Lifestyle, body mass index, diabetes, and the risk of pancreatic cancer in a nationwide population-based cohort study with 7.4 million Korean subjects.

BACKGROUND: Large-scale epidemiological studies on pancreatic cancer in non-Western populations are insufficient. We investigated the risk factors for pancreatic cancer. METHODS: Using the Korean National Health Insurance database, subjects who participated in the health examination program between 2005 and 2006 were identified and followed up until 2017. Adjusted hazard ratios (HRs) for pancreatic cancer risk were estimated using a Cox proportional hazards model. RESULTS: During 11.5 years follow-up, 22,543 of 7,445,947 participants were newly diagnosed with pancreatic cancer. Compared with normal-weight subjects, pancreatic cancer risk was increased in those with severe obesity (BMI ≥ 28 kg/m2) (HR = 1.16; 95% CI, 1.11-1.23). Subjects with diabetes had an increased risk compared with those without diabetes (HR = 1.48; 95% CI, 1.43-1.53). Current smokers had a higher risk than never smokers (HR = 1.43; 95% CI, 1.38-1.48). Current smoking combined with diabetes increased the risk compared with never smokers without diabetes (HR = 2.13; 95% CI, 2.00-2.28). Current smoking combined with BMI ≥ 25 kg/m2 had an increased risk compared with never smokers with BMI < 23 kg/m2 (HR = 1.55; 95% CI, 1.46-1.65). CONCLUSION: Smoking, obesity, and diabetes are significant risk factors for pancreatic cancer in Koreans. Lifestyle modifications for smoking and obesity would be beneficial for pancreatic cancer prevention.

The Significance of the Prognostic Nutritional Index for All Stages of Pancreatic Cancer.

Nutritional status affects the prognosis of various tumors. The prognostic nutritional index (PNI) is the known predictor of postoperative outcome in resectable pancreatic cancer patients. This study aimed to validate the prognostic value of PNI in all stages of pancreatic cancer. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed at Severance Hospital between January 2006 and December 2011. The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3) at initial diagnosis. The median patient age was 62 yr, and 289 were men. The study group comprised resectable disease (n = 121), locally advanced disease (n = 118), and metastatic disease (n = 260). Univariate and multivariate analysis revealed that PNI ≤ 49.5 at initial diagnosis, together with performance status, platelet count, and clinical stage, was significantly associated with overall survival (hazard ratio, 1.562; all P < 0.05). Patients with PNI ≤ 49.5 (n = 208) had shorter median overall survival compared to patients with high PNI (9.8 vs. 14.2 mo; log rank, P < 0.001). In clinical stage subgroup analysis, initial PNI ≤49.5 independently predicted shorter overall survival, especially in resectable and metastatic disease (P = 0.041, P = 0.002, respectively).

Best options for preoperative biliary drainage in patients with Klatskin tumors.

Operative treatment combined with PBD has been established as a safe management strategy for Klatskin tumors. However, controversy exists regarding the preferred technique for PBD among percutaneous transhepatic biliary drainage (PTBD), endoscopic biliary stenting (EBS), and endoscopic nasobiliary drainage (ENBD). This study aimed to identify the best technique for preoperative biliary drainage (PBD) in Klatskin tumor patients. METHODS: This study evaluated 98 Klatskin tumor patients who underwent PBD prior to operation with a curative aim between 2005 and 2012. The PTBD, EBS, and ENBD groups included 43, 42, and 13 patients, respectively. Baseline characteristics, technical success rate, complications of PBD, and surgical outcomes were compared. RESULTS: Initial technical success rates (97.3 %, PTBD; 90.2 %, endoscopic methods, including EBS and ENBD) and mean duration until biliary decompression (31.0, PTBD; 28.7, EBS; 35.8 days, ENBD) were not significantly different between the groups. Total frequency of complications did not significantly differ between the EBS group (42.9 %) and the PTBD (27.9 %, p = 0.149) and ENBD (15.4 %, p = 0.072) groups. The ENBD group showed a significantly higher rate of conversion to other methods (76.9 %) than the PTBD (4.7 %, p < 0.0001) and EBS (35.7 %, p = 0.009) groups. CONCLUSIONS: PTBD, EBS, and ENBD showed comparable results regarding initial technical success rates, complication rates, and surgical outcomes. As Klatskin tumor patients must undergo PBD prior to 3 weeks before surgery, PTBD and ENBD are uncomfortable and disadvantageous in terms of compliance. EBS was the most suitable method for initial PBD in terms of compliance among Klatskin tumor patients.

Visceral Obesity is Associated with Poor Prognosis in Pancreatic Adenocarcinoma.

An association between obesity and unfavorable outcomes for various types of malignancy has been established. Nevertheless, the impact of visceral obesity (VO) on outcomes in pancreatic cancer is still unknown and controversial. The aim of this study was to uncover an association between VO and pancreatic cancer outcomes. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed and treated in Severance Hospital from January 2006 to December 2011. Compared to the low-VO group (n = 260), the high-VO group (n = 239) was mostly male (68.2% vs. 31.8%, P < 0.001) and was more likely to have current smoking status (29.7% vs. 17.7%, P < 0.001), current alcohol intake status (52.3% vs. 26.4%, P < 0.001) and diabetes mellitus (54.4% vs. 31.9%, P = 0.028). The progression free survival (PFS) and overall survival (OS) were found to be significantly shorter by the Kaplan-Meier method in the high-VO group than in the low-VO group (PFS; P = 0.044, OS: P = 0.013). In addition, the higher percentage of visceral fat was correlated with more lymph node metastasis and shorter OS (P = 0.011 and P = 0.017, respectively). In patients with pancreatic cancer, VO at the time of diagnosis is associated with negative outcomes, such as shorter PFS and OS.

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

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

Gemcitabine based neoadjuvant chemoradiotherapy therapy in patients with borderline resectable pancreatic cancer.

BACKGROUND: Surgical resection is the only curative treatment for pancreatic cancer, but surgical outcomes for borderline resectable pancreatic cancer (BRPC) are generally poor because of the complexity of the surgery and the advanced nature of the tumor. The aim of this study was to evaluate whether neoadjuvant concurrent chemoradiation therapy (CCRT) in BRPC patients could improve surgical outcome. METHODS: Baseline characteristics and treatment outcomes for patients who underwent surgery for BRPC with (CCRT (+) group) and without neoadjuvant treatment (CCRT (-) group) were retrospectively compared. Treatment outcomes measured included overall survival, recurrence-free survival, and perioperative complications. RESULTS: A total of 30 patients were included in the CCRT (+) group and 21 patients in the CCRT (-) group. Baseline characteristics were not different before CCRT, but pathological examination after resection revealed reduced tumor size and a lower neurovascular invasion rate in the CCRT (+) group. Overall median survival time was 45.0 months in the CCRT (+) group and 23.5 months in the CCRT (-) group (p = 0.045). The CCRT (+) group had a lower recurrence rate (50.0% vs. 81.0%; p = 0.024) and a longer median disease-free survival period (21.0 months vs. 10.6 months; p = 0.004) than the CCRT (-) group. Perioperative complication rates were not different between the two groups. CONCLUSIONS: Neoadjuvant chemoradiation therapy combined with surgical resection yielded better treatment outcomes in patients with BRPC compared with surgery alone. Further larger prospective clinical trials with well defined enrollment criteria and treatment plan are needed.

Endoscopic papillary large balloon dilatation alone is safe and effective for the treatment of difficult choledocholithiasis in cases of Billroth II gastrectomy: a single center experience.

BACKGROUND: Endoscopic treatment of difficult common bile duct (CBD) stones (diameter ≥ 10 mm, or four or more) is difficult in patients who have undergone Billroth II (B-II) gastrectomy. Endoscopic sphincterotomy (EST) can be particularly troublesome due to anatomical changes effected by the gastrectomy. AIM: We evaluated the efficacy and safety of endoscopic papillary large balloon dilation (EPLBD) with large-diameter dilation balloons in the treatment of difficult CBD stones in patients who have undergone B-II gastrectomy. MATERIALS AND METHODS: From June 2006 to April 2011, patients with difficult CBD stones and who had undergone B-II gastrectomy previously were included in this study. EPLBD was performed with a 10-18 mm balloon catheter. When selective cannulation through the sphincter was possible, EPLBD was performed without EST. EPLBD was otherwise performed after fistulotomy with needle knife. RESULTS: A total of 40 patients (32 male) underwent EPLBD for the retrieval of CBD stones, and concurrent fistulotomy was performed in seven patients. The median diameter of CBD was 13 mm (range 10-20 mm) and the balloon was 12 mm (range 10-17 mm). CBD stones were successfully removed in all patients. In only three patients, repeated sessions of ERCP were required for complete removal of CBD stones. Mechanical lithotripsy was required in only one case. Acute complications from EPLBD included mild pancreatitis in two patients (5.0 %). Severe complications, including perforation and bleeding, were not observed. Late complications included stone recurrence in one patient (2.5 %) and cholecystitis in four patients (10.0 %). CONCLUSIONS: In cases of B-II gastrectomy, EPLBD without EST is a safe and highly effective technique for the retrieval of difficult CBD stones. EPLBD should be considered as an alternative tool to conventional EST.

High serum CA19-9 levels are associated with an increased risk of cholangiocarcinoma in patients with intrahepatic duct stones: a case-control study.

BACKGROUND: Hepatolithiasis is a known risk factor for cholangiocarcinoma (CC). Due to the high risk of complications that accompany endoscopic and surgical stone removal, it is often difficult to decide whether it is beneficial to remove intrahepatic ductal stones. We conducted a case-control study to determine the risk of developing CC and the benefit of stone removal in patients with hepatolithiasis. METHODS: Twenty-three patients with CC group between 2002 and 2012 were included in this study. For each patient with CC, four control patients with hepatolithiasis were enrolled based on age and sex matching. Finally, 115 patients with hepatolithiasis were enrolled. RESULTS: The mean length of time that intrahepatic stones were present was 116.57 (± 98.77) months in the CC group and 80.56 (± 101.10) months in the control group. History of gastrectomy [OR 5.756 (1.329-24.930), p = 0.019], history of choledochoenterostomy (OR 4.938 [1.129-21.595], p = 0.034), serum CA19-9 level [OR 1.001 (1.000-1.001), p = 0.022], and complete removal of stones [OR 0.167 (0.052-0.539), p = 0.003] were independent predictive factors of CC. In patients who had undergone incomplete removal of stones, the occurrence of CC was significantly reduced overall as well as in a subgroup of patients with elevated CA19-9 (p = 0.015 and p = 0.006, respectively) compared to patients with a CA19-9 of <22 U/mL (p = 0.477). CONCLUSIONS: History of gastrectomy or choledochoenterostomy, high levels of serum CA19-9, and incomplete removal of stones were potential predictive factors of CC in patients with hepatolithiasis. Additionally, complete removal of stones may reduce the risk of CC in patients with high serum CA19-9 levels (>22 U/mL).

Folfox4 as a rescue chemotherapy for gemcitabine-refractory pancreatic cancer.

BACKGROUND/AIMS: This phase II study assessed the efficacy and safety of FOLFOX4 as a rescue therapy in patients with gemcitabine-refractory pancreatic cancer. METHODOLOGY: The study included patients with advanced pancreatic cancer who had failed gemcitabine-based chemotherapy. FOLFOX4 was administered biweekly as follows: oxaliplatin, 85 mg/m² as a 2-hour infusion (day 1); leucovorin, 200 mg/m²/day as a 2-hour infusion (days 1 and 2); 5-fluorouracil, bolus 400 mg/m²/day and 600 mg/m²/day as a 22-hour infusion (days 1 and 2). RESULTS: Forty-four patients received a total of 264 cycles of chemotherapy. There was 1 complete response (2.2%), 4 partial responses (9.1%), and 13 stable diseases (29.5%). The objective response rate was 11.4% and the tumor stabilization rate was 40.9%. The median time to progression was 9.9 weeks (95%CI: 8.2-11.5) and the median overall survival was 31.1 weeks (95%CI: 24.4-37.9). The common adverse events were hematologic toxicities: grade 3 or 4 neutropenia in 19 patients (43.2%), anemia in 9 patients (20.5%), and thrombocytopenia in 6 patients (13.5%). Grade 3 or 4 neuropathy occurred in 4 patients (9.1%). CONCLUSIONS: In gemcitabine-refractory pancreatic cancer, FOLFOX4 showed encouraging activity and was generally well-tolerated. However, careful attention needs to be paid to hematologic toxicities.

Clinical advantages of a metal stent with an S-shaped anti-reflux valve in malignant biliary obstruction.

BACKGROUND AND AIM: Transpapillary stent insertion is the standard treatment for palliating malignant biliary obstruction. However, luminal occlusion often occurs due to sludge formation, tumor ingrowth, or tumor overgrowth. Currently, influx of duodenal contents by duodenobiliary reflux is considered a mechanism of stent obstruction. The aim of the present study was to evaluate the efficacy and safety of a metal stent with an anti-reflux valve in distal malignant biliary obstruction. METHODS: Thirty-two patients diagnosed with unresectable malignant biliary obstruction were enrolled. This trial was conducted at two tertiary hospitals in Korea from June 2009 to June 2011. An uncovered metal stent (M.I.Tech) with an S-type anti-reflux valve was placed. RESULTS: A total of 32 patients were enrolled. The technical success rate of stent insertion was 100%. The median duration of stent patency was 14.4 months. Stent occlusion occurred in 11 cases, which was caused by sludge formation in six cases, tumor ingrowth in four cases, and migration of the stent membrane in one case. During the follow-up period, there were no episodes of ascending cholangitis, acute pancreatitis, or bleeding. CONCLUSIONS: The new metal stent with an S-shaped anti-reflux valve demonstrated a relatively long duration of stent patency. This was attributable to reductions in duodenobiliary reflux by the anti-reflux valve. Also, the stent with an S-shaped anti-reflux valve is technically feasible and very safe. However, further prospective, randomized comparison studies of stents with anti-reflux valves and conventional stents are needed to evaluate the duration of stent patency.

Safety evaluation of self-expanding metallic biliary stents eluting gemcitabine in a porcine model.

BACKGROUND AND AIM: Palliative biliary decompression by metal stent is the treatment of choice for unresectable malignant biliary obstruction; however, conventional stents provide only mechanical palliation and exert no anti-tumor effects. Gemcitabine (GEM) has been reported to be more effective in unresectable pancreatic cancer and biliary cancer compared with other chemotherapeutic drugs. We evaluated the safety of a GEM-eluting stent by analyzing histologic responses of the porcine bile duct. METHODS: Stents containing GEM (0%, 10%, 15%, and 20% [w/v]) were surgically inserted into bile ducts of pigs (each group, n = 2). The animals were euthanized after 4 weeks, and the stented bile duct segment underwent gross and microscopic examination. Laboratory assay was performed for aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, and gamma-glutamyl transferase (γ-GTP). RESULTS: Moderate to severe inflammation was observed in the bile ducts in contact with stents containing 15 and 20% GEM, compared with no inflammation with 0% GEM and mild inflammation with 10% GEM. Fibrous reactions observed in the submucosal layer did not differ among groups. Transmural necrosis and perforations were not observed in any animal. No abnormal laboratory test findings were directly caused by GEM. CONCLUSION: Our newly developed GEM eluting stents can be used safely in normal bile ducts. Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application.

Clinical features and outcomes of primary hepatic neuroendocrine carcinomas.

BACKGROUND AND AIM: Primary hepatic neuroendocrine carcinomas (PHNECs) are extremely rare, with only about 150 cases having been reported in the English-language literature. Because of the rarity of PHNECs, its clinical features and treatment outcomes are not well understood. Here, we report our experiences with PHNECs. METHODS: We identified patients diagnosed with PHNEC and analyzed their demographics, baseline laboratory data, tumor characteristics, treatment modalities and outcomes. RESULTS: A total of 218 consecutive patients were identified with pathologically confirmed neuroendocrine carcinoma. Of these, 12 patients were diagnosed with PHNECs; the median age was 66.5 years (range, 37 to 80 years), and seven patients (58.3%) were male. Two patients who each had a single hepatic mass underwent curative surgical resection. One patient who was of inoperable status at the initial diagnosis because of multiple intrahepatic metastases showed a partial response after the ninth round of systemic chemotherapy and then underwent surgical resection. The median overall survival in the 12 patients was 16.5 months (range, 0.7 to 41.7 months). Three patients who underwent surgical treatment are alive without recurrence for 15.2 months, 18.0 months, and 36.9 months, respectively. CONCLUSIONS: Primary hepatic neuroendocrine carcinoma should be considered as a possible differential diagnosis in the management of hepatic tumors. The liver can be the primary origin of neuroendocrine tumors, and if the tumors are diagnosed as primary hepatic neuroendocrine tumors, surgical resection must be considered for curative treatment.

Preoperative serum CA 19-9 level as a predictive factor for recurrence after curative resection in biliary tract cancer.

BACKGROUND: Complete surgical removal of biliary tract cancer (BTC) offers the only chance of cure; however, long-term survival remains very limited because of frequent recurrence after surgery. The purpose of our study was to evaluate whether the preoperative serum carbohydrate antigen (CA) 19-9 level could predict recurrence after curative resection of BTC. METHODS: We performed a retrospective review of the medical records of patients who were diagnosed with BTC and underwent curative resection. The optimal cutoff value for the preoperative serum level of CA 19-9 that predicted recurrence was determined by a ROC curve. Preoperative and postoperative risk factors for recurrence were evaluated using log-rank test. RESULTS: A total of 101 patients were eligible for this study. The optimal cutoff value of preoperative serum CA 19-9 level to predict recurrence was 55 U/mL. Forty-five patients (44.6%) experienced recurrence after curative resection with a median follow-up period of 28.4 months. Recurrence occurred in 33 (61.1%) of 54 patients with CA 19-9 levels ≥55 U/mL compared with only 12 (25.5%) of 47 patients with CA 19-9 levels <55 U/mL. The recurrence rate was significantly higher in patients with baseline CA 19-9 serum levels ≥55 U/mL (hazard ratio, 3.282; 95% confidence interval, 1.684-6.395; P < 0.001). CONCLUSIONS: Elevated preoperative serum CA 19-9 was associated with a high risk of recurrence after curative resection of BTC. Different treatment plans might be needed for patients with BTC and high serum levels of CA 19-9.

Comparison of outcomes among secondary covered metallic, uncovered metallic, and plastic biliary stents in treating occluded primary metallic stents in malignant distal biliary obstruction.

BACKGROUND: The self-expandable metallic stent (SEMS) has been widely used for unresectable malignant biliary obstruction but eventually becomes occluded by tumor ingrowth/overgrowth and sludge. Therefore, we aimed to determine the therapeutic effectiveness of secondary stents and to find differences according to various combinations of the first and second stents for the management of occluded SEMSs in patients with malignant distal biliary obstruction. METHODS: Between 1999 and November 2008, 77 patients with malignant biliary obstruction underwent secondary biliary stent placement as "stent-in-stent" at three university hospitals in Korea (40 covered, 26 uncovered, and 11 plastic stents). The membrane of the covered SEMS was regarded as the barrier against tumor ingrowth. We categorized the patients into three groups based on whether the covered SEMS was either the first or the second stent: membrane-SEMS (18 covered-covered; 9 covered-uncovered; 22 uncovered-covered SEMS), bare-SEMS (17 uncovered-uncovered SEMS), and plastic stent (3 covered-plastic; 8 uncovered-plastic). RESULTS: The median patency of second stents was 138, 109, and 88 days (covered, uncovered, and plastic stents). The second covered SEMSs had a significantly longer patency than plastic stents (p=0.047). In a multivariate analysis including membrane-SEMS, bare-SEMS, and plastic stent groups, the bare-SEMS had a worse cumulative stent patency (HR=2.04, CI=1.08-3.86) and survival time (HR=2.37, CI=1.25-4.49) than the membrane-SEMS. Patients with ampulla of Vater cancer had better stent patency (HR=0.27, CI=0.08-0.98) and survival (HR=0.17, CI=0.04-0.77) than those with other pancreatobiliary malignancies. In addition, antitumor treatment prolonged survival time (HR=0.50, CI=0.26-0.99). CONCLUSIONS: The placement of additional biliary stents using the "stent-in-stent" method is an effective treatment for an occluded metallic primary stent. In addition, double biliary SEMS placement using at least one covered SEMS (in the primary and/or secondary procedure) might provide longer cumulative stent patency and survival than using uncovered SEMSs in both procedures.

Prospective phase II trial of gemcitabine in combination with irinotecan as first-line chemotherapy in patients with advanced biliary tract cancer.

BACKGROUND: Chemotherapy is a critical treatment option in advanced biliary tract cancer (BTC), which is often diagnosed at advanced stage and is therefore inoperable. The aim of this phase II trial was to evaluate the efficacy and safety of a combination therapy with gemcitabine and irinotecan as the first-line chemotherapy in patients with previously untreated advanced BTC. PATIENTS AND METHODS: Patients with pathologically confirmed advanced BTC received gemcitabine (1,000 mg/m(2) over 30 min) and irinotecan (100 mg/m(2) over 2 h) on days 1 and 8 every 3 weeks. RESULTS: Of 39 patients eligible for this trial, 6 had intrahepatic bile duct cancer, 2 had extrahepatic bile duct cancer and 31 had gallbladder cancer. A total of 193 cycles of chemotherapy were administered, with a median of 4 cycles per patient (range 1-18). The objective response rate was 20.5%, and the disease control rate was 66.7% in intention-to-treat analysis. The median progression-free survival was 4.3 months (95% CI 2.70-5.90), and overall survival was 7.6 months (95% CI 4.56-10.64). Grade 3 and 4 toxicities included anemia (20.5% of patients), thrombocytopenia (2.3%), neutropenia (10.3%), aspartate transaminase increase (10.3%), alanine transaminase increase (5.1%) and emesis (5.1%). CONCLUSION: Combination therapy of gemcitabine and irinotecan had an efficacy comparable to historic control and can be a viable treatment option. It was well tolerated by patients with advanced BTC.

Contrasting activity of Hedgehog and Wnt pathways according to gastric cancer cell differentiation: relevance of crosstalk mechanisms.

Gastric cancer displays different biological behaviors according to histological differentiation. The different biological behavior might involve the activation of distinct signaling pathways necessary for the growth and survival of cancer cells in gastric cancer. We investigated the differentiation-related signal interaction between Hedgehog and Wnt pathways in gastric cancer cells. Differentiation of gastric cancer cells was induced by sodium butyrate. The sonic Hedgehog (SHH) signal expressions were increased during cellular differentiation. In contrast, the expression of Wnt signaling was decreased during differentiation. Ectopic expression of glioma-associated oncogene-1 (GLI1) increased the level of secreted frizzled related protein-1 (SFRP1) transcript, whereas inhibition of GLI1 reduced the level of SFRP1 transcript. ChIP assay showed that GLI1 induced the transcriptional regulation of SFRP1 gene expression. Ectopic expression of GLI1 decreased the nuclear beta-catenin staining, but the inhibition of GLI1 induced the reversal of nuclear beta-catenin overexpression. Ectopic expression of beta-catenin also decreased the expression of GLI1 in the butyrate treated cancer cells. SHH and GLI1 immunoexpression was greater in well differentiated gastric cancer tissues compared to poorly differentiated tissues, and nuclear beta-catenin immunoexpression was lower in well differentiated compared to poorly differentiated tissues. The SHH and Wnt pathways are differentially involved according to gastric cancer cell differentiation.

Intraductal ultrasonography combined with percutaneous transhepatic cholangioscopy for the preoperative evaluation of longitudinal tumor extent in hilar cholangiocarcinoma.

BACKGROUND AND AIM: In hilar cholangiocarcinoma, an accurate assessment of preoperative resectability is important to optimize surgical resection. We investigated the accuracy of the combination of intraductal ultrasonography (IDUS) and percutaneous transhepatic cholangioscopy (PTCS) for evaluating longitudinal extent in hilar cholangiocarcinoma. METHODS: Patients diagnosed with hilar cholangiocarcinoma underwent multidetector computed tomography (MDCT) and magnetic resonance cholangiography (MRC) for tumor staging and Bismuth type. Percutaneous transhepatic biliary drainage was performed at the left or right bile duct of the liver section that was anticipated to be preserved in the surgical treatment. After tract dilation, PTCS with cholangioscope-directed biopsy and IDUS were sequentially performed to evaluate Bismuth type. Surgical treatment was executed according to tumor staging and longitudinal tumor extent. Postoperative histological Bismuth types were compared to preoperative Bismuth types based on MDCT, MRC, PTCS with biopsy, and IDUS. RESULTS: From June 2006 to November 2008, 25 patients with hilar cholangiocarcinoma were enrolled, with 20 of these patients evaluable. The accuracy of MDCT, MRC, PTCS with biopsy, and IDUS for the evaluation of Bismuth type was 80%, 84.2%, 90%, and 85.0%, respectively, in 20 patients, and 82.4%, 82.4%, 94.1%, and 88.2%, respectively, in 18 patients with Bismuth type IIIa, IIIb, or IV cancer. The accuracy of the combination of IDUS and PTCS with biopsy was 95% in 20 patients, and 100% in 18 with Bismuth type IIIa, IIIb, or IV cancer. CONCLUSIONS: The combination of IDUS and PTCS with biopsy was highly accurate for assessing Bismuth type and may help in the identification of an optimal surgical plan for the treatment of hilar cholangiocarcinoma, especially in Bismuth type IIIa, IIIb, or IV.

Carbohydrate antigen 19-9 elevation without evidence of malignant or pancreatobiliary diseases.

Although carbohydrate antigen 19-9 (CA 19-9) may be elevated in benign diseases, elevated CA 19-9 may cause a fear of cancer and unnecessary follow-up studies. Research on how to approach systematically in this case is very limited. The purpose of this study was to analyze the clinical features and the causes of CA 19-9 elevation without evidence of malignant or pancreatobiliary diseases. We retrospectively reviewed the medical records of patients who had CA 19-9 elevation (≥80 U/mL) and were found to be unrelated to cancer after follow-up. After exclusion, 192 patients were included in this study. The median level of CA 19-9 was 136.5 U/mL. The causes of CA 19-9 elevation were determined in 147 (76.6%) patients, and that was unknown in 45 (23.4%). The estimated causative diseases were hepatic diseases in 63 patients, pulmonary diseases in 32, gynecologic diseases in 38, endocrine diseases in 13, and spleen disease in 1. Of 45 patients with unknown cause, 35 had normalization of CA 19-9 and 10 had persistently elevated CA 19-9. In conclusion, CA 19-9 elevation without malignancies or pancreatobiliary diseases should be systematically evaluated and followed up. We suggest an algorithm to investigate the causes and follow up these patients.

A population-based epidemiology of Wilson's disease in South Korea between 2010 and 2016.

Very few population-based studies have examined the epidemiology of Wilson's disease (WD). We investigated the epidemiology of WD using the National Health Insurance Service (NHIS) database in South Korea. We analyzed not only the statistical variables of WD, but also those of WD-related diseases. WD patients were identified with the relevant International Classification of Diseases-10 code out of 50.5 million people. We used the NHIS database from 2009 to 2016 and analyzed the incidence rate, prevalence, and clinical symptoms of WD. A total of 1,333 patients were identified. The average annual incidence rate was 3.8 per million person-years. The prevalence was 38.7 per million people. The mean diagnostic age was 26.1 ± 17.2 with earlier diagnosis in men (P = 0.0003). Among the patients, 988 (74.1%) had hepatic symptoms, 510 (38.3%) had neurologic symptoms, and 601 (45.1%) had psychiatric symptoms. Before the diagnosis of WD, 350 (26.3%) had neurologic symptoms, and 427 (32%) had psychiatric symptoms. The annual mortality rate was 0.7%. Age, liver cirrhosis, and liver failure correlated with a fatal prognosis (P < 0.05). Many patients showed neurologic and psychiatric symptoms before they were diagnosed with WD. Prognosis correlated with age, liver cirrhosis, and liver failure.

Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer.

BACKGROUND: High mobility group box-1 (HMGB1) is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer. METHODS: A total of 227 subjects were classified into 5 disease groups according to the 'gastritis-dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Clinical parameters, International Union Against Cancer (UICC) TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables. RESULTS: The serum HMGB1 levels were significantly different among disease groups (ANOVA, p < 0.05) and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (p < 0.05). However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (p > 0.05). The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml) for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml) for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA) (30-40% of sensitivity). CONCLUSION: HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.