Preoperative evaluation of local invasion and metastatic lymph nodes of colorectal cancer and mesenteric vascular variations using multidetector-row computed tomography before laparoscopic surgery.

OBJECTIVE: To evaluate local invasion and lymph nodes metastasis of colorectal cancer and mesenteric vascular variations using multidetector-row computed tomography (MDCT) before laparoscopic colorectal surgery. METHODS: Fifty-one patients with colorectal cancer underwent MDCT. The evaluation items were as follows: (1) local invasion; (2) detected lymph nodes evaluated by short-axis diameter, long-axis diameter, short/long axis diameter ratio, and computed tomography (CT) attenuation; and (3) visualization of mesenteric artery and vein by 3-dimensional-CT angiography. RESULTS: First, in the evaluation of local invasion, overall accuracy was 94.1%. Second, the point of 0.8 or greater in short/long-axis diameter ratio was best index for the diagnosis of metastatic lymph nodes. Using this index, the accuracy of the diagnosis per node was 80.5%. Third, 3-dimensional-CT angiography correctly demonstrated variations of the mesenteric artery and vein. CONCLUSIONS: The MDCT was effective for evaluation of local invasion and lymph nodes metastasis of colorectal cancer and mesenteric vascular variations before laparoscopic surgery.

The diagnostic values of measuring the liver volume in detecting occult hepatic metastases from colorectal cancer.

BACKGROUND/AIMS: Some studies have shown the reduction of portal blood flow in patients with occult hepatic metastases, which may lead to a decrease in the liver volume. The aim of this study was to assess volumetric changes of the liver with occult colorectal metastases. METHODOLOGY: Sixty-three consecutive patients with colorectal cancer who underwent curative resection were studied retrospectively. The ratio of the preoperative computerized tomography (CT)-estimated liver volume to the standard liver volume (CV/SV ratio) was calculated as a uniform parameter to compare the volume between the liver with and without occult hepatic metastases. RESULTS: The CT-estimated liver volume was 841 +/- 102 (mean-SD) mL in 8 patients who subsequently developed overt hepatic metastases during a 2-year follow-up and 1145 +/- 232 mL in 55 patients without metastases (p = 0.0004). The CV/SV ratio was significantly smaller in patients with metachronous hepatic metastases than in those without (0.78 +/- 0.09 versus 1.02 +/- 0.14; p < 0.0001). CONCLUSIONS: The results suggest the possibility that the liver with occult colorectal metastases decreases in size before metastatic tumors develop to be detectable with conventional imaging techniques. The measurement of the CV/SV ratio may be of value in detecting occult hepatic metastases from colorectal cancer.

Diagnostic value of measuring liver volume for detecting occult hepatic metastases from colorectal or gastric cancer.

Some studies have shown reduced portal blood flow in patients with occult hepatic metastases, which may lead to decreased liver volume. A retrospective study was conducted in patients undergoing curative resection for colorectal (n = 63) or gastric (n = 52) cancer. The ratio of the preoperative computed tomography (CT)-estimated liver volume to the standard liver volume (CV/SV ratio) was calculated. The mean +/- SD CT-estimated liver volume was 858 +/-109 in 14 patients who subsequently developed hepatic metastases and 1173 +/- 230 ml in 101 patients without metastases (p < 0.0001). The CV/SV ratio was smaller in patients with metachronous hepatic metastases than in those without (0.78 +/- 0.08 vs. 1.02 + 0.13; p < 0.0001). The results suggest that the liver with occult metastases decreases in size before metastases develop that are detectable using conventional imaging techniques. The CV/SV ratio may be of value in detecting occult hepatic metastases from colorectal and gastric cancer.

Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas.

Survivin, a novel member of the inhibitor of apoptosis protein (IAP) family, has been markedly overexpressed in most types of human carcinoma, and recognized as a potential target in anticancer therapy. In addition, two splice variants of survivin, survivin-2B and survivin-deltaEx3, have recently been identified. However, expression analysis on its splice variants has not been reported in colorectal carcinomas. Therefore, we investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and the correlation between transcript expression levels and pathological findings was analyzed. Tumor tissue samples were provided from 52 cases with colorectal adenocarcinoma resected at the Osaka Medical College from 1995 to 1996. Transcription levels were measured by performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) using primer pairs specific for survivin and either of its splice variants, then normalized by the glyceraldehyde 6-phosphate dehydrogenase. The transcription levels of survivin and its splice variants were significantly higher in the tumor tissue samples, and significantly lower in the normal tissue samples. In addition, approximately 40% of the normal tissue samples did not have any survivin expression. The relative expression level of survivin-2B to survivin (survivin-2B/survivin) was significantly higher in the tumor tissue samples than in the normal ones. In contrast, survivin-deltaEx3/survivin revealed no difference between tumor and normal samples. When Comparing the histological disease stages (stage I and II vs. stage III and IV), there were no significant differences in the expression levels of survivin and its splice variants. The expression level of survivin-2B/survivin for stage III and IV was lower than the one for stage I and II. In addition, a higher level of survivin-2B/survivin significantly correlated with a better prognosis in the present series. The present study demonstrates high expression level of survivin and its splice variants, which is relatively specific in tumor tissue and suggests that they have important roles in the progression of human colorectal carcinomas.

Adenoviral infection of survivin antisense sensitizes prostate cancer cells to etoposide in vivo.

BACKGROUND: We aimed to investigate whether use of a survivin antisense fragment carried by an adenovirus vector (Ad.survivin-AS) could enhance the therapeutic efficacy of chemotherapy for androgen-independent prostate cancer. METHODS: We used Ad.survivin-AS to promote apoptosis through inhibition of survivin expression. Recombinant adenoviruses alone or in combination with chemotherapeutic agents were tested for anti-cancer activity both in vitro and in vivo. RESULTS: Infection with Ad.survivin-AS strongly inhibited survivin expression in a dose- and time-dependent manner, resulting in significant antitumor activity in vitro and in vivo. Downregulation of survivin expression potentiated induction of apoptosis by the chemotherapeutic agents docetaxel and etoposide in DU145 cells. In particular, the combination of etoposide and Ad.survivin-AS demonstrated dramatic growth inhibition with no tumor regrowth being observed during the experimental period. CONCLUSIONS: The prominent synergy of this combination may provide a basis for clinical application of Ad.survivin-AS as a chemosensitizer of etoposide.

[Development of a novel gene therapy using survivin antisense expressing adenoviral vectors].

BACKGROUND: Survivin, a novel inhibitor of apoptosis, is undetectable in normal adult tissues but becomes notably expressed in the most common human cancers, and is recognized as a potential target in anticancer therapy. METHODS: In this study we evaluated a survivin antisense expressing replication-incompetent adenoviral vector under the control of the cytomegalovirus promoter (pAd.CMV-SAS) for cytoreductive effects in human HT-29 colon cancer cells in vitro and in vivo. RESULTS: Infection of tumor cells with pAd.CMV-SAS caused down-regulation of survivin expression and the potential for spontaneous apoptosis in tumor cells. In contrast, pAd.CMV-SAS did not affect cell viability of normal human cells including fibroblasts. In addition, infection of tumor cells with pAd.CMV-SAS resulted in an increase of the G0/G1 phase population in the cell cycle, and increased their sensitivity to chemotherapeutic drugs in vitro. The efficacies of pAd.CMV-SAS were inversely correlated with survivin expression level. In nude mice, pAd.CMV-SAS suppressed tumor formation, as well as decreased the tumor volumes to approximately 30% of the control tumors. Furthermore, it was confirmed that the anti-tumor efficacy of pAd.CMV-SAS was also enhanced in combination with chemotherapeutic drugs in vivo. CONCLUSIONS: These findings suggest that targeting of survivin using adenoviral antisense vectors may have a potential role in the selective therapy of colon cancer.

Downregulation of survivin expression by induction of the effector cell protease receptor-1 reduces tumor growth potential and results in an increased sensitivity to anticancer agents in human colon cancer.

Survivin, a novel inhibitor of apoptosis, is expressed in cancer cells and not in normal adult tissues, and is recognised as a potential target in anticancer therapy. The induction of a natural antisense of survivin, effector cell protease receptor-1 (EPR-1), in a human colon cancer cell line resulted in a downregulation of survivin expression, with a similar decrease in cell proliferation, an increase in apoptosis and an increase in the sensitivity to anticancer agents. In addition, subcutaneous (s.c.) tumours from EPR-1 transfectants showed a significant reduction in size compared with parental cells, and this antitumour efficacy was further enhanced in combination with anticancer agents. These findings suggest that regulation of survivin by the induction of EPR-1 cDNA may have significant potential as a therapy for human colon cancer.

Regular finger dilation for preventing anastomotic stenosis after low anterior resection.

PURPOSE: This study evaluated the usefulness of performing regular finger dilation (RFD) of the anastomosis to prevent stenosis after low anterior resection (LAR). METHODS: Defecatory function was assessed in 22 patients who had undergone LAR more than 6 months earlier. The patients were divided into an RFD group, comprising 15 patients who had undergone regular RFD, and a non-RFD group, comprising 7 patients who had dropped out of our follow-up with RFD. The physiological and clinical findings in relation to defecatory function were compared. RESULTS: The type and size of the stapler and anal manometric parameters were similar. The RFD group had significantly better defecatory function in terms of bowel movement and sensation of incomplete evacuation (P < 0.01, respectively) with a significantly wider anastomotic diameter and higher evacuation rate (P < 0.01, respectively). CONCLUSION: These findings demonstrate that RFD is useful for preventing anastomotic stenosis and achieving favorable defecatory function after LAR. Therefore, a prospective randomized study should be scheduled.

New predictor for the defecatory function after sphincter-preserving operation: lumen score.

Few studies on sphincter-preserving surgery have analyzed the colon used for the anastomotic segment. We evaluated the usefulness of measuring the square of the diameter of the sigmoid colon (cm(2)) (lumen score, LS) as a predictor of defecatory function after very low anterior resection (VLAR) for rectal cancer. Measurements were done by radiography with semiliquid barium, and the LS was calculated. A total of 24 patients [straight coloanal reconstruction (VLAR-S), n = 17; colonic J pouch reconstruction (LVAR-J), n = 7] were studied more than 6 months after the operation. VLAR-S was divided by the LS results: the high-LS group had an LS of 12 or more (n = 5), and the low-LS group had an LS of less than 12 (n = 12). The neorectal capacity, anal manometry, and defecatory function were studied. In the VLAR-S group, LS had a significant positive correlation with neorectal capacity (gamma = 0.81, p <0.01) and a negative correlation with bowel frequency (gamma = -0.67, p <0.05). Regarding neorectal capacity, the high-LS group had a significantly larger capacity than the low-LS group (118.0 vs. 88.3 ml; p <0.05). The low-LS group had unfavorable defecatory function compared with that of the high-LS group, which was equal to that of the VLAR-J group. We concluded that the LS is a useful predictor of successful colonic J pouch reconstruction.