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Pancreatic Neoplasms: HELP
Articles by Yoh Zen
Based on 29 articles published since 2010
(Why 29 articles?)
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Between 2010 and 2020, Yoh Zen wrote the following 29 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Tumefactive Inflammatory Diseases of the Pancreas. 2019

Zen, Yoh / Deshpande, Vikram. ·Department of Diagnostic Pathology, Kobe University, Kobe, Japan. · The James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: vdeshpande@mgh.harvard.edu. ·Am J Pathol · Pubmed #30558726.

ABSTRACT: Advances in the past two decades have resulted in the recognition of several tumefactive pancreatic lesions that, on histologic evaluation, show a varying combination of inflammation and fibrosis. Autoimmune pancreatitis, the prototypic tumefactive pancreatic fibroinflammatory lesion, is composed of two distinct diseases, type 1 autoimmune pancreatitis and the less common type 2 autoimmune pancreatitis. Although designated as autoimmune pancreatitis, the two diseases show little morphologic or pathogenic overlap. In type 1 disease, subsets of T lymphocytes (type 2 helper T cells, regulatory T cells, and T follicular helper 2 cells) are hypothesized to drive the inflammatory reaction. The B-cell response is characterized by an oligoclonal expansion of plasmablasts, with dominant clones that vary among patients and distinct clones that emerge at the time of relapse. Although the precise role of IgG4 in this condition remains uncertain, recent studies suggest that other IgG subclasses (eg, IgG1) may mediate the immune reactions, whereas IgG4 represents a response to dampen excessive inflammation. A recent study of type 2 autoimmune pancreatitis highlights the role of CXCL8 (alias IL-8), with duct epithelium and infiltrating T lymphocytes expressing this chemokine; the latter may contribute to the distinct form of neutrophilic inflammation in this disease. The review also highlights other forms of mass-forming chronic pancreatitis: follicular pancreatitis, groove pancreatitis, and those associated with rheumatologic diseases.

2 Review [The molecular pathology of pancreatic cancers]. 2015

Zen, Yoh. ·Department of Diagnostic Pathology, Kobe University. ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #26638781.

ABSTRACT: -- No abstract --

3 Review Type 1 autoimmune pancreatitis. 2011

Zen, Yoh / Bogdanos, Dimitrios P / Kawa, Shigeyuki. ·Institute of Liver Studies, King's College Hospital and King's College London School of Medicine, Denmark Hill, London SE5 9RS, UK. yoh.zen@kcl.ac.uk ·Orphanet J Rare Dis · Pubmed #22151922.

ABSTRACT: Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed to be involved in the underlying immune reaction. IgG4 antibodies have two unique biological functions, Fab-arm exchange and a rheumatoid factor-like activity, both of which may play immune-defensive roles. However, the exact role of IgG4 in this disease still remains to be clarified. It seems important to recognize this unique entity given that the disease is treatable with steroids.

4 Article Pancreatobiliary-type intraductal papillary mucinous neoplasm of the pancreas may have 2 subtypes with distinct clinicopathologic and genetic features. 2019

Shimizu, Takashi / Akita, Masayuki / Sofue, Keitaro / Toyama, Hirochika / Itoh, Tomoo / Fukumoto, Takumi / Zen, Yoh. ·Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: shimiz323@yahoo.co.jp. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: bokuakkey70033@gmail.com. · Department of Radiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: keitarosofue@yahoo.co.jp. · Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tymhr@me.com. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tomitoh@med.kobe-u.ac.jp. · Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: fukumoto@med.kobe-u.ac.jp. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Institute of Liver Studies, King's College Hospital & King's College London, London SE5 9RS, United Kingdom. Electronic address: yoh.zen@nhs.net. ·Hum Pathol · Pubmed #31175918.

ABSTRACT: We recently experienced cases of pancreatobiliary-type intraductal papillary mucinous neoplasms (PB-IPMNs) with imaging features resembling pancreatic ductal adenocarcinomas (PDACs), and histologic appearance of purely pancreatobiliary morphology and highly distorted papillary growth, which led to the present study aiming to systematically investigate PB-IPMNs in comparison with PDACs. Surgical cases of PB-IPMNs (n = 31) and PDACs (n = 24) were examined. PB-IPMNs were classified into monotypic tumors (n = 12; 39%) consisting of entirely high-grade pancreatobiliary-type neoplastic cells and polytypic cases (n = 19; 61%) associated with components of low-grade dysplasia and/or other histologic types (eg, gastric, intestinal, or oncocytic types). Clinically, monotypic PB-IPMNs less commonly had dilatation of the ampullary orifice (0% versus 74%) and mucin hypersecretion (17% versus 89%) than did polytypic cases. In most cases of monotypic PB-IPMNs, cystic dilatation of the lesional ducts was less obvious on imaging; therefore, 33% were radiologically diagnosed as PDACs. Histologically, intraductal tumors in monotypic cases showed a highly complex papillary architecture with tubular/cribriform glands and irregular branching, and all these cases were associated with invasive malignancy. GNAS mutations were detected in polytypic PB-IPMNs (6/19; 32%), but there were no GNAS mutations in monotypic cases. The recurrence-free survival of patients with monotypic PB-IPMN or PDAC was similar and significantly worse than that of patients with polytypic PB-IPMN. In conclusion, some cases of monotypic PB-IPMNs lacked the classic characteristics of IPMNs and shared features with PDACs, raising the possibility that these cases may be better classified as a papillary variant of PDACs rather than IPMNs.

5 Article Significance of pancreatic calcification on preoperative computed tomography of intraductal papillary mucinous neoplasms. 2019

Tsujimae, Masahiro / Masuda, Atsuhiro / Shiomi, Hideyuki / Toyama, Hirochika / Sofue, Keitaro / Ueshima, Eisuke / Yamakawa, Kohei / Ashina, Shigeto / Yamada, Yasutaka / Tanaka, Takeshi / Tanaka, Shunta / Nakano, Ryota / Sato, Yu / Ikegawa, Takuya / Kurosawa, Manabu / Fujigaki, Seiji / Kobayashi, Takashi / Sakai, Arata / Kutsumi, Hiromu / Zen, Yoh / Itoh, Tomoo / Fukumoto, Takumi / Kodama, Yuzo. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. · Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. · Center for Clinical Research and Advanced Medicine Establishment, Shiga University of Medical Science, Ōtsu, Shiga, Japan. · Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. ·J Gastroenterol Hepatol · Pubmed #31111533.

ABSTRACT: BACKGROUND AND AIM: Chronic pancreatitis is a risk factor for pancreatic cancer. Pancreatic calcification is a characteristic of chronic pancreatitis; however, its significance for intraductal papillary mucinous neoplasm (IPMN) oncogenesis remains unknown. Therefore, we investigated the relationship between pancreatic calcification and invasive IPMN. METHODS: This study included 157 patients who underwent resection for IPMN between April 2001 and October 2016 (intraductal papillary mucinous adenoma, n = 76; noninvasive intraductal papillary mucinous carcinoma [IPMC], n = 32; and invasive IPMC, n = 49). We divided the subjects on the basis of the presence/absence of pancreatic calcification on preoperative computed tomography (CT). The factors associated with pancreatic calcification were investigated in univariate analyses. Then, multivariate logistic regression analyses of the relationship between pancreatic calcification and invasive IPMC (after adjusting for clinical or imaging characteristics) were conducted. RESULTS: Preoperative CT revealed pancreatic calcification in 17.2% (27/157) of the resected IPMN. In the univariate analyses, jaundice, high serum carbohydrate antigen 19-9 levels, and invasive IPMC were significantly associated with pancreatic calcification (4/27 [14.8%] vs 4/130 [3.1%], 0.01; 12/27 [44.4%] vs 31/130 [23.8%], 0.03; and 15/27 [55.6%] vs 34/130 [26.2%], 0.001, respectively). Pancreatic calcification was significantly associated with invasive IPMC (multivariate odds ratio = 2.88, 95% confidence interval [95% CI] = 1.15-7.21, 0.03, adjusted for clinical characteristics; odds ratio = 5.50, 95% CI = 1.98-15.3, 0.001, adjusted for imaging characteristics). CONCLUSIONS: Pancreatic calcification on CT is associated with invasive IPMC. Pancreatic calcification might be a predictor of invasive IPMC.

6 Article Serum Elastase 1 Level as a Risk Factor for Postoperative Recurrence in Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms. 2018

Nanno, Yoshihide / Toyama, Hirochika / Zen, Yoh / Akita, Masayuki / Ando, Yasuhisa / Mizumoto, Takuya / Ueda, Yuki / Ajiki, Tetsuo / Okano, Keiichi / Suzuki, Yasuyuki / Fukumoto, Takumi. ·Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. toyama@med.kobe-u.ac.jp. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. · Department of Gastroenterological Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan. ·Ann Surg Oncol · Pubmed #30054822.

ABSTRACT: PURPOSE: This study was designed to assess the potential role of the preoperative serum level of elastase 1 as a risk factor for recurrence in patients with resectable well-differentiated pancreatic neuroendocrine neoplasms (PanNETs). METHODS: Preoperative serum elastase 1 levels were measured in 53 patients with PanNETs who underwent complete tumor resection in two tertiary referral centers between January 2004 and June 2017. The preoperative elastase 1 levels were correlated with clinicopathological characteristics, including tumor recurrence and recurrence-free survival. RESULTS: The median elastase 1 level was 96 ng/dL (range: 21-990 ng/dL). Preoperative serum elastase 1 levels were significantly higher in those with tumors ≥ 20 mm in diameter (vs. < 20 mm, P = 0.018), WHO grade 2 (vs. grade 1, P = 0.035), and microscopic venous invasion (vs. without venous invasion, P = 0.039). The median preoperative serum level of elastase 1 was higher in patients with recurrence than in those without recurrence (251 vs. 80 ng/dL, P = 0.004). Receiver operating characteristic analysis of elastase 1 levels showed that a cutoff level of 250 ng/dL was associated with postoperative recurrence, with 63% sensitivity, 100% specificity, and 94% overall accuracy. Patients with higher elastase 1 levels showed significantly worse recurrence-free survival than that of those with lower levels (2-year recurrence-free survival rate: 25% and 92%, respectively, P < 0.001). CONCLUSIONS: Our data provide the first evidence that high preoperative elastase 1 levels may be a risk factor for postoperative recurrence in patients with resectable PanNETs.

7 Article [Diagnostic utility of endoscopic ultrasonography elastography and contrast-enhanced harmonic endoscopic ultrasonography in a patient with type 2 autoimmune pancreatitis]. 2018

Yokode, Masataka / Shiomi, Hideyuki / Itai, Ryosuke / Mikami, Sakae / Yamashita, Yukimasa / Nakano, Ryota / Ezaki, Takeshi / Masuda, Atsuhiro / Zen, Yoh. ·Department of Gastroenterology, Kobe City Medical Center West Hospital. · Department of Gastroenterology, Kobe University Graduate School of Medicine. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine. ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #29887592.

ABSTRACT: A referring hospital diagnosed a 57-year-old man with a pancreatic head mass. The initial endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) was inconclusive because of the small sample size. Endoscopic ultrasonography elastography (EUS-EG) and contrast-enhanced harmonic endoscopic ultrasonography (CE-EUS), conducted at our institute, raised the possibility of mass-forming pancreatitis or autoimmune pancreatitis (AIP). A repeat EUS-FNA revealed inflammatory changes, including a neutrophilic duct injury suggestive of type 2 AIP. The pancreatic lesion responded well to the steroid therapy. The present case suggests that EUS-EG and CE-EUS may be useful for diagnostic exclusion of pancreatic cancers, and the combined use of EUS-EG and CE-EUS, with EUS-FNA, may help characterize inflammatory pancreatic lesions.

8 Article Multifocal cysts and incidence of pancreatic cancer concomitant with intraductal papillary mucinous neoplasm. 2018

Ikegawa, Takuya / Masuda, Atsuhiro / Sakai, Arata / Toyama, Hirochika / Zen, Yoh / Sofue, Keitaro / Nakagawa, Takashi / Shiomi, Hideyuki / Takenaka, Mamoru / Kobayashi, Takashi / Yoshida, Masaru / Arisaka, Yoshifumi / Okabe, Yoshihiro / Kutsumi, Hiromu / Fukumoto, Takumi / Azuma, Takeshi. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. Electronic address: atmasuda@med.kobe-u.ac.jp. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan. · Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan. · Department of Radiology, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology and Hepatology, Kinki University Hospital, Faculty of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology, Nissay Hospital, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology, Kakogawa Central City Hospital, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Center for Clinical Research and Advanced Medicine Establishment, Shiga University of Medical Science, Japan. ·Pancreatology · Pubmed #29685673.

ABSTRACT: OBJECTIVES: The present study was conducted in order to elucidate the relationship between the number of cyst-existing regions and incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN), which currently remains unclear. METHODS: Subjects comprised 141 patients undergoing resection for IPMN (Non-invasive IPMN (IPMN with low-to high-grade dysplasia): N = 94, invasive IPMN: N = 31, and PDAC concomitant with IPMN: N = 16) between November 2000 and February 2017. A logistic regression analysis was performed to assess the relationship between the number of cyst-existing regions (one region/two or more regions) and incidence of PDAC concomitant with IPMN, adjusted by clinical characteristics. Cyst-existing regions were defined by the number of anatomical parts of the pancreas: the head/body/tail of the pancreas. RESULTS: Multiple cyst-existing regions (two or more regions) correlated with the incidence of PDAC concomitant with IPMN (PDAC concomitant with IPMN in one region vs. two or more regions: 3/66 vs. 13/75, multivariable odds ratio [OR] = 4.11, 95% confidence interval [CI] = 1.22 to 18.8, P = 0.02). In contrast, multiple cyst-existing regions did not correlate with the incidence of IPMN (invasive IPMN in one region vs. two or more regions: 13/66 vs. 18/75, OR = 1.19, 95% CI = 0.52 to 2.76, P = 0.67). CONCLUSIONS: Multifocal cysts correlated with the incidence of PDAC concomitant with IPMN, and may be a high-risk factor for PDAC concomitant with IPMN.

9 Article High-grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer. 2018

Yokode, Masataka / Akita, Masayuki / Fujikura, Kohei / Kim, Mi-Ju / Morinaga, Yukiko / Yoshikawa, Seiichi / Terada, Takuro / Matsukiyo, Hiroshi / Tajiri, Takuma / Abe-Suzuki, Shiho / Itoh, Tomoo / Hong, Seung-Mo / Zen, Yoh. ·Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. · Department of Gastroenterology and Hepatology, Kobe City Medical Center West Hospital, Kobe, Japan. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. · Department of Gastroenterology, Nagaoka Red Cross Hospital, Nagaoka, Japan. · Department of Surgery, Fukuiken Saiseikai Hospital, Fukui, Japan. · Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan. · Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Tokyo, Japan. ·Histopathology · Pubmed #29660164.

ABSTRACT: AIMS: This study aimed to identify the pathological features of high-grade PanIN that presents with imaging-detectable abnormalities. METHODS AND RESULTS: Ten cases of isolated, main-duct, high-grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with two being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all seven cases examined. In resected specimens, high-grade PanIN was present chiefly in the main pancreatic duct, with longitudinal extension ranging between 3 and 40 mm in length (median = 18 mm). In four cases, in which hypoechoic or hypovascular masses were observed on imaging, radiopathology correlations suggested that they represented parenchymal atrophy and subsequent fibrosis around affected ducts, but not invasive malignancy. On immunohistochemistry, the loss of p16 expression was found in five (50%), p53 overexpression in two (20%) and loss of SMAD4 expression in none (0%). KRAS mutations were detected in nine cases, with two dominant clones being found in three by ultrasensitive droplet digital polymerase chain reaction, suggesting the genetic heterogeneity of dysplastic cells composing individual lesions. Mutant GNAS was also observed in one case. CONCLUSIONS: Isolated high-grade PanIN may present with pancreatic duct stenosis. Therefore, intensive investigations including pancreatic juice cytology will be required for patients with unexplained pancreatic duct stenosis. The abnormal expression of p53 and SMAD4 is infrequent, while GNAS may be mutated in premalignant lesions mainly affecting the main pancreatic duct, similar to KRAS.

10 Article Pancreatic inflammation and atrophy are not associated with pancreatic cancer concomitant with intraductal papillary mucinous neoplasm. 2018

Yagi, Yosuke / Masuda, Atsuhiro / Zen, Yoh / Shiomi, Hideyuki / Toyama, Hirochika / Sofue, Keitaro / Takenaka, Mamoru / Kobayashi, Takashi / Nakagawa, Takashi / Yamanaka, Kodai / Ikegawa, Takuya / Hoshi, Namiko / Yoshida, Masaru / Arisaka, Yoshifumi / Okabe, Yoshihiro / Kutsumi, Hiromu / Fukumoto, Takumi / Ku, Yonson / Azuma, Takeshi. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology, Nissay Hospital, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. Electronic address: atmasuda@med.kobe-u.ac.jp. · Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan. · Department of Radiology, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology and Hepatology, Kinki University Hospital, Faculty of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Internal Medicine, Rokko Island Konan Hospital, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology, Kakogawa Central City Hospital, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Center for Clinical Research and Advanced Medicine Establishment, Shiga University of Medical Science, Japan. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan; Department of Surgery, Kohnan Hospital, Japan. ·Pancreatology · Pubmed #29269290.

ABSTRACT: BACKGROUND: Inflammation-induced carcinogenesis in pancreatic ductal adenocarcinoma (PDAC) has been reported; however, its involvement in PDAC with intraductal papillary mucinous neoplasm (IPMN) remains unclear. We herein investigated the relationship between pancreatic atrophy and inflammation and the incidence of PDAC concomitant with IPMN. METHODS: This study included 178 consecutive patients who underwent surgical resection for PDAC with IPMN (N = 21) and IPMN (N = 157) between April 2001 and October 2016. A multivariable logistic regression analysis was conducted to assess the relationship between pancreatic inflammation and atrophy and the incidence of PDAC concomitant with IPMN, with adjustments for clinical characteristics and imaging features. Pathological pancreatic inflammation and atrophy were evaluated in resected specimens. RESULTS: High degrees of pancreatic inflammation and atrophy were not associated with the incidence of PDAC with IPMN (multivariable odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.07 to 3.33, P = .52, adjusted by clinical characteristics, OR = 0.9, 95% CI = 0.10 to 5.86, P = .91, adjusted by imaging studies; OR = 0.2, 95% CI = 0.009 to 1.31, P = .10, adjusted by clinical characteristics, OR = 0.2, 95% CI = 0.01 to 1.43, P = .12, adjusted by imaging studies, respectively). CONCLUSIONS: Pancreatic inflammation and atrophy were not associated with pancreatic cancer concomitant with IPMN.

11 Article Chronic Pancreatitis Finding by Endoscopic Ultrasonography in the Pancreatic Parenchyma of Intraductal Papillary Mucinous Neoplasms Is Associated with Invasive Intraductal Papillary Mucinous Carcinoma. 2017

Takenaka, Mamoru / Masuda, Atsuhiro / Shiomi, Hideyuki / Yagi, Yosuke / Zen, Yoh / Sakai, Arata / Kobayashi, Takashi / Arisaka, Yoshifumi / Okabe, Yoshihiro / Kutsumi, Hiromu / Toyama, Hirochika / Fukumoto, Takumi / Ku, Yonson / Kudo, Masatoshi / Azuma, Takeshi. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. ·Oncology · Pubmed #29258092.

ABSTRACT: BACKGROUND/OBJECTIVES: The recent guideline for intraductal papillary mucinous neoplasms (IPMNs) focuses on morphological features of the lesion as signs of malignant transformation, but ignores the background pancreatic parenchyma, including features of chronic pancreatitis (CP), which is a risk factor for pancreatic malignancies. Endoscopic ultrasonography frequently reveals evidence of CP (EUS-CP findings) in the background pancreatic parenchyma of patients with IPMNs. Therefore, we investigated whether background EUS-CP findings were associated with malignant IPMN. METHODS: The clinical data of 69 consecutive patients with IPMNs who underwent preoperative EUS and surgical resection between April 2010 and October 2014 were collected prospectively. The association of EUS-CP findings (total number of EUS-CP findings; 0 vs. ≥1) with invasive IPMN was examined. The association of EUS-CP findings with pathological changes of the background pancreatic parenchyma (atrophy/inflammation/fibrosis) was also examined. RESULTS: Among patients with EUS-CP findings, invasive intraductal papillary mucinous carcinoma (IPMC) was significantly more frequent than among patients without EUS-CP findings (42.5% [17/40] vs. 3.4% [1/29], p = 0.0002). In addition, patients with EUS-CP findings had higher grades of pancreatic atrophy and inflammation than patients without EUS-CP findings (atrophy: 72.5% [29/40] vs. 34.5% [10/29], p = 0.003; inflammation: 45.0% [18/40] vs. 20.7% [6/29], p = 0.04). CONCLUSIONS: In IPMN patients, detection of EUS-CP findings in the background pancreatic parenchyma was associated with a higher prevalence of invasive IPMC. Accordingly, EUS examination should not only assess the morphological features of the lesion itself, but also EUS-CP findings in the background parenchyma.

12 Article A case report of mixed acinar-endocrine carcinoma of the pancreas treated with S-1 chemotherapy: Does it work or induce endocrine differentiation? 2017

Yokode, Masataka / Itai, Ryosuke / Yamashita, Yukimasa / Zen, Yoh. ·aDepartment of Gastroenterology and Hepatology, Kobe City Medical Center West Hospital bDepartment of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. ·Medicine (Baltimore) · Pubmed #29137060.

ABSTRACT: RATIONALE: Acinar cell carcinomas (ACCs) and mixed acinar-endocrine carcinomas (MAECs) of the pancreas are rare, accounting for only 1% of pancreatic tumors. Although both typically present at an advanced stage, chemotherapeutic regimes have not yet been standardized. PATIENT CONCERNS: A 65-year-old man presented with a large mass in the pancreatic tail with multiple liver metastases. DIAGNOSIS, INTERVENTIONS, OUTCOMES: He was initially treated with gemcitabine for suspected ductal carcinoma of the pancreas, but no response was observed. S-1, administered as second-line chemotherapy, showed an approximately 38% reduction in the size of the primary tumor and metastatic deposits with therapeutic effects being maintained for 12 months. When the tumor progressed again, he underwent a percutaneous liver biopsy, which led to the diagnosis of MAEC. Combination therapy with cisplatin and etoposide targeting the endocrine component was administered, and this was based on the endocrine component potentially being less sensitive to S-1 than the ACC element. However, therapy was stopped due to the development of neutropenia, and the patient is currently receiving best supportive care. LESSONS: Given the previous studies suggested that S-1 is more effective for ACCs than gemcitabine, MAECs may also respond to S-1 chemotherapy, similar to ACCs. Another potential interpretation is that S-1 was effective when the condition was ACC, and eventually showed decreased effectiveness when the condition shifted to MAEC. Future studies are needed to conclude whether S-1 chemotherapy truly works against MAECs or induces endocrine differentiation in ACCs as a part of the drug-resistance process.

13 Article Mucinous cystic neoplasms of the liver and pancreas: relationship between KRAS driver mutations and disease progression. 2017

Fujikura, Kohei / Akita, Masayuki / Abe-Suzuki, Shiho / Itoh, Tomoo / Zen, Yoh. ·Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. ·Histopathology · Pubmed #28570009.

ABSTRACT: AIMS: To compare the oncogenic mutation status among mucinous cystic neoplasms (MCNs) of different histological grades and between liver and pancreatic MCNs. METHODS AND RESULTS: KRAS, GNAS, RNF43 and PIK3CA were sequenced in 25 surgical cases of hepatopancreatic MCN. Molecular features were correlated with clinicopathological and immunohistochemical findings. KRAS mutations were identified in five cases (20%), whereas GNAS, RNF43 and PIK3CA were wild-type in all cases. KRAS mutations were uncommon in cases of low-grade dysplasia (1/20, 5%), whereas KRAS was mutated in all cases of higher grades, except for one liver MCN with intermediate-grade dysplasia (4/5, 80%; P = 0.002). This genetic alteration was slightly more frequent in the pancreas than in the liver [4/17 (24%) versus 1/8 (13%), P = not significant]. KRAS-mutated MCNs more commonly had a multilocular cystic appearance (P = 0.040) and expression of mucin (MUC) 1 (P = 0.040), MUC2 (P = 0.016) and MUC5AC (P = 0.015) than KRAS-wild-type tumours. In cases of KRAS-mutated MCNs with intermediate-grade or high-grade dysplasia, identical mutations were also detected in areas of adjacent low-grade dysplasia. CONCLUSIONS: KRAS mutations appear to be major driver genetic alterations in both liver and pancreatic MCNs. As identical KRAS mutations were present in low-grade and higher-grade areas in individual cases, KRAS mutations occurring in low-grade MCNs may lead to tumour progression. Thus, preoperative KRAS testing may contribute to estimations of malignant potential. The lower incidence of KRAS mutations in liver MCNs may also explain why the risk of malignant transformation in liver MCNs is lower than that in pancreatic MCNs.

14 Article Resection of carcinoma in situ and minimally invasive carcinoma of the pancreas in a patient presenting with stenosis and post-stenotic dilatation of the main pancreatic duct on endoscopic ultrasonography and positive serial pancreatic juice aspiration cytology. 2017

Ohtsubo, Koushiro / Mouri, Hisatsugu / Yamashita, Kaname / Makino, Isamu / Tajima, Hidehiro / Ohta, Tetsuo / Inoue, Dai / Gabata, Toshifumi / Ikeda, Hiroko / Zen, Yoh / Watanabe, Hiroyuki. ·Division of Cancer Center, Kanazawa University Hospital. ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #28381785.

ABSTRACT: We report a rare case of a 67-year-old man who underwent resection of carcinoma in situ and minimally invasive carcinoma of the pancreas. The patient presented with upper abdominal and back pain. No definite pancreatic mass was detected on abdominal ultrasonography, computed tomography, magnetic resonance imaging (MRI), or endoscopic ultrasonography (EUS). However, EUS and MRI demonstrated stenosis of the main pancreatic duct (MPD) in the body and post-stenotic dilatation, resulting in mild dilatation of MPD in the tail. Serial pancreatic juice aspiration cytology after endoscopic nasopancreatic drainage was suggestive of pancreatic adenocarcinoma. Examination of the distal pancreatectomy specimen demonstrated carcinoma in situ in MPD and branches, with multiple intraepithelial neoplastic lesions in the background pancreas and an additional focus of minimally invasive carcinoma.

15 Article Smoking Status and the Incidence of Pancreatic Cancer Concomitant With Intraductal Papillary Mucinous Neoplasm. 2017

Nakagawa, Takashi / Masuda, Atsuhiro / Toyama, Hirochika / Shiomi, Hideyuki / Zen, Yoh / Sofue, Keitaro / Takenaka, Mamoru / Kobayashi, Takashi / Yagi, Yosuke / Yamanaka, Kodai / Yoshida, Masaru / Arisaka, Yoshifumi / Okabe, Yoshihiro / Kutsumi, Hiromu / Fukumoto, Takumi / Ku, Yonson / Azuma, Takeshi. ·From the *Division of Gastroenterology, Department of Internal Medicine, †Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, ‡Division of Diagnostic Pathology, §Department of Radiology, Kobe University Graduate School of Medicine, Hyogo; and ∥Center for Clinical Research and Advanced Medicine Establishment, Shiga University of Medical Science, Otsu, Japan. ·Pancreas · Pubmed #28099253.

ABSTRACT: OBJECTIVES: The effect of smoking status on the incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) has not been clarified. This study investigated the association of smoking status with PDAC concomitant with IPMN. METHODS: The subjects were 124 consecutive patients undergoing resection of IPMNs (intraductal papillary mucinous adenoma (IPMA): N = 77, invasive IPMN: N = 31, and PDAC with IPMN: N = 16) between April 2008 and October 2015. The associations between smoking status (never/former/current smoker) or cumulative pack-years (0-19/20-39/≥40) and the incidence of PDAC concomitant with IPMN or invasive IPMN were evaluated. RESULTS: Current smoking, not former smoking, was associated with the incidence of PDAC concomitant with IPMN (PDAC with IPMN vs IPMN alone; P = 0.004, PDAC with IPMN vs IPMA; P = 0.004, PDAC with IPMN vs invasive IPMN; P = 0.04, respectively), but not that of invasive IPMN (invasive IPMN vs IPMA; P = 0.85). Cumulative pack-years were higher in patients who had PDAC concomitant with IPMN than in patients with invasive IPMN (P = 0.04). Cumulative pack-years were not associated with smoking status (current vs former). CONCLUSIONS: Current smoking, not former smoking, was associated with the incidence of PDAC concomitant with IPMN. Cessation of smoking may be recommended for patients with IPMN.

16 Article Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence. 2017

Nanno, Yoshihide / Toyama, Hirochika / Matsumoto, Ippei / Otani, Kyoko / Asari, Sadaki / Goto, Tadahiro / Ajiki, Tetsuo / Zen, Yoh / Fukumoto, Takumi / Ku, Yonson. ·Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: toyama@med.kobe-u.ac.jp. · Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. ·Pancreatology · Pubmed #28043759.

ABSTRACT: BACKGROUND: The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). METHODS: Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. RESULTS: Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). CONCLUSIONS: Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence.

17 Article Association between serum SPan-1 and lymph node metastasis in invasive intraductal papillary mucinous neoplasm of the pancreas. 2017

Yamanaka, Kodai / Masuda, Atsuhiro / Toyama, Hirochika / Shiomi, Hideyuki / Zen, Yoh / Sofue, Keitaro / Takenaka, Mamoru / Kobayashi, Takashi / Sakai, Arata / Yagi, Yosuke / Nakagawa, Takashi / Yoshida, Masaru / Arisaka, Yoshifumi / Okabe, Yoshihiro / Kutsumi, Hiromu / Fukumoto, Takumi / Ku, Yonson / Azuma, Takeshi. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. Electronic address: atmasuda@med.kobe-u.ac.jp. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan. · Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan. · Department of Radiology, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology and Hepatology, Kinki University Hospital, Faculty of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Center for Clinical Research and Advanced Medicine Establishment, Shiga University of Medical Science, Japan. ·Pancreatology · Pubmed #27979602.

ABSTRACT: BACKGROUND AND AIM: Lymph node metastasis predicts poorer prognoses in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Factors associated with lymph node metastasis of invasive IPMN remain unclear. Therefore, this study aimed to define factors associated with lymph node metastasis of invasive IPMN. METHODS: Between June 2000 to August 2015, 156 consecutive patients with IPMN underwent surgical resection at Kobe University Hospital, and were enrolled in this study. The relationship between lymph node metastasis and clinical characteristics, including imaging studies and serum tumor markers, was evaluated. A multivariate logistic regression analysis was performed to assess the relationship between serum tumor markers and the presence of lymph node metastasis of IPMN, adjusted for clinical characteristics. RESULTS: Lymph node metastasis was observed in 7.7% (12/156) of IPMNs via a pathological examination. The multivariate logistic regression analysis revealed that serum SPan-1 was associated with the presence of lymph node metastasis of IPMN (odds ratio [OR] = 7.32; 95% confidence interval [CI] = 1.10 to 56.0; P = 0.04). In addition, survival was poorer among serum SPan-1-positive patients than SPan-1 negative patients (Log-rank test; P = 0.0002). Lymph node enlargement was detected preoperatively on computed tomography scans in only 16.7% (2/12) of cases that were positive for lymph node metastasis. CONCLUSIONS: Elevated serum SPan-1 was associated with lymph node metastasis in this cohort of patients who underwent resection for invasive IPMN.

18 Article CD133 expression in well-differentiated pancreatic neuroendocrine tumors: a potential predictor of progressive clinical courses. 2017

Sakai, Yasuhiro / Hong, Seung-Mo / An, Soyeon / Kim, Joo Young / Corbeil, Denis / Karbanová, Jana / Otani, Kyoko / Fujikura, Kohei / Song, Ki-Byung / Kim, Song Cheol / Akita, Masayuki / Nanno, Yoshihide / Toyama, Hirochika / Fukumoto, Takumi / Ku, Yonson / Hirose, Takanori / Itoh, Tomoo / Zen, Yoh. ·Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: sakaiyasuhiro@gaia.eonet.ne.jp. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: smhong28@gmail.com. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: soyan21@gmail.com. · Department of Pathology, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea. Electronic address: lepetit80@hanmail.net. · Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, Dresden 01307, Germany. Electronic address: denis.corbeil@biotec.tu-dresden.de. · Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, Dresden 01307, Germany. Electronic address: jana.karbanova@biotec.tu-dresden.de. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: otanikyo@med.kobe-u.ac.jp. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: kofujikura@gmail.com. · Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: mtsong21c@naver.com. · Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: drksc@amc.seoul.kr. · Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: bokuakkey70033@gmail.com. · Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yos_3n@hotmail.com. · Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tymhr@me.com. · Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: fukumoto@med.kobe-u.ac.jp. · Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yonson@med.kobe-u.ac.jp. · Department of Pathology, Hyogo Cancer Center, Akashi 673-8558, Japan. Electronic address: thirose@hp.pref.hyogo.jp. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tomitoh@med.kobe-u.ac.jp. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yohzen@med.kobe-u.ac.jp. ·Hum Pathol · Pubmed #27864124.

ABSTRACT: The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses.

19 Article Pancreatic Duct Involvement in Well-Differentiated Neuroendocrine Tumors is an Independent Poor Prognostic Factor. 2017

Nanno, Yoshihide / Matsumoto, Ippei / Zen, Yoh / Otani, Kyoko / Uemura, Jun / Toyama, Hirochika / Asari, Sadaki / Goto, Tadahiro / Ajiki, Tetsuo / Okano, Keiichi / Suzuki, Yasuyuki / Takeyama, Yoshifumi / Fukumoto, Takumi / Ku, Yonson. ·Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. ippeimm@gmail.com. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. · Department of Gastroenterological Surgery, Kagawa University Faculty of Medicine, Takamatsu, Kagawa, Japan. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. ·Ann Surg Oncol · Pubmed #27822631.

ABSTRACT: BACKGROUND: The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs. METHODS: The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection. RESULTS: MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P < 0.001), with a 5 years recurrence-free rate of 41%. On multivariate analysis, MPD involvement was significantly associated with nodal metastasis [odds ratio (OR) 16; 95% confidence interval (CI) 3.8-89; P < 0.001] and recurrence (OR 8.0; 95% CI 1.7-46; P = 0.009). The radiology-pathology correlation revealed that stenosis of the MPD was due to periductal and/or intraductal tumor invasion. Cases with MPD involvement had microscopic venous invasion (P = 0.010) and perineural infiltration (P = 0.002) more frequently than did those with no ductal infiltration. CONCLUSIONS: MPD involvement in PNETs may serve as an imaging sign indicating an aggressive clinical course.

20 Article Predictive value of low serum pancreatic enzymes in invasive intraductal papillary mucinous neoplasms. 2016

Yagi, Yosuke / Masuda, Atsuhiro / Zen, Yoh / Takenaka, Mamoru / Toyama, Hirochika / Sofue, Keitaro / Shiomi, Hideyuki / Kobayashi, Takashi / Nakagawa, Takashi / Yamanaka, Koudai / Hoshi, Namiko / Yoshida, Masaru / Arisaka, Yoshifumi / Okabe, Yoshihiro / Kutsumi, Hiromu / Fukumoto, Takumi / Ku, Yonson / Azuma, Takeshi. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan. Electronic address: atmasuda@med.kobe-u.ac.jp. · Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Department of Gastroenterology and Hepatology, Kinki University Hospital, Faculty of Medicine, Japan. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan. · Department of Radiology, Kobe University Graduate School of Medicine, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; Center for Clinical Research and Advanced Medicine Establishment, Shiga University of Medical Science, Japan. ·Pancreatology · Pubmed #27394653.

ABSTRACT: BACKGROUND: Despite evidence suggesting a role of chronic pancreatitis in pancreatic carcinogenesis, its relationship with invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. Low levels of pancreatic enzymes are predictive markers of advanced chronic pancreatitis. We investigated whether low pancreatic enzyme levels were associated with a higher incidence of invasive IPMN. METHODS: This study included 146 consecutive patients who underwent surgical resection of IPMN between April 2001 and October 2014. Multivariable logistic regression analysis was conducted to assess the association between serum pancreatic enzymes and the incidence of invasive IPMN, with adjustment for clinical characteristics including alcohol consumption. The association of serum pancreatic enzymes with pathological pancreatic atrophy and inflammation in areas adjacent to or distant from the tumor was also evaluated. RESULTS: Low serum levels of pancreatic amylase and lipase were associated with a higher incidence of invasive IPMN (multivariable odds ratio [OR] = 9.6, 95% confidence interval [CI] = 2.99 to 35.1, P = 0.0001; OR = 14.2, 95% CI = 2.77 to 112, P = 0.001, respectively). Low serum pancreatic amylase and lipase levels were also associated with higher grade pancreatic atrophy in areas adjacent to the tumor (P = 0.011 and P = 0.017, respectively) and in areas distant from the tumor (P = 0.0002 and P = 0.001, respectively). Furthermore, low serum pancreatic amylase and lipase levels were associated with higher grade inflammation in areas distant from the tumor (P < 0.0001 and P = 0.001, respectively). CONCLUSIONS: Low serum pancreatic enzymes may be a predictive marker of invasive IPMN. Excessive alcohol consumption did not influence the association of low pancreatic enzyme levels with invasive IPMN.

21 Article Microscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence. 2016

Nanno, Yoshihide / Toyama, Hirochika / Otani, Kyoko / Asari, Sadaki / Goto, Tadahiro / Terai, Sachio / Ajiki, Tetsuo / Zen, Yoh / Fukumoto, Takumi / Ku, Yonson. ·Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: toyama@med.kobe-uc.ac.jp. · Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. ·Pancreatology · Pubmed #27350059.

ABSTRACT: BACKGROUND: Microscopic venous and lymphatic invasion is a known prognostic factor for various cancers, but its prognostic relevance for pancreatic neuroendocrine tumors (PNETs) is unclear. METHODS: Thirty-two consecutive patients with PNET who had complete resection were included in this study. Venous and lymphatic invasion was identified on elastic tissue or immunohistochemical staining, and correlated with other clinicopathological factors, including recurrence-free survival. RESULTS: Venous and lymphatic invasion was identified in nine (28%) and three (9%) patients, respectively. Tumors with venous invasion were of significantly larger size, higher Ki-67 index, and higher mitotic counts. Patients with venous invasion showed significantly worse prognosis than those without venous invasion (P = 0.001). Five of nine patients (56%) with venous invasion had tumor recurrence, while a relapse was found in one case in patients without venous invasion (n = 23). Lymphatic invasion was not correlated with any other clinicopathological parameters including lymph node metastasis and recurrence-free survival. Predictive factors for recurrence in univariate analysis included microscopic venous invasion, tumor size ≥ 20 mm, non-functionality, and WHO grades. In multivariate analysis where WHO grades and microscopic venous invasion were applied, venous invasion remained a significant predictor of poor recurrence-free survival (P = 0.021). CONCLUSIONS: Microscopic venous invasion may serve as a predictive factor for tumor recurrence in patients with resectable PNET. The combination of WHO grades and microscopic venous invasion may assist in the stratification of the patients for risk of tumor recurrence.

22 Article Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. 2014

Britton, David / Zen, Yoh / Quaglia, Alberto / Selzer, Stefan / Mitra, Vikram / Löβner, Christopher / Jung, Stephan / Böhm, Gitte / Schmid, Peter / Prefot, Petra / Hoehle, Claudia / Koncarevic, Sasa / Gee, Julia / Nicholson, Robert / Ward, Malcolm / Castellano, Leandro / Stebbing, Justin / Zucht, Hans Dieter / Sarker, Debashis / Heaton, Nigel / Pike, Ian. ·Proteome Sciences plc, Cobham, United Kingdom. · Institute of Liver Studies, King's College Hospital, London, United Kingdom. · Cardiff School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom. · Faculty of Medicine, Department of Surgery & Cancer, Imperial College, London, United Kingdom. ·PLoS One · Pubmed #24670416.

ABSTRACT: OBJECTIVE: LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application. METHODS: Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset. RESULTS: Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power. CONCLUSION: Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

23 Article Intraductal papillary neoplasms and mucinous cystic neoplasms of the hepatobiliary system: demographic differences between Asian and Western populations, and comparison with pancreatic counterparts. 2014

Zen, Yoh / Jang, Kee-Taek / Ahn, Soomin / Kim, Dong Hun / Choi, Dong Wook / Choi, Seong Ho / Heo, Jin Seok / Yeh, Matthew M. ·Histopathology Section, Institute of Liver Studies, King's College Hospital, London, UK. ·Histopathology · Pubmed #24456415.

ABSTRACT: AIMS: To improve the characterization of intraductal papillary neoplasm of the bile duct (IPNB) and mucinous cystic neoplasm of the liver (MCN-L). METHODS AND RESULTS: A retrospective review of pathology archives (1999-2011) in our three institutions identified cases of IPNB (n = 138) and MCN-L (n = 54). The IPNB/MCN-L ratio was 5.7:1 at Samsung Medical Centre in Seoul, which was significantly higher than those at the University of Washington Medical Center in Seattle (1:3.0) and King's College Hospital in London (1:6.3). This difference was mainly attributable to the considerably larger number of patients with IPNB in Seoul (n = 131) than in Seattle and London (n = 7). Western patients with IPNB were all non-Asian in ancestry. IPNB differed from pancreatic intraductal papillary neoplasm in its higher histological grade, more advanced stage of an associated invasive cancer, and worse prognosis. In contrast, MCN-L showed significantly lower histological grade than its pancreatic counterpart (P = 0.022). Unlike in pancreatic mucinous cystic neoplasm, malignant transformation was very rare in MCN-L (10% versus 2%). CONCLUSIONS: This study demonstrated demographic differences in IPNB and MCN-L among regions. IPNB and MCN-L differ from their pancreatic counterparts in the risk of malignant transformation and patients' prognosis.

24 Article Elevated Ki-67 labeling index in 'synchronous liver metastases' of well differentiated enteropancreatic neuroendocrine tumor. 2013

Zen, Yoh / Heaton, Nigel. ·Histopathology Section, King's College London School of Medicine at King's College Hospital, London, UK. ·Pathol Int · Pubmed #24274715.

ABSTRACT: There is no consensus as to whether or not metastatic nodules in the liver should be biopsied for tumor grading in cases of neuroendocrine tumors with 'synchronous liver metastasis'. In this study, we compared the Ki-67 labeling index between the primary tumor and synchronous liver metastasis in 30 patients, who had received simultaneous resections. Examined tumors were of the small bowel (n = 18) or pancreas (n = 12), and G1 or G2 in primary histologic grade. In 20 patients (67%), the Ki-67 index was similar between the primary tumor and liver metastasis, but 10 (33%) showed an elevation of 3.4-14.4% in the liver, which increased the tumor grade in 4 cases. The Ki-67 elevation in the liver was more common in G2 than G1 neoplasms (P = 0.002). The size, but not number, of liver metastases was significantly larger in patients with an elevated Ki-67 index (P = 0.006). Using 40 mm as a provisional cutoff for the greatest diameter of liver metastases, the positive predictive value of this discriminator for elevated Ki-67 was 56%, and the negative predictive value was 93%. In conclusion, synchronous liver metastases can yield a higher Ki-67 labeling index than primary neuroendocrine tumours, particularly when the secondary is greater than 40 mm.

25 Article Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. 2013

Hart, Phil A / Kamisawa, Terumi / Brugge, William R / Chung, Jae Bock / Culver, Emma L / Czakó, László / Frulloni, Luca / Go, Vay Liang W / Gress, Thomas M / Kim, Myung-Hwan / Kawa, Shigeyuki / Lee, Kyu Taek / Lerch, Markus M / Liao, Wei-Chih / Löhr, Matthias / Okazaki, Kazuichi / Ryu, Ji Kon / Schleinitz, Nicolas / Shimizu, Kyoko / Shimosegawa, Tooru / Soetikno, Roy / Webster, George / Yadav, Dhiraj / Zen, Yoh / Chari, Suresh T. ·Division of Gastroenterology and Hepatology, Mayo Clinic, , Rochester, Minnesota, USA. ·Gut · Pubmed #23232048.

ABSTRACT: OBJECTIVE: Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. DESIGN: 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. RESULTS: The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. CONCLUSIONS: AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.

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