Clinicopathological features of pancreatic intraepithelial neoplasias and their relationship to intraductal papillary-mucinous tumors

Pancreatic intraepithelial neoplasia (PanIN) is a recently proposed nomenclature for putative precursor lesions of pancreatic cancer, which are designated as PanIN-1 through -3 according to their increasing grade of dysplasia. A stepwise progression model of PanINs has been proposed, and multistep genetic alterations in PanINs are being investigated. PanIN-1A and PanIN-1B may remain unchanged for a long period. PanIN-3 potentially progresses toward invasive ductal carcinoma (IDC), and there are several case reports suggesting such progression. In these reported patients, PanIN-3 was found in specimens from partial pancreatectomies, and IDC manifested in the pancreatic remnant 17 months to 29 years after the surgery. We describe herein a patient with PanIN-3, in whom IDC manifested in the distal remnant pancreas 69 months after segmental pancreatectomy. Of the reported cases, including the present one, four of the patients were male and three were female, and the age at the first operation ranged from 46 to 70 years. Intraductal papillary-mucinous tumor (IPMT) is an entity that is distinct from PanIN. However, IPMTs of small size resemble PanINs morphologically. Loss of Dpc4 expression has been reported in the invasive component of IPMT, as well as in PanIN-3 and IDC. Analysis of mucin expression patterns has been reported, suggesting that, in practice, MUC1-positive MUC2-negative IPMTs may not be distinguishable from PanINs. There may be overlapping lesions between PanINs and IPMTs. Should the paradigm of the ductal origin of IDC be accepted, PanINs and a fraction of IPMTs would represent precursors of IDC.     

Clinicopathologic study of intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas

BACKGROUND/AIMS: We analyzed clinicopathologic and imaging findings of intraductal papillary-mucinous tumors (IPMTs) and mucinous cystic tumors (MCTs) of the pancreas to evaluate the difference between IPMTs and MCTs, and to identify the signs indicative of malignancy in IPMTs. METHODOLOGY: Clinicopathological features of 20 patients with IPMT and six patients with MCT of the pancreas were studied. RESULTS: The patients with IPMT comprised 16 males and four females with a mean age of 62.9 years. Eighty percent of IPMTs were located in the pancreatic head, and the mean tumor size was 38.6mm. Recurrence was observed in one patient, who died of IPM adenocarcinoma. In contrast, all patients with MCT were females, with a mean age of 53.0 years. None of the MCTs arose in the pancreatic head, and the mean tumor size was 42.7mm. One patient died of MC adenocarcinoma, but all of the others survived without recurrence. The difference in gender, location of the tumor, and connection to the pancreatic duct reached statistical significance between IPMTs and MCTs. A significant connection to the pancreatic duct and high level of serum carbohydrate antigen 19-9 (CA19-9) was observed in the adenocarcinoma and moderate dysplasia groups of IPMT. CONCLUSIONS: The main duct type and an elevation of serum CA19-9 level suggested malignancy in IPMTs.     

Intraductal papillary-mucinous tumor of the pancreas concomitant with ductal carcinoma of the pancreas

Background: Despite the recent progress of diagnostic and therapeutic modalities, the clinical course of patients with ductal carcinoma (DC) of the pancreas remains dismal. Intraductal papillary-mucinous tumor of the pancreas (IPMT) is sometimes accompanied by malignant diseases of the other organs and pancreatic adenocarcinoma. Thus, IPMT may be a potential diagnostic clue to DC of the pancreas at early phase. Methods: Clinico-pathologic findings of 7 Japanese patients with IPMT of the pancreas concomitant with independent DC were examined and compared with those of 69 patients with IPMT alone and of 70 with DC alone. Results: The seven patients corresponded to 9.2% of 76 patients with IPMT and 9.1 % of 77 patients with DC. The seven male patients ranged from 55 to 75 years with a mean of 64.3. DC was synchronous with IPMT in five patients, metachronous to IPMT (4 years after IPMT) in one, and synchronous with IPMT and metachronous to IPMT and DC (7 years after IPMT) in the other. In 4 patients, the presence of IPMT led to the diagnosis of DC. All the 7 IPMTs were of branch type with a mean diameter of 3.0 cm. The IPMT was located in the head of the pancreas in 3, body in 2 and tail in the other 2. All the 7 IPMTs were adenoma with mild dysplasia. Two of the 7 patients with DC had in situ carcinoma, 1 minimally invasive carcinoma and the remaining 4 invasive carcinoma. The mean diameter of seven DCs (3.0 cm) with IPMT were smaller than that of 70 DCs (3.6 cm) (8P = 0.0295). Stage (stage I/II/III/IV = 3/0/3/1) of the seven DCs concomitant with IPMT were significantly earlier than that (stage I/II/III/IV = 5/6/28/31) of the other 70 (p = 0.0203). The survival curve of the 7 patients with IPMT and DC was significantly better than that of the 70 with DC alone (p = 0.0460). Conclusions: Clinicians should pay attention to the possible presence of DC of the pancreas in male patients with intraductal papillary-mucinous adenoma of the pancreas of branch type in their 6th to 8th decades.     

Surgical treatment of intraductal papillary-mucinous tumor (IPMT) of the pancreas: operative indications based on surgico-pathologic study focusing on invasive carcinoma derived from IPMT

Background/Purpose. Between 1979 and 2000, 51 patients with intraductal papillary-mucinous tumor (IPMT) of the pancreas underwent surgical resection. Methods. The patients were reviewed to disclose the surgical pathology of invasive carcinoma derived from IPMT and to determine the surgical indications for IPMT on the basis of the pathologic findings. Results. The incidence of invasive carcinoma derived from IPMT according to the localization of the tumor was as follows: 4/9 (44%) in the main pancreatic duct (MPD type), 4/9 (44%) showing ductal spread from the MPD to branch ducts (mixed type), and 2/33 (6%) in the 2 branch duct (branch type). The maximal size of the intraductal spread of invasive carcinomas (8 of 18 cases in the MPD and mixed type together and 2 of 33 cases in the branch type) was as follows: 6/8 (75%) in the MPD and mixed type were over 6?cm in size, and the 2-branch-type invasive carcinomas were within the 3-cm size range. Conclusions. We concluded that for both invasive and noninvasive IPMTs, surgical resection was necessary for any MPD or mixed-type IPMTs, and that surgical resection was appropriate for branch-type lesions larger than or equal to 3?cm in diameter, or for lesions smaller than 3?cm showing rapid growth on clinical images.     

Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis

AIM/BACKGROUND: MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis. METHODS: Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically. RESULTS: The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival. CONCLUSION: The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC 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.     

MUC1 overexpression is the most reliable marker of invasive carcinoma in intraductal papillary-mucinous tumor (IPMT)

BACKGROUND/AIMS: To clarify the development of pancreatic cancer we performed immunohistochemical analysis of the presence of the major apomucin and cell-cycle regulatory proteins using the tissues of IPMT and ductal adenocarcinoma (DC) of the pancreas. METHODOLOGY: Formalin-fixed and paraffin-embedded tissues of 24 IPMT and 21 DC cases were subjected to immunohistochemical staining for MUC1, MUC2, p16, p53 and DPC4. According to the WHO classification, there were 10 intraductal papillary-mucinous adenomas (IPMA); 3 borderline intraductal papillary-mucinous neoplasms (IPMB); 4 intraductal papillary-mucinous carcinomas (IPMC), non-invasive type (nIPMC); 4 IPMCs with invasive muci nous carcinoma (IPMC/muc); and 3 IPMCs with invasive tubular adenocarcinoma (IPMC/tub). RESULTS: MUC1 expression was seen in 6 of 7 invasive IPMCs (86%) and in all DCs (100%). MUC2 was only seen in non-invasive IPMT and in a part of IPMC/muc. p53 nuclear staining was positive only in 3 of 7 invasive IPMCs (43%) and 9 of 21 DCs (43%). DPC4 nuclear expression was positive in almost all cases of non-invasive IPMT, but negative or reduced in 4 of 7 invasive IPMCs (57%), and 14 of 21 DCs (67%). CONCLUSIONS: MUC1 overexpression is considered to be the most sensitive and specific marker of invasive carcinoma, followed by DPC4 and p53 with less sensitivity.     

Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma

BACKGROUND AND AIMS: Intraductal papillary mucinous tumours (IPMT) of the pancreas constitute a unique pathological entity with an overall incidence of associated invasive malignancy of 20%. The malignant potential of an individual IPMT cannot be accurately predicted. Preoperative estimation of the risk of associated invasive malignancy with IPMT would be of significant clinical benefit. As aberrations in cell cycle regulatory genes are associated with the progression of precursor pancreatic ductal lesions to invasive adenocarcinoma, we examined expression of key cell cycle regulatory genes in the cyclin D1/retinoblastoma pathway and the transforming growth factor beta/Smad4 signalling pathway in a cohort of patients with surgically resected IPMT. METHODS: Sections of formalin fixed paraffin embedded pancreatic tissue from a cohort of 18 patients with IPMT were examined using immunohistochemistry for protein expression of cell cycle regulatory genes p16(INK4A), p21(CIP1), p27(KIP1), cyclin D1, pRb, and p53, as well as the cell signalling molecule Smad4. A comparison of expression levels was made between adenoma/borderline IPMT (10 patients) and intraductal papillary mucinous carcinoma (IPMC) (eight patients, four of whom harboured invasive carcinoma). Statistical analysis was performed using the chi(2) and Fisher's exact tests. RESULTS: Aberrant expression of the proteins examined increased in frequency from adenoma/borderline IPMT to IPMC. Specifically, there was a significantly greater incidence of loss of p16(INK4A) expression in IPMC: 8/8 lesions (100%) compared with 1/10 (10%) adenoma/borderline IPMT (p<0.001). Similarly, loss of Smad4 expression was associated with IPMC: 3/8 (38%) versus adenoma/borderline IPMT 0/10 (p<0.03). Loss of Smad4 expression within the IPMT was the best marker for the presence of invasive carcinoma (p<0.001). CONCLUSIONS: These data indicate that loss of p16(INK4A) and Smad4 expression occur more frequently in IPMC alone, or with associated invasive carcinoma, compared with adenoma/borderline IPMT. Aberrant protein expression of these cell cycle regulatory genes in IPMT and pancreatic intraepithelial neoplasia in the current model of pancreatic cancer progression suggest similarities in their development and may also represent the subsequent risk of invasive carcinoma.     

Immunohistochemical studies of mucin antigens in pancreas and intrahepatic bile-duct tumors

Our previous studies of pancreatic and intrahepatic bile-duct tumors revealed that MUC2 mucin (“secretory mucin”, detected by a polyclonal antibody, anti-MRP) was highly expressed in intraductal papillary-mucinous tumors of the pancreas (IPMTs) and bile duct cystadenocarcinomas of the liver (BDCs) with expansive growth pattern and favorable prognosis, whereas it was rarely or not expressed in invasive ductal carcinomas of the pancreas (IDCs) and cholangiocarcinomas of the liver (CCs) with invasive growth pattern and poor prognosis. In contrast, MUC1 mucin (“membrane-bound mucin” detected by the monoclonal antibody, DF3) was rarely or not expressed in IPMTs and BDCs, but was always expressed in IDCs and CCs (Cancer 71:2191—2199, 1993;Int J Cancer 55:82—91, 1993). The results of these studies suggest that the difference in the expression of MUC1 and MUC2 mucins is a useful indicator of malignant potential in neoplasms of the pancreas and intrahepatic bile duct. This article is a review of our previous studies described above. In addition, we present longer-term follow-up data for the cases reported in our previous studies as well as demonstrating pathological prognostic factors, such as lymph node status, lymphatic infiltration, and perineural invasion. We also examined several additional cases of IPMTs and analyzed the same prognostic factors. We could confirmed the findings of our previous studies, and found that most IPMTs and BDCs with a MUC1(?) and MUC2(+) expression pattern showed less aggressive pathological factors than most IDCs and CCS with a MUC1(+) and MUC2(?) expression pattern.     

Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells

Vaccination of patients with cancer using dendritic cells (DCs) was shown to be effective for B-cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu- or MUC1-derived peptides. Ten patients were included in this pilot study. The DC vaccinations were well tolerated with no side effects. In 5 of 10 patients, peptide-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood using both intracellular IFN-gamma staining and (51)Cr-release assays. The major CTL response in vivo was induced with the HER-2/neu-derived E75 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, suggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Our results show that vaccination of DCs pulsed with a single tumor antigen may induce immunologic responses in patients with breast and ovarian cancer. This study may be relevant to the design of future clinical trials of other peptide-based vaccines.     

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms

BACKGROUND: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. AIMS: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. METHODOLOGY: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. RESULTS: Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015). CONCLUSIONS: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.     

Vaccination against the HER-2/neu oncogenic protein

The HER-2/neu oncogenic protein is a well-defined tumor antigen. HER-2/neu is a shared antigen among multiple tumor types. Patients with HER-2/neu protein-overexpressing breast, ovarian, non-small cell lung, colon, and prostate cancers have been shown to have a pre-existent immune response to HER-2/neu. No matter what the tumor type, endogenous immunity to HER-2/neu detected in cancer patients demonstrates two predominant characteristics. First, HER-2/neu-specific immune responses are found in only a minority of patients whose tumors overexpress HER-2/neu. Secondly, immunity, if detectable, is of low magnitude. These observations have led to the development of vaccine strategies designed to boost HER-2/neu immunity in a majority of patients. HER-2/neu is a non-mutated self-protein, therefore vaccines must be developed based on immunologic principles focused on circumventing tolerance, a primary mechanism of tumor immune escape. HER-2/neu-specific vaccines have been tested in human clinical trials. Early results demonstrate that significant levels of HER-2/neu immunity can be generated with active immunization. The T-cell immunity elicited is durable after vaccinations have ended. Furthermore, despite the generation of CD8(+) and CD4(+) T-cells responsive to HER-2/neu in a majority of patients, there is no evidence of autoimmunity directed against tissues that express basal levels of the protein. Cancer vaccines targeting the HER-2/neu oncogenic protein may be useful adjuvants to standard therapy and aid in the prevention of relapse in patients whose tumors overexpress the protein. Furthermore, boosting HER-2/neu-specific T-cell frequencies via active immunization may allow the ex vivo expansion of HER-2/neu-specific T-cells for use in adoptive immunotherapy, a therapeutic strategy directed against the treatment of established disease.     

Intraductal papillary-mucinous tumor of the pancreas head with complete absence of the ventral pancreatic duct of Wirsung

A case of intraductal papillary mucinous tumor of the pancreas with complete absence of the ventral pancreatic duct of Wirsung is presented. A 74-year-old Japanese man was admitted to our hospital because of elevated serum amylase concentration. Abdominal computed tomography (CT) scanning revealed diffuse dilatation of the main pancreatic duct and a diffuse and uncircumscribed area with heterogeneous density in the pancreas head. Endoscopic retrograde cholangiopancreatography revealed that the main pancreatic duct was connected with an accessory papilla and was diffusely dilated, without any irregularity of the duct wall being observed in the entire length of the duct. The common bile duct was detected only by cannulation through Vater’s papilla, and no pancreatic duct or its communicating branch was found. Some branches, directed to the dorsal portion of the pancreas head, were found arising from the accessory pancreatic duct. Intraductal ultrasound examination performed through the accessory papilla and the common bile duct revealed a small tumor with a heterogeneous echo level in the pancreas head. From these findings, intraductal papillary-mucinous tumor (IPMT) occurring in the pancreas head was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen revealed IPMT in the pancreas head. A roentgenographic study of the resected specimen revealed a defect caused by the tumor located in the pancreatic duct connected with the accessory papilla and showed that there was complete absence of the pancreatic duct connected with Vater’s papilla. Surgical resection enabled us to completely analyze the duct system of pancreas divisum. Although it is not known whether there is a relationship between the pathogenesis of IPMT and embryological anomaly of the pancreatic duct system, this case may provide an insight into the pathogenesis of IPMT.     

Total pancreatectomy for intraductal papillary-mucinous tumor of the pancreas: reappraisal of total pancreatectomy

BACKGROUND/AIMS: Total pancreatectomy is rarely performed as the treatment of pancreatic carcinoma because of markedly impaired quality of life and poor prognosis. Intraductal papillary-mucinous tumor (IPMT) of the pancreas is characterized by extensive intraductal spread and favorable outcome even in its invasive stage. The role of total pancreatectomy was reappraised in the treatment of IPMT. METHODOLOGY: A total of five Japanese patients with IPMT underwent total pancreatectomy and their clinical follow-up data were reviewed. RESULTS: Total pancreatectomy was performed due to massive involvement of the entire pancreas in two patients, positive surgical margins on frozen section in one, benign IPMT with concomitant pancreatic cancers in one and recurrent IPMT in the remnant pancreas after distal pancreatectomy for IPMT in the other. Three of them underwent total pancreatectomy of the Whipple type, another underwent total gastrectomy and the other underwent the pylorus-preserving method. Surgical margins were negative by histology and no lymph node metastases were evident. Two patients had severe infection including liver abscess in one and pneumonia in the other. The former died on postoperative day 82 and the latter was controlled by medical treatment and discharged on postoperative day 73. The other three patients had an uneventful postoperative course and were discharged from 29 to 62 days after the operation. Long-term follow-up of the four patients revealed that three patients had hypoglycemic attacks, two diabetic retinopathy and two fatty liver. The four patients were doing well from 683 to 4,140 days after the operation without signs of recurrence. CONCLUSIONS: Total pancreatectomy would be indicated as a treatment of benign or malignant IPMT with extensive involvement when patients' condition permits and gives a chance of cure, although careful long-term medical care and follow-up are essential.     

Immunohistochemical analysis of molecular biological factors in intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas

BACKGROUND: To investigate the malignancy and differentiation of intraductal papillary-mucinous tumors (IPMTs) and mucinous cystic tumors (MCTs) of the pancreas, clinicopathologic characteristics and immunohistochemical features were analyzed. METHODS: The clinicopathologic characteristics and immunohistochemical features of 24 patients with IPMT and 8 with MCT who underwent pancreatic resections at our hospital were examined. Immunohistochemical features analyzed included expression of p53 protein, proliferating cell nuclear antigen, integrins, interleukin-1 receptor type I, and hormone-associated receptors, and the factors correlated with malignancy were identified by multiple logistic regression. RESULTS: Among the IPMTs, there were 16 intraductal papillary adenomas, 5 intraductal papillary adenocarcinomas, and 3 moderate dysplasias. Among the MCTs, there were 6 mucinous cyst adenomas and 2 mucinous cyst adenocarcinomas. Multivariate analysis revealed that of the clinicopathologic characteristics, only the presence of mural nodules (odds ratio (OR) 7.12, P = 0.044) was independently correlated with the malignancy of IPMTs, and that of the immunohistochemical features, only alpha integrin subunit expression was independently correlated with malignancy of pancreatic mucinous tumors (OR 15.6, P = 0.036), especially IPMTs (OR 35.7, P = 0.012). CONCLUSION: These results indicate that alpha-containing integrin expression can be a significant marker of malignancy in pancreatic mucinous tumors.     

Differential diagnosis of intraductal papillary‐mucinous tumor of the pancreas by endoscopic ultrasonography and intraductal ultrasonography

Background: Intraductal papillary‐mucinous tumor (IPMT) of the pancreas has a broad spectrum of histology ranging from hyperplasia to adenocarcinoma. Therefore, it is important to differentiate between the malignant and benign lesions to determine the therapeutic strategy for IPMT. Patients and Methods: Thirty‐nine patients with IPMT (27 men and 12 women, mean age: 63.3 years) underwent surgery between January 1985 and March 2002. The size of the cystic lesion, the maximum diameter of the main pancreatic duct (MPD), and the height of the papillary tumor inside the cyst were investigated by endoscopic ultrasonography (EUS) and/or intraductal ultrasonography (IDUS) before operation. These preoperative clinical findings were compared with the pathological findings of the resected specimen. Results: The size of the cystic lesion, the diameter of MPD, and the height of the papillary tumor in cases with malignant IPMT (invasive and non‐invasive carcinoma) were larger than those in cases with benign IPMT (adenoma and hyperplasia). Analysis of the images of the lesions revealed that the following three factors are important for diagnosing IPMT: (i) the size of the cystic lesion is ≥ 30 mm; (ii) the diameter of MPD is ≥ 8 mm; (iii) the height of the papillary tumor inside the cyst is ≥ 3 mm. It was not significant to differentiate between benign and malignant IPMT based on factor (i), but statistically significant (P < 0.001) based on factors (ii) and (iii). Conclusions: EUS and IDUS are useful in the differential diagnosis of IPMT, especially in the differentiation between malignant and benign IPMT.     

Natural history of intraductal papillary mucinous tumors of the pancreas: actuarial risk of malignancy.

BACKGROUND & AIMS: Natural history of intraductal papillary mucinous tumors of the pancreas (IPMTs) is unknown. Cross-sectional studies suggest that exclusive branch duct (BD) involvement is associated with a lower risk of carcinoma than main pancreatic duct (MPD) involvement. The aim of our study was to calculate longitudinal risk of malignant transformation of IPMT since the first sign. METHODS: All the patients with a diagnosis of highly probable or histologically proven IPMT were included. Actuarial risks of occurrence of at least low-grade dysplasia (>or=LGD), high-grade dysplasia (>or=HGD), or invasive carcinoma (IC) were calculated by Kaplan-Meier method from the first sign attributable to IPMT. The risks according to sex, acute pancreatitis, tumor size, and involvement of MPD were compared by log-rank test. RESULTS: One hundred six patients were included with a proven (n = 76) or probable (n = 30) IPMT. The tumor was confined to BD in 53 cases. Median duration since the onset of the first sign to the end of follow-up was 21 months (range, 0-241). Ten-year actuarial risk that IPMT grade was >or=LGD, >or=HGD, or IC was 67%, 49%, and 29%, respectively. The only morphologic risk factor of malignant transformation was involvement of MPD, with a 5-year actuarial risk of >or=HGD of 63% in the MPD group compared with 15% in the BD group (P < .001). CONCLUSIONS: Longitudinal risk of at least HGD or IC is time-dependent. Patients with BD IPMT present a much lower risk, justifying a nonoperative surveillance.     

Intraductal papillary-mucinous tumor of the pancreas: presentation in a young adult

Intraductal papillary-mucinous tumor (IPMT) of the pancreas is a premalignant lesion that can result in the hypersecretion of mucous and subsequent pancreatitis. In this report, one of the youngest cases of IPMT is described. Initial pancreaticogram was normal. Pathognomonic changes of the pancreatic duct were found only years later; otherwise, the recurrent pancreatitis seen in this patient might have been repeatedly misdiagnosed as idiopathic. Pre- and perioperative evaluation resulted in pancreaticoduodenectomy for what was felt to be a curative resection. However, the patient suffered an aggressive metastatic course. More extensive surgery may be needed in IPMT, such as total pancreatectomy, especially in cases of diffuse ductal dilation of the pancreas.