Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin and clarithromycin.

AIM: To investigate the effect of different proton pump inhibitors, S-mephenytoin 4'-hydroxylase (CYP2C19) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori. METHODS: One hundred and eighty-seven H. pylori-infected peptic ulcer patients were randomly treated with either rabeprazole (10 mg b.d.) or lansoprazole (30 mg b.d.) plus amoxicillin (750 mg b.d.) and clarithromycin (400 mg b.d.) for 1 week. The antibiotic susceptibility and CYP2C19 genotype (extensive or poor metabolizer) were investigated. RESULTS: The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) and lansoprazole-amoxicillin-clarithromycin (LAC) groups were 75% and 69%, respectively, on an intention-to-treat basis, and 80% and 75%, respectively, on a per protocol basis. The eradication rate for clarithromycin-resistant strains was significantly lower than that for clarithromycin-sensitive strains (24% vs. 86%, P < 0.05). For clarithromycin-sensitive strains in the LAC group, there was a tendency for a lower eradication rate in extensive than poor metabolizers. The eradication rate in extensive metabolizers in the RAC group tended to be higher than that in extensive metabolizers in the LAC group (89% vs. 78%, P = 0.079726). CONCLUSIONS: The success of the 1-week proton pump inhibitor-amoxicillin-clarithromycin regimen depends on the susceptibility of H. pylori to clarithromycin. Moreover, differences in CYP2C19 genotype influence the eradication rates of lansoprazole-based therapy, and the rabeprazole-based regimen has an advantage especially in extensive metabolizers.

[Evaluation of percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis].

We performed percutaneous transhepatic gallbladder drainage (PTGBD) in 71 of 129 patients with acute cholecystitis. In 70 of 71 patients, clinical symptoms and laboratory data were rapidly improved by PTGBD. In order to evaluate the degree of acute cholecystitis, the clinical symptoms, laboratory data and ultrasonographic findings of these patients were analyzed by the quantification theory of Hayashi. As a result, irregular thickening of the gallbladder wall and gallbladder swelling presented by US and physical findings with Blumberg's sing or defence in the abdomen were most important findings to assess the severity of acute cholecystitis. Based on these data, we originally introduced the Severity Score of this disease and used it a criterion of PTGBD indication. The patients with the score above 0.5 were considered to be indicative for emergent PTGBD. In high risk patients (e.g., the aged or of diabetes mellitus) with the score above 0, this procedure should be indicated. In 24 of 71 patients, Percutaneous Transhepatic Gallbladder Scope (PTGBS) were attempted to retrieve stones, and it was completely successful in 16 patients.

[Preoperative diagnosis and staging of pancreatic cancer by endoscopic ultrasonography (EUS)--a comparative study with other diagnostic tools].

Endoscopic ultrasonography (EUS), ultrasonography (US), computed tomography (CT), and angiography (Angio) were performed in 26 patients with pancreatic cancer which were all resected. Preoperative findings of each diagnostic tools were compared with histological findings. In order to discuss the effectiveness of each body imagings, the preoperative staging of pancreatic cancer was evaluated in direct invasion to the anterior pancreatic capsule and stomach (S), direct invasion to the duodenum (D), direct invasion to the retroperitoneal adjacent vessels (Rp), and regional lymph node metastasis (N). The overall accuracy rate was 77% with EUS (50% with US, 38% with CT, 56% with Angio) in S, 81% with EUS (44% with US, 38% with CT, 63% with Angio) in D, 77% with EUS (58% with US, 42% with CT, 73% with Angio) in Rp, and 65% with EUS (58% with US, 38% with CT) in N. EUS revealed high accuracy rates because EUS images of the whole pancreas, surrounding organs and major vessels were clearly visualized through the gastroduodenal walls. Also, the accuracy rates of Angio in Rp and US in N were almost the same as those of EUS in Rp and N. However, it was difficult for every procedure to diagnose the retroperitoneal perineural invasion. From these results, EUS is one of the most beneficial procedures for detecting of the extent of cancer. EUS is expected to be popularized in the diagnosis and staging of the pancreatic cancer.

[Prevalence of K-ras gene mutations in human colorectal cancers].

It has been reported that mutations in the human ras gene family convert these genes into active oncogenes. In the present study using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the oligonucleotide hybridization assay, a total of 86 colorectal cancers were analyzed for the point mutations at codon 12 and 13 of K-ras genes. Mutations were present in 33 of the 86 colorectal cancers examined; 32 of the 33 mutations were at codon 12 of this gene and one of them was at codon 13. There was no apparent correlation between the presence of a ras gene mutation in a carcinoma and its anatomical location, level of differentiation, depth of invasion, degree of lymphnode metastasis or stage of progression, however, the high incidence of K-ras mutations was observed in early stage carcinomas (depth m and sm). This results support the concept that the point mutation of K-ras gene is early event in tumorigenesis of colorectal cancer.

[Management of polypoid lesions of the gallbladder by endoscopic ultrasonography (EUS)--a retrospective study to establish the diagnostic criteria and a prospective study to evaluate its reliability].

The diagnostic criteria of endoscopic ultrasonography (EUS) in the management of polypoid lesions of the gallbladder was established by a retrospective study using 57 cases with polypoid lesions of the gallbladder that were all resected and confirmed histologically. By this study, EUS findings of polypoid lesions of the gallbladder were classified into the following six groups; Type I with a foamy high echogram, Type II with a globular high echogram, Type III with a papillary high echogram, Type IV with a papillary solid echogram, Type V with a nodular solid echogram and Type VI with a nodular solid echogram including multiple spotty an-echoic areas which suggested the presence of Rokitansky-Aschoff sinus. Comparing the types of EUS findings with histological diagnosis, Type I and II corresponded to cholesterol polyps. Type III and IV contained benign pseudo tumors such as cholesterol polyp or hyperplastic polyp as well as tumorous lesions such as adenocarcinoma or adenoma. Type III with over 10 mm in size and IV with over 5 mm in size had a possibility of tumorous lesions. Type V usually corresponded to adenocarcinoma, and Type VI to adenomyomatous hyperplasia. From these results, the following criteria was established; (1) Polypoid lesions showing Type I, II, III with less than 10 mm in size, IV with less than 5 mm in size and VI should be followed-up as benign diseases. (2) Polypoid lesions of Type III with over 10 mm in size and IV with over 5 mm in size was considered to be relative indications for surgery as tumors. (3) Polypoid lesions of Type V was an absolute surgical indication as malignant. The reliability of this EUS criteria was followingly evaluated by a prospective study using 94 cases with polypoid lesions of the gallbladder; 32 cases with open or laparoscopic cholecystectomy and 62 cases with over one year follow-up observations. The criteria corresponded well with the histological or follow-up findings in Type I, II, III with less than 10 mm in size, IV with less than 5 mm in size, V and VI. It had, however, a tendency of over indications to surgery in Type III with over 10 mm in size and IV with over 5 mm in size because these types were widely set not to overlook tumorous lesions such as adenoma and small adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

[Endoscopic sphincterotomy for lithotripsy (EST-L) of bile duct stones].

We performed EST-L for 555 patients with choledocholithiasis between 1981 and 1992. With the aid of conventional occlusion balloons and dormia-type baskets, calculi < or = 1.5 cm was extracted with relative ease. In patients with larger stone (> 1.5 cm), the mechanical lithotripter, extracorporeal shock wave lithotripsy (ESWL) and electrohydrolic lithotripsy were used for the lithotripsy. The overall success rate was 95%. Important early and late complications from these procedures occurred in 6.9% and 9.1% of all cases respectively. This result reveal that EST-L is safe and effective therapeutic procedures for choledocholithiasis. We would recommend EST-L is adopted as an initial measure to remove common bile duct stones.

Endoscopic treatment for early stage colorectal tumors: the comparison between EMR with small incision, simplified ESD, and ESD using the standard flush knife and the ball tipped flush knife.

BACKGROUND: Early stage colorectal tumors can be removed by endoscopic mucosal resection but larger such tumors (20 mm) may require piecemeal resection. Endoscopic submucosal dissection (ESD) using newly developed endo-knives has enabled en-block resection of lesions regardless of size and shape. However ESD for colorectal tumor is technically difficult. Therefore, we performed EMR with small incision (EMR with SI) for more reliable EMR, ESD with snaring (simplified ESD) and ESD using the standard Flush knife and the novel ball tipped Flush knife (Flush knife BT) for easier and safer colorectal ESD. AIMS: The aims of our study were (1) to compare the treatment results of the following 3 methods (EMR with SI/si-mplified ESD/ESD) for early stage colorectal tumors, and (2) to assess the performance of Flush knife BT in colorectal ESD. METHODS: We treated 24/44/468 colorectal tumors and examined the clinicopathological features and treatment results such as tumor size, resected specimen size, procedure time, en-bloc resection rate, complication rate. We also treated 58 colorectal tumors (LST-NG:20, LST-G:36, other:2) using standard Flush knife and 80 colorectal tumors (LST-NG:32, LSTG:44, other:2) using Flush knife BT, and examined the clinicopathological features and treatment results mentioned above and also the procedure speed. RESULT: The median tumor size (mm) (EMR with SI/ simplified EMR/ESD) was 20/17/30 (EMR with SI vs. simplified ESD: p = n.s, simplified ESD vs. ESD: p < 0.0001). The median resected specimen size (mm) was 22.5/26/41 (EMR with SI vs. simplified ESD: p = 0.0018, simplified ESD vs. ESD: p < 0.0001). The procedure time (min.) was 19/27/60 (EMR with SI vs. simplified ESD: p = n.s, simplified ESD vs. ESD: p < 0.0001) The en-block resection rate (%) was 83.3/90.9 /98.9. The complication rate (post-operative bleeding rate/perforation p=n.s). In the treatment results of ESD for LSTs by knives, there was no difference between standard Flush knife and Flush knife BT for clinicopathological features and treatment results (procedure time, complication rate and en bloc R0 resection rate). However, procedure speed (cm2/min.) of LST-G was significantly faster in the Flush knife BT than in standard Flush knife. (standard Flush knife: 0.21 vs. Flush knife BT: 0.27, p = 0.034). CONCLUSION: EMR with small incision (EMR with SI) and ESD with snaring (simplified ESD) are good option to fill the gap between EMR and ESD in the colorectum, and also considered to become the nice training for the introduction of ESD. Flush knife BT appears to improve procedure speed compared with standard Flush knife, especially for LST-G in colo-rectal ESD.

Point mutations in the c-K-ras 2 gene in multiple colorectal carcinomas.

The c-K-ras 2 gene mutations were examined in colorectal tumours from patients with synchronous or metachronous tumours in order to investigate tumorigenesis. Sixty-seven colorectal carcinomas from patients with a single lesion, 50 from patients with synchronous lesions, and 12 from patients with metachronous lesions were analysed for the presence of point mutations in codons 12 and 13 of c-K-ras proto-oncogene. In the patients with metachronous or synchronous lesions, the finding of the mutation in one tumour was not associated with a greater frequency of the mutation in other carcinomas from the same patient. In the patients with tumours that each contained the mutation, the mutations were not always the same. In tumours from the patients with original and synchronous lesions, the mutation frequency was significantly lower in advanced carcinomas invading through the entire muscularis propria (10.5%) than in early carcinomas confined to the mucosa (47.8%), and the mutation frequency in carcinomas invading through the entire muscularis propria was significantly lower in patients with synchronous lesions (10.5%) than in patients with a single lesion (37.7%). These results suggest that the tumorigenesis of colorectal carcinomas from patients with synchronous lesions is different from that in patients with a single lesion.

Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations. METHODS: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE. RESULTS: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. CONCLUSIONS: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.

Expression of cathepsin E in pancreas: a possible tumor marker for pancreas, a preliminary report.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions.

Pepsinogen C gene polymorphisms associated with gastric body ulcer.

This study was aimed to investigate the association of restriction fragment length polymorphisms (RFLPs) for pepsinogen genes with peptic ulcer disease. Eighty unrelated controls, 61 patients with gastric ulcer, and 57 patients with duodenal ulcer were studied. No genetic polymorphisms for pepsinogen A were detected by EcoRI digestion in Japanese subjects but a 100 base pairs insertion-deletion RFLP for the pepsinogen C gene was observed. The allele frequencies of the large (3.6 kilobase EcoRI fragment) and the small fragment (3.5 kilobase EcoRI fragment) were 80.6% and 19.4% respectively in controls, 55.4% and 44.6% in patients with gastric body ulcer, 79.4% and 20.6% in patients with gastric angular ulcer, 71.4% and 28.6% in patients with gastric antral ulcer, and 75.4% and 24.6% in patients with duodenal ulcer. The allele frequency of the small fragment was significantly higher in patients with gastric body ulcer than in controls and in patients with gastric angular or antral ulcer. The genotypes which possessed the small fragment were significantly more frequent in patients with gastric body ulcer (78.4%) than in controls (33.8%) and in patients with gastric angular or antral ulcer (37.5%). These results suggest that there is a significant association between the genetic polymorphism at the pepsinogen C gene locus and gastric body ulcer, and that the pepsinogen C RFLP is a useful marker of the genetic predisposition to this disorder. These results also indicate genetic heterogeneity of gastric ulcer disease, and suggest that the pepsinogen C RFLP may be a useful subclinical marker to explain the differences in genetic aetiologies of gastric body ulcer and gastric angular or antral ulcer.