Highly sensitive diagnostic method for colorectal cancer using the ratio of free DNA fragments in serum.

OBJECTIVES: The correlations of the ratio of long-/short-chain DNA fragments in blood with the existence of cancer and the clinicopathological features of colorectal cancer (CRC) were examined. The potential use of this ratio for diagnostic screening was evaluated. METHODS: DNA concentrations were amplified using Alu247 for long-chain DNA fragments and Alu115 for long- and short-chain DNA fragments. The Alu247/115 ratio was calculated for 60 patients with CRC and 24 healthy volunteers. The correlation of the Alu247/115 ratio with clinicopathological variables and the efficacy of this ratio as a tumor marker were examined. The Alu247/115 ratio cut-off value was set using a receiver operating characteristic (ROC) curve. RESULTS: The Alu247/115 ratio was significantly higher in patients with CRC than in healthy volunteers (P<0.001). The Alu247/115 ratio was also significantly higher in patients with Dukes stage A or B CRC than in healthy volunteers (P=0.034) as well as in patients with Dukes C or D CRC than in those with Dukes A or B CRC (P=0.016). Among patients with CRC, the Alu247/115 ratio was significantly higher in those with than without venous invasion (P=0.031). Using the cut-off value set from the ROC curve, the sensitivity of the Alu247/115 ratio was significantly higher than that of the carcinoembryonic antigen level (P=0.004) or the carbohydrate antigen 19-9 level (P<0.001). CONCLUSION: Our data suggest that the Alu247/115 ratio is a promising tool for highly sensitive and early detection of CRC.

Laparoscopic sigmoidectomy combined with uterus excision for colouterine fistula caused by sigmoid colon diverticulitis: A case report.

A case of colouterine fistula caused by colonic diverticulitis that was successfully treated laparoscopically is presented. A 74-year-old woman visited us with lower abdominal discomfort and vaginal excretion with minor fecal contamination. Mild tenderness was observed in her lower abdomen. Blood examinations revealed elevated white blood cell count and C-reactive protein. Sigmoid colon diverticulitis was revealed on CT, and her condition was diagnosed as colouterine fistula. Hinchey classification was stage I. After 2 weeks of conservative therapy, her symptoms were reduced, and the white blood cell count and C-reactive protein level decreased. However, fecal contaminated vaginal excretion continued. The patient underwent laparoscopic sigmoidectomy combined with uterus excision, and she has been in good health for the 3 years since the operation. Although colouterine fistula is usually treated with open surgery, patients with controlled and well-localized inflammation may be good candidates for a laparoscopic approach.

Gene expression and effects of orally active derivatives of fluoropyrimidine on gastric and colorectal cancer.

The effects of chemotherapy on gastrointestinal cancer are influenced by the chemotherapeutic sensitivity of the cancer cells. Determining the expression of genes related to chemotherapeutic sensitivity has been used as a molecular method. The aim of the study was to clarify the relationships between the expression of genes related to chemotherapeutic sensitivity and the effects of orally active derivatives of fluoropyrimidine on gastric and colorectal cancer. Forty-five patients who underwent adjuvant chemotherapy containing orally active derivatives of fluoropyrimidine after undergoing curative surgery for gastric or colorectal cancer were enrolled. Twenty-four patients had colorectal cancer and 21 patients had gastric cancer. Total RNA was extracted from formalin-fixed, paraffin-embedded specimens of the resected tumors, and the expression of 11 genes was measured using the RT-PCR method. We then analyzed the relationships between the gene expression and the postoperative relapse rate as well as the relationships between clinicopathological factors and postoperative relapse rate. The median observation period of the subjects was 41 months. Twelve out of the 21 gastric cancer patients (57%) and 11 out of the 24 colorectal cancer patients (46%) relapsed. Although the results of a univariate analysis revealed that expression of none of the evaluated genes was related to relapse in the gastric cancer patients, excision repair cross-complementing gene 1 (ERCC1) overexpression was related to the relapse rate in colorectal cancer patients (p=0.023). When 1.295 was set as the cut-off value for ERCC1 overexpression using the receiver operating characteristic (ROC) curve, 67% of patients with ERCC1 overexpression and 25% of patients without ERCC1 overexpression relapsed. The relapse-free survival rate was lower in the group with ERCC1 overexpression than in the group without ERCC1 overexpression (p=0.046). ERCC1 overexpression appears to be a useful predictor of relapse in colorectal cancer patients receiving adjuvant therapy with regimens including orally active derivatives of fluoropyrimidine.

Increase in E-selectin expression in umbilical vein endothelial cells by anticancer drugs and inhibition by cimetidine.

E-selectin is expressed on the surfaces of stimulated vascular endothelial cells and is sometimes involved in cancer cell metastasis. The H2-receptor antagonist cimetidine inhibits the increase in E-selectin expression on vascular endothelial cells that is induced by interleukin-1beta (IL-1beta) and cimetidine. It also inhibits the adhesion of sialyl-Lewis-antigen-positive cancer cells to vascular endothelial cells, ultimately inhibiting hematogenous metastasis. Anticancer drugs are essential to cancer therapy, but whether they can alter the expression of E-selectin in vascular endothelial cells remains unclear. Whether cimetidine inhibits the expression of E-selectin in the same manner in the presence or absence of anticancer drugs also remains unknown. Human umbilical vein endothelial cells were cultured with 5-fluorouracil (5-FU), doxorubicin (DXR), cisplatin (CDDP), or IL-1beta and with or without cimetidine. The expression of E-selectin at the mRNA and protein levels was then determined using quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining, respectively. The E-selectin mRNA level increased in cells exposed to 5-FU, DXR, or CDDP, but the addition of cimetidine had no effect on the E-selectin mRNA level. The expression of E-selectin protein was also significantly higher after the addition of 5-FU, DXR, or CDDP, compared with that of a negative control. However, when cimetidine was added prior to the addition of 5-FU, DXR, or CDDP, the expression of E-selectin was significantly suppressed. Thus, cimetidine significantly inhibited the expression of E-selectin at the protein level without affecting its expression at the mRNA level in cells treated with anticancer drugs. In conclusion, anticancer drugs increased the expression of E-selectin and this increase was inhibited by cimetidine. These findings suggest that the administration of cimetidine during treatment with anticancer drugs might be useful for preventing metastasis.

The ultrasonic trocar provides an easy, sharp, bloodless, and repeatable approach to the abdominal cavity.

Reusable trocars have the advantage of being more cost-effective than disposable trocars. However, the reusable trocar does lose its sharpness on insertion with repetitive insertion. Nonreusable trocars are expensive, but the sharpness of the knife facilitates insertion. Nonreusable trocars have a safety shield system designed to decrease abdominal organ injury, though the potential problem of bleeding from the abdominal wall port site has yet to be resolved. We therefore developed a novel ultrasonic vibrating trocar that does not lose its sharpness even with repetitive insertion. This trocar prevents bleeding by means of an ultrasonic cavitation effect. The ultrasonic vibrating trocar has the advantage of ease of insertion, and the force required for new reusable trocar insertion was only 34% of the force required for insertion of commercially available nonreusable trocars. The force required for multiply used conventional reusable ultrasonic vibrating trocar insertion, ie, 900 insertions, was maintained at less than 46% of the force required by the corresponding nonreusable trocars. Bleeding from the abdominal wall was prevented by an ultrasonic cavitation effect.