Circulating p53 antibody in patients with colorectal cancer: relation to clinicopathologic features and survival.

The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I-IIIb/ Dukes classification A-C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.

Prognosis for pedunculated hepatocellular carcinoma.

We retrospectively compared the outcome of 13 patients at our institution and that of 163 reported cases of pedunculated hepatocellular carcinoma (HCC) with that of conventional HCC subdivided by tumor diameter (group A: less than 2 cm; group B: 2-5 cm, group C: more than 5 cm). The survival of patients with pedunculated HCC in the 163 reported cases was no different from that of group B, but less favorable than in group A (p < 0.01) and more favorable than in group C (p < 0.01). Among the 163 patients with pedunculated HCC, the 113 cases of surgically treated patients had higher survival than the 21 patients treated with transcatheter arterial embolization (n = 16) or transcatheter arterial infusion chemotherapy (n = 5) (p < 0.01) and than 29 conservatively treated patients (p < 0.001). A total of 70 patients out of 163 (42%) died within 1 year after diagnosis. Additionally, almost all cases of pedunculated HCC showed histologically moderately or poorly differentiated characteristics according to Edmondson and Stainer's classification or the WHO classification. These results suggest that pedunculated HCC has not a favorable prognosis if appropriate surgical resection has not been performed very early within a few months because of its rapid progressive nature.

Inhibition of hepatocellular carcinoma by glycyrrhizin in diethylnitrosamine-treated mice.

Glycyrrhizin (GL) is widely used in Japan as a therapeutic agent for chronic active liver diseases. However, its action on hepatocarcinogenesis remains to be elucidated. To clarify its effect, mice treated with diethylnitrosamine (NDEA) with or without GL were analyzed. Five-week-old male BALB/c mice were divided into two groups, GL (n=50) and C (n=47). Mice in the GL group intramuscularly received 2 mg of GL 3 days a week, and mice in the C group received the same volume of saline in the same way. After 2 weeks, the mice were treated with an i.p. injection of 75 mg/kg body wt of NDEA weekly for 3 weeks and 100 mg/kg body wt of NDEA weekly for the following 3 weeks. Thirty additional mice that did not receive NDEA treatment were divided into two groups, GC (n=15) and SC (n=15). They received GL or saline, respectively. Mice in the 4 groups were killed every 5 weeks after the last injection of NDEA from 7 weeks to 32 weeks. Liver function tests such as AST and albumin were significantly improved in the GL group compared with the C group (P < 0.05, each). Although liver nodules appeared in the C group at 22 weeks, they were not observed until 32 weeks in the GL group. At 32 weeks, the mean number of liver tumors, composed of adenoma and hepatocellular carcinoma (HCC), in the GL group was 0.71, which was significantly decreased compared with 1.64 of the C group (P < 0.05). The mean number of HCC in the GL group was 0.29/liver, which was lower than 0.82/liver in the C group (P < 0.05). The incidence rate of HCC at 32 weeks was 64% in the C group and 21% in the GL group (P < 0.05, C versus GL group). Our results suggest that GL treatment inhibits the occurrence of HCC.

Mutation in the exon 10 (R173W) of the hydroxymethylbilane synthase gene in two unrelated Japanese families with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an inherited disorder characterized by a deficiency of hydroxymethylbilane synthase (EC 4.3.1.8.; HMBS), the third enzyme in the heme biosynthetic pathway. To date, 113 different HMBS gene mutations have been reported in the world. However, there were a few reports of the gene mutations in the Japanese AIP patients. We studied the gene mutation in two unrelated AIP families in the San-in district, a local area of Western Japan. The overlapping 6 fragments of the HMBS gene, amplified by the reverse transcript-polymerase chain reaction, were analyzed by the single-strand conformation polymorphism with silver staining technique. The abnormal fragment from a member of one family was sequenced to detect the C to T substitution at 517 nucleic acid position of cDNA, which led to a missense mutation of arginine to tryptophan exchange at an amino acid level (R173W). This mutation located in exon 10 created a new site of the MSP 1 restriction endonuclease and was screened by the amplified fragment of exon 10 from genomic DNA with the MSP 1 digestion. The mutation was detected totally in three members of the family and interestingly also in two patients of an unrelated family. This mutation has been reported widely in the world independently, such as in a Swedish, a Canadian, a Finnish, and a French family, but is the first in Japanese patients. The screening method for this mutation is useful for diagnosis in Japanese AIP patients.

Minute hepatocellular carcinoma originating in the caudate lobe with a long-term surviving of 9 years 6 months after surgical resection: a case report.

An extremely rare case of minute hepatocellular carcinoma originating in the caudate lobe who was resected and surviving for 9 years 6 months is presented. A 52 year-old male patient was diagnosed as having a minute hepatocellular carcinoma originating in the caudate lobe by lipiodol computed tomography and celiac angiography. Although the caudate lobectomy was successfully performed, refractory ascites developed for 4 months after surgical procedure. After remission of ascites, the patient is well and surviving for 9 years 6 months without recurrence of hepatocellular carcinoma. This case suggests that early detection and treatment of hepatocellular carcinoma can lead to a long-term survival even when the caudate lobe of the liver is involved.