• insufflation gas
• laparoscopic surgery
• pain

• Humans
• Pain, Postoperative/prevention & control
• Pain, Postoperative/etiology
• Female
• Double-Blind Method
• Laparoscopy/methods
• Laparoscopy/adverse effects
• Carbon Dioxide/administration & dosage
• Pneumoperitoneum, Artificial/methods
• Pneumoperitoneum, Artificial/adverse effects
• Nitrous Oxide/administration & dosage
• Adult
• Middle Aged
• Prospective Studies
• Oxygen/administration & dosage
• Gynecologic Surgical Procedures/methods
• Gynecologic Surgical Procedures/adverse effects
• Pain Measurement
• Insufflation/methods
• Insufflation/adverse effects
• Belgium

• Boric acid
• Laparotomy
• Post-operative intra-abdominal Adhesions
• Testis

• HuoXueTongFu formula
• Intraperitoneal adhesion
• Macrophage
• MerTK
• Neutrophil extracellular traps (NETs)

• Animals
• Proto-Oncogene Proteins c-akt/metabolism
• Drugs, Chinese Herbal/pharmacology
• Mice
• c-Mer Tyrosine Kinase/metabolism
• Signal Transduction/drug effects
• Male
• Macrophages/drug effects
• Macrophages/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Tissue Adhesions/prevention & control
• Tissue Adhesions/metabolism
• Extracellular Traps/drug effects
• Extracellular Traps/metabolism
• Disease Models, Animal

• Adhesions
• Complications
• Laparoscopy
• Mixed gas
• Pneumoperitoneum

• Animals
• Humans
• Mice
• Carbon Dioxide/administration & dosage
• Insufflation/methods
• Laparoscopy/methods
• Minimally Invasive Surgical Procedures/methods
• Models, Animal
• Nitrous Oxide/administration & dosage
• Oxygen/administration & dosage
• Pneumoperitoneum, Artificial/methods
• Pneumoperitoneum, Artificial/adverse effects
• Tissue Adhesions/prevention & control

• adhesions
• histological examination
• tuboperitoneal infertility

• Pregnancy
• Humans
• Female
• Infertility, Female/etiology
• Infertility, Female/surgery
• Tissue Adhesions/complications
• Tissue Adhesions/prevention & control
• Tissue Adhesions/surgery
• Laparoscopy/adverse effects
• Pregnancy, Ectopic/surgery
• Abortion, Induced/adverse effects

• adhesion
• film
• phospholipid
• polycaprolactone
• postoperative
• quercetin
• silver

• Adhesion
• Benign
• Development
• Disorders
• Fibro-proliferative
• Postoperative

• CO(2) pneumoperitoneum +4% oxygen
• Laparoscopy
• Mesothelial trauma
• Peritoneum
• Postoperative adhesions
• electron microscopy

• Artificial ascites
• liver neoplasms
• local tumor progression
• risk factor
• tumor ablation

Postoperative peritoneal adhesion (PPA) is a common postoperative complication caused by any peritoneal inflammatory process. This study aimed to identify the biological function of large intergenic non-coding RNAs (lincRNAs) Cox-2 in the inflammation reaction of adhesion formation. The Cox-2 expression in peritoneal adhesion tissues and normal tissues was detected. The human peritoneal mesothelium cells (HPMCs) were treated with lipopolysaccharide (LPS) to induce inflammatory injury. The effect of Cox-2 suppression on cell viability, apoptosis and inflammatory factors of LPS induced HPMCs injury were explored. The regulatory correlation between Cox-2 and miR-21, as well as the targeted genes of miR-21 were identified. Meanwhile, the regulatory mechanism of Cox-2/miR-21 axis on NF-κB pathway was explored. It indicated that Cox-2 was highly expressed in peritoneal adhesion tissues compared with that in normal tissues. Suppression of Cox-2 ameliorated LPS induced HMPCs injury as cell viability was promoted, and cell apoptosis and the production of inflammatory factors were inhibited. And suppression of Cox-2 reversed the LPS induced HPMCs injury by regulation of miR-21 negatively. miR-21 was negatively correlated with TLR4, and TLR4 was predicted as target gene of miR-21. Furthermore, the suppression of miR-21 on LPS induced HPMCs injury was reversed by knockdown of TLR4, which could inhibited the activation of NF-κB pathway axis. It suggested that the effect of Cox-2 on LPS induced HPMCs injury was achieved by negatively regulation of miR-21 and targeted TLR4 through NF-κB pathway axis. The findings may provide a new insight into preventing postoperative peritoneal adhesion.

Microsurgical tenets and peritoneal conditioning during laparoscopic surgery (LS) decrease postoperative adhesions and pain. For a trial in human, the strong beneficial effects of N₂O needed to be confirmed in open surgery (OS).

In a mouse model for OS, the effect of the gas environment upon adhesions was evaluated. Experiment I evaluated desiccation and the duration of exposure to CO₂, N₂O or CO₂ + 4%O₂. Experiment II evaluated the dose-response curve of adding N₂O to CO₂. Experiment III compared humidified CO₂ + 10% N₂O during LS and OS.

In OS, 30- and 60-min exposure to non-humidified CO₂ caused mortality of 33 and 100%, respectively. Mortality was prevented by humidification, by dry N₂O or dry CO₂ + 4%O₂. Adhesions increased with the duration of exposure to CO₂ (p < 0.0001) and decreased slightly by humidification or by the addition of 4% O₂. N₂O strongly decreased adhesions at concentrations of 5% or greater. With humidified CO₂ + 10% N₂O, adhesion formation was similar in OS and LS.

The drug-like and strong beneficial effect of low concentrations of N₂O is confirmed in OS.

• Conditioning
• Humidification
• Microsurgery
• Microsurgical principle
• N2O
• Postoperative adhesions

Abdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox) is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions.

Female C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT) to induce fibrosis, together with chemical (ß-aminoproprionitrile–BAPN) or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC) were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α) and progesterone to determine effects on Lox mRNA in vitro.

NT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro.

Our results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development.

• Abdominal Cavity/surgery
• Aminopropionitrile/pharmacology
• Animals
• Collagen/antagonists & inhibitors
• Collagen/genetics
• Collagen/metabolism
• Dexamethasone/pharmacology
• Epithelium/drug effects
• Epithelium/metabolism
• Epithelium/pathology
• Extracellular Matrix Proteins/antagonists & inhibitors
• Extracellular Matrix Proteins/genetics
• Extracellular Matrix Proteins/metabolism
• Female
• Gene Expression
• Humans
• Interleukin-1alpha/pharmacology
• Mice
• Mice, Inbred C57BL
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Molecular Targeted Therapy
• Nanotubes, Carbon/toxicity
• Peritoneal Fibrosis/chemically induced
• Peritoneal Fibrosis/genetics
• Peritoneal Fibrosis/pathology
• Peritoneal Fibrosis/prevention & control
• Primary Cell Culture
• Progesterone/pharmacology
• Protein-Lysine 6-Oxidase/antagonists & inhibitors
• Protein-Lysine 6-Oxidase/genetics
• Protein-Lysine 6-Oxidase/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Tissue Adhesions/chemically induced
• Tissue Adhesions/genetics
• Tissue Adhesions/pathology
• Tissue Adhesions/prevention & control

• Wellcome Trust
• 110126/Z/15/Z Wellcome Trust
• G0701127 Medical Research Council
• G0900550 Medical Research Council

• Surgery
• adhesion prevention
• conditioning
• endometriosis
• peritoneum

• Body temperature
• Humidity
• Laparoscopy
• Pain
• Pneumoperitoneum
• Post-operative adhesions

• Animals
• Carbon Dioxide/therapeutic use
• Cold Temperature
• Hot Temperature
• Humans
• Humidity
• Hypothermia/prevention & control
• Insufflation
• Laparoscopy/methods
• Pain, Postoperative/prevention & control
• Peritoneum/pathology
• Tissue Adhesions/prevention & control

• experimental research
• ligustrazine
• peritoneal mesothelial cells
• transforming growth factor β/Smad

• Abdominal adhesions
• Angiogenesis
• Electroacupuncture
• Inflammation
• ST36

• Abdominal Wound Closure Techniques
• Animals
• Cecum/pathology
• Electroacupuncture
• Inflammation/metabolism
• Inflammation/prevention & control
• Male
• Neovascularization, Pathologic/metabolism
• Neovascularization, Pathologic/prevention & control
• Platelet Endothelial Cell Adhesion Molecule-1/metabolism
• Random Allocation
• Rats, Sprague-Dawley
• Tissue Adhesions/pathology
• Tissue Adhesions/prevention & control
• Tumor Necrosis Factor-alpha/metabolism
• Vascular Endothelial Growth Factor A/metabolism

The aim of this study is to verify that 10 % 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 86 % of CO₂, 10 % of N₂O, and 4 % 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 100 % N₂O. Tongue tip pain (n = 15), on VAS scale, was lower with 86 % CO₂ + 10 % N₂O + 4 % O₂ (2.4 ± 1.4, P = 0.005) and much lower with 100 % N₂O (0.3 ± 0.6, P < 0.0007) than with pure CO₂ (3.6 ± 1.7). The pH of saline (n = 5) decreased from 7.00 ± 0.07 to 4.18 ± 0.04 (P = 0.001), 6.98 ± 0.08 (NS), and 4.28 ± 0.04 (P = 0.01) with 100 % CO₂, 100 % N₂O and the Gas Mixture_, respectively. The pH of Hartmann’s solution (n = 5) decreased similarly from 7.00 ± 0.07 to 5.18 ± 0.04 (P = 0.01), 7.02 ± 0.19 (NS), and 5.3 ± 0.4 (P = 0.01), respectively. These data demonstrate that a mixture with 10 % of N₂O and 4 % 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.

• Anesthesia
• Conditioning
• Gas
• Laparoscopy
• Pain
• Pneumoperitoneum

• Bioconjugates
• Evaluation
• Hyaluronic acid
• Pro-drug
• Synthesis

Although laparoscopy has the potential to reduce peritoneal trauma and post-operative peritoneal adhesion formation, only one randomized controlled trial and a few comparative retrospective clinical studies have addressed this issue. Laparoscopy reduces de novo adhesion formation but has no efficacy in reducing adhesion reformation after adhesiolysis. Moreover, several studies have suggested that the reduction of de novo post-operative adhesions does not seem to have a significant clinical impact. Experimental data in animal models have suggested that CO₂ pneumoperitoneum can cause acute peritoneal inflammation during laparoscopy depending on the insufflation pressure and the surgery duration. Broad peritoneal cavity protection by the insufflation of a low-temperature humidified gas mixture of CO₂, N₂O and O₂ seems to represent the best approach for reducing peritoneal inflammation due to pneumoperitoneum. However, these experimental data have not had a significant impact on the modification of laparoscopic instrumentation. In contrast, surgeons should train themselves to perform laparoscopy quickly, and they should complete their learning curves before testing chemical anti-adhesive agents and anti-adhesion barriers. Chemical anti-adhesive agents have the potential to exert broad peritoneal cavity protection against adhesion formation, but when these agents are used alone, the concentrations needed to prevent adhesions are too high and could cause major post-operative side effects. Anti-adhesion barriers have been used mainly in open surgery, but some clinical data from laparoscopic surgeries are already available. Sprays, gels, and fluid barriers are easier to apply in laparoscopic surgery than solid barriers. Results have been encouraging with solid barriers, spray barriers, and gel barriers, but they have been ambiguous with fluid barriers. Moreover, when barriers have been used alone, the maximum protection against adhesion formation has been no greater than 60%. A recent small, randomized clinical trial suggested that the combination of broad peritoneal cavity protection with local application of a barrier could be almost 100% effective in preventing post-operative adhesion formation. Future studies should confirm the efficacy of this global strategy in preventing adhesion formation after laparoscopy by focusing on clinical end points, such as reduced incidences of bowel obstruction and abdominal pain and increased fertility.

• Peritoneal adhesions
• Laparoscopy
• Abdomen
• Gastrointestinal surgery
• Inflammation
• Learning curve
• Anti-adhesion
• Animal models
• Clinical studies
• Laparoscopic resection of gastrointestinal

• Animals
• Digestive System Surgical Procedures/adverse effects
• Digestive System Surgical Procedures/methods
• Gastrointestinal Tract/surgery
• Humans
• Laparoscopy/adverse effects
• Models, Animal
• Peritoneal Diseases/etiology
• Peritoneal Diseases/pathology
• Peritoneal Diseases/prevention & control
• Tissue Adhesions
• Treatment Outcome

• Colon cancer
• Colonic anastomosis
• Ileus
• Iloprost
• Obstruction

• Anastomosis, Surgical
• Animals
• Body Weight/drug effects
• Collagenases/metabolism
• Colon/enzymology
• Colon/surgery
• Disease Models, Animal
• Hydroxyproline/metabolism
• Ileus/complications
• Ileus/drug therapy
• Iloprost/pharmacology
• Iloprost/therapeutic use
• Injections, Intraperitoneal
• Male
• Pressure
• Random Allocation
• Rats
• Surgical Wound Dehiscence/etiology
• Tissue Adhesions/etiology
• Vasodilator Agents/pharmacology
• Vasodilator Agents/therapeutic use
• Wound Healing/drug effects

The addition of 4 % O₂ and 10 % N₂O to the CO₂ pneumoperitoneum (PP), together with slight cooling and humidification (conditioning), contributes to reducing adhesions by preventing mesothelial damage. We investigated the effect of peritoneal damage during laparoscopy on tumor implantation.

In Experiment 1, different tumor cell concentrations were injected into control mice without PP and into mice with 60-min dry CO₂PP (mesothelial damage). In Experiment 2, tumor cells were injected into control mice (group I) and in mice with mesothelial damage (group II). In groups III to VI, mesothelial damage was decreased by adding humidification, humidification + 10 % N₂O, humidification + 10 % N₂O + 4 % O₂, and conditioning, respectively.

In Experiment 1, the tumors increased with the number of cells injected and with mesothelial damage in the abdominal cavity (p = 0.018) and abdominal wall (p < 0.0001). Experiment 2 confirmed that 60 min of dry CO₂PP increased the number of tumors in the abdominal cavity and wall (p = 0.026 and p = 0.003, respectively). The number of tumors was decreased in the abdominal cavity by conditioning (p = 0.030) and in the abdominal wall using humidified CO₂ (p = 0.032) or conditioning (p = 0.026).

Tumor implantation was enhanced by peritoneal damage (60 min of dry CO₂PP and desiccation), but this was prevented by conditioning. If confirmed in humans, conditioning would become important for oncologic surgery.

• N(2)O
• O(2)
• Pneumoperitoneum
• adhesions
• bleeding
• laparoscopy
• peritoneal conditioning

• Animals
• Blood Transfusion/methods
• Carbon Dioxide/administration & dosage
• Dose-Response Relationship, Drug
• Drug Combinations
• Female
• Humans
• Laparoscopy
• Mice
• Mice, Inbred BALB C
• Nitrous Oxide/administration & dosage
• Retropneumoperitoneum/blood
• Retropneumoperitoneum/etiology
• Retropneumoperitoneum/prevention & control
• Retrospective Studies
• Tissue Adhesions/blood
• Tissue Adhesions/etiology
• Tissue Adhesions/prevention & control
• Treatment Outcome

• Animals
• Epithelium/drug effects
• Epithelium/ultrastructure
• Membranes, Artificial
• Microscopy, Electron, Scanning
• Peritoneal Diseases/pathology
• Peritoneal Diseases/prevention & control
• Rats
• Rats, Wistar
• Tissue Adhesions/pathology
• Tissue Adhesions/prevention & control