Leila Adamyan

Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery

BackgroundTo translate the concept of full-conditioning (FC) from animal experiments to the human, and to evaluate the efficacy for adhesion prevention. FC consisted of decreasing acute inflammation by 86% CO2+ 10% N2Ou2009+u20094% O2 for the pneumoperitoneum, cooling of the peritoneal cavity, humidification, heparinized rinsing solution and 5xa0mg of dexamethasone as demonstrated in animal models.MethodsA randomized controlled trial (RCT: NCT01344486) comparing standard laparoscopy with full conditioning together with a barrier in a 2/3 ratio in 44 women undergoing deep endometriosis surgery at KULeuven. The primary aim was reduction of adhesions. Secondary aims were CO2 resorption, postoperative pain and recovery. Randomization was performed after signing informed consent. Adhesion scoring during second look laparoscopy and pain scoring were done blindly.ResultsIn the FC group (nu2009=u200916) adhesions were completely prevented in 12/16 women whereas in the control group (nu2009=u200911) all women had severe adhesions (Pu2009<u20090.0005). Also the area, density and severity of adhesions were less. (P <0.001). In the control group, severity, density and area of adhesions were strongly interrelated (Pu2009=u20090.0001 for all areas) suggesting a common enhancing factor. In the FC group CO2 resorption (Pu2009<u20090.001), postoperative pain (Pu2009<u20090.001), and CRP concentrations (Pu2009<u20090.01) were lower while clinical recovery was faster (Pu2009<u20090.0001) and time to first flatus (Pu2009<u20090.002) shorter.In conclusionThis translational research confirms in the human the efficacy of FC in reducing CO2 resorption and adhesions with in addition less postoperative pain, lower postoperative CRP concentrations and an accelerated recovery.

Pathogenesis CO2 Pneumoperitoneum-Induced Metabolic Hypoxemia in a Rabbit Model

STUDY OBJECTIVEnTo investigate the effects of carbon dioxide (CO(2)) pneumoperitoneum-induced changes in blood gases, acid-base balance, and oxygen homeostasis in rabbits.nnnDESIGNnProspective, randomized, controlled study (Canadian Task Force classification I).nnnSETTINGnUniversity training and teaching center.nnnSUBJECTSnTwenty-six adult female New Zealand white rabbits.nnnINTERVENTIONnAnesthesia and pneumoperitoneum.nnnMEASUREMENTS AND MAIN RESULTSnIn anesthetized rabbits arterial blood gases, acid-base balance, oxygenation values, and lactate concentrations were assayed during 2 hours. Spontaneous breathing, superficial and optimal ventilation without pneumoperitoneum, and with pneumoperitoneum at low (6 mm Hg) and higher (10 mm Hg) insufflation pressures were compared. The CO(2) pneumoperitoneum profoundly affected blood gases, acid-base balance, and oxygen homeostasis. Carboxemia with increasing end-tidal CO(2) and partial pressure of CO(2) (p <0.001), acidosis with decreasing pH (p <0.001), and base deficiency with decreasing actual base excess (p <0.001), standard base excess and standard bicarbonate and acid excess with increasing hydrogen bicarbonate (p <0.05 and <0.01) were found. Desaturation (p <0.01) with decreasing oxyhemoglobin p <0.05) and hemoglobin oxygen affinity (p <0.01) were also found. Carboxemia with acidosis was more pronounced with higher (p <0.01) than with lower (p >0.05) intraperitoneal pressures, and also with spontaneous breathing (p <0.05) and superficial ventilation (p <0.001) than with optimal ventilation, resulting in metabolic hypoxemia.nnnCONCLUSIONnIn superficially ventilated and spontaneously breathing rabbits, CO(2) pneumoperitoneum profoundly affected blood gases, acid-base balance, and oxygen homeostasis, resulting in metabolic hypoxemia. With optimal ventilation and low intraperitoneal pressure carboxemia, respiratory acidosis, and changes in oxygen metabolism were minimal.

Reduction of CO2‐pneumoperitoneum‐induced metabolic hypoxaemia by the addition of small amounts of O2 to the CO2 in a rabbit ventilated model. A preliminary study

BACKGROUNDnCO(2)-pneumoperitoneum used in endoscopic surgery induces system effects by CO(2) absorption. This study investigated the effect of the addition of O(2) to CO(2)-pneumoperitoneum, upon CO(2) absorption.nnnMETHODSnThe effect of a pneumoperitoneum using 100% CO(2) or 94% CO(2) + 6% O(2) upon arterial blood gases, acid base and O(2) homeostasis was evaluated. In series A suboptimal ventilation and a pneumoperitoneum pressure (PP) of 10 mmHg was used. In series B adequate ventilation and PP of 6 mmHg was used.nnnRESULTSnCO(2)-pneumoperitoneum profoundly affected blood gases and acid base homeostasis i.e. increasing pCO(2), HCO(3)(P < 0.001) and lactate concentrations (P < 0.05) and decreasing pH, actual base excess and standard bicarbonate (P < 0.001), resulting in metabolic hypoxaemia with desaturation, lower pO(2) (P < 0.001) and O(2)Hb (P < 0.05). These effects were more pronounced with higher PP and suboptimal ventilation.nnnCONCLUSIONnCO(2)-pneumoperitoneum profoundly affected blood gases and acid base homeostasis resulting in metabolic hypoxaemia. The addition of 6% of O(2) to the CO(2)-pneumoperitoneum prevented these effects to a large extent. If these preliminary data are confirmed in the human, the addition of a few percent of O(2) to CO(2) could become important for endoscopic surgery of long duration, especially in obese patients with limited cardiorespiratory adaptation and steep Trendelenburg.

Role of the peritoneal cavity in the prevention of postoperative adhesions, pain, and fatigue.

A surgical trauma results within minutes in exudation, platelets, and fibrin deposition. Within hours, the denuded area is covered by tissue repair cells/macrophages, starting a cascade of events. Epithelial repair starts on day 1 and is terminated by day 3. If repair is delayed by decreased fibrinolysis, local inflammation, or factors in peritoneal fluid, fibroblast growth starting on day 3 and angiogenesis starting on day 5 results in adhesion formation. For adhesion formation, quantitatively more important are factors released into the peritoneal fluid after retraction of the fragile mesothelial cells and acute inflammation of the entire peritoneal cavity. This is caused by mechanical trauma, hypoxia (e.g., CO2 pneumoperitoneum), reactive oxygen species (ROS; e.g., open surgery), desiccation, or presence of blood, and this is more severe at higher temperatures. The inflammation at trauma sites is delayed by necrotic tissue, resorbable sutures, vascularization damage, and oxidative stress. Prevention of adhesion formation therefore consists of the prevention of acute inflammation in the peritoneal cavity by means of gentle tissue handling, the addition of more than 5% N2O to the CO2 pneumoperitoneum, cooling the abdomen to 30°C, prevention of desiccation, a short duration of surgery, and, at the end of surgery, meticulous hemostasis, thorough lavage, application of a barrier to injury sites, and administration of dexamethasone. With this combined therapy, nearly adhesion-free surgery can be performed today. Conditioning alone results in some 85% adhesion prevention, barriers alone in 40%-50%.

The role of the peritoneal cavity in adhesion formation

The article by Barcz et al. (1) deserves a comment since it should make us think. Differences in peritoneal fluid constituents between women with and without endometriosis have been studied repetitively since the late 1970s in order to gain insight into the pathophysiology of endometriosis and associated infertility. Endometriosis is associated with a low-grade inflammation with more and more activated macrophages in peritoneal fluid. Despite the huge amount of data available, as this article also contributes to the data of cytokine concentrations, a comprehensive conclusion was never reached. More specifically, for most factors it remains speculative which are contributing to the development of endometriosis and which are a consequence of endometriosis (2). Peritoneal adhesions following surgery remain a major problem leading to chronic pelvic pain, infertility, and occasional bowel obstructions. The use of barriers to prevent adhesion formation was based on the prevailing concept that peritoneal healing and adhesion formation is decided in a few days, resulting from a local inflammatory process between opposing lesions. In this process, fibrin deposition and fibrinolysis play a major role. Efficacy of a barrier, however, rarely exceeded 50%. Recent evidence has demonstrated the importance of the entire peritoneal cavity and of factors in peritoneal fluid to enhance adhesion formation. While peritoneal lesions and the associated local inflammatory reaction remain essential to start the process, factors from the peritoneal cavity are quantitatively much more important for the severity and extend of adhesion formation. That slight manipulation of bowels in the upper abdomen can increase adhesions at a surgical lesion in the lower abdomen unequivocally points to factors from the upper abdomen reaching the lower abdomen through the peritoneal fluid (3). A series of experiments in a laparoscopic mouse model pointed to an acute inflammation of the entire peritoneal cavity as the driving mechanism (4). This acute inflammatory reaction is caused by the cumulative mesothelial trauma either mechanically or bymesothelial hypoxia (CO2 pneumoperitoneum) (5) or hyperoxia (exposure to air, as in open surgery), or desiccation. Prevention thus should aim at a mesothelial partial oxygen pressure between 10 and 70 mmHg (achieved by adding a few percent of oxygen to the CO2 pneumoperitoneum), while preventing any desiccation. Slight cooling of the peritoneal cavity is beneficial, since the mesothelial cell becomes more resistant to trauma. It should be realized that in order to combine absence of desiccation and cooling, the latter should be performed independently (e.g. by sprinkling saline at room temperature). If the temperature of the incoming humidified gas is slightly higher condensation will occur. If the temperature of the incoming gas is lower than the peritoneal temperature it will be heated and desiccation will occur. Since bothmechanisms of adhesion formation are complementary (local inflammatory process enhanced by factors from the peritoneal cavity), prevention should address both mechanisms. In animal models (6) and in the human (in preparation) the sequential minimalization of mesenchymal damage during

Granulosa Cell Tumors of the Ovary and Inhibin B

We present the results of immunoenzyme detection of inhibin B in blood serum of patients with adult-type granulosa cell tumors of the ovary. Blood concentration of inhibin B at the end of menstrual cycle in patients with tumor relapse was significantly higher than in patients during remission and in virtually healthy women. The increase in inhibin B concentration preceded clinical manifestation of the disease relapse by 2–13 months, which demonstrates high diagnostic sensitivity of this marker and suggests that it can be recommended for the use in diagnostics and monitoring of granulosa cell tumors of the ovaries.

Effects of adding small amounts of oxygen to a carbon dioxide-pneumoperitoneum of increasing pressure in rabbit ventilation models

OBJECTIVEnTo evaluate the metabolic consequences of the addition of oxygen to the CO(2)-pneumoperitoneum.nnnDESIGNnProspective randomized study in rabbits. After 30 minutes of ventilation pneumoperitoneum was maintained for 90 minutes with pure CO(2) or CO(2) with 2% or 6% of oxygen. The intraperitoneal pressure was increased from 10 to 15 and 20 mm Hg every 30 minutes. Ventilation rate was either fixed or a progressive hyperventilation. End points were changes in arterial blood gases (Pco(2), Po(2)), pH, acid-base balance (actual base excess [ABE], standard bicarbonate [SBC], standard base excess [SBE], hydrogen carbonate [HCO(3)(-)], concentration of total carbon dioxide [Tco(2)]); oxygen and oximetry (oxyhemoglobin [O(2)Hb], oxygen saturation [So(2)], reduced hemoglobin [RHb], total oxygen concentration [To(2)], and oxygen tension at half saturation assessing hemoglobin oxygen affinity [p50]); and lactate concentrations assayed every 15 minutes.nnnSETTINGnUniversity research center.nnnANIMALSnTwenty-four adult female New Zealand white rabbits.nnnINTERVENTION(S)nAnesthesia, mechanical ventilation, and pneumoperitoneum.nnnRESULT(S)nThe effects of CO(2)-pneumoperitoneum on all end points increased with the elevated intraperitoneal pressure and were more pronounced when ventilation was fixed. Changes were less when 2% or 6% of oxygen had been added to the CO(2)-pneumoperitoneum. With use of logistic regression, the addition of oxygen, intraperitoneal pressure, and ventilation were found to be independent variables affecting Pco(2), pH, ABE, SBE, HCO(3)(-), O(2)Hb, So(2), p50, and end-tidal CO(2).nnnCONCLUSION(S)nThe metabolic consequences of the combined effect of increased intraperitoneal pressure and CO(2)-pneumoperitoneum were less when 2% to 6% of oxygen was added or when animals were hyperventilated. We suggest that metabolic and mesothelial hypoxemia caused by CO(2) absorption can be reduced by adding small amounts of oxygen and by hyperventilation.

Epidemiology of subtle, typical, cystic, and deep endometriosis: a systematic review

Endometriosis is known as a cause of pelvic pain and infertility. The epidemiology of endometriosis is important since the prevalence and severity of endometriosis might be linked to pollution and to our modern lifestyle, comprising food intake, chemical disruptors, postponement of the first pregnancy, and stress, as indicated by “a career women’s disease.” Epidemiological data based upon hospital discharge records should be viewed with caution. Indeed, that subtle lesions are considered pathology causes a major increase in prevalence, while the laparoscopic recognition and histological confirmation of subtle and typical lesions vary with the expertise and interest of the surgeon. The epidemiological data published by surgical groups on severe forms, as cystic and deep endometriosis, have a referral bias and lack the numbers required for meaningful statistics. Fundamental to understanding epidemiology of endometriosis is that it is unclear that all presentations of endometriosis constitute one disease. We therefore performed a systematic review of the incidences and severity of subtle, typical, cystic, and deep endometriosis lesions separately. The only data found were that severe endometriosis carries a greater hereditary risk and that the prevalence of subtle endometriosis decreases with age whereas the prevalences of typical, cystic, and deep endometriosis increase with age. Surgeons that witnessed over the last 20xa0years in over 1000 interventions each the evolution of deep endometriosis, however, had a strong impression that severity and prevalence of deep endometriosis are increasing. In conclusion, there are no solid epidemiologic data of each type of endometriosis separately. With all restrictions imposed by the referral bias and by a clinical impression, the consistency of the observation of deep endometriosis surgeons should be a reason for concern. The investigation of the epidemiology of deep endometriosis is suggested since it is relevant because it is clinically severe pathologic and feasible since it can be done from hospital-based records. Indeed, most women will ultimately have surgery with solid information on severity and an unbiased diagnosis if defined as “adenomyosis externa.”

A mixture of 86% of CO2, 10% of N2O, and 4% of oxygen permits laparoscopy under local anesthesia: a pilot study

The aim of this study is to verify that 10xa0% of N2O in CO2 sufficiently reduces pain to permit laparoscopy under local anesthesia. In nine patients undergoing laparoscopy under local anesthesia for tubal sterilization, a mixture of 86xa0% of CO2, 10xa0% of N2O, and 4xa0% of oxygen (the Gas Mixture) was used for the pneumoperitoneum. For CO2, N2O, and for the Gas Mixture, the pain when blowing over the tongue tip and the pH changes of saline and Hartmann’s solution were estimated. In all nine patients, discomfort was minimal and the intervention was well tolerated, similar to 100xa0% N2O. Tongue tip pain (nu2009=u200915), on VAS scale, was lower with 86xa0% CO2u2009+u200910xa0%xa0N2Ou2009+u20094xa0% O2 (2.4u2009±u20091.4, Pu2009=u20090.005) and much lower with 100xa0% N2O (0.3u2009±u20090.6, Pu2009<u20090.0007) than with pure CO2 (3.6u2009±u20091.7). The pH of saline (nu2009=u20095) decreased from 7.00u2009±u20090.07 to 4.18u2009±u20090.04 (Pu2009=u20090.001), 6.98u2009±u20090.08 (NS), and 4.28u2009±u20090.04 (Pu2009=u20090.01) with 100xa0% CO2, 100xa0% N2O and the Gas Mixture, respectively. The pH of Hartmann’s solution (nu2009=u20095) decreased similarly from 7.00u2009±u20090.07 to 5.18u2009±u20090.04 (Pu2009=u20090.01), 7.02u2009±u20090.19 (NS), and 5.3u2009±u20090.4 (Pu2009=u20090.01), respectively. These data demonstrate that a mixture with 10xa0% of N2O and 4xa0% of O2 in CO2 permits laparoscopy under local anesthesia. This result cannot be explained by direct irritation estimated by tongue tip pain or by pH changes.

Macroscopic and functional assessment of the efficacy of ovary regeneration with fibrin glue and various suture materials following its V-shaped resection

LITERATURE CITED 1. G. G. Avtandilov, N. I. Yabluchanskii, K. D. Salbiev, and L. M. Nepomnyashchikh, Quantitative Morphology and Mathemat i ca l Simulat ion of Myocardial Infarction [in Russian], Novosibirsk (1984). 2. A. F. Aleinikov, A. S. Osennii, and G. L. Vereshchagin, Modem Express Methods in Plant and Animal Research [in Russian], Novosibirsk, p. 26. 3. M. N. Kondrashova and Yu. V. Evtodienko, Biophysics of Complex Systems and Radiation Injuries [in Russian], Moscow 11977), p. 249. 4. L. A. Semenova, L. M. Nepomnyashchikh, and D. E. Semenov, Morpholog7 of Plastic Insufficiency of Heart Muscle Cells [in Russian], Novosibirsk (1985). 5. B. N. Tarusov, Arkh. Biol. Nauk, 52, No. 2, 172 (1938). 6. Electric Impedance of Biological Tissues [in Russian], Moscow 11990).