Kiyohiko Yamashita

Double muscularis mucosae in Barrett's esophagus

To clarify the histology and morphogenesis of the double muscularis mucosae in Barretts esophagus, eight specimens resected from patients with Barretts esophagus were compared histopathologically with 352 specimens resected from patients without Barretts esophagus. A double muscularis mucosae was observed in seven (87.5%) of the eight cases with Barretts esophagus, but in none of the 352 cases without Barretts esophagus. The mucosa in the segment of Barretts esophagus consisted of columnar epithelium, a superficial lamina propria, a superficial muscularis mucosae, a deep lamina propria, and a deep muscularis mucosae. The distal end of the superficial muscularis mucosae was connected to the deep muscularis mucosae at the esophagogastric junction, and its proximal end was located in fibrous tissue below the squamocolumnar junction of the mucosal epithelium or the distal edge of the erosive lesion. The deep muscularis mucosae in the portion with Barretts esophagus was continuous with the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. Barretts esophagus is considered to be not merely a metaplastic lesion within the epithelium, but a newly developed lesion containing columnar epithelium, lamina propria, and a superficial muscularis mucosae on the lamina propria of the esophageal mucosa.

Sclerotherapy plus ligation versus ligation for the treatment of esophageal varices: a prospective randomized study

BACKGROUND We devised a new combined method of endoscopic variceal ligation and injection sclerotherapy, namely, endoscopic scleroligation, for the treatment of esophageal varices. The aim of this prospective randomized trial was to compare endoscopic scleroligation with endoscopic variceal ligation alone with regard to efficacy, complications, variceal recurrence, and survival. METHODS Fifty-one patients with cirrhosis and esophageal varices were randomly assigned to be treated by endoscopic scleroligation (n = 25) or endoscopic variceal ligation (n = 26). In the initial session in the endoscopic scleroligation group, endoscopic injection sclerotherapy was performed with injection of 5% ethanolamine oleate around the lower esophagus to obliterate the feeding veins. This was followed by endoscopic variceal ligation from the injection site to the most orad varix. In subsequent sessions, endoscopic injection sclerotherapy was performed with 1% polidocanol. In the endoscopic variceal ligation group, that procedure was performed in all treatment sessions. RESULTS Both methods were equally effective in achieving complete eradication of esophageal varices. Among the cases in which complete eradication was achieved, the 1- and 3-year cumulative recurrence rates in the endoscopic scleroligation group (9.5%, 22.1%) were significantly lower than those in the endoscopic variceal ligation group (61.9%, 72.2%) (p < 0.01). The survival rates and incidences of treatment-related complications have been similar among patients treated by both methods. CONCLUSIONS Endoscopic scleroligation is superior to endoscopic variceal ligation in preventing variceal recurrence.

Helicobacter pylori infection increases the risk of colorectal adenoma and adenocarcinoma, especially in women

BackgroundRecent reports suggest that Helicobacter pylori infection can potentially increase the risk of colorectal cancer. The purpose of this study was to assess the association between H. pylori infection and the risk of colorectal adenoma and adenocarcinoma, and to evaluate any differences on the basis of sex.MethodsThe subjects were 669 (40- to 80-year-old) patients who underwent both barium enema examination and total colonoscopy, and who were evaluated for H. pylori infection by 13C-urea breath test, urease test, or histological diagnosis of biopsied gastric specimens. There were 142 H. pylori-negative and 527-positive patients. The odds ratios (ORs) for H. pylori-positive patients with colorectal adenoma and adenocarcinoma, and for tumor patients with either adenoma or adenocarcinoma were calculated.ResultsAmong the H. pylori-negative patients, there were 52 patients without tumor, 63 with adenoma, 27 with adenocarcinoma, and 90 with tumor. Among the H. pylori-positive patients, there were 136, 264, 127, and 391 patients respectively. Pooling all subjects, those infected with H. pylori had a significantly increased OR for adenoma, adenocarcinoma, or tumor, compared to H. pylori-free patients (OR, 1.60, 1.80, and 1.66, respectively). For female H. pylori-positive subjects, the risk of having adenocarcinoma or tumor was significantly higher than that for their H. pylori-free counterparts, while for male H. pylori-positive and -negative subjects, there was no such significant difference.ConclusionsThe results therefore suggest that, in patients aged 40–80 years, H. pylori infection increased the risk of colorectal adenoma and adenocarcinoma, with significantly higher risks for female patients.

Prognostic significance of intramural metastasis in patients with esophageal carcinoma.

Clinicopathologic data on 201 patients who underwent surgical resection of esophageal squamous cell carcinoma, with or without intramural metastasis (IM), were analyzed to determine the significance of IM for patient prognosis and survival. In 24 (11.9%) patients IM was observed. There was one (1.4%) in 74 cases in Stage 0, I, or II, and 23 (18.1%) in 127 cases in Stage III or IV, based on the new pTNM classification. There was a statistically significant Cox‐Mantel test difference in the percentage survival curves of the patients, both in all stages (P < 0.01) and in only Stages III and IV (P < 0.05), as a function of the presence or absence of IM. Lymph node metastasis and distant organ metastasis were observed in 22 (91.7%) and seven (29.2%) of the 24 patients, respectively, with IM and in 111 (62.7%) and 13 (7.3%) of the 177 patients without IM. For both types of metastasis, the incidence was significantly lower in the patients without IM (P < 0.01). Seventy percent of IM on the proximal side was detected during preoperative clinical examination. These data indicate that the presence of IM is an important factor for preoperative and postoperative evaluation of the prognosis of patients with esophageal squamous cell carcinoma.

Endoscopic dexamethasone injection following balloon dilatation of anastomotic stricture after esophagogastrostomy

BACKGROUND Anastomotic stricture is common after esophagogastrostomy. Recent advances in nonsurgical treatment include the silicon bougie and balloon dilatation. However, simple dilatation alone with a silicon bougie or endoscopic balloon dilator was repeated a mean of 4.7+/-5.4 times to control anastomotic stricture because of its temporary effect. METHODS For 11 patients, endoscopic injection of dexamethasone (8 mg) around the anastomosis was done immediately after balloon dilatation (40 psi for 5 minutes). RESULTS This method significantly reduced the number of the dilatations to 1.1+/-0.3 (P < 0.05). Ten of the 11 patients did not need any further treatment. There were no side effects or complications of dexamethasone injection. CONCLUSION A combination of endoscopic balloon dilatation and dexamethasone injection provided an easy and safe method for preventing the recurrence of anastomotic stricture.

Role of Helicobacter pylori infection in perforation of peptic ulcer : An age- and gender-matched case-control study

Evidence showed a marked decrease in recurrence rate of peptic ulcer after eradication of Helicobacter pylori infection. However, whether H. pylori infection is etiologically related to perforation of peptic ulcer remains to be clarified. We therefore conducted an age- and gender-matched case-control study between perforated and nonsurgical peptic ulcers in H. pylori infection and examined differences in the cytotoxin genes cagA and vacA. Serum H. pylori IgG antibody (ELISA) was positive in 20/21 (95%) of perforated vs. 37/40 (93%) of nonsurgical duodenal ulcers and in 5/5 (100%) of perforated vs. 24/28 (86%) of nonsurgical gastric ulcer patients. Positivity of H. pylori DNA in gastric juice, which was amplified by PCR and identified by Southern blot hybridization, was 17/23 (74%) of perforated vs. 32/45 (71%) in the nonsurgical duodenal ulcer group. Positivity of the cytotoxin genes cagA and vacA in H. pylori DNA-positive gastric juice was as follows: perforated vs. nonsurgical duodenal ulcer, cagA 11/ 13 (85%) vs. 24/27 (89%); vacA1: 9/13 (69%) vs. 22/27 (82%); vacA2 8/13 (62%) vs. 21/27 (78%). There were no significant differences between the perforated and nonsurgical peptic ulcer groups for these H. pylori serum and gene markers. It is assumed that H. pylori infection is not etiologically related to perforation of peptic ulcer.

Cytochrome P4502E1 (CYP2E1) genetic polymorphism in a case-control study of gastric cancer and liver disease.

Cytochrome P4502E1 (CYP2E1) activates carcinogenic N-nitrosamines, benzene, urethane and other low molecular weight compounds. This enzyme is also inducible by ethanol, and metabolizes alcohol. A restriction fragment length polymorphism (RFLP) using the Rsa I restriction enzyme has been identified in the CYP2E1 transcription regulatory region; recent studies suggest that this polymorphism may affect gene expression. We investigated the frequency of the Rsa I RFLP in a Japanese population in relation to gastric cancer and liver disease susceptibility. The frequency of this polymorphism was determined in 150 gastric cancer, 16 hepatocellular cancer, 48 liver cirrhosis and 203 benign gastric disease (controls) patients. This preliminary study shows no association of the specific genotype with gastric cancer in all subjects (odds ratio = 1.04, 95% CI = 0.74-3.08 for the heterozygote and 0.57, 95% CI = 0.22-1.50 for the homozygous rare allele, respectively). To further confirm this lack of association, an age and gender matched case-control study should be performed. Separately, there was no association of the Rsa I RFLP with hepatocellular carcinoma (p = 0.911), but there was a suggested difference between the non-viral associated liver cirrhosis patients and control patients. Thus, this polymorphism may be related to ethanol metabolism and consequential liver diseases in a Japanese population.

Cytotoxin genes of Helicobacter pylori in chronic gastritis, gastroduodenal ulcer and gastric cancer : An age and gender matched case-control study

Helicobacter pylori (H. pylori) infection is involved in many gastrointestinal diseases, such as chronic gastritis (CAG), peptic ulcer and gastric cancer (GCA). Both host factors and H. pylori strain differences may contribute to differences in the diseases. Thus, we conducted an age and gender matched case‐control study of 35 patients each with CAG, gastric ulcer (GUL), duodenal ulcer (DUL) and gastric cancer (GCA) to examine the role of strain differences of the H, pylori cytotoxin genes cagA and vacA in these diseases. We employed polymerase chain reaction to examine the gastric juice for H. pylori DNA. The test was positive for 26 (74.3%) CAG, 29 (82.9%) GUL, 28 (80.0%) DUL and 27 (77.1%) GCA patients, showing no statistically significant difference among the diseases (P= 0.84). cagA and vacA genes (picked up by using a vacAl+vacA2 primer pair which detected nonvariable regions of the vacA gene) were detected by PCR in the H. pylori DNA‐positive cases as follows: CAG, 92.3% and 76.9%; GUL, 100% and 86.2%; DUL, 89.3% and 89.3%; GCA, 92.6% and 85.2%, respectively. No statistically significant differences were found in the frequencies of these cytotoxin genes in H. pylori ‐positive cases among the various gastric diseases (P=0.39 for cagA and P=0.64 for vacA).

Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.

Detection ofHelicobacter pylori DNA in gastric juice by the polymerase chain reaction: Comparison with findings in bacterial culture and the detection of tissue IgA and serum IgG antibodies againstHelicobacter pylori

The detection ofHelicobacter pylori in gastric juice by the polymerase chain reaction (PCR) was undertaken in 124 patients with peptic ulcer or chronic gastritis. PCR products were evaluated by agarose gel electrophoresis and Southern hybridization ofH. pylori-specific DNA sequences. Positive and negative results of the PCR analysis in 72 examinations were compared with those from bacterial culture, and with the detection of tissue IgA antibody againstH. pylori by enzyme-linked immunosorbent assay ELISA; Serion, Wuerzburg, Germany, and detection of serum IgG antibody againstH. pylori by ELISA; Radim Pomezia, Italy. Thirty-four PCR-positive samples evaluated by electrophoresis and hybridization coincided with positive samples in 56% of bacterial cultures, 59% of tissue IgA antibody identifications, and 94% of serum IgG antibody evaluations; 26 PCR-negative samples coincided with negative samples in 96% of bacterial cultures, 81% of tissue IgA antibody evaluations, and 38% of serum IgG assessments. We compared the detection achieved with theH. pylori PCR assay in gastric juice with that in biopsies taken from the antrum and upper corpus in 90 examinations, and found them to be both positive in 34 (38%) and 36 (40%) of specimens, both negative in 37 (41%) and 30 (33%) specimens, gastric juice-positive but biopsynegative in 10 (11%) and 12 (13%) specimens, and vice versa in 9 (10%) and 12 (13%) specimens, when detected by electrophoresis and hybridization, respectively, showing equivalent detection rates. In relation to the type of disease, the positive PCR assay results with gastric juice, evaluated by electrophoresis and hybridization, respectively, were: gastric ulcer 34/53 (64%) and 39/53 (74%), duodenal ulcer 23/38 (61%) and 25/38 (66%), and chronic gastritis 20/33 (61%) and 23/33 (70%), showing no significant difference in positive rates between peptic ulcer and chronic gastritis. Of the samples of 16 patients withH. pylori-positive gastric juice by the PCR assay, 7 were negative by PCR assay analyzed by electrophoresis and hybridization after the completion of treatmentH. pylori. However, after treatment, 3 were negative on electrophoresis but still had positive results with hybridization, indicating that a minimal number of bacilli may have still remained. Detection ofH. pylori in gastric juice has potential advantages for examiningH. pylori infection in the entire stomach and for follow up after treatment for the eradication ofH. pylori.