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.     

Branch-duct intraductal papillary mucinous neoplasms: observations in 145 patients who underwent resection

BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas arising in branch ducts are thought to be less aggressive than their main-duct counterparts, and guidelines for their conservative management were recently proposed. This study describes the combined experience of 2 tertiary centers with branch-duct IPMNs aiming to validate these recommendations. METHODS: A review of 145 patients with resected, pathologically confirmed, branch-duct IPMNs between 1990 and 2005 was conducted. RESULTS: Sixty-six patients (45.5%) had adenoma, 47 (32%) borderline tumors, 16 (11%) carcinoma in situ, and 16 (11%) invasive carcinoma. Median age was similar between benign and malignant subgroups (66 vs 67.5 years, respectively). Jaundice was more frequent in patients with cancer (12.5% vs 1.8%, respectively, P = .022) and abdominal pain in patients with benign tumors (45% vs 25%, respectively, P = .025). Forty percent of tumors were discovered incidentally. Findings associated with malignancy were the presence of a thick wall (P < .001), nodules (P < .001), and tumor diameter >or=30 mm (P < .001). All neoplasms with cancer were larger than 30 mm in size or had nodules or caused symptoms. After a mean follow-up of 45 months, the 5-year disease-specific survival for branch-duct IPMNs with noninvasive neoplasms was 100% and, for invasive cancer, was 63%. CONCLUSIONS: This large cohort of resected branch-duct IPMNs shows that cancer is present in 22% of cases and validates the recent guidelines that indicate absence of malignancy in tumors <30 mm, without symptoms or mural nodules.     

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.     

Total pancreatectomy in six patients with intraductal papillary mucinous tumour of the pancreas: the treatment of choice

BackgroundIntraductal papillary mucinous tumours (IPMT) were described as a distinct entity in l982.The extent of surgical resection remains controversial.MethodsSix patients with a diffuse dilatation of the main pancreatic duct were treated with total pancreatectomy for cure of IPMT.ResultsHistological examination showed one IPM adenoma, four IPM non-invasive carcinomas and one IPM invasive carcinoma. In all but one case multifocal extensive intraductal changes were found, affecting either most of the pancreas or the whole organ. All patients survived the operation and remain alive 5–56 months later. Post-pancreatectomy diabetes has been moderately well controlled.DiscussionIPMTs represent a subgroup of pancreatic neoplasms with a favourable prognosis, and the resection should aim at removing all dysplastic foci. In cases with diffuse dilatation of the main pancreatic duct, widespread tumour involvement of the duct system can be expected, so total pancreatectomy should be the operation of choice.     

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.     

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.     

Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms

AIM: To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. RESULTS: CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P<0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. CONCLUSION: Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.     

内镜黏膜下剥离术切除胃内异位胰腺伴导管内乳头状黏液性肿瘤1例

异位胰腺伴导管内乳头状黏液性肿瘤形成是一种罕见的疾病,国内鲜见报道,主要位于胃、肝内胆管和小肠。本文报道1例病例,病变位于胃壁,术前超声内镜显示病变位于黏膜下层,内部回声局部呈中高回声,可见囊腔样无回声区,经内镜黏膜下剥离术完整切除,术后病理为异位胰腺伴导管内乳头状黏液性肿瘤（胃型）。