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Base de datos Cochrane de Revisiones Sistemáticas Protocolo - Intervención

Routine cholecystectomy during Roux‐en‐Y gastric bypass with or without choledocholithiasis

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Versión publicada: 26 agosto 2013 Historial de versiones

https://doi.org/10.1002/14651858.CD010715
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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To evaluate the efficacy and safety of routine cholecystectomy for all patients during RYGB compared to alternative regimes.

Background

Description of the condition

Morbid obesity is a major risk factor for developing gallstones (Amaral 1985; Fakhry 1987; Fobi 2002; Liddle 1989; Maclure 1989; Schmidt 1988). In the severely obese, the gallbladder bile concentration of cholesterol is increased without sufficient increase in bile salt and phospholipid to keep cholesterol in solution. Due to increased cholesterol secretion by liver in morbidly obese patients, they have a high cholesterol concentration in the bile without a proportionate increase in phospholipids and bile salts (Faloon 1988) which leads to precipitation of cholesterol in gall bladder leading to formation of gall stones. Obese patients also have a larger and hypo‐contractile gallbladder and increased nucleation factors further predisposing to high incidence of cholesterol gallstones (Marzio 1988). Worldwide prevalence of morbid obesity has reached epidemic proportions (Flegal 2010) and Rouxen‐Y gastric bypass (RYGB) is a fast and mostly permanent way to lose weight for those with severe obesity (Hamad 2003; Villegas 2004). Surgical management of obesity leads to improvement in overall health and quality of life by alleviating their weight related medical problems (Choban 1999). However, rapid weight loss due to RYGB leads to increased formation of gallstones in these patients (Guadalajara 2006; Jones 1995) with the reported incidence ranging from 30% to 53% (Iglézias Brandão de Oliveira 2003; Villegas 2004). Increased gall stone formation in after RYGB is attributed to cholesterol super‐saturation of bile from mobilized tissue stores,reduced gallbladder contractility and excess mucin production (Carey 1993; Everhart 1993; Iglézias Brandão de Oliveira 2003; Shiffman 1991). Cholecystokinin is secreted from the upper gastrointestinal tract by stimulation from contents. After RYGB, enteric contents are not able to reach the upper gastrointestinal tract which leads to absence of cholecystokinin secretion. Absence of cholecystokinin results in poor gallbladder emptying, and altering the entero‐hepatic circulation of biliary salts.

Description of the intervention

RYGB promotes weight loss by restricting food intake and by decreasing the absorption of food.In this surgery a small pouch is created by dividing the upper end of the stomach. After that a section of small intestine is cut, making it shorter. This Y‐shaped section of the small intestine is re attached to the pouch. The procedure creates a direct connection from the stomach to the lower segment of the small intestine.This procedure leads to bypassing portions of the lower stomach, duodenum and jejunum that absorb most of calories and nutrients. At present, there are several approaches of treating gallstone disease in patients undergoing RYGB have been advocated: Routine prophylactic cholecystectomy in all patients at RYGB to remove gallstones or to prevent gallstone formation (Fobi 2002; Kim 2009; Leim 2004) screening of patients preoperatively with ultrasonography and cholecystectomy in patients only with positive findings (Tucker 2008), cholecystectomy after positive intraoperative finding of gallstones with ultrasound (Scott 2003), routine administration of ursodeoxycholic acid to all patients to prevent gallstone formation (Swartz 2005), and no screening and no routine cholecystectomy,unless the patient has symptoms consistent with biliary disease (Patel 2006).

How the intervention might work

Prophylactic cholecystectomy prevents the gallstone‐related complications such as cholecystitis and gallstone‐pancreatitis which can be quite difficult to diagnose and manage after RYGB since the procedure disturbs the anatomy and makes endoscopic retrograde cholangiopancreatography (ERCP) difficult . Further the morbidity and mortality of choledocholithiasis and its complications can be quite high . However there are technical difficulties and additional procedure related morbidity to be considered especially with laparoscopic RYGB. There are similar concerns with the asymptomatic gallbladder pathology since it is usually associated with insignificant morbidity and doesn't require intervention, so a group of surgeons don't even warrant screening of the asymptomatic patients.

Why it is important to do this review

Management of the gallbladder in patients undergoing RYGB is controversial. Despite the well‐documented high risk of gallbladder complications after bariatric surgery, there is still no commonly accepted therapeutic approach to this problem. Some surgeons justify routine cholecystectomy at RYGB surgery and others advocate concurrent cholecystectomy only in patients with pathological gallbladder findings. Surgeon who are in favour of routine cholecystectomy cite ease and feasibility of cholecystectomy and up to 95% pathologic findings in the gallbladder specimens (Fobi 2002; Leim 2004; Schmidt 1988; Seinige 1991) and overall low morbidity rates due to second procedure, choledocholithiasis and gallstone pancreatitis (Fobi 2002; Hamad 2003; Leim 2004). But others believe that bariatric candidates should be routinely screened by ultrasonography for gallbladder pathology before the operation and that cholecystectomy should be performed in patients with pathological findings since concomitant cholecystectomy can be difficult, and can lead to significantly longer operative times and hospital stays. A recently published study (Worni 2012) found that concomitant cholecystectomy has higher rates of postoperative complications and mortality and similar results were reported by a recently published meta‐analysis of observational studies which found that a prophylactic concomitant cholecystectomy during RYGB has more complications in patients without cholelithiasis and should be performed only in patients with symptomatic biliary disease (Warschkow 2013). This raises the need to perform a systematic review and analysis of the available data to help surgeons make an informed decision regarding routine cholecystectomy during RYGBS in patients with and without choledocholithiasis.

Objectives

To evaluate the efficacy and safety of routine cholecystectomy for all patients during RYGB compared to alternative regimes.

Methods

Criteria for considering studies for this review

Types of studies

  1. Randomized controlled trials (RCTs)

  2. Cohort studies

Types of participants

Participants of any age who received a laparoscopic or open RYGB for treatment of obesity.

Types of interventions

  1. RYGB with routine cholecystectomy versus RYGB alone and screening of patients preoperatively with ultrasonography and cholecystectomy in patients only with positive findings

  2. RYGB with routine cholecystectomy versus RYGB alone and cholecystectomy after positive intraoperative finding of gallstones with ultrasound

  3. RYGB with routine cholecystectomy versus RYGB alone and no cholecystectomy and routine administration of ursodeoxycholic acid

  4. RYGB with routine cholecystectomy versus RYGB alone and no cholecystectomy and no screening, unless the patient has symptoms consistent with biliary disease

Types of outcome measures

Primary outcomes

  1. Increased overall (surgical and non‐surgical) morbidity

  2. Increased overall (surgical and non‐surgical) mortality

  3. Rate of subsequent cholecystectomy

Secondary outcomes

  1. Delayed post‐surgical complications

  2. Operative time

  3. Length of hospital stay

  4. Discharge status (routine, non‐routine)

  5. Biliary complications after RYGB without prophylactic cholecystectomy

  6. Intra‐ and postoperative complications

Search methods for identification of studies

We will conduct a comprehensive literature search to identify all relevant RCTs. There will be no language restrictions and translation of articles will be performed as required. Trials published as abstracts only will be considered for inclusion and any additional information required to assess study quality will be sought from the abstract authors.

Electronic searches

We will search the following electronic databases for identifying potential studies.

  1. The Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Specialized Trials Register (Appendix 1).

  2. MEDLINE (1966 to present) (Appendix 2).

  3. EMBASE (1984 to present) (Appendix 3).

  4. ClinicalTrials.gov (http://clinicaltrials.gov/) to identify ongoing studies.

Searching other resources

Both authors will handsearch the published abstracts from the conference proceedings in Digestive Disease Week and United European Gastroenterology Week. We will also contact authors of trial reports published only as abstracts. We will also screen reference lists included in studies found by the above search to identify further relevant trials.

Data collection and analysis

Selection of studies

Both authors (THB, SK) will independently screen the titles and abstracts of the studies identified from the literature searches. If it is clear from the study title or abstract that study does not meet the selection criteria then it will be excluded. If it is unclear, then full text of article will be retrieved and assessed for selection criteria. Where there is insufficient published information to make a decision about inclusion, we will contact the first author of the relevant trial. We will resolve any disagreement by discussion.

Data extraction and management

We will design data extraction forms to record relevant information such as study characteristics, patients, interventions, comparisons, outcomes, eligibility for inclusion or reasons for exclusion. Both authors (THB, SK) will extract data independently using standardized data extraction sheets and will enter the data into the Cochrane Collaboration's statistical software, Review Manager 2013.

Assessment of risk of bias in included studies

Both authors (THB, SK) will use the Cochrane Collaboration's tool for assessing risk of bias to evaluate the quality of RCTs.

We will assess the following factors:

  1. sequence generation (i.e. was the allocation sequence adequately generated?);

  2. allocation sequence concealment (i.e. was allocation adequately concealed?);

  3. blinding (i.e. was knowledge of the allocated intervention adequately prevented during the study?);

  4. incomplete outcome data (i.e. were incomplete outcome data adequately addressed?);

  5. selective outcome reporting (i.e. were reports of the study free of suggestion of selective outcome reporting?); and

  6. other potential sources of bias (i.e. was the study apparently free of other problems that could put it at a high risk of bias?).

We will judge each included study using the categories 'low risk of bias', 'high risk of bias', and 'unclear risk of bias'. Disagreements will be resolved by consensus. We will contact study authors for further information when insufficient information is provided to determine the risk of bias

Measures of treatment effect

We will perform all analyses using Review Manager 2013. We will use a fixed‐effect model unless significant heterogeneity (I2 > 50%) is identified, in which case a random‐effects model will be used.

Dichotomous data 

If appropriate for pooled analysis, we will pool dichotomous data from the included studiesand calculate the Mantel‐Haenszel estimates on an intention‐to‐treat basis. We will present ooled‐analysis findings as risk ratios (RRs) with 95% confidence intervals (CIs).

Continuous data 

For continuous variables, we will calculate a mean difference (MD), or standardised mean difference (SMD), along with 95% confidence intervals, based on the following criteria: 

  • when two or more studies present their data derived from the same instrument of evaluation, and with the same units of measurement,  the data will be pooled and results will be presented as MD;

  • conversely, when primary studies express the same variables through different instruments, and different units of measurement, we will present data as SMD.

Time‐to‐event outcomes

For time‐to‐event outcomes such as survival, biliary complications , we will calculate the hazard ratio (HR) with 95% CI.

Unit of analysis issues

Cluster randomized trials

If we find any cluster randomized trials we will analyze them using the generic inverse variance method (Higgins 2011).

Dealing with missing data

We will retrieve data that were measured but not reported from study authors. If there is a discrepancy in the number randomized and the number analyzed in each treatment group, the percentage lost to follow up will be calculated in each group and reported. We will use a sensitivity analysis for all trials with missing data.

Assessment of heterogeneity

We will assess heterogeneity between pooled trials using:

  1. Chi2 test of heterogeneity (where a significance level of less than 0.10 is interpreted as evidence of heterogeneity);

  2. I2 statistic which describes the percentage of the variability in effect estimates that is due to heterogeneity rather than sampling error, or chance (Higgins 2011).

We will interpret the I2 value as:

  • 0% to 40%: might not be important;

  • 41% to 60%: may represent moderate heterogeneity;

  • 61% to 100%: may represent substantial heterogeneity;

Assessment of reporting biases

We will use funnel plot asymmetry to assess potential reporting bias only if more than 10 trials are available.  We will assess potential reporting biases and any association of treatment estimates with study size by preparing a funnel plot. We will then perform a visual inspection of funnel plot. Asymmetry in the plot may be attributed to publication bias, poor methodology quality, or due to true heterogeneity. We will explore bias according to Egger's methods (Egger 1997).

Data synthesis

We will carry out statistical analysis using Review Manager 2013 according to the statistical guidelines referenced in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will use random‐effects meta‐analysis. for combining data. However, if heterogeneity is substantial, we will not perform a meta‐analysis at all because the effect estimate does not reliably reflect the 'true' value, and we will perform narrative, qualitative summary instead.

Subgroup analysis and investigation of heterogeneity

We will explore heterogeneity where possible by conducting a subgroup analysis ofr open versus laproscopic RYGB.

Sensitivity analysis

We will conduct a sensitivity analysis to examine the stability of the results in relation to a number of factors relating to the way the study was done if we identify a sufficient number of studies:

  1. excluding studies of poor overall methodological quality;

  2. excluding studies of low statistical power;

  3. excluding unpublished studies;

  4. excluding studies funded by industry;

  5. according to the statistical model (fixed‐effect versus random‐effects models).

Summary of findings

We will use the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of the body of evidence associated with outcomes mentioned in our review and construct a 'Summary of findings' table (Guyatt 2008).

Domains that may decrease the quality of the evidence are as follows:

  1. the study design;

  2. risk of bias;

  3. inconsistency of results;indirectness (i.e. non‐generalisability);

  4. imprecision (i.e. insufficient data);

  5. and other factors (e.g. reporting bias).

We will reduce the quality of the evidence by one level for each domain where poor quality is encountered. We will assess all plausible confounding factors and consider their effects as a reason to reduce any claimed effect and dose response gradient.

We will define levels of evidence as below.

  • High‐quality evidence:

    • the following statement applies to all of the domains: 'Further research is very unlikely to change our confidence in the estimate of effect. There are consistent findings, that are generalisable to the population of interest, in 75% of RCTs with low risk of bias. There are sufficient data, with narrow confidence intervals. There are no known or suspected reporting biases'.

  • Moderate‐quality evidence:

    • the following statement applies to one of the domains: 'Further research is likely to have an important impact on our confidence in the estimate of effect, and may change the estimate'.

  • Low‐quality evidence:

    • the following statement applies to two of the domains: 'Further research is very likely to have an important impact on our confidence in the estimate of effect, and is likely to change the estimate'.

  • Very low‐quality evidence:

    • the following statement applies to three of the domains: 'We are very uncertain about the estimate'.

  • No evidence:

    • the following statement applies: 'No RCTs were identified that measured the outcome of interest'.

We will also consider a number of other factors to place the results into a wider clinical context: temporality, plausibility, strength of association, adverse events and costs.