Whole-body PET imaging with [18F]fluorodeoxyglucose in management of recurrent colorectal cancer.

HYPOTHESIS: Metabolic imaging by positron emission tomography (PET) using [18F]fluorodeoxyglucose will be more accurate than anatomic imaging by computed tomography (CT) for detection of recurrent colorectal cancer. More accurate staging of recurrent tumor by PET will lead to more appropriate management decisions. DESIGN: Prospective blinded study comparing PET with CT, using histologic diagnosis, serial CT imaging, and clinical follow-up as criterion standards, with a fully blinded, retrospective reinterpretation of PET studies. Changes in diagnosis resulting from PET findings were correlated with subsequent treatment and surgical findings. Potential cost savings resulting from use of PET for preoperative staging were calculated. SETTING: Private practice in an outpatient tertiary referral center. PATIENTS: A group of 155 consecutive patients with imaging for diagnosis or staging of recurrent colorectal cancer. Twenty-one patient (14%) were excluded due to lack of a criterion standard. Computed tomographic scans were available for comparison for 115 patients. RESULTS: Positron emission tomographic scan sensitivity and specificity were 93% and 98%, respectively, compared with 69% and 96% for CT. Ninety-five percent confidence intervals for the differences between the modalities were 16% to 32% for sensitivity and 1% to 5% for specificity. The sensitivity of both modalities varied with anatomic site of recurrence. Positron emission tomographic scans were true positive in 12 (67%) of 18 patients with elevated serum carcinoembryonic antigen levels and negative CT findings. In 23 (29%) of 78 preoperative studies in which CT showed a single site of recurrence, PET showed tumor at additional sites. At surgery, nonresectable, PET-negative tumor was found in 7 (17%) of 42 patients who had PET evidence of localized recurrence only. Potential savings resulting from demonstration of nonresectable tumor by PET were calculated at $3003 per preoperative study. CONCLUSIONS: Positron emission tomography was more sensitive and specific than CT for detection of recurrent colorectal cancer. Preoperative detection of nonresectable tumor by PET may avoid unnecessary surgery, and thereby reduce the cost of patient treatment.

Analysis of restriction enzyme-induced chromosomal aberrations by fluorescence in situ hybridization.

Fluorescence in situ hybridization and Giemsa staining of metaphase chromosomes were used to determine the relative frequencies of symmetric exchange aberrations (translocations) and asymmetric exchange aberrations (rings, dicentrics, and polycentrics) after exposure of human lymphoblastoid cells to restriction enzymes or X-rays. The yield of symmetric exchanges was determined with the use of chromosome-specific probes for human chromosomes 2 or 4, which were hybridized to metaphase chromosomes from cells exposed to the enzymes PvuII, SacI, or XbaI or 3 or 5 Gy of X-rays. The yield of asymmetric exchanges was determined in Giemsa-stained metaphase chromosomes from the same enzyme-treated or irradiated cell population. About 1.5- to 3-fold more symmetric than asymmetric exchanges were induced after restriction enzyme treatment. However, after X-ray treatment the yield of dicentrics relative to the yield of reciprocal translocations was close to the expected 1:1 ratio.

Chromosomal aberration induction in CHO cells by combined exposure to restriction enzymes and X-rays.

The potential interaction between restriction enzyme-induced double-strand breaks (dsb) and X-ray-induced lesions in the formation of chromosomal aberrations was investigated in Chinese hamster ovary cells. Either Alu I, which induces blunt-end dsb, or Sau 3AI, which induces cohesive-end dsb, was electroporated into cells, which were irradiated with 2 Gy of X-rays immediately or 15, 30, 60, 120, or 180 min after electroporation. A significant increase in Alu I-induced chromosomal aberrations was observed when cells were irradiated with 0, 15, 30, or 60 min after enzyme exposure, but only additive effects were found when cells were irradiated 120 or 180 min after enzyme exposure. In one of three experiments, cells exposed to Sau 3AI showed a large increase in aberrations when X-irradiated 0 or 15 min after Sau 3AI exposure, and no increase at any time-points thereafter. These results indicate that restriction enzyme-induced dsb can interact with X-ray-induced lesions, resulting in a synergistic increase in chromosomal aberration formation. Furthermore, this interaction depends on both the type of dsb and the time between enzyme and X-ray exposure.

Induction of chromosome damage by restriction enzymes during mitosis.

Once electroporated into the nucleus of eukaryotic cells, restriction enzymes will bind at specific DNA sequences and cleave DNA to make double-strand breaks. These induced breaks can lead to chromosome aberrations and consequently offer one approach to determining the mechanism(s) of aberration formation. Because the higher-order structure of DNA in eukaryotic cells might influence the ability of restriction enzymes to locate their recognition sequence, bind, and cleave DNA, we have investigated whether enzymes will cut DNA during metaphase when the chromosomes are most condensed. Chinese hamster ovary cells synchronized in mitosis and treated with either AluI or Sau3AI showed few chromosome aberrations when held in mitosis for 1, 2, or 3 h after enzyme treatment. However, some disruption of chromosome morphology was seen, especially after exposure to Sau3AI. When cells were allowed to complete one cell cycle after enzyme treatment in the preceding mitosis, there was extensive chromosome damage, with the most abundant type of lesion being the interstitial deletion. It appears that restriction enzymes will cleave the highly condensed DNA in mitotic cells but that decondensation, DNA replication, and recondensation are required before the aberrations are manifested.