Successfully treated case of cervical abscess and mediastinitis due to esophageal perforation after gastrointestinal endoscopy.

Perforations of the esophagus are uncommon complications of flexible gastrointestinal endoscopy. Perforations after endoscopy are likely to occur in the cervical esophagus, where fiber insertion is difficult anatomically. The diagnosis should be made as soon as possible, because mediastinitis and sepsis frequently develop following esophageal perforations. The surgical strategies are dependent on the location of the perforations and the condition of the patients. For a successful outcome, surgery is a preferred treatment for most perforation cases, and non-operative treatment, such as antibiotics, parental nutrition, and no food intake by mouth, should be applied carefully.

Clinicopathologic variables affecting survival of distal colorectal cancer patients with macroscopic invasion into the adjacent organs.

A total of 506 distal colorectal cancer patients were classified into two groups, to clarify the variables affecting survival of the patients with macroscopic invasion into the adjacent organs: 47 cases showed invasion (invasive group) while the other did not show invasion (noninvasive group). Differences between the invasive and noninvasive groups were found in eight variables; female, large tumor size, gross types 3 and 4, moderately or poorly differentiated adenocarcinomas and signet-ring cell or mucinous carcinomas, deep cancer invasion, lymphatic invasion, peritoneal and liver metastases, and curability B-C were found significantly more frequently in the invasive group. The survival curve of the former was significantly (P < 0.05) lower than that of the latter. However, no significant difference was found between the survival curves of the patients with curability A (no residual tumors) in both groups. A multivariate analysis in the invasive groups revealed six variables to be significantly related to a good prognosis including a young age, females, a location above the peritoneal reflection, well differentiated adenocarcinoma, negative lymphatic invasion, and curability A. Surgery with curability A should be performed to improve the survival in distal colorectal cancer patients with macroscopic invasion into the adjacent organs.

Expression of nm23-H1 in colorectal cancer: no association with metastases, histological stage, or survival.

The correlations of nm23-H1 expression in primary cancer lesions with the already confirmed 14 prognostic variables and survival were examined in 52 advanced colorectal cancer patients, because the clinical roles of nm23-H1 expression in the cancer lesions remain controversial. An immunohistochemical expression of nm23-H1 was found in 23 lesions (positive group) but not found in 29 lesions (negative group). No significant difference between the positive and negative groups was found according to 12 clinicopathological variables including vascular invasion, lymph node and liver metastases, and histological stage. The carcinoembryonic antigen levels (21.5+/-33.4 ng/ml) of the draining venous blood and argyrophilic nucleolar organizer regions score (3.35+/-1.36 per nucleus) of the cancer cells in the positive group were not significantly diffeent from those (34.1+/-102.9 ng/ml and 3.32+/-1.00 per nucleus, respectively) in the negative group. In addition, no significant difference was found in the survival curves or the 5-year survival rates of the positive and negative groups. From these results, it may be concluded that the nm23-H1 expression was not associated with the aforementioned prognostic variables and the prognosis of advanced colorectal cancer patients.

Immunohistochemical evaluation of thymidylate synthase in gastric carcinoma using a new polyclonal antibody: the clinical role of thymidylate synthase as a prognostic indicator and its therapeutic usefulness.

BACKGROUND: Before this study was conducted, the clinical and therapeutic significance of immunohistochemical evaluation of thymidylate synthase (TS) in patients with gastric carcinoma had not yet been clarified. METHODS: TS was immunohistochemically evaluated in 134 gastric carcinomas using anti-TS antibody. TS expression, 11 clinicopathologic variables, and survival were studied, and the correlations among them were investigated. RESULTS: The groups with high and low TS levels consisted of 56 and 78 patients, respectively. Granular cytoplasmic staining patterns of tumor cells were produced by immunohistochemical staining of the gastric carcinoma tissues. The grade of TS staining was significantly correlated with three clinicopathologic variables: depth of invasion, peritoneal metastasis, and stage of the carcinoma (P < 0.05). A univariate analysis revealed that the 5-year survival was significantly better for the low TS group than for the high TS group (P < 0.05): 65.2% for the low TS group and 43.2% for the high TS group. The group with high grade TS staining who received chemotherapy because of the advanced stage of their disease had worse prognoses even if they received adjuvant chemotherapy. A multivariate analysis revealed that four variables (peritoneal metastasis, lymphatic invasion, liver metastasis, and TS staining grade) independently contributed to survival (P < 0.05). The hazard ratio for the group with low grade TS staining was 0.464 compared with the group with high grade staining. CONCLUSIONS: The immunohistochemical evaluation of TS using this anti-TS antibody may be clinically and therapeutically useful in determining the prognosis of gastric carcinoma patients.

A predictive value of carcinoembryonic antigen in draining venous blood for colorectal cancer patients with postoperative hematogenous metastases.

Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood and postoperative hematogenous metastases (HM) were examined in 76 advanced (T2-4) colorectal adenocarcinoma patients, to clarify a predictive value of dCEA and the gradient (d-pCEA) between d- and pCEA levels in patients with HM. HM were found in 19 patients (HM group), but not found in 57 patients (non-HM group). The mean value (27.4 ng/ml) of dCEA and positive rates (100 and 89.5%) of d- and d-pCEA levels were significantly higher than those (9.8 ng/ml and 57.9%) of pCEA in the HM group, though no significant difference was found among p-, d-, and d-pCEA values and positive rates in the non-HM group. Significant linear correlations, Y (log dCEA, ng/ml) = -0.039X (month) + 2.016 and Y (log d-pCEA, ng/ml) = -0.039X (month) + 1.823, were found between d- and d-pCEA levels and HM-diagnostic period. These results suggest that colorectal cancer patients with HM are more effectively predicted by the determination of d- and d-pCEA levels than of pCEA levels and that they are patients with positive d- and d-pCEA levels. These patients seem to have a high possibility of early HM.

Isolation of plactins A, B, C and D, novel cyclic pentapeptides that stimulate cellular fibrinolytic activity.

Four novel cyclic pentapeptides, designated plactins A, B, C and D, were isolated by solvent extraction and reverse-phase HPLC from mycelium of a fungal strain F165 that belongs to the order of Agonomycetales. By a combination of chemical and spectroscopic analyses and chemical synthesis, the structures of plactins A, B, C and D were determined to be cyclo(-D-Val-L-Leu-D-alloIle-L-Try-D-Arg-), cyclo(-D-Val-L-Leu-D-Leu-L-Tyr-D-Arg-), cyclo(-D-Val-L-Leu-D-alloIle-L-Phe-D-Arg-) and cyclo(-D-Val-L-Leu-D-Leu-L-Phe-D-Arg-), respectively. Plactins stimulated U937 cell-mediated degradation of 125I-fibrin plates by 50% at a concentration of 7.5 approximately 32 microM.

Potential carcinogenicity of 5,6-dimethoxysterigmatocystin in rats.

The potential carcinogenic activity of 5,6-dimethoxysterigmatocystin (DMSC) was examined by oral administration in rats. In Experiment I, all of eight effective ACI/N rats given DMSC in the diet at a concentration of 50 p.p.m. developed neoplastic nodules of the liver. Five rats developed hepatocellular carcinomas and four rats had hemangioendothelial sarcomas of the liver. Two other rats developed osteosarcomas. In Experiment II, F344 rats were given DMSC by gavage once every 2 weeks at dose of 2 mg/0.15 ml dimethylformamide. Out of 24 effective animals 19 rats developed neoplastic nodules of the liver, and eight rats had hepatocellular carcinomas. Hemangioendothelial sarcoma of the liver was seen in one rat. Two rats developed osteosarcomas in the upper legs. Proliferative fibrous lesions which were considered to be a preneoplastic change of the bone tumors were seen in the thighbones of four rats. Results obtained from these two experiments indicate that DMSC is hepatocarcinogenic, as is sterigmatocystin, and that the compound is probably weakly carcinogenic for the bone.

Immunohistochemical localization of human lung adenocarcinoma-associated antigen with a monoclonal antibody.

The monoclonal antibody, 5C7, reacted immunohistochemically with 62 out of bronchial cells of normal lung tissue, adjacent to neoplastic lesions, were negative for lung adenocarcinoma-associated antigen. Reactions with the antibody were observed in half the cases of squamous cell lung cancer, but were only sporadic. The antibody appears to react with an antigen which is either restricted to malignant cells or is at least greatly amplified in expression by malignant cells compared to normal human tissues. The major value of this monoclonal antibody at present is in classifying lung cancers as either adenocarcinoma or non-adenocarcinoma.

Hepatocarcinogenic activities of hydroxymethyl derivatives of 4-(N,N-dimethylamino)azobenzene in ACI/N rats.

The hepatocarcinogenic potencies of three newly identified hydroxymethyl derivatives of 4-(N,N-dimethylamino)azobenzene [(DAB) CAS: 60-11-7], i.e., 2'-CH2OH-DAB, 3'-CH2OH-DAB, and 4'-CH2OH-DAB, were strictly evaluated in a long-term test (400 days) and compared to the potency of 3'-CH3-DAB. ACI/N rats, known to be less sensitive to azo dye carcinogenesis, were given one of these compounds in their diets for 120 days. The incidence of hepatocellular carcinoma in group 2 (20/20), which was given 3'-CH2OH-DAB, was much higher than that in any of the other groups: group 1 (2'-CH2OH-DAB; 4/19), group 3 (4'-CH2OH-DAB; 1/25), or group 4 (3'-CH3-DAB; 3/24). These data suggest that 3'-CH2OH-DAB is the most potent hepatocarcinogen in the series of azo dyes. Possible reasons for the potency of the chemical are discussed.

Inhibitory effect of reserpine on N-2-fluorenylacetamide-induced hepatocarcinogenesis in rats.

The effect of reserpine on N-2-fluorenylacetamide (FAA)-induced hepatocarcinogenesis was examined in female ACI rats. The incidence of hepatocellular altered foci (number/cm2) in rats of group 1 given FAA (0.02% in diet) and reserpine (subcutaneous injections of 1 microgram/g body weight, once a week) simultaneously for 10 weeks, and fed a basal diet for 17 weeks was significantly smaller than that of group 3 exposed to FAA alone for 10 weeks and given the basal diet for the subsequent 17 weeks (1.51 +/- 0.58 vs. 11.46 +/- 3.13, P less than 0.001). Similarly, the incidence of the foci of group 2 given reserpine for 16 weeks after discontinuation of FAA exposure for 10 weeks and a one-week interval of basal diet, was also significantly smaller than that of group 3 (1.51 +/- 0.62 vs. 11.46 +/- 3.13, P less than 0.001). No hepatocellular foci were seen in rats of group 4 given reserpine alone for 27 weeks and group 5 (untreated controls). These results indicate that reserpine has an inhibitory effect on FAA-initiated hepatocarcinogenesis.

Carcinogenicity of betel quid. III. Enhancement of 4-nitroquinoline-1-oxide- and N-2-fluorenylacetamide-induced carcinogenesis in rats by subsequent administration of betel nut.

The effect of betel nut on chemical carcinogenesis in the upper digestive tract and liver was examined in two different experimental models with ACI rats. The incidences of neoplasms and preneoplastic lesions of the tongue in animals given 5 ppm 4-nitroquinoline-1-oxide (4-NQO; CAS: 56-57-5) in the drinking water for 16 weeks and followed by 20% betel nut in the diet for 40 weeks were significantly higher than those in animals given 4-NQO alone. No enhancing effect from betel nut on the incidences of neoplastic and preneoplastic lesions in the upper digestive tract was found in animals administered 4-NQO for 12 weeks. The number of altered liver cell foci in rats given 200 ppm N-2-fluorenylacetamide (FAA; CAS: 53-96-3) in the diet for 8 weeks and followed by the betel nut diet for 16 weeks was significantly greater than that in animals fed the FAA diet alone. These results indicate enhancing effects of dietary administration of betel nut on oral carcinogenesis by 4-NQO and hepatocarcinogenesis initiated by FAA.

Enhancing effect of cholecystectomy on colon carcinogenesis induced by methylazoxymethanol acetate in hamsters.

The effect of cholecystectomy on colon carcinogenesis induced by methylazoxymethanol (MAM) acetate was examined in four groups of Syrian golden hamsters. For the sexes combined, the incidences of total large intestinal neoplasms and adenomas in Group 1, which received cholecystectomy and a single intravenous injection of MAM acetate (20 mg/kg body weight), were significantly higher than those of hamsters in Group 2, which were given MAM acetate alone. The combined multiplicities of total large intestinal neoplasms from male and female hamsters, and the multiplicities of those in females of Group 1 were also significantly higher than those in animals in Group 2, respectively. No intestinal tumors were observed in hamsters in Group 3 (cholecystectomy alone) or Group 4 (untreated control). These results indicate an enhancing effect of cholecystectomy on MAM acetate-induced large intestinal carcinogenesis in hamsters.

Inhibitory effects of polyprenoic acid (E-5166) on N-2-fluorenylacetamide-initiated hepatocarcinogenesis in rats.

The effects of the newly synthesized polyprenoic acid, 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166) on N-2-fluorenylacetamide (FAA)-initiated hepatocarcinogenesis were examined in 6 groups of male ACI rats. The numbers of altered hepatocellular foci in rats of group 1 given a basal diet containing 0.02% FAA for 13 weeks and in rats of group 2 which received E-5166 by gavage (40 mg/kg, 3 times/week) at the same time as receiving the FAA diet were almost the same, indicating that E-5166 had no effect at the stage of carcinogen exposure. However, the number of foci in group 4, in which rats were given the basal diet and E-5166 after the termination of the carcinogen exposure, and were sacrificed 16 weeks later, was significantly smaller than that in group 3 maintained on the basal diet alone (P less than 0.05). The results suggests some anticarcinogenic activity of E-5166, possibly involving the phenotypic expression of the preneoplastic foci. Furthermore, the number of altered foci in rats of group 6 (given the liver-tumor promoter phenobarbital with E-5166 for 16 weeks after the administration of carcinogen) was also significantly smaller than that in rats of group 5, which received the promoter (P less than 0.05). The incidence of neoplastic nodules of the liver in group 6 at the end of the experiment was also lower than in group 5 (P less than 0.0014). These results suggest an antipromoting effect of the polyprenoic acid E-5166 on rat chemical hepatocarcinogenesis.

Inhibitory effect of chlorogenic acid on methylazoxymethanol acetate-induced carcinogenesis in large intestine and liver of hamsters.

The effect of dietary chlorogenic acid on methylazoxymethanol (MAM) acetate-induced carcinogenesis was examined in Syrian golden hamsters. The combined incidence of total large intestinal tumors from male and female hamsters, and the combined incidence of large intestinal adenocarcinomas or the incidence of the carcinomas of male or female animals of the group given a single intravenous injection of MAM acetate (20 mg/kg body wt) and then fed the diet containing 0.025% chlorogenic acid for 24 weeks were significantly lower than those of hamsters given MAM acetate alone. The numbers of hyperplastic liver cell foci in male and female hamsters given MAM acetate and chlorogenic acid were also significantly smaller than those of hamsters given MAM acetate alone. These results indicate an inhibitory effect of chlorogenic acid on MAM acetate-induced carcinogenesis in hamsters.

Syncarcinogenic effects of methyl methanesulfonate with methylazoxymethanol acetate in rat small intestine and liver.

The carcinogenic potency of methyl methanesulfonate (MMS) and its combination effect with methylazoxymethanol (MAM) acetate were evaluated in rats. MMS was suggested to be weakly carcinogenic for the small intestine. Syncarcinogenic effects of MMS and MAM acetate which could be due to summation of their genotoxic influences were obtained in the small intestine and liver.

Genotoxicity of a variety of mycotoxins in the hepatocyte primary culture/DNA repair test using rat and mouse hepatocytes.

Twenty-eight mycotoxins were studied in the hepatocyte primary culture/DNA repair test using rat and mouse hepatocytes. DNA repair synthesis was elicited by several compounds of unknown carcinogenicity, 5,6- dimethoxysterigmatocystin , versicolorins A and B, averufin , xanthomegnin , luteosporin , and chrysazin , as well as by the carcinogenic myocotoxins , aflatoxin B1, sterigmatocystin, luteoskyrin , ochratoxin A, azaserine, mitomycin C, and actinomycin D. The positive results with compounds of unknown carcinogenicity suggest that they are possibly genotoxic carcinogens. The carcinogenic mycotoxins, penicillic acid, patulin, griseofulvin, and rugulosin , which did not elicit repair synthesis may be nongenotoxic carcinogens.