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  Table of Contents  
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 43-46

Related factors of postoperative gallstone formation after distal gastrectomy: A meta-analysis

Department of Surgical Oncology, Ningbo No. 2 Hospital, Ningbo, China

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. Y Li
Department of Surgical Oncology, Ningbo No. 2 Hospital, Ningbo
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_91_17

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 » Abstract 

Aim: The aim of this study was to evaluate the risk factor of gallstone occurrence after distal gastrectomy (DG) for gastric cancer. Methods: Relevant documents published from 2000 to 2016 were retrieved in PubMed, Web of Knowledge, and Ovid's database, and a metaanalysis was performed with RevMan 5.0 software for odds ratios (ORs) and 95% confidence intervals (CIs). Results: Eight studies met the final inclusion criteria. From the pooled analyses, nonphysiological reconstruction (OR = 1.51; 95% CI = 1.10–2.08; P = 0.01) and vagus nerve resection (OR = 2.79; 95% CI = 1.57–4.96; P = 0.0005) were significantly associated with increased risk of gallstone after DG. Conclusion: Our analysis indicated that digestive tract reconstruction and vagus nerve resection were strongly and consistently associated with gallstone formation after DG.

Keywords: Distal gastrectomy, gallstone formation, gastric cancer, meta-analysis

How to cite this article:
Chen Y, Li Y. Related factors of postoperative gallstone formation after distal gastrectomy: A meta-analysis. Indian J Cancer 2017;54:43-6

How to cite this URL:
Chen Y, Li Y. Related factors of postoperative gallstone formation after distal gastrectomy: A meta-analysis. Indian J Cancer [serial online] 2017 [cited 2021 Jul 24];54:43-6. Available from: https://www.indianjcancer.com/text.asp?2017/54/1/43/219605

 » Introduction Top

The incidence of gallstone formation has been regarded as one of the most common complications after gastrectomy.[1],[2],[3] The underlying pathophysiology of this phenomenon for this postoperative disease has included alterations in gallbladder motility, release of cholecystokinin (CCK), and gallbladder responses.[4],[5] Such changes may be caused by the various surgical procedures included resection of the vagal nerve, nonphysiological reconstruction of the gastrointestinal tract, and altered response to and secretion of CCK.[4],[5],[6] Cancers occur most often in the distal stomach, the lesser curvature of the antrum, and the prepyloric region.[7] Billroth-I (B-I), B-II, and Roux-en-Y (R-Y) reconstructions have commonly been performed after distal gastrectomy (DG). However, few studies with sufficient data are available about risk factors for gallstone after DG.

The present study was to evaluate the incidence of gallstone formation and the risk factors for their development after DG for gastric cancer.

 » Materials and Methods Top

Search strategy

PubMed, Web of Knowledge, and Ovid's database were searched from January 2000 to December 2016 without language restrictions. The search terms used were “gastric cancer,” “gallstone,” “distal gastrectomy,” and “gallbladder stone.” The reference lists of relevant studies were checked manually to locate any missing study.

Study selection

Cohort, case–control studies, and randomized controlled trials were assessed for eligibility for inclusion in the review by scrutinizing the titles, abstracts, and keywords of every record retrieved. Clinical studies concern perioperative factors directly influencing the postoperative gallstone occurrence after DG.

Data extraction

Two coauthors (Li Y and Chen Y) independently selected studies for inclusion and exclusion and reached consensus when they did not agree in the initial assignment. The following variables were recorded: patient baseline characteristics (age, gender, and number of patients), perioperative clinical data, operative methods, and postoperative events. If necessary, the corresponding authors of studies were contacted to obtain supplementary information. Initially, we scrutinized in detail the literature on DG to identify all possible risk factors for gallstone occurrence. After initial research, two factors that were considered to be easily measured in routine clinical practice and had been analyzed in at least three studies. In this meta-analysis, we compared the risk of developing gallstone in patients with factors of digestive tract reconstruction and vagotomy.

Quality assessment

The Newcastle–Ottawa scale was used to assess the quality of observational studies based on the following nine questions: (1) representativeness of the exposed cohort; (2) selection of the nonexposed cohort; (3) ascertainment of exposure; (4) demonstration that the outcome was not present at outset of study; (5) comparability; (6) assessment of outcome; (7) length of follow-up sufficient; (8) adequacy of participant follow-up; and (9) total stars. Maximum score on this scale is a total of 9.[8] “Good” was defined as a total score of 7–9; “fair,” a total score of 4–6; and “poor,” a total score of <4.

Statistical analysis

A formal meta-analysis was carried out for all included studies to estimate the association between the clinical factors and development of gallstone after DG. The odds ratios (ORs) and 95% confidence interval (CI) were calculated for each study. Pooled estimates of outcomes were calculated using a fixed-effects model, but a randomized-effects model was used according to heterogeneity. Heterogeneity was explored using I2 statistics, a measure of how much the variance between studies, rather than chance, can be attributed to interstudy differences. I2 >50% was regarded to indicate strong heterogeneity. The Cochrane Collaboration's Review Manager Software (RevMan version 5.0, Cochrane Collaboration, Oxford, United Kingdom) was utilized for the data analysis.

 » Results Top

Study selection

Our initial search yielded 53 potential literature citations [Figure 1]. After exclusion of duplicate references, none-relevant literature, and those that did not satisfy inclusion criteria, 25 candidate articles were considered for the meta-analysis. After careful review of the full text of these articles, eight studies were included in this study. The study characteristics were summarized in [Table 1] and [Table 2].
Figure 1: Flowchart of the results of the literature search

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Table 1: Characteristics of selected studies

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Table 2: Characteristics of selected studies

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Patient demographics for the eight studies are presented in [Table 1] and [Table 2]. All papers were of retrospective studies. The publication dates ranged from January 2000 to December 2016. Study sizes ranged from 64 to 474 patients.

Outcome measures

Gallstone formation is a common complication after DG and occurred in 20.0% (296/1558) of whole patients analyzed in this study, which was within the frequency range of 10%–47% cited in previous reports.[1],[3],[9],[10] The baseline characteristics of the included patients are shown in [Table 1] and [Table 2]. There were no significant differences in age and sex between the two groups.

Digestive tract reconstruction

Five studies [11],[12],[13],[14],[15] evaluated whether physiological reconstruction or nonphysiological reconstruction was associated with the lower incidence of gallstone. Gallstone occurred in 20.6% of patients with nonphysiological reconstruction versus 18.2% with physiological reconstruction. From the pooled analysis, nonphysiological reconstruction was significantly associated with increased risk of gallstone occurrence after DG (OR = 1.51; 95% CI = 1.10–2.08; P = 0.01) [Figure 2].
Figure 2: Pooled odds ratio for gallstone occurrence after distal gastrectomy by nonphysiological reconstruction versus physiological reconstruction

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Vagus nerve preserving

Four studies [11],[14],[16],[17] compared the impact of DG on the development of gallstone were included in this study. The pooled analysis showed that the incidence of gallstone was 9.4% in the 265 patients with vagus nerve preserving, compared to 23.9% in the 176 patients without vagus nerve preserving. Findings from the meta-analysis show a significant association between vagus nerve resection and gallstone occurrence (OR = 2.79; 95% CI = 1.57–4.96; P = 0.0005) [Figure 3].
Figure 3: Pooled odds ratio for gallstone occurrence after distal gastrectomy by vagus nerve resection versus vagus nerve preserving

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 » Discussion Top

The expected survival of gastric cancer patients has been significantly prolonged due to remarkable progress in surgical techniques.[18] However, the prevalence of gallstone formation after gastrectomy is obviously higher than the general population without gastrectomy.[19] We, therefore, aimed to elucidate the relationship between DG and gallstones.

There were several reports indicating that the type of reconstruction did not affect gallstone formation, interpreting that gallstone formation was unrelated to whether or not food passes through the duodenum.[2],[13],[20] On the other hand, Kobayashi et al. investigated that exclusion of the duodenum reduced the secretion of CCK, thus decreasing gallbladder contraction and increasing the risk of gallstones.[4] Jun et al. reported that exclusion of the duodenum during reconstruction, such as B-II or R-Y, is associated with the development of gallstones.[9] This study illustrates that the incidence of gallstone formation differed significantly in patients who underwent nonphysiological reconstruction and physiological reconstruction for DG.

The vagal nerve controls hepatopancreaticobiliary function, movement of the alimentary tract including the biliary system.[21],[22] It dominates gallbladder movement and keeps gallbladder tension. Vagal nerve stimulation promotes gallbladder contraction and Oddis sphincter relaxation to excrete bile. Injury of vagal nerve in gastrectomy results in Oddis sphincter tension increasing and gallbladder contraction weakness; therefore, the bile excretion was difficult, generating bile cholestasis and gallstone formation.[23] Hence, destruction of vagal nerve is one of the risk factors for the formation of gallstones after gastrectomy.[4],[6] Previous studies have indicated high incidences of gallstone formation after open gastrectomy without vagal nerve preservation.[12],[13],[24] It is regarded as injury to the hepatic branches from the anterior vagal trunk and autonomic nerves around the common hepatic artery leading to gallstone.[23],[25] In addition, Inokuchi et al. found that preserving the celiac branch of the vagal trunk independently contributes to the prevention of gallstone formation during long-term follow-up after gastrectomy.[16]

Three studies reported that gallstones formed more frequently after D2 dissection than after D1 dissection.[3],[13],[24] It is often assumed that dissection of lymph node would damage surrounding nerves and blood vessels. D2 dissection usually includes dissection of lymph nodes 7, 8, and 9, which are located near the hepatic branches of the vagus nerve. Kobayashi et al. demonstrated that dissection of lymph nodes 8 and 9 correlated significantly with the development of gallstones.[4] The higher the dissection degree is, the greater the damage and this will influence the contraction of the gallbladder and give rise to gallstone. However, few studies are available about gallstone disease after DG with D2 dissection.

In previous studies, gallstone formation largely occurred within 2 years of gastrectomy.[1],[2],[13] It seldomly took place after 5 years of gastrectomy which may be related to recovery of the contractive ability of the gallbladder.[26]

Is prophylactic cholecystectomy necessary during DG? Two previous studies reported that concomitant cholecystectomy during standard surgery for gastric malignancies was safe but does not mean it is recommendable.[27],[28] Although a significantly higher incidence of gallstones was observed in gastrectomy patients, only 4.3% developed symptoms or cholecystitis and required subsequent cholecystectomy.[29] Accordingly, prophylactic cholecystectomy is unnecessary for the large majority of patients who undergo gastric surgery.

Some limitations of this meta-analysis should be noted. First, the pooled studies differed in inclusion and exclusion criteria. These may be the major source of heterogeneity. Second, the data included in some studies may have been too crude and also subject to measurement error. Finally, it is important to mention that all included studies are retrospective, a possibility of residual confounding by unmeasured factors cannot be eliminated.

 » Conclusions Top

Our analysis provides evidence that digestive tract reconstruction and vagus nerve resection were strongly and consistently associated with gallstone formation after DG. Future studies with long-term follow-up are needed to confirm the findings of this study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

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Kobayashi T, Hisanaga M, Kanehiro H, Yamada Y, Ko S, Nakajima Y. Analysis of risk factors for the development of gallstones after gastrectomy. Br J Surg 2005;92:1399-403.  Back to cited text no. 4
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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]

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