Hideo Yanai

Endoscopic ultrasonography and endoscopy for staging depth of invasion in early gastric cancer: a pilot study ☆ ☆☆ ★

BACKGROUND We compared the accuracy of endoscopic ultrasonography (EUS) for staging depth of invasion of early gastric cancer with that of conventional endoscopy. PATIENTS AND METHODS We assessed the depth of invasion of 108 lesions (104 patients) using EUS with a thin 20 MHz probe and compared the results with those of conventional endoscopy and of histologic examination of endoscopically or surgically resected specimens. RESULTS The overall accuracy rates for staging depth of invasion for conventional endoscopy and EUS were 72.2% and 64.8%, respectively. Lesions that were classified as limited to the mucosa on both conventional endoscopy and EUS were very likely (92.2%) to be limited to the mucosa on histologic examination. The rates for understaging and overstaging were 16.7% and 11.1%, respectively, for conventional endoscopy; and 7.4% and 24.1%, respectively, for EUS. The highest rate for understaging based on conventional endoscopy occurred for lesions in the gastric body (including cardia, 23.9%). CONCLUSIONS EUS appears to be useful in combination with conventional endoscopy for staging depth of invasion of early gastric cancer. In particular, the two techniques in tandem may accurately predict that a lesion is limited to the mucosa, and EUS may be useful to overcome the potential for understaging by conventional endoscopy, particularly in the gastric body.

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

Association of the -173G/C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis

BackgroundMacrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and has been shown to be involved in the development of chronic murine colitis. In the +173 G/C polymorphism of the MIF gene, the presence of C creates the binding motif of activator protein 4. This study explored the association of this polymorphism with ulcerative colitis (UC).MethodsGenotyping was carried out, with a tetra-primer polymerase chain reaction (PCR) method, for 659 DNA specimens from 438 healthy volunteers and 221 patients with UC. Genotype distribution between cases and controls and the association of patients’ genotypes with clinical parameters were statistically evaluated.ResultsNo significant difference in genotype distribution was found between UC patients and healthy controls. However, when the relation of the C/C genotype to clinical parameters in UC patients was evaluated by Fisher’s exact test, it was found that the frequency of the C/C genotype was higher in patients with pancolitis type than in those with other types restricted to the distal or left-sided colon (odds ratio [OR], 10.781; 95% confidence interval [CI], 1.342–86.619; P = 0.0074).ConclusionsThese data suggest that the MIF −173 G/C polymorphism may be related to the extent of disease in UC in a Japanese population.

Epstein-Barr virus infection of the colon with inflammatory bowel disease

ObjectiveEpstein-Barr virus (EBV)-infected cells can evoke severe host immune responses, as shown in infectious mononucleosis and EBV-associated gastric carcinoma. To investigate the possible pathological role of EBV in inflammatory bowel disease (IBD), we tested for the presence of EBV in the colon in IBD patients.MethodsSurgically resected colonic specimens of 11 patients with Crohns disease, five patients with ulcerative colitis, nine noninflammatory controls (disease-free area of the colorectal carcinoma), and 10 appendicitis cases were tested using highly sensitive in situ hybridization for EBV-encoded small RNA1 (EBER-1).ResultsEBER-1 was detected in 63.6% of Crohns disease cases and 60% of ulcerative colitis cases, but not at all in noninflammatory controls and appendicitis cases. EBER-1–positive cells were very rare in the noninflammatory areas of colonic specimens from IBD patients. EBER-1–positive cells were nonepithelial cells (mainly B lymphocytes and a few histiocyte-shaped cells) located in erosive or ulcerative areas of the colonic specimens.ConclusionsThe limited presence of EBV-infected cells in the diseased areas of IBD colonic specimens indicated that EBV infection may be related to such diseases.

Endoscopic ultrasonography of superficial esophageal cancers using a thin ultrasound probe system equipped with switchable radial and linear scanning modes

BACKGROUND Detailed information on the depth of invasion of superficial esophageal cancer is required for endoscopic mucosal resection. As a pretherapeutic diagnostic procedure, endoscopic ultrasonography using conventional 7.5 MHz systems has been ineffective at providing sufficient details. A newly developed, thin ultrasound probe system provides both radial and linear scanning for evaluation of superficial esophageal cancer. METHODS Endoscopic ultrasonography was performed in 16 patients using a switchable probe driven at 20 MHz. Seventeen lesions of superficial esophageal cancer were evaluated for depth of invasion to discriminate mucosal from submucosal penetration. RESULTS The overall accuracy of staging was 64.7%. In all six errors, mucosal cancers were overstaged as submucosal invasion. The diagnostic accuracy was 80% when the muscularis mucosae was visualized. CONCLUSION A 20 MHz linear-radial switchable probe is a useful new method in the staging of superficial esophageal cancer.

Epstein–Barr virus infection in non-carcinomatous gastric epithelium

Gastric tissue specimens from 20 patients with chronic atrophic gastritis, one of whom also had an early gastric carcinoma, were studied for evidence of Epstein–Barr virus (EBV) infection by Southern blot analysis, DNA and RNA in situ hybridization, and immunohistochemistry for the presence of the EBV‐determined nuclear antigen 1 (EBNA‐1) and the latent membrane protein 1 (LMP‐1). EBV DNA was detected in two cases with chronic atrophic gastritis and in the case with early gastric carcinoma by Southern blot hybridization. DNA in situ hybridization showed EBV genomes in the epithelial cells of two other cases with chronic atrophic gastritis and in non‐carcinomatous and carcinomatous epithelial cells of the early gastric carcinoma case. EBNA‐1 was detected in all cases. LMP‐1 was detected in areas of intestinal metaplasia in eight patients with chronic atrophic gastritis. EBV‐encoded small RNA 1 (EBER‐1) expression was limited to carcinoma cells. These results show that gastric epithelium is frequently infected with EBV and suggest that prolonged EBV persistence may contribute to the development of gastric carcinoma.

Endoscopic ultrasonography for diagnosis of submucosal invasion in early gastric cancer

Abstract: Endoscopic ultrasonography (EUS) is considered to be useful for deciding the treatment course for early gastric cancer. To determine reliable indications suggesting submucosal tumor invasion, we retrospectively analyzed EUS images of the hyperechoic third layer, which corresponds to the submucosa. The subjects enrolled in this study were 75 patients, with 78 gastric cancers (diagnosed as mucosal cancer without ulcerous changes on endoscopy and as histologically differentiated adenocarcinoma on biopsy), who were also examined by EUS. We retrospectively classi-fied EUS features of the third layer (submucosa) into five groups: (1) irregular narrowing, (2) budding sign, (3) multiple echo-free spots, (4) unclear, and (5) no changes. In endoscopically diagnosed gastric mucosal cancer, 16 of the 78 lesions were associated with histologic submucosal invasion. EUS features that were associated with a high incidence of histological submucosal tumor invasion were irregular narrowing (submucosal invasion, 60.0%) and the budding sign (85.7%), and 90.9% of lesions with either of these features had submucosal invasion of tumors when tumorous changes in the third layer exceeded 1 mm in depth. Endosonographic irregular narrowing and a budding sign of more than 1 mm in depth in the third layer are useful for the diagnosis of submucosal invasion in gastric cancers that are diagnosed as mucosal cancers without ulcerous change on endoscopy.

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.

Usefulness of endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of pancreatic cancer.

BackgroundEndoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has come into widespread use, mainly in Western countries, as an efficient and safe method for the cytologic or histologic diagnosis of pancreatic cancer. However, it still has received relatively little attention in Japan. To evaluate the clinical status of EUS-FNAB in Japan, we retrospectively analyzed the results with regard to the ability of EUS-FNAB to diagnose pancreatic cancer, as well as its safety.MethodsA total of 52 patients (37 male, 15 female; mean age, 62.5 years; range, 33–85 years) with focal pancreatic lesions underwent EUS-FNAB at our group of hospitals in one region of Japan. Final diagnosis was confirmed by histologic examination of surgical specimens or clinical follow-up.ResultsThe final diagnoses were malignant tumors in 32 patients and benign ones in 20. Insertion of the needle into the lesion was successful in 50 of the 52 patients (96.2%). Adequate specimens were obtained by EUS-FNAB from 47 of the 50 pancreatic lesions (94.0%). With five false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 89.4%, 82.1%, 100%, 100%, and 79.2%, respectively. No complications occurred.ConclusionsEUS-FNAB is an efficient and safe method for the histologic diagnosis of pancreatic cancer. It should be considered as one of the indispensable modalities for the histological diagnosis of pancreatic cancer in Japan, as it is in Western countries.