Evaluation of whole-body cancer screening using 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography: a preliminary report.

OBJECTIVE: (18)F-2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) is a promising screening modality targeting whole body. However, the validity of PET cancer screening remains to be assessed. Even the screening accuracy for whole-body screening using FDG-PET has not been evaluated. In this study, we investigated the screening accuracy of PET cancer screening. METHODS: A total of 2911 asymptomatic participants (1629 men and 1282 women, mean age 59.79 years) underwent both FDG-PET and other thorough examinations for multiple organs (gastrofiberscopy, total colonofiberscopy or barium enema, low-dose thin section computed tomography and sputum cytology, abdominal ultrasonography, an assay of prostate-specific antigen, mammography, mammary ultrasonography, Pap smear for the uterine cervix, and magnetic resonance imaging for the endometrium and ovaries) between February 2004 and January 2005, and followed sufficiently. The detection rate, sensitivity, specificity, and positive predictive value of FDG-PET were calculated using cancer data obtained from all examinations along with a 1 year follow-up. RESULTS: From among 2911 participants FDG-PET found 28 cancers, 129 cancers were PET negative. PET-positive cancers comprised seven colorectal cancers, four lung cancers, four thyroid cancers, three breast cancers, two gastric cancers, two prostate cancers, two small intestinal sarcomas (gastrointestinal stromal tumors), one malignant lymphoma, one head and neck malignancy (nasopharyngeal carcinoid tumor), one thymoma, and one hepatocellular carcinoma. PET-negative cancers included 22 gastric cancers and 20 prostate cancers that were essentially difficult to detect using FDG-PET. The overall detection rate, sensitivity, specificity, and positive predictive value were estimated to be 0.96%, 17.83%, 95.15%, and 11.20%, respectively. CONCLUSIONS: FDG-PET can detect a variety of cancers at an early stage as part of a whole-body screening modality. The detection rate of PET cancer screening was higher than that of other screening modalities, which had already shown evidence of efficacy. However, the sensitivity of PET cancer screening was lower than that of other thorough examinations performed at our institute. FDG-PET has some limitations, and cancer screening using only FDG-PET is likely to miss some cancers.

A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer.

BACKGROUND: There have been few randomized controlled clinical trials until now to determine the effectiveness of adjuvant treatments for pancreatic cancer, and the results reported so far are inconsistent. METHODS: Patients with invasive ductal pancreatic cancer who underwent radical surgery with clear histological margins at 11 Japanese institutions were enrolled and randomly assigned to one of two groups: surgery-alone group (no further treatment after surgery) and the surgery + chemotherapy group [two courses of postoperative adjuvant systemic chemotherapy with cisplatin (80 mg/m(2), Day 1) and 5-fluorouracil (500 mg/m(2)/day, Days 1-5)]. Patients with a positive resectional margin or with resected distant metastases were excluded from the trial in order to minimize the influence of residual cancer. RESULTS: Between 1992 and 2000, 89 patients were randomized into the two arms of the trial (45 patients to the surgery + chemotherapy arm and 44 patients to the surgery-alone arm). Four patients in total were found to be ineligible (three in the surgery + chemotherapy group and one in the surgery-alone group). The baseline characteristics were comparable between the two groups. In the surgery + chemotherapy group, four patients did not receive the adjuvant treatment because of patient refusal. Toxicity was minor and acceptable among the eligible patients in the surgery + chemotherapy group. The estimated 5-year survival rates were 26.4% in the surgery + chemotherapy group and 14.9% in the surgery-alone group, and the median duration of survival was 12.5 months and 15.8 months, respectively. The recurrence rates at 5 years were 73.6 and 80.8%, respectively, in the surgery + chemotherapy and the surgery-alone groups. The differences in the survival and recurrence rates between the two groups were not statistically significant. CONCLUSIONS: Postoperative adjuvant chemotherapy using cisplatin and 5-fluorouracil was safe and well tolerated; however, no clear survival benefit could be demonstrated.

[Prostate cancer. Introduction].

Basic, epidemiological and clinical issues to be solved on prostate cancer were discussed as a preface. Sharp increase of prostate cancer incidence in Asian countries, almost constant level of latent cancer are intriguing epidemiological and pathological issues. Treatment of locally advanced prostate cancer, hormone-refractory prostate cancer has been a long-standing clinical challenge. New radiotherapy is expected for further advancement. Heterogeneity, clonility, multiplicity of prostate cancer are interesting pathological challenges.

Promotion of carcinogenesis and oxidative stress by dietary cholesterol in rat prostate.

The association between prostate cancer risk and dietary fat consumption is well documented and explained partly by accelerated lipid peroxidation. We explored the possible effects of high dietary cholesterol on carcinogenesis and oxidative stress in the prostate of ACI/Seg rats. The rats develop prostate cancer spontaneously late in the life, providing an appropriate model to explore prolonged dietary conditions. Two groups of 20-week-old male rats, 28 each, were fed either a basal diet or a basal diet supplemented with 1% cholesterol (high cholesterol diet), and killed at 100 weeks of age. Rats on the high cholesterol diet developed adenocarcinoma in the ventral prostate more frequently (26 versus 4%, P = 0.023). In the repeat study, 26 rats each were treated similarly and killed at 80 weeks for histology and oxidative stress assay. Oxidative stress was assessed by measuring the plasma and intra-prostatic levels of vitamin E, vitamin C, uric acid and the oxidized and reduced forms of coenzyme Q(9). The relative amount of oxidized form of coenzyme Q(9) is a sensitive marker of oxidative stress. Rats on the high cholesterol diet demonstrated a higher incidence of atypical prostatic hyperplasia (24 versus 4%, P = 0.049). Also, the prostate showed a 2-fold increase (203% of the control) in the relative amounts of the oxidized form of coenzyme Q(9) and reciprocal reduction of vitamin C (9.5% of the control) and uric acid (46% of the control) levels (P < 0.01), with a minimal change in vitamin E. The plasma levels of these compounds were not affected by dietary conditions. These results indicated that long-term feeding of a 1% cholesterol diet promoted carcinogenesis and tissue oxidative stress in rat prostate. The role of dietary fat and oxidative stress in prostate carcinogenesis needs further investigation.

The effect of 5-year vitamin C supplementation on serum pepsinogen level and Helicobacter pylori infection.

We conducted a population-based, double-blind, randomized controlled trial to examine the effect of vitamin C supplementation on serum pepsinogen (PG) level, Helicobacter pylori (H. pylori ) infection, and cytotoxin-associated gene A (Cag A) status. Subjects aged 40 to 69 years living in one village in Akita prefecture, a high-risk area for gastric cancer in Japan, were recruited through annual health check-up programs. Among 635 subjects diagnosed as having chronic gastritis on the basis of serum PG levels, after excluding ineligible cases, 439 subjects were assigned to one of four groups using a 2 x 2 factorial design (0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C). However, based on the results from two beta-carotene trials in the United States, we discontinued beta-carotene (vitamin C supplementation was continued). Finally, 120 subjects in the low-dose group (vitamin C 50 mg), and 124 subjects in the high-dose group (vitamin C 500 mg) completed the 5-year supplementation. The difference in the change of PGI/II ratio between baseline and after 5-year follow up was statistically significant between the intervention groups among those who completed the supplementation: - 0.25 for the low-dose group and - 0.13 for the high-dose group (P = 0.046). To conclude, vitamin C supplementation may protect against progression of gastric mucosal atrophy.

No inhibition of urinary bladder carcinogenesis in rats with intravesical instillation of alpha-galactosylceramide.

The immunostimulatory a-galactosylceramide, KRN 7000 ((2S,3S,4R)-1-O-(a-D-galactopyranosyl)-2-(N-hexacosnoylamino)-1,3,4-octadecatrienol), may be anticipated to have antitumor activity in vivo apart from any direct toxicity to cancer cells. In this experiment, inhibition of rat bladder carcinogenesis by intravesically instillated KRN7000 was investigated. Male Fischer 344 rats, 6-weeks-old at the start, were divided into 4 groups, all first receiving the carcinogen, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine, in their drinking water for 12 weeks. Then groups 1 and 2 respectively were administered 500 and 50 mg/kg of KRN7000 intravesically once weekly for 17 weeks. Group 3 similarly received only 0.3 micro/l of saline (vehicle control). Group 4 did not undergo bladder catheterization. On macroscopic examination at 30 weeks, multiplicities and sizes of bladder tumors in the KRN 7000 high and low-dose groups were not significantly different from those of the vehicle control group. Histologic examination confirmed no significant variation in incidences of carcinomas or preneoplastic lesions in the bladder among groups 1 to 4. Thus the results indicate that intravesical instillation of KRN7000 does not inhibit bladder carcinogenesis in rats.