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Background: Differences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified., Methods: Forty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups., Results: 1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%)., Conclusions: Because characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds., (Copyright © 2023. Published by Elsevier B.V.)

BACKGROUND Intraductal papillary mucinous neoplasm of the pancreas (IPMN) and pancreatic ductal adenocarcinoma (PDAC) often coexist in the same pancreas. Almost all IPMNs involving PDACs concomitant with IPMN have been shown to be branch duct type IPMNs (BD-IPMNs), and their histological subtypes are gastric type. Therefore, PDACs concomitant with main duct type IPMNs (MD-IPMNs) are considered to be rare. We herein report a rare case preoperatively diagnosed as being a PDAC concomitant with MD-IPMN on the basis of imaging findings and histological findings of pancreatic specimens endoscopically obtained from 2 lesions. CASE REPORT A 67-year-old man was referred to our hospital due to an enlarged pancreas. Using imaging studies, a solid mass was found in the pancreatic head and intraductal papillary masses in the dilated main pancreatic duct of the body and tail with a fistula in the duodenum. On the basis of histological results using specimens endoscopically obtained from each of the 2 lesions, total pancreatectomy was planned due to suspected PDAC concomitant with an MD-IPMN. Finally, resected specimens were used to confirm the presence of a rare case of PDAC concomitant with MD-IPMN. CONCLUSIONS We encountered a rare case of a PDAC concomitant with an MD-IPMN which could be preoperatively diagnosed by using imaging studies and histological specimens endoscopically obtained. In addition to invasive cancers derived from IPMNs, PDACs concomitant with IPMNs can rarely develop in the pancreas involving MD-IPMNs.

Objectives: The efficacy of and indications for cytological reexamination to detect malignant changes in branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) have not been studied in detail. We conducted a retrospective study to evaluate the efficacy and indications of cytological reexamination by using pancreatic juice (repeated cytology) for BD-IPMNs., Methods: Forty-five patients who underwent repeated cytology after a diagnosis of benignancy by using initial cytology were recruited for this study., Results: Thirty-eight patients, excluding 7 patients with lack of surveillance period after the final cytology, were classified into Malignancy (n = 13) and Benignancy groups (n = 25) on the bases of the findings from resected specimens or changes in BD-IPMNs after repeated cytology. The sensitivity and specificity to detect malignant changes in BD-IPMNs by using repeated cytology were 62% and 100%, respectively. For the 12 patients with mural nodules (MNs) ≥ 5 mm (67% of them were malignant), the sensitivity was 50%, whereas, for the 26 patients without MNs ≥ 5 mm (19% of them were malignant), it was 80%. In addition, malignant changes in BD-IPMNs after initial cytology occurred in 62% of the patients with changes in the MNs and 27% of the patients with an increase in the cyst size., Conclusion: Repeated cytology can play a role in the determination for surgery even after a diagnosis of benignancy by using initial cytology, especially for BD-IPMNs without MNs ≥5 mm. In addition, changes in the MNs or cyst size may be appropriate indications for repeated cytology., Competing Interests: Declaration of competing interest Authors declare no conflict of interests for this article., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

A 13-mm mass was observed in the pancreatic head of a 70-year-old woman who had undergone melanoma resection in the nasal cavity 10 years earlier. Endoscopic ultrasonography (EUS) showed that the mass consisted of multiple hypoechoic nodules. EUS-guided fine needle aspiration and pancreatic juice cytologies revealed neoplastic cells positive for HMB45 and melan-A staining with a few melanin granules, indicating the presence of a metastatic malignant melanoma. These additional stainings were evaluated after surgery. In the surgically resected specimen, the mass had multiple nodule-like structures, some of which were brown colored. Immunocytochemistry and electronic microscopy findings confirmed the diagnosis of malignant melanoma. Microscopic findings were similar to the nasal specimen; therefore, the pancreatic lesion was considered to be a metastasis from the nasal cavity.

Purpose: To elucidate predictive factors for malignant main duct type IPMN (MD-IPMN)., Methods: All 29 subjects had mural nodules (MNs) in the main pancreatic duct (MPD) on preoperative endoscopic ultrasonography and underwent surgery (19, malignant; 10, benign). Possible predictive factors for malignancy such as background, imaging, and histological factors including histological subtype (HS), were evaluated., Results: Multivariate analysis revealed an MPD diameter of ≥12 mm (p = 0.042) and non-gastric type (p = 0.001) to be the statistically significant predictive factors for malignancy. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to detect malignancy by using "an MPD diameter of ≥12 mm and/or non-gastric type" were 95%, 70%, 86%, 88%, and 86%, respectively. In 7 subjects in whom HS was preoperatively evaluated using pancreatic specimens obtained before surgery, the agreement rate of the preoperative HS with definitive HS evaluated using resected specimens was 86%., Conclusions: For MD-IPMNs with MNs, "an MPD diameter of ≥12 mm and/or non-gastric type" are indicated for surgery. On the other hand, careful surveillance without immediate pancreatic surgery may be an option for MD-IPMNs showing both an MPD diameter of <12 mm and gastric type., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to identify an association of pancreatic anaplastic carcinoma (APC) with the epithelial-mesenchymal transition (EMT)., Methods: Resected APCs (n = 24) were examined to assess components of APCs, including carcinomatous, transitional, and sarcomatous regions. Analysis was performed based on the immunoreactivity of E-cadherin and 3 EMT-related proteins: Slug (zinc finger protein SNAI2), Twist (Twist-related protein 1), and Zeb1 (zinc finger E-box-binding homeobox 1). Expression score was determined based on staining intensity and stained area of the target cells. Finally, we performed a hierarchical clustering based on the expression pattern of E-cadherin and EMT-related proteins of the sarcomatous component., Results: The expression score of E-cadherin decreased in the order of sarcomatous > transitional > carcinomatous components (P < 0.01). Although there were significant differences in the immunohistochemical scores of Slug, Twist, and Zeb1 between carcinomatous and transitional components (P < 0.01), the significant difference in immunohistochemical score of Zeb1 between transitional and sarcomatous components was found (P < 0.05). Furthermore, APCs were divided into 2 subgroups based on the expression patterns of E-cadherin and EMT-related proteins (hierarchical clustering analysis). Consequently, these subgroups were distinguished by Twist expression., Conclusions: Epithelial-mesenchymal transition plays an essential role in the pathogenesis of APC.

An 83-year-old man with main pancreatic duct (MPD) stenosis in the pancreatic body had undergone surveillance with semiannual imaging studies for 3 years. During surveillance, magnetic resonance cholangiopancreatography revealed gradual enlargement of a small cyst near the MPD stenosis and contrast-enhanced computed tomography revealed locally progressive atrophic parenchyma in the pancreatic body. On endoscopic retrograde pancreatography, the MPD stenosis was more severe than it had been at diagnosis 3 years earlier. Endoscopic ultrasonography (EUS) showed a 10-mm hypoechoic mass adjacent to the MPD stenosis. The mass was pathologically diagnosed as an adenocarcinoma using EUS-guided fine needle aspiration, and distal pancreatectomy was performed. On histopathological examination, the resected specimen was found to be a moderately differentiated 9-mm invasive ductal carcinoma. Additionally, multiple high-grade pancreatic intraepithelial neoplasms (i.e., carcinoma in situ) were detected in the MPD and branch ducts near the invasive carcinoma.

We herein report the case of a 74-year-old man who underwent surgery 9 years after his initial visit and who was pathologically diagnosed with signet-ring cell carcinoma (SRCC) derived from a main-duct-type intraductal papillary mucinous neoplasm (MD-IPMN). At the first imaging examination, only a small pancreatic cyst with mild dilation of the main pancreatic duct (MPD) was detected in the pancreatic head. Eventually, MD-IPMN with mural nodules and MPD dilation (30 mm) developed in the pancreatic body, while the pancreatic head cyst remained unchanged. Total pancreatectomy was performed and the MD-IPMN was pathologically diagnosed as SRCC derived from an intestinal-type MD-IPMN.

Background and Aims: The aim of this study was to elucidate the efficacy of pancreatic juice cytology with the cell-block method (CB-PJC) for the determination of surgery in patients with branch duct intraductal papillary mucinous neoplasm (BD-IPMN)., Methods: In 138 patients with BD-IPMN from whom pancreatic juice was collected under ERCP for CB-PJC, we retrospectively evaluated the following: (1) the rate of successfully evaluated CB-PJC; (2) the ability of CB-PJC to diagnose malignancy and to identify pathologic subtypes in resected BD-IPMNs; (3) the rate of development into invasive cancer and progression of BD-IPMNs in patients with BD-IPMNs diagnosed as benignancy by CB-PJC; and (4) post-ERCP adverse events., Results: (1) The success rate of CB-PJC was 89.9%. (2) The sensitivity and specificity of CB-PJC for preoperative diagnosis of malignancy were 50% and 100%, respectively, with only hematoxylin and eosin staining, whereas they were 79% and 100%, respectively, by adding immunohistologic staining. The agreement rate of the preoperative subtypes by CB-PJC with the subtypes of resected specimens was 93%. (3) The onset of invasive cancer was not detected at all on imaging studies, whereas the progression of IPMN was detected in 14 patients. Multivariate analysis revealed the risk factor of progression to be non-gastric type. The cumulative 5-year progression rate in this group was 89%. (4) Post-ERCP pancreatitis developed in 13 patients (7.7%)., Conclusions: The diagnostic efficacy of preoperative CB-PJC for malignant BD-IPMN was excellent. The results may suggest the feasibility of applying preoperative subtyping by CB-PJC for decisions as to whether surgery is indicated., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: It has been reported that many branch duct intraductal papillary mucinous neoplasms (BD-IPMN) with a mural nodule (MN) reveal adenocarcinomas. On the other hand, invasive cancer derived from BD-IPMN without MN on endoscopic ultrasound (EUS) also exists. The aim of this study was to elucidate the clinicopathological features of invasive cancer derived from BD-IPMN without MN on EUS., Methods: Twenty-one patients pathologically diagnosed with invasive cancer derived from BD-IPMN were included in this study., Results: Based on the height of MNs on EUS, the subjects could be clearly classified as 12 patients whose background BD-IPMNs had high MNs (nodule-forming type IPMN) and nine whose background BD-IPMNs showed no MNs (flat type IPMN). The background BD-IPMN of the 12 patients with nodule-forming type IPMN were non-gastric type. On the other hand, the background BD-IPMN of the nine patients with flat type IPMN was gastric type. The recurrence rate was higher (33% vs. 67%) and the 5-year survival was worse (76% vs. 33%) in flat type IPMN., Conclusions: There may be a pathway for the development of invasive cancer without the formation of an MN in BD-IPMN, and attention should be paid even to the patients with BD-IPMN which does not present an MN., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background and Aim: There is a paucity of data on the cell block (CB) method for bile cytology. We compared the diagnostic efficacy of the CB method with that of conventional smear cytology for bile obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial manner., Methods: A total of 137 patients with biliary tract lesions suspicious of malignancy who had undergone bile collection under ERCP were recruited to this study. After sampling, the bile was randomized to the CB method (n = 69) or to smear cytology (n = 68). CB sections were prepared using the sodium alginate method and subjected to hematoxylin-eosin, Alcian blue-periodic acid-Schiff stain, and immunohistochemical stains. Both Papanicolaou and Giemsa stains were used for smear cytology., Results: The final diagnosis was malignancy in 94 patients: bile duct cancer, 42; pancreatic head cancer, 34; gallbladder cancer, 16; and ampullary cancer, two. The diagnostic accuracy of the CB method and that of smear cytology were 64% and 53%, respectively (P = 0.20). The sensitivity of the CB method (53%) was significantly better than that of smear cytology (28%; P = 0.014). Their respective sensitivities were 80% and 31% (P = 0.002) for bile duct cancer, 20% and 15% (P = 1.0) for pancreatic head cancer, and 30% and 67% (P = 0.30) for gallbladder cancer., Conclusion: The CB method for bile cytology showed a higher diagnostic yield than smear cytology. Its diagnostic sensitivity was satisfactory in cases of bile duct cancer., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

Background/aims: The present study aimed to elucidate the relationship between microvessel count (MVC) according to CD34 expression and clinicopathological characteristics or prognosis in pancreatic carcinoma (PC) patients who underwent hepatectomy., Methodology: CD34 expression was analyzed using immunohistochemical methods. Mean MVC in 5 areas per specimen and clinicopathological factors were consecutively examined in 42 PC patients., Results: Median MVC for PC patients was 123/mm2, which was applied as a cut-off value. Higher MVC was significantly associated with the advanced Japanese tumor-node-metastasis stage IVa and IVb (p=0.034). Univariate survival analysis identified higher carcinoembryonic antigen (CEA) and CA19-9 level, infiltrative type on macroscopic examination, invasive ductal carcinoma, node metastasis and higher tumor-node-metastasis classification were significantly associated with poor survival. The 5-year overall survival rate in the higher MVC group tended to be lower than that in the higher MVC group (37 vs. 55%), but not statistically significant (p=0.15)., Conclusions: Tumor MVC might be a candidate prognostic marker of PC patient survival after pancreatectomy and further investigation in a larger series is warranted to clarify the significance of this marker.

In advanced cancers of hepatobiliary and pancreatic lesions, major vascular resection and reconstruction are necessary to accomplish curative resection. Stenosis of vascular anastomosis is a concern in case of portal or superior mesenteric venous anastomosis with different vascular calibers. We attempted to apply parachute anastomosis in such a situation, which has often been used in the field of cardiovascular surgery. We applied this procedure in 4 cases of two hepatectomies in intrahepatic cholangiocarcinomas and two pancreatectomies in pancreatic carcinomas, in which combined vascular resection was necessary. After anastomosis, the orifice of anastomotic veins was well matched and did not show stenosis or poor blood flow on ultrasonographic examination. Parachute anastomosis in the portal or superior mesenteric vein is a useful procedure to prevent vascular stenosis, particularly in case of anastomosis with different calibers.

Background/aims: Surgical resection is a radical treatment option for pancreatic carcinoma (PC); however, it is still difficult to cure and patient prognosis is poor at this stage., Methodology: We examined the demographics, surgical records and outcome in 64 patients with hilar PC undergoing surgical resection., Results: Pancreatoduodenectomy (PD) was carried out in 48 patients, distal pancreatectomy (DP) in 14 and total pancreatectomy in two. Postoperative complications were observed in 18 patients (28%) but no hospital deaths. All stage I patients showed carcinoma in situ of intraductal papillary mucinous carcinoma (IPMC). Postoperative adjuvant chemotherapy was performed in 15 patients (23%) using gemcitabine or S-1. Cancer recurrence was observed in 36 patients (56%) and 31 died of carcinoma. The 5-year cancer-free and overall survival rate was 12% and 14%, respectively. CA19-9 level, morphological type, T category, lymph node metastasis, extrapancreatic nerve plexus invasion, retropancreatic tissue invasion, distal bile duct invasion, duodenal invasion and arterial system invasion were significant poor prognostic factors; however, portal vein system invasion was not significantly associated with prognosis. Cancer infiltration at bile duct cut-end and dissected peripancreatic tissue margin and presence of residual tumor showed a poor prognosis. Surgical prognosis in only non-invasive IPMC was satisfactory., Conclusions: Radically extended surgical resection is necessary and newly effective adjuvant chemotherapy is a promising modality to improve patient survival in PC patients.

Aim:   To elucidate the diagnostic efficacy of the cell block (CB) method by comparing it with that of conventional smear cytology for pancreatic juice obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial fashion., Methods:   A total of 170 patients with pancreatic lesions suspicious of being malignant who underwent pancreatic juice collection without giving secretin under ERCP were enrolled in this study. After sampling, the pancreatic juice was randomized to the CB method (n = 85) or to smear cytology (n = 85). CB sections were subjected to hematoxylin-eosin, periodic acid Schiff-Alcian blue, and immunohistochemical stains. Both Papanicolaou stain and Giemsa stain were used for smear cytology., Results:   The final diagnosis was malignancy in 54 patients: pancreatic cancer, 45; intraductal papillary-mucinous carcinoma, six; and endocrine tumor, three. The number of patients with a cytological borderline malignancy in the CB group (3.5%) was significantly smaller than that in the smear group (27.1%) (P < 0.001). The diagnostic accuracy of the CB method and that of smear cytology were 76.5% (65/85) and 74.1% (63/85), respectively (P = 0.72), and their respective sensitivities were 50% (14/28) and 38.5% (10/26) (P = 0.39). The sensitivity of the CB method (88.9%) was better than that of smear cytology (42.9%) for invasive ductal carcinoma in the pancreas head (P = 0.048)., Conclusions:   The CB method using immunostaining for pancreatic juice cytology showed a much lower rate of equivocal borderline malignancy and a tendency for a higher diagnostic yield compared with smear cytology. Its diagnostic sensitivity, however, was not satisfactory except for pancreatic-head cancer., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)

We herein report a case of pancreatic undifferentiated carcinoma involving intraductal pedunculated polypoid growth. Duodenoscopy disclosed a congested polypoid mass protruding from the orifice of the papilla of Vater. Endoscopic retrograde pancreatography (ERP) showed a polypoid lesion in Wirsung's duct and Santorini's duct. Pancreatic juice cytology using the cell block method revealed the presence of undifferentiated carcinoma. No extraductal invasion was detected on endoscopic ultrasonography and or intraductal ultrasonography. The patient therefore underwent pancreaticoduodenectomy. A histological examination revealed an intraductal polypoid tumor with a thin stalk without extraductal invasion. The tumor was composed of an abundant mixture of pleomorphic cells, spindle cells, giant cells, and a small amount of adenocarcinoma.

Background: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas tend to spread intraepithelially along the pancreatic duct wall. We evaluated histopathological intraductal lateral spread (LS) along the main pancreatic duct (MPD) from branch-duct IPMN and investigated the usefulness of intraductal ultrasonography (IDUS) for its preoperative diagnosis., Patients and Methods: Twenty-four patients with branch-duct IPMN who had undergone preoperative IDUS and surgery were reviewed clinicopathologically. The prevalence and histological length of LS along the MPD from branch-duct IPMN, characteristics of the patients with LS, and efficacy of LS assessment by IDUS were examined., Results: LS along the MPD was observed in 54% of the subjects. In the group of patients with LS, its mean length was 25.2±16.8mm (5-50mm) and the diameter of the MPD was 6mm or greater. Of the patients with LS, those in whom the length of LS along the MPD was longer than the diameter of the cystically dilated branch accounted for 30%. The diameter of the MPD in the group with LS was significantly greater than that in the group without LS (P=0.03). The sensitivity, specificity, and overall accuracy of IDUS in the detection of LS were 92%, 91%, and 92%, respectively., Conclusion: LS along the MPD was detected in about half of the resected cases of branch-duct IPMN. Preoperative transpapillary IDUS may be beneficial for the determination of the resection line, especially in those branch-duct IPMN patients in whom the MPD is 6 mm or greater in diameter., (© 2010 The Authors. Digestive Endoscopy © 2010 Japan Gastroenterological Endoscopy Society.)

Background: It is difficult to diagnose lymph node metastasis in biliary and pancreas carcinomas before surgery., Aim: The aim of this study was to assess the utility of the combination of multi-detector computed tomographic (MDCT) findings and serum carbohydrate antigen (CA)19-9 level in the diagnosis of lymph node metastasis in biliary and pancreas carcinomas., Methods: The subjects were 139 patients with biliary and pancreas carcinomas who underwent surgical resection. We calculated the positive predictive values (PPV), sensitivities, specificities, positive likelihood ratios (PLR) and accuracies of diagnosis by MDCT alone, serum CA19-9 level alone, and their combination., Results: The PPV and sensitivity were higher for node metastasis in hepatoduodenal ligament than in common hepatic artery (CHA) or para-aortic region (PAR). Specificity, accuracy and PLR were highest for CHA in biliary carcinoma. With pancreatic carcinoma, PLR was slightly higher in PAR compared to other regions. The sensitivity of CA19-9 for node metastasis was higher than that of MDCT, while the PPV, specificity, accuracy and PLR were low for both biliary and pancreas carcinoma. The combination of positive CT findings and high CA19-9 level had the highest positive rate for node metastasis for both types of carcinomas. Nodes around the supra-mesenteric vein could not be fully observed on CT., Conclusion: The combination of high-resolution MDCT and CA19-9 is useful for the diagnosis of lymph node metastasis in biliary and pancreas carcinomas.

Background: This study assessed the mechanism of fistula formation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas., Methods: A total of 274 patients with IPMN who had been diagnosed by endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography (EUS) at our center were enrolled. The patients with IPMN which had fistula formation into other organs were investigated retrospectively as to (1) clinical prevalence and the organs penetrated by IPMN, (2) analysis of the mechanism of fistula formation by immunohistopathological study, (3) efficacy of EUS in progression assessment, and (4) prognosis., Results: Among the subjects, fistula formation into other organs was observed in 18 patients (6.6%) and into 28 organs. There were 7 patients (39%) in whom multiple organs were penetrated. Of 16 patients who had undergone investigation of the expression of mucin markers, 94% had an intestinal-type tumor. Of 9 patients who had undergone surgery or autopsy, 67% showed mechanical penetration without invasion around the fistula. Only papillary protrusions were seen by EUS in 4 of these patients with noninvasive papillary adenocarcinoma showing mechanical penetration. All 5 patients who had pancreatic parenchymal invasion showed a mass with a mixed-echo pattern in addition to papillary protrusions shown by EUS, corresponding to colloid carcinoma., Conclusions: There were 2 processes in the development of fistulas in IPMN. Of those patients showing fistula formation, 94% had intestinal-type IPMN, and 67% showed mechanical penetration. Delineation of a mass with the mixed-echo pattern suggested an invasive penetration due to colloid carcinoma.

Background: The diagnostic efficacy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology may vary greatly depending on the treatment of the samples obtained and the level of proficiency of the cytopathologist or cytoscreener., Methods: We prospectively evaluated the diagnostic efficacy of the cell block (CB) method and that of smear cytology using tissue samples obtained in the same needle pass at EUS-FNA in 33 patients with pancreatic tumors, abdominal tumors or swollen lymph nodes. An average of 3.1 passes were applied during the procedure without affirmation by rapid cytology. About half of the material obtained by each single pass was subjected to smear cytology, while the other half was evaluated by the CB method. Four to 12 glass slides were prepared for both Papanicolaou stain and Giemsa stain. The CB sections were prepared using the sodium alginate method and subjected to HE, PAS-AB and immunohistochemical stains. Two pathologists independently made cytological and histological diagnoses. The final diagnosis was based on integration of cytohistological findings, diagnostic imaging, and clinical course., Results: The diagnostic accuracy of the CB method and that of smear cytology were 93.9 and 60.6%, respectively (p = 0.003), and their respective sensitivities were 92.0 and 60.0% (p = 0.02). It was easier to make a definite diagnosis of not only malignancies but also benign conditions by the CB method than by the smear method., Conclusion: The CB method with immunostaining showed a higher diagnostic yield than smear cytology in patients who had undergone EUS-FNA without rapid on-site cytology.

Background/aims: Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP) is a sensitive serum marker for metastatic bone carcinomas and may also be associated with invasiveness of various carcinomas. To clarify the significance of 1CTP in hepato-biliary pancreas malignancies, we examined the relationship between clinicopathological features and serum level of 1CTP., Methodology: The subjects were 75 patients who underwent surgical resections including 27 patients with liver carcinomas, 15 with extra-hepatic biliary carcinomas, 14 pancreatic carcinomas and 19 benign diseases., Results: 1CTP level tended to be higher in the malignant diseases than in benign diseases but this difference was not significant (p = 0.065). Compared to benign adenoma, 1CTP level in the malignant diseases was significantly higher (p = 0.049). 1CTP level tended to be higher in patients with cholangitis compared to those with no inflammation or benign tumors (p = 0.065). 1CTP was not correlated with any tumor markers. 1CTP was not associated with node status and vascular infiltrations. 1CTP level tended to be lower in patients with poor differentiation., Conclusions: Serum level of 1CTP might be a predictive marker for hepatobiliary pancreas malignancies but also reflects the degree of co-existing cholangitis.

A 56-year-old woman was admitted to our department for further evaluation of a hypoechoic mass in the pancreatic head detected by abdominal ultrasonography during a medical check-up. Abdominal and endoscopic ultrasonography demonstrated a demarcated round hypoechoic mass 15 mm in size without dilation of the main pancreatic duct, and ERP showed a normal main pancreatic duct and branch duct. Because pancreatic cancer was strongly suspected based on dynamic CT and MRI findings, she underwent pancreatoduodenectomy. Pathologically, the tumor was diagnosed as well-differentiated adenocarcinoma in the pancreatic head, 13 mm in diameter, 10mm apart from the main pancreatic duct. The main pancreatic duct was completely free of cancer cells and the origin of the cancer was considered to be the epithelium of a peripheral branch duct.

We present a case of small pancreatic head cancer with pancreas divisum preoperatively diagnosed by pancreatic juice cytology. A 60-year-old woman was referred to our hospital for evaluation of a dilated main pancreatic duct (MPD). A small and poorly reproducible low-echoic lesion in the pancreas was suspected by ultrasonography (US) and endoscopic ultrasonography (EUS). Magnetic resonance cholangiopancreatography (MRCP) failed to visualize the ventral pancreatic duct, and the upstream dorsal pancreatic duct was dilated. Endoscopic retrograde cholangiopancreatography (ERCP) was indicative of pancreas divisum, and complete obstruction of the MPD in the pancreatic head was seen. Cytology of pancreatic juice obtained from the dorsal pancreas after minor papilla sphincterotomy revealed the presence of adenocarcinoma cells. Pancreatoduodenectomy was performed under the diagnosis of pancreatic head cancer with pancreas divisum. Histological examination revealed moderately-differentiated tubular adenocarcinoma 20 mm in diameter, located in the pancreatic head. Dilatation of the dorsal pancreatic duct is sometimes observed in cases with pancreas divisum without the presence of tumors. When pancreatic duct stenosis also exists in such cases, even if a tumor is not clearly visualized by diagnostic imaging, vigorous examinations such as pancreatic juice cytology are recommended to establish an accurate diagnosis.

Many causes of biliary stricture are iatrogenic including postoperative complication such as a cholecystectomy. We examined the clinical demographics, surgical records and outcome in 7 patients undergoing biliary surgery between 1994 and 2006. Diseases included gall stone in 6 patients and neuroendocrine tumor of the pancreas head in one. Causes of biliary stricture included bile duct injury during cholecystectomy in 4 patients, and stenosis of hepaticojejunostomy in 3 (Repair of biliary injury in two and reconstruction after pancreaticoduodenectomy (PD) in one). Treatment modalities included surgical resection of stricture and reconstruction in 4 patients, extension by balloon catheter in one, and conservative treatment in two. Six patients have been cured and, however, one patient died of biliary cirrhosis and progressive hepatic failure at 4 years after PD. When improvement by the extension of stricture was not observed, surgical approach should be necessary. Complete resection of stricture and anastomosis between normal bile duct and intestine might be necessary. Indication of placement of metallic stent in stricture was thought to be carefully considered.

Background/aims: Characteristics of intraductal papillary mucinous neoplasms of pancreas (IPMN) have been clarified by a worldwide survey and meeting. However, the malignant behavior or prognosis of the disease is not always uniform., Methodology: We examined the clinicopathologic demographics, surgical records and outcome according to degree of histologic malignancy in 18 IPMN patients between 1994 and 2006., Results: Main duct type was observed in 3 patients, branch duct type in 6, and mixed type in 9. Eight of 18 patients (44.4%) had other malignancies, and other synchronous tumors were observed in the adenoma group. CA 19-9 was increased in invasive carcinomas. The size of the main pancreatic duct and cysts were not correlated with degree of malignancy. Mural nodules were more frequently observed in minimally invasive and invasive carcinomas. Segmental resection or observation was selected in the adenoma group; however, combined resection of main vessels was performed in invasive carcinoma groups. Although 3 of 5 patients with invasive carcinomas had a recurrence and poor patient prognosis, recurrence was not observed in other groups., Conclusions: Surgical results for IPMN were satisfactory; however, it is necessary to determine the operative indication before the carcinoma becomes invasive as such lesions have a poor prognosis.

Background/aims: In advanced cancers of hepatobiliary and pancreatic lesions, major vascular resection and reconstruction are necessary to accomplish curative resection, which may provide better patient outcomes., Methodology: Surgical records, morbidity and mortality, and prognosis were examined in patients with combined vascular resection. Thirty-six patients underwent 18 hepatectomies and 18 pancreatectomies., Results: In 18 patients who underwent hepatic resection, the resected vessels were the portal vein (PV) in 10, vena cava or hepatic vein in 9 and right hepatic artery (RHA) in 3. An artificial graft was used in 2 to replace the vena cava. Vascular bypass was performed in 5 patients. Morbidity was due to biliary stricture in 1 patient and adult respiratory distress syndrome in another who died during hospital stay. Fourteen (82%) had cancer recurrence, of whom 12 died of cancer, one died of other disease, and 2 survived cancer-free. The 5-year survival was 28%. In 18 patients who underwent pancreatectomy, resected vessels were PV in 18 and RHA in 1. An artificial graft was used in 3 and vascular passive bypass was performed in 6. One patient died of sepsis after total pancreatectomy during hospital stay. Eleven (64%) had cancer recurrence, of whom 11 died of cancer, 2 died of other disease, and 4 survived cancer-free. The 3-year survival was 27%., Conclusions: Complete surgical resection (R0) combined with main vascular resection could be safely performed in many patients with disease of the hepatobiliary and pancreas, which achieved longer survival in some patients even in the advanced stage.

Background: The aim of this study was to evaluate histopathologically the frequency, direction, and length of intraductal spread (IS) along the main pancreatic duct from the main tumor of small pancreatic cancer., Methods: Resected specimens from 20 cases of pTS1 (histologically 2 cm or less in diameter) pancreatic cancer (September 1983 to December 2005) were examined histopathologically. As controls, 40 resected specimens from cases of pTS2 (more than 2 cm and less than 4 cm in diameter) or larger sized pancreatic cancer (pTS2

The aims of this study were to investigate morbidity, mortality, and survival of patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy without (group 1) or with (group 2) en bloc portal vein resection and to study the degree of carcinoma invasion of the portal vein in group 2. The medical records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In addition, the degree of invasion of the wall of the portal vein was categorized histologically into three types: type I, transmural invasion involving the intima; type II, invasion of the wall of the vein without intimal involvement; and type III, compression of the wall of the vein by surrounding carcinoma without true invasion. The morbidity and mortality in group 1 (26% and 4%) were not different from those in group 2 (32% and 4%). Similarly, there was no difference in survival between the two groups. Survival tended to vary directly with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9 months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These findings suggest that en bloc resection of the pancreas and the portal vein does not increase mortality and morbidity after pancreatectomy; survival after en bloc resection was similar to that of patients not requiring portal vein resection. Combined resection of the pancreas with the portal vein could be an option in the treatment of pancreatic cancer with direct invasion of the portal vein.

Sialyl-Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. In the present study, we compared the serum level of STn antigen in 14 patients with benign diseases of the biliary tract and pancreas, 15 patients with bile duct cancers, and 9 patients with cancer of the pancreas. High levels of serum STn (>45 U/ml) were frequently detected in patients with carcinoma of the biliary tract (53.3%) or pancreas (55.6%), compared with the detection of high levels in those with benign diseases (14.3%; P < 0.05). Serum levels of STn did not correlate with the presence of jaundice, cholangitis, or pancreatitis, or with the level of carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9. In cancer tissues, the expression of STn antigen detected by immunostaining correlated significantly with serum STn (P < 0.05). Our results indicate that measurement of serum STn level may be potentially useful for the diagnosis of carcinomas of the biliary tract and pancreas, particularly when combined with other tumor markers such as CEA or CA19-9.

We described a rare form of giant cell tumor of the pancreas composed of mixed osteoclastic/pleomorphic-type giant cell tumor with ductal adenocarcinoma. Immunohistochemical study showed positive staining of cytokeratin and epithelial membrane antigen for pleomorphic-type giant cells and ductal adenocarcinoma but negative for osteoclastic-type giant cells. Vimentin stained positive in both types of giant cells but negative in adenocarcinoma. Osteoclastic-type giant cells were strongly positive for CD68 and tartarate-resistant acid phosphatase was present in these cells, suggesting the osteoclast-like character. CD68 was negative for both pleomorphic-type giant cells and ductal adenocarcinoma. From these findings, we consider that this tumor might be a carcinosarcoma-like neoplasm consisting of both an epithelial and a histiocytic-mesenchymal component.

Background/aims: Basement membrane disruption is a characteristic of invasive carcinoma. Gelatinases (also called type IV collagenases) that degrade type IV collagen are believed to play an important role in tumor invasion and metastasis. Intraductal neoplasm (IDN) of the pancreas is a unique tumor that grows intraductally with an infrequent stromal invasion. However, in IDN, basement membrane anomaly and gelatinase expression have not been clarified. The aim of this study was to examine the relationships between basement membrane disruption and the expression of gelatinase A in relation to the biological behavior of IDN or pancreatic duct cell carcinoma (DCC)., Methods: Disruption of basement membrane and expression of gelatinase A were immunohistochemically investigated in 14 cases of IDN and 16 cases of DCC., Results: Basement membrane was intact in all cases of IDN, whereas focal to severe disruption was observed in DCC. Stromal expression of gelatinase A was higher in DCC than in IDN, and the intensity of expression was related to the degree of disruption of the basement membrane in DCC., Conclusions: Stromal expression of gelatinase A and disruption of basement membrane, common characteristics of invasive cancer, were not prominent in IDN. This may be related to the benign biological behavior of IDN.

In order to clarify whether the detection of a point mutation in the c-Ki-ras gene at codon 12 in tumor tissues can assist in predicting the tumor's biological grade of malignancy, two types of tumors were investigated; one was called "carcinoma in the pancreatic head region," and the other was intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN). Dot hybridization and a modified PCR technique developed by Haliassos et al. were employed. Among 16 cases of tumors in the pancreatic head region, the point mutation was detected with a high frequency only in pancreatic ductal cell carcinomas (five out of six cases, 83.3%), but was not detected in extrahepatic bile duct carcinomas (0/5) or in ampullary carcinomas (0/5). In pancreatic ductal cell carcinomas, no relation was found between the occurrence of the point mutation and the histological type of the tumor. Among 20 cases of IMHNs, the point mutation was found in 11 cases (55%). No relation was found between the occurrence of the mutation and the size of IMHNs. However, as the grade of cell atypia increased, the frequency of the mutation tended to become higher. These results suggest that detection of this point mutation might be useful for distinguishing pancreatic ductal cell carcinoma from those of other origins in the pancreatic head region, and for the determination of the histopathological grade of malignancy in IMHNs.

Background: Intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN) is a unique tumor that has a tendency to spread intraductally. The clinical outcome of IMHN generally is far better than that of pancreatic ductal cell carcinoma. Because of the presence of various cell atypia within the same tumor, it sometimes is difficult to make an accurate histopathologic diagnosis and, therefore, predict its biologic behavior. It has been shown that overexpression of c-erbB-2 protein in breast cancer with lymph node metastases is related to a poor prognosis. Overexpression of c-erbB-2 protein has been reported as an infrequent event in pancreatic ductal cell carcinoma, but little is known in the case of IMHN., Methods: The expression of c-erbB-2 protein was immunohistochemically investigated in the formaldehyde-fixed, paraffin-embedded tissues of 17 cases of IMHN, and 14 cases of pancreatic ductal cell carcinoma (8 cases with lymph node metastasis), using polyclonal and monoclonal c-erbB-2(p185) antibodies by the avidin-biotin method., Results: Both the polyclonal and monoclonal antibodies showed similar immunostaining for the c-erbB-2 product. Overexpression of the c-erbB-2 product was observed frequently in IMHN (13/17), especially in that with moderate- to high-grade cell atypia (12/12), whereas it was detected in only 1 of 14 cases of pancreatic ductal cell carcinoma (1/14). Among eight cases of pancreatic ductal cell carcinoma with lymph node metastases, overexpression of the c-erbB-2 product in metastatic lesions was detected in two, one of whose primary lesions also overexpressed the oncogene product., Conclusions: These observations suggest the genetic expression of c-erbB-2 is related to the pathogenesis of IMHN.

The point mutation of c-K-ras oncogene at codon 12 was investigated in 15 cases of mucin-producing cystic tumor of the pancreas by a modified polymerase chain reaction (PCR) method. Three percent formalin-fixed and paraffin embedded materials were employed for the present investigation. These fifteen cases were histopathologically classified into five categories (from group I to V) according to Kozuka's classification which was based on cell atypia of the tumor cells; 5 cases were judged as group V, 4 cases as group IV, and 6 cases as group III. The frequency of point mutation was 5/5 in group V, 3/4 in group IV, and 2/6 in group III. The frequency of point mutation was correlated with morphologically determined cell atypia. Among group III, the point mutation was noticed in the cases with larger tumor size. From genetical point of view, the results indicated more malignant biological feature of mucin-producing cystic tumor of the pancreas than has generally been accepted.