The impact of carbon dioxide and helium insufflation on experimental liver metastases, macrophages, and cell adhesion molecules.

BACKGROUND: Laparoscopic insufflation, proposed to reduce hepatic perfusion, may enhance hepatic tumor spread. It is unknown whether intraabdominal pressure or the gas itself influences hepatic tumor growth. In contrast to carbon dioxide, the alternative gas helium is believed to reduce malignant cell growth. METHODS: For this study, 36 WAG/Rij rats were randomized in two experimental groups. The animals were laparoscopically insufflated with carbon dioxide ( n = 19) or helium gas ( n = 17). Liver metastases were induced by laparoscopic injection of 50,000 CC531 cells into the portal vein. Macroscopic and microscopic analyses of CC531 tumor cell growth, macrophages, and CD44v5, v6 were performed. Data were analyzed by Kruskal-Wallis, Dunn, and Holm tests. RESULTS: No significant differences in macroscopic and microscopic analyses were found between carbon dioxide and helium gas insufflations ( p > 0.05). CONCLUSIONS: Recent studies have shown that insufflation with carbon dioxide may result in increased hepatic tumor growth. The current study comparing carbon dioxide and helium insufflations could show for the first time either oncologic nor immunologic differences in relation to the liver between two different gases. In conclusion, elevated intraabdominal pressure during gas insufflation is responsible for hepatic disadvantages during pneumoperitoneum, not carbon dioxide gas itself.

Impact of laparoscopic CO2-insufflation on tumor-associated molecules in cultured colorectal cancer cells.

BACKGROUND: Laparoscopic CO2-insufflation is believed to stimulate proliferation and metastatic potential of gastrointestinal carcinomas. E-cadherin, I-CAM1, I-CAM2, and CD44 are involved into the metastatic process of different cancer cell lines. The current study investigates the influence of CO2-insufflation on the expression of E-cadherin, I-CAM1, I-CAM2, and CD44 in vitro. METHODS: CX-2 and CC531 colon carcinoma cells (human/rat) were exposed to pneumoperitoneal CO2-insufflation. E-cadherin, I-CAM1, I-CAM2, and CD44 were measured 0, 12, 24, 48, and 72 h after CO2-insufflation using flowcytometry. Control groups were exposed to room air. Data were analyzed by the Wilcoxon-Mann-Whitney U-test. RESULTS: Both cell lines showed significant alteration in E-cadherin, I-CAM1, and CD44 expression after CO2 exposure (p <0.05). No significant differences were found regarding I-CAM2 expression. CONCLUSION: The present study demonstrates CO2-insufflation to influence the expression of E-cadherin, I-CAM1 and CD44. Whether these changes increases the metastatic potential of colorectal cancer cells in vivo needs further investigation.

Early experiences of robotic surgery in children.

BACKGROUND: Laparoscopic surgery using a robotic system (Da Vinci) was recently introduced into surgical practice for adult patients. To investigate the feasibility of this system in pediatric surgery, laparoscopic fundoplication (Thal and Nissen), cholecystectomy, and bilateral salpingo-oophorectomy were performed. METHODS: Eleven children with a mean age of 12 years (range, 7-16 years) underwent either laparoscopic anterior partial fundoplication (Thal, n = 8) or Nissen fundoplication (n = 3) for correction of gastroesophageal reflux disease in the presence of uncontrolled symptoms of regurgitation and pulmonary infection. Two children underwent laparoscopic cholecystectomy due to symptomatic cholecystolithiasis. One child underwent bilateral salpingo-oophorectomy due to a gonadoblastoma. RESULTS: Mean operating time for fundoplication was 146 min (range, 105-180 min), the operating times for cholecystectomy were 150 and 105 min, and that for salpingo-oophorectomy was 95 min. No complications were registered during either the robotic procedures or the postoperative courses. CONCLUSIONS: Compared to conventional laparoscopy, the three-dimensional high-quality vision, advanced instrument movement, and improved ergonomic position of the surgeon appear to enhance surgical precision. Robotic surgery in children using the Da Vinci system seems to be feasible and safe. However, the technique is limited due to the fact that instruments adapted to the size of small children are not available. Furthermore, the high costs and prolonged system setup are disadvantages.

Impact of dopamine and endothelin-1 antagonism on portal venous blood flow during laparoscopic surgery.

BACKGROUND: Recent data indicate that pneumoperitoneal carbondioxide (CO2) insufflation impairs hepatic macro- and microcirculation. Whether dopamine and endothelin-1 (ET-1) antagonists might restore liver blood during laparoscopic surgery has not yet been investigated. METHODS: For this study, 30 male WAG/Rij rats were randomized into two groups to obtain pneumoperitoneum with CO2 (n=15) or helium (n = 15). All the animals were implanted with a polyethylene-50 cannula into the right vena jugularis and a Doppler ultrasound flow probe around the portal vein. In each group, the rats were administered dopamine (n = 5); JKC-10, JKC-301, which is a selective endothelin-1 (ET-1) antagonist (n = 5), or sodium chloride as a control (n = 5). Portal blood flow was measured during intraabdominal pressures 2 to 12 mmHg. Data were analyzed using the Kruskal-Wallis h-test. RESULTS: The application of dopamine and ET-1 antagonists significantly improved portal blood flow over that of the control animals (p <0.05). No significant differences were found between CO2 and helium insufflation (P > 0.05). CONCLUSIONS: Dopamine and ET-1 antagonism restore portal blood flow during laparoscopic surgery independently of the insufflation gas. Whether improved hepatic perfusion might have beneficial effects on liver function needs further investigation.

Oncologic implications of laparoscopic and open surgery.

Although instrumental manipulation and mechanical tumor cell spillage seem to play the major role in port-site metastases from laparoscopic cancer surgery, minimally invasive procedures are used more and more in the resection of malignancies. However, port-site metastases also have been reported after resection of colon cancer in International Union Against Cancer (UICC) stage I [2, 14]. Therefore, changes in the peritoneal environment during laparoscopy also might influence intra- and extraperitoneal tumor growth during laparoscopy and pneumoperitoneum. Different results of experimental studies presented at the Third International Conference for Laparoscopic Surgery are analyzed and discussed.

Influence of laparoscopy and laparotomy on systemic and peritoneal T lymphocytes in a rat model.

Little is known about the local influence of pneumoperitoneum on components of the peritoneal immune defense mechanisms. We investigated CD25, CD4, CD8 expression and CD4/CD8 ratio of systemic and peritoneal T lymphocytes in a rat model. Fifty male Sprague Dawley rats underwent laparotomy, CO2 pneumoperitoneum, helium pneumoperitoneum, gasless laparoscopy, or anesthesia only. After 24 h venous blood was drawn, and peritoneal lavage was performed to harvest CD25+, CD4+, and CD8+ cells. CD4+, CD8+, and CD25+ T lymphocytes were determined. A significantly lower peritoneal CD4/CD8 ratio was found after CO2 and helium laparoscopy than in controls (P<0.05). However, no significant differences in systemic CD4/CD8 ratio or peritoneal or systemic CD25 expression were found between the different operative groups. Pneumoperitomeum independently of the insufflation gas (CO2 or helium) leads to comparable postoperative immunmodulations of peritoneal CD4+ and CD8+ T-lymphocytes. The mechanical pressure of the pneumoperitoneum seems to aggravate peritoneal T lymphocytes.

Effect of insufflation gas and intraabdominal pressure on portal venous flow during pneumoperitoneum in the rat.

BACKGROUND: Carbon dioxide, the primary gas used to establish a pneumoperitoneum, causes numerous systemic effects related to cardiovascular function and acid-base balance. Therefore, the use of other gases, such as helium, has been proposed. Furthermore, the pneumoperitoneum itself, with the concomitant elevation of intraabdominal pressure, causes local and systemic effects that have been only partly elucidated. Portal blood flow, which plays an important role in hepatic function and cell-conveyed immune response, is one of the affected parameters. METHODS: An established animal model (rat) of laparoscopic surgery was extended by implanting a periportal flow probe. Hemodynamics in the portal vein were then measured by transit-time ultrasonic flowmetry during increasing intraabdominal pressure (2-12 mmHg) caused by gas insufflation (carbon dioxide vs helium). RESULTS: The installation of the pneumoperitoneum with increasing intraperitoneal pressure led to a significant linear decrease in portal venous flow for both carbon dioxide and helium. At higher pressure levels (8-12 mmHg), portal blood flow was significantly lower (1.5-2.5-fold) during carbon dioxide pneumoperitoneum. An intraabdominal pressure of 8 mmHg caused a decrease to 38.2% of the initial flow (helium, 59.7%); whereas at 12 mmHg, portal flow was decreased to 16% (helium, 40.5%). CONCLUSION: Elevated intraabdominal pressure generated by the pneumoperitoneum results in a reduction of portal venous flow. This effect is significantly stronger during carbon dioxide insufflation. Portal flow reduction may compromise hepatic function and cell-conveyed immune response during laparoscopic surgery.

CO2 environment influences the growth of cultured human cancer cells dependent on insufflation pressure.

BACKGROUND: Experimental and clinical studies, have suggested that the CO2 pneumoperitoneum influences the development of intraabdominal tumor dissemination and port site metastases. Previous experiments performed both in vitro and in vivo have proved that CO2 insufflation stimulates malignant cell growth. Therefore, we designed a study to investigate the influence of CO2 insufflation administered at different pressures on the growth of cultured human tumor cells. METHODS: Two human tumor cell lines (CX-2 colon adenocarcinoma, DAN-G pancreas adenocarcinoma) were exposed to a CO2 environment maintained at different pressures (0 mmHg, 6 mmHg, 12 mmHg). Tumor growth was determined at different times after exposure to CO2 using fluorescence photometry. Cytotoxity of the CO2 environment different pressures was investigated using flow cytometry. RESULTS: At 1-4 days after exposure to CO2 insufflation, CX-2 and DAN-G tumor cell growth was decreased significantly (p < 0.01). Proliferation of pancreatic adenocarcinoma DAN-G increased significantly from day 5 to day 15 independent of the insufflation pressure (p < 0.01). Proliferation of colon adenocarcinoma CX-2 increased significantly from day 5 to day 15 but was found to be dependent on the insufflation pressure. CX-2 growth increased significantly with higher pressures (p < 0.05). CONCLUSION: CO2 insufflation influences the growth of cultured human tumor cells. After a short period of suppression, the CO2 environment stimulates malignant cell growth. The insufflation pressure may also have additional effects in promoting tumor growth.

Impact of laparoscopic surgery on experimental hepatic metastases.

BACKGROUND: Metastatic disease to the liver is one of the major factors determining outcome after colonic resection with curative intention. The influence of laparoscopic surgery on metastatic disease in the liver is still largely unknown. METHODS: An intrasplenic tumour cell inoculation was performed in 30 WAG-Rij rats. After 7 days the rats were randomized into three operative groups: laparotomy (n = 10), laparoscopy with 7 mmHg carbon dioxide pneumoperitoneum (n = 10) and gasless laparoscopy (n = 10). A small bowel segmental resection was carried out in all rats. Some 21 days later the rats were evaluated for number and diameter of tumour nodules and cancer index score at eight different abdominal sites. RESULTS: Hepatic tumour growth scored with the cancer index was significantly reduced in the gasless laparoscopy group compared with that in the carbon dioxide laparoscopy group (P = 0.04) and the laparotomy group (P = 0.02). Tumour growth at the port site and total tumour load were significantly reduced in the gasless group compared with the laparotomy group (P < or = 0.04). CONCLUSION: Laparoscopy with carbon dioxide insufflation seems to stimulate the growth of dormant tumour cells into overt liver metastases. Gasless laparoscopy on the other hand may have a protective effect against metastatic disease in the liver. The promoting and inhibiting effects of laparoscopic procedures on growth of liver metastases need further evaluation.

Hepatic tumor spread of colorectal cancer in a laparoscopic animal model.

BACKGROUND: We devised a standardized animal model to study the impact of laparoscopic colorectal surgery on intrahepatic tumor cell growth. METHODS: The technique of laparoscopic surgery in the rat was extended by endoscopic inoculation of colon cancer cells (CC531) into the portal vein (1 x 10(4), 5 x 10(4), 1 x 10(5), 3 x 10(5), 5 x 10(5) cells/ml) of WAG/Rij rats (n = 25). As controls, five animals underwent laparotomy and open intraportal inoculation of 5 x 10(4) cells/ml. RESULTS: Hepatic tumor growth occurred after inoculation of 5 x 10(4), 1 x 10(5), 3 x 10(5), and 5 x 10(5) cells/ml. Extrahepatic tumor and conflating hepatic tumor was observed after the inoculation of 1 x 10(5), 3 x 10(5), and 5 x 10(5) cells/ml. Concentrations of 5 x 10(4) cells/ml injected either laparoscopically or via an open technique led to single hepatic tumor nodules. No tumor growth was seen after inoculation of 1 x 10(4) cells/ml. CONCLUSIONS: Laparoscopic intraportal tumor cell inoculation is a feasible technique to create hepatic metastases. The inoculation of 5 x 10(4) CC531 cells leads to reliable cell growth that can be used to investigate the impact of various laparoscopic techniques on tumor spread.

Carbon dioxide pneumoperitoneum is associated with increased liver metastases in a rat model.

BACKGROUND: In patients with primary colorectal cancer, liver metastases are the most important indicators of prognosis and survival; the effect of laparoscopic surgery on the development of hepatic tumor spread is still largely unknown. METHODS: Thirty WAG/Rij rats were randomly divided into 3 operative groups for intraportal tumor cell inoculation: carbon dioxide pneumoperitoneum (group I, n = 10), gasless laparoscopy (group II, n = 10) and open laparotomy (group III, n = 10). The total operating time was 90 minutes with tumor cell injection (50,000 CC531 colon carcinoma cells/mL) performed 45 minutes after the start of the procedure. Hepatic tumor growth and the total tumor load were evaluated 28 days after surgery. RESULTS: Hepatic tumor growth and total tumor load were significantly reduced in the gasless laparoscopy group (group II) as compared with the carbon dioxide pneumoperitoneum group (group I) and the open laparotomy group (group III) (P < .05). No significant difference was found between the carbon dioxide and the open laparotomy groups. CONCLUSIONS: Insufflation of carbon dioxide may actually stimulate metastatic disease of the liver. Gasless laparoscopy seems to preserve hepatic resistance against tumor growth.

Impact of laparoscopic colonic resection on tumour growth and spread in an experimental model.

BACKGROUND: The influence of surgical manipulation and carbon dioxide pneumoperitoneum on intraperitoneal tumour growth and port-site metastasis during laparoscopic colon resection is still unknown. METHODS: Some 33 male WAG/Rij rats were randomized into three experimental groups: a laparoscopy group with carbon dioxide pneumoperitoneum (n = 11), a gasless laparoscopy group (n = 11) and a laparotomy group (n = 11). After transanal injection of a tumour cell suspension (1 x 106 CC 531 cells) into the distal colon, a colon segment resection and an end-to-end anastomosis (laparoscopy; intra-abdominal technique) were performed. Tumour growth was scored semiquantitatively 24 days after the operation. Data were analysed by the Kruskal-Wallis test. RESULTS: The tumour indices from the four locations with the greatest tumour growth were significantly decreased in the laparoscopy group with carbon dioxide pneumoperitoneum compared with the gasless laparoscopy and laparotomy groups (P < 0.01). Port-site metastases were significantly decreased in the carbon dioxide pneumoperitoneum group compared with the gasless laparoscopy group (P = 0.05). CONCLUSION: A full laparotomy incision promotes greater tumour growth than does carbon dioxide pneumoperitoneum. Surgical manipulation stimulates local tumour spread more than the establishment of a carbon dioxide pneumoperitoneum.