Impact of laparoscopic gases on peritoneal microenvironment and essential parameters of cell function.

UNLABELLED: Several experimental studies confirm the hypotheses that laparoscopic gases influence the development of tumor metastases [12, 14, 23]. The mechanism for this alteration of malignant tumor growth is still unknown. One reason might be an influence of the in sufflation gas on essential cell function regulating parameters. To investigate the changes of the intra- and extracellular milieu, four parameters--extra- and intracellular pH, intracellular free calcium levels, and tissue oxygen partial pressure--were measured during insufflation with carbon dioxide (CO2), helium (He), or a nonhypoxic gas mixture consistent of 80% CO2 and 20% O2. STUDY DESIGN: (In vitro experiments) Intracellular calcium and pH levels were measured in DHD/K12/TRb colon adenocarcinoma cells using fluorescence imaging microscopy. (In vivo experiments) Tissue oxygen partial pressure was measured using a flexible micro catheter (Licox CMP) implanted in the abdominal wall of rats. After establishing the pneumoperitoneum an optical system and an aspirator were inserted to control the position of the micro catheter and to aspirate wound exudates for pH measurements of the wound fluid. RESULTS: Creating of pneumoperitoneum with both CO2 and helium caused a decrease in partial pressure of oxygen in the abdominal wall to about 5 mm Hg whereas insufflation with a nonhypoxic gas mixture (80% CO2 and 20% O2) induced no significant changes. The intra- and extra cellular pH values dramatically decreased during CO2 insufflation (7.4 to 6.2) in vitro. Helium caused a pH increase up to 7.6. Free intracellular calcium was enhanced during CO2 insufflation, whereas helium insufflation did not cause any changes in [Ca2+]i. Nevertheless, a significant decrease of [Ca2+]i was observed during reoxygenation following helium-induced hypoxia. CONCLUSION: Our study demonstrates that insufflation with either CO2 or He causes significant changes of intra- and extracellular parameters regulating essential cell functions such as oxidative phosphorylation to produce ATP, cell proliferation, or onset of apoptosis.

Increased rates of pulmonary metastases following sham laparotomy compared to CO2 pneumoperitoneum and the inhibition of metastases utilizing perioperative immunomodulation and a tumor vaccine.

BACKGROUND: Subcutaneous tumor growth and establishment is increased after laparotomy; significantly smaller increases have been noted after CO2pneumoperitoneum (CO2 pneumo). Less is known about the impact of surgery on the fate of blood borne tumor cells. The extent of surgical abdominal wall trauma also correlates with the extent of early postoperative immunosuppression and the inflammatory response. These changes may favor lung metastases (mets) formation. This study's hypotheses were: (a) a reduction in surgical trauma or (b) a perioperative (periop) tumor vaccine or nonspecific immune up-regulation would limit lung mets formation. An intravenous tumor cell injection lung met model was used to test these hypotheses. METHODS: Study 1 determined the incidence of lung mets after sham laparotomy (OP) and CO2 pneumo. Three groups were studied (n=25/group) : Anesthesia control (AC), CO2 pneumo, and OP. 1 x 105 TA3Haushka adenocarcinoma cells were inoculated via tail vein injection into all mice immediately after surgery. Study 2 determined the impact of perioperative immunomodulation on lung mets formation. Five groups were studied (n=20/group) : AC, OP, OP + Monophosphoryl Lipid A (MPLA), OP + lysed tumor cells (LTC), or OP + MPLA + LTC. The vaccine consisted of 5 x 105 lysed TA3Ha tumor cells (LTC) and was given 5 times preop and once postop to the vaccine groups. MPLA, the nontoxic moiety of lipopolysaccharide, was used both as a vaccine adjuvant in the OP + MPLA + LTC group and as a nonspecific perioperative immune up-regulator in the OP + MPLA group. Five periop injections of MPLA were given to the OP + MPLA group. All mice were given tail vein injections of tumor cells after surgery. Fourteen days after surgery all mice were sacrificed, the lungs transected en bloc, and India ink injected into the trachea. The lungs were placed in Fekete's solution to counterstain the tumor foci white. The number of surface lung metastases was determined by two blinded observers, separately. RESULTS: In Study 1, there were significantly more lung tumors in the OP group (median=31.5) than the AC group (median=9; p<0.05) or the CO2 Pneumo group (median=6.5; p<0.05). There were no significant differences in the number of metastases between the AC and the CO2 Pneumo groups or in the incidence of animals in each group with 1 or more lung mets. In Study 2 significantly fewer metastases were noted for the Op + LTC group (median=3; p<0.05) and the OP + LTC + MPLA group (median=0; p<0.05) when compared to the OP group (median=20). Although the OP + MPLA group mice had fewer metastases (median=4) than the OP group, this difference was not significant. Significantly fewer of the OP + LTC + MPLA group mice developed one or more lung tumors than in the OP, OP + MPLA, and the OP + LTC groups. CONCLUSIONS: Full sham laparotomy was associated with more postoperative lung metastases than CO2 pneumo or anesthesia alone in this murine model. Up-regulation of the immune system in the perioperative period with lysed tumor cells, alone or in combination with MPLA, resulted in significantly fewer postoperative lung metastases. MPLA alone resulted in a less marked reduction of lung metastases.

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.

Laparoscopic repositioning of a ventriculo-peritoneal catheter tip for a sterile abdominal cerebrospinal fluid (CSF) pseudocyst.

Abdominal cerebrospinal fluid (CSF) pseudocyst is an uncommon but well-described complication that is reported to occur in <1% of ventriculo-peritoneal (VP) shunts. Management options for pseudocysts include various types of shunt revisions, which recently have been conducted laparoscopically. We report the case of an 11-year-old girl in whom a sterile abdominal CSF pseudocyst was successfully fenestrated and the VP catheter repositioned using laparoscopy. This technique in the setting of a noninfected pseudocyst has proven to be safe, with results comparable to the conventional open technique. However, the long-term success rate is still unknown.

Influence of intraperitoneal and systemic application of taurolidine and taurolidine/heparin during laparoscopy on intraperitoneal and subcutaneous tumour growth in rats.

BACKGROUND: Recent clinical and experimental studies investigated the problem and possible pathomechanisms of portsite metastases after laparoscopic resection of malignant tumours. A generally accepted approach to prevent these tumour implantations does not exist so far. METHODS: After subcutaneous and intraperitoneal injection of 10(4) cells of colon adenocarcinoma (DHD/K12/TRb) the influences of either taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumour growth were investigated in 105 rats undergoing laparoscopy with carbon dioxide. The animals were then randomised into seven groups. A pneumoperitoneum was established using carbon dioxide for 30 min (8 mmHg). Three incisions were used: median for the insufflation needle, and a right and left approach in the lower abdomen for trocars. To investigate the intraperitoneal (local) influence of either taurolidine and heparin on tumour growth the substances were instilled intraperitoneally. Systemic effects were expected when the substances were applied intravenously (iv). Synergistic influences were tested when both application forms were combined. The number and the weight of tumours as well as the incidence of abdominal wall and port-site metastases were determined four weeks after intervention. Blood was taken to evaluate the influences of taurolidine and heparin on systemic immunologic reactions: seven days before laparoscopy. two hours, two days. seven days, and four weeks after operation, and the peripheral lymphocytes were determined. RESULTS: Intraperitoneal (ip) tumour weight in rats receiving taurolidine (median 7 mg) and taurolidine/heparin (0 mg) intraperitoneally was significantly reduced when compared to the control group (52 mg) (P = 0.001). There was no difference of subcutaneus tumour growth among the groups (P = 0.4). Trocar recurrences were decreased when taurolidine was applied ip (3115). ipiv (4/15), and ip in combination with heparin (4/15) in comparison to the control group (10/15). Immediately after intervention treated and untreated groups showed a peripheral lymphopenia. CONCLUSIONS: The intraperitoneal therapy with taurolidine and the combination with heparin inhibits the intraperitoneal tumour growth and trocar recurrences. Neither the intraperitoneal nor the systemic application or the combination of taurolidine and heparin did reduce the subcutaneous tumour growth. The intervention caused a lymphopenia which was compensated on day two.

Influence of different gases and intraperitoneal instillation of antiadherent or cytotoxic agents on peritoneal tumor cell growth and implantation with laparoscopic surgery in a rat model.

BACKGROUND: A generally accepted approach to prevent tumor implantation with laparoscopic surgery does not exist. Alternative gases in combination with intraperitoneal instillation of different antiadherent or cytotoxic agents have not been evaluated. METHODS: The effect of taurolidine, heparin, and povidone-iodine on the growth of colon adenocarcinoma DHD/K12/TRb was measured in rats undergoing laparoscopy with carbon dioxide (n = 40), helium (n = 40), or xenon (n = 40). In the procedure, 10(4) tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 min at 8 mmHg with the different gases. The rats additionally received intraperitoneal instillation with one of the following: 1 ml of Ringer's solution, 1 ml of 0.5% taurolidine, 1 ml 0.5% taurolidine with heparin (10 U/ml), or 1 ml 0.25% of povidone-iodine. Tumor growth was measured after 4 weeks. RESULTS: Median intraperitoneal tumor weight was lower in rats receiving taurolidine (CO(2): 10 mg; helium: 50 mg; xenon: 39.5 mg) or taurolidine with heparin (CO(2): 4 mg; helium: 4.5 mg; xenon: 46.5 mg) in all gas groups than in the control groups (CO(2): 427 mg; helium: 268 mg; xenon: 345 mg) (p < 0.001). Whereas povidone-iodine caused significantly lower tumor growth in the CO(2) group (56.5 mg) (p < 0.01), the combination of helium (145 mg) and xenon (457 mg) with povidone-iodine produced no reduction of tumor growth as compared with the control groups (helium: 268 mg; xenon: 345 mg). CONCLUSIONS: Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum. Only povidone-iodine caused significant decrease of tumor growth in combination with CO(2). The combination of xenon and povidone-iodine should not be used in patients with cancer because of increased tumor growth.