Peritoneal Damage in Laparoscopic Surgery

Study Overview
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Brief Summary
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The investigators hypothesized that applying a low intraperitoneal pressure pneumoperitoneum (≤ 8mmHg) during laparoscopic cholecystectomy, the adverse impact on the surgical peritoneal environment (measured as gene expression of extracellular matrix, adhesion and inflammatory cytokine as well as oxidative stress response and apoptotic index), can be minimized and probably clinical outcomes might be better.

Detailed Description
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Cholelithiasis is one of the most frequent abdominal diseases requiring surgical treatment. Laparoscopic cholecystectomy is currently the procedure of choice to remove the gallbladder. There is growing evidence that increased intra-abdominal pressure pneumoperitoneum, even for short periods of time, is associated with both transient and sometimes persistent adverse effects that might negatively affect the surgical peritoneal environment .There are some studies that have demonstrated that using low intraperitoneal pressure pneumoperitoneum, undesired effects like adverse impact on peritoneal tissue and negative clinical outcomes could be reduced.Therefore intraperitoneal pressure target during laparoscopy should be the lowest to allow surgery be securely performed. Many strategies have been tested in order to improve the volume of gas can be insufflated inside the abdominal cavity while maintaining low pneumoperitoneum pressure during laparoscopy.So far the most studied strategy has been deep neuromuscular blockade.However the effect of the depth of neuromuscular blockade in the intraabdominal volume is still controversial as sometimes in humans its benefits are marginal.There is scarce information in the medical literature regarding the adverse impact on peritoneal tissue of high pneumoperitoneum pressure during laparoscopy in humans. In addition available data are provided by non-prospective, non-randomized and small sample studies, so randomized controlled trials are required to ascertain this issues.To our knowledge our study is the first prospective and randomized controlled trial in humans aiming to study the adverse impact of high pressure pneumoperitoneum on peritoneal tissue as well as to associate it with clinical outcomes.

Official Title
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Characterization of Changes in Peritoneal Cells Gene Expression After Standard Versus Low Pressure Laparoscopic Cholecystectomy and Its Clinical Correlation

Conditions
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Peritoneal Damage

Intervention / Treatment
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* Procedure: Low pressure pneumoperitoneum
* Procedure: standard pneumoperitoneum pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years, signed informed consent, undergoing laparoscopic cholecystectomy for symptomatic cholelithiasis or gallbladder polyps. Exclusion Criteria: Emergency surgery. Previous surgery at supramesocolic compartment. Previous peritoneal inflammatory process. Pregnancy or breastfeeding. Patient refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low pneumoperitoneum pressure.<br>Pneumoperitoneum pressure at 8 mmHg or lower. | Procedure: Low pressure pneumoperitoneum<br>* Low pressure pneumoperitoneum<br>|
| Active Comparator: standard pneumoperitoneum pressure<br>Pneumoperitoneum pressure at 12 mmHG or higher | Procedure: standard pneumoperitoneum pressure<br>* standard pneumoperitoneum pressure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory Peritoneal Markers | logaritmic levels of mRNA of the different markers at time 1 hour after creation of the pneumoperitoneum | he values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1). | 
| Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | f. CTGF connective tissue growth factor. g. MMP-9 matrix metalloproteinase-9. h. PAI-I plasminogen activator inhibitor-I. i. E-selectin. Samples will be processed to obtain total RNA with TRI Reagent™ (Sigma) and will be quantified with NanoDrop spectrophotometer. | The values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1). | 
| Oxidative Stress Response Marker:MDA (Malondialdehyde) | MDA (malondialdehyde) determination will be done with ELISA | The values of the main variables will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1) | 
| Apoptotic Index | This measure is reported as the mean of the difference of the percentage of apoptotic cells at baseline minus the final | The values of the main variables will be obtained from the study of peritoneal tissue samples, one hour after the creation of the pneumoperitoneum compared to basal peritoneal tissue samples. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low pressure pneumoperitoneum, standard pressure pneumoperitoneum, laparoscopy cholecystectomy