were asymptomatic. Unilocular type (79%) was more frequent than the multilocular type (21%) on gross morphology. The tumor size of invasive mucinous cystic neopolasms was larger than that of non-invasive mucinous cystic neoplalsms (p=0.01). Abdominal pain was more frequent in invasive mucinous cystic neoplasms (p=0.026). On gross morphology, mural nodules were detected in 4 of 6 patients with invasive mucinous cystic neoplasms. However, they were not detected in any patients with non-invasive mucinous cystic neoplasms. Recurrence developed in none of the 35 patients with non-invasive mucinous cystic neoplasms, however 2 of the 6 patients with invasive mucinous cystic neoplasms died within 5 years. CONCLUSIONS: Clinical predictors of invasive mucinous cystic neoplasms are suggested to be tumor size and abdominal pain. The prognosis of the non-invasive mucinous cystic neoplasms is excellent when curative resection is performed.     

CLINICAL SIGNIFICANCE OF INTRADUCTAL ULTRASONOGRAPHY FOR DIAGNOSIS OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS

Intraductal ultrasonography (IDUS) is useful for evaluating the horizontal spread along the main pancreatic duct in cases of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, thus providing valuable information for the determination of the resection line at surgery. Differentiation between benign and malignant IPMN is also indispensable for management decisions. Measurement of the height of mural nodules by IDUS is expected to be useful for differential diagnosis of IPMN. Because IDUS cannot always demonstrate whole lesions, especially in branch duct IPMN, endoscopic ultrasonography plays a complementary role in such cases.     

Imaging IPMN: take home messages and news

IPMN is a frequent disease involving pancreatic duct. This disease could be malignant (parenchymal invasive adenocarcinoma), particularly if the main pancreatic duct is involved (this involvement is considered present if > 6 mm), if this enlargement reaches 10 mm or more, and if the pathological phenotype is biliopancreatic or intestinal (malignancy is less frequent if gastric one). Invasiveness is suspected if hypodense parenchymal lesion is present, particularly near a cystical lesion or MPD, a mural nodule of the wall, or if MPD wall has got a contrast uptake. Mural nodules inside cystic branch duct are associated with in situ grade 3 malignancies. MPD IPMN must be resected to prevent malignancy. The follow-up of isolated branch duct cysts relies upon MDCT and MRI, every two years if lesion is less than 1cm. Every one year if bigger, particularly if more than to 3 cm.     

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

Background/Purpose

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs.

Methods

Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct’s largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations.

Results

Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2–8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2–5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323).

Conclusions

The incidence of K-ras mutation may be associated with the hypersecretion of mucin.