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To investigate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in the treatment of patients with advanced or metastatic gastric cancer.Chemonaive patients with histologically confirmed advanced or recurrent inoperable gastric cancer were enrolled in the present study. Treatment consisted of paclitaxel (75 mg/m(2)) and leucovorin (40 mg/m(2)) as a 2-h intravenous infusion, followed by 5-fluorouracil (2,400 mg/m(2)) as a 46-h continuous infusion. Cycles were repeated every 2 weeks.Thirty patients were enrolled in this study. There were 12 partial responses, giving an overall response rate of 40.0%. At a median follow-up of 10.6 months, the median time to progression and median overall survival were 3.9 and 8.8 months, respectively. The most common hematological toxicity was grade 1-2 anemia, which was seen in 83.3% of patients. No grade 4 leukopenia, thrombocytopenia, or anemia was noted. The most common non-hematological toxicity was anorexia, which was seen in 70% of patients, although grade 3 anorexia was noted in only 10% of cases. There was no severe treatment-related morbidity or death.Combination chemotherapy consisting of biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin was effective and well tolerated in patients with advanced gastric cancers.

There is currently no data available about the gene expression profiles of gallbladder cancer. The purpose of this study was to identify potential markers for gallbladder cancer and to examine the genetic differences between early and advanced gallbladder cancers. Total RNA was extracted from 17 gallbladder tissue specimens, including 6 advanced gallbladder cancers, 6 early gallbladder cancers and 5 normal control samples. The genes were localized with DNA microarrays and their presence was verified by performing real-time PCR. When the gallbladder cancer isolates were compared to the normal control samples, we identified 4,682 genes, including 2,270 that were overexpressed genes and 2,412 that were underexpressed genes in the gallbladder cancer. We selected 9 overexpressed genes (SERPINB5, BCL10, CD44, ARHGEF11, SERPINB2, RELA, PAK4, PPARD and BUB1B) and 1 underexpressed gene (CAV2) for real-time PCR analysis. When the advanced gallbladder cancer isolates were compared with the early gallbladder cancer isolates, we identified only 12 genes with greater than a 1.7-fold change in gene expression. We have identified several genes that may be tumor markers for gallbladder cancer. The close genetic similarity found between the early and advanced gallbladder cancers may help explain the poor prognosis of this disease.

Aberrant expression of Sonic hedgehog (Shh) has been reported in many human cancers including ductal carcinoma of the pancreas. The intraductal papillary mucinous tumor (IPMT) has been considered as one of the precursor lesions of invasive ductal carcinoma of the pancreas. Shh expression in pancreatic IPMT has not been reported. We investigated an immunohistochemical (IHC) expression of Shh in 55 cases of pancreatic IPMT. We analyzed the IHC expression of Shh in the following histologic grades of tumor: adenoma (AD), moderate dysplasia (MD), noninvasive carcinoma (NIC), and invasive carcinoma (IC), and with the following histologic subtype classification: intestinal, pancreatobiliary, null, and unclassifiable type. IHC Shh expression was noted in 6 (46.2%) of 13 AD, 5 (35.7%) of 14 MD, 12 (80%) of 15 NIC, and 11 (84.6%) of 13 IC. Shh expression was significantly increased in malignant IPMT (NIC+IC) compared with nonmalignant IPMT (AD+MD) (82.1% vs. 40.7%, P=0.0005). IHC Shh expression was found in 11 (68.8%) of 16 intestinal types, 13 (92.8%) of 14 pancreatobiliary types, 8 (38.1%) of 21 null types, and 2 (50%) of 4 unclassifiable types. Intestinal and pancreatobiliary subtypes showed a high expression of Shh compared with the null and unclassifiable type of IPMT. All 3 cases of node metastasis showed IHC Shh expression in tumor cells of metastatic lymph nodes. Therefore, Shh expression may have a critical role in the late stage of carcinogenesis of IPMT, and may impact metastatic progression to the lymph nodes in malignant IPMT.

To identify differential findings of biliary cystic intraductal papillary mucinous tumor (IPMT) and biliary cystadenoma/cystadenocarcinoma on CT images.Records of 7 patients with biliary cystic IPMT and 17 patients with biliary cystadenoma/cystadenocarcinoma were accessed. A pathologist reviewed gross morphologic and microscopic findings and confirmed the diagnosis. Two radiologists who were blind to the pathologic diagnosis reviewed CT images regarding size of cystic mass, mural nodule, septa, calcification, dilatation of the proximal, and distal bile ducts to the tumor, and the results were analyzed using multivariate analysis.Mural nodule and dilatation of the bile ducts distal to the cystic tumor were more commonly seen in patients with cystic IPMT than in patients with biliary cystadenoma/cystadenocarcinoma and these are statistically significant, the P values being 0.029 and 0.016, respectively. Size of the cystic tumor, presence of septa, calcification, and dilatation of the bile duct proximal to the cystic tumor were not statistically different.Biliary cystic IPMT could be differentiated from biliary cystadenoma/cystadenocarcinoma on CT images based on the presence of mural nodules and dilatation of the bile ducts distal to the cystic tumor.

OBJECTIVES The purpose of this study was to screen for genes related to lymph node metastasis by comparing the differences in the expression profile between pancreatic cancer with lymph node metastasis and one without, and to predict the invasiveness and the progression of pancreatic cancer on the basis of these findings. METHODS The total RNA of the tissues was extracted from 10 pancreatic cancer specimens, including those with lymph node metastasis and those with no metastasis. It was studied by means of a DNA microarray (oligo chip) consisting of 37,842 genes. We screened out 1.5-fold or more differential gene expressions in at least 5 pairs of samples. We classified both samples and genes using a 2-way clustering analysis. The screened-out genes were identified using real-time polymerase chain reaction. RESULTS We identified 194 genes, including 66 overexpressed and 128 underexpressed genes, in pancreatic cancer with lymph node metastasis. Among them, we identified some genes related to lymph node metastasis in patients with pancreatic cancer: oncogenes, tumor suppressor genes, apoptosis and antiapoptosis genes, tumor angiogenesis factors, and cell cycle regulators. Genes promoting the growth of tumor cells were highly expressed in lymph node-positive pancreatic cancer, whereas genes inducing apoptosis were underexpressed. CONCLUSIONS We have identified genes that may play an important role in metastasis and survival in patients with pancreatic cancer. These results provide new insight into the study of human pancreatic cancer metastasis, including lymph node metastasis, and ultimately may lead to improving early diagnosis and discovering innovative therapeutic approaches for cancer.

Background/Aims Controversy remains over the optimal approach to preoperative biliary drainage in patients with resectable perihilar cholangiocarcinoma. We compared the clinical outcomes of endoscopic biliary drainage (EBD) with those of percutaneous transhepatic biliary drainage (PTBD) in patients undergoing preoperative biliary drainage for perihilar cholangiocarcinoma. Methods A total of 106 consecutive patients who underwent biliary drainage before surgical treatment were divided into two groups: the PTBD group (n=62) and the EBD group (n=44). Results Successful drainage on the first attempt was achieved in 36 of 62 patients (58.1%) with PTBD, and in 25 of 44 patients (56.8%) with EBD. There were no significant differences in predrainage patient demographics and decompression periods between the two groups. Procedure-related complications, especially cholangitis and pancreatitis, were significantly more frequent in the EBD group than the PTBD group (PTBD vs EBD: 22.6% vs 54.5%, p

Background/Aims: Several precut techniques have been used to gain biliary access for difficult cases. The aim of this study was to evaluate the success and complication rates of two precut techniques, transpancreatic septotomy (TPS) and needle knife infundibulotomy (NKI), in difficult biliary cannulation due to the presence of unintended pancreatic cannulation. Methods: Eighty-six patients who failed standard biliary cannulation were included. TPS was performed when we failed to achieve biliary access despite 5 minutes of attempted cannulation or when more than three attempted unintended pancreatic cannulations occurred. If deep cannulation was not achieved within 5 minutes for any duct, NKI was performed. If this failed, we crossed over to the other technique in the second attempt. Results: The initial total success rate of biliary cannulation was 88.4% (86.6% for the TPS group and 94.7% for the NKI group, p=0.447). After crossover of the techniques, the final success rate was 95.3%. The complication rate was 20.9% in patients with TPS and 15.8% in patients with NKI (p=0.753). Conclusions: The use of different strategies based on the presence of unintended pancreatic cannulation may help increase the success rate for difficult biliary cannulation without increasing complication rates. (Gut Liver 2015;9:534-539)

9605 Background: Dexamethasone has a high therapeutic index for the prevention of chemotherapy-induced nausea and vomiting; however, the chronic use of high-dose glucocorticoids is associated with ...

The purpose of this study was to report on the clinical course and imaging findings of hemobilia after radiofrequency (RF) ablation in four patients with hepatocellular carcinoma (HCC). From July 2000 to December 2005, we experienced four cases of hemobilia after 1574 sessions of ultrasonography (US)-guided RF ablation in 1037 patients with HCCs. All ablation procedures were percutaneously performed with an internally cooled RF electrode system. The diagnosis of hemobilia was made if the patient complained of melena after RF ablation and biliary dilatation with high attenuating bile was noted at CT obtained immediately after RF ablation. We evaluated the clinical course and imaging findings of hemobilia caused by RF ablation. All patient well tolerated RF ablation procedures without any incident during the procedure. Three of four patients complained of melena with an interval from 1 day to 4 days after RF ablation. One patient was asymptomatic. The melena symptom in all symptomatic patients spontaneously improved in 2 days. None of the patients showed substantial change in vital sign and the level of hemoglobin during the admission period. In all four patients, biliary (including GB) dilatation with high attenuating bile was noted at immediate follow-up CT. The CT findings in all four patients disappeared at 1 month follow-up CT. Hemobilia is a rare potential complication of RF ablation with a favorable prognosis. Clinicians who use this technique should be aware of the characteristic CT findings and clinical course of hemobilia after RF ablation for liver tumors.

Pancreatic neuroendocrine tumors (PNET) are rare and manifest as functioning tumor (FT) or non-functioning tumor (NFT). Although malignant changes are observed in some cases, its prognosis is better than pancreatic cancer. We evaluated clinicoradiologic features and prognosis of FT and NFT. In addition, we tried to find the predictive factors for the recurrence of NFT after resection.Between October 1994 and June 2004, we retrospectively evaluated the clinicopathologic features and prognosis of 12 cases of FT and 31 cases of NFT diagnosed by surgical pathology at single medical center in Korea.PNET included 6 insulinomas, 4 gastrinomas, 1 glucagonoma, 1 somatostatinoma and 31 NFT. The major clinical manifestations were neuroglycopenic symptoms (100%) in insulinoma, abdominal ulcer symptoms (75%) in gastrinoma, dermatitis (100%) in glucagonoma, steatorrhea (100%) in somatostatinoma, and abdominal discomfort or pain (45%) in NFT. NFT was located more proximally when compared to FT (p=0.023). NFT showed more malignant (64.5%) behavior compared to FT (41.7%) despite the lack of statistical significance. Curative resections were done without postoperative death in 38 cases. Six cases of NFT (21.4%) and 1 case of FT (10%) recurred with an average of 26.5 months. In the recurrent NFT, the findings of diabetes mellitus (p=0.010), abnormal pancreatic duct (p=0.026), Whipple's operation (p=0.013) and tumor emboli (p=0.03) were more common than in non-recurrent NFT.FT and NFT showed different clinicoradiologic features. In addition, NFT should be monitored more carefully because of frequent recurrence.

Objectives: It is known that intraductal papillary mucinous neoplasm (IPMN) is associated with a high incidence of extrapancreatic neoplasms. We tried to uncover the characteristics and gene expressions of IPMNs that coexist with other extrapancreatic gastrointestinal cancers. Methods: We retrieved the surgical specimens from 54 IPMN patients, including 7 cases of IPMNs that coexisted with extrapancreatic gastrointestinal cancers. The immunohistochemical staining (p21, Bcl-2, p53, intestinal-type secretory mucin [MUC2], and MUC5AC) and the pathological subtypes of the tumor papillae (the intestinal type, pancreaticobiliary type, null type, or unclassified type) were analyzed. Results: MUC2 expression was noticed more frequently in the IPMN coexisting with extrapancreatic cancers (6/7) than in the IPMN without extrapancreatic cancers (18/47; P = 0.04). There were no differences in p21 (P = 0.12), p53 (P = 0.25), and MUC5AC (P = 1.0) expressions between the 2 groups. IPMN with extrapancreatic cancers was noticed in all subtypes of papillae. Conclusions: Regardless of the subtypes of papillae, transcription of the MUC2 might be related with the synchronous extrapancreatic gastrointestinal cancer development that is seen with IPMN. Therefore, careful systemic surveillance is needed to detect coexisting gastrointestinal cancer for all the subtypes of IPMN with MUC2 expression.

Schwannomas or neurilemmomas are uncommon tumors arising from schwann cells of neural sheath, which most frequently affect the extremities, trunk, head and neck area. Moreover, benign schwannoma in the porta hepatis is extremely rare. Approximately, 2 cases of benign schwannoma in the porta hepatis have been reported in the literatures. We report a case of benign schwannoma in the porta hepatis occurring in a 53-year-old woman who was asymptomatic and incidentally found to have a mass. Abdominal CT scan showed a 4.5 cm-sized low attenuating mass with septum-like enhancing solid portion at porta hepatis. Abdominal exploration revealed a yellowish, cystic and encapsulated mass attached to portal vein, common bile duct, liver and duodenal wall above the hepatoduodenal ligament. There has been no evidence of recurrence during 11 months of follow-up.

The authors performed a Phase II study of combination chemotherapy with gemcitabine and cisplatin in patients with inoperable biliary tract cancer to evaluate efficacy and toxicity of this combination. In addition, the correlation between the CA 19-9 response and clinical outcome was analyzed.The eligibility criteria for this study were 1) histologically or cytologically confirmed inoperable biliary tract cancer in patients with metastatic or recurrent disease; 2) age between 18 and 70 years; 3) at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; 4) an Eastern Cooperative Oncology Group (ECOG) performance statusor = 2; 5) a life expectancy of at least 3 mos; and 6) adequate bone marrow, hepatic, and renal function. The patients received gemcitabine (1250 mg/m(2), Days 1 and 8) and cisplatin (60 mg/m(2), Day 1) every 3 weeks. Tumor response was assessed by RECIST criteria every 2 cycles of chemotherapy. Treatment was continued until progression of disease was documented.Twenty-nine patients were enrolled. The median age of these patients was 52 years (range, 37 to 69 yrs), and the median ECOG performance status was 1. No complete response was observed, and 10 of 29 patients had partial responses. The overall response rate was 34.5% (95% confidence interval [CI], 17.9-54.3) for the intent-to-treat analysis. Stable disease was observed in 4 (13.8%) patients and progressive disease in 13 (44.8%) patients. The median follow-up time was 10.0 months (95% CI, 7.2-12.8). The median time to progression (TTP) was 3.0 months (95% CI, 2.12-3.88), and the median overall survival was 11 months (95% CI, 5.49-16.5). Although these results showed a better response rate (57.1 % vs. 27.3%) and survival (12 vs. 10 mos) in patients with a decline in CA 19-9 of at least 25%, these data were statistically not significant. In addition, there was a significant positive correlation between the increment in CA 19-9 values and tumor progression as determined with RECIST criteria (r = 0.96, P0.01). However, there was no definite correlation between the CA 19-9 response and the response according to RECIST criteria (P = 0.087). National Cancer Institute (NCI) common toxicity criteria (CTC) Grade 3 or 4 hematologic toxicities included neutropenia in 4 (14%) patients and anemia in 1 (3%) patient. Two of 4 patients with Grade 3 or 4 neutropenia had febrile episodes (7%) and required hospital admissions. NCI-CTC Grade 3 or 4 nonhematologic toxicity included nausea in 1 (3%) patient. There were no treatment-related deaths.The combination chemotherapy with gemcitabine and cisplatin in inoperable biliary tract cancer was tolerable for most patients and showed modest response rates. The role of CA 19-9 monitoring as a surrogate biomarker in patients with BTC treated with gemcitabine chemotherapy should be further investigated.

Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma.We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained:5%, weakly stained: 5-50%, and strongly stained:50%).All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p0.001).Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.

Background/Aims: No reliable nationwide clinical data about chronic pancreatitis (CP) was available in Korea. The etiology and clinical features of CP were investigated using a multicenter nationwide study. Methods: 814 cases of CP were enrolled retrospectively over the past 4 years at 13 hospitals. The following data were obtained from all patients: etiology, symptoms, complications, and surgery. Result: Alcohol (64.3%) was the major cause of CP and idiopathic CP (20.8%) was the second most common form. Mean patient age was 50.6 years and the male:female ratio was 6:1 (24:1 for alcoholic CP vs. 2:1 in idiopathic CP, p < 0.001). Diabetes (31.6%), pseudocysts (28.4%), biliary stricture (13.9%), and pancreatic ascites (6.6%) were the main complications. Of these, diabetes (35 vs. 26%) and pseudocyst (33.7 vs. 21.9%) were more frequent in alcoholic than in idiopathic CP. Pancreatic cancer developed in 25 patients (3.1%) during follow-up and their mean age was 59.1 years. Conclusions: In Korea, alcohol is the most common etiology of CP. Moreover, diabetes and pseudocysts are frequent complications, especially in alcoholic CP, and pancreatic cancer development is not infrequent.

Background and Aim: Although the prognosis for pancreatic cancer is generally poor, it is well known that the survival rate for resected pancreatic cancer is much higher than that for more conservative treatment. The importance of early detection is emphasized for resection of pancreatic cancer. Measurement of serum carbohydrate antigen (CA) 19-9 has shown satisfactory sensitivity and predictive value in symptomatic patients, but no available data has been found on healthy asymptomatic subjects. Thus, the authors aimed to determine the clinical usefulness of CA 19-9 as a screening tool for pancreatic cancer in asymptomatic subjects. Methods: From December 1994 to November 2000, 70 940 asymptomatic persons visiting the Health Promotion Center at the Samsung Medical Center, Seoul, Korea, participated. All subjects underwent abdominal ultrasonography and serum CA 19-9 measurement. The authors analyzed the sensitivity, specificity, and predictive values of CA 19-9 for detecting pancreatic cancer. Also, those subjects who had a serum CA 19-9 level above the cut-off value were followed up using a serial check of CA 19-9, computed tomography, or endoscopic retrograde cholangiopancreatography. Results: The number of subjects with a level of CA 19-9 above the cutoff of 37 U/mL was 1063 (1.5%), including four cases diagnosed with pancreatic cancer. The prevalence of pancreatic cancer over the age of 30 years is 13.66 per 100 000 population in Korea. Therefore, the sensitivity is 100% and the specificity 98.5%. However, the positive predictive value of CA 19-9 for detecting pancreatic cancer is only 0.9% in the asymptomatic population. Conclusion: Mass screening for pancreatic cancer using CA 19-9 levels in asymptomatic subjects is ineffective because of a very low positive predictive value, despite its high sensitivity and specificity.

Serous cystadenoma of the pancreas is a rare disease and is usually benign. Mucinous cystadenoma, another cystic neoplasm of the pancreas, has a malignant potential. Serous cystadenoma is usually composed of many small cysts lined by small, cuboidal or flattened cells containing abundant glycogen. With the finding of endoscopic retrograde pancreatography, a communication between the cyst and pancreatic duct is observed occasionally in the mucinous cystadenoma, but rarely in the case of serous cystadenoma of the pancreas. We experienced a case of serous cystadenoma of the pancreas that had a communication between a cyst and the pancreatic duct.

There has been no report for the expression of cyclooxygenase-2 (COX-2) and its clinicopathologic and biologic significance in ampulla of Vater cancer. This study was aimed for the clarification of COX-2 expression and its biologic roles in ampulla of Vater cancer. Fourty-six patients with ampulla of Vater cancer were enrolled and their COX-2 expression and clinicopathologic features were analyzed. The median age of patients was 60 yr and the mean duration of follow-up was 35 months (range: 14-82 months). Immunohistochemical stainings for COX-2, Ki-67, CD34 and TUNEL staining were performed. The immunoreactive COX-2 expression was present in 24 (52.2%) patients of ampulla of Vater cancer and mainly localized in cytosolic and perinuclear region. There was no significant difference in the length of survival between COX-2 postive and negative group (p=0.9420 by Log Rank test). Also, there were no significant differences of proliferation index (p=0.326), apoptotic index (p=0.764) and microvessel density (p=0.135) between COX-2 positive and negative group. Initial pTNM stage (p=0.0028 by Log Rank test) and blood transfusion over 4 pints during operation (p=0.0254 by Log Rank test) were independent prognostic factor in patients with ampulla of Vater cancer. It is suggested that immunoreactivity of COX-2 is not correlated with clinicopathologic and biologic features of ampulla of Vater cancer.

AIM: To determine the relevance of the 10-mm size criterion of the generally accepted surgical indication for gallbladder polyps (GBPs). METHODS: We collected data of patients who were confirmed to have GBPs through cholecystectomy at Samsung Medical Center between January 1997 and December 2012. Among the patients who underwent cholecystectomy for GBP, those with a definite evidence for malignancy such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp larger than 20 mm, absence of preoperative imaging study results, and patients having gallstones were excluded. We retrospectively collected and analyzed information on patient’s clinical characteristics, symptoms, ultrasonographic findings, and blood laboratory tests. RESULTS: A total of 836 patients who had undergone cholecystectomy were retrospectively analyzed. Seven hundred eighty patients (93%) had benign polyps, whereas 56 patients (7%) had malignant polyps. Of the 56 patients with malignancy, 4 patients (7%) had borderline GBP (10-12 mm) and a patient had small GBP (< 10 mm) with T2 stage. We conducted an ROC curve analysis to verify the 10-mm size criteria (AUC = 0.887, SD = 0.21, P < 0.001). In the ROC curve for polyp size and malignancy, sensitivity and specificity of the 10-mm size criterion was 98.2% and 19.6%, respectively. The specificity of the 11-mm and 12-mm size criteria was 44.6% and 56%, respectively, whereas the sensitivity of these two size criteria was similar. We defined the GBPs of 10 to 12 mm as a borderline-sized GBP, which were found in 411 patients (49%). In this group, there was a significant difference in age between patients with benign and malignant GBPs (47 years vs 60 years, P < 0.05). CONCLUSION: GBPs larger than 13 mm need immediate excision whereas for borderline-sized GBPs detected in young patients, careful medical observation can be a rational decision.

Background/Aims: Early detection of gallbladder (GB) cancer is essential for better survival rates. Most cases of GB cancer are diagnosed incidentally via pathology of the cholecystectomy specimen. Data on the clinical characteristics of early GB cancer are lacking. The aim of the current study was to investigate the clinical characteristics of early GB cancer to aid earlier diagnosis. Methods: Sixty-four patients who were diagnosed with early GB cancer after surgical resection at the Samsung Medical Center were enrolled in this study. Clinical characteristics, preoperative diagnoses, preoperative tumor size, laboratory findings including carbohydrate antigen 19-9 (CA19-9) levels, imaging features, and survival rate were investigated. Results: Clinical symptoms and serum tumor markers such as carcinoembryonic antigen and CA19-9 levels were not helpful indicators of early GB cancer. Radiologic modalities showed abnormal findings in every case of early GB cancer; a polypoid mass was the most common feature. Less common features included GB wall thickening, cholecystitis, and GB stones. The clinical outcome of early GB cancer was excellent. Conclusions: Screening with imaging modalities such as computed tomography (CT) or ultrasonography (US) is helpful in detecting early GB cancer. Even in the presence of GB wall thickening, cholecystitis, or GB stones on the CT or US, any abnormal findings should prompt careful examination and intensive follow up, considering the possibility of occult gallbladder cancer. (Korean J Med 2015;88:161-167)

e15150 Background: Patients with biliary tract cancer have a poor prognosis and the palliative chemotherapy has shown limited efficacy. This phase II study aimed to evaluate the efficacy and safety...

e15260 Background: In a phase III trial, the addition of erlotinib to gemcitabine improved the survival in advanced pancreatic cancer compared with gemcitabine alone. In addition, gemcitabine in co...

Background and Study Aims: Although abdominal ultrasonography (US) is a good initial screening method for detection of biliary tract disease, we sometimes encounter patients who only have findings of dilatation of the common bile duct (CBD) on US, without specific biliary symptoms or jaundice. This study aimed to evaluate the causes and clinical significance of dilatation of the CBD in patients without biliary symptoms, jaundice, or causative lesions at US. Patients and Methods: A total of 77 patients who had no biliary symptoms and whose internal CBD diameter was more than 7 mm, without definite causative lesions on US, were enrolled. Of these, 49 underwent endoscopic retrograde cholangiopancreatography (ERCP) and 28 underwent follow-up US or computed tomography (CT) instead of ERCP. We excluded patients whose bilirubin level had increased beyond the upper normal level or who had previous history of upper abdominal surgery including cholecystectomy. Results: The ERCP findings were as follows: no lesion in 20 patients (40.8 %), juxtapapillary duodenal diverticulum (JDD) in 11 (22.5 %), benign stricture in ten (20.4 %), distal CBD mass in two (4.1 %), choledochal cyst in two (4.1 %), anomalous union of the pancreaticobiliary duct (AUPBD) in two (4.1 %), and choledochal cyst with AUPBD in two (4.1 %). There were no differences in age or in alkaline phosphatase or gamma-glutamyl transpeptidase (GGT) levels between the patients who had causative lesions revealed at ERCP and those who did not. Among the 28 patients who did not undergo ERCP, 12 had returned to normal and eight had no change in CBD diameter on follow-up US. Among eight patients who underwent CT, there were four with normal findings, one with JDD, and three with suspected choledochal cysts. Conclusions: We detected a significant number of causative biliary tract lesions in asymptomatic adults with dilatation of the CBD on routine abdominal US; no laboratory or demographic parameters were useful for discrimination. Further diagnostic study will be helpful for the early diagnosis of biliary tract disease in such patients.

One of the major limitations of curative resection in patients with pancreatic cancer is local tumor extension to the mesenteric vessels. Thus, the purposes of our study were to assess the clinical value of contrast-enhanced spiral computed tomography (CT) in predicting the resectability and survival of patients with pancreatic cancer with suspicious vascular invasion and to assess the influence of curative resection on the survival of these patients. We enrolled 40 patients with pancreatic cancer who were suspected of having an involvement of the adjacent large vessels and who subsequently underwent operation with curative intent in the study. Resectability and survival were correlated with CT findings such as segment length, degree of encasement, and type and number of vessels involved. The survival rate was compared between the curative and palliative resection groups, and survival rate was compared between the resected and unresected groups. Of the 40 patients with adenocarcinoma of the pancreas, 14 had curative resections and 26 had palliative resections. The probability of curative resection was higher in patients with segment lengths less than 2 cm, as compared with segment lengths more than 2 cm. However, there was no difference in survival between the two groups. There were no differences in resectability and survival according to the degree of encasement and type and number of vessels involved. There was no difference in survival between the curative and palliative resection groups. There was no difference in survival between the resected and unresected groups. A survival benefit was not achieved by curative resection in patients with pancreatic cancer with vascular invasion. Therefore, it would be better to avoid aggressive surgery in patients with pancreatic cancer with vascular invasion.

Korea-Japan symposium for autoimmune pancreatitis was held in Yonsei medical college, Seoul on August 31, 2007. Many pancreatologists from Korea and Japan attended to discuss about the latest findings regarding autoimmune pancreatitis (AIP). The session was divided into two parts: various features of AIP including imaging, serology, histology, other organ involvement and steroid responsiveness, and the currently used Japanese and Korean criteria with prospects of what should be included for an ideal diagnostic criteria. AIP is a relatively recently recognized disease entity that is receiving much attention by gastroenterologists because of its close clinical resemblance to pancreatic cancer and its good response to steroid therapy. Both Japanese and Korean diagnostic criteria are similar in that characteristic imaging features of AIP-diffusely enlarged pancreas with diffuse narrowing of the main pancreatic duct- are essential for diagnosis. In recognition of more localized form of AIP, revised Japanese criteria of 2006 included localized enlargement and segmental narrowing of the duct as well. To go a step further, revised Korean criteria, which have been proposed in this symposium, also included mass forming type in the imaging criteria. Both criteria require addition of either positive serologic markers or histopathology consistent with AIP in addition to imaging for diagnosis. Serologic markers for AIP include serum IgG4, IgG and autoantibodies. Serum IgG4, although more sensitive, is more costly, takes longer for results and is not as widely available as serum IgG. Currently, both criteria include both serum IgG and IgG4 for serologic diagnosis. Professor Kawa from Shinshu University gave lecture on serology and presented that ANA was positive in 60% of AIP patients and rheumatoid factor (RF) was positive in about 25%. Later, Professor Okazaki from Kansai Medical University presented data that positive result was obtained in 90% of patients using more specific autoantibodies combination of anti-lactoferrin and anti-carbonic anhydrase antibodies. As for histopathologic diagnosis, Professor Se Jin Jang from Asan Medical center gave us a brief review. As widely recognized, periductal lymphoplasmacytic infiltration and fibrosis are histopathologic characteristics of AIP. In addition, vasculitis preferentially involving vein, which is termed obliterative phlebitis, is frequently observed. Another histological characteristic emphasized in the lecture was that inflammation was at similar stage for all involved sites unlike that of ordinary chronic pancreatitis, which shows some active and some inactive stage such as fibrosis and calcification differing by the region. This he named temporal and spatial homogeneity and considered important in differentiating from other causes. Also mentioned was finding of predominantly intralobular fibrosis with intact reticulin framework, and use of tissue IgG4 immunohistochemical stain for detection of IgG4 plasma cell infiltration in AIP diagnosis. Recently, disease concept of AIP has been changing. What used to be considered associated autoimmune diseases with AIP in now considered as other organ involvement with similar pathogenesis. This concept of AIP as systemic fibroinflammatory disease was first proposed by Professor Kamisawa, who also gave lecture later in the symposium; infiltration of IgG4 positive plasma cells were not only found in pancreas, but also in other organs such as bile duct, gallbladder, stomach, salivary gland, lymph node and even bone marrow. Thus, the associated organ involvement such as salivary gland enlargement, retroperitoneal fibrosis, intra/extrahepatic bile duct strictures, and hilar lymphadenopathy are now considered to be of similar pathogenesis as pancreatic lesion, and they all respond well to steroid therapy. Professor Ito from Kyushu Univ presented a lecture on the associated other organ involvement. By studying 191 AIP patients from 7 institutions in Japan, the order of frequently involved extrapancreatic sites were sclerosing cholangitis (50%), hilar lymphadenopathy (30%), and salivary gland involvement (20%). Professor Nishimori from Kochi Medical School presented a lecture on steroid response. Steroid responsiveness was studied by two nationwide surveys in Japan. From the data, initial steroid dose was most commonly 30-40 mg (0.6 mg/kg). Recurrence rate after steroid withdrawal was shown to be nearly 50%, and this recurrence rate was reduced to 24% by maintenance steroid dose of 5-7.5 mg continued for up to 3 years, because the recurrence of AIP usually occurs within 3 years. In the second session, lectures centered on the diagnostic criteria of AIP and what should be included in the ideal criteria. Professor Ji Kon Ryu from Seoul National University gave an overview of diagnostic criteria of AIP starting from historical background to the latest criteria that have been published. Professor Kyu Taek Lee from Samsung Medical Center compared the diagnostic criteria of Japanese, Korean, and one from Mayo clinic of USA. Lastly, Professor Myung-Hwan Kim from Asan Medical Center and Professor Kamisawa from Tokyo Metropolitan Komakome Hospital gave lecture on the ideal criteria and gave prospects for new Korean Criteria and Asian criteria for AIP. At the end of the second session, the most debated topic among Japanese and Korean pancreatologists was whether steroid response should be included for diagnosis of AIP. Steroid response is included in the Korean criteria, but not included in the Japanese diagnostic criteria. Japanese doctors were cautious in including it because inflammatory change associated with pancreatic cancer, the main differential diagnosis of AIP, may also show improvement with steroid trial, and facile usage of steroid trial without proper work up to rule out pancreas cancer may lead to misdiagnosis. Professor Myung-Hwan Kim remarked that although inflammatory pseudotumor associated with pancreatic cancer may improve, reversal of ductal narrowing seen in AIP is its unique feature. Japanese doctors also acknowledged that steroid responsiveness is a useful characteristic for AIP diagnosis for some cases that do not show either positive serology or histopathology. Above has been a brief summary of some of the materials from the Korea-Japan Symposium for autoimmune pancreatitis.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that leads to mucocutaneous telangiectasias, epistaxis, and gastrointestinal bleeding. Depending on the severity and manifestation of the disease, various therapeutic modalities have been used, from local bleeding control to surgery or concomitant drug therapy. Several articles under review have presented guidelines for treatment of HHT with bevacizumab as a direct anti-angiogenesis strategy. Still, neither the exact optimal dose nor the minimum effective dose of intravenous bevacizumab in patients with severe HHT has been reported. A 55-year-old man presented with long-standing epistaxis, recent melena, dizziness, and a three-generation family history of chronic epistaxis, anemia, and regular blood transfusions. Treatment with argon plasma coagulation (APC) for the gastrointestinal bleeding failed to raise hemoglobin levels, we considered using the bevacizumab. We report a patient with severe HHT, who was treated with low-dose bevacizumab (2 mg/kg) and improved substantially.

s / Pancreatology 13 (2013) S1–S80 S45 Background/aim: Distinguishing pancreatic adenocarcinomas from other pancreatic masses remains challenging in clinical practice. Contrastenhanced harmonic endoscopic ultrasound (CEH-EUS) is a promising method for characterizing pancreatic lesions due to its noninvasiveness. The clinical significance according to the change of enhancement pattern from arterial to venous phaseswas not established. The purpose of this study is to investigate the accuracy of CEH-EUS in the differentiation of pancreatic solid lesions by visualizing enhancement pattern during contrast infusion time. Methods: Between July, 2011 and March, 2013, 116 patients who referred for EUS examination of pancreatic lesions were consecutively enrolled. CEH-EUS was performed with a conventional radial echoendoscope after intravenous bolus injection of contrast agent (SonoVue). Enhancement pattern of target lesion was classified into three groups (hypo-, isoor hyper-enhancement) and also described as contrast injection time; early (10w 30 seconds), late (30w 60 seconds) and delay phase (60 w 90 seconds). The enhancement pattern of pancreatic adenocarcinoma was compared with that of other pancreatic lesions. Results: A total of 83 patients (51 male, median age 68, range 25–91) were evaluated for pancreatic solid lesions. The final diagnoses were pancreatic adenocarcinoma in 63 (75.9%), neuroendocrine tumor in 8 (9.6%), chronic pancreatitis in 3 (3.6%), autoimmune pancreatitis in 3 (3.6%), pancreatic metastasis in 2 (2.4%), malignant lymphoma in 2 (2.4%) and each cases of pancreatic abscess and solid pseudopapillary neoplasm (2.4%). In 63 pancreatic lesions with adenocarcinoma, hypoenhancement during arterial, late and delay phase was observed in 52 (82.5%), 59 (93.7%), and 62 (98.4%), respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for adenocarcinoma as hypoenhancement at CEH-EUS showed at table 1. Conclusions: CEH-EUS could characterize pancreatic mass lesions with relatively high accuracy during late phase and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

e22199 Background: Lymphangiogenesis plays an important role in cancer metastasis. Although animal models show a strong relationship between lymphangiogenesis and lymph node metastasis and survival, the clinical significance of lymphangiogenesis in colorectal cancer (CRC) remains uncertain. The goal of this study was to evaluate the association between c-Met and lymphangiogenic factors and to elucidate their prognostic significance for patients with CRC. Methods: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC in Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined by immunohistochemistry. The expression of each marker and clinical factors were analyzed. Results: Three hundred and one of 379 (79.4%) tissues had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < .001) and VEGFR-3 (P = .001). But, there was no statistically significant association with podoplanin (P = .587) and VEGF-D (P = .096). Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = .020), positive lymph node status (P = .038), and high expression of VEGF-C (P = .020). But, there was no statistically significant association with podoplanin (P = .518), VEGFR-3 (P = .085), VEGF-D (P = .203), and overall survival (P = .360). Conclusions: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factors. But, c-Met expression in patients with CRC are not prognostic indicator for overall survival in this retrospective study.

11030 Background: The ability to achieve pathologic down staging after neoadjuvant chemoradiotherapy (CRT) is correlated with improved survival. However, there is no effective method of predicting which patients will response to neoadjuvant CRT. Neoadjuvant CRT can change the expression of angiogenic factors. However, little is known about its possible changes in response to preoperative CRT. We examined the expression of angiogenic factors in rectal cancer tissues before preoperative CRT and after surgery. Methods: Fifty five patients with locally advanced rectal cancer were studied. All patients were given preoperative CRT of 5040 cGy for 5-6 weeks with concurrent administration of 5-fluorouracil and leucovorin. Surgical resection was performed 6–8 weeks later in all patients. Immunohistochemical staining for angiogenenic markers (vascular endothelial growth factor [VEGF], placenta growth factor [PLGF], hypoxia inducible factor 1α [HIF 1α], stromal cell derived factor [SDF 1α]) were performed on specimens obtained before preoperative CRT and after surgery. A semiquantitative-immunohistochemical score established from the extension and intensity of the angiogenic factors was used for analysis. Results: The positive expression rate of VEGF, PLGF, SDF 1α, and HIF 1α was 56.4% (31/55), 65.5% (36/55), 70.9% (39/55), and 47.3% (26/55), respectively. The expression rate of VEGF, PLGF, SDF 1α, and HIF 1α was increased by 3.6% (2/55), 7.3% (4/55), 30.9% (17/55), and 1.8% (1/55) after neoadjuvant CRT, respectively. Expression of VEGF, PLGF, and HIF 1α protein was downregulated after neoadjuvant CRT in the rectal cancer tissues (P < 0.001, P = 0.001, P = 0.044, respectively). However, SDF 1α was upregulated after neoadjuvant CRT (P < 0.001). And also, upregulated expression of SDF 1α after neoadjuvant CRT was significantly associated with resistance to CRT (P = 0.035). However, SDF 1α showed no correlation with other clinical factors (age, sex, clinical stage). Conclusions: Expression of SDF-1α was increased in the rectal cancer tissue after neoadjuvant CRT, as well as has been associated with CRT resistance. Our data suggests that SDF 1α should be evaluated as new target for antiangiogenic therapy.

Mo1491 Endoscopic Ultrasound-Guided Fine Needle Aspiration of Solid Masses: Histological and Immunohistochemical Evaluation Young Sik Woo*, Se-Ok Lee, Ki Joo Kang, Kwang Hyuck Lee, Jong Kyun Lee, Kyu Taek Lee, Poong-Lyul Rhee Department of Medicine, Division of Gastroenterology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea; Department of Medicine, Hallym University College of Medical School, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Objective: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been demonstrated to be useful in the diagnosis of lesions adjacent to the gastrointestinal tract. The aim of this study was to evaluate the clinical utility of histological and immunohistochemical (IHC) analyses of specimens obtained by EUS-FNA. Methods: This study was consisted of two parts; a retrospective and a prospective study. The retrospective study was performed on 116 patients who underwent EUS-FNA of solid masses for cytological smear, histological analysis, and combined analysis including IHC staining. In the prospective study, 79 patients were enrolled to evaluate quality and accuracy of EUS-FNA histological analysis and feasibility of IHC staining. Results: The final diagnosis of patients was 126 pancreatic cancer, 21 non-pancreatic cancer, 27 other neoplasm, and 21 benign lesions. In retrospective study, the combined analysis was more sensitive than cytological analysis alone (P 0.01). Overall sensitivity of cytology, histological analysis, and combined analysis were 69.8%, 67.2%, and 81.8% respectively. In the prospective study, 64.2% of all punctures were helpful to make a diagnosis and 40.7% showed tissues enough to perform IHC staining. Histological analysis was helpful for diagnosis in 74.7 % of patients and IHC stains were needed for definite diagnosis in 11.4% of patients, especially nonmalignant lesions. Conclusions: Histological analysis and IHC study of EUS-FNA specimen were useful to make a proper diagnosis of pancreatic and peripancreatic lesion. Combined analysis showed significant higher sensitivity than cytology alone because IHC stains was helpful for a diagnosis in some patients. Diagnostic accuracy of Cytological, Histological, and Combined Analyses in Retrospective data

To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B(12) deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.

Introduction A ABC-02 trial of gemcitabine plus cisplatin combination showed prolongation of overall survival in biliary tract cancer (BTC) patients. In this multicenter retrospective study, we evaluated the treatment outcomes of combination group compared with gemcitabine alone (G) in Korean BTC patients. Methods 151 patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 9 institutions between July 2000 and May 2011. 100 patients were treated with gemcitabine-platinum (GP) combination chemotherapy and the other 51 were treated with gemcitabine (G) monotherapy. Results With a median follow-up of 7.7 months (range, 0.4-38.3 months), the median overall survival was 9.2 months (95% Confidence Interval(CI) 7.5-10.9 months) among the 51 patients in the G group and 6.9 months (95% CI 5.9-7.9 months) among the 100 patients in the GP group (P Conclusion There is no difference in ORR, PFS and OS for patients treated with the G group or GP group. We showed the differences between this study and ABC-02 study. Gemcitabine monotherapy could also be effective in Korean BTC patients.