Gastrointestinal transit and stress response after laparoscopic vs conventional distal pancreatectomy in the canine model.

BACKGROUND: Several authors have presented the feasibility of laparoscopic pancreatic surgery. However, the pathophysiological effect of laparoscopic pancreatic surgery is not well known. METHODS: Ten mongrel dogs were randomly operated for laparoscopic and conventional distal pancreatectomy. Fed state gastrointestinal transit times were assessed using radiopaque markers. To assess surgical stress, we determined serum IL-1 and cortisol. RESULTS: Postoperative mouth-to-anus transit time in the laparoscopic group was not prolonged while it was significantly prolonged in the conventional group compared with the baseline study, but no significant differences between groups were detected. First defecation was observed significantly earlier in the laparoscopic group. Serum cortisol levels were elevated significantly at 4 h after skin incision in both groups and decreased thereafter. In the laparoscopic group, they returned close to the normal level at 8 h after incision, but were still significantly higher in the conventional group. The level of IL-1 was elevated significantly higher in conventional group at 24 h after the skin incision. CONCLUSION: Thus, we conclude that laparoscopic distal pancreatectomy demonstrated faster recovery of the bowel transit and less stress than conventional distal pancreatectomy in dogs.

Perfusion to colorectal cancer liver metastases is not uniform and depends on tumor location and feeding vessel.

Future effective therapies for hepatic metastases may depend on a better understanding of perfusion to these tumors. The purpose of this project was to define blood flow to colorectal cancer liver metastases using quantitative autoradiography (QAR). Liver tumors were established in F1 hybrids of WF x BN rats by intrasplenic injection of a DMH-induced rat colon adenocarcinoma. Rats underwent laparotomy 4-5 weeks later and [14C]iodoantipyrine (a radiotracer) was infused via the hepatic artery (HA) or portal vein (PV). Livers were harvested, frozen in liquid nitrogen, and sectioned at 20 microns through all tumors. QAR compared optical density of cross sections of tumors to surrounding normal liver tissue. Tumor:liver perfusion ratios (T/L PR) and tumor center:tumor periphery perfusion ratios (C/P PR) were calculated. All groups were analyzed with regard to tumor location and size. Seventy-seven tumors in 6 rats in the HA infusion group were analyzed; 74 tumors in 8 rats in the PV group were analyzed. Statistical analysis was by repeated measures analysis of variance. Mean HA T/L PR = 0.97 +/- 0.13, mean PV T/L PR = 0.25 +/- 0.11. Mean HA T/L PR for deep tumors was 1.38 +/- 0.17 and for superficial tumors was 0.57 +/- 0.15 (P < 0.01). Mean HA T/L PR for small tumors was 1.09 +/- 0.12 and for large tumors was 0.86 +/- 0.21 (P = 0.27). Mean PV T/L PR for deep tumors was 0.27 +/- 0.14 and for superficial tumors was 0.24 +/- 0.15 (P = 0.71). Mean PV T/L PR for small tumors was 0.31 +/- 0.15 and for large tumors was 0.20 +/- 0.14 (P = 0.54). Mean HA C/P PR = 1.15 +/- 0.15, mean PV C/P PR = 0.81 +/- 0.14 (P = 0.06). Mean HA C/P PR for small tumors was 1.37 +/- 0.16 and for large tumors was 0.92 +/- 0.17 (P = 0.01). Mean PV C/P PR for small tumors was 0.78 +/- 0.18 and for large tumors was 0.72 +/- 0.13 (P = 0.71). HA perfusion of tumors is significantly higher than PV perfusion compared to surrounding normal liver tissue. HA perfusion varies significantly depending on tumor location. There was a trend toward HA perfusion to the tumor center being slightly greater than to the periphery whereas the reverse was seen for PV perfusion. Tumor size did not affect overall perfusion but it did affect regional HA tumor perfusion.

The effect of tamoxifen on established human colorectal cancer cell lines in vitro.

UNLABELLED: The purpose of this study was to evaluate the effect of the anti-estrogenic tamoxifen (Tx) on the growth of human colorectal cancer cells. METHODS: Serial concentrations (0.005 microM, 0.05 microM, 0.5 microM, 5 microM, and 50 microM) of the anti-estrogenic tamoxifen (Tx) were added and analyzed for their effect on the growth of established human colorectal cancer cells. HT-29 and SW-620 colon cancer cells and SW-1463 rectal cancer cells were tested in both serum-free media and serum-containing media (10% fetal calf serum). COLO-205 colon cancer and SW-837 rectal cancer cells were only tested in 10% fetal calf serum-containing media. Cell growth was measured with the hexosaminidase assay and was compared among the different groups. Cells were analyzed for estrogen receptors using enzyme immunoassay. RESULTS: In serum-free media, Tx inhibited the growth of HT-29 (P = .05) and SW-620 (P = .01) colon cancer cells at all concentrations tested. RESULTS: In serum-containing media, Tx inhibited (P = .04) the growth of the SW-837 rectal cancer cells at all concentrations and SW-1463 (P = .05) rectal cancer cells at the concentrations of 0.05 microM and 0.5 microM Tx. The inhibition of cell growth in HT-29, SW-620 and SW-1463 line was greater (P < .001) under serum-free media conditions. Estrogen receptors were not detected in any of the cell lines tested. CONCLUSIONS: Hormonal manipulation with colo-rectal cancers is possible, but the effect of Tx on the growth of colon cancer cells differs from the effect on rectal cancer cells under various conditions. The mechanism of inhibition is not clear yet, and further studies are warranted before any clinical implications can be postulated.

Development of a reliable colorectal cancer liver metastasis model.

UNLABELLED: The liver is the most frequent and most fatal site of distant spread of colorectal cancer. Most current animal models of liver metastases utilize direct liver or intravascular injection (dissimilar to mechanisms of metastasis) or immunosuppression to establish metastases. AIM: The aim of this study was to develop a reliable rat model of liver metastases in immunocompetent hosts, whereby metastases spread hematogenously as in colorectal cancer. METHODS: WB-2054 is a poorly differentiated colon adenocarcinoma induced by 1,2 DMH in a WF x BN F1 hybrid rat. WB-2054-M0, Ml, M2, M3, and M4 are successive metastatic variant cell lines obtained through serial application of the Fidler hypothesis. WF x BN F1 rats were inoculated intrasplenically with 1 x 10(6)(M0) or 5 x 10(6)(M0-M4) cells; the spleen was left intact. Animals were evaluated 4 to 12 weeks postinjection and, if no metastases were found, reexplored 1-2 weeks later. Animals with liver metastases were sacrificed, and full abdominal and thoracic zoopsy was performed. Livers were excised and serially sectioned, to determine size, number, and location of liver metastases, and studied histologically to confirm the nature of the metastases. RESULTS: 44% (4/9), 80% (8/10), 86% (65/76), 94% (34/36), and 100% (65/65) of animals inoculated with the M0, M1, M2, M3, and M4 cell lines, respectively, developed liver metastases. Metastases were uniformly spread throughout all lobes of the livers. CONCLUSION: We have developed an extremely hepatotrophic metastatic colorectal cancer cell line. Intrasplenic injection of WB-2054-M4 cells is a reliable model for producing colorectal cancer liver metastases without the need for immunosuppression and should prove valuable in colorectal liver metastasis experiments.

Surgical anatomy of the celiac artery and portal vein of the rat.

The study of liver function and diseases requires detailed knowledge of the regional anatomy of and surgical approach to the vascular supply of the liver. The objective of this study was to systematically describe the regional anatomy of the circulation to the rat liver to facilitate the planning and performance of future studies of the liver in this animal. Twelve adult rats underwent general anesthesia and vivisection of the celiac axis and portal vein using an operating microscope. The major vessels of these vascular systems were evaluated for their origin, course, relationship with neighboring structures, diameter, and length. All vessels were easily visualized by a ventral approach after mobilization of the intermediate lobe of the liver and its papillary process. The origin and course of the major vessels are similar to those of humans, and variability in vessel origin was identified in this small number of animals. Median vessel diameters were between 0.5 and 1 mm (range, 0.25 to 1 mm) for the celiac artery and its branches, and 3 mm for the portal vein (range, 2 to 3 mm). Median vessel length was between 3 and 7 mm (range, 2 to 8 mm) for the celiac artery and its branches, and 7 mm for the portal vein (range, 4 to 8 mm). The anatomic description obtained in this study is important for the appropriate selection of vessels for cannulation or ligation during study design, as well as vessel isolation during performance of the study. The diameter and length of vessels are important in the selection of appropriately sized catheters and perivascular devices.

The effect of tamoxifen and fenretinimide on human colorectal cancer cell lines in vitro.

BACKGROUND: The natural history of colorectal neoplasia may be influenced by steroid hormones and nutritional compounds. We evaluated the effect of the anti-estrogenic tamoxifen (Tx), and the synthetic retinoid fenretinimide (4-HPR) on the growth of human colorectal cancer cells. METHODS: DLD-1, CACO-2, SW-620, and COLO-205 colon cancer cells, and SW-1463 and SW-837 rectal cancer cells were cultured under serum-free conditions. Quadruplicates wells (4 x 10(4) cells/well) were created for each treated, and untreated groups in each cell line. Cells were treated with 1 microM Tx, 5 microM Tx, 1 microM 4-HPR, 1 microM Tx with 1 microM 4-HPR, and 5 microM Tx with microM 4-HPR. Cell growth was measured colorimetrically with the hexosaminidase assay (405 nm), and was compared among the different groups. Cells were analyzed for estrogen receptors using an enzyme immunoassay. RESULTS: Tamoxifen, 4-HPR, or both, inhibited the growth in DLD-1 (P = .001), COLO-205 (P = .02), SW-620 (P = .001), and CACO-2 (P = .02) cell lines. Tamoxifen with 4-HPR inhibited cell growth more (P = .03) than did either Tx or 4-HPR in DLD-1, COLO-205, and SW620 cancer cells. Tamoxifen, 4-HPR, or both, had no effect on the growth of SW-837 (P = .14) cancer cells. Tamoxifen with 4-HPR promoted (P = .02) growth in SW-1463 cells, but not when added separately. Estrogen receptors were not found in any of the cells. CONCLUSIONS: Under serum-free conditions, Tx, 4-HPR, or both, inhibit the growth of human colon cancer cells but not of rectal cancer cells. Combined treatment with Tx and 4-HPR is more effective than treatment with either of the agents alone in inhibiting of cell growth. The mechanism of inhibition is not clear yet, and further studies are warranted.