Eric J. Hanly

CO2 Pneumoperitoneum modifies the inflammatory response to sepsis.

ObjectiveTo analyze the effect of CO2 pneumoperitoneum on the inflammatory response induced by sepsis during laparoscopy. Summary Background DataA growing body of evidence challenges the once generally accepted notion that smaller incisions alone account for the observed benefits of the laparoscopic approach. Furthermore, laparoscopic surgery is now being applied to a broad spectrum of patients, including those in whom the inflammatory response is ignited. Delineation of the effects of CO2 pneumoperitoneum on the inflammatory response induced by sepsis is needed. MethodsSepsis was induced in rats by cecal ligation and puncture (CLP) performed either open or laparoscopically using CO2 or helium as insufflation gases. Animals were killed 24 hours postoperatively, at which time whole blood was collected for complete blood cell counts and livers were harvested for analysis of hepatic expression of the rat acute phase genes &agr;2-macroglobulin and &bgr;-fibrinogen. ResultsLaparoscopic CLP using CO2 resulted in significantly reduced hepatic expression of the rat acute phase gene &agr;2-macroglobulin compared to both laparoscopic CLP using helium and open CLP. Hepatic expression of another rat acute phase gene, &bgr;-fibrinogen, paralleled that of &agr;2-macroglobulin and was significantly reduced following laparoscopic CLP using CO2 compared to laparoscopic CLP using helium. Total white blood cell and neutrophil counts following CLP were both significantly higher when CLP was performed laparoscopically using CO2 than when CLP was performed open or laparoscopically using helium. ConclusionsIntra-abdominal CO2 present during laparoscopy attenuates the acute phase inflammatory response associated with perioperative sepsis.

Reliable gastric closure after natural orifice translumenal endoscopic surgery (NOTES) using a novel automated flexible stapling device

BackgroundReliable closure of the translumenal incision is one of the main challenges facing natural orifice translumenal endoscopic surgery (NOTES). This study aimed to evaluate the use of an automated flexible stapling device (SurgASSIST) for closure of the gastrotomy incision in a porcine model.MethodsA double-channel gastroscope was advanced into the stomach. A gastric wall incision was made, and the endoscope was advanced into the peritoneal cavity. After peritoneoscopy, the endoscope was withdrawn into the stomach. The SurgASSIST stapler was advanced orally into the stomach. The gastrotomy edges were positioned between the opened stapler arms using two endoscopic grasping forceps. Stapler loads with and without a cutting blade were used for gastric closure. After firing of the stapler to close the gastric wall incision, x-ray with contrast was performed to assess for gastric leakage. At the end of the procedure, the animals were killed for a study of closure adequacy.ResultsFour acute animal experiments were performed. The delivery and positioning of the stapler were achieved, with technical difficulties mostly due to a short working length (60 cm) of the device. Firing of the staple delivered four rows of staples. Postmortem examination of pig 1 (when a cutting blade was used) demonstrated full-thickness closure of the gastric wall incision, but the cutting blade caused a transmural hole right at the end of the staple line. For this reason, we stopped using stapler loads with a cutting blade. In the three remaining animals (pigs 2–4), we were able to achieve a full-thickness closure of the gastric wall incision without any complications.ConclusionsThe flexible stapling device may provide a simple and reliable technique for lumenal closure after NOTES procedures. Further survival studies are currently under way to evaluate the long-term efficacy of gastric closure with the stapler after intraperitoneal interventions.

Hybrid minimally invasive surgery—a bridge between laparoscopic and translumenal surgery

BackgroundThe peroral transluminal approach to the peritoneal cavity appears safe, feasible, and may further reduce the invasiveness of surgery. However, flexible endoscopes have multiple limitations inside the peritoneal cavity, which can potentially be overcome by blending the use of both a laparoscope and a flexible upper endoscope—a hybrid approach. The goal of the present study was to evaluate a hybrid minimally invasive technique for cholecystectomy in a porcine model.MethodsHybrid cholecystectomies were performed in acute experiments on 50-kg pigs under general anesthesia. Pneumoperitoneum was created with a Veress needle, and a laparoscopic 10-mm port was inserted. Under laparoscopic observation, the gastric wall incision was done with an endoscopic needle-knife and sphincterotome, and the upper endoscope was advanced into the peritoneal cavity. A laparoscopic 10-mm port was inserted into the right upper quadrant of the abdomen for gallbladder traction to facilitate exposure of the cystic duct and artery. Via the biopsy channel of the flexible endoscope, and using a knife with an isolated tip, a needle knife, and clips, both the cystic duct and artery were identified, clipped, and transected. The gallbladder itself was then dissected and retracted through the mouth, and the gastric wall incision was closed with endoscopic clips.ResultsFive hybrid cholecystectomies were performed without complications. The laparoscopic port enabled a stable pneumoperitoneum, good traction and counter-traction, and improved spatial orientation and visualization. Necropsy did not reveal any intraperitoneal complications.ConclusionsThe hybrid approach increases safety of initial gastric puncture and gastric wall incision, improves orientation and navigation of the flexible endoscope inside the peritoneal cavity, simplifies peroral transgastric cholecystectomy, and could be used to decrease invasiveness of laparoscopic surgery and to facilitate development and clinical introduction of transgastric endoscopic procedures.

General anesthesia delays the inflammatory response and increases survival for mice with endotoxic shock.

ABSTRACT Anesthesia is an indispensable component of any operative procedure. In this study, we demonstrate that continuous isoflurane anesthesia for 1 h after a lethal dose (20 mg/kg of body weight) of Escherichia coli lipopolysaccharide (LPS) results in a significant increase in survival of C57BL/6J (B6) mice in comparison with survival of nonanesthetized mice. Protection by anesthesia correlates with a delay in plasma LPS circulation, resulting in a delayed inflammatory response, particularly DNA binding activity of NF-κB and serum levels of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-10. Disparate classes of anesthetic agents produce the same effects on the inflammatory response, which is also independent of the inbred mouse strain used. These results suggest that anesthesia has an important impact on the outcome from endotoxemia. Moreover, the immunomodulatory effects of anesthetics should be considered when interpreting data from experimental animal models.

Transcontinental telesurgical nephrectomy using the da Vinci robot in a porcine model.

OBJECTIVES Robotic telesurgery has been demonstrated over long distances and offers theoretical benefits to urologic training and the care of patients in remote regions. The multiple arms and three-dimensional vision of the da Vinci robotic system provide a platform conducive to long-distance telementoring and telesurgery. Whereas prior telesurgical efforts have used dedicated lines for information transmission, the public Internet offers a less expensive alternative. It was the intent of this study to test the validity of using the da Vinci system in urologic telesurgery, and to conduct telerobotic nephrectomies using the public Internet. METHODS We performed four right nephrectomies in porcine models using the da Vinci robotic system. Telementoring and telesurgical approaches were used, with resident surgeons operating a console adjacent to the swine, while attending surgeons simultaneously operated a second console at distances of 1300 and 2400 miles from the operating room. RESULTS All four procedures and both telementoring and telesurgical models were successful. Round-trip delays from 450 to 900 ms were demonstrated. Blood loss was minimal, and there were no intraoperative complications. CONCLUSIONS This study represents the first use of the da Vinci Surgical System in urologic telesurgery and the first successful telesurgical nephrectomy in an animal model.

Comparison of intraabdominal pressures using the gastroscope and laparoscope for transgastric surgery

BackgroundThe peroral transgastric endoscopic approach for intraabdominal procedures appears to be feasible, although multiple aspects of this approach remain unclear. This study aimed to measure intraperitoneal pressure in a porcine model during the peroral transgastric endoscopic approach, comparing an endoscopic on-demand insufflator/light source with a standard autoregulated laparoscopic insufflator.MethodsAll experiments were performed with 50-kg female pigs under general anesthesia. A standard upper endoscope was advanced perorally through a gastric wall incision into the peritoneal cavity. The peritoneal cavity was insufflated with operating room air from an endoscopic light source/insufflator. Intraperitoneal pressure was measured by three routes: (1) through the endoscope biopsy channel, (2) through a 5-mm transabdominal laparoscopic port, and (3) through a 16-gauge Veress needle inserted into the peritoneal cavity through the anterior abdominal wall. The source of insufflation alternated between on-demand manual insufflation through the endoscopic light source/insufflator using room air and a standard autoregulated laparoscopic insufflator using carbon dioxide (CO2).ResultsSix acute experiments were performed. Intraperitoneal pressure measurements showed good correlation regardless of measurement route and were independent of the type of insufflation gas, whether room air or CO2. On-demand insufflation with the endoscopic light source/insufflator resulted in a wide variation in pressures (range, 4–32 mmHg; mean, 16.0 ± 11.7). Intraabdominal pressures using a standard autoregulated laparoscopic insufflator demonstrated minimal fluctuation (range, 8–15 mmHg; mean, 11.0 ± 2.2 mmHg) around a predetermined value.ConclusionUse of an on-demand unregulated endoscopic light source/insufflator for translumenal surgery can cause large variation in intraperitoneal pressures and intraabdominal hypertension, leading to the risk of hemodynamic and respiratory compromise. Safety may favor well-controlled intraabdominal pressures achieved with a standard autoregulated laparoscopic insufflator.

Carbon dioxide pneumoperitoneum prevents mortality from sepsis

BackgroundCarbon dioxide (CO2) pneumoperitoneum has been shown to attenuate the inflammatory response after laparoscopy. This study tested the hypothesis that abdominal insufflation with CO2 improves survival in an animal model of sepsis and investigated the associated mechanism.MethodsThe effect of CO2, helium, and air pneumoperitoneum on mortality was studied by inducing sepsis in 143 rats via intravenous injection of lipopolysaccharide (LPS). To test the protective effect of CO2 in the setting of a laparotomy, an additional 65 animals were subjected to CO2 pneumoperitoneum, helium pneumoperitoneum, or the control condition after laparotomy and intraperitoneal LPS injection. The mechanism of CO2 protection was investigated in another 84 animals. Statistical significance was determined via Kaplan– Meier analysis for survival and analysis of variance (ANOVA) for serum cytokines.Results Among rats with LPS-induced sepsis, CO2 pneumoperitoneum increased survival to 78%, as compared with using helium pneumoperitoneum (52%; p < 0.05), air pneumoperitoneum (55%; p = 0.09), anesthesia control (50%; p < 0.05), and LPS-only control (42%; p < 0.01). Carbon dioxide insufflation also significantly increased survival over the control condition (85% vs 25%; p < 0.05) among laparotomized septic animals, whereas helium insufflation did not (65% survival). Carbon dioxide insufflation increased plasma interleukin-10 (IL-10) levels by 35% compared with helium pneumoperitoneum (p < 0.05), and by 34% compared with anesthesia control (p < 0.05) 90 min after LPS stimulation. Carbon dioxide pneumoperitoneum resulted in a threefold reduction in tumor necrosis factor-α (TNF-α) compared with helium pneumoperitoneum (p < 0.05), and a sixfold reduction with anesthesia control (p < 0.001).ConclusionAbdominal insufflation with CO2, but not helium or air, significantly reduces mortality among animals with LPS-induced sepsis. Furthermore, CO2 pneumoperitoneum rescues animals from abdominal sepsis after a laparotomy. Because IL-10 is known to downregulate TNF-α, the increase in IL-10 and the decrease in TNF-α found among the CO2-insufflated animals in our study provide evidence for a mechanism whereby CO2 pneumoperitoneum reduces mortality via IL-10-mediated downregulation of TNF-α.

Abdominal insufflation with CO2 causes peritoneal acidosis independent of systemic pH

We have shown that the inflammation-attenuating effects of CO2 pneumoperitoneum during laparoscopy are not due to changes in systemic pH. However, acidification of peritoneal macrophages in an in vitro CO2 environment has been shown to reduce LPS-mediated cytokine release. We tested the hypothesis that the peritoneum is locally acidotic during abdominal insufflation with CO2deven when systemic pH is corrected. Rats (n = 20) were anesthetized and randomized into two groups: continued spontaneous ventilation (SV) or intubation and mechanical ventilation (MV). All animals were then subjected to abdominal insufflation with CO2. Mean arterial pH among SV rats decreased significantly from baseline after 15 and 30 minutes of CO2 pneumoperitoneum (7.329→7.210→7.191, P < 0.05), while arterial pH among MV rats remained relatively constant (7.388→7.245→7.316, P = NS). In contrast, peritoneal pH dropped significantly from baseline and remained low for both groups during CO2 abdominal insufflation (SV 6.74 → 6.41 → 6.40, P < 0.05; MV 6.94 → 6.45 → 6.45, P < 0.05). In a second experiment, rats (n = 10) were randomized to receive abdominal insufflation with either CO2 or helium. Abdominal insufflation with helium did not significantly affect peritoneal pH (7.10 → 7.02 →6.95, P = NS), and the decrease in pH among CO2-insufflated animals was significant compared with helium-insufflated animals (P < 0.05). Peritoneal pH returned to baseline levels in all groups within 15 minutes of desufflation in both experiments. A significant local peritoneal acidosis occurs during laparoscopy which is specifically attributable to the use of CO2 and which is independent of systemic pH. These data provide additional evidence that localized peritoneal acidosis is central to the mechanism of CO2-mediated attenuation of the inflammatory response following laparoscopic surgery.

Comparison of the stress response after laparoscopic and open cholecystectomy.

AbstractBackground: We designed a prospective controlled animal study to compare the stress response induced after laparoscopic and open cholecystectomy. Methods: Twelve female pigs (20–25 kg body weight) were anesthetized with ketamine, pentobarbital, and fentanyl. The animals were randomized into the following four groups: control (C), pneumoperitoneum with CO2 at 14–15 mmHg (P), laparoscopic cholecystectomy (LC), and open cholecystectomy (OC). The average duration of the procedure in each group was 35 min. Results: Central venous pressure, mean arterial pressure, pulmonary capillary wedge pressure, and cardiac output were monitored. Measurements were recorded when animals were anesthetized (baseline), immediately before and after surgery, and thereafter every 30 min for a maximum of 3 h. White blood cell count (WBC) was determined from blood samples taken before and after 3 h of surgery. Ultrasound-guided liver biopsies were done preoperatively and after 3 h of surgery. Total RNA was isolated from the liver biopsy specimens. Steady-state mRNA levels of β-fibrinogen (β-fib), α 1-chymotrypsin inhibitor (α1-CTI), metallothionein (MT), heat shock protein 70 (Hsp70), and polyubiquitin (Ub) were detected by Northern blot/hybridization. There were no statistical differences in the hemodynamic parameters among the groups. The number of circulating neutrophils and monocytes decreased only after LC. Expression of Hsp70 was not induced after any surgical procedure, and the mRNA levels of Ub did not change after surgery. The expression of α1-CTI and β-fib (acute phase genes) were similarly increased after LC and OC. Steady-state mRNA levels of MT were slightly increased after P and LC but not after OC. Conclusion: These data indicate that there are no significant differences between LC and OC in terms of induction of the stress response.

Value of the SAGES Learning Center in introducing new technology.

BackgroundThe Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Learning Center is a group of educational “classrooms” designed to tutor meeting attendees on specific technology-intensive content areas. The objectives of the Robotics Station were to familiarize participants with basic laparoscopic skills as implemented with surgical robotic assistance and to help them explore the benefits and drawbacks of using robotics in their institutions.MethodsSixty-six volunteer surgeon attendees of the 2003 SAGES meeting representing a diverse group of backgrounds and possessing varying levels of surgical experience were directed through a series of drills on two different surgical robots. Each participant was directed through a series of three drills that practiced surgically relevant skills. Participants were given feedback on their performance. They then completed a 12-question computer-based questionnaire that surveyed their personal demographic backgrounds, their impressions of robotic surgery, and their opinions regarding the learning center’s utility in educating them about new technology.ResultsSixty-eight percent of participants had never used a surgical robot, and 89% had never used a robot clinically. Eighty-eight percent of respondents found one or both robots easier to use than they had expected, and 91% found that one or both robots made simple surgical tasks easier compared to standard laparoscopy. Sixty-four percent of participants stated that they were more likely to pursue purchase of a robotic system for use in their practice as a result of their exposure to robotics in the Learning Center. After completing the Robotics Station, 80% of surgeons believed that current surgical robots are of clinical benefit. However, 71% of participants stated that surgical robotic systems priced above