Koji Sasajima

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.

Primary undifferentiated small cell carcinoma of the esophagus

Abstract We histologically examined undifferentiated small cell carcinoma of the esophagus from 21 patients and used immunohistochemical methods for detection of chromogranin A and p53, bc1–2, and Rb oncoproteins. Nine (43%) of the 21 carcinomas consisted solely of undifferentiated cells, but heterogeneous components of in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma were observed in the other 12 (57%) tumors. Squamous cell carcinoma in situ was observed in the mucosa adjacent to the main tumor in 7 (50%) of the 14 resected esophageal specimens. An admixture of invasive squamous cell carcinoma and undifferentiated carcinoma was observed in 4 (19%) of the 21 tumors, and mucoepidermoid carcinoma was noted in one case. Chromogranin A staining yielded a positive reaction in two (10%) undifferentiated components but was negative in all heterogeneous components. Multiple sites of p53 immunopositivity were seen in the undifferentiated component of 17 (81%) of the 21 tumors, as well as in the in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma components of 9 (75%) of 12 tumors. Seven (33%) of the 21 tumors showed positive bc1–2 immunoreactivity in the small cell component, but all of the heterogeneous components were negative. Rb protein immunoreactivity was observed in the small cell component of one (5%) case and in 9 (75%) of the 12 heterogeneous components. Six (86%) of the seven in situ squamous cell carcinoma components were positive for Rb protein. Eighteen (86%) of the 21 patients died within 24 months of diagnosis. Two patients (10%) who survived for more than 24 months had received chemotherapy.

Correlation of telomere lengths in normal and cancers tissue in the large bowel.

The hypothesis that telomeres in colorectal cancer cells exhibit age-related shortening, as in normal cells of the colorectal epithelium, was tested with samples of non-cancerous mucosa and cancer tissue from 124 patients (aged 29-97 years). Shortening with aging could be demonstrated for both normal and cancer tissues; regression analysis showed rates for length reduction of 44 and 50 base pair/year, respectively. Straight, essentially parallel, lines were obtained for the two cases, normal tissue values being about 2 kilobase pairs (kbp) higher, with a significant correlation between data at the individual patient level.

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.

Telomerase activity in esophageal carcinoma

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA. Immortalized and carcinoma cells show no loss of telomere length during cell division. Telomerase activity has been demonstrated in carcinomas of various organs, but not in nonneoplastic tissues. In patients with esophageal carcinoma, no data have been reported concerning the relationship between telomerase activity and clinicopathological findings.

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.

Oncocytic Adenocarcinoma of the Stomach: Parietal Cell Carcinoma

We report 10 cases of an unusual type of gastric adenocarcinoma that occurred in elderly patients 58–81 years of age. Histologically, the tumors were well to moderately differentiated tubular adenocarcinomas with very eosinophilic, finely granular cytoplasm. Immunohistochemical stains for antimitochondrial antibody were strongly positive. Ultrastructurally, the tumor cells had numerous mitochondria in their cytoplasm and occasional intracytoplasmic lumina with associated long microvilli. These histologic and ultrastructural features are similar to those of parietal cells in normal gastric fundic mucosa, but immunohistochemical staining of the tumors using four different antiparietal cell antibodies (anti-H+-K+-adenosine triphosphatase antibodies) was negative in all cases. Therefore, we think that these tumors were not parietal cell carcinomas but could be termed oncocytic adenocarcinomas, or adenocarcinomas with oncocytic differentiation. Previously reported cases of parietal cell carcinoma have been said to have a favorable prognosis, but it will be necessary to study a larger number of cases to determine the prognosis of oncocytic adenocarcinoma.

Intestinal metaplasia and adenocarcinoma induced in the stomach of rats by N-propyl-N′-nitro-N-nitrosoguanidine

SummaryPNNG, the propyl derivative of MNNG, was administered to Wistar rats at a concentration of 59.5 μg/ml in the drinking water for 4, 8, and 12 months and the rats were killed in the 15th month. Intestinal metaplasia was induced in the glandular stomachs of 25%, 75%, and 83% of the rats treated with PNNG for 4, 8, and 12 months, respectively. Metaplastic glands were found in the pyloric region, especially near the pyloric ring. These glands contained goblet cells and columnar cells with striated borders. No tumors were found in the stomach of rats after 4-months treatment, but adenomas were found after 8-months treatment, and both adenomas and adenocarcinomas after 12-months treatment.

Structures of the normal esophagus and Barrett?s esophagus

This article reviews and discusses several topics, mainly relating to the histology of the normal esophagus and of Barrett’s esophagus, in order to facilitate the understanding of Barrett’s esophagus. The border between the esophagus and stomach is considered in Japan to be the lower limit of longitudinal vessels which are visible in the lower segment of the esophagus at endoscopy. This definition has been authorized by the Japanese Society for Esophageal Diseases. The longitudinal vessels are also visible through the metaplastic columnar epithelium of Barrett’s esophagus. Identification of the esophageal glands proper in biopsy specimens can assist in the histologic diagnosis of Barrett’s esophagus. The histologic diagnosis of Barrett’s esophagus in biopsy specimens, in relation to the presence of esophageal glands proper, is discussed. Ciliated pseudostratified epithelium is discussed in detail, including the fact that it is thought to be an intermediate stage between squamous and columnar epithelium at the esophagogastric junction and at ectopic gastric mucosa in the upper esophagus. The differences in the histopathologic criteria for a diagnosis of Barrett’s adenocarcinoma between Western countries and Japan are also discussed. The four editions of the Comprehensive Registry of Esophageal Cancer in Japan, and the Long Term Results of Esophagectomy in Japan (1988–2000), published by the Japanese Society for Esophageal Diseases and available on its website (http://jsed.umin.ac.jp), are introduced. These editions give detailed information on the pathology, endoscopic features, radiation treatment, and surgery of esophageal cancer in Japan.

Quantitative Detection of p53 Mutations in Plasma DNA from Tobacco Smokers

In lung tumors, the p53 tumor suppressor gene is commonly mutated with a characteristic mutation spectrum. The amount of and alterations in plasma DNA, such as mutations in p53, were associated with several cancers. Few studies used quantitative methods of high sensitivity. Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay. Based on our observation of an increased p53 mutation load in nontumorous lung tissue in smokers, we hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke exposure and will be an effective biomarker of lung cancer or smoking exposure. We modified the p53 mutation load assay to detect mutations at p53 codons 248 and 249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of 1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital controls (n = 21), and population controls (n = 20) from a larger study. Controls were selected to consist of equal numbers of both ever and never smokers. The p53 mutation load (mutated p53 copies per total number of p53 copies) was associated with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the individuals with p53 mutations observed in plasma DNA were ever smokers and the p53 mutation load was higher in those who smoked for longer durations (P = 0.04). In summary, we were able to detect p53 mutations in plasma DNA from healthy individuals and our data suggest that p53 mutations in plasma DNA may be a marker of carcinogen exposure from tobacco smoke.