Comparison of the postoperative outcome with and without intraoperative leak testing for sleeve gastrectomy: a systematic review and meta-analysis of 469 588 cases

Objective: Postoperative staple line leakage (SLL) after sleeve gastrectomy (SG) is a rare but serious complication. Many surgeons routinely test anastomosis with an intraoperative leak test (IOLT) as part of the SG procedure. This meta-analysis aims to determine whether an IOLT plays a role in reducing the rate of postoperative staple line related complications in patients who underwent SG. Methods: The authors searched the PubMed, Web of science, the Cochrane Library, and Clinical Trials.gov databases for clinical studies assessing the application of IOLT in SG. The primary endpoint was the development of postoperative SLL. Secondary endpoints included the postoperative bleeding, 30 days mortality rates, and 30 days readmission rates. Results: Six studies totaling 469 588 patients met the inclusion criteria. Our review found that the SLL rate was 0.38% (1221/ 324 264) in the IOLT group and 0.31% (453/ 145 324) in the no intraoperative leak test (NIOLT) group. Postoperative SLL decreased in the NIOLT group compared with the IOLT group (OR=1.27; 95% CI: 1.14–1.42, P=0.000). Postoperative bleeding was fewer in the IOLT group than that in the NIOLT group (OR 0.79; 95% CI: 0.72–0.87, P=0.000). There was no significant difference between the IOLT group and the NIOLT group regarding 30 days mortality rates and 30 days readmission rates (P>0.05). Conclusion: IOLT was correlated with an increase in SLL when included as a part of the SG procedure. However, IOLT was associated with a lower rate of postoperative bleeding. Thus, IOLT should be considered in SG in the situation of suspected postoperative bleeding.


Introduction
As the prevalence of obesity has continued to increase worldwide, the number of performed bariatric procedures grows in parallel [1] .Among all bariatric procedures, laparoscopic sleeve gastrectomy (SG) is widely used worldwide in the surgical treatment of morbid obesity.It is considered to be a minimally invasive and safe surgery with low complications and mortality rates [2] .In SG, the stomach has its capacity reduced by approximately two-thirds [3] , which results in the patient eating less and losing weight [4] .Many advantages were shown in SG, such as reducing serum liver enzyme concentrations [5] , alleviating type 2 diabetes mellitus [5] , decreasing blood lipids [6] , and improving quality of life [7,8] etc.
Intraoperative leak testing (IOLT) is a common intraoperative intervention to identify staple line leaks, defects, bleeding, and stricture.IOLT is often performed using air insufflation or methylene blue dye injection via upper gastrointestinal endoscopy or nasogastric tube [9] .Some studies recommend routine usage of the intraoperative leak test in SG [10][11][12] .However, the utility of these tests is controversial.The international SG expert panel failed to reach a consensus (48% consensus) about whether routine intraoperative leak tests should be performed [13] .A study showed that an IOLT using air insufflation or methylene blue dye was performed in 81.9% of cases and the leak rate was higher in patients with air insufflation or methylene blue versus without (0.8 vs 0.4%, P < 0.01) [14] .In addition, IOLT has the possibility to cause iatrogenic injury due to excessive dilation of the remaining gastric pouch [15,16] .
To the best of our knowledge, this is the first meta-analysis regarding whether the IOLT procedure carries higher risk for postoperative staple line leakage.The aim of this study was to compare postoperative staple line leakage, postoperative bleeding, 30 days mortality rates, and 30 days readmission rates of IOLT with no intraoperative leak test (NIOLT) for SG.

Literature search strategy
The literature search for this systematic review was performed in January 2023 according to the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses (PRISMA) guidelines [17] , and Assessing the methodological quality of systematic reviews (AMSTAR) Guidelines [18] .The study protocol was written and registered at The International Prospective Register of Systematic Reviews (Prospero) before data extraction.A systematic review of literature was performed by two authors independently using the databases PubMed, Web-of-Science, Cochrane Library, and Clinical Trials.govdatabases along with a cross-reference search of eligible papers or trials.The following search strategy was used in PubMed and modified in other databases accordingly: ((sleeve gastrectomy) and (endoscopy) and (intraoperative) and (staple line leak)) or ((sleeve gastrectomy) and (stomach tube) and (intraoperative) and (staple line leak)) or ((sleeve gastrectomy) and (endoscopy) and (intraoperative leak testing)) or ((sleeve gastrectomy) and (stomach tube) and (intraoperative leak testing)) or ((bariatric surgery) and (stomach tube) and (intraoperative leak testing)) or ((bariatric surgery) and (endoscopy) and (intraoperative) and (staple line leak)) or ((bariatric surgery) and (stomach tube) and (intraoperative) and (staple line leak)) or ((bariatric surgery) and (stomach tube) and (intraoperative) and (staple line leak)) or ((endoscopy) and (intraoperative) and (staple line leak)) or ((stomach tube) and (intraoperative) and (staple line leak)) or ((endoscopy) and (intraoperative leak testing)) or ((stomach tube and (intraoperative leak testing)).
All studies comparing the postoperative outcomes of IOLT with NIOLT were included.Papers published before January 2023 were included.Moreover, we attempted to find all relevant literature by thoroughly looking through the references of included clinical articles.After analyzing the full texts, we identified a total of six studies that were suitable to be included in our meta-analysis.

Study selection
Studies were included in the meta-analysis if they met the following criteria: 1) they conducted clinical trials comparing the postoperative outcomes of IOLT and NIOLT; 2) the study was published as a full-text in the English language; and 3) valid data and a full-text of the study could be obtained successfully.

Study exclusion
Studies were excluded if they included patients that underwent any of the following procedures: mini-loop gastric bypass, endoscopic therapy, intragastric balloon, clinical trial, or experimental therapy.In addition, animal studies, conference abstract, comments, reviews, guidelines, and studies with fewer patients than 20 were excluded.

Statistical extraction
Articles were first screened independently by two authors according to title and abstract, with disputes being resolved by a third author.This process was then repeated with a full-text review in which we extracted data including author, year of publication, country, study design, number of patients, sex, age, BMI, postoperative staple line leakage, postoperative bleeding, 30 days mortality rates, and 30 days readmission rates.

Outcome
The primary endpoint was the development of postoperative staple line leakage.In this study, postoperative staple line leakage was defined as a leak after SG, which included intraoperative and postoperative finding leaks.Secondary endpoints included the postoperative bleeding, 30 days mortality rates, and 30 days readmission rates.The risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Intervention Tool [19] , which was shown in Table 1.

Quality assessment
Quality assessment of the included studies was completed with the Newcastle-Ottawa Scale (NOS) [25] .Using this scale, each study was judged on eight items, categorized into three groups: the selection of the study groups; the comparability of the groups; and the exposure evaluation groups.Stars were awarded for each quality item and the highest quality studies were awarded up to nine stars.Scores of 7-9 points indicated high-quality studies, those of 4-6 points indicated moderate-quality studies, and those of 1-3 points indicated low-quality studies.

Statistical analysis
For retrospective compared study, odds ratio (OR) was calculated.The Mantel-Haenszel method was used for dichotomous data, and the OR with 95% CIs was presented.To assess the significance in study heterogeneity, Cochran's P statistic and I² were reported.If the data was found to be lacking in the published articles, authors were contacted for further inquiry.When heterogeneity was high, the random-effects model was used; otherwise, the fixed-effects model was used.Heterogeneity was explored using I² statistics and the analyses were illustrated with forest plots.Heterogeneity was calculated using the I² statistic and defined as low, moderate, and high when I² was more than 25, 50, and 75%, respectively [26] .We performed further subgroup analysis of the studies type of IOLT.Stata software (version 17.0; Stata Corporatio; College Station) was used to perform all analysis.

Literature search results
Our systematic search revealed a total of 1016 publications for possible inclusion.Based on a review of the title and abstract of each article, irrelevant publications, duplicate publications, and those not fitting our inclusion criteria were excluded.A further nine publications were excluded based on review of the full-text, leaving six retrospective studies that were included [9,[20][21][22][23][24] (Fig. 1).

Study characteristics
The meta-analysis included 469 588 patients, of which 324 264 were assigned to the IOLT group and 145 324 to the NIOLT group.The studies were published between 2016 and 2022.One study originated from Turkey, while the other five originated from the United States.All studies performed intraoperative endoscopic or nonendoscopic methods (naso/orogastric tube insertion), which used air injection or used methylene blue to test for leakage.Details information on study characteristics are present in Table 2.Among the six studies in total, three of them reported positive results for IOLT [9,20,22] .Only two patients were reported as having a positive IOLT, which allowed for the reinforcement of the sutures.In the remaining three studies [21,23,24] , the IOLT group provided the leak rate after surgery instead of reporting positive results of IOLT.Details of distal clamp occlusion in IOLT were reported in three studies [9,21,22] , which showed in Table 3.

Study quality
When using the NOS for case-control studies, the quality assessment of the included studies ranged from 6 to 8. All six studies had NOS quality scores greater than or equal to 6, indicating that all these studies had a high level of methodological quality.Table 4 shows the NOS quality scores of the included studies.

Subgroup analysis
We performed further subgroup analysis of the included studies, which was done accordance with the method of every study of IOLT.In two included studies, the methylene blue test was adopted in the IOLT group [21,22] .The postoperative staple line leakage rate was 0.25% (356/142 673) in the IOLT group, and 0.23% (98/42 317) in the NIOLT group.The meta-analysis showed no statistically significant differences in the IOLT group and in the NIOLT group (OR = 1.09; 95% CI: 0.87-1.36,P = 0.458).However, in three included studies, air insufflation or methylene blue dye were adopted in the IOLT group [9,20,23] .The postoperative staple line leakage rate was 0.44% (259/59 110) in the IOLT group, and 0.34% (198/57 534) in the NIOLT group.The postoperative staple line leakage was lower in the NIOLT

Studies Types of IOLT Distal clamp occlusion
Sethi et al. [9] Air insufflation Distal occlusion of the pylorus Methylene blue dye Distal obstruction of the duodenum Mayir et al. [22] Methylene blue dye Pylorus was laparoscopically closed with a bowel clamp Yolsuriyanwong et al. [21] Methylene blue dye The bowel was clamped distal to the anastomosis or staple line IOLT, intraoperative leak test.group than that in the IOLT group (OR = 1.22; 95% CI: 1.02-1.48,P = 0.033).Only one study was suitable for metaanalysis, which used endoscopic or nasogastric air insufflation or methylene blue in the IOLT group [24] (Fig. 3).

Discussion
SG, also known as vertical SG or gastric sleeve, was initially described in 1988 [27] and is a commonly performed surgery for weight loss [3] .Postoperative SLL is one of the most severe complications following SG [13] .The incidence of SLL after SG is relatively low, with a reported incidence ranging from 0 to 8% [28][29][30] .To the best of our knowledge, this is the first metaanalysis regarding whether the IOLT procedure carries higher risk for postoperative staple line leakage.In this study, we observed that NIOLT has a lower rate of postoperative staple line leakage compared to IOLT.One possible explanation for this is that postoperative leakage may occur due to a fault in the testing mechanism.For example, the calibration tube is already present in the stomach before stapling.When the test is about to be conducted, the calibration tube is gradually drawn up to the upper stomach, and then the test is performed.Therefore, there may be no need to insert it, thus reducing the risk of staple line injury.
A few different techniques for IOLT have been reported [9,31] .In a study by Burgos AM, IOLT involved administering methylene blue through a nasogastric tube placed after the removal of the bougie, with the goal of protecting against suture-line leaks and aiding in the evaluation of gastric capacity [9] .In another  study by Sethi M, IOLT included methylene blue testing upon completing the sleeve, followed by the removal of the bougie and the placement of an orogastric or nasogastric tube under direct vision [9] .Another potential explanation for the higher leak rate is that many surgeons employ the orogastric tube method for IOLT [31] .This method, due to its blind insertion nature, can potentially cause trauma to the freshly constructed staple line, possibly leading to postoperative leaks.Additionally, the pressures exerted during the air insufflation leak test can weaken the staple line, increasing the risk of postoperative leak development [32] .
IOLT is safe and effective in gastric bypass surgery [33][34][35] .The following reasons can explain the increased leakage rate of IOLT in SG in specific.First, Roux-en-Y gastric bypass is a more  complicated procedure with multiple anastomoses, making it harder to completely visualize the anastomosis, particularly on the posterior side [36] .Compared to gastric bypass, SG involves a simpler linear stapling.Therefore, the data supporting IOLT during Roux-en-Y gastric bypass cannot necessarily be extrapolated to SG [20] .Second, SG, in comparison to gastric bypass, retains the intact pylorus and has higher intraluminal pressure, which may lead to an increased leak rate [28] .
Our findings are in accordance with recent studies that indicated increased postoperative leak rates when IOLT was performed in SG [14,24,37] .A consensus report published in the Netherlands showed that IOLT was not considered to be a key step in SG [38] .A 494 patients study showed that the routine use of an IOLT did not reduce the incidence of postoperative leak, and in fact was associated with a higher leak rate after SG [37] .Furthermore, the usage of air insufflation or methylene blue dye tests were not completely advantageous and could add operative times and unnecessary costs to the surgery [9] .In addition, a negative methylene blue test does not eliminate the possibility of a leak [39] .Some studies showed that routine tests to rule out leaks seem to be superfluous [40,41] .However, some studies showed that an intraoperative leak test was an effective method for detecting leakage after SG [10][11][12] .Other studies found that performing IOLT was not associated with postoperative leak in patients who underwent SG [20,21,37,42] .
There are patients experiencing leak postoperative even though IOLT was negative.Some possible explanations are as follows.First, IOLT can only detect the rare leaks due to technical failure in the staple line, such as stapler misfire [40] .Second, it has been reported that IOLT has a low sensitivity and specificity, which does not result in decreased postoperative leak rates after SG [20] .A study showed that upper gastrointestinal radiography found leaks, but the IOLT result was negative [20] .
We found that the postoperative bleeding was significantly lower in the IOLT group.Our findings are in align with recent studies indicating that IOLT during for SG was associated with lower rates of postoperative bleeding (0.6 with leak testing versus 0.8%; P < 0.001) [24] .An observational cohort study has also  demonstrated that patients who had underwent IOLT during SG had lower postoperative bleeding rates [21] .Furthermore, a separate study has shown that IOLT was associated with a decrease in postoperative bleeding rates in SG patients (0.6 with IOLT versus 0.8% without IOLT, P = 0.002) [23] .One possible explanation for this is that the potential postoperative bleeding, when detected through IOLT, allows surgeons to promptly implement hemostatic measures [23] .It has been reported that leak testing may be justified in cases of revisional surgery, intraoperative complications, or in the case of a surgeon who is in the learning curve stage [9] .Thus, we suggest that IOLT should be considered in SG in the situation of suspected postoperative bleeding.
Additionally, our study showed that regardless of whether patients had received IOLT or not, the rates of postoperative 30 days mortality rates and 30 days readmission rates were not significantly different(P>0.05).Our findings are in accordance with recent studies indicating that there were no significant differences between the IOLT and NIOLT groups in terms of 30 days mortality and 30 days readmission rates [21] .In addition, a study found that performing IOLT was not associated with changes in rates of 30 days readmission rates [23] .
Our study has some limitations.First, all included studies were conducted retrospectively, which may introduce selection bias and potentially reduce the reproducibility of our results.Second, the technique of IOLT was not standardized; some studies employed endoscopy with methylene blue and air tests for IOLT while others used only an orogastric tube with methylene blue or air tests.Additionally, the pressure of IOLT in the remnant of gastric sleeve was not monitored.Third, only three studies reported the positive cases of IOLT, making it difficult to calculate the salvage rates, which would have allowed reinforcing the staple line when intraoperative leaks were detected.
In conclusion, IOLT was correlated with an increase in staple line leakage.However, IOLT was associated with a lower rate of postoperative bleeding.Prospective studies proposing a systematic way of performing IOLT are still needed.Further studies, perhaps incorporating manometric factors into IOLT, should be considered.

Research registration unique identifying number (UIN)
The International Prospective Register of Systematic Reviews (Prospero) (CRD:42023393776).

Figure 1 .
Figure 1.Flow diagram of study selection.

Figure 2 .
Figure 2. Forest plot of postoperative staple line leakage.

Figure 3 .
Figure 3. Forest plot of subgroup analysis of leaking test type.

Figure 5 .
Figure 5. Forest plot of 30 days mortality rates.

Table 1
Analysis for risk of bias of the studies included in the meta-analysis using the Risk of Bias in Non-Randomized Studies of Intervention Tool.

Table 3
The details of distal clamp occlusion in intraoperative leak test.

Table 4
Quality assessment of included studies.