Clinicopathologic features of early rectal carcinoma and indications for endoscopic treatment.

PURPOSE: This study was undertaken to clarify the indications for endoscopic treatment. METHODS: Clinical and pathologic features of 191 lesions in 180 patients with early rectal carcinoma were examined, including 110 intramucosal carcinomas and 81 carcinomas with submucosal invasion (submucosal carcinomas). All lesions had been endoscopically or surgically resected at the National Cancer Center Hospital between 1976 and 1990. RESULTS: Metastasis to regional lymph nodes (LN metastasis) was seen in 0 percent (0/39) of intramucosal carcinomas and 9.2 percent (6/65) of submucosal carcinomas in the surgically treated patients. The incidence of LN metastasis was higher for lesions larger than 10 mm in diameter, for those showing massive submucosal invasion, and for moderately differentiated adenocarcinomas. LN metastases were associated significantly with lymphatic invasion. CONCLUSIONS: These results suggest that early rectal carcinomas should be resected surgically if they 1) show massive submucosal invasion, 2) are classified as moderately differentiated adenocarcinomas, and 3) are larger than 10 mm in diameter. In patients with both scanty submucosal invasion and features of well-differentiated adenocarcinoma or intramucosal carcinoma and if no other risk factors for LN metastasis are present, such as lymphatic invasion by the primary lesion, surveillance may suffice after endoscopic resection.

Small depressed cancer of the large bowel: report of three cases.

This report describes three patients in whom colonoscopy detected small depressed cancers (without an elevated component) that had invaded the submucosa. They represent 0.4% (3/884) of all patients with invasive cancers and 3% (3/101) of patients with submucosal cancers in the National Cancer Center Hospital between January 1990 and February 1994. This type of cancer may have been overlooked in the past because of its small, flat nature. A slight deformity of the lumen, a faint color change (slightly reddish), and a loss of a vascular network pattern were important colonoscopic findings. Small depressed cancers may follow a different pathway to advanced cancer than polypoid cancers, although both pathways are included in the adenoma-carcinoma sequence. We should be aware of these lesions in our efforts to detect colorectal cancers in the early stage.

Helicobacter pylori infection, serum pepsinogen level and gastric cancer: a case-control study in Japan.

We conducted a case-control study to evaluate the effect of Helicobacter pylori (HP) infection on the risk of gastric cancer in Tokyo, Japan. The sera at the time of diagnosis from 282 gastric cancer cases and 767 sex- and age-matched cancer-free controls were tested for the presence of anti-HP IgG antibody (HM-CAP ELISA kit) and serum pepsinogen (PG) level (PG I and PG II Riabead). No significant association was observed in all sets [matched odds ratio (OR) = 1.04, 95% confidence interval: 0.73-1.49]. In subgroup analyses, however, an association was suggested in females [OR = 1.57], a younger population (< 50 years) [OR = 1.86], early cancer [OR = 1.53] and small cancer (< 40 mm) [OR = 1.55]. Furthermore, we observed a tendency for odds ratios to decrease with an increase in age or cancer growth (depth of tumor invasion and tumor size). Considering that the spontaneous disappearance of HP due to extended mucosal atrophy may lead to these decreasing odds ratios, we applied the conditional logistic model adjusted for the PG I/II ratio as a measure of atrophic gastritis. This analysis showed a positive association with HP infection in all sets [OR = 1.69; 1.01-2.81], distal cancer [OR = 1.88; 1.07-3.31] and intestinal-type cancer [OR = 3.76; 1.39-10.18]. We concluded that the risk of cancer associated with HP infection may be underestimated in studies with cross-sectional exposure because of spontaneous disappearance of HP due to extended mucosal atrophy.

[Endoscopic diagnosis of scirrhous gastric carcinoma].

There have been many names similar to the name of scirrhous gastric cancer, and for a correct endoscopic diagnosis, an understanding of the delicate differences between these names is necessary. Another prerequisite is a thorough knowledge of the pathological/macroscopic morphology. In endoscopy examination accompanied by frequent belching, there is often a normal stomach with much tension, so one should always keep in mind the possibility of scirrhous gastric carcinoma. Since there is severe stenosis in such scirrhous gastric cancers, one can only observe the cardiac orifice side, and the biopsy may show false negative. For an improved prognosis, discovery and treatment in the very early stages is the only way.

"Very well differentiated tubular adenocarcinoma" of the stomach: its endoscopic and histopathological characteristics.

Between 1986 and 1991, 31 patients having tubular adenocarcinoma with low cellular and structural atypism ("very well differentiated tubular adenocarcinoma:" tub 0) underwent surgery at the National Cancer Center Hospital (NCCH). Histologically, the 31 lesions in the 31 patients were very similar to those observed in gastric adenoma (World Health Organization) with severe atypism. Their malignancy could be diagnosed only on the basis of cellular atypism, i.e., uneven distribution of chromatin in the nucleus accompanied by irregularity in the size or shape of the spindle-form nucleus, abnormal nuclear polarity and/or obvious nucleoli. Histologically, the border between the tub 0 and adenomatous areas ('front line' of carcinoma) could not be identified within the neoplastic lesion, which showed relatively regularly shaped tubuli (less structural atypism). Of the 31 cases, 30 were solitary early gastric cancer (EGC). Their clinicopathological features were compared with those of 34 cases of gastric adenoma, 237 cases of solitary well differentiated (tub 1) and 127 cases of moderately differentiated (tub 2) tubular adenocarcinoma which had been resected at the NCCH during the same period. Most (75%) of the 30 tub 0 EGCs were type IIc (depressed) macroscopically, despite their histological similarity to gastric adenoma which showed a high (90%) elevated appearance incidence. The incidence of small lesions, < 2 cm in diameter, was highest in gastric adenoma (82%), followed by tub 0 (64%), although the tub 0 lesions showed a wide range of sizes. Small lesions were less frequent in the tub 1 (43%) and tub 2 (33%) cases. The incidence of submucosal invasion was significantly lower in tub 0 cases (17%) than in tub 1 (39%) and tub 2 (46%) cases (P < 0.05). No lymph node metastasis was seen in tub 0 cases, but was seen in 6.4% and 9.4% of tub 1 and tub 2 cases, respectively. With regard to the endoscopic appearance of depressed mucosal cancer, the incidence of encroachment (moth-eaten appearance) on the tips of folds was significantly lower (10%) and the appearance of marginal elevation was significantly higher (79%) in tub 0 than in tub 1 (each P < 0.05) or tub 2 (each P < 0.01). The results suggest that 'tub 0' can be regarded as a less malignant but not benign tumor, and that its endoscopic characteristics provide valuable information which can be used to ensure that patients receive suitable treatment.

[Helicobacter pylori infection in gastric cancer].

The relationship between Helicobacter pylori (H. pylori) infection and gastric cancer becomes the topics in the world, since some reports thereon in 1991. The purpose of this study was to know the prevalence of H. pylori infection in many patients with gastric cancer. We examined the H. pylori IgG antibody in 507 patients with gastric cancer resected surgically in our hospital from 1989 to 1991, retrospectively. For the test of H. pylori IgG antibody, HM-CAP EIA kit (Italy, ENTERIC PRODUCTS Co.) was used. The overall detection rate of H. pylori IgG antibody was 75% (378/507). H. pylori infection was significant significantly frequent in early cancer (80%, 231/288) than advanced cancer (67%, 147/219). But, the other clinicopathological features such as sex, age, histological type, location and the degree of intestinal metaplasia were not significantly correlated with H. pylori infection. To evaluate the risk of H. pylori infection for gastric cancer, we are going to plan a matched-pair case-control study.

Helicobacter pylori may be transmitted through gastrofiberscope even after manual Hyamine washing.

Endoscopy is an effective diagnostic technique for gastric cancer, which is believed to be associated with Helicobacter pylori. Manual Hyamine washing is a widely used fiberscope cleaning method. Urease B gene of Helicobacter pylori was detected in 50% of the wash-out samples from the biopsy-suction channel of a fiberscope after manual Hyamine washing by nested polymerase chain reaction, and bacterial culture revealed viable Helicobacter pylori in 19%. However, Helicobacter pylori was not detected by either of the above methods in the biopsy-suction channel of the fiberscope after mechanical washing. These findings indicate that manual Hyamine washing of fiberscopes is insufficient to prevent iatrogenic Helicobacter pylori transmission, and that mechanical washing after manual Hyamine washing is essential.

Laser endoscopic treatment for upper gastrointestinal cancers.

We report the effective clinical use of endoscopic laser in Japan using the results of a nationwide survey and our own experience with more than 100 cases. The Nd:YAG laser and argon dye laser with hematoporphyrin derivative (photodynamic therapy) were most commonly used in digestive endoscopy and were investigated as new modalities of cancer therapy. Photodynamic therapy was fairly effective, especially in superficial esophageal cancer and the ill-defined lesions of early gastric cancer. Endoscopic laser treatment was carried out on 80 patients with 86 lesions of early gastric cancer at our hospital, and the following tumor types were proven highly curable by this means: focal cancer, IIa and so-called "gastritis-like" tumors less than 2 cm in size. The Nd:YAG laser provides a new approach to palliative treatment, such as recanalization of neoplastic obstruction in the advanced stage of gastrointestinal cancers.

[Study of local interstitial hyperthermia induced by low power Nd:YAG laser].

A comparative study of local interstitial hyperthermia induced by low power Nd:YAG laser (laser hyperthermia) and microwave hyperthermia was carried out in vivo and in vitro in an attempt to clarify the therapeutic effect and the mechanism. Both therapies, after seven days, caused marked amounts of coagulated necroses in the transplanted tumors of human pancreatic carcinoma. Immediately after those therapies, electron microscopic examination of the tumor tissues showed membranous, cytoplasmic, nuclear and mitochondrial damage; however, this damage was much more extensive in laser hyperthermia compared to microwave hyperthermia. The cytocidal effects of heating alone, laser hyperthermia and microwave hyperthermia were also studied in vitro. Of the three, laser hyperthermia demonstrated the most notable decrease in viability. Thus, in the mechanism of laser hyperthermia, it seems that the immediate effect is cellular damage caused by both heat energy and Nd:YAG laser light followed by subsequent damage of tumor vessels.

Laserthermia. A new method of interstitial local hyperthermia using the contact Nd:YAG laser.

Laserthermia is a new method of delivering interstitial local hyperthermia using a synthetic contact probe with a computer-controlled Nd:YAG laser to deliver both pulsed and continuous laser energy. The system allows an easily controllable increase in temperature (for example, from 42 to 43 degrees C) over a fixed period of time (for example, 20 minutes) to be delivered to tissue. A single or multiple channel system can be used depending on the volume of tissue to be treated. Tumor necrosis appears to be related to avascular infarction. Early clinical results support the beneficial therapeutic effects of Laserthermia in its oncologic applications.

[Non-granulomatous anterior uveitis and HLA-B27 antigen].

In Caucasians, there is close correlation between acute anterior uveitis and histocompatibility antigen HLA-B27. But in Japanese, this is not clear. Therefore, we examined 58 patients with non-granulomatous anterior uveitis (NGAU) about HLA typing in our uveitis clinic at Tokyo Women's Medical College Hospital. HLA-B27 was identified in 20 out of 58 patients (34.5%) with NGAU and it was statistically significant. We also studied the clinical features of patients with HLA-B27 positive NGAU. We found that in HLA-B27-positive NGAU, the visual acuity was more strongly affected during the attack and the duration of inflammation was longer than HLA-B27 negative NGAU patients. The duration of the first attack was longer than re-attack, and the duration of the first attack was longer than HLA-B27 negative NGAU patients. It was less commonly associated with systemic disorders in Japanese HLA-B27 positive anterior uveitis than in Caucasian. However, in Japanese NGAU patients without systemic disorders, there was the same tendency concerning the HLA-B27 positive rate as in Caucasians.

[Effect of sodium thiosulfate on the antitumor effect and nephrotoxicity of CDDP in human gastric cancer transplanted in nude mice].

Sodium thiosulfate (STS) is known to decrease the nephrotoxicity of cisplatin (CDDP). CDDP has been recognized effective in some type of gastric cancers, and there has been an attempt to examine the optimal dose of STS, which suppresses the CDDP-induced nephrotoxicity without interfering its anticancer effect. The gastric cancer cell lines (KATO-III and MKN 45) were transplanted into BALB/c nu/nu mice. CDDP was injected intraperitoneally once a week 5 times with various doses of STS, and the effects of STS on the antitumor effect as well as the nephrotoxicity of CDDP were examined. The antitumor effect of CDDP (9 mg/kg) was suppressed by 30% with the simultaneous injection of 372 mg/kg (50 fold-molar radio of STS to CDDP) and abolished by 1,488 mg/kg (200 fold-molar radio) of STS. The elevated serum BUN and the kidney content of platinum following CDDP administration were at the normal ranges in the nude mice received these doses of STS. Also, the atrophic and regenerative changes of the kidney tubules induced by CDDP were scarcely observed in these nude mice. From these results, only 50 fold-molar radio of STS to CDDP suppresses the nephrotoxicity of CDDP without interfering its antitumor effect, and this rather smaller amounts of STS is considered to be optimal. Further studies, however, will be needed for clinical application.

[The influence of sodium thiosulfate on the antitumor effect of cisplatin in human gastric cancer cell lines].

It is well known that the sodium thiosulfate (STS) decrease not only the nephrotoxicity which is a dose limiting factor of cisplatin (CDDP) chemotherapy but also its antitumor activity. Therefore, we examined the antitumor effect of CDDP in the human gastric cancer cell lines under various concentrations of STS. The cell lines used were KATO-III, MKN 28, MKN 45 and MKN 74. The consistency of STS in relation to CDDP (2.0 ng/ml) was 25-250 fold-molar ratio. The chemosensitivity of CDDP was positive in the 3 cell lines, KATO-III, MKN 28 and KATO-III in order. When STS was used with 50 fold-molar ratio in KATO-III and MKN 28 and 100 fold in MKN 45, a CDDP colony inhibition rate of more than 80% was maintained. This results suggest that the antitumor effect of CDDP will not be suppressed not so much when the low dose of STS was used in CDDP with STS chemotherapy, even though used through the same route of administration and simultaneously.

Local hyperthermia using a low powered Nd: YAG laser for pancreatic and gastric carcinoma.

The use of local interstitial hyperthermia using a low powered Nd: YAG laser (known as laserthermia) has been studied both in vivo and in vitro on two gastrointestinal carcinomas. Human pancreatic carcinoma subcutaneously transplanted into nude mice (n = 28) was treated using an interstitially placed frosted sapphire probe with a Nd: YAG laser at 3 watts maintaining a temperature increase of 42 degrees C - 43 degrees C for up to 20 minutes. Seven days after treatment, a marked necrosis of the pancreatic tumor was found resembling an ischemic infarction. The potential cytocidal effect of heat and low powered Nd: YAG laser energy was also tested in vitro using three different kinds of human gastric and pancreatic cancer cells. The cytocidal effect of heat was potentiated by the photolytic effect of the low powered Nd: YAG laser energy.

[Indications and problems of endoscopic treatment for gastrointestinal tract cancers, with special reference to early gastric cancer].

We carried out a clinicopathologic and endoscopic investigation of the relationship between the presence/absence of lymph node or distant metastasis and several crucial factors using resected specimens of early gastric cancer, and concluded that endoscopic treatment was indicated for four types of early gastric cancer: 1) type IIa less than 2 cm in size, 2) focal cancer, 3) so called "gastritis-like" early cancer less than 2 cm in size and 4) polypoid type with mucosal involvement. Up to now, cases of early gastric cancer have been treated by polypectomy, strip biopsy and laser endoscopy. Residual cancer cells were found in 10 out of 20 resected cases. In 2 out of 54 cases followed up for more than one year without any surgical treatment, cancer cells were discovered by biopsy. The effectiveness rate was estimated to be 84% (62/74). Endoscopic treatment was able to provide high efficiency for early gastric cancer of the above types. Causes of ineffectiveness were a lesion more than 2 cm in size, vertical invasion of the lesion into the submucosa and the location of a lesion in a difficult area such as the prepylorus or the cardia.