Yoshiki Hirooka

Interleukin-8 Promoter Polymorphism Increases the Risk of Atrophic Gastritis and Gastric Cancer in Japan

Host genetic susceptibility may influence gastric carcinogenesis caused by Helicobacter pylori infection. We aimed to clarify the relationship of interleukin (IL)-8 polymorphism with the risk of atrophic gastritis and gastric cancer. We examined IL-8 −251 T > A, IL-1B −511 C > T, and IL-1RN intron 2 polymorphisms in 252 healthy controls, 215 individuals with atrophic gastritis, and 396 patients with gastric cancer. We also investigated the effect of the IL-8 polymorphism on IL-8 production and histologic degree of gastritis in noncancerous gastric mucosa. Although no correlation was found in the analysis of the IL-1B and IL-1RN polymorphisms, IL-8 −251 A/A genotype held a higher risk of atrophic gastritis [odds ratio (OR), 2.35; 95% confidence interval (CI), 1.12-4.94] and gastric cancer (OR, 2.22; 95% CI, 1.08-4.56) compared with the T/T genotype. We also found that the A/A genotype increased the risk of upper-third location (OR, 3.66; 95% CI, 1.46-9.17), diffuse (OR, 2.79; 95% CI, 1.21-6.39), poorly differentiated (OR, 2.70; 95% CI, 1.14-6.38), lymph node (OR, 2.50; 95% CI, 1.01-6.20), and liver metastasis (OR, 5.63; 95% CI, 1.06-30.04), and p53-mutated (OR, 1.91; 95% CI, 1.13-3.26) subtypes of gastric cancer. The A/A and A/T genotypes were significantly associated with higher levels of IL-8 protein compared with the T/T genotype. Neutrophil infiltration score was significantly higher in the A/A genotype than in the T/T genotype. In conclusion, we showed that the IL-8 −251 T > A polymorphism is associated with higher expression of IL-8 protein, more severe neutrophil infiltration, and increased risk of atrophic gastritis and gastric cancer.

Intraductal ultrasonography in diagnosing tumor extension of cancer of the papilla of Vater

BACKGROUND Intraductal ultrasonography is clinically useful in assessing various pancreatobiliary diseases. This study was carried out to evaluate the usefulness of intraductal ultrasonography in diagnosing tumor extension of cancer of the papilla of Vater. METHODS Thirty-two patients with cancer underwent intraductal ultrasonography. According to the spatial relationship between the tumor echo and the hypoechoic layers representing Oddis muscle layer or the duodenal muscularis propria layer, the images were classified into four grades. We attempted to diagnose tumor extension using this grading system. Lymph nodes measuring over 10 mm were evaluated as involved. Findings were compared with postoperative histopathologic findings classified as follows: d0, tumor limited to Oddis muscle layer; d1, tumor invading the duodenal submucosal layer; d2, tumor invading the duodenal muscularis propria layer; and panc(+), tumor invading the pancreas. RESULTS Diagnostic accuracy rate was 100% (6 of 6) in d0 cases, 92.3% (12 of 13) in d1 cases, 100% (1 of 1) in a d2 case, and 75% (9 of 12) in panc(+) cases. Overall accuracy rate was 87.5% (28 of 32). In assessing lymph node metastases, sensitivity was 66.7% (6 of 9) and specificity was 91.3% (21 of 23). CONCLUSION Intraductal ultrasonography examination is useful in diagnosing tumor extension of cancer of the papilla of Vater.

Endoscopic resection of Peutz-Jeghers polyps throughout the small intestine at double-balloon enteroscopy without laparotomy

BACKGROUND Small-bowel enteroscopy with the double-balloon method was developed to improve access to the small intestine. This study evaluated the usefulness of this method for the resection of small-intestinal Peutz-Jeghers polyps. METHODS Two patients with Peutz-Jeghers syndrome underwent nonsurgical double-balloon enteroscopic resection of polyps throughout the small intestine. OBSERVATIONS Multiple polyps in the jejunum were successfully resected via the oral route, as were the polyps in the ileum via the anal route. All 18 polyps (10-60 mm in size) were resected without subsequent bleeding or perforation. Histopathologically, 3 large polyps (>30 mm diameter) were hamartomas with adenomatous components. CONCLUSIONS Double-balloon enteroscopy was safe and useful for the diagnosis and the treatment of Peutz-Jeghers polyps throughout the small intestine. Double-balloon enteroscopic polypectomy might preclude complications of Peutz-Jeghers syndrome, including intussusception, bleeding, and tumorogenesis, thereby obviating the need for multiple laparotomies.

Intraductal papillary mucinous neoplasms of the pancreas: differentiation of malignant and benign tumors by endoscopic ultrasound findings of mural nodules.

Background and Aim:Intraductal papillary mucinous neoplasms (IPMNs) have a wide pathologic spectrum and it is difficult to differentiate malignant from benign tumors. The aim of this study was to identify predictors of malignancy using contrast-enhanced endoscopic ultrasound (CE-EUS). Subjects and Methods:In our institute, main duct type and mixed type IPMNs, branch duct type IPMNs with mural nodules, and IPMNs with coexistent invasive ductal cancer were indications for surgery. Eighty-seven IPMNs (14 main duct, 25 mixed, and 48 branch duct type) were resected and CE-EUS findings were compared with pathologic findings. Twelve clinicopathological variables and CE-EUS morphologic findings were assessed. Mural nodules defined as blood flow supplied protrusions were classified into 4 types: type I: low papillary nodule, type II: polypoid nodule, type III: papillary nodule, and type IV: invasive nodule. Results:Forty-two, 26, 16, and 3 were pathologically diagnosed as adenoma, noninvasive carcinoma, invasive IPMNs, and coexistent invasive ductal cancer, respectively. Multivariable logistic regression analysis showed that types III/IV mural nodule (odds ratio = 10.8; 95% confidential intervals = 2.75–56.1) and symptomatic IPMNs (odds ratio = 4.31; 95% confidential intervals = 1.37–14.7) were significant for malignancy. For mural nodule diameter, invasive IPMNs were significantly larger, but types III and IV mural nodules were more frequently associated with malignancy, particularly invasive cancer, at 88.9% and 91.7%, respectively. The diagnosis of IPMNs with types III or IV mural nodule as malignant resulted in a sensitivity of 60%, specificity of 92.9%, and accuracy of 75.9%. Conclusions:In conclusion, new morphologic criteria were useful to identify the malignant potentials of IPMNs.

Outcome after enteroscopy for patients with obscure GI bleeding : diagnostic comparison between double-balloon endoscopy and videocapsule endoscopy

BACKGROUND Double-balloon endoscopy (DBE) and videocapsule endoscopy (VCE) have been useful in managing obscure GI bleeding (OGIB). OBJECTIVE This study compared diagnostic yields of OGIB between DBE and VCE, and evaluated the outcome after DBE. DESIGN A single-center retrospective study. SETTING A tertiary-referral hospital. PATIENTS Between June 2003 and February 2007, 162 consecutive patients with OGIB were enrolled and treated. The diagnostic yield between VCE and DBE was compared in 74 patients. MAIN OUTCOME MEASUREMENTS Comparison of diagnostic yields between DBE and VCE, and the prognosis after DBE. RESULTS Of 162 patients, 95 (59%) were diagnosed with small-bowel diseases. They were treated by medical, enteroscopic, and surgical therapies (n = 35, 30, and 30, respectively). A comparison of the overall diagnostic yield between DBE (64%) and VCE (54%) was not significantly different. The 4 VCE-positive DBE-negative cases were because of inaccessibility of DBE. The 11 VCE-negative DBE-positive cases were because of a failure to detect lesions in the proximal small bowel and the Roux-en-Y loop, and because of diverticula. At a median follow-up of 555 days after DBE, 11 patients with small-bowel diseases developed rebleeding; all were treated by enteroscopic or medical therapies. Vascular diseases, comorbidities, especially portal hypertensive disease and chronic renal failure that required hemodialysis, and severe anemia (Hb </=7.0 g/dL) were associated with rebleeding. LIMITATIONS A retrospective comparative study, and participation bias. CONCLUSIONS A complementary combination between DBE and VCE was useful for the management of OGIB. In particular, patients with vascular disease, comorbidities, and severe anemia should be intensively treated.

MDM2 Promoter Polymorphism Is Associated With Both an Increased Susceptibility to Gastric Carcinoma and Poor Prognosis

PURPOSE Recently, a single-nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to lower the age of onset of tumors and increase the occurrence of multiple primary tumors in Li-Fraumeni syndrome, and accelerate the development of sporadic adult soft tissue sarcoma. The aim of this study was to determine whether SNP309 is associated with susceptibility to gastric carcinoma and its prognosis. PATIENTS AND METHODS In a case-control study including 438 controls and 410 patients with sporadic gastric carcinoma, MDM2 SNP309 was genotyped. Serum pepsinogens (PGs) I and II were measured in 438 control subjects and 253 cases selected from 410 patients. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using polymerase chain reaction-based single strand conformational polymorphism analysis and direct sequencing. RESULTS The risk of overall gastric carcinoma for SNP309 (G/G) was significantly increased when compared with T carriers (P = .039), especially carcinomas with extragastric tumors (P = .005), carcinoma with severe atrophic gastritis positive for PG assay (PG I level < 70 ng/mL and PG I/II < 3.0; P = .005), antral carcinoma (P = .020), intestinal-type carcinoma (P = .023), p53-immunopositive carcinoma (P = .007), and carcinoma with p53 mutations (P = .007). No significant difference in age at diagnosis was observed among genotypes. SNP309 (G/G) was an independent marker of poor overall survival in advanced carcinoma (hazard ratio, 3.16; 95% CI, 1.22 to 8.20; P = .018). CONCLUSION This study provides evidence supporting the association of SNP309 with gastric carcinogenesis via p53 tumor suppressor pathway, extragastric tumorigenesis, and poor prognosis.

Small-bowel obstruction: diagnostic comparison between double-balloon endoscopy and fluoroscopic enteroclysis, and the outcome of enteroscopic treatment.

BACKGROUND Small-bowel obstruction (SBO) sometimes remains undiagnosed and untreatable without surgery. OBJECTIVE To evaluate the diagnostic yields of SBO between double-balloon endoscopy (DBE) and fluoroscopic enteroclysis (FE), and the outcome of enteroscopic treatment. DESIGN Single-center, retrospective, and prospective study. SETTING Tertiary-referral hospital. PATIENTS Between June 2003 and July 2007, 66 consecutive patients with SBO were enrolled, investigated, and treated. MAIN OUTCOME MEASUREMENTS A comparison of diagnostic yields between DBE and FE, and the prognosis after enteroscopic balloon dilation. RESULTS The diagnostic yield of DBE for SBO (95%) was higher than that of FE (71%) in 59 patients who underwent both examinations (P= .004). The first treatment included 27 surgical, 25 enteroscopic, and 14 conservative therapies. Of 47 enteroscopic balloon dilation procedures in 22 patients, 45 (96%) were successful. Of 16 patients with Crohns disease, 11 (69%) remained asymptomatic over the postdilation follow-up period but 5 relapsed: 2 recovered by repeated dilations, but 3 required surgery. Of 6 patients who had diseases other than Crohns disease, 4 (67%) remained asymptomatic but 2 relapsed: one with remission of metastasis recovered by repeated dilations, and one with ischemic enteritis required surgery. Anastomotic stricture was an independent marker of the symptom-free outcome (hazard ratio 0.037-0.084, P= .037). Two acute pancreatitis, one perforation, and one exacerbation of SBO complications occurred. LIMITATIONS Small sample size and participation bias. CONCLUSIONS DBE was useful for the diagnosis of SBO. Balloon dilation is considered an alternative to surgery in patients with fibrotic strictures both related and unrelated to Crohns disease.

Prospective clinical study of EUS-guided choledochoduodenostomy for malignant lower biliary tract obstruction.

OBJECTIVES:Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has recently been reported as an alternative to percutaneous transhepatic biliary drainage (PTBD) in cases of biliary obstruction, when endoscopic biliary drainage (EBD) is unsuccessful. However, prospective studies of EUS-CDS have not yet been performed. We conducted a prospective study to evaluate the safety, feasibility, and efficacy of EUS-CDS in patients with malignant lower biliary tract obstruction.METHODS:A prospective study to confirm the safety of EUS-CDS was carried out in 6 patients, followed by a trial to evaluate the feasibility and efficacy of EUS-CDS in 12 additional patients. We placed a plastic stent from the duodenal bulb into the extrahepatic bile duct under EUS guidance using an oblique viewing echoendoscope, needle knife, guidewire, and biliary dilators.RESULTS:The site of extrahepatic bile duct puncture was the common hepatic duct in 15 patients and the common bile duct in 3 patients. Mean diameter of the punctured extrahepatic bile ducts was 10 mm (range: 6–20 mm). Technical and functional success rates were 94% (17/18) and 100% (17/17), respectively. Median procedure time was 30 min (range: 10–52 min). Median duration to first oral intake after the procedure was 1 day (range: 1–3 days). Early complications were encountered in three (17%) patients, including focal peritonitis in two patients and hemobilia in one patient. During the follow-up period (median: 163 days; range: 46–484 days), 12 stent occlusion events were observed in nine patients. Re-intervention with exchange of the occluded stent was successful in 8 of 12 (66%) times. Severe early and late complications were not encountered in any patients in this study. Median duration of stent patency by Kaplan–Meier analysis was 272 days.CONCLUSIONS:EUS-CDS is safe, feasible, and effective as an alternative to PTBD and EBD in cases of malignant distal biliary tract obstruction. Prospective randomized studies are needed to compare the safety and efficacy of various kinds of endoscopic devices used in EUS-CDS and to compare EUS-CDS with PTBD or EBD.

Efficacy of antiviral therapy with lamivudine after initial treatment for hepatitis B virus-related hepatocellular carcinoma

Aim:  The aim of this study was to determine whether antiviral therapy with lamivudine is beneficial in patients after initial treatment for hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC).

Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects : a prospective, randomized, double-blinded, placebo-controlled, cross-over study

BackgroundAlthough obscure gastrointestinal bleeding cannot be detected by colonoscopy or upper endoscopy, wireless video capsule endoscopy (VCE) is capable of imaging it. Few data are available on medical therapy for patients with nonsteroidal anti-inflammatory drug (NSAID)-induced small-intestinal mucosal injuries. The aim of this study was to compare prevention by rebamipide and placebo of NSAID-induced smallintestinal injury in healthy subjects.MethodsTen healthy subjects who provided written informed consent were enrolled. Rebamipide or placebo plus diclofenac was administered with omeprazole for 7 days, and for an additional 7-day period with treatments reversed in the same subjects, with a 4-week washout period between treatments. VCE of the small intestine was performed four times, before and after each of the two study periods.ResultsThe number of subjects with small-intestinal mucosal injuries was higher in the placebo group (8/10) than in the rebamipide group (2/10) (P = 0.023). Two cases of ulcer and one of bleeding were observed in the placebo group, while no ulcer or bleeding was observed in the rebamipide group.ConclusionsRebamipide had significantly higher efficacy than placebo in preventing NSAID-induced small-intestinal mucosal injury.