Enhancement of port site metastasis by hyaluronic acid under CO2 pneumoperitoneum in a murine model

Background

The mechanism underlying the development and progression of port site metastasis after laparoscopic surgery for cancer is still not understood. Hyaluronic acid secreted from mesothelial cells is thought to be a key factor that causes adhesion between cancer cells and mesothelial cells. Using a murine model of carbon dioxide (CO₂) pneumoperitoneum, we evaluated the effect of exogenous hyaluronic acid on port site metastasis.

Methods

BALB/c mice were injected with 5×10⁶ human gastric carcinoma (MKN45) cells and divided into four groups treated with or without hyaluronic acid and with or without pneumoperitoneum. Three weeks later, the frequency and weight of port site metastases were determined. The effects of hyaluronic acid on tumorigenicity and tumor with MKN45 cells.

Results

Port site metastasis occurred significantly less frequently in the pneumoperitoneum-only group than in the pneumoperitoneum-with-hyaluronic-acid group (75% vs 100%, p<0.05). The port site metastatic tumor weighed significantly less in the control group (anesthesia only) than in the hyaluronic acid group (89±17 vs 288±35mg, p<0.05); it also weighed less in the pneumoperitoneum-only group than in the pneumoperitoneum-with-hyaluronic-acid group (87±24 vs 298±51 mg, p<0.05). The frequency and weight of tumors in the subcutaneous tissue were not significantly different between groups with or without hyaluronic acid injection (95% vs 90%, 331±128 vs 322±115 mg).

Conclusions

Under CO₂ pneumoperitoneum, exogenous hyaluronic acid increased the frequency and weight of port site metastasis in a murine model. Hyaluronic acid secreted from mesothelial cells may be associated with the formation of port site metastasis after laparoscopic surgery for cancer under pneumoperitoneum.     

腹腔镜气腹对腹腔及腹壁组织透明质酸含量影响的实验研究

目的:通过建立二氧化碳气腹及开腹手术干预后腹腔及腹壁组织透明质酸含量变化的鼠模型,评价腹腔镜手术中二氧化碳气腹与穿刺针道肿瘤种植转移(PSM)的关系。方法:选择8 ~10周龄雄性BALA/c小鼠,麻醉后建立气腹,测定不同气体(二氧化碳、氦气)、不同气腹干预时间(5、30min)、不同压力( 0. 133 ~0. 400kPa、0. 800~1. 07kPa)、气腹干预后不同时段(6、12、18、24、48、72h)鼠腹腔及腹壁组织透明质酸的含量,同时建立开腹手术模型,测定开腹手术后腹腔及腹壁组织透明质酸的含量。测定结果进行统计学分析,比较不同干预条件对鼠腹腔及腹壁组织透明质酸含量的影响差异。结果:腹腔内透明质酸浓度于二氧化碳气腹干预后6h已经升高, 24h达峰值, 72h明显降低。24及48h腹腔透明质酸浓度二氧化碳气腹组高于开腹组(P<0. 05),不同气体(二氧化碳、氦气)气腹间腹腔透明质酸浓度的变化差异无统计学意义(P>0. 05)。二氧化碳气腹0. 800 ~1. 07kPa/30min组与0. 133~0. 400kPa/30min组及0. 800~1. 07kPa/5min组比较,腹腔透明质酸含量差异有统计学意义(P<0. 05)。开腹手术组手术切口处腹壁组织透明质酸含量明显高于二氧化碳气腹组穿刺针道处腹壁组织透明质酸含量(P<0. 05 )。结论:与开放手术比较,二氧化碳气腹引起腹膜透明质酸分泌明     

Morphological changes in hepatic vascular endothelium after carbon dioxide pneumoperitoneum in a murine model

Background: Liver metastasis is an important prognostic factor in advanced colorectal cancer. Several studies have demonstrated that carbon dioxide (CO₂) pneumoperitonem enhances liver metastasis in an animal model. In the present study, we used scanning electron microscopy (SEM) to investigate morphological changes in hepatic vascular endothelium after CO₂ pneumoperitoneum in a murine model.Methods: Thirty-three male BALB/c mice were randomized to undergo pneumoperitoneum (CO₂, air, or helium ), open laparotomy, and anesthesia alone. After each procedure, the animals’ livers were excised at days 0, 1, and 3 and examined by SEM.Results: In the CO₂ pneumoperitoneum group, we observed rough surface and derangement of the hepatic vascular endothelial cells and intercellular clefts on day 1. In the other groups, no major morphologic changes were observed at any time.Conclusions: Hepatic vascular endothelium changes after CO₂ pneumoperitoneum. Such characteristic changes may play an important role in establishing liver metastasis after CO₂ pneumoperitoneum.     

Port-site metastasis after CO<Subscript>2</Subscript> pneumoperitoneum

Background Port-site metastasis is a continuing problem in laparoscopic cancer surgery. To clarify the role of adhesion molecules in the development of port-site metastasis, particularly with regard to prevention, we performed experiments in which port-site metastasis was inhibited using antibodies against extracellular matrix proteins or the active Arg–Gly–Asp (RGD) peptide after CO₂ pneumoperitoneum in a murine model.Methods We examined the development of port-site metastasis under the following conditions: (1) CO₂ pneumoperitoneum with or without hyaluronic acid and anti-integrin or anti-CD44 antibody and (2) CO₂ pneumoperitoneum and a RGD peptide or pseudo-RGD sequence peptide (FC-336). BALB/c mice (n = 130) were injected with 5 × 10⁵ human gastric cancer cells (MKN45) and either antibody or peptide, treated with CO₂ pneumoperitoneum, and injected intraperitoneally with antibody or peptide for 5 days. Three weeks after CO₂ pneumoperitoneum, the frequency and weight of port-site metastatic tumors were determined.Results Anti-integrin antibody significantly decreased the weight of port-site metastatic tumors without hyaluronic acid (control vs anti-integrin: 8.2 ± 7.1 vs 3.6 ± 4.5 mg; p < 0.05) but not the frequency of port-site metastases. With hyaluronic acid, the frequency of port-site metastasis and the weight of port-site metastatic tumors were significantly decreased both by anti-integrin and by anti-CD44 antibody (control vs anti-integrin and anti-CD44; 95% and 8.5 ± 7.2 mg vs 50% and 3.1 ± 4.3 mg and 55% and 3.3 ± 5.1 mg, respectively; p < 0.05). RGD peptide and FC-336 also inhibited port-site metastasis in a dose-dependent manner.Conclusion Cell adhesion molecules integrin and CD44 play an important role in the development of port-site metastasis after laparoscopic cancer surgery. Intraperitoneal injection of RGD peptide or pseudo-RGD sequence peptide (FC-336) can prevent port-site metastasis.     

Liver metastasis and ICAM-1 mRNA expression in the liver after carbon dioxide pneumoperitoneum in a murine model

Background Liver metastasis of colorectal malignancies is an important prognostic factor. Several studies have demonstrated that carbon dioxide (CO₂) pneumoperitoneum enhances liver metastasis in animal models. Little is known about intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-(α) mRNA expression in the liver after CO₂ pneumoperitoneum. Methods Forty-five male BALB/c mice were randomly divided into three groups after intra-splenic tumor cell (colon 26) inoculation and the following procedures were performed: CO₂ pneumoperitoneum (n = 15), open laparotomy (n = 15), and anesthesia alone (n = 15). On day 7 after each procedure, the livers were excised and the number and diameter of the tumor nodules and the cancer index score were determined. Another 90 male BALB/c mice were randomly divided into three groups as described above, and they underwent each procedure (n = 30 each). After each procedure, the livers were excised on days 0, 1, 3, and ICAM-1 and TNF-α mRNA expression were examined by real-time RT-PCR using SYBR Green I. Results The number of tumor nodules and the cancer index score were larger in the CO₂ pneumoperitoneum group than in the control group (p < 0.05). The mean diameter of the tumor nodules was not different among the three groups. The expression of ICAM-1 in the CO₂ pneumoperitoneum group was higher than that in the other groups on day 1 (p < 0.05), and the TNF-α mRNA was higher than that in the control group on day 1 (p < 0.05). Conclusions CO₂ pneumoperitoneum enhances liver metastasis compared with anesthesia alone, and ICAM-1 expression in the liver after the pneumoperitoneum plays an important role in establishing liver metastasis in a murine model.     

The influence of different insufflation pressures during carbon dioxide pneumoperitoneum on the development of pulmonary metastasis in a mouse model

Background: The effects of different insufflation pressures on the development of pulmonary metastasis was investigated in a mouse laparoscopy model. Methods: BALB/C mice intravenously inoculated with colon 26 cells were randomized to one of five treatment groups (10 mice per group): pneumoperitoneum at different pressures of 5, 10 or 15 mmHg; full laparotomy for 60 min; or anesthesia control. Cancer nodules on the lung surface 19 days postoperatively were compared between groups. Results: (a) As compared with the control group, pneumoperitoneum at 10 and 15 mmHg and laparotomy enhanced the growth of pulmonary metastases (p < 0.01). (b) The growth of metastases also was greater in laparotomy group mice than in mice undergoing pneumoperitoneum at 5 and 10 mmHg (p < 0.05). Conclusions: These results suggest that the effects of different insufflation pressures on the growth of pulmonary metastases are not identical, and that pneumoperitoneum with high pressure may promote pulmonary metastases similar to those with laparotomy. Received: 4 November 1999/Accepted: 20 December 1999/Online publication: 25 April 2000     

Hemodynamic and pulmonary changes during open, carbon dioxide pneumoperitoneum, and abdominal wall-lifting cholecystectomy

Background: Carbon dioxide (CO2) pneumoperitoneum effects are still controversial. The aim of this study was to investigate cardiopulmonary changes in patients subjected to different surgical procedures for cholecystectomy. Methods: In this study, 15 patients were assigned randomly to three groups according to the surgical procedure to be used: open cholecystectomy (OC), CO2 pneumoperitoneum cholecystectomy (PP), and laparoscopic gasless cholecystectomy (abdominal wall lifting [AWL]), respectively. A pulmonary artery catheter was used for hemodynamic monitoring in all patients. A subcutaneous multiplanar device (Laparo Tenser) was used for abdominal wall lifting. To avoid misinterpretation of results, conventional anesthesia was performed with all parameters, and the position of the patients held fixed thoroughout surgery. The following parameters were analyzed: mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), systemic vascular resistances index (SVRI), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistances index (PVRI), peak inspiratory pressure (PIP), end-tidal CO2 pressure (ETCO)2, CO2 arterial pressure (PaCO2), and arterial pH. Results: All the operations were completed successfully. The Laparo Tenser allowed good exposition of the surgical field. A slight impairment of the cardiopulmonary functions, with reduction of SVRI, MAP, and CI and elevation of pulmonary pressures and vascular resistance, followed induction of anesthesia. However, these effects tended to normalize in the OC and AWL groups over time. In contrast, CO2 insufflation produced a complex hemodynamic and pulmonary syndrome resulting in increased right- and left side filling pressures, significant cardiac index reduction, derangement of the respiratory mechanics, and respiratory acidosis. All of these effects normalized after desufflation. Conclusions: Cardiopulmonary adverse effects of general anesthesia were significant but transitory and normalized during surgery. Carbon dioxide pneumoperitoneum caused a significant impairment in cardiopulmonary functions. In high-risk patients, gasless laparoscopy may be preferred for reliability and absence of cardiopulmonary alterations. apd: 21 December 2000     

Alterations in hemodynamics and left ventricular contractility during carbon dioxide pneumoperitoneum

Background: Carbon dioxide (CO₂) pneumoperitoneum has been shown to adversely affect hemodynamics in patients. This study specifically examines the potential contribution of altered left ventricular contractility (LVC) to hemodynamic changes observed during CO₂ pneumoperitoneum. Methods: In a canine model, LV volumes, LV pressure, and intrathoracic and central venous pressures were recorded both at basal intra-abdominal pressure (IAP) and after CO₂ insufflation to produce IAPs of 5–25 mmHg. Results: At IAPs greater than 15 mmHg, cardiac output and LV end-diastolic volume decreased. Mean arterial pressure and heart rate were unchanged. LVC, quantified using the linear Frank-Starling relationship, was not affected by increases in IAP. Conclusions: This study is the first to quantify LVC during CO₂ pneumoperitoneum and demonstrates no changes in contractility over IAPs from 5 to 25 mmHg. In the dog model, any hemodynamic alterations induced by CO₂ pneumoperitoneum are secondary to altered LV preload and not alterations in contractility or LV afterload. Received: 8 March 1996/Accepted: 23 April 1996     

三氧化二砷对CO2气腹下小鼠肿瘤腹壁戳口种植影响的实验研究

目的 研究腹腔内注射三氧化二砷(arsenic trioxide,As2O3)对小鼠CO2气腹下肝癌H22转移的影响. 方法 昆明鼠40只(清洁级),中腹部穿刺置入1 mm套管针,自套管针注入1×106肿瘤细胞后,建立CO2气腹,压力8 mm Hg,时间30 min.术后随机分4组,每组10只,分别腹腔内注入生理盐水,1 ml;As2O3(2 mg/kg),1 ml;As2O3(4 mg/kg),1 ml;As2O3(4mg/kg)+肝素(10 U/ml),共1 ml.气腹后第3、7天测量肿瘤黏附因子(CD44)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的变化;比较各组生存状态、腹围、体重变化及转移瘤直径.结果 气腹后第3、7天,与对照组相比,各As2O3组CD44、VEGF表达均明显降低(P＜0.05).2个高剂量组的气腹后第3天VEGF、第7天CD44比低剂量组降低明显(P＜0.05).4组戳口种植率分别为9/10、8/10、7/10、6/10,差异无显著性(x2=2.667,P=0.446). 结论 As2O3对CO2气腹腹腔镜肿瘤生长转移有抑制作用.     

Liver histology alterations during carbon dioxide pneumoperitoneum in a porcine model

Background This study aimed to investigate the time course changes in liver histology during carbon dioxide (CO₂) pneumoperitoneum in a large animal model. Methods For this study, 14 white pigs were anesthetized. Liver biopsies performed 0, 1, and 2 h after establishment of CO₂ pneumoperitoneum (at 12 mmHg) and after peritoneal desufflation were sent for histologic examination. Heart rate, mean blood pressure, hepatic artery flow, portal vein flow, and aortic flow were recorded in 10-min increments. Three animals served as control subjects. Results A statistically significant time course increase was observed in portal inflammation, intralobular inflammation, edema, sinusoidal dilation, sinusoidal hyperemia, centrilobular dilation, centrilobular hyperemia, pericentrilobular ischemia, and focal lytic necrosis scores. There were no significant changes in the control group. This eliminated an effect of anesthesia only. The portal vein flow increased as much as 21%, and the hepatic artery flow decreased as much as 31% of baseline, but these differences did not attain statistical significance. Aortic flow remained relatively stable. Conclusion Histomorphologic changes occurred, indicating liver tissue injury during CO₂ pneumoperitoneum at an intraabdominal pressure of 12 mmHg in the porcine model. Portal vein flow increased, and hepatic artery flow decreased, whereas aortic flow remained relatively unaffected in this experiment. Presented in part orally at the 10th World Congress of Endoscopic Surgery, Berlin, September 2006     

两种腹腔镜胆囊切除术术式对机体血气参数及PET CO2的影响

目的观察对比气腹腹腔镜与悬吊腹腔镜胆囊切除术对心肺功能正常患者血气分析及呼吸末CO2分压（PET CO2）的影响。方法选择60例心电图、胸部正位片正常的患者,均在全身麻醉下行腹腔镜胆囊切除术,按术式分为气腹组和悬吊组,每组30例。分别于麻醉后5 min（T1）、术中气腹或悬吊后20 min（T2）、术后停气腹或悬吊后30 min（T3）抽取患者足背动脉血行血气分析,记录各个时段动脉血pH值、PaCO2、CO2总量以及T1、T2时段的PET CO2。结果两组术前及术后各项指标差异无统计学意义（P〉0.05）,术中两组间各项指标差异有统计学意义（P〈0.05）。气腹组术前、术中各项指标及术中、术后各项指标比较差异有统计学意义（P〈0.05）,术前、术后比较仅pH值差异有统计学意义（P〈0.05）。悬吊组术前、术中、术后各项指标两两比较差异无统计学意义（P〉0.05）。结论气腹腹腔镜手术对机体血气的影响大于悬吊腹腔镜手术,合并心肺功能障碍、老年患者、预计手术时间长的患者,提倡选择悬吊腹腔镜手术。     

Increased susceptibility to liver damage from pneumoperitoneum in a murine model of biliary atresia

Hypothesis

We hypothesized that livers with biliary atresia (BA) are more susceptible to the harmful effects of a high-pressure CO₂ pneumoperitoneum (PP) than healthy livers.

Methods

A murine model of BA was used in this experiment. Mice were divided into 6 groups: (1) control Balb/c; (2) control Balb/c, CO₂-PP; (3) control BA; (4) BA-sham; (5) BA, CO₂-PP; and (6) BA, air-PP. Mice from groups 2, 5, and 6 underwent an 8-mm Hg-PP for 60 minutes. Liver samples were collected for histology, colorimetry, and flow cytometry analysis 18 to 24 hours after the procedure. Markers of apoptosis were investigated as indicators of acute cell damage.

Results

We observed a statistically significant higher rate of apoptosis in livers with BA exposed to a prolonged CO₂-PP or air-PP compared with control groups. There were no significant differences between groups 1 and 2, or between groups 5 and 6.

Conclusions

In this animal model, we have shown that livers with BA are more susceptible than healthy livers to injury by a prolonged PP. This injury was caused by both CO₂ and air-PP, implying that it is the direct result of pressure. These results may have implications for the success of minimally invasive Kasai procedures.     

Effect of carbon dioxide pneumoperitoneum and wound closure technique on port site tumor implantation in a rat model

Background The purpose of this study was to evaluate the effects of carbon dioxide (CO₂) pneumoperitoneum and wound closure technique on port site tumor implantation.Methods A standard quantity of rat mammary adenocarcinoma (SMT2A)was allowed to grow in a flank incision in Wistar-Furth rats (n = 90) for 14 days. Thereafter, 1-cm incisions were made in each animal in three quadrants. There were six control animals. The experimental animals were divided into a 60-min CO₂ pneumoperitoneum group (n = 42) and a no pneumoperitoneum (n = 42) group. The flank tumor was lacerated transabdominally in the experimental groups. The three wound sites were randomized to closure of (a) skin; (b) skin and fascia; and (c) skin, fascia, and peritoneum. The abdominal wounds were harvested en bloc on postoperative day 7.Results Histologic comparison of the port sites in the pneumoperitoneum and no-pneumoperitoneum groups did not demonstrate a statistically significant difference in tumor implantation for any of the closure methods. Evaluation of the closure techniques showed no statistical difference between the pneumoperitoneum group and the no-pneumoperitoneum group in the incidence of port site tumor implantation. Within the no-pneumoperitoneum group, there was a significant increase (p = 0.03) in tumor implantation with skin closure alone vs all three layers. Additionally, when we compared all groups by closure technique, the rate of tumor implantation was found to be significantly higher (p = 0.01) for skin closure alone vs closure of all three layers.Conclusions This study suggests that closure technique may influence the rate of port site tumor implantation. The use of a CO₂ pneumoperitoneum did not alter the incidence of port site tumor implantation at 7 days postoperatively.     

Laparoscopic surgery in a small animal model

Background: An adequate laparoscopic small-animal model would benefit surgical oncologic research. Immunobiologic data and reagents available for the rodent make them an ideal species. We developed a simple, inexpensive, reproducible technique for laparoscopic surgery in rodents. Methods: Carbon dioxide pneumoperitoneum is achieved in anesthetized animals. Through a 0.5-cm midline incision a 4.8-mm bronchofiberscope is inserted into the peritoneal cavity and secured with a purse-string suture (PSS). Three additional PSSs are made to introduce the dissectors. Under fiberscopic vision, a blunt dissection of the retroperitoneum exposes the inferior vena cava and aorta. Necropsy 24 h after verifies the adequacy of dissection. Results: Eighteen animals survived. The only death resulted from bleeding. Mortality was 5.26%. Surgical time was 24.72±8.93 min with all animals active 2 h postlaparoscopy. Conclusions: Laparoscopic surgery (LS) can be done inexpensively without sophisticated equipment. The rodent is ideal for examining the immunologic consequences of laparoscopic surgery and pneumoperitoneum.     

Liver metastasis following pneumoperitoneum with different gases in a mouse model

apd: 20 October 2000     

Insufflation profile and body position influence portal venous blood flow during pneumoperitoneum

Background: We investigated changes in portal venous blood flow (PVBF) during carbon dioxide (CO₂) pneumoperitoneum to evaluate the effects of different insufflation profiles and body positions. Methods: An established rat model was extended by implanting a portal vein flow probe that would enable us to measure PVBF for 60 min [t₀–t₆₀] in animals subjected to a CO₂ pneumoperitoneum with an intraabdominal pressure (IAP) of 9 mmHg. Forty-eight male Sprague-Dawley rats were randomized into the following four experimental and two control groups: decompression group D1 (n = 8), desufflation for 1 min every 14 min; decompression group D2 (n = 8), desufflation for 5 min, after 27 min; position group P1 (n = 8), 35° head-up position; position group P2 (n = 8), 35° head-down position; negative control group C1 (n = 8), no insufflation; positive control group C2 (n = 8), constant IAP of 9 mmHg for 60 min. Results: Pneumoperitoneum and body positions, respectively, reduced PVBF [t₁–t₆₀] significantly (p < 0.001) by 32.0% C2, 32.8% D1, 31.1% D2, 40.8% P1, and 48.5% P2, as compared to PVBF at t₀ in each group. There was a significant difference in PVBF reduction between P1 and P2 and also between C2 and both P1 and P2 (p < 0.04). Conclusions: CO₂ pneumoperitoneum reduces PVBF significantly (>30%). Extreme body positions (35° tilt) significantly intensify PVBF reduction. PVBF reduction is significantly more dramatic in subjects placed in a 35° head-down position. Short desufflation periods did not improve mean PVBF, but it may have beneficial immunological and oncological effects that warrant further investigation. Presented at the annual meeting of the European Association for Endoscopic Surgery (EAES), Lisbon, Portugal, 2002.     

腹腔镜手术CO_2气腹及体位改变对眼内压的影响

目的 研究CO2气腹及手术体位对眼内压(IOP)的影响.方法 全麻下腹腔镜手术患者36例分为盆腔手术(A组)和胆囊切除术(B组)两组,每组18例.手术体位:A组头低位25°,B组头高位25°.记录麻醉前(T0)、气管插管后5 min(T1)、气腹后5 min(T2)、体位改变后5 min(T3)、体位改变后30 min(T4)和PETCO2降低至正常后(T5)的IOP.结果 两组IOP在全麻诱导后明显下降.A组T4时IOP逐渐增高至(21.0±1.6)mm Hg,T5时降低至(14.6±1.6)mm Hg.B组T4时IOP逐渐增高至(12.1±2.9)mm Hg,T5时降低至(11.1±1.2)mm Hg.两组术中的IOP与PETCO2呈正相关.结论 用丙泊酚全麻诱导可显著降低IOP.头高位手术和保持PETCO2于正常水平是避免IOP升高的重要因素.     

Port-site recurrence reproduced in the VX-2 rabbit carcinoma model: an in vivo model comparing laparoscopic port sites and open incisions.

BACKGROUND: The use of advanced laparoscopy remains controversial in the field of surgical oncology because the potential for port-site recurrence may violate sound oncologic principles. Two mechanisms are theorized to be the cause of port-site recurrences: first, indirect contamination caused by pneumoperitoneum, aerosolization, or intraperitoneal spread, and second, direct contamination by physical trocar seeding. METHODS: A VX-2 carcinoma cell suspension was transferred under the left renal capsule of 31 rabbits with either an open flank incision (16) or laparoscopy (15). Animals were observed for tumor recurrence at the video port, the working port, and the open incision. Intraoperative findings and necropsy were used to document recurrence. RESULTS: The open incision technique resulted in local tumor recurrence in 1/16 animals with 16/16 viable intraabdominal tumors. The laparoscopic technique resulted in 0/15 video port-site recurrences and 9/15 working port-site recurrences, with 14/15 viable intraabdominal tumors. Recurrence at the laparoscopic working port occurred more frequently than in the open (P < 0.02) or laparoscopic video port groups (P < 0.007). No significant difference existed in recurrence between the open incision and the laparoscopic video port (P > 0.5). CONCLUSIONS: Laparoscopic port-site recurrences can be reproduced using the transplantable VX-2 rabbit carcinoma model. In the VX-2 model, trocar recurrence is the result of direct contamination via surgical instrumentation of viable tumor cells. The effect of the pneumoperitoneum or intraperitoneal cytological spillage (indirect contamination) does not have any effect on trocar recurrence. This model can be used to test and improve laparoscopic techniques to minimize the risk of port-site recurrence. Until technological advances have eliminated the risk of trocar recurrences, direct contact between malignant cells and laparoscopic instruments should be performed with caution.     

Hemodynamic and arterial blood gas changes during carbon dioxide and helium pneumoperitoneum in pigs

The effects of pneumoperitoneum with carbon dioxide and helium on systemic hemodynamics and arterial blood gases were investigated in pigs in an attempt to clarify the mechanisms by which pneumoperitoneum may induce organ dysfunction. A total of 16 anesthetized female pigs underwent pneumoperitoneum with carbon dioxide or helium (n=8 each) in a stepwise fashion to intraabdominal pressures of 8, 10, 12, 16, and 20 mmHg. Changes in cardiac output; renal and hepatic blood flow; mean arterial, mean pulmonary arterial, mean pulmonary arterial wedge, inferior vena caval, and portal venous pressures; and total peripheral resistance were measured. Arterial blood samples were obtained at the same time the above parameters were determined. Urine volume was measured as an indicator of renal function. Pneumoperitoneum with either carbon dioxide or helium significantly increased venous pressures and simultaneously decreased cardiac output. These changes were associated with decreases in organ blood flow due to increased peripheral resistance. Urinary output was reduced to a similar degree in the two groups. Blood gas analysis revealed pneumoperitoneum-induced metabolic acidosis in both groups, although hypercapnia was observed only in the carbon dioxide group. These findings suggest that pneumoperitoneum-related organ dysfunction may be due to increased intraperitoneal pressure rather than to hypercapnia.