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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>The serum HMGB1 levels were significantly different among disease groups (ANOVA, <it>p < 0.05</it>) 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 (<it>p < 0.05</it>). 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 (<it>p > 0.05</it>). 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).</p> <p>Conclusion</p> <p>HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.</p

A Case of More Abundant and Dysplastic Adenomas in the Interposed Colon than in the Native Colon

We report a 60-year-old woman with intramucosal adenocarcinoma arising in the interposed colon, 40 years after the esophageal reconstruction for lye induced esophageal stricture. Although synchronous adenomas were also found in the native colon where the graft was taken, the number of adenomas was greater in the interposed colon and more dysplastic, even progressed to adenocarcinoma, than that of the native colon. The microsatellite instability-testing performed in the intramucosal carcinoma from interposed colon showed absence of microsatellite instability. Changing of location and functional deman]d of colonic segment, and the exposure to different intraluminal contents might have facilitated the adenomacarcinoma transformation in the interposed colon

Gastropericardial Fistula as a Complication in a Refractory Gastric Ulcer after Esophagogastrostomy with Gastric Pull-Up

A gastropericardial fistula, defined as penetration of a gastric lesion into the pericardium, is a rare occurrence. Such a fistula is usually associated with a huge ulcer in the gastric fundus, an ulcer within a hiatus hernia, a history of esophagogastric surgery, the concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs), or Zollinger-Ellison syndrome. The patient in this case presented with shoulder pain and melena, caused by a gastropericardial fistula that had occurred as a late complication of postoperative esophagogastrostomy and a refractory gastric ulcer. Despite the severity of the condition, the patient showed great improvement after medical treatment and the fistula was cured at the end

Endoscopic Papillary Balloon Dilation with Large Balloon after Limited Sphincterotomy for Retrieval of Choledocholithiasis

Endoscopic papillary balloon dilation (EBD) for choledocholithiasis is known to be comparable to endoscopic sphincterotomy (EST) especially in cases of small stones. With larger stones, EBD with conventional balloon, which have a diameter of 6-8 mm, was reported as less effective for extraction of stones. We evaluated the efficacy and complications of EBD with large balloons (10-15 mm) after limited EST for retrieval of choledocholithiasis. From February 2005, we have performed EBD with limited EST for retrieval of common bile duct (CBD) stones. The patients who admitted with hyperamylasemia and gallstone pancreatitis were excluded. In cases without CBD dilation, EPBD with 12 mm for 40 seconds was performed. And in cases with CBD dilation, we dilated the sphincters with 15 mm sized balloon for 40 seconds. Total 22 patients (11 of male) were performed EBD with limited EST for retrieval of CBD stones. The median diameter of the stones was 10 mm (5-25 mm). Ten cases had multiple stones and 6 cases periampullary diverticuli. Successful stone removal in the initial session of ERCP with EBD was accomplished in 16 patients (72.7%). And complete retrieval of bile duct stones was achieved in all patients with repeated ERCP. In the aspect of complications, any episodes of perforation, bleeding was not developed. Only one case of mild grade of post-procedural pancreatitis was noted. However, post-procedural hyperamylasemia was developed in 16 cases (68.2%). EBD with larger balloon seems to be a feasible and safe alternative technique for conventional EST in CBD stone extraction

Hepatic Artery Pseudoaneurysm Associated with Plastic Biliary Stent

The increased use of interventional procedures and laparoscopic cholecystectomy in the management of hepatobiliary disorders is associated with an increased incidence of hemobilia and hepatic artery aneurysm. Here we report a case of hepatic artery pseudoaneurysm associated with a plastic biliary stent. Multiple factors were involved in the formation of the hepatic artery aneurysm (HAA) and it was successfully treated by embolization

Bile Acid Analysis in Biliary Tract Cancer

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin ≤ 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium

Role of 18F-FDG PET Scans in Patients with Helicobacter pylori-Infected Gastric Low-Grade MALT Lymphoma

BACKGROUND/AIMS: Endoscopic ultrasound (EUS) plays a crucial role in the assessment and treatment of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma; however, interobserver variation, inadequate accuracy in judging the depth of tumor invasion, and histological heterogeneity of the tumor can limit its role. Thus, we have assessed the role of (18)F-FDG PET scans in the management of Helicobacter pylori-infected gastric MALT lymphoma. METHODS: Eighteen patients with H. pylori-infected low-grade gastric MALT lymphoma underwent an (18)F-FDG PET scan prior to receiving H. pylori eradication therapy. We analyzed these patients' clinicopathologic data and measured the baseline and change in the metabolic activity of the tumor using standardized uptake values (SUVs). RESULTS: Two patients failed to achieve complete remission of the low-grade gastric MALT lymphoma after successful H. pylori eradication. The baseline SUVs were significantly higher in these patients compared to successfully treated patients, 13.35±0.07 vs 2.98±0.93, respectively (n=2 vs n=16, p<0.001). The reduction in the SUV was significantly greater in the complete remission patients compared to treatment failure patients (p=0.018). CONCLUSIONS: A high SUV at baseline (18)F-FDG PET and a lower reduction in the SUV within 3 months after eradication therapy are associated with treatment failure in H. pylori-positive low-grade gastric MALT lymphoma patients undergoing eradication treatment.ope

The Relationship of Anatomic Variation of Pancreatic Ductal System and Pancreaticobiliary Diseases

The aims of this study were to identify the morphological diversities and anatomical variations of pancreatic ductal system and to define the relationships between pancreatic ductal systems, pancreaticobiliary diseases, and procedure-related complications, including post-ERCP pancreatitis. This study included 582 patients in whom both pancreatic duct (PD) and common bile duct were clearly visible by ERCP. PD systems were categorized into four types according to the relationship between common bile duct and PD. In types A and B, Wirsung duct formed the main PD. In type C, Wirsung duct did not form the main PD. If PD system did not fall into any of these three types, it was categorized as type D. The distribution of types among pancreatic ducts examined was as follows: type A: 491 cases (84.4%), type B: 56 cases (9.6%), type C: 20 cases (3.4%), and type D: 15 cases (2.6%). The anomalous anatomic variations of PD systems were divided into migration, fusion, and duplication anomalies. PD anomalies were noted in 51 patients, of which 19 (3.3%) were fusion anomalies (12 complete pancreas divisum, 7 incomplete pancreas divisum), and 32 (5.5%) were duplication anomalies (5 number variations, 27 form variations). No significant relationships between various PD morphologies and pancreaticobiliary diseases were found. However, post-ERCP hyperamylasemia was more frequently found in types C (41.7%), D (50%) and A (19.8%) than in type B (9.4%). In summary, whether Wirsung duct forms the main PD and the presence or absence of the opening of the Santorini duct are both important factors in determining the development of pancreatitis and hyperamylasemia after ERCP

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie