[From Dokushoan Nagatomi to Genshun Koishi].

In the middle part of the Edo period (around the later half of the 18th Century), several new-ideated physicians did appear. Among them, Dokushoan Nagatomi and Genshun Koishi were eager to learn western style autopsy. The former got the knowledge from imported Dutch books with the aid of interpreters at Nagasaki and the latter, upon influence of the former, eventually performed on autopsy by himself, aiming at understanding relationships between organ changes and the nature of the diseases of the patients. This article describes an outline of the story of two physicians as pioneers of anatomy and pathological anatomy in this country.

[Introduction to the knowledge of physiology in "Ihan Teiko," compared with that of "Jyutei-Kaitaishinsho"].

By translating imported Dutch books on anatomy and physiology, Udagawa Genshin (1769-1824) wrote the book titled "Ihan Teiko" (Concise Model of Medicine) in 1805. Owing to the vast volume of this book, his pupil Fujii Hohtei summarized it to 3 volumes. With these procedures, the book became widely known and read among physicians who had an interest in Dutch style medicine, especially the function of the organs, and tissue. The physiological functions of each organ and tissue were described, with anatomical explanations. In this article, stress is put on the consideration of physiology. From the viewpoint of present knowledge, the shortages and misunderstandings of the functions are also commented on. Although this book shows such classical inmaturities, it had great influence on Japanese physicians in promoting the level of knowledge from pre-modern to modern medicine, even in the time of the closed-door policy.

Cooperative clinical trial of photodynamic therapy with photofrin II and excimer dye laser for early gastric cancer.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is a recently developed endoscopic method for treating malignant tumors. For obtaining more photodynamic action with less thermal effect, we employed as the excitation light source for PDT an excimer dye laser, which is a pulsed laser with extremely high peak power, instead of an argon dye laser, which is a continuous wave laser and has been used conventionally. STUDY DESIGN/MATERIALS AND METHODS: The effect of PDT using Photofrin II and the excimer dye laser was evaluated in 27 patients with early gastric cancer. RESULTS: Complete responses (CR) were obtained in 88% of 24 assessable patients and the response rate was 100%. CR was observed in all cases of lesions of superficial depressed type without ulceration and/or with tumor diameter less than 2 cm. Regarding toxicity, mild cutaneous reaction and photosensitivity were seen and lasted several weeks. There were no serious abnormalities in laboratory tests. CONCLUSION: We conclude that PDT is a promising modality for early gastric cancer.

[Treatise on Kankeru (cancer) written in the book "Komo Ijutsu Monsho" by Goda Daisuke].

"Komo Ijutsu Monsho" (Book on Dutch Style Medicine) was written by Goda Daisuke (1738-1795), who was a physician in Sanuki (Kagawa Prefecture) and younger brother of the author of "Komo Igen" (Introductory Note on Dutch Internal Medicine) Goda Kyugo, by listening to the Japanese interpreters Yoshio Kogyu and Rofu of Nagasaki, around the 1760's. In this book, he noted the nature of Kankeru (cancer), especially of the breast, and also referred to the fact that the disease is curable when it was removed in its early stage. Later on, this information led to the success of surgical resection of breast cancer by Hanaoka Seishu in 1805 by the use of general anesthesia, which he invented. This article introduces the pioneering work of Goda Daisuke.

["Komo Igen" written by Goda Kyugo].

In 1762, three years after the publication of "Zoshi" (the first anatomical book written by a Japanese) by Yamawaki Toyo, Goda Kyugo, one of the disciples of Toyo, went to Nagasaki. During his two and a half month stay there he learned Dutch style medicine, especially internal medicine, from the translator Yoshio Kogyu and his younger brother, by the aid of imported Dutch medical books. Kyugo recorded their lectures in five volume notes and entitled it "Komo Igen" (Medicine of the Netherlands). The natures, symptoms and diagnoses of several diseases, including infectious and epidemic diseases and the way of treatments were recorded in the notes. This manuscript attempts to introduce the contents of "Komo Igen" together with its back ground and stresses the importance of these notes for the beginnings of modern medicine in 18th century Japan. The significance of the "Komo Igen" as a historical medical literature is also pointed out.

[Therapeutic treatment of Borrmann type 4 (scirrhous) gastric cancer-chemotherapy and histopathological studies].

Up to now, there has been no investigation documenting clearly the effectiveness of chemotherapy for Borrmann type 4 gastric cancer from a histopathological viewpoint. In this paper, we present a few representative cases of Borrmann type 4 gastric cancer in which microscopic examination revealed the therapeutic effectiveness (degradation of cancer cells) of neoadjuvant chemotherapy. Further, comparative studies will be needed to clarify the relationship between the assessed effectiveness of therapy by roentgenological and histopathological examination.

Retrospective histological studies on biopsied gastric lesions of patients in whom cancer was diagnosed at follow-up examination.

Serial biopsy specimens of gastric lesions of patients in whom cancer was diagnosed at follow-up examination were reexamined retrospectively; the source materials were 17,429 gastric biopsies carried out on 14,779 patients from 1971 to 1985 at Aichi Cancer Center Hospital. Among these cases, cancers were found at follow-up in 34 cases at locations distinct from the initially biopsied lesions, and in 41 cases, cancerous changes were detected at follow-up at the locations of the original lesions. These 41 cases amounted to 0.5% of the total biopsied cases with negative results. The average interval from the first to the last endoscopic examination in these 41 cases was 52.1 months and the longest interval was 150 months in the case of a scarred lesion. Based on the reexamination of the histology of the biopsy specimens taken at the first examination, these 41 cases were classified into three subgroups: 1) no precancerous atypical changes were observed, 2) doubtful precancerous changes were observed and 3) minute or slight malignant changes did exist but had been overlooked. The number of cases in the first category was 33 (80.5%), among which ulcer or its scar was most common, the number in the second category was 6 (14.6%), most of them being polypoid lesions, and the number in the third category was 2 (4.9%). Histological features of some cases in each subgroup are presented and the results are discussed.

[Histological studies concerning the development of gastric stump carcinoma by endoscopic mucosal biopsies].

225 patients who received partial gastrectomies more than five years ago were examined by endoscopy with mucosal biopsies. In the biopsies taken from mucosa close to the anastomosis, hyperplasia of the foveolar epithelium and glandular cysts, findings identical with "gastritis cystica polyposa", were most often seen following Billroth II resection. Cases in which more than 20 years had elapsed since Billroth II resection revealed the highest rate (65.2%) of such mucosal changes. A close relationship between 2 cases (B-II Group) of gastric stump carcinoma detected near the gastro-enteric anastomosis and such mucosal changes is suggested.

Gastric cancer preceded by severe dysplasia.

For elucidation of histogenesis of gastric cancer derived from relatively flat mucosa, 77 cases of surgically resected stomachs with lesions of severe dysplasia in cancerous mucosae or with cancerous changes in severely dysplastic mucosae were detected out of 380 recently examined cases of early gastric cancer. Several examples of early gastric cancer of the superficial type, showing histological changes indicating that they had developed on the preexisted dysplastic mucosal lesions, have been presented, together with the background data. The frequency for detecting such changes was higher in the slightly elevated lesions than in the depressed or eroded ones.

[Initial changes in the development of gastric cancer].

Among 123 cases of surgically resected stomachs bearing minute cancerous foci, which comprised 9.5% of all the early gastric cancers obtained, six cancerous foci with either intestinal type of diffuse-type histology showing the earliest changes of development were selected and the macroscopic and histological features of the foci were presented. Foci of the former type were found in the deepest layer of the gastric foveolae in severely metaplastic mucosa in a budding-like growth pattern and tended to enlarge the area toward the surface of the mucosa, which resulted in tiny focal depressions of the affected mucosa. On the other hand, lesions of the latter type were found in the neck zone of the mucosa with little or no intestinal metaplasia and spread laterally into the surrounding mucosa by infiltrative growth as groups of signet-ring type cancer cells, which resulted in cancerous erosion of the affected mucosa.

Two cases of gastric cancer-bearing double choledochus with ectopic drainage into the stomach.

Two cases of double choledochus with ectopic drainage into the stomach associated with gastric carcinoma were reported. The stomachs were resected because of the presence of cancer, and the orifices of the ectopic bile duct were found in the oral side of the lesions. In these two cases, hyperplasia of gastric foveolas and atrophy of fundic gland, with its cystic dilatation, were observed around the orifices. A possible correlation between direct flow of bile juice into the stomach through the ectopic bile duct and the development of gastric cancer was discussed. The literature regarding double choledochus was reviewed.

UDP-GalNAc:GalNAc-mucin alpha-N-acetylgalactosamine transferase activity in human intestinal cancerous tissues.

GalNAc transferase activities of 6 human intestinal cancerous tissues were examined using bovine submaxillary gland mucin and its desialylated derivative, asialomucin, as acceptors. A Triton X-100 extract of these tissues was used an an enzyme source. All the tissues examined had GalNAc transferase that catalyzes the transfer of GalNAc from UDP-GalNAc to serine or threonine residues of the polypeptide chain. One of 6 specimens showed in addition UDP-GalNAc:GalNAc-mucin alpha-GalNAc transferase activity, synthesizing a disaccharide unit, GalNAc alpha----GalNAc, when asialomucin was used as an acceptor. This carbohydrate structure was deduced on the basis of results of gel filtration, exoglycosidase digestion, and high-voltage paper electrophoresis.

Gastric dysplasia. Significance and pathologic criteria.

In view of uncertainty regarding the criteria and significance of gastric dysplasia as a precancerous lesion, members of the Pathology Panel of the International Study Group on Gastric Cancer (ISGGC) reviewed microslides of 93 gastric lesions showing varying degrees of mucosal abnormality, and reached the following consensus: (1) immature and proliferating gastric epithelium can be divided into two categories: hyperplastic and dysplastic; (2) the term dysplasia, especially of high-grade type, should be restricted to precancerous lesions, and hyperplasia is applied to regenerative changes; (3) regenerative hyperplasia may be simple or atypical, but dysplasia includes both moderate and severe abnormalities, since they often coexist and can not be sharply separated; and (4) occasionally the possibility of malignancy can not be excluded in a severely dysplastic epithelium; in such a case rebiopsy and diligent follow-up are necessary to establish the diagnosis. Criteria for diagnosing dysplasia and hyperplasia are presented and discussed. The opinions are offered as guidelines for establishing the diagnosis of gastric dysplasia and for prospective studies.

The influence of gastro-jejunal anastomosis on gastric carcinogenesis in rats.

The effect of reflux of the duodenal contents on the development of gastric stump carcinoma induced in male rats was studied. Two gastro-jejunal anastomoses were made in the resected stomach of 28 rats and about half of the rats were also given a single dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Well-differentiated adenocarcinomas developed in the resected stomachs with and without MNNG administration at incidences of 40% in the former and 23% in the latter. All the carcinomas were localized in the vicinity of the gastro-jejunal anastomosis, at which the proximal jejunal segment was drained. Several mucosal changes were found predominantly in the fundic mucosa surrounding the anastomosis, i.e., ulcer, foveolar hyperplasia, intestinal metaplasia and atypical hyperplasia. On the other hand, there was little mucosal change surrounding the gastro-jejunal anastomosis of the distal jejunal segment. These findings suggest a direct correlation between the exposure of mucosa of the anastomotic region to the duodenal contents and the development of adenocarcinoma.

Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein.

Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. To determine the structures of oligosaccharides 2, 3, and 4, a mixture of the three was subjected to methylation analysis which revealed that the N-acetylgalactosaminitol was substituted at both C-3 and C-6 and other sugars at the nonreducing ends. Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. Anomeric configurations were determined by exoglycosidase digestions except for galactose which was analyzed by chromium trioxide oxidation.

Isolation and characterization of a glycoprotein from a human rectal adenocarcinoma.

A mucin-type glycoprotein was isolated from a human rectal adenocarcinoma, mainly be gel filtration and hydroxyapatite treatment. The glycoprotein, designated as rectal mucin-type glycoprotein (RMG), was great in amount, accounting for about 1% of the wet tissue weight. From a non-cancerous area of the patient's intestine, a similar glycoprotein reacting with anti-RMG antibodies was obtained, but the tissue content was less than 10% of the RMG content. Purified RMG contained about 70% carbohydrate in mass, and is composed of about equimolar amounts of sialic acid, galactose, N-acetylglucosamine and N-acetylgalactosamine. The polypeptide core was characterized by high contents of threonine, serine, and proline. A marked difference between RMG and the normal glycoproteins was that the sialic acid content was much higher in RMG. Of the total N-acetylgalactosamine convertible to N-acetylgalactosaminitol by reductive cleavage with alkaline borohydride, about 15% was free and the rest occupied the reducing ends of acidic oligosaccharides. The acidic oligosaccharides were fractionated into a fraction of high molecular weight and a series of oligosaccharides in which di- and trisaccharides containing sialic acid were dominant. The high molecular weight fraction contained esterified sulfate.

Dysplasia of the gastric mucosa and its relation to the precancerous state.

In an Expert Committee of the WHO, dysplastic changes of the stomach were defined as those having the following three histological features: (i) cellular atypia, (ii) abnormal differentiation and (iii) disorganized mucosal architecture. The changes were classified into three grades--mild, moderate and severe. This paper describes and illustrates each grade of dysplasia and discusses in detail the histological differences between severe dysplasia and intramucosal carcinoma. From the viewpoint of development of gastric cancer, severe dysplasia can be considered as one of the precursors. The clinical implications of dysplastic changes found in biopsied specimens are discussed.

Precancerous conditions and epithelial dysplasia in the stomach.

A distinction can be made between a precancerous condition and a precancerous lesion. The former is a clinical state associated with a significantly increased risk of cancer, whereas a precancerous lesion is a histopathological abnormality in which cancer is more likely to occur than in its apparently normal counterpart. Up to the present time atrophic gastritis, gastric ulcer, pernicious anaemia, gastric stumps, gastric polyps, and Ménétrier's disease have all been considered as precancerous conditions and lesions of the stomach. Of these, only atrophic gastritis, pernicious anaemia, gastric stumps, and certain types of gastric polyp can now be regarded as having any really significant malignant potential. The precancerous lesion common to these is epithelial dysplasia which can occur in ordinary (foveolar) gastric epithelium as well as in intestinal metaplasia. The criteria for grading dysplasia in gastric epithelium into mild, moderate, and severe grades are given, and attention is drawn to the problems of differentiating inflammatory or regenerative change from mild dysplasia and intramucosal carcinoma from severe dysplasia. The clinical and epidemiological implications of gastric dysplasia are discussed with suggestions for further research.

Primary tumors of the esophagus other than squamous cell carcinoma--histologic classification and statistics in the surgical and autopsied materials in Japan.

Clinicopathological features of 405 patients with esophageal tumors other than squamous cell carcinoma, which were resected surgically at 68 institutions in Japan, were analyzed and compared with those of 4,995 cases of esophageal malignant neoplasms autopsied during 19 years (1958-1976) in Japan. Of 405 surgical cases, 149 were benign tumors, most of which (89%) were leiomyomas. The incidence of malignant tumors other than squamous cell carcinoma was 2.1% in the surgical, and 7.2% in the autopsied cases of esophageal cancer. Malignancies were classified into 15 histologic types. Most of them did not differ in sex and age incidence or location of the primary site from squamous cell carcinoma, except for adenocarcinomas, in which there was a greater incidence of occurrence in the lower portion of the esophagus. Carcinosarcomas and pseudosarcomas showed peculiar clinical and pathological characteristics. Overall prognosis was poor except in cases of pseudosarcoma and leiomyosarcoma.

Recent changes in the morphology of gastric cancer in Japan.

The macroscopical and histological features of 4,428 cases of gastric cancer resected stomachs was noted.d surgically between 1953 and 1974 were studied. Of these cases, 81.9% were in an advanced stage and 18.1% in an early stage. The following changes were observed. (1) In the group of advanced cancers, a gradual decrease in the frequency of Borrmann II type was noted. Most of these tumors were well-differentiated adenocarcinomas. (2) In the group of early cancers, a gradual increase in the proportion of "cancerous erosion" was detected. The majority of these tumors were poorly differentiated adenocarcinomas or infiltrating signet-ring cell cancers. (3) At intervals of 10 years, 5-10% decrease in the frequency of intestinal metaplasia in resected stomachs was noted.