Mikio Karita

Endoscopic therapy for early colon cancer: the strip biopsy resection technique

Strip biopsy is an endoscopic tissue resection technique in which a lesion and its surrounding tissues are first elevated using physiological saline. The saline solution is injected into the submucosa at the site of the lesion with the help of needle forceps. A snare is placed around the elevated tissue, which is then resected endoscopically by electrocoagulation. The specimen obtained includes both submucosal and mucosal tissues. The authors used this technique to resect a total of 71 lesions of the colon. They were classified histologically as 21 adenocarcinomas, 46 adenomas, 3 metaplastic polyps, and 1 juvenile polyp. All lesions were confirmed to be entirely intramucosal by histological examination. The strip biopsy technique permits resection of tissue down to the submucosal layer regardless of the morphological type of the lesion. This suggests that strip biopsy is an effective new form of endoscopic treatment for early colon cancer.

Diagnostic utility of 20-megahertz linear endoscopic ultrasonography in early gastric cancer

BACKGROUND Because of the widespread endoscopic treatment of early gastric cancer (EGC), accurate pretherapeutic staging of the invasion depth of EGC differentiating those limited within the mucosa from cancers invading the submucosa has become important. METHODS We staged the depth of tumor invasion of 47 lesions of EGC using 20 MHz linear endoscopic ultrasonography (EUS). The EUS probe was introduced via the instrument channel of a standard endoscope. RESULTS The accuracy of 20 MHz EUS in staging the mucosa or submucosa was 72.3%. There was 19.1% overstaging, 2.1% understaging, and 6.4% indeterminant. The principal causes of errors were inflammation associated with ulcers, benign cystic glands in the submucosal layer, and attenuation of the high-frequency ultrasound beam. CONCLUSIONS 20 MHz EUS is useful in the pretherapeutic staging of EGC.

Significance of Strip Biopsy, with Particular Reference to Endoscopic “Mucosectomy”

1) Evalution of gastric biopsy The forceps or bite biopsy used at present is said to have been developed by Kenamore’) during the era of the flexible gastroscope. When this type of biopsy forceps emerged, complications of bleeding drew attention, and from then on the history of gastric biopsy may be regarded as a search for greater safety. With the development and introduction of the fiberscope in Japan, Takagi (1964) devised a method for gastric biopsy under fiberoptical control, using a polyvinyl chloride tube taped a long side of the fiberscope. While later, Takemoto (1964) developed a fiberscope with a biopsy channel (FCS-Bl). Owing to these advances bite biopsy became the predominant approach to the diagnosis of early gastric carcinoma. However, as expressed by Schindler’s criticism of the specimens obtained by suction biopsy as “being too small and superficial’’ even back in the gastroscope era, specimens obtained by bite biopsy were suspected to be inadequate for definite and accurate diagnosis2). This shortcoming constituted one of the reasons for the confusion concerning the diagnosis of borderline lesions in Japan during the 1969s. Because of this, pathologists defined a group classification to be used as a practical guide in arriving at a pathological diagnosis of these small size biopsy specimens. According to this classification, Group I11 lesions include benign adenoma, borderline

Genetic Transformation in Helicobacter pylori

Genetic transformation in Helicobacter pylori was investigated by using its chromosomal and plasmid DNAs. Six out of the eight strains exhibited the natural competence for incorporation of H. pylori chromosomal DNA, and all the strains incorporated the donor DNA efficiently by washing and concentrating the cells, with a glycerol solution. The much higher frequency of transformation was obtained in each strain by means of electroporation. Electroporation experiments were also conducted by use of the recombinant DNAs consisting of the H. pylori and Escherichia coli plasmids as the donors, and the occurrence of the homologous recombination was demonstrated between the incoming H. pylori plasmid‐derived region and the corresponding region of the originally residing plasmid in H. pylori.

Delineation of the gastric muscularis mucosae and assessment of depth of invasion of early gastric cancer using a 20-megahertz endoscopic ultrasound probe.

Using a 20 MHz endoscopic ultrasound system, delineation of the gastric muscularis mucosae and estimation of the depth of malignant invasion was attempted by in vivo scanning during the process of routine endoscopic observation or in vitro scanning of excised sections of 34 early gastric cancers in 32 patients. The muscularis mucosae was visualized as a single hypoechoic layer in 16 of 32 lesions (50%) scanned in vitro. Comparison of lesions in which delineation of the muscularis mucosae was or was not possible revealed no significant differences with respect to either the thickness of the lamina propria and muscularis mucosae or with respect to the degree of inflammatory cell infiltration of the lamina propria or the conditions of the boundary between the lamina propria and the muscularis mucosae. This indicates that improvement of the operability characteristics of the ultrasonic apparatus will be needed to achieve improved delineation of the muscularis mucosae. The accuracy of invasion depth estimation of early gastric cancer was 67% (16 of 24 lesions scanned in vivo) and 73% (8 of 11 lesions) in cases in vivo where the muscularis mucosae and the tumor were delineated on the same screen. The principal factors causing erroneous staging were the presence of dilated benign glandular ducts, ulcer scars, and attenuation of the ultrasound waves.

Chlamydia pneumoniae in coronary and iliac arteries of Japanese patients with atherosclerotic cardiovascular diseases.

Recent studies suggest the association of atherosclerotic cardiovascular diseases with Chlamydia pneumoniae infection in western populations. It is of great interest whether such an association exists in Asians with their distinct genetic background. Symptomatic patients with coronary heart disease (29) or arteriosclerosis obliterans (10) who underwent directional endo-atherectomy were studied. Atherectomy specimens of coronary and iliac arteries were examined for C. pneumoniae by culture, nested PCR and immunohistochemical stain (IHC) with one Chlamydia genus-specific, two C. pneumoniae species-specific, and two C. trachomatis species-specific monoclonal antibodies. Among the 29 patients with coronary artery disease, C. pneumoniae was detected in the coronary arteries of 13 by IHC, 16 by PCR and 20 by IHC or PCR, or both. C. pneumoniae was also found in the iliac arteries of four patients by IHC, three by PCR and five by IHC or PCR, or both, of the 10 patients with arteriosclerosis obliterans. Attempts to isolate C. pneumoniae by culture were unsuccessful. The re-stenotic rate after atherectomy was higher in the C. pneumoniae-positive group than in the negative group, but not significantly so. These findings support the high incidence of C. pneumoniae in atherosclerotic lesions of symptomatic patients with coronary heart disease and arteriosclerosis obliterans in Asians.

Growth medium containing cyclodextrin and low concentration of horse serum for cultivation of Helicobacter pylori

The growth of Helicobacter pylori, a Gram‐negative microaerophilic bacterium, is often difficult and requires complex media with the supplementation of 5% to 10% blood or blood derivatives. We have found that Brucella broth supplemented with 1% heated horse serum and 0.1% β‐cyclodextrin supports the good growth of H. pylori. The degree of growth and production of urease and vacuolating cytotoxin in this medium were equal to those in the medium supplemented with 5% horse serum. This medium was found to be suitable for both the routine laboratory culture and primary isolation of H. pylori from biopsy samples.

Role of epidermal growth factor in protection and repair of gastric mucosal injury.

A role of epidermal growth factor (EGF) in protection and repair of gastric mucosal injury caused by p.o. administration of 0.6 N HCl was investigated in male Wistar rats. Previous to the study on the role of EGF in gastric mucosal protection and repair, changes of gastric mucosal EGF level was determined sequentially by RIA for 180 min after treatment with 0.6 N HCl and intraperitoneal injection of recombinant hEGF. Concentration of incorporated hEGF into the gastric mucosa reached the peak level at 30 min after injection of hEGF. On the other hand, the gastric endogenous EGF level fell remarkably immediately after treatment with 0.6 N HCl. Successively, an association with the mucosal levels of incorporated hEGF and gastric ulcer indices was investigated in the rats in which hEGF was injected intraperitoneally 30 min prior to or at the same time as oral administration of 0.6 N HCl. In conclusion, pretreatment with hEGF protected significantly against gastric mucosal injury with 0.6 N HCl, whereas simultaneous administration of hEGF could not protect against mucosal injury but indicated possible stimulation of the repair process from acute gastric mucosal damage.

Prevalence of Chlamydia pneumoniae in acute lower respiratory infection in the pediatric population in Japan

Chlamydia pneumoniae has been established as an important etiologic agent of acute respiratory tract infection in humans, especially in adults. However, there is little information available on C. pneumoniae infection in the pediatric age group. The microimmunofluorescence test and Chlamydia pneumoniae‐specific polymerase chain reaction (PCR) method were applied to reveal the role of C. pneumoniae as an etiologic agent of acute lower respiratory tract infection in children in Japan. Among 136 patients aged between 2 months and 15 years with acute lower respiratory tract infection, five patients with pneumonia were found to have recent C. pneumoniae infection by the microimmunofluorescence test. C. pneumoniae‐specific PCR products were detected from specimens of four patients among these five. Neither C. trachomatis nor C. psittaci infection was found in this population. These results suggest that C. pneumoniae is an important causative agent of acute childhood pneumonia and may be the most prevalent pathogen among the genus Chlamydia that causes acute lower respiratory disease in this age group in Japan.

The Size of cagA Based on Repeat Sequence Has the Responsibility of the Location of Helicobacter pylori in the Gastric Mucus and the Degree of Gastric Mucosal Inflammation

The aim of this study was to examine whether there is a relationship between cagA size of Japanese Helicobacter pylori strains and the location of these strains in the mucous layer, the degree of gastric inflammation and acid survival. Upper gastrointestinal endoscopies were done to 144 patients with dyspeptic symptom with informed consent, sera, biopsy specimens and H. pylori strains were obtained, and gastric histology and susceptibility to pH 3 of the strains were evaluated. To determine cagA size of Japanese strains using PCR, cagA of strain CPY3401 was sequenced. 74 H. pylori samples (72 cagA +) were obtained from the body and 56 samples (56 cagA +) obtained from the antrum. cagA size of 72 H. pylori strains from the body was mainly classified into 3 groups (short (48), middle (8), long (9), and others (7)) by PCR and all of that of 56 strains from the antrum except 2 was short. The size of cagA of isolated strains from the body is associated with enhanced gastritis, acid survival, and the location in the mucus. The long size cagA of which strain is acid sensitive, may be a strong selective pressure on strain that colonizes close to the host, which enhanced gastritis.