Intraductal Papillary Mucinous Neoplasms Of Pancreas Research Articles

Risk for Extrapancreatic Malignancies Among Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas (IPMNs)

Risk for Extrapancreatic Malignancies Among Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas (IPMNs)

Undetermined cystic lesions of the distal pancreas: When resection is not warranted regardless of the diagnosis

Some biliary diseases mimic pancreatic diseases pathologically as well as pathogenetically. Such diseases can be called “biliary diseases with pancreatic counterparts”. Biliary intraepithelial neoplasm (BilIN), intraductal papillary neoplasm of bile ducts (IPNB), hepatobiliary mucinous cystic neoplasm (hMCN), and IgG4-inflammatory pseudotumor represent the biliary counterparts of pancreatic intraepithelial neoplasm (PanIN), intraductal papillary mucinous neoplasm of pancreas (IPMN), pancreatic MCN, and mass forming type 1 autoimmune pancreatitis (AIP), respectively. BilIN and PanIN represent pre-invasive intraepithelial stages of nodular sclerosing cholangiocarcinoma and pancreatic ductal adenocarcinoma, respectively. IPNB and IPMN are grossly visible, predominant papillary, intraductal neoplasms that may progress to invasive carcinoma. Morphologically similar MCNs with subepithelial ovarian-like stroma occur in both the hepatobiliary system as well as the pancreas. IgG4-inflammatory pseudotumor, usually of the lymphoplasmacytic type, and mass forming type 1 AIP represent IgG4-related disease in the biliary tree and pancreas respectively. The biliary tract, which is associated with the peribiliary glands, including the pancreatic acini, can be regarded as an incomplete pancreas, so several diseases mimicking pancreatic diseases may be expected to occur in the biliary tract (biliary diseases with pancreatic counterparts).

Characterization of intraductal papillary neoplasm of bile duct with respect to histopathologic similarities to pancreatic intraductal papillary mucinous neoplasm

Intraductal papillary neoplasm of bile duct (IPNB) is a papillary tumor covered by well-differentiated neoplastic epithelium with fine fibrovascular cores in the dilated bile ducts. It reportedly shows similarities to intraductal papillary mucinous neoplasm of pancreas (IPMN), to various degrees. Herein, IPNB was pathologically analyzed by classifying 52 cases into 4 groups based on the histopathologic similarities to IPMN: group A (identical to IPMN, 19 cases), group B (similar to but slightly different from IPMN, 18 cases), group C (vaguely similar to IPMN, 5 cases), and group D (different from IPMN, 10 cases). In group A, intrahepatic and perihilar regions were mainly affected, most cases were of low/intermediate or high grade without invasion, and gastric type was the most common phenotype, followed by oncocytic and intestinal types. In groups C and D, perihilar and distal bile ducts were affected, almost all cases were of high grade with invasion, and most of them were of intestinal and pancreatobiliary phenotypes. Most group B cases were of intestinal phenotype, and all were of high grade with or without invasion. In conclusion, these 4 groups of IPNB showed unique pathologic features and behaviors. Group A cases were less aggressive and shared many features with IPMN, whereas group C and D cases were more aggressive and mainly found in perihilar and distal bile ducts. Group B resembling IPMN was intermediate between them. This classification may be useful in clinical practice and holds promise for a novel approach to analyze IPNB tumorigenesis.

Intracholecystic papillary-tubular neoplasm of the gallbladder

The pathologic description for neoplastic polyps of the gallbladder (GB) was controversial. Although current WHO suggest adenoma and papillary neoplasm for precursor lesions, the distinction is not clear. In recent study for 123 GB cases, we found tumoral preinvasive neoplasms (≥ 1 cm) were analogous to their pancreatic and biliary counterparts. They show variable cellular lineages, a spectrum of dysplasia, and a mixture of papillary or tubular growth patterns, often with significant overlap, warranting their classification under one unified parallel category, intracholecystic papillary-tubular neoplasm (ICPN). We found that ICPN have similarity with intraductal papillary-mucinous neoplasm of pancreas (IPMN) and intraductal papillary neoplasm of bile duct (IPNB). ICPN of GB showed similar cell lineage and mucin core protein expression pattern with IPMN and IPNB. It is suspected that ICPN might be a GB counterpart with IPMN and IPNB. We think these polypoid precursor lesions of pancreatobiliary tract and GB may correspond to tumoral intraepithelial neoplasia, whereas the pancreatic intraepithelial neoplasia and biliary intraepithelial neoplasia correspond to the flat intraepithelial neoplasia. We also found there is a geographic difference of ICPN incidence between East and West. ICPN was more common in East whereas conventional flat dysplasia was more frequently found in West.

Tumeurs intracanalaires papillaires et mucineuses du pancréas découvertes fortuitement : à propos d’un cas

Intraductal papillary mucinous neoplasms of pancreas (IPMN) are cystic lesions of the pancreas than can be associated with extra-pancreatics malignancies. We report a case of intraductal papillary mucinous neoplasm discovered incidentally during the staging of rectal adenocarcinoma. This observation illustrates the high frequency of IPMN incidentally discovered, for instance during the work-up of an extrapancreatic tumor.

The application value of contrast-enhanced ultrasound in the differential diagnosis of pancreatic solid-cystic lesions

To retrospectively determine the accuracy of baseline ultrasound (BUS) and of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of pancreatic solid-cystic lesions. Fifty-four pancreatic solid-cystic lesions in 52 patients were examined with BUS and CEUS, two different seniority radiologists read the images independently, Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic value of BUS and CEUS in the diagnosis of benign or malignant pancreatic solid-cystic lesions, the diagnostic consistency between different seniority radiologists was evaluated by Kappa statistics. Among the 54 lesions, there were pancreatic cyst five cases, pancreatic pseudocyst twenty cases, pancreatic cystadenoma eight cases, pancreatic cystadenocarcinoma seven cases, intraductal papillary mucinous neoplasm of pancreas (IPMN) three cases, pancreatic carcinoma combined liquefied six cases, solid-pseudopallary tumor of pancreas (SPTP) three cases, pancreatic myopericytoma one case, pancreatic lymphangioma one case. After ROC analysis, the areas under the ROC curve (Az) were 0.752 by BUS, 0.928 by CEUS to resident radiologist, and 0.896 by BUS, 0.954 by CEUS to staff radiologist. The correct diagnosis rate of specific disease was 42.6% by BUS, 64.8% by CEUS to staff radiologist (P<0.05), and 33.3% by BUS, 53.7% by CEUS to resident radiologist (P<0.05). The interobserver agreement in CEUS is higher than that in BUS, the Kappa value was 0.889 ± 0.062 and 0.428 ± 0.126 respectively. Compared with BUS, CEUS can significantly enhance the diagnostic rate of pancreatic solid-cystic lesions.

Predictive Value of Serum Carbohydrate Antigen 19‐9 in Malignant Intraductal Papillary Mucinous Neoplasms

The goal of the present study was to evaluate the predictive value of serum carbohydrate antigen 19-9 (CA 19-9) in the diagnosis of malignant intraductal papillary mucinous neoplasms of pancreas (IPMNs). Eighty-six patients with pathological diagnosis of IPMNs in Zhongshan Hospital between March 1999 and November 2008 were retrospectively reviewed. Data reflecting clinical characteristics, tumor marker level, and prognosis were collected. The potential predictive value of CA 19-9 was analyzed by receiver operating characteristic (ROC) curve. Eighty-six consecutive patients with IPMNs all underwent surgical intervention. A high level of CA 19-9 or carcinoembryonic antigen (CEA) was associated with more advanced stage of malignant IPMNs. Carbohydrate antigen 19-9 was significant for judging malignant IPMNs in the binary logistic regression model (p=0.047). The hazard ratio was 1.014, whose 95.0% confidence interval was 0.91-1.028. Receiver operating characteristic analysis showed that the serum CA 19-9 level had good predictive value for malignant or invasive IPMNs, postoperative survival, and disease-specific recurrence. The area under the curve (AUC) was 0.856, 0.893, 0.815, and 0.857 (p<0.05), respectively. According to the follow-up, mean survival time for groups with CA 19-9>63.60 U/ml was dramatically shorter than that for groups with CA 19-9≤63.60 U/ml (57.38±2.85 versus 29.24±5.82 [months]; p<0.01). Serum CA 19-9 level has good predictive value for malignant or invasive IPMNs. Patients with CA 19-9 > 63.60 U/ml had poor postoperative prognosis in IPMNs. Preoperative abnormal serum CA 19-9 might be predictive for an aggressive surgical intervention in IPMNs.

Clinical role of regulatory T cell in intraductal papillary mucinous neoplasms

e15537 Background: Intraductal papillary mucinous neoplasms of pancreas (IPMNs) have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. Recently, several investigators have reported that regulatory T cells (Foxp3+CD4+ T cells including CD4+CD25+ T cells and CD4+CD25- T cells) play important roles in anti-tumor immunity. We previously reported clinical role of increased populations of Foxp3+CD4+ T cells (Treg) in peripheral blood from advanced pancreatic cancer patients (Pancreas 2006). This study was conducted to clarify the clinical role of Treg for surveillance of IPMNs. Methods: Thirty-five patients with IPMNs (IPMC: n=8, IPMB: n=2, IPMA: n=5) and pancreas cancer (n=20) who underwent surgical resection were included in this study. Peripheral blood was withdrawn from IPMN patients (IPMC: n=5, IPMA: n=2) and PC patients (n=20), as well as healthy volunteer donors (n=20) as controls. The peripheral blood mononuclear cells (PBMCs) were subjected to FACScan analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Immunohistochemical expression of Foxp3 (abcam: FOXP3 antibody, 236A/E7), Fascin (Dako: Fascin antibody, 55K-2) and TGF-β (Santa Cruz: TGF-β1 antibody, SC146) in main tumor was assessed in all IPMN patients. Results: The Treg population among the PBMCs was significantly increased in IPMC patients (median: 4.50%) and PC patients (median: 3.06%) compared with healthy donors (median: 1.30%). No significant difference in the Treg population among the PBMCs was observed between IPMC and PC patients. On the other hand, in IPMA patients (n=2), the Treg population among the PBMCs was equivarent to healthy donors (2.40 and 1.85% respectively). In immnohistochemical staining, the positive expression of Foxp3 was 87.5% (7 of 8) in IPMC patients, while in IPMA and IPMB patients, the expression of Foxp3 was not observed. The expression of Fascin and TGF-β was not correlated to malignant potential of IPMNs Conclusions: Increase of Foxp3+CD4+ T cells in the PBMCs is a new promising marker for malignant potential in IPMNs patients. No significant financial relationships to disclose.

[Clinical features and prognosis of intraductal papillary mucinous neoplasms of pancreas: analysis of 38 cases].

To explore the diagnosis, clinical manifestation, treatment, and prognosis of intraductal papillary mucinous neoplasms (IPMNs) of pancreas. The clinical data of 38 patients with IPMNs, 23 males and 15 females, aged 64.1 +/- 10.7 (41 - 81), were analyzed respectively. The main symptoms included abdominal pain and jaundice. Pancreaticoduodenectomy was performed on 32 patients, total pancreatectomy on 1 patient, distal pancreatectomy on 3 patients; and pancreatic biopsy on 2 patients. One patient died during the peri-operational period. Pathology showed 15 cases of main-duct type, 14 cases of branch-duct type, 1 case of mixed type, and 8 cases being un-differentiated, all with dilatation of pancreatic duct at different degrees 4.6 mm in diameter on average. There were 30 cases of invasive IPMNs, with significantly higher level of carbohydrate antigen 19-9 (CA19-9), and 8 non-invasive. The median survival time was 18.5 months in general. In the invasive IPMN group the general median survival time was 16.1 months, and the 1, 2, and 5-year survival times were 54%, 31%, and 21% respectively; and in the non-invasive IPMN group the median survival time was 24.3 months, and the 1, 2, and 5-year survival times were 58% and 38% respectively; without significant differences in the survival times between these 2 groups. TMN staging showed 6 cases of stage 0, 15 cases of stage I, 9 cases of stage II, and 4 cases of stage III among the 34 patients of malignant IPMNs. The median survival times of the patients of the stages 0, I, II, and III were 31.3, 27, 9.1, and 8.9 months respectively with significant differences among them (P = 0.0124). IPMN of pancreas has no specific clinical manifestation. Dilatation of pancreatic duct is a manifestation in imaging examination characteristic of IPMN. The serum CA19-9 level is significantly higher in the patients with invasive IPMN. There are significant differences in survival rate among different groups according to TMN staging.

Genetic alterations in adenoma-carcinoma sequencing of intraductal papillary-mucinous neoplasm of the pancreas

We investigated the adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm from the aspect of genetic changes. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from patients with 16 intraductal papillary-mucinous adenoma of the pancreas (IPMA) and 10 intraductal papillary-mucinous carcinoma of the pancreas (IPMC) were provided for DNA extraction after microdissection. SSCP-DNA sequencing analysis demonstrated K-ras mutations at codon 12 in 75% of IPMA and 70% of IPMC, while those at codon 13 were observed neither in IPMA nor IPMC. There were no characteristic K-ras mutation types in IPMA and IPMC and no significant differences in incidence of K-ras mutations between the two categories. The frequencies of p53 mutations analyzed by SSCP-DNA sequencing were not high in IPMA (18.8%) and IPMC (30%), showing no significant difference between them. LOHs of APC in IPMA and IPMC were infrequent (6.3 and 20%, respectively) and showed no significant difference in incidence between the two categories. The LOH frequencies of DCC in IPMA and IPMC were 31.3 and 40%, respectively, and were not statistically different from each other. Taken together, genetic changes such as K-ras, p53, APC and DCC mutations may not be associated with adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm of pancreas.