A serum-soluble factor(s) stimulates tumor growth following laparotomy in a murine modelrid=""id=""Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), San Antonio, TX, 26 March 1999

Background: Our laboratory and others have previously demonstrated that tumors grow larger and are more easily established following laparotomy than after CO₂ pneumoperitoneum. The etiology of increased tumor growth after surgery is unknown. We hypothesized that, following laparotomy, a serum soluble factor(s) is generated that causes tumors to proliferate more rapidly. The purpose of the current study was to determine if in vitro tumor cells proliferate faster when incubated with serum from laparotomized mice than cells incubated with sera from mice who have undergone CO₂ pneumoperitoneum or anesthesia alone. Methods: In the first experiment, female Balb/C mice (n= 84) were randomly divided into the following three groups: (a) control (AC), (b) CO₂ insufflation (INS), and (c) laparotomy (OPEN). The AC mice underwent no procedure. The INS group underwent CO₂ pneumoperitoneum at 4–6 mmHg for 20 min. The OPEN group had a midline incision from xiphoid to pubis. The serum of seven mice from each group were collected on postoperative days (POD) 1, 2, 4, and 7 via a cardiac puncture. The sera at each time point for each group were pooled. Twenty thousand C-26 colon cancer cells were incubated separately in growth media containing 10% mouse serum from each group (seven determinations/group) at each time point. In the second experiment, female Balb/C (n= 30) mice were divided into AC and OPEN groups. On POD4, sera were collected and pooled. Three separate studies were performed for the second experiment. In the first study, tumor cells were incubated with 10% AC sera or varying concentrations of OPEN mice sera (4–10%). In the second study, aliquots of sera from the OPEN group mice were then heated at 100°C for 1 or 5 min. Tumors were then incubated separately in media with 10% AC, OPEN, or heated OPEN group sera. In the third study, aliquots of sera from the OPEN group mice were dialyzed against PBS through a 3.5-kD or an 8-kD dialysis membrane tubing for 24 h. Tumors were then incubated separately in media with 10% AC, OPEN, or dialyzed OPEN group sera. For both experiments, tumor proliferation was determined and compared between groups after 72 h of incubation. Results: Tumor cells incubated with POD2 and POD4 sera from OPEN group mice proliferated twice as fast as those incubated with sera from either AC or INS group mice. The difference in proliferation was maximal on POD4 and started to decline by POD7. Proliferative activity from the OPEN group sera decreased significantly when heated for 1 min and was completely ablated after 5 min of heating. Proliferative activity from the OPEN group sera was completely ablated after dialysis. Conclusions: We conclude that there is a serum-soluble factor(s) present postoperatively that stimulates tumors to grow significantly faster after laparotomy. The mitogenic effect of laparotomized mice sera is dilutable. It is uncertain whether the factor is heat labile, since heating most likely destroys other necessary proteins in the sera. The size of the factor is undeterminable using the dialysis method. Further efforts to identify these factors are currently underway. Received: 8 February 1999/Accepted: 23 June 1999/Online publication: 24 March 2000     

Effects of laparoscopic vs laparotomy treatment of E. coli peritonitis on hemodynamic responses in a porcine model

Background: Laparoscopic surgery is being used now for increasingly diverse clinical applications, including diagnosis and treatment of appendicitis and bacterial peritonitis. However, some concerns and controversies exist regarding the effectiveness of laparoscopic irrigation of the abdominal cavity compared with that achieved during laparotomy. Of no less importance is concern that establishing a CO₂ pneumoperitoneum in patients with cardiopulmonary insufficiency or endotoxemic shock may compromise hemodynamic function. The objective of this randomized, controlled study was to determine the effects of laparoscopic versus laparotomy intervention on hemodynamic and outcome measurements using a porcine model of Escherichia coli peritonitis. Methods: For this study, 24 specific pathogen-free Hanford pigs underwent surgical placement of carotid, Swan-Ganz, and peritoneal catheters. After a 24-h recovery period, one subset of pigs (n= 12) received a bolus infusion of 9 × 10⁸ CFU/kg E. coli intraperitoneally (septic) and intravenous fluid resuscitation. The remaining 12 pigs were not challenged with E. coli (control). Twenty-four hours later, all 24 pigs underwent either laparoscopic or open peritoneal irrigation with saline, then were reevaluated 48 h after surgical intervention. Standard cardiopulmonary, hematologic, and bacteriologic assessments were obtained both perioperatively and 48 h after surgical intervention. Results: Pigs given E. coli exhibited significantly elevated heart rates and core temperatures and decreased O₂ saturation during the initial 6 h. Within 24 h, these pigs exhibited respiratory alkalosis, altered blood leukocyte profiles, and E. coli–infected peritoneal fluid. Random blood samples from the septic pigs tested negative for E. coli. Mean pulmonary artery and capillary wedge pressures were lower (p < 0.05) in septic than in control pigs before and after surgical intervention. Septic pigs that underwent laparoscopy had significantly lower (p < 0.05) arterial pH and higher arterial pCO₂ levels than septic pigs after laparotomy. Other cardiopulmonary responses were similar irrespective of the surgical modality used. One of six septic pigs from each surgical group still had E. coli growth in its peritoneal fluid 48 h after surgical intervention. Conclusion: Laparoscopic intervention demonstrated effectiveness equal to that of laparotomy for treating acute E. coli peritonitis in pigs without septic shock. Received: 26 June 1998/Accepted: 12 January 1999     

Laparoscopic management of acute small-bowel obstruction

Background: A retrospective review is given of the authors' experience with a consecutive series of acute small-bowel obstruction unresponsive to medical management. Methods: There were 33 exploratory laparoscopies. The etiology was accurately diagnosed in 100% of the cases. Twenty-five (76%) were secondary to postoperative adhesions, of which 18 (72%) were successfully treated by laparoscopic lysis of adhesions. Minilaparotomy was needed to treat iatrogenic perforation (two), gangrenous bowel (one), and Meckel's diverticulectomy (one). Formal laparotomy was utilized for small-bowel resection (two), malignant adhesions (two), and intolerance of pneumoperitoneum (one). Four cases of incarcerated hernias were treated by conventional herniorrhaphy. Results: Overall, 67% of our cases were spared formal laparotomy. Conclusion: We conclude that laparoscopy is an excellent diagnostic modality in acute small-bowel obstruction, the majority of which can be simultaneously managed laparoscopically. Laparotomy should be reserved for malignant adhesions, surgical misadventure, or when the pathology dictates. Received: 4 March 1996/Accepted: 13 May 1996     

Laparoscopic splenectomy using a wall-lifting procedure

A laparoscopic splenectomy using a hanger wall-lifting procedure is herein described. The patient is placed in the right lateral position. The left lower chest and left abdominal wall are then lifted by three wires in two directions, left laterally and vertical to the abdominal wall. The view of the operative field thus obtained is excellent. The lifting wires and bars do not hinder the movement of the forceps, since the angles of the instruments to approach the spleen are different from those of the wires. A laparoscopic splenectomy using this wall-lifting procedure avoids the usual complications associated with pneumoperitoneum while still being technically comparable to a procedure with pneumoperitoneum. Received: 7 October 1998/Accepted: 22 February 1999     

The clinical impact of warmed insufflation carbon dioxide gas for laparoscopic cholecystectomy

Background: Reports suggest that the insufflation of cold gas to produce a pneumoperitoneum for laparoscopic surgery can lead to an intraoperative decrease in core body temperature and increased postoperative pain. Methods: In a randomized controlled trial with 20 patients undergoing laparoscopic cholecystectomy, the effect of insufflation using carbon dioxide gas warmed to 37°C (group W) was compared with insufflation using room-temperature cold (21°C) gas (group C). Intraoperative body core and intra-abdominal temperatures were determined at the beginning and end of surgery. Postoperative pain intensity was evaluated using a visual analog scale and recording the consumption of analgesics. Results: There were no significant group-specific differences during the operation, neither in body temperature (group W: 36.1 ± 0.4°C vs group C: 35.7 ± 0.6°C) nor in intra-abdominal temperature (group W: 35.9 ± 0.3°C vs group C: 35.6 ± 0.6°C). Postoperatively, the two groups did not differ in pain susceptibility and need of analgesics. Conclusion: The use of carbon dioxide gas warmed to body temperature to produce a pneumoperitoneum during short-term laparoscopic surgery has no clinically important effect. Received: 13 August 1999/Accepted: 24 September 1999/Online publication: 9 August 2000     

Hormone-cytokine response

Background: Changes in blood hormone and cytokine were investigated in patients who underwent laparoscopic cholecystectomy via insufflation (CO₂ group) vs those who had abdominal wall-lifting (Air group). Methods: Seventeen female patients with cholecystolithiasis were randomly divided into two groups. Peripheral blood samples were obtained during perioperative period, and plasma hormone levels (ACTH, cortisol) and serum cytokine levels (TNFα, IL-1β, IL-6, IL-10) were measured. Results: The number of circulating lymphocytes significantly decreased at 1 h after surgery in both groups, but the decrease in the CO₂ group was significantly smaller than that in the Air group. There was no significant difference in hormone elevation between groups. Serum concentrations of IL-6 and IL-10 in the Air group were significantly higher than in the CO₂ group. Conclusions: CO₂ insufflation may reduce cytokine production in laparoscopic cholecystectomy. Received: 10 November 1996/Accepted: 19 February 1997     

Effects of laparotomy vs pneumoperitoneum on the hepatic catabolic stress response in ambulatory and stationary settings in pigs

Background: We recently demonstrated that laparoscopic cholecystectomy is followed by a much smaller hepatic catabolic stress response than conventional cholecystectomy. It is not known what is responsible for this difference. Methods: Thirty pigs were randomly allocated to the following five treatment groups: (1) laparotomy, (2) pneumoperitoneum, (3) pneumoperitoneum with insertion of four trocars, (4) laparotomy, (5) pneumoperitoneum. Groups 1–3 were operated on in an ambulatory setting, whereas groups 4 and 5 were operated on in a stationary setting. Urea synthesis, as quantified by functional hepatic nitrogen clearance, and the response of stress hormones and cytokines were assessed. Results: Laparotomy increased the functional hepatic nitrogen clearance by 195% (p < 0.001); pneumoperitoneum and trocars increased it by 145% (p < 0.001); and pneumoperitoneum alone increased it by 113% (p < 0.001). The difference between laparotomy and both pneumoperitoneum groups was significant. If the stress factor of ambulatory surgery was eliminated, the increase in functional hepatic nitrogen clearance was reduced to 87% (p < 0.01) after laparotomy and 38% (NS) for animals subject to pneumoperitoneum. There were significant differences in concentrations of stress hormones, tumor necrosis factor α, and interleukin 8 among groups intra- and postoperatively. Conclusions: The magnitude of the postoperative hepatic stress response after laparotomy compared to pneumoperitoneum with and without insertion of trocars seems to be caused by the greater trauma to the abdominal wall. Furthermore, an ambulatory setting seems to be an important postoperative stress factor in itself. Received: 28 April 1998/Accepted: 18 August 1998     

Lack of neurohumoral response to pneumoperitoneum for laparoscopic cholecystectomy

Background: Pneumoperitoneum (PP) for laparoscopic surgery induces prompt changes in circulatory parameters. The rapid onset of these changes suggests a reflex origin, and the present study was undertaken to evaluate whether release of vasopressor substances could be responsible for these alterations. The influence of two different anesthesia techniques was also evaluated. Methods: American Society of Anesthesiologists (ASA) class I patients, scheduled for laparoscopic cholecystectomy, were investigated. The first group (n= 10) was anesthetized intravenously. The second group (n= 6) had inhalation anesthesia. Plasma vasopressin, catecholamines, and plasma renin activity were investigated as neurohumoral vasopressor markers of circulatory stress. The general stress response to surgery was assessed by analysis of plasma cortisol. Results: Induction of pneumoperitoneum caused no apparent activation of vasopressor substances, although several hemodynamic parameters responded promptly. Conclusion: The hemodynamic alterations, seen at the establishment of PP during stable anesthesia, cannot be explained by elevation of vasopressor substances in circulating blood. Received: 7 April 1997/Accepted: 3 December 1997     

The effects of pneumoperitoneum on gastric blood flow and traditional hemodynamic measurements

Background: The purpose of this study was to investigate the effects of increasing intraabdominal pressure (IP) on gastric blood flow, as measured by gastric tonometry and traditional hemodynamic measurements. Methods: Nine swine were anesthetized, intubated, and ventilated. Arterial and pulmonary artery catheters were placed by cutdown, a trocar was placed in the abdomen, and a gastric tonometer was placed in the stomach. Serial measurements of arterial and mixed venous blood gases, cardiac output, wedge pressure, lactic acid, and gastric intramucosal pH (pH_i) were collected at intraperitoneal pressures of 0, 8, 10, 12, 14, 16, and 18 mm Hg after 30 min equilibration. Statistical analysis included Pearson correlation and Student's t test. Results: Increasing levels of IP were correlated with decreased arterial pH (p < 0.00003), increased mixed venous CO₂ (p < 0.003), decreased intramucosal pH (p < 0.014), and increased arterial CO₂ (p < 0.015). Gastric pH_i differed significantly from baseline at IP levels of 16 mm Hg (p < 0.004) and 18 mm Hg (p < 0.01). No significant effects were observed on cardiac output or arterial lactate. No significant effects were observed in a control group that had been insufflated to 8 mm Hg and held constant over 3 h. Conclusions: In this model, gastric blood flow is adversely affected by increasing IP with pronounced effects in excess of 15 mm Hg. These results suggest that gastric tonometry may be used to monitor the adverse effects of pneumoperitoneum. Gastric pH_i may be an earlier indicator of altered hemodynamic function during laparoscopy than traditional measures. Received: 25 March 1997/Accepted: 30 June 1997     

Effect of carbon dioxide pneumoperitoneum on bacteremia and severity of peritonitis in an experimental model

Background: Laparoscopy is increasingly used in conditions complicated by peritonitis. A theoretical concern is that carbon dioxide pneumoperitoneum may increase bacteremia. Method: In 60 rats peritonitis was induced by cecostomy. Animals were randomly allocated to pneumoperitoneum (PP) and control groups. Blood cultures and intraabdominal swabs were assessed. A peritonitis severity score (PSS) was computed based on histology from peritoneal biopsy. Results: One hour after cecostomy neither in abdominal swabs nor in blood samples bacteria were reproduced in PP and control groups. Three hours after cecostomy the frequency of positive blood cultures was 80% and 20% in PP and control groups, respectively (p < 0.0001). Six hours after cecostomy the frequency of positive blood cultures was 100% in each group (p > 0.05). One hour after cecostomy the mean peritoneal severity score was significantly higher in the PP group than in the control group, but there was not any significant difference between groups 3 and 6 h after cecostomy. The mean peritoneal severity scores were found to be significantly increased with time when the PP groups compared with each other. Conclusion: In rats, pneumoperitoneum can't cause a more severe peritonitis but it does induce an increase in the rate of bacteremia within the early 6-h period of peritonitis. Received: 14 April 1997/Received: 18 September 1997     

The influence of laparotomy and laparoscopy on tumor growth in a rat model

Background: The effects of laparotomy and laparoscopy with different gases on subcutaneous and intraperitoneal tumor growth have not been evaluated yet. Methods: Tumor growth of colon adenocarcinoma DHD/K12/TRb was measured in rats after laparotomy, laparoscopy with CO₂ or air, and in control group. Cell kinetics were determined after incubation with carbon dioxide or air in vitro and tumor growth was measured subcutaneously and intraperitoneally after surgery in vivo. Results: In vitro, tumor cell growth increased significantly after incubation with air and CO₂. In vivo, intraperitoneal tumor weight was increased after laparotomy (1,203 ± 780 mg) and after laparoscopy with air (1,085 ± 891 mg) and with CO₂ (718 ± 690 mg) compared to control group (521 ± 221 mg) (p < 0.05). Subcutaneous tumor growth was promoted after laparotomy (71 ± 35 mg) and even more after laparoscopy with air (82 ± 45 mg) and CO₂ (99 ± 55 mg) compared to control group (36 ± 33 mg). Conclusions: Insufflation of air and CO₂ promote tumor growth in vitro. In vivo, intraperitoneal tumor growth seems to be promoted primarily by intraperitoneal air and subcutaneous tumor growth by CO₂. Received: 7 November 1996/Accepted: 3 December 1996     

Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum

Objective: Any route of entry into the abdomen contributes to alterations of the intraperitoneal organs with different clinical consequences. Characteristic alterations of the peritoneum after CO₂ pneumoperitoneum used in laparoscopic surgery is examined. Methods: A CO₂ pneumoperitoneum with an intraperitoneal pressure of 6 mmHg was applied for 30 min in 32 nude mice. In the course of 4 days, the animals were killed and the peritoneal surface of the abdominal wall was studied by means of scanning electron microscopy. Results: Already 2 h after release of the pneumoperitoneum, mesothelial cells were bulging up. The intercellular clefts thereby increased in size, and the underlying basal lamina became visible. This reaction peaked after 12 h. Subsequently, peritoneal macrophages and lymphocytes filled all gaps, thereby recovering the basal lamina. Conclusion: The morphologic integrity of the peritoneum is temporarily disturbed by a CO₂ pneumoperitoneum. Received: 9 March 1998/Accepted: 24 July 1998     

The adverse hemodynamic effects of anesthesia, head-up tilt, and carbon dioxide pneumoperitoneum during laparoscopic cholecystectomy

Background: The increased intra-abdominal pressure during pneumoperitoneum, together with the head-up tilt used in upper abdominal laparoscopies, would be expected to decrease venous return to the heart. The goal of our study was to determine whether laparoscopy impairs cardiac performance when preventive measures to improve venous return are taken, and to analyze the effects of positioning, anesthesia, and increased intra-abdominal pressure. Methods: Using invasive monitoring, hemodynamic changes were investigated in 15 ASA class I or II patients under isoflurane–fentanyl anesthesia during laparoscopic cholecystectomy. Before laparoscopy, the patients received an intravenous (IV) infusion of colloid solution if cardiac filling pressures were low, and their legs were wrapped from toes to groin with elastic bandages. Measurements were taken while the patients were awake in the supine (baseline) and head-up tilt (15–20°) positions, and after the induction of anesthesia in the same positions. Measurements were repeated at regular intervals during laparoscopy (intra-abdominal pressure at 13–16 mmHg), after deflation of the gas, and in the recovery room. Results: With the passive head-up tilt in awake and anesthetized patients, the cardiac index (CI), stroke index (SI), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) decreased, and systemic vascular resistance increased. With the patient under anesthesia, SI decreased, but CI did not change significantly as a result of the compensatory increase in heart rate. Carbon dioxide (CO₂) insufflation at the start of laparoscopy produced increases in CVP and PCWP as well as mean systemic and mean pulmonary arterial pressures without changes in CI or SI. Toward the end of the laparoscopy, CI decreased by 15%. The hemodynamic values returned to nearly prelaparoscopic levels after deflation of the gas, and CI was elevated during the recovery period, whereas systemic vascular resistance was decreased in comparison with the baseline. Conclusions: By correcting relative dehydration and preventing the pooling of blood, CI decreased less than 20% during pneumoperitoneum as compared with the baseline awake level. The head-up positioning accounts for many of the adverse effects in hemodynamics during laparoscopic cholecystectomy. Received: 6 November 1998/Accepted: 8 July 1999     

Time-related changes in hemodynamic parameters and pressure-derived indices of left ventricular function in a porcine model of prolonged pneumoperitoneum

Background: Advanced laparoscopic procedures require prolonged pneumoperitoneum. Increased intra-abdominal pressure causes a number of hemodynamic changes including a drop in cardiac output, but it is unclear whether there is a direct effect on cardiac contractility. In this experimental study, we sought to determine whether there is a direct impact of pneumoperitoneum on cardiac contractility. We also examined the time-related changes taking place during the insufflation period. Methods: Six young pigs were anesthetized and mechanically ventilated. Pneumoperitoneum was established by insufflating carbon dioxide to a pressure of 15 mmHg and maintained for a period of 180 min. Hemodynamic parameters including left ventricular dP/dT were invasively recorded every 15 min. All hemodynamic changes were statistically evaluated, and parameters were correlated with time. Results: Cardiac output decreased with insufflation from a baseline of 3.37 ± 0.34 lt/min and reached the lowest value at 165 min of pneumoperitoneum (2.86 ± 0.30 l/min; p= 0.023). Systemic vascular resistance (SVR) significantly increased from 2236 ± 227 dyne/s/cm⁵ to a maximum of 3774 ± 324 dyne/s/cm⁵ (p= 0.005). Left ventricular dP/dT maximum did not change significantly with insufflation. The decrease in cardiac output strongly correlated with the increase in SVR (r=−0.949). Time of insufflation correlated with cardiac output (r=−0.762) and dP/dT maximum (r=−0.727). Conclusions: Pneumoperitoneum at 15 mmHg negatively affects cardiac output without significantly affecting cardiac contractility. A significant increase in SVR appears to be the driving event for the decreased cardiac output. Prolonged pneumoperitoneum may have an additional negative effect on hemodynamic parameters. Received: 5 January 2000/Accepted: 4 May 2000/Online publication: 26 July 2000     

Portal venous flow during CO2 pneumoperitoneum in the rat

Backround: CO₂ gas insufflation is routinely used to extend the abdominal wall. The resulting pneumoperitoneum has a number of local and systemic effects on the organism. 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 modified by implanting a perivascular flow probe. Hemodynamics in the portal vein were then measured during increasing intraabdominal pressure generated by carbon dioxide insufflation. Results: Using this technique, an adequate flowmetry of the portal vein was achieved in all animals. The creation of a CO₂ pneumoperitoneum with increasing intraabdominal pressure led to a linear decrease in portal venous flow. Conclusions: Elevated intraabdominal pressure caused by carbon dioxide insufflation may compromise hepatic function and cell-conveyed immune response during laparoscopic surgery. Received: 28 January 1998/Accepted: 22 June 1998     

Is it necessary to lift the abdominal wall when preparing a pneumoperitoneum?rid=""

Background: In order to create a pneumoperitoneum with the Veress needle, it is generally advocated that the abdominal wall should be lifted. Lifting is aimed at increasing the distance between the abdominal wall and the intraabdominal structures. This study was conducted to compare lifting (L) and nonlifting (NL) of the abdominal wall. Methods: All patients scheduled for laparoscopic surgery without previous abdominal surgery or morbid obesity were included in the study group. The number of attempts needed for proper positioning of the needle was assessed. Results: A total of 150 patients were randomized. There were no complications. The number of attempts needed for correct positioning of the Veress needle was significantly higher in the L group than in the NL group (31 of 75 vs nine of 75, p < 0.001). The body mass index (BMI) of patients in whom peritoneal entry needed more than one puncture was significantly higher than the BMI of patients with immediate proper placement (28.3 vs 24.7 kg/m², p < 0.05). Conclusion: Abdominal wall lifting is not necessary. Received: 20 September 1999/Accepted: 14 December 1999/Online publication: 8 May 2000     

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator

Background: Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. Methods: We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO₂), creating a ``therapeutic pneumoperitoneum.' A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesion-modulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. Results: The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO₂ pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no system-related complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. Conclusions: As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesions. Received: 27 May 1998/Accepted: 5 January 1999     

Intraperitoneal immunity and pneumoperitoneum

Background: Carbon dioxide (CO₂) pneumoperitoneum has been implicated as a possible factor in depressed intraperitoneal immunity. Using in vitro functional assays, CO₂ has been shown to decrease the function of peritoneal macrophages harvested from insufflated mice. However, an effective in vivo assessment is lacking. Listeria monocytogenes (LM), an intracellular pathogen, has served as a well-established in vivo model to study cell-mediated immune responses in mice. This study examines the immune competence of mice based on their ability to clear intraperitoneally administered LM following CO₂ vs helium (He) insufflation. Methods: Eighty-five mice (C57Bl/6, males, 4–6 weeks old) were divided between the following four treatment groups: CO₂ insufflation, He insufflation, abdominal laparotomy (Lap), and control (anesthesia only). Immediately postoperatively, each group was inoculated percutaneously and intraperitoneally with a sublethal dose (.015 × 10⁶ org) of virulent LM (EGD strain). Half of the animals were killed on postoperative day 3 and half on day 5. Spleens and livers (sites of bacterial predilection) were harvested, homogenized, and plated on TSB agar. The amount of bacteria (1 × 10⁶ LM/spleen and liver) from each group was then compared. Statistical significance was set at p≤ 0.05. Results: Control animals had nominal bacteria on day 3 (0.016 × 10⁶ LM/spleen and liver), and the bacterial burden remained low at day 5 (0.038 × 10⁶ LM/spleen and liver) postchallenge. On day 3, the bacterial burden was significantly higher in the CO₂ group (5.46 × 10⁶ LM/spleen and liver) as compared to He (0.093 × 10⁶ LM/spleen and liver) and controls. The Lap group (3.44 × 10⁶ LM/spleen and liver) had significantly more bacteria than the controls. There were no significant differences between any of the groups on day 5. Conclusions: In this animal model, CO₂ pneumoperitoneum impaired cell-mediated intraperitoneal immunity significantly more than He pneumoperitoneum and controls on day 3. Also on day 3, laparotomy caused impairment of intraperitoneal immunity when compared to controls. Finally, intraperitoneal immunosuppression resolved by day 5. Received: 22 July 1998/Accepted: 3 March 1999     

Laparoscopic cholecystectomy and time-course changes in renal function

Background: Recently, the retraction method has been used to reduce intraabdominal pressure (IAP) during laparoscopic surgery. The purpose of this study was to determine the serial changes in renal function during laparoscopic cholecystectomy (LC) using the retraction method. Methods: Urine output, effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) were measured serially in seven patients who underwent LC with 12 mmHg pneumoperitoneum (High-IAP group) and five who underwent LC using the retraction method with 4 mmHg pneumoperitoneum (Low-IAP group). Results: Urine output, ERPF, and GFR were decreased during pneumoperitoneum in the High-IAP group, whereas no significant changes in any of these parameters were observed in the Low-IAP group. Conclusions: Our findings demonstrate that reduction of IAP to 4 mmHg using the retraction method prevents the transient renal dysfunction caused by prolonged 12 mmHg pneumoperitoneum during LC, suggesting that the retraction method reduces the risk of perioperative renal dysfunction during laparoscopic surgery. Received: 26 March 1996/Accepted: 27 July 1996     

Adrenocortical response and regional T-lymphocyte activation patterns following minimally invasive surgery in a rat model

Background: Laparoscopic surgery is associated with less tissue trauma and postoperative pain as well as a more rapid recovery than open surgery. We hypothesized that these factors may result in less immune impairment following laparoscopic surgery. Methods: We measured mitogen-induced surface interleukin-2 receptor (IL2R) expression and lymphocyte proliferation in CD4⁺ and CD8⁺ T-lymphocytes as well as serum corticosterone levels in rats 24 h following open (OP) and laparoscopic (LAP) fundoplication. Results: Serum corticosterone levels were lower in LAP vs OP rats (p= 0.02). CD4⁺ IL2R expression was higher in the blood, but not in the spleen, in LAP vs OP animals (p= 0.02). CD8⁺ IL2R expression was similar in both groups. Mitogen-induced lymphocyte proliferation was no different in the blood but decreased in the spleen in LAP vs OP rats (p= 0.03). Conclusions: Compared to open surgery, laparoscopic fundoplication in the rat results in lower adrenocortical hormone levels and better-preserved T-helper-cell activation in the blood. Lymphocyte proliferation is suppressed in the spleen 24 h after laparoscopic surgery. Minimally invasive surgery may better preserve cell-mediated immunity in the early postoperative period. Received: 2 April 1997/Accepted: 15 July 1997