Intraductal Papillary Mucinous Carcinoma Research Articles

Usefulness of KL-6 in the subtyping of intraductal papillary mucinous neoplasia of the pancreas, including carcinoma, dysplasia, and hyperplasia.

KL-6 is known as a useful serum biomarker of the disease activity in interstitial pneumonias. We investigated its usefulness as a biomarker for subtyping intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. IPMNs are generally divided into 4 subtypes, namely pancreatobiliary (PB), intestinal (INT), gastric (GS), and oncocytic (ONC). Aside from the KL-6 antibody, the MUC1, MUC2, MUC5AC, MUC6, and MIB-1 antibodies were also examined. Eighteen IPMN cases were examined, including 12 cases of intraductal papillary mucinous carcinomas (IPMCs) simultaneously associated with dysplasia (IPMDs) and hyperplasia (IPMHs) and 6 IPMD cases with IPMH. KL-6 antibody was positive in the 8 IPMC cases, corresponding to a MUC2-negative PB subtype, but negative in 4 IPMC cases, corresponding to the INT subtype, which is positive for MUC2. IPMD of moderate-to-severe degree positively stained for the KL-6 antibody in the IPMC cases of the PB subtype but not in those of the INT subtype. The IPMH cases were mostly negative for KL-6, similar to the mild IPMD cases. In the 6 cases of mild IPMD and/or IPMH, KL-6 and MUC2 expressions were mostly negative. In conclusion, the KL-6 antibody is immunohistochemically a good biomarker of the PB subtype of IPMC, but not the INT subtype. Identifying IPMN subtypes based on KL-6 stainability would be useful. Clinicopathological studies with more IPMC cases might be needed for further progress in this field of study.

Tu1615 Prognostic Value of Additional Pancreatic Resection for Cancer Positive Cut Margins During Pancreaticoduodenectomy for Pancreatic Head Cancer

Background: Invasive ductal carcinoma of the pancreas often shows microscopic infiltration in the peripheral pancreatic parenchyma. Because this infiltration is difficult to recognize on preoperative imaging, invasive cancer at the pancreatic cut margin may be observed during pancreatectomy. However, the prognostic significance of additional pancreatic resection to achieve a final negative margin has not been determined. Patients and methods: We retrospectively reviewed the records of 308 consecutive patients who underwent pancreaticoduodenectomy (PD) for pancreatic cancer, excluding invasive intraductal papillary mucinous carcinoma, at our hospital from 2000 to 2012. All patients underwent intra-operative frozen section analysis (IOFSA) of the pancreatic stump, with the need for additional pancreatic resection determined by the operating surgeon. Patients who underwent R2 resection, were positive for lavage cytology or para-aortic lymph node metastasis, received preoperative chemotherapy, or died in-hospital were excluded. Based on the final pathologic diagnosis of pancreatic cut margins, patients were divided into three groups: initial margins negative for invasive cancer (Group A); initial margins positive for invasive cancer, but negative after additional pancreatic resection (Group B); and final margins positive for invasive cancer (Group C). Patients who required conversion to total pancreatectomy (TP) were included in Group B. The clinicopathological characteristics and prognoses of the three groups were compared. Results: IOFSA of the initial pancreatic stump showed that 71 patients harbored invasive cancer, 20 had PanIN3 and 25 had PanIN1 or 2. Additional pancreatic resection was performed in 99 patients, with 76 patients undergoing one, 14 undergoing two, four undergoing three, and five undergoing four or more resections. Eight patients required conversion to TP. IOFSA results were inconsistent with the final pathological diagnosis in 7 patients. Groups A, B and C consisted of 234, 63 and 11 patients, respectively, with median survival times of 31, 24, and 11 months, respectively, and 3-year survival rates of 44%, 40%, and 11%, respectively (A vs. B; P=0.410, A vs. C; P=0.001, B vs. C; P=0.012, Figure 1). Patients who underwent TP had a median survival time of 24 months and a 3year survival rate of 43%. Rates of lymph node metastasis, R1 resection, portal vein resection and severe perineural invasion were significantly higher in Groups B and C than in group A. Survival was similar among the 85 patients in Groups A, B and C who underwent R1 resection (Figure 2). Conclusion: Pancreatic margin status during PD should be confirmed, even if a curative resection is macroscopically expected. Additional pancreatic resection to achieve negative cut margins may improve postoperative survival.

Comparison of enhanced magnetic resonance imaging and magnetic resonance cholangiopancreatography in the differential diagnosis of benign and malignant intraductal papillary mucinous neoplasms of the pancreas

To compare the value of liver acquisition with volume acceleration (LAVA) and magnetic resonance cholangiopancreatography (MRCP) in diagnosing benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the pancreas. The MR findings of 35 IPMN patients confirmed by pathology were analyzed retrospectively, and the sequences included T1WI, T2WI, LAVA, and MRCP. All patients were divided into two groups: the group of MRI enhancement (including T1WI, T2WI, and MRI enhancement) and the group of MRCP (including T1WI, T2WI, and MRCP). Two groups were evaluated by the receiver operating characteristic (ROC) curve. Totally 23 cases of intraductal papillary mucinous tumors and 12 cases of intraductal papillary mucinous carcinomas were diagnosed. Finally, 29 cases (29/35) of IPMN were diagnosed correctly in the group of MR enhancement, and 25 cases (25/35) diagnosed correctly in the group of MRCP. The differential diagnostic accuracy of the group of MRI enhancement (82.9%) was higher than that of the group of MRCP (71.4%), although the difference was not statistically significant (P=0.068). The sensitivity, specificity, positive predictive value, and the area under the ROC curve (AUC) of the group of MRI enhancement were 83.3%, 82.6%, 71.4%, and 0.850, and those of the group of MRCP were 75.0%, 69.6%, 52.3%, and 0.723. The AUC of the group of MRI enhancement was significantly larger than that of the group of MRCP (P=0.0465). MRI enhancement is more valuable than MRCP in the differential diagnosis of benign and malignant IPMN.

Key endoscopic ultrasound features of pancreatic ductal adenocarcinoma smaller than 20 mm

Background and study aims. Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis compared with other solid pancreatic tumors. Diagnosis of PDAC in the earliest possible stage is important to improve the prognosis. Although endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been the gold-standard modality for diagnosing pancreatic lesions, its diagnostic yield is not satisfactory for pancreatic tumors smaller than 20 mm. The purpose of this study was to determine the EUS findings that are useful for differentiating PDAC from other solid pancreatic tumors when the lesions are smaller than 20 mm. Patients and methods. We performed a retrospective review of 126 patients with pancreatic tumors smaller than 20 mm who had undergone EUS. According to the final pathological diagnoses, they were categorized into either the PDAC or non-PDAC group. We, then, compared the EUS findings between the two groups. Results. Among the 126 patients, we diagnosed PDAC in 75 patients and non-PDAC in the remaining patients, including neuroendocrine tumor in 43 patients, intraductal papillary mucinous carcinoma in 3 patients, solid pseudopapillary neoplasm in 2 patients, and inflammatory pseudotumor in 3 patients. Of all EUS findings, three factors were significantly indicative of PDAC: an irregular tumor edge, main pancreatic duct dilation, and tumor location in the pancreatic head. The predicted probability for PDAC was 80%, 92.6%, and 74.1%, respectively. Conclusions. EUS could be a useful modality for differentiating PDAC from other solid pancreatic tumors, when the diagnostic yield of EUS-FNA is unsatisfactory, even for lesions smaller than 20 mm.

Synchronous Malignant Intraductal Papillary Mucinous Neoplasms of the Bile Duct and Pancreas Requiring Left Hepatectomy and Total Pancreatectomy

Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) and intraductal papillary mucinous neoplasm of the pancreas (IPMN-P) have striking similarities and are recognized as counterparts. However, simultaneous occurrence of IPMN-B and IPMN-P is extremely rare. A 66 year-old female presented with recurrent epigastric pain and fever. During the past 9 years, she had three clinical episodes related to intrahepatic duct stones and IPMN-P in the pancreas head and was managed by medical treatment. Laboratory test results at admission revealed leukocytosis (12,600/mm(3)) and elevated CA 19-9 level (1,200 U/mL). Imaging study demonstrated liver abscess in the Couinaud's segment 4, IPMN-B in the left lobe, and IPMN-P in the whole pancreas with suspicious malignant change. Liver abscess was drained preoperatively, followed by left lobectomy with bile duct resection and total pancreatectomy with splenectomy. On histologic examination, non-invasive intraductal papillary mucinous carcinoma arising from various degree of dysplastic mucosa of the liver and pancreas could be observed. However, there was no continuity between the hepatic and pancreatic lesions. This finding in our case supports the theory that double primary lesions are more likely explained by a diffuse IPMN leading to synchronous tumors arising from both biliary and pancreatic ducts rather than by a metastatic process. Herein we present a case of simultaneous IPMN of the bile duct and pancreas which was successfully treated by surgical management.

Subcellular localization of KL-6 mucin in intraductal papillary mucinous neoplasm of the pancreas.

This study aimed to clarify the expression profile of KL-6 mucin in intraductal papillary mucinous neoplasm (IPMN) and its relation to tumor malignancy. Expression of KL-6 mucin in 38 IPMNs (intraductal papillary mucinous adenoma (IPMA), 24 cases; minimally invasive intraductal papillary mucinous carcinoma (MI-IPMC), 8 cases; invasive carcinoma originating from IPMC (IC-IPMC), 6 cases) and 66 pancreatic ductal adenocarcinomas (PDACs) was evaluated immunohistochemically. IC-IPMCs and MI-IPMCs had positive staining of KL-6 mucin whereas 58% of IPMAs tested negative. Subcellular localization of KL-6 mucin varied among IPMNs whereas all of the PDAC had positive expression in the circumferential membrane and cytoplasm of cancer cells. IC-IPMCs and MI-IPMCs had a higher frequency of circumferential membrane and cytoplasmic localization of KL-6 mucin than did IPMAs. These results suggest that localization of KL-6 mucin could be used to predict the malignancy of IPMN.

Effect of pancreatic juice cytology and/or endoscopic ultrasound‐guided fine‐needle aspiration biopsy for pancreatic tumor

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) can now provide a cytopathological diagnosis of pancreatic malignancy with higher success rates. However, EUS-FNA cannot be carried out for lesions of minimally invasive carcinoma because they cannot be detected by endoscopic ultrasonography, and in cases of intraductal papillary mucinous carcinoma (IPMC) because of the potential for needle tract seeding. A recent study has shown that pancreatic juice cytology (PJC) is useful for diagnosing pancreatic cancer. This study's aim was to evaluate whether PJC strengthens the diagnostic power of EUS-FNA for pancreatic masses. A total of 161 patients, who were suspected to have a pancreatic mass on conventional ultrasound and/or computed tomography, was enrolled. EUS-FNA was carried out in 121 cases, and PJC was performed in 83 cases. An adequate specimen was obtained for EUS-FNA in 96.0% and for PJC in 98.9%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 86.0%, 100%, 100%, 70.5%, and 89.5% for EUS-FNA, and 71.4%, 100%, 100%, 84.4%, and 88.8% for PJC, respectively. EUS-FNA and/or PJC for the diagnosis of pancreatic tumor had a sensitivity of 92.5%, specificity of 100%, positive predictive value of 100%, negative predictive value of 91.7%, and accuracy of 95.9%. The diagnostic accuracy of EUS-FNA and/or PJC was significantly higher than that of EUS-FNA alone or PJC alone. PJC improved the diagnostic utility of EUS-FNA for pancreatic tumor.

Disease Spectrum of Intraductal Papillary Mucinous Neoplasm With an Associated Invasive Carcinoma

Current version of World Health Organization classification introduced the concept of ‘‘intraductal papillary mucinous neoplasm(IPMN) with an associated invasive carcinoma.’’ The authors investigated the clinicopathologic characteristics and prognosis of this disease category according to tumor morphology and percentage of invasive component. Fifty-nine patients who underwent surgical resection of IPMN with an associated invasive carcinoma at Seoul National University Hospital were subgrouped according to the invasive component of less than 5% (minimally invasive [MI] intraductal papillary mucinous carcinoma [IPMC] [MI-IPMC]), 5%- 50% (invasive IPMC [IPMC-I]),and 50% or greater (pancreatic ductal adenocarcinoma [PDAC]-associated IPMN [PDAC-IPMN]). Prognosis was compared with 219 curatively resected conventional PDAC. Eleven MI-IPMCs (18.6%), 24 IPMC-Is (40.7%), and 24PDAC-IPMNs (40.7%) were identified. With the transition from MIIPMC to IPMC-I and PDAC-IPMN, percentage of advanced T (P G0.001) or N stage (P = 0.001), expression of S100A4 (P = 0.004), p53(P = 0.028), and CD24 (P = 0.009) increased; and SMAD4 expression decreased (P G 0.001). The overall 5-year survival rates for MIIPMC,IPMC-I, and PDAC-IPMN were 80.8%, 59.0%, and 29.3%,respectively (P G 0.001). Pancreatic ductal adenocarcinoma-associated IPMN had poor prognosis compared with MI-IPMC (P = 0.011) or IPMC-I (P = 0.026) but had comparable prognosis with conventional PDAC (P = 0.138). Pancreatic ductal adenocarcinoma-associated IPMN has different clinicopathological characteristics compared with the IPMC-I.Intraductal papillary mucinous neoplasm with an associated invasive carcinoma is composed of a wide spectrum of disease.

Results of a surveillance protocol for pancreatic BD-IPMNs

s / Pancreatology Methods: We retrospectively analysed the clinicopathological factors of 184 patients (114 men, median age 63 yr) undergoing resection for branch duct type IPMNs at 14 tertiary hospitals in Korea, to identify malignant predictors of this neoplasm. Malignant IPMNs were defined as those with noninvasive and invasive intraductal papillary mucinous carcinoma. Results: Among 184 patients with branch duct type IPMN, eighty-two patients had adenoma, 78 borderline, 10 noninvasive carcinoma, and 14 invasive carcinoma. Malignant pancreatic tumor distinct from IPMN developed in 7 patients (3.8%). We found significant factors for malignancy in these patients in a univariate analysis; cyst size > 3 cm (P 3 cm, and main pancreatic duct dilatation were independent factors associated with malignancy. By receiver operating characteristics curve analysis, a tumor size of > 3 cm was the most valuable cutoff point. In patients (n1⁄4110) who had endoscopic ultrasonography (EUS), an increase in the size of mural nodule with EUS significantly affected the sensitivity to predict malignancy. The area under the curve for the size of predictors for malignant branch duct IPMNs was 0.7998, and the sensitivity and specificity were 72.7% and 78.8%, respectively, when the cutoff value was set at 7.5 mm. Conclusions: We identified 3 useful predictive factors for malignancy in branch duct type IPMN; a mural nodule size, cyst size > 3 cm, and main pancreatic duct diameter. The size of mural nodule with EUS showed high predictative ability.

Tu1390 The Combination of Pancreatic Juice Cytology With Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy Raised the Diagnostic Ability for Pancreatic Tumor

Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) can now provide a cytopathological diagnosis of pancreatic malignancy with higher success rates. However EUS-FNA can not detect minimal invasive carcinoma and intraductal papillary mucinous carcinoma (IPMC). Recent study has shown the usefulness of pancreatic juice cytology for pancreatic cancer. In present study, therefore we evaluated if the combination of pancreatic juice cytology strengthens the diagnostic power of EUS-FNA in pancreatic masses.

Abstract 2511: Comprehensive metabolic profiling of hepatocellular carcinoma and pancreatic tumors by capillary electrophoresis-mass spectrometry.

Abstract (Background) Most cancer types have been widely known to generate energy primarily by glycolysis rather than oxidative phosphorylation even under normoxia (Warburg effect). However, inadequate blood supply resulting from defective angiogenesis is often observed in different kinds of cancer tissues, and their microenvironment is considered nutritionally unfavorable. How these cancer cells generate ATP is therefore still unclear. We previously reported enhanced glycolysis and significant accumulation of all amino acids except glutamine in both colon and stomach cancer tissues (Hirayama A, et al Cancer Res 2009). (Methods) Here, we investigated the metabolic microenvironment of hepatocelluar carcinoma (HCC)(n=28, HBV-positive (B) 7, HCV-positive (C) 6, NonBnonC (NBNC) 15), and pancreatic tumors (n=40, Invasive ductal adenocarcinoma (PDAC) 21, Intraductal papillary mucinous adenoma (IPMA) 5, Intraductal papillary mucinous carcinoma (IPMC) 14), using capillary electrophoresis-mass spectrometry (CE-MS). (Results) The amount of glucose were more than ten times higher in liver tissues, which indicates that liver tissue exist in nutritionally favorable microenvironment even in tumor tissue compared with pancreas tissue. Significant lactate accumulation was found in all cancer tissues (HCC, IPMC, and PDAC), which imply enhanced glycolysis. However, significant organ-specific differences were found in the levels of amino acids. Organ and etiology-specific difference were found in intermediates of TCA cycle. For example, citrate was increased in B-HCC, malate was decreased in NBNC-HCC, fumarate was decreased in B-HCC, NBNC-HCC, and PDAC, citrate was decreased in IPMC, iso-citrate was decreased in PDAC, compared to normal tissue, significantly. The concentration of most amino acids were not changed between normal and tumor tissues in HCC and pancreatic tumors, which suggests that these type of cancers do not depend on autophagy for their amino acid source. (Conclusions)Overall, these results provide metabolic phenotypes of different cancer tissues that reflect the tumor microenvironment. Citation Format: Motohisa Tada, Akiyoshi Hirayama, Fumihiko Kanai, Hideyuki Yoshitomi, Masayuki Ohtsuka, Masaru Miyazaki, Tomoyoshi Soga, Osamu Yokosuka. Comprehensive metabolic profiling of hepatocellular carcinoma and pancreatic tumors by capillary electrophoresis-mass spectrometry. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2511. doi:10.1158/1538-7445.AM2013-2511

Evaluation of SOX9 Expression in Pancreatic Ductal Adenocarcinoma and Intraductal Papillary Mucinous Neoplasm

Sex-determining region Y (SRY) box 9 (SOX9) is an important transcription factor required for development and has been implicated in several types of cancer. Sex-determining region Y box 9 has never been linked to pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The aim of this study was to investigate the relationship between SOX9 and PDAC and that between SOX9 and IPMN. Surgical specimens were obtained from 55 patients with PDAC and 68 patients with IPMN and were investigated using SOX9 immunohistochemical analysis. The rate of SOX9 positive cells to total pancreatic duct epithelial cells in a normal pancreas was 82.7%. On the other hand, the SOX9 positive rate in PDAC was 0.8%. There was a significant difference between the normal pancreas and PDAC (P = 0.0002). In IPMN, the SOX9 positive rate gradually decreased according to tumor progression, with the following rates observed: intraductal papillary mucinous adenoma (66.3%); noninvasive intraductal papillary mucinous carcinoma (46.3%); minimally invasive intraductal papillary mucinous carcinoma (30.5%); and invasive carcinoma originating in intraductal papillary mucinous carcinoma (2.3%). There were significant differences between each group (P < 0.05). Our data suggested that SOX9 might contribute to carcinogenesis in PDAC and IPMN.

MiR‐197 induces epithelial–mesenchymal transition in pancreatic cancer cells by targeting p120 catenin

Invasive ductal adenocarcinoma (IDA) of the pancreas manifests poor prognosis due to the early invasion and distant metastasis. In contrast, intraductal papillary mucinous adenoma or carcinoma (IPMA or IPMC) reveals better clinical outcomes. Various molecular mechanisms contribute to these differences but entire picture is still unclear. Recent researches emphasized the important role of miRNA in biological processes including cancer invasion and metastasis. We previously described that miR-126 is down-regulated in IDA compared with IPMA or IPMC, and miR-126 regulates the expression of invasion related molecule disintegrin and metalloproteinase domain-containing protein 9 (ADAM9). Assessing the difference of miRNA expression profiles of IDA, IPMA, and IPMC, we newly identified miR-197 as an up-regulated miRNA specifically in IDA. Expression of miR-197 in pancreatic cancer cells resulted in the induction of epithelial-mesenchymal transition (EMT) along with the down-regulation of p120 catenin which is a putative target of miR-197. Direct interaction between miR-197 and p120 catenin mRNA sequence was confirmed by 3'UTR assay, and knockdown of p120 catenin recapitulated EMT induction in pancreatic cancer cells. In situ hybridization of miR-197 and immunohistochemistry of p120 catenin showed mutually exclusive patterns suggesting pivotal role of miR-197 in the regulation of p120 catenin. This miR-197/p120 catenin axis could be a novel therapeutic target.

Usefulness of peripheral regulatory T-cells induced by Notch signaling pathway-driven indoleamine 2, 3-dioxygenase positive dendritic cell as a biomarker for the decision for IPMN surgical indications.

181 Background: This study was performed to elucidate the expression of the Notch signaling pathway regulated by dendetric cell (DC) and their correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs) as a new biomarker for surgical indications. We already reported that regulatory T cells (Tregs) play an important role in tumor immunity (Pancreas 2006, ASCO-GI 2009), however, the whole mechanism of control of peripheral Tregs remains unclear. It is reported that Indoleamine 2, 3-dioxygenase (IDO) induces active Treg from naïve CD4+Tcells through dendritic cells. Otherwise, we also reported that the Notch signaling pathway is involved in tumor growth and DC function (JI 2010). Thus we focused that Indoleamine 2,3-deoxygenase(IDO)-Treg axis driven by Notch signaling in IPMNs. Methods: Peripheral blood samples and resected specimens from 20 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, anti-Notch2-intracellular domain and anti-IDO antibody staining) and compared to clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer. Results: Disease-free survival was significantly worse in the Notch1 high-expression group (P&lt;0.05). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P&lt; 0.05; Notch2-intracellular domain, P &lt; 0.05). Jagged1 and IDO expressions were significantly higher in IPMC than in IPMA (P &lt; 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P &lt; 0.01). Conclusions: Notch signaling, especially Jagged1 expression, regulated by IDO+DC reflects IPMN aggressiveness. Our data strongly suggest that peripheral Treg induced by Notch signaling pathway driven IDO+DC may be a nobel biomarker for the decision for IPMN surgical indications.

The role of EUS and EUS-FNA in the management of pancreatic masses: five-year experience.

The efficacy of endoscopic ultrasound with fine-needle aspiration (EUS-FNA) in the diagnosis and staging of pancreatic malignancy is quite well established. The aim of this study is to describe a single-centre's experience. Data were collected retrospectively on all patients with solid pancreatic masses undergoing EUS-FNA from January 2006 to March 2011. In tumor cases, TNM staging using EUS was compared with the results of histopathological staging. EUS-FNA of pancreatic lesions was performed in 125 patients. Of these patients, data of 75 were available (69% men, mean age 59.97±11.12 (SD) years); 58 (76%) of the lesions were ductal adenocarcinoma, 11 (14.5%) were chronic pancreatitis, 4 (%5) were intraductal papillary mucinous carcinoma (IPMN) and 2 (%3) were insulinoma. Diagnostic yield of the EUS-FNA procedure was 74.7% (56/75). Specimens from six patients were inadequate. In multivariate analysis, lesion diameter below 2cm was an independent predictor for the inadequacy of material (p=0.04). In patients with pancreatic mass with suspected malignancy, EUS-FNA provided a diagnosis with accuracy rate of 75%. Inadequate material with EUS-FNA was significantly more frequent in lesions below 2cm.

Bilateral subclavian artery stenosis found by inter-arm blood pressure difference during distal pancreatectomy

Bilateral subclavian artery stenosis found by inter-arm blood pressure difference during distal pancreatectomy

A case of intraductal papillary mucinous carcinoma found with acute obstructive suppurative pancreatic ductitis and liver abscess, and associated with a pancreatobiliary fistula

A case of intraductal papillary mucinous carcinoma found with acute obstructive suppurative pancreatic ductitis and liver abscess, and associated with a pancreatobiliary fistula

Gastrointestinal Cancers in a Peutz-Jeghers Syndrome Family: A Case Report

A 17-year-old man was diagnosed as Peutz-Jeghers syndrome (PJS) because of pigmented lip and multiple gastrointestinal polyps. He had anemia and underwent polypectomy on the duodenum and colon. His maternal family members were patients with PJS. His mother used to be screened with endoscopy to remove large polyps. One and half years later, he underwent jejunal segmental resection due to intussusceptions. He underwent endoscopic polypectomy every 2 to 3 years. When he was 23 years old, high-grade dysplasia was found in colonic polyp and his mother underwent partial pancreatectomy due to intraductal papillary mucinous carcinoma. When he was 27 years old, diffuse gastric polyps on the greater curvature of corpus expanded and grew. Therefore, wide endoscopic polypectomy was done. Histological examination revealed focal intramucosal carcinoma and low-grade dysplasia in hamartomatous polyps. We report cases of cancers occurred in first-degree relatives with PJS.

High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas

Background and aimsMolecular target therapy against L-type amino acid transporter 1 (LAT1) is unique and expected to be developed soon. LAT1 expression was investigated in pancreatic cancer as a prognostic...

Cystic Papillary Pattern in Pancreatic Ductal Adenocarcinoma

The prototypic pancreatic ductal adenocarcinoma shows small-caliber glands that are placed within an exuberant desmoplastic stromal reaction. A number of histologic patterns have been described, and the majority of these patterns are genetically and biologically related to conventional ductal adenocarcinomas. In this report we describe our experience with a heretofore undescribed histologic pattern of pancreatic adenocarcinoma that mimics intraductal papillary mucinous carcinoma, both morphologically and radiologically. We identified 10 cases of pancreatic adenocarcinoma with large-caliber malignant glands and an intraluminal papillary pattern. The demographic, clinical, radiologic, and outcome data were recorded. In addition to a review of the histologic features we also performed elastin stains, immunohistochemistry for selected oncogenes and tumor suppressor genes including SMAD4. Immunohistochemical staining for MUC proteins was also performed. The median age of the patients was 67 years, and there were 6 women and 4 men. Grossly, the cut surface in 6 of these cases showed an admixture of solid and cystic areas. The papillary cystic architecture was intimately mixed with areas of conventional adenocarcinoma, the latter characterized by invasive small-caliber tubular structures. None of the tumors showed a pure papillary cystic pattern; however, in 8 cases, this was the predominant pattern (>50% of the tumor). The cysts and papillae were lined predominantly by tall columnar hypermucinous epithelium. Elastin fibers were not identified around these dilated malignant cysts and glands. The intratumoral stroma was paucicellular and hyalinized. Seven of the 10 tumors were negative for SMAD4. The lack of pericystic elastin fibers and loss of SMAD4 in the majority of cases argue against these lesions representing an intraductal papillary mucinous neoplasm. All 10 tumors stained for MUC1; focal MUC2 reactivity was noted in 1 case. The majority of cases were positive for MUC5AC (9/10) and MUC6 (8/10). Seven patients died of their disease, whereas 1 patient is alive with widely metastatic disease. Two patients were lost to follow up. The adenocarcinoma described herein is a unique morphologic pattern of pancreatic ductal adenocarcinoma. The biology and genetics (as estimated by immunohistochemistry) are no different from that of conventional ductal adenocarcinoma but are distinctly different from that of an intraductal papillary mucinous carcinoma, its closest morphologic mimic.