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The present study was designed to investigate the effects of dietary miso and NaCl supplementation on the development of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in male F344 rats. A total of 76 rats, six weeks of age, were divided into seven groups and given weekly subcutaneous injections of AOM (15 mg/kg body wt) for three weeks to induce ACF. The animals were placed on diets one week before the first AOM dosing. Group 1 was fed a normal diet as a control. Groups 2-4 were fed diets containing 5%, 10%, and 20% miso, respectively, and Groups 5 and 6 were fed diets containing 2.2% and 4.4% NaCl, respectively, for five weeks. Group 7 was fed a normal diet without carcinogen exposure. Dietary miso inhibited the development of ACF in a dose-dependent manner (y = -3.9x + 140, r = -0.94). Thus the mean numbers of ACF per colon were significantly lower in Groups 3 and 4 than in Group 1 (p < 0.01), and there were fewer aberrant crypts per colon in Group 4 than in Group 1. NaCl supplementation was associated with fewer ACF, but this was not statistically significant. 5-Bromo-2'-deoxyuridine labeling indexes in the colonic epithelium were significantly lower in Group 3 than in Group 1 (p < 0.05). The present results indicate that dietary miso could act as a chemopreventive agent for colon carcinogenesis.

今回, 我々はserrated adenomaの多発を認めた若年者大腸癌の1例を経験したので報告する. 症例は29歳の女性. 腹部腫瘤の自覚で近医を受診. 精査にて横行結腸に限局潰瘍型の腺癌とS状結腸から横行結腸にかけてポリープの多発を認めた.結腸右半切除術・D3のリンパ節郭清を施行した. 病理組織学的所見では限局潰瘍型病変は高分化腺癌 (壁深達度se, 脈管侵襲ly1, v1)) であった. 切除標本上の多数の小隆起性病変はhyperplastic polypとserrated adenomaであった.正常部・腫瘍部に対し遺伝子不安定性を検討したがreplication errorは認めなかった. 補助化学療法はテガフールーウラシル配合剤300mg/dayの経口投与を施行している. 術後経過良好にて軽快退院し, 術後18か月の現在, 癌の転移・再発, 第2癌の発癌は認めていない.

The effects of heavy ion and X-ray irradiation on tumorigenesis in B6C3F1 mice were compared. Six-week-old animals were divided into 6 groups and exposed to 0.426 Gy heavy ion irradiation of 290 MeV/u carbon-ion beam (LET 60-210 KeV/micron) at the dose rate of 0.4 +/- 0.2 Gy/min; 0.5 Gy of X-ray irradiation at 0.1 Gy/min or 5 Gy of X-ray irradiation at 1 Gy/min. The mice were killed and an autopsy performed 13.5 months after the whole body irradiation. Body weights were heaviest for both sexes in the 0.5 Gy group and lightest in the 5 Gy one. Total tumor incidences in the males were 30, 56 and 13% respectively in the heavy ion, 5 Gy and 0.5 Gy X-irradiated groups, stomach tumors, lymphomas and adrenal tumors being the most common outcome of the high dose X-rays. Liver tumor induction did not differ significantly among the groups. In the females tumorigenicity was significantly lower for heavy ion than for 0.5 Gy and 5 Gy X-ray irradiation (P < 0.05), the respective incidences, mainly ovary one, being 73%, 17% and 41%. Non-cancerous lesions, such as graying of the hair, glomerular sclerosis and amyloidosis appeared in the 5 Gy group. These findings indicate that 0.426 Gy of heavy ion irradiation induced lower carcinogenicity than 5 Gy of X-irradiation and higher carcinogenicity than that of 0.5 Gy X-irradiation in male mice.

X-ray induction of tumors were examined in five-week-old male CD(SD) : Crj rats, treated with two 10 Gy doses to the gastric region with a 3-day interval (total 20 Gy). After irradiation, the rats received a 1% NaCI supplement in the diet and survivors were killed 22 months after the first X-irradiation. The total tumor incidence was 59% (48 of 82 effected rats), the first animal demonstrating a sarcoma at day 273. Islet tumors of the pancreas appeared from the 455 day time point. Pancreatic and kidney tumors developed in 15 rats (18%) each, and apocrine tumors at the irradiated site and sarcomas in 9 rats (11%) and 5 (6%), respectively. Gastric tumors were found in 3 rats (4%). Immunohistochemistry revealed the islet tumor cells to be generally positive for insulin, although some cells contained somatostatin or glucagon, but not gastrin. The present results thus showed that the insulinomas and tumors other than gastric lesions are induced by X-irradiation of the upper peritoneal region.

The stomach region of male hypocatalasemic (Cbs), C3H, and BALB mice of both sexes was irradiated once with a dose of 20 Gy of X-ray. After irradiation the Cbs mice were administered with 0.1% hydrogen peroxide (H2O2) solution as their drinking water, or 10% sodium chloride (NaCl) in their diet. The resultant total tumor incidences were 50% to 100% by the end of the experiment after 13 months. More female mice died in the early phase after X-irradiation than males. Well differentiated tumors were observed in the glandular stomachs of 35 to 100% and signet ring cell carcinomas in 0 to 22% of the animals. Squamous cell carcinomas (SCCs) were most frequently encountered in BALB mice of both sexes. The present results indicate that X-ray induction of adenocarcinomas, signet ring cell carcinomas, and SCCs of the glandular stomach in CS mice is not promoted by H2O2 or NaCl.

Hypocatalasemic mice were treated with N-methyl-N-nitrosourea (MNU) in their drinking water or gastric intubation for 16 weeks or were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in their drinking water for 6 months. With MNU treatment in the drinking water, well differentiated tumors were observed in the glandular stomachs of one male (4%) and 5 female (15%) animals. Sarcomas of the dermis also appeared in 10 males (40%). Adrenal lesions developed in I I females (35%) along with kidney, ovary, and uterus tumors. In the Group given MNU intubation, squamous cell carcinomas of the forestomach appeared from 122 days after the first treatment, reaching incidences of 81% in males, 94% in females, with invasion of the diaphragm in 3 male cases and the diaphragm, liver, pancreas, or adrenal in I I female cases. Glandular stomach tumors occurred in 12 males (52%), with 3 being signet ring cell carcinomas, and in 12 females (35%). In a sub-Group undergoing forestomach removal after MNU intubation esophagectasis appeared from 80 days after the operation at incidences of 63% in males and 74% in females. The glandular stomach tumors including 3 signet ring cell carcinomas were found in 17 of 46 (40%) males, 2 of 18 (11%) females demonstrated lesion, one being a signet ring cell carcinoma. In the Group receiving MNNG treatment, anemia appeared from the 5.5 month time point and no gastric tumors were observed. The present results do not support the conclusion that MNU induction of glandular stomach lesions in hypocatalasemic mice may provide a useful model of signet ring cell carcinomas

1980年から1991年の間に切除された全周性大腸癌は107例であり, このうちA群 (イレウスを伴った症例 : 16例), B群 (軽度の閉塞症状を伴った症例 : 37例), C群 (閉塞症状をまったく有しなかった症例 : 54例) に分類し, A群の臨床病理学的特徴および予後に関して他の2群と比較検討した. 年齢, 性別, 肉眼型, リンパ節転移度, 脈管侵襲および組織学的進行度では3群間に有意差は認められなかった. 腫瘍径ではA群はC群に比べ縦径は有意に短く (P

Recently colorectal carcinomas have been increasingly reported, multiple carcinomas of the colon and rectum are not rare, and the hereditary factor seems to be involved in the etiology of such multiple occurrence. Thirty-seven cases of multiple colorectal cancers experienced at the department in a recent 14-year period were clinicopathologically studied. Of these 37 patients, seven patients (15 lesions) had a family history of colorectal cancer within the first degree relatives (positive group) and the remaining 30 patients (65 lesions) had no family history (negative group). Patients in the positive group were younger than those in the negative group. Carcinomas of the positive group were located in more prpximal colon than those of the negative group. Histological examination revealed that most of the first lesions in the positive group were moderately differentiated adenocarcinomas while the second lesions were commonly well differentiated adenocarcinomas. Presence of associated adenomatous polyps was more common in the negative group than in the single carcinomas. The cumulative 5-year survival rate was 62.5% in the positive group and 42.0% in the negative group. All patients in the positive group satisfied the diagnosis criteria of HNPCC (hereditary nonpolyposis colorectal cancer), but the negative group may include initiator of HNPCC.

過去16年間に当科で手術を施行した75歳以上の高齢者大腸癌は60例で,50歳以上70歳未満の対照者群319例,39歳以下の若年者群18例の内,主に単発癌を比較の対象とし臨床的特徴と遠隔成績を検討した.高齢者群は,(1)占拠部位では右側結腸に有意に多かった.(2)壁深達度は,漿膜内にとどまる症例が多く比較的浅い傾向.(3)リンパ節転移陽性率は低い傾向.(4)手術直接死亡例はないが他病死例が多く,他病死を除いたら5年生存率は対照者群と比べて差はなかった.高齢者大腸癌は,壁深達度は浅く,リンパ節転移率も低い傾向にあり,D2もしくはD3の適切なリンパ節郭清にて根治度AまたはBの切除が可能であり,高齢といえども患者の状態の許す限り積極的に対照者群と同様の郭清を伴った根治切除術を心がけるべきである.高齢者では術前より全身状態の悪い症例が多く,合併疾患の術前後の管理を充分に行えば対照者群と同等の成績が期待できる.

The present study was undertaken to determine the response of colon mucosa implanted into the fundus of stomach in 6-week old male F344 rats to oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Samples of colonic tissue about 8 mm in diameter were obtained from various colon sites and surgically implanted into the anterior wall of the fundus by isografting. MNNG was chronically administered at a concentration of 100 mg/l in the drinking water for 16 weeks starting 4 weeks after the operation and the grafted colon mucosa was examined at 12 months after the operation. Control rats received a sham-operation and the same amount of MNNG. In the MNNG administered groups, only one adenoma containing Paneth cells was noted in the implanted colon tissue whereas over 40% incidence of gastric tumors was observed in the pyloric mucosa. In the operated rats not given MNNG no gastric tumors were observed in either the grafted site or the pylorus.

The present study was designed to investigate the modifying effects of dietary exposure to NaCl and four kinds of crude salts on the induction and development of aberrant crypt foci in Fischer 344 rats. A total of 57 male rats were divided into five groups at six weeks of age, and all were given weekly injections of azoxymethane (15 mg/kg body wt s.c.) for three weeks. Group 1 was fed a normal diet throughout the experiment as control group. Groups 2, 3, 4, and 5 were fed diets containing 4.4% pure NaCl, 4.4% cooking salt, 4.4% rock salt, and 4.4% beach salt, respectively, from one week before the first azoxymethane dosing. The mean numbers of aberrant crypt foci and aberrant crypts per colon were significantly lower in Groups 3-5 than in Group 1 (p < 0.01). The present results suggest that the other mineral components (e.g., calcium and magnesium) of these crude salts, rather than pure NaCl, may be chemopreventive agents for colonic tumorigenesis.

Experiments were conducted to determine whether following genetic damage at germ cell stages induced by paternal exposure to 252 Cf fission neutron could lead to tumorigenesis in the offspring. Seven-week-old C3H/HeNCrj male mice were irradiated with 252 Cf fission neutrons, at doses of 0 and 12.5 cGy and were mated with nine-week-old C57BL/6NCrj females two weeks after the exposure. Three weeks later, it was found that the proportion of abnormal sperm in the 12.5 cGy-irradiated males was higher than that of 0 cGy-irradiated group. Embryo lethality among the F 1 offspring was also found to be higher in the 12.5 cGy group than in the 0 cGy group, while the incidence of liver tumors among the F 1 offspring increased in males only. These results suggest that the paternal 12.5 cGy radiation exposure may have caused genetic transmission of liver tumor-associated traits, which is in line with findings that show steep increase in incidence of tumorigenesis in B 6 C 3 F 1 .

The present study was undertaken to determine the effect of azoxymethane (AOM) administration on intestinal metaplasia induced by X-irradiation in male Donryu rats. Five-week-old animals were X-irradiated with two doses of 10 Gy each at a 3-day interval or three X-ray doses of 10 Gy at a 2-day interval and then received AOM injections i.m. at a dose of 15 mg/kg body weight once weekly for 3 weeks, 6 months after irradiation. Alkaline phosphatase positive foci were decreased after AOM treatments, but aberrant crypt like-foci appeared within areas of intestinal metaplasia. In contrast no induction was observed in normal-appearing gastric mucosa.

When intact male C3H or 252Cf neutron irradiated B6C3F1 mice were fed on a diet containing 10% miso for 13 months, the frequency and multiplicity of liver tumors were significantly reduced in both cases. In irradiated females only a tendency for a similar reduction was observed. B6C3F1 male mice i.p. injected once with diethylnitrosamine (DEN) at 15 days of age and exposed to neutrons at four weeks of age also demonstrated a significantly decreased multiplicity of liver tumors when given a diet supplemented with either 10% miso or 20ppm biochanin A (5,7-dihydroxy-4-methoxyisoflavone). In Sprague-Dawley (CD) rats treated with 100ppm N-methyl-N’ nitro-N-nitrosoguanidine (MNNG) for 16 weeks in their drinking water, the net incidence of gastric tumors per mg MNNG intake was reduced with a miso-supplemented diet. In addition, when six-week-old rats were given s.c. injections of azoxymethane (AOM, 15mg/kg body weight) once a week for three weeks, and fed on diets containing 5%, 10%, or 20% miso and 10ppm biochanin A from five weeks of age, the numbers of aberrant crypt foci four weeks after the first administration of AOM were decreased with increasing miso in a dose-dependent manner. The present results indicate that administration of a miso-supplemented diet may inhibit the development of liver and gastric tumors, as well as aberrant crypt foci, in experimental animals.

Inflammatory fibroid polyps (IFPs) are rarely found in the gastrointestinal tract. The majority of IFPs are sessile-pedunculated or pedunculated polypoid lesions, whereas a polyp presenting like a Borrmann type II lesion is extremely unusual. This report describes the case of a 74-year-old man with a history of intussusception, in whom a preoperative diagnosis of a cecal tumor of the ileocecal valve was made. A laparotomy subsequently revealed a lesion similar to a Borrmann type II tumor located 15 cm above the ileocecal valve, but not at the valve. The lesion was diagnosed as an IFP which had been caused by repeated colostomy irrigation. The aim of the present report is to draw attention to this entity, which should be included in the differential diagnosis of intussusception and small bowel obstruction.

A newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) was investigated to determine its suitability for evaluation of enteric bacteria. This compound, PABA-UDCA, was deconjugated by cholylglycine hydrolase to release free PABA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriologic experiments almost all the microorganisms that split glycocholic acid deconjugated PABA-UDCA. In rat experiments urinary excretions of PABA were measured during 6 h after oral administration of 10 mg PABA-UDCA (PABA-UDCA administration test). Ten control rats excreted 338.5 +/- 13.8 micrograms (mean +/- SE) of PABA; 10 rats with intestinal stagnant loop excreted more (673.6 +/- 70.2 micrograms; P less than 0.01); whereas 10 rats in each of 7 groups pretreated with oral administration of various antibiotics excreted less (P less than 0.001; polymixin B + tinidazole, 14.0 +/- 2.5 micrograms; polymixin B, 224.9 +/- 23.5 micrograms; tinidazole, 42.7 +/- 8.6 micrograms; kanamycin, 50.3 +/- 5.8 micrograms; clindamycin, 57.4 +/- 7.4 micrograms; vancomycin, 70.4 +/- 8.5 micrograms; and paromomycin, 160.4 +/- 16.4 micrograms). This result was reflected by the bacterial mean count of feces. In the PABA-UDCA administration test, after 2 months of feeding with different diets, rats with high-fiber diet (n = 10) excreted less PABA in urine (70.9 +/- 15.9 micrograms; P less than 0.001) than rats on a control diet (n = 10) and a high-protein-high-fat diet (n = 10) (288.9 +/- 34.5 micrograms and 386.7 +/- 61.2 micrograms, respectively). Fecal bacteriologic status was consistently altered. In human volunteers 250 mg PABA-UDCA was tested. Amounts of PABA excreted in urine during 6 h after dosing were 21.11 +/- 2.02 mg in controls (n = 5) and 12.20 +/- 1.01 mg in the group treated with polymixin B plus tinidazole (n = 5; P less than 0.01). No adverse effect was observed. These basic studies indicate that this compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms without use of radioisotopes or expensive, special equipment.