Zun-Gon Kim

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

BackgroundCarbon 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.MethodsAn 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).ResultsThe 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%).ConclusionElevated 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.

BackgroundExperimental 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.MethodsTwo 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.ResultsAt 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).ConclusionsCO2 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 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 expo-sed 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.

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

BackgroundRecent 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.MethodsFor 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.ResultsThe 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).ConclusionsDopamine and ET-1 antagonism restore portal blood flow during laparoscopic surgery independantly of the insufflation gas. Whether improved hepatic perfusion might have beneficial effects on liver function needs further investigation.

Hepatic tumor spread of colorectal cancer in a laparoscopic animal model

AbstractBackground: 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 × 104, 5 × 104, 1 × 105, 3 × 105, 5 × 105 cells/ml) of WAG/Rij rats (n= 25). As controls, five animals underwent laparotomy and open intraportal inoculation of 5 × 104 cells/ml. Results: Hepatic tumor growth occurred after inoculation of 5 × 104, 1 × 105, 3 × 105, and 5 × 105 cells/ml. Extrahepatic tumor and conflating hepatic tumor was observed after the inoculation of 1 × 105, 3 × 105, and 5 × 105 cells/ml. Concentrations of 5 × 104 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 × 104 cells/ml. Conclusions: Laparoscopic intraportal tumor cell inoculation is a feasible technique to create hepatic metastases. The inoculation of 5 × 104 CC531 cells leads to reliable cell growth that can be used to investigate the impact of various laparoscopic techniques on tumor spread.

Der Einfluss von Dopamin und Endothelin-1-Rezeptorblockade auf den portalen Blutfluss während der laparoskopischen Chirurgie

During the recent advent of laparoscopic surgery, clinical and experimental studies have revealed adverse hemodynamic effects of the pneumoperitoneum. Laparoscopic insufflation with carbon dioxide is well described to alter splanchnic blood flow. Furthermore, an impaired hepatic macro- and microcirculation has been demonstrated during laparoscopic CO2-insufflation. Exogenous administration of dopamine and endothelin-1 antagonists increases splanchnic perfusion and portal venous blood flow to the liver. Whether dopamine or endothelin-1 antagonists might restore portal blood flow impairment during laparoscopic surgery has not been investigated yet.

Der Einfluss verschiedener laparoskopischer Insufflationsdrücke auf das Wachstum kolorektaler Lebermetastasen

Recent experimental studies have demonstrated increased tumor spread from the portal system to the liver during laparoscopy with CO2 pneumoperitoneum. Elevated intraabdominal pressure (IAP) and circulatory changes in the liver are believed to impair hepatic function and local resistance against tumor take. Whether reduced IAP might have beneficial effects on hepatic resistance against tumor cell growth has not been investigated yet. In total, 38 male WAG rats were randomized into three operative groups to obtain laparoscopy with different IAPs: 0-mmHg “gasless” laparoscopy (n=11), 4-mmHg CO2 laparoscopy (n=13) and 10-mmHg CO2 laparoscopy (n=14). To induct liver metastases 50 000 CC531 tumor cells were injected laparoscopically into the portal vein. Total operating time was 90 min. At 28 days following surgery hepatic tumor growth and total tumor take were evaluated. Hepatic tumor growth and total tumor load were significantly reduced after 0-mmHg “gasless” laparoscopy and 4-mmHg CO2 laparoscopy as compared to 10-mmHg CO2 laparoscopy (p 0.05). Elevated IAP may increase metastatic tumor spread to the liver. Reduced IAP has beneficial effects on the growth of liver metastases from colorectal carcinoma.

Der Einfluss eines experimentellen CO2-Pneumoperitoneums auf die Expression verschiedener tumor-assoziierter Moleküle

Recent clinical and experimental data propose laparoscopic CO2 insufflation to enhance proliferation and metastatic potential of different gastrointestinal cell lines. But the pathophysiological mechanisms for these findings are still unknown. E-cadherin, ICAM-1, ICAM-2 and CD44 are cell surface molecules which are involved in the metastatic process, metastatic invasiveness and tumor behaviour of different tumor cell lines. Therefore, the aim of the current study was to analyze the influence of CO2 exposure on the expression of tumor-associated cell adhesion molecules of different cultured tumor cells. Two colon cancer cell lines, CX-2 (human colon carcinoma) and CC-531 (rat colon carcinoma) were exposed for 60 min to a CO2 environment at 12 mmHg. Control groups were exposed for 60 min to room air. The expression of E-cadherin, ICAM-1, ICAM-2 and CD44 was measured directly 12 h, 24 h, 48 h and 72 h after CO2 exposure by flow cytometry. Data were analyzed using the Wilcoxon-Mann-Whitney U-test. Expression of E-cadherin significantly decreased, while expression of ICAM-1 and CD44 significantly increased after exposure to CO2 insufflation, when compared to room air controls (p < 0.05). The current study demonstrates CO2 exposure to alter the expression of tumor-associated molecules in cultured colorectal cancer cells. Whether decreased E-cadherin expression and increased ICAM-1, ICAM-2 and CD44 expression due to CO2 insufflation might promote the metastatic potential of colorectal malignancies in vivo needs further investigations.

Untersuchung der Lebermetastasierung nach Anlage eines Pneumoperitoneums: CO2 versus Helium

Hintergrund: Der portale Blutflus und die Grose des chirurgischen Traumas beeinflussen Manifestation und Wachstum von Lebermetastasen. Der Einflus des Insufflationsgases bei laparoskopischen Operationen auf das Wachstum von Tumorzellen in der Leber ist bisher unklar. Experimentelle Untersuchungen haben generell einen potentiellen onkologischen Vorteil bei der Verwendung eines Pneumoperitoneums mit Helium gegenuber CO2 gezeigt. In der vorliegenden Studie wird die Inzidenz und das Wachstum von Lebermetastasen nach laparoskopischer intraportaler Injektion von Tumorzellen unter Verwendung eines Pneumoperitoneums mit CO2 bzw. Helium untersucht.

Reduktion des portalen Blutvolumenflusses durch ein Pneumoperitoneum in der Ratte in Abhängigkeit von intraabdominalem Druck und verwandtem Insufflationsgas

Mit erweitertem Anwendungsspektrum und vermehrter Nutzung der laparoskopischen Chirurgie wurde zunehmend klar, das die Anlage eines Pneumoperitoneums erhebliche Auswirkungen auf hamodynamische und respiratorische Funktionen nach sich ziehen kann. Als Insufflationsgas kommt heutzutage uberwiegend Kohlendioxid (CO2) zur Anwendung. Die Absorption von CO2 uber die peritoneale Oberflache fuhrt dabei per se schon zu einer deutlichen Veranderung des Saure-Basen-Haushaltes mit nachfolgenden Veranderungen der pulmonalen und cardiovaskularen Tatigkeit [7]. Die Verwendung von Helium bei der Anlage des Pneumoperitoneums wird deshalb als ernstzunehmende Alternative diskutiert, da so die systemischen Auswirkungen des erhohten Kohlendioaxidpartialdrucks vermieden werden konnten [4, 8]. Auf der anderen Seite scheint jedoch primar der schnelle Anstieg des intraabdominalen Drucks von entscheidender Bedeutung fur die hamodynamischen Veranderungen im Rahmen laparoskopischer Eingriffe zu sein [3,5]. Die Auswirkungen im Splanchnicusgebiet und die daraus resultierenden pathophysiologischen und immunologischen Effekte sind allerdings noch weitgehend unbekannt. Wir haben zu diesem Zweck ein etabliertes Tiermodell an der Ratte [2] weiterentwickelt, um die Veranderungen des portalen Blutvolumenflusses durch ein Pneumoperitoneum in Abhangigkeit von intraabdominalem Druck bei unterschiedlichen Insufflationsgasen (CO2 versus Helium) untersuchen zu konnen.