Invasive carcinoma derived from intraductal papillary mucinous carcinoma of the pancreas

BACKGROUND/AIMS: Most patients with intraductal papillary mucinous tumors of the pancreas have a favorable prognosis after surgical treatment. However, recurrent disease frequently occurs in patients with invasive carcinoma derived from intraductal papillary mucinous carcinoma. The objective of this study was to clarify the clinicopathological features of invasive carcinoma derived from intraductal papillary mucinous carcinoma. METHODOLOGY: We performed a retrospective review of the 29 patients with intraductal papillary mucinous tumor including 10 patients with invasive carcinoma who underwent pancreatic resection between June 1995 and December 2001 at the National Cancer Center Hospital East. RESULTS: Of 10 patients with invasive carcinoma derived from intraductal papillary mucinous carcinoma, 7 patients had lymph node involvement and 8 patients had retroperitoneal invasion. The overall 1-, 2-, 4-year actuarial survival rate for invasive carcinoma derived from intraductal papillary mucinous carcinoma was 39%, 26%, 13%. Recurrence occurred as liver metastasis in 3 patients, carcinomatous peritonitis in 3, local recurrence in 3, and lung metastasis in 1. All patients with adenoma, non-invasive carcinoma, and minimally invasive carcinoma are alive without recurrent disease after pancreatic resection. CONCLUSIONS: Patients with invasive carcinoma derived from intraductal papillary mucinous carcinoma had a worse prognosis. Margin-negative pancreatic resection is essential for treating this disease.     

p53 protein expression in intraductal papillary mucinous tumors (IPMT) of the pancreas as an indicator of tumor malignancy

BACKGROUND/AIMS: Intraductal papillary mucinous tumors, as a cystic disease in the pancreas, clinically has a more indolent and favorable course than invasive ductal pancreas carcinoma. However, some cases of intraductal papillary mucinous tumors show invasive and rapid progression like ductal pancreas carcinoma and the prognosis of such patients is sometimes poor. In the current study, we carried out immunohistochemical staining of intraductal papillary mucinous tumor tissues for p53 and investigated whether positive staining indicates tumor malignancies and has a prognostic value for intraductal papillary mucinous tumors. METHODOLOGY: Nineteen (19) patients who underwent pancreatic resection under the diagnosis of intraductal papillary mucinous tumors at the Chiba University Hospital between April 1992 and December 1996 were studied. We performed immunohistochemical staining of p53 as well as of PCNA, Ki-67 and Bcl-2 using their respective antibodies. Pathological findings revealed that 9 cases were intraductal papillary adenoma, 9 were intraductal papillary adenocarcinoma, and one was invasive ductal papillary adenocarcinoma. RESULTS: p53 expression could only be detected in the 1 case with invasive ductal papillary adenocarcinoma. Significant association could not be found between histological features and immunohistochemical staining of PCNA, Ki-67 and Bcl-2. CONCLUSIONS: p53 protein expression could be detected after progression to invasive type of intraductal papillary mucinous tumors. The present results demonstrate that p53 expression might be an indicator of invasive progression in intraductal papillary mucinous tumors, and might represent a surgical indicator of intraductal papillary mucinous tumors.     

Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas

Recently, attention has been drawn to papillary neoplasm of the pancreatobiliary systems. In the pancreas, the disease entity of intraductal papillary mucinous neoplasm (IPMN-P) is widely recognized. In contrast, the pathological characteristics of biliary papillary tumors, such as biliary papilloma(tosis) and papillary cholangiocarcinoma, have not yet been well documented. In this study, we compared the pathological features and post-operative prognosis among biliary papillary tumors (10 cases of biliary papilloma(tosis) and 22 cases of papillary cholangiocarcinoma), conventional non-papillary cholangiocarcinoma (15 cases), and IPMN-P (31 cases). Macroscopically, all biliary papillary tumors were characterized by the prominent intraductal papillary proliferation, and macroscopic mucin-hypersecretion was seen in 9 of 32 cases (28%). Histologically, biliary papillary tumors consisted of three types of tumor cells (pancreaticobiliary, intestinal and gastric types), whereas only the pancreaticobiliary type was observed in non-papillary cholangiocarcinoma. Immunohistochemically, biliary papillary tumors were characterized by the common expression of MUC2, CDX2 and cytokeratin 20. In addition, biliary papillary tumors could be associated with two types of invasive lesions: tubular adenocarcinoma (9 cases) and mucinous carcinoma (5 cases). Patients with tubular adenocarcinoma had a poor prognosis compared to non-invasive papillary tumor or papillary tumor with mucinous carcinoma. These pathological characteristics and the survival status of biliary papillary tumors were different from those of non-papillary cholangiocarcinoma, and rather closely resembled those of IPMN-P. In conclusion, biliary papillary tumors may be the biliary counterpart (intraductal papillary neoplasm of the bile duct) of IPMN-P.     

Operative indications for cystic lesions of the pancreas with malignant potential--our experience

BACKGROUND/AIMS: There are still many important but unclear points regarding the differential diagnosis and operative indications of cystic lesions of the pancreas with malignant potential. Studies of the clinicopathological and molecular biological characteristics of such diseases are necessary. In this paper, we discuss operative indications for this condition based on a review of the literature and our own experience. METHODOLOGY: Seven cases of serous cystadenoma and 9 cases of mucinous cystadenoma or cystadenocarcinoma of the pancreas that were operated on or autopsied in our department from 1980 to 1996 were analyzed clinicopathologically. Small cystic lesions incidentally found in 300 autopsied cases were also studied. Finally, mucin-producing tumors described in several reports were reviewed, and the branch type of this tumor was especially investigated. RESULTS: A marked disappearance of pancreatic acini in the upstream pancreas was found when serous cystadenoma became large. Papillary projection was histologically found in all of the cases. Tumorous invasion to the interstitium was suspected in tumors more than 5 cm in diameter, and malignancy was reported when tumors were larger than 6 cm. As for mucinous cystadenocarcinoma, the patients had a poor prognosis. In 2 of 42 cases with a pseudocyst, small duct cell carcinoma was incidentally found adjacent to the pseudocyst on the duodenal side. With regard to branch-type intraductal papillary neoplasm, 80% of the tumors larger than 4 cm were malignant. Most of the small cystic lesions found in elderly autopsy cases were accompanied by hyperplastic epithelia without evidence of malignancy. CONCLUSIONS: Based on our experience, an operation should be considered and resection is recommended under the following circumstances: 1) cystic lesions in the body and tail of the pancreas in middle-aged women; 2) typical serous cystadenoma larger than 4 cm; 3) mucinous cystadenoma of any size; 4) branch-type intraductal papillary neoplasm larger than about 3 cm; and, 5) pseudocysts of unknown cause. Small cystic lesions in elderly patients should not necessarily be operated on, but should be followed-up carefully.     

Intraductal papillary mucinous neoplasms of the pancreas: clinicopathological features and long term outcome related to histopathological group

Background/Aims: To investigate the clinicopathological features of intraductal papillary mucinous neoplasms and evaluate the prognosis between histopathological groups. Methodology: Retrospective review of 55 consecutive patients operated between 1991 and 2006, analysis of clinicopathological features and survival. Results: Group I comprised of 9 mild and 14 moderate dysplasias, group II of 11 carcinomas in situ and group III of 21 invasive cancers. Age, diabetes, anorexia and jaundice were significantly more frequent in group III. Thirty-two patients (58.2%) presented main duct type which was more frequently associated with invasive carcinoma. Mean tumoral size progress from group I to group III (26.1mm vs. 27.4mm vs. 32.0mm p=0.015) as the mean size of the pancreatic duct (6.7mm vs. 7.9mm vs. 11.5mm p=0.008). Median follow-up was 154 months with 5-year survival rate of 60.7 %. For group I, II and III it was 76.3 %, 100 % and 25.8 % respectively (p=0.00007). Lymph node positivity was associated with poor outcome: 44.1% vs. 0% (N0 vs. N+) (p=0.0019). Conclusions: The prognosis of non-invasive intraductal papillary mucinous neoplasms of the pancreas is favourable. For patients with invasive cancer, nodal invasion is a factor of worst prognosis.     

P53 mutation but not p16/MTS1 mutation occurs in intraductal papillary mucinous tumors of the pancreas

BACKGROUND/AIMS: Intraductal papillary mucinous tumors of the pancreas are rare lesions, which typically show a benign clinical course. However, some of these tumors have a malignant nature and grow in an invasive manner. The purpose of the study was to determine the prevalence of p53-, p16/MTS1- and K-ras mutations in benign and malignant intraductal papillary mucinous tumors with intent to value their importance for tumor progression. METHODOLOGY: Thirteen different archival tumor specimens were obtained at the Department of Pathology, University of Ulm. Three cases showed an invasive component of the tumor. Genomic DNA was extracted after laser capture microdissection of tumor cells from paraffin-embedded tissue sections. The corresponding sequences of p53 (exon 5, 6, 7, 8) and p16/MTS1 (exon 2) were amplified by polymerase chain reaction and subjected to single strand conformation polymorphism analysis. Codon 12 of K-ras was analyzed by the enrichment polymerase chain reaction-restriction fragment length polymorphism method. Positive samples were further investigated by sequencing. RESULTS: K-ras mutations occurred in benign and malignant intraductal papillary mucinous tumors (4/13), whereas an alteration of the coding p53 gene sequence could only be detected in the intraductal and invasive component of one malignant tumor. None of the tissue specimens revealed mutations in exon 2 of p16/MTS1. CONCLUSIONS: In contrast to K-ras mutations, alterations in the p53 gene may characterize ductal papillary mucinous carcinomas, which could be of major interest for their early diagnosis. The lack of mutations in the p16/MTS1 gene suggests that other genes may be involved in the formation of intraductal papillary mucinous neoplasias.     

European experts consensus statement on cystic tumours of the pancreas

Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6 mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.     

A mucous histochemical and immunohistochemical study of precancerous and neoplastic lesions in the human pancreas

Summary A total of 44 cases of pancreatic lesions, including hyperplasia (six) cases, adenoma (mucinous cystadenomas [eight] and intraductal papillary adenoma [eight]), noninvasive intraductal papillary tumors (five), and invasive ductal carcinomas (17) were investigated possibly to establish a diagnostic marker. We examined the type of mucin secreted and immunoreactivities of antibodies toras-p21 and c-erbB-2 oncogene products. A significant decrease in the amount of mucin was found in invasive lesions, and this was associated with a shift toward production of neutral mucins and especially sialomucins. Hyperplasia and adenoma, in contrast, demonstrated a predominance of neutral mucin. The sulfated mucins found in normal epithelium were only very weakly stained in any of the tumor types. Thirty-three percent of non-invasive intraductal papillary tumors and 88% of invasive ductal adenocarcinomas demonstrated strong binding of theras-p21 antibody. In contrast no obvious differences in expression of c-erbB-2 were evident between the groups. In conclusion, a combined mucin histochemical/immunohistochemical approach may facilitate accurate diagnosis.     

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.     

Clinical results of extended lymphadenectomy and intraoperative radiotherapy for pancreatic adenocarcinoma

BACKGROUND/AIMS: The efficacy of extended lymphadenectomy and intraoperative radiotherapy for resectable pancreatic cancer is controversial. The objective of this study was to clarify the surgical outcome after pancreatic resection with extended lymphadenectomy or intraoperative radiotherapy in patients with pancreatic adenocarcinoma. METHODOLOGY: Between 1992 and 2002, 105 patients with pancreatic adenocarcinoma undergoing surgical resection were retrospectively analyzed. Eighty-eight patients had invasive ductal adenocarcinoma and 17 had invasive intraductal papillary mucinous adenocarcinoma. Seventy-six patients underwent pancreatic resection with extended lymphadenectomy and 44 received 20 Gy intraoperative radiotherapy. RESULTS: Patients with invasive intraductal papillary mucinous adenocarcinoma had a similar prognosis to those with invasive ductal adenocarcinoma. There was no significant difference in survival (p = 0.86) between patients with and without extended lymphadenectomy. There was no significant difference in survival (p = 0.053) between patients with and without intraoperative radiotherapy. Patients without lymph node metastasis had a significantly better prognosis (p = 0.0015) than those with nodal involvement. CONCLUSIONS: Neither extended lymphadenectomy nor intraoperative radiotherapy showed a survival advantage in patients with resectable pancreatic adenocarcinoma. Pancreatic cancer patients without nodal involvement had a significantly better prognosis than those with nodal involvement.     

EUS FNA in intraductal papillary mucinous tumors of the pancreas

BACKGROUND/AIMS: There is little information concerning the potential role of fine-needle aspiration guided by endoscopic ultrasonography in the pathologic diagnosis of intraductal papillary mucinous tumors of the pancreas. METHODOLOGY: Patients with an intraductal papillary mucinous tumor of the pancreas suggested by endoscopic ultrasonography underwent fine-needle aspiration guided by endoscopic ultrasonography in order to investigate the presence of mucin and/or cytologic changes consistent with this diagnosis. A group of 111 patients with other pancreatic lesions explored during the same period of time was used as a control group. RESULTS: Fine-needle aspiration guided by endoscopic ultrasonography was safely performed in 19 patients and supported the diagnosis in 17 of them. Nine out of the 17 patients with suspicion of intraductal papillary mucinous tumors of the pancreas went to surgery and this diagnosis was confirmed in the resected specimen in all of them. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS FNA in the diagnosis of IPMT were 82%, 100%, 100%, 92% and 94% respectively. CONCLUSIONS: Fine-needle aspiration guided by endoscopic ultrasonography is a good technique to support the diagnosis of intraductal papillary mucinous tumors of the pancreas and should be considered in this group of patients if pathologic confirmation is judged to be necessary.     

Intraductal papillary mucinous tumors and mucinous cystic tumors of the pancreas: imaging

Most cystic lesions of the pancreas are nonneoplastic and inflammatory in nature. However, approximately 5%–15% of cystic pancreatic masses may be neoplastic. Among the cystic neoplasms are the mucin-producing tumors, both the intraductal papillary mucinous neoplasms and the mucinous cystic neoplasms. Their imaging features on contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) can assist in the differentiation of these lesions. The imaging findings of both intraductal papillary mucinous neoplasm and mucinous cystic neoplasm are reviewed with attention to CT and MRI.     

Intraductal papillary and mucinous tumor of the pancreas: a case report of successful surgical treatment with decompression

Intraductal papillary mucinous tumor of the pancreas is commonly regarded as histopathologically low-grade malignancy. As yet, no fixed strategy of treatment for the advanced aged patient with intraductal papillary mucinous tumor exists. An 80-year-old woman was admitted to our hospital in July 1996 because of back pain due to pancreatitis. Examinations showed a widely opened orifice of the ampulla of Vater, the mural nodule in the cystic lesion of the pancreas uncus, and a mucinous plug in the diffusely dilated main pancreatic duct, so the patient was diagnosed as having intraductal papillary mucinous tumor in the pancratic head. However, in view of the patient's advanced age and the fact that intraductal papillary mucinous tumor is commonly regarded as a slow growing and histopathologically low-grade malignancy, we refrained from radical operation and selected the best supportive care. Four years subsequent to this, her symptoms became uncontrollable and she returned to our hospital. In consideration of her age, side-to-side pancreaticojejunostomy as minimally invasive surgery was employed. The postoperative course was uneventful. The symptoms, biochemical profiles and images improved and she was discharged from the hospital 28 days after the operation. No event has been observed in the patient for one year after operation. Surgical decompression is considered to be effective minimally invasive surgery for intraductal papillary mucinous tumor.     

EUS in the evaluation of pancreatic cystic lesions

BACKGROUND: The differential diagnosis in pancreatic cystic lesions is often difficult despite the availability of various modern imaging modalities. This study assessed the role of EUS in the following: (1) discrimination of pseudocysts from pancreatic cystic tumors, (2) differential diagnosis between serous cystadenoma and mucinous cystic tumor, and (3) prediction of accompanying malignancy in intraductal papillary mucinous tumor. METHODS: EUS findings in 75 patients with pancreatic cystic lesions (58 cystic tumors, 17 pseudocysts) were evaluated. In the comparison of pseudocysts and cystic tumors, the latter included intraductal papillary mucinous tumor, mucinous cystic tumors, and serous cystadenomas, but not solid-pseudopapillary tumors. RESULTS: In univariate analysis, pseudocysts exhibited echogenic debris and parenchymal changes more often than cystic tumors did (respectively, 29% vs. 6%, p < 0.05; and 65% vs. 4%, p < 0.001). In contrast, septa and mural nodules were found more frequently in cystic tumors than pseudocysts (respectively, 69% vs. 12%, p < 0.001; 56% vs. 12%, p < 0.01). Multivariate analysis revealed that parenchymal changes (odds ratio [OR] = 83.59; p < 0.01); septa (OR = 30.75; p < 0.05); and mural nodules (OR = 21.38; p < 0.05) were independent predictors of differentiation between pseudocysts and cystic tumors. Serous cystadenoma exhibited diverse EUS features, as well as a honeycomb appearance. Mural nodules were found more often in mucinous cystic tumors than in serous cystadenomas (p < 0.05). There were no factors that predicted malignancy in intraductal papillary mucinous tumor. CONCLUSIONS: EUS is a useful complementary imaging method for differentiation of pancreatic cystic lesions.     

Molecular assessment of endoscopically collected pancreatic juice and duodenal fluid from patients with pancreatic diseases

One concern associated with pancreatic diseases is the poor prognosis of pancreatic cancer. Even with advances in diagnostic modalities, risk stratification of premalignant lesions and differentiation of pancreatic cysts are challenging. Pancreatic lesions of concern include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystadenomas, pseudocysts, and retention cysts, as well as cystic degeneration of solid tumors such as solid pseudopapillary neoplasms and pancreatic neuroendocrine neoplasms. Pancreatic juice obtained during endoscopic retrograde cholangiopancreatography has previously been used for the detection of KRAS mutation. Recently, duodenal fluid, which can be obtained during the relatively minimally invasive procedures of endoscopic ultrasound (EUS) and esophagogastroduodenoscopy, and cyst fluid collected by EUS-guided fine-needle aspiration (FNA) were used for molecular biological analysis. Furthermore, advanced analytic methods with high sensitivity were used for the detection of single and multiple markers. Early detection of malignant pancreatic tumors and risk stratification of premalignant tumors can be performed using duodenal fluid samples with a single marker with high sensitivity. Technological advances in simultaneous detection of multiple markers allow for the differentiation of cystic pancreatic tumors. One thing to note is that the clinical guidelines do not recommend pancreatic cyst fluid and pancreatic juice (PJ) sampling by EUS-FNA and endoscopic retrograde cholangiopancreatography, respectively, in actual clinical practice, but state that they be performed at experienced facilities, and duodenal fluid sampling is not mentioned in the guidelines. With improved specimen handling and the combination of markers, molecular markers in PJ samples may be used in clinical practice in the near future.     

Precursor lesions of pancreatic cancer: molecular pathology and clinical implications.

BACKGROUND: Pancreatic cancer is a lethal disease, with near uniform 5-year mortality rates. The key to improving survival of pancreatic cancer rests upon early detection of this neoplasm at a resectable, and hence potentially curable, stage. METHODS: We review the current state of the literature vis-à-vis the three common precursor lesions of pancreatic adenocarcinoma: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. We also discuss two clinical scenarios of emerging importance, namely asymptomatic pancreatic cysts ('pancreatic incidentalomas') and the significance of precursor lesions in familial pancreatic cancer kindreds. RESULTS: Pancreatic intraepithelial neoplasias are the microscopic precursor lesions of pancreatic adenocarcinomas, while intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are macroscopic, cystic precursor lesions. All three noninvasive entities demonstrate a multistep morphologic and genetic progression that culminates in frank invasive adenocarcinoma. Despite these commonalities, each precursor lesion harbors a unique repertoire of clinicopathologic and genetic characteristics that has an impact on natural history and prognosis of these lesions. Due to improvements in radiological techniques, asymptomatic pancreatic cysts are being increasingly discovered in the general population; intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are the most common underlying histology in resected incidentalomas of the pancreas. Pancreatic asymptomatic cysts present an enormous challenge in terms of accurate diagnosis and management stratification. Incorporating molecular signatures of cystic precursor lesions into the diagnostic algorithm will likely become a standard of care for asymptomatic pancreatic cysts. High-risk individuals from familial pancreatic cancer kindreds are another group of individuals where knowledge of precursor lesions has had a therapeutic impact; sensitive imaging technologies have enabled the identification and subsequent resection of pancreatic cancer precursors in these high-risk individuals, preventing the progression to invasive cancer. CONCLUSIONS: Precursor lesions of pancreatic adenocarcinomas represent a unique opportunity for diagnosis and intervention for a malignancy with near uniform lethality. Further studies on these precursors will enable the development of rational early detection and therapeutic strategies in order to ameliorate pancreatic cancer survival.     

Intraductal papillary mucinous tumors of the pancreas: the preoperative value of cytologic and histopathologic diagnosis

BACKGROUND: The preoperative diagnosis of intraductal papillary mucinous tumors of the pancreas must be as certain as possible because removal of a large portion of the pancreas or even total pancreatectomy may be necessary. The value of cytologic and histopathologic analysis of specimens obtained by preoperative endoscopic investigations is unknown. The aim of this study was to assess the value of such analyses of specimens obtained by EUS-guided FNA and/or biopsy, or transpapillary biopsy specimens obtained during endoscopic retrograde pancreatography for the diagnosis of intraductal papillary mucinous tumors of the pancreas and for the detection of malignancy. METHODS: Between 1992 and 2001, 42 patients (22 men, 20 women; median age 64 years) underwent surgical resection for intraductal papillary mucinous tumors of the pancreas and had preoperative pancreatic tissue sampling. In the case of isolated dilatation of pancreatic ducts, pancreatic juice was obtained by EUS-guided FNA for cytologic analysis. In the presence of a solid lesion or main pancreatic duct stenosis, biopsy specimens were obtained by EUS-guided FNA biopsy or endoscopic retrograde pancreatography, which permitted histopathologic assessment. The accuracy of cytology and histopathology was evaluated for the following: (1) positive diagnosis of intraductal papillary mucinous tumors of the pancreas and (2) assessment of malignancy, by comparison with histopathologic examination of surgical resection specimens. RESULTS: Cytologic analysis was performed in 19 patients; it was positive in 4 (21%) and noninformative in 15 (79%). Histopathologic analysis was performed in 23 patients; it was positive in 21 (91%) and negative in 2 (9%). Histopathologic analysis yielded a positive result in 83% of patients who did not have extrusion of mucus from a patulous papilla. The sensitivity, specificity, and positive and negative predictive values of histopathologic analysis for the diagnosis of malignancy were, respectively, 44%, 100%, 100%, and 33%. When histopathologic analysis was positive, the tumor grade was similar to that determined by final histopathologic examination in 38% of patients, whereas the grade was underestimated in 62%. No complication occurred as a result of tissue sampling. CONCLUSIONS: The sensitivity of histopathologic analysis of EUS-guided FNA biopsy specimens or transpapillary biopsy specimens is 91% for the positive diagnosis of intraductal papillary mucinous tumors of the pancreas with a solid component, which is of particular interest as extrusion mucus from the papilla was absent in most patients. Histopathologic analysis of biopsy specimens of malignant intraductal papillary mucinous tumors of the pancreas often underestimates tumor grade. The result for cytologic analysis of juice obtained from dilated pancreatic ducts is disappointing.     

Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas

BACKGROUND & AIMS: The aim of this study was to determine recurrence and long-term survival after resection of pancreatic intraductal papillary mucinous neoplasm and to correlate recurrence and survival with histology, extent of resection, and duration of follow-up. METHODS: A single pathologist, without knowledge of previous interpretations of histology or clinical data, retrospectively reviewed and classified 113 resected intraductal papillary mucinous neoplasms as invasive carcinoma (n = 40) or as noninvasive neoplasms (adenoma, borderline, or carcinoma in situ; n = 73). Data on recurrence (locoregional or metastatic), follow-up, and cause of death were obtained from patient records and/or by contacting patients and their physicians. RESULTS: In invasive intraductal papillary mucinous neoplasm, recurrence was similar after partial pancreatectomy (18/27; 67%) and total pancreatectomy (8/13; 62%) and occurred within 3 years of resection in 91%. Among noninvasive neoplasms, 5 of 60 (8%) recurred after partial pancreatectomy (median follow-up, 37 months); none recurred after total pancreatectomy (n = 13; median follow-up, 32 months). Recurrence after resection in noninvasive neoplasms was diagnosed after a median of 40 months (range, 23-75 months); recurrence was noninvasive in 3 and invasive cancer in 2. Five-year survival was better for noninvasive compared with invasive intraductal papillary mucinous neoplasm (84.5% vs. 36%; P < 0.001). CONCLUSIONS: Invasive intraductal papillary mucinous neoplasm recurs frequently even after a complete "curative" resection and portends poor survival. In contrast, noninvasive intraductal papillary mucinous neoplasm recurs infrequently after resection, and survival is excellent regardless of the degree of epithelial dysplasia in the tumor.     

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.     

Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients.

BACKGROUND/AIM: The clinical presentation, pancreatographic findings, and outcome of patients with intraductal papillary mucinous tumours have not been reported in a large patient series in the English literature. This study reviewed 32 patients diagnosed between 1980 and 1994, with special attention to these features. PATIENTS/METHOD: Data on 24 operated and eight non-operated patients were abstracted from inpatient, outpatient, and procedure records. RESULTS: Acute pancreatitis was the most common presentation seen in 56% of patients. Relapses occurred during an average of 43 months before diagnosis. A patulous papilla was observed in 55% of the cases. Endoscopic pancreatography showed communicating cysts, a diffusely dilated main pancreatic duct, and amorphous defects in 42, 71, and 97% respectively. An invasive carcinoma was found in nine of 24 (37.5%) of operated patients: six of the patients (66%) died or developed metastases within three years after surgery. No mortality was related to the tumour in absence of invasive carcinoma. Benign recurrence on the remaining pancreas was unusual and occurred late after surgery. CONCLUSIONS: Intraductal papillary mucinous tumours must be considered in the differential diagnosis of relapsing pancreatitis. Despite slow growing, these tumours have an obvious malignant potential and a very poor prognosis when invasive carcinoma has developed. Early recognition and resection are the cornerstones of treatment.