M. Lorenz

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.

Right hemihepatectomy for bile duct injury following laparoscopic cholecystectomy

Laparoscopic cholecystectomy (LC) has become the treatment of choice for patients with symptomatic cholecystolithiasis. But with the introduction of this technique, the incidence of bile duct injuries has increased. We report the case of a 33-year-old man who was transferred from an affiliated hospital to our department for the treatment of a bile duct injury 2 weeks after LC. Prior to transfer, a laparotomy had been performed, with insertion of a T-tube and a Robinson drain on day 5 after LC. Endoscopic retrograde cholangiography (ERC) on admission day revealed an extensive defect of the right biliary system, which could not be treated endoscopically. An emergency laparotomy had to be performed at night for acute bleeding from the portal vein. Due to massive inflammation in the porta hepatis and intraparenchymal destruction of the right bile duct, liver resection was performed 2 days later, after the patient had stabilized in the intensive care unit (ICU). The patient had a prolonged postoperative course, but he finally recovered well from these operations. In conclusion, the management of bile duct injuries should include ultrasound to detect and drain fluid collections and ERC to classify the injury. Emergency laparotomy should never be performed without these examinations, since the majority of bile duct injuries can be treated endoscopically. Surgery for this serious complication should always be performed at specialized centers for hepatobiliary surgery.

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.

Multimodales Therapiekonzept mit forciertem Kostaufbau und verkürzter Krankenhausverweildauer bei Kolonresektion: Erste Ergebnisse

Einleitung:Die klassische Form der fruhen postoperativen Ernahrung nach Koloneingriffen ist die Gabe spezieller Nahrstofflosungen uber einen zentralen oder peripheren Venenkatheter, gefolgt von einem schrittweise langsamen Kostaufbau nach einigen Tagen. Grundlage dieser uberlegung ist es, durch den verzogerten enteralen Nahrungsaufbau die Darmanastomose zu schutzen und bei eingeschrankter postoperativer Magen- und Darmmotorik eventuellen Passagestorungen entgegenzuwirken. In der vorliegenden Arbeit wird ein multimodales Therapiekonzept nach elektiven Kolonresektionen im Rahmen einer prospektiv, randomisierten Studie vorgestellt, dass es den Patienten ermoglicht bereits am ersten postoperativen Tag leichte orale Kost zu sich zu nehmen und ggf. am zweiten postoperativen Tag das Krankenhaus zu verlassen. Material und Methode:10 Patienten wurden im Rahmen einer prospektiv randomisierten Studie fur das multimodale Konzept ausgelost und gebeten bereits zwei Tage vor der Operation jeweils zu den Mahlzeiten eine proteinreiche Trinklosung zu sich zu nehmen. Unmittelbar praoperativ wurde den Patienten durch einen Anasthesisten ein Periduralkatheter (PDK) auf die Hohe Th 8 - 12 gelegt. Am Abend der Operation sollten die Patienten maximal 1500 ml Flussigkeit und zwei proteinreiche Getranke zu sich nehmen und wurden, wenn moglich, fur eine kurze Gehstrecke mobilisiert. Am ersten postoperativen Tag erhielten die Patienten bereits leichte Kost plus 4 Proteingetranke bei gleicher Trinkmenge und wurden bereits vier mal aus dem Bett fur einen langere Gehstrecke mobilisiert. Am zweiten postoperativen wurde die Trinkmenge auf 2000 ml erhoht. Bei Schmerz- und Beschwerdefreiheit, guter Mobilisation und ausreichender hauslicher Versorgung konnten die Patienten sechs Stunden nach Entfernung des PDK’s bereits das Krankenhaus verlassen. Entlassungsfahigkeit wurde mit komplikationslosen Verlauf, eingesetzter Peristaltik/Stuhlgang, Vertraglichkeit der oralen Kost und selbststandiges Laufen fur ca. 120m definiert. Ergebnisse:Der Altersdurchschnitt betrug 65,8 Jahre (Karnofsky Index 90%, ASA II). Darmgerausche und Stuhlgang setzte bei allen Patienten spatestens am ersten postoperativen Tag ein. 5 Patienten konnten am zweiten postoperativen Tag bereits eine Gehstrecke von > 250 m zurucklegen, nur 2 Patienten wurden zu diesem Zeitpunkt nur kurz auf dem Gang mobilisiert. Die durchschnittliche Krankenhausverweildauer betrug 6 Tage. Bei Entlassung waren alle Patienten in der Lage eine Gehstrecke von mindestens 100 m zuruckzulegen und Treppen zu steigen. 5 Patienten hatten bereits am ersten postoperativen Tag keine Schmerzen mehr und nur 3 Patienten klagten uber gelegentliche, leichte Schmerzen. 2 Patienten hatten nur bei bestimmten Bewegungen leichte Schmerzen. Der PDK lag durchschnittlich 2,8 Tage. 9 Patienten waren eine Woche nach der Operation zu Hause vollstandig mobil und in das tagliche Leben integriert, eine Patientin bedurfte noch hauslicher Pflege. 9 Patienten berichteten retrospektiv von guten bis sehr guten Erfahrungen, lediglich eine Patientin auserte sich zufrieden stellend. 3 Patienten klagten postoperativ uber einen Wundinfekt, der im Laufe der ambulanten Weiterbetreuung vollkommen rucklaufig war. 2 Patienten erhielten im Rahmen der stationaren Therapie parenteral Flussigkeit. Diskussion:Das vorgestellte multimodale Therapiekonzept nach elektiven Dickdarmoperationen hat sich bei der postoperativen Behandlung bewahrt, da alle Patienten fruhzeitig mobilisiert und kostaufge baut werden konnten. Auch waren die Patienten uber den gesamten Verlauf fast schmerzfrei und die Krankenhausverweildauer betrug lediglich 6 Tage. Die hohe Rate an Wundinfektionen (30%) ist wahrscheinlich auf die hoheobilitat der Patienten zuruckzufuhren und sollte Gegenstand zukunftiger uberlegungen bei der Wundbehandlung sein. Allerdings waren die Wundinfekte nicht sehr ausgepragt und unter konservativer Therapie vollkommen rucklaufig, was auch die hohe Akzeptanz (90%) unter Beweis stellt.

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.

Management der kontinuierlichen ambulanten Chemotherapie

Bei kolorektalen Karzinomen oder Magenkarzinomen konnte eine Verbesserung der Uberlebenszeit und der Lebensqualitat durch eine 24-Stunden-5FU-Therapie nachgewiesen werden. Zum Erhalt der Lebensqualitat und aufgrund der Wirtschaftlichkeit ist es notwendig, das diese kontinuierliche Therapie ambulant durchgefuhrt wird. Das Management der Therapie umfast folgende Schritte:1. Ambulante Portimplantation; 2. Wundkontrolle am ersten postoperativen Tag; 3. Anstechen des Ports; 4. Pumpenfullung und -management; 5. Chemotherapie. Eine 24-Stunden-5FU-Therapie wurde zunachst bei 32 Patienten nach Tumorprogression unter einer vorherigen 5FU-Therapie durchgefuhrt. Hier zeigte sich bei 11 von 32 Patienten eine Ruckbildung und bei 9 von 32 Patienten kein weiteres Wachstum. 269 der 580 Applikationen waren ohne Nebenwirkungen. Hamatologische Nebenwirkungen traten in keinem Fall auf. Nur in 2 von fast 600 Zyklen wurde eine lebensbedrohliche Diarrhoe beobachtet.