Influence of different gases used for laparoscopy (helium, carbon dioxide, room air, and xenon) on tumor volume, histomorphology, and leukocyte-tumor-endothelium interaction in intravital microscopy.

BACKGROUND: Previous studies indicate that helium pneumoperitoneum used for laparoscopic surgery suppresses whereas carbon dioxide pneumoperitoneum increases postoperative tumor growth. The pathomechanisms of decreased tumor growth by helium are unknown. This study was designed to examine the effect of the gases helium, carbon dioxide (CO(2)), and air, and xenon, which can be used to induce pneumoperitoneum in laparoscopy on tumor volume, histomorphology, and leukocyte-endothelium interaction measured by intravital microscopy in rats with implanted liver malignoma (Morris hepatoma 3924A). METHODS: In 46 rats, Morris hepatoma 3294A cells were implanted intrahepatically. After implantation, rats were randomized into two main groups. In the first main group, 10 animals were prepared for examination of leukocyte-endothelium interaction by intravital video microscopy and were randomized into two groups. Five days after implantation they underwent laparoscopy using either helium (n = 5) or CO(2) (n = 5). Ten days after implantation the rats underwent intravital video microscopy to assess leukocyte-endothelium interaction in the tumor and liver vessels. In the second main group 36 rats were prepared for examination of tumor volume arid histomorphology. They were randomized into five groups. Five days after implantation they underwent laparoscopy using helium (n = 7), carbon dioxide (n = 7), room air (n = 7), or xenon (n = 8). The control group (n = 7) received anesthesia only. Rats were killed 10 days after tumor implantation to assess tumor volume and histomorphology. RESULTS: Compared to the control group or groups that received CO(2), room air, or xenon for pneumoperitoneum, the establishment of helium pneumoperitoneum caused a significantly smaller tumor volume (Kruskal-Wallis test, p = 0.001; median tumor-volume: control group, 44 mm(3); helium 19 mm(3)). There was no significant difference in histomorphology between the groups. There was only a statistically significant difference in the development of central tumor necrosis in accordance to tumor volume (Mann-Whitney test, p = 0.03). In the tumor samples, roller counts were statistically significantly higher in the helium group compared to the CO(2) group (p = 0.04). For sticker counts, no statistically significant effects due to liver/tumor (p = 0.13) or treatment (p = 0.48) were observed. CONCLUSIONS: There was a significant decrease in tumor volume using helium pneumoperitoneum for laparoscopy compared to the other gases. Here, we demonstrate that suppression of tumor growth is not due to variation of histomorphology. It seems that helium pneumoperitoneum effects a higher leukocyte-endothelium interaction and thereby a higher immune activation. This could be one explanation for the statistically significantly smaller tumor volume after laparoscopy with helium compared to laparoscopy with CO(2).

Influence of different gases used for laparoscopy (helium, carbon dioxide, room air, xenon) on tumor volume, proliferation, and apoptosis.

BACKGROUND: Previous reports suggest that helium pneumoperitoneum used for laparoscopic surgery suppresses postoperative tumor growth. The present study was designed to determine the effects of gases used in laparoscopy on tumor volume, proliferation, and apoptosis in rats with implanted malignoma. METHODS: In 36 rats Morris hepatoma 3294A cells were implanted intrahepatically. Then, after 5 days, they underwent laparoscopy using helium ( n = 7), CO(2) ( n = 7), room air ( n = 7), or xenon ( n = 8). One group received anesthesia only ( n = 7). Rats were killed 10 days after implantation to assess tumor volume, proliferation, and apoptosis. RESULTS: Helium pneumoperitoneum caused a significant smaller tumor volume compared to other groups (Kruskal-Wallis test: p = 0.001; median tumor volume: control: 44 mm3; helium: 19 mm3). There was no significant difference in tumor cell proliferation (PCNA) and apoptosis (TUNEL reaction) between the groups. CONCLUSIONS: There was a significant decrease of tumor volume using helium pneumoperitoneum compared to the other gases, but no decreased tumor cell proliferation or increased tumor cell apoptosis.

Helium pneumoperitoneum reduces tumor recurrence after curative laparoscopic liver resection in rats in a tumor-bearing small animal model.

BACKGROUND: After exposure of neoplastic tissue to helium, a significant reduction of tumor growth has been detected in experimental studies, both in vitro and in vivo. This tumor-suppressive effect of helium is controversly discussed in the literature. It was therefore the aim of this study to investigate the influence of pneumoperitoneum with CO2, room air, or helium in a tumor-bearing small animal model comparing laparoscopic partial hepatic resection for hepatocellular carcinoma with conventional open partial hepatectomy. METHODS: One-hundred forty-eight male American Cancer Institute rats underwent partial hepatectomy for curative resection of previously induced hepatocellular carcinoma (Morris hepatoma 3924A). Resection was performed either in open laparotomy (n = 30) or laparoscopically under the employment of CO2 (n = 30), room air (n = 30), or helium (n = 30) for the pneumoperitoneum. Twenty-eight animals served as controls receiving anesthesia but no tumor resection. All animals were sacrificed on postoperative days 21, 35, or 56 for autopsy and evaluation of possible tumor recurrence and metastasis. RESULTS: Significant reduction of postoperative tumor recurrence and metastasis was observed in the group of animals receiving laparoscopic tumor resection under helium insufflation compared to open surgery or laparoscopic resection with air pneumoperitoneum. CONCLUSIONS: The results of this study suggest a suppressive effect of helium pneumoperitoneum on postoperative tumor growth and metastatic spread. Furthermore, tumor exposure to room air appears to have a stimulative influence on tumor recurrence and metastasis compared to a pneumoperitoneum established with CO2.

Comparison of laparoscopic versus conventional technique in colonic and liver resection in a tumor-bearing small animal model.

BACKGROUND: Laparoscopic procedures in oncological surgery are either done in curative or palliative intent. We present two experiments comparing laparoscopic to conventional surgery in the curative and palliative setting regarding short-term (stress and immune alteration) and long-term aspects (survival time and recurrence rate). METHODS: We established two syngenic tumor-bearing small animal models for curative liver resection (Morris hepatoma 3924A, ACI rats) and palliative colon resection (BSp73 ASML, BOX rats). Male rats were operated on, performing laparoscopic and conventional liver resection as well as laparoscopic and conventional colon resection; control groups (anesthesia) were included. The following parameters of the stress and immune system were measured: corticosterone, neopterine, Il-1-b, Il-6, and body weight as a parameter of postoperative recovery. Analyzed long-term parameters were survival time, tumor weight, and recurrence rate (histology). RESULTS: After colon resection, analysis of variance showed significant differences in all short-term parameters, including body weight after laparoscopic versus conventional colon resection (p <0.05). In the case of laparoscopic versus conventional liver resection, only Il-6 showed globally statistically significant differences for the short-term parameters (p = 0.05). Long-term parameters were not significantly different between the laparoscopic and conventional groups, regardless of the type of resection (colon or liver) or the operative setting (curative or palliative). However, there were differences after curative liver resection compared to the control group (anesthesia alone). CONCLUSION: These results suggest that the type of intraabdominal operation (colon or liver) may influence the degree of trauma of an operation more than the type of technique (laparoscopic or open). The perioperative alteration of stress and immune function has no implications on the long-term results, such as survival time or recurrence, neither in the curative nor in the palliative setting. The thesis that laparoscopic surgery results in less pain, which in turn means less stress and less alteration of the immune system and therefore results in a lower rate of postoperative metastasis is only valid for laparoscopic colonic resection in our model. The part of the thesis that states that fewer metastases should occur after laparoscopic oncological surgery cannot be confirmed in our study.

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 liver surgery in the rat: description of a new technique.

BACKGROUND: We devised a safe and simple method of liver resection with a wire loop in a small animal model. Herein the method is evaluated and combined with a tumor model for further immunological, oncological, and laparoscopic research. METHODS: With the aid of a wire loop and an adapted electric generator, a liver lobe resection can be performed through three trocars (first trocar: camera; second and third trocars: instruments). This operative procedure was evaluated in 10 rats (group 1). In a second group of ACI rats, a Morris hepatoma (1 mm(3)) was induced. After 11 days, a liver lobe resection was performed. One week after the resection an autopsy and a histological examination were performed in all animals. RESULTS: Ten ACI rats underwent laparoscopic liver resection to evaluate the operative technique with the wire loop (group 1). All rats returned to normal feeding and activity on the 1st postoperative day. There were no deaths. At autopsy, the resection area was inconspicuous, without any sign of hematoma or bilioma. In the second group, 10 days after tumor induction, the induced hepatoma was increased (1 cm(3)) and localized in the left liver lobe. In all rats, the liver lobe was resected without touching or laceration of the tumor. At autopsy, the resection area was inconspicuous. No tumors were found in the histological workup of liver and lungs. CONCLUSION: This model of laparoscopic liver resection in the rat allows a safe and simple liver lobectomy, including a total tumor resection. It should also facilitate basic oncological, immunological, and laparoscopic research.

Hypoglycemic effects of insulin-like growth factor-1 in experimental uremia: can concomitant growth hormone administration prevent this effect?

The risk of hypoglycemia limits the clinical application of insulin-like growth factor-1 (IGF-1). Our studies aimed to evaluate the mode of occurrence as well as the prevention of this side effect. Acute administration (i.v. infusion) of IGF-1 in subtotal nephrectomized uremic (U), sham-operated ad libitum fed control (C) and sham-operated pair-fed control (P) rats led to hypoglycemia, though more expressed in P. Serum glucose levels decreased within 60 min after the IGF-1 administration by 40% in U, by 45% in C and by 52% in P (p < 0.05, U vs. P). Chronic administration (7 days) of 1, 4 and 8 mg/kg/day IGF-1 in U rats led to hypoglycemia in an increasing manner as the dose of IGF-1 increased. On the first day, 2 h after injection, serum glucose levels were 116.5 +/- 8.6, 110.4 +/- 12.4, 60,3 +/- 19.2 and 50.6 +/- 18.3 mg/dl, respectively (p < 0. 01). One week later, IGF-1 therapy proved to be less hypoglycemic in all the groups. On day 7, 2 h after injection the serum glucose levels were 118.9 +/- 23.8, 89.0 +/- 23.9 and 66.0 +/- 32.0, respectively (in comparison to day 1 for 4 and 8 mg/kg/day IGF-1 p < 0.05). The combined effect of 4 mg/kg/day IGF-1 and 10 IU/kg/day growth hormone (GH) was also studied in U and P animals. Two hours after the first injections of IGF-1 serum glucose levels decreased in U from 120.0 +/- 11.3 to 49.2 +/- 21.6 mg/dl, while IGF-1 plus GH decreased the glucose level from 122.0 +/- 15.5 to 81.3 +/- 24.7 mg/dl (p < 0.05 IGF-1 vs. IGF-1 + GH). The hypoglycemic effect of IGF-1 was less expressed by long-term treatment and simultaneous administration of GH overcame the glucose-lowering effect of IGF-1 (serum glucose levels on day 11 one hour after the injections: 73.7 +/- 15.3 mg/dl with IGF-1, and 111.0 +/- 7.8 mg/dl with IGF-1 + GH). Methylprednisolone (MP) did not significantly alter the former effects of IGF-1 and GH. In summary, IGF-1 leads to hypoglycemia in control and uremic rats in a dose-dependent manner. This effect becomes less expressed after prolonged administration. GH attenuates the hypoglycemic effect of IGF-1. This suggests that the combined GH and IGF-1 treatment is more effective and less dangerous in correcting uremic growth failure.