Abstract
Background
Gastric cancer is the fifth most common cancer diagnosed worldwide. Due to improved early detection rates of gastric cancer and technological advances in treatments, a significant improvement in survival rates has been achieved in people with cancer undergoing gastrectomy. Subsequently, there has been increasing emphasis on postgastrectomy syndrome (e.g. fullness, delayed emptying, and cold sweat, amongst others) and quality of life postsurgery. However, it is uncertain which types of reconstruction result in better outcomes postsurgery.
Objectives
To assess the evidence on health‐related quality of life and safety outcomes of Roux‐en‐Y and Billroth‐I reconstructions after distal gastrectomy for people with gastric cancer.
Search methods
We searched the Cochrane Library and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase on 4 May 2021. We checked the reference lists of the included studies and contacted manufacturers and professionals in the field. There were no language restrictions.
Selection criteria
Randomised controlled trials (RCTs) allocating participants to Roux‐en‐Y reconstruction or Billroth‐I reconstruction after distal gastrectomy for gastric cancer.
Data collection and analysis
Two review authors independently screened studies identified by the search for eligibility and extracted data. The primary outcomes were health‐related quality of life after surgery and incidence of anastomotic leakage. The secondary outcomes included body weight loss, incidence of bile reflux, length of hospital stay, and overall morbidity. We used a random‐effects model to conduct meta‐analyses. We assessed risk of bias of the included studies in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, and the certainty of the evidence using the GRADE approach.
Main results
We included eight RCTs (942 participants) in the review. One study included both cancer patients and benign disease patients such as stomach ulcers. Two studies compared Roux‐en‐Y, Billroth‐I, and Billroth‐II reconstructions, whilst the other studies compared Roux‐en‐Y and Billroth‐I directly.
For the primary outcomes, the evidence suggests that there may be little to no difference in health‐related quality of life between Roux‐en‐Y and Billroth‐I reconstruction (standardised mean difference 0.04, 95% confidence interval (CI) −0.11 to 0.18; I² = 0%; 6 studies; 695 participants; low‐certainty evidence due to study limitations and imprecision). The evidence for the effect of Roux‐en‐Y versus Billroth‐I reconstruction on the incidence of anastomotic leakage is very uncertain (risk ratio (RR) 0.63, 95% CI 0.16 to 2.53; I² = 0%; 5 studies; 711 participants; very low‐certainty evidence). The incidence of anastomotic leakage was 0.6% and 1.4% in the Roux‐en‐Y and Billroth‐I groups, respectively.
For the secondary outcomes, the evidence suggests that Billroth‐I reconstruction may result in little to no difference in loss of body weight compared to Roux‐en‐Y reconstruction (mean difference (MD) 0.41, 95% CI −0.77 to 1.59; I² = 0%; 4 studies; 541 participants; low‐certainty evidence). Roux‐en‐Y reconstruction probably reduces the incidence of bile reflux compared to Billroth‐I reconstruction (RR 0.40, 95% CI 0.25 to 0.63; I² = 22%; 4 studies; 399 participants; moderate‐certainty evidence). Billroth‐I reconstruction may shorten postoperative hospital stay, but the evidence for this outcome is very uncertain (MD 0.96, 95% CI 0.16 to 1.76; I² = 56%; 7 studies; 894 participants; very low‐certainty evidence). Billroth‐I reconstruction may reduce postoperative overall morbidity compared to Roux‐en‐Y reconstruction (RR 1.47, 95% CI 1.02 to 2.11; I² = 0%; 7 studies; 891 participants; low‐certainty evidence).
Authors' conclusions
The evidence suggests that there is little to no difference between Roux‐en‐Y and Billroth‐I reconstruction for the outcome health‐related quality of life. The evidence for the effect of Roux‐en‐Y versus Billroth‐I reconstruction on the incidence of anastomotic leakage is very uncertain as the incidence of this outcome was low. Although the certainty of evidence was low, we found some possibly clinically meaningful differences between Roux‐en‐Y and Billroth‐I reconstruction for short‐term outcomes. Roux‐en‐Y reconstruction probably reduces the incidence of bile reflux into the remnant stomach compared to Billroth‐I reconstruction. Billroth‐I reconstruction may shorten postoperative hospital stay compared to Roux‐en‐Y reconstruction, but the evidence is very uncertain. Billroth‐I reconstruction may reduce postoperative overall morbidity compared to Roux‐en‐Y reconstruction. Future trials should include long‐term follow‐up of health‐related quality of life and body weight loss.
Plain language summary
Roux‐en‐Y versus Billroth‐I reconstruction after surgery for gastric cancer
Review question
We reviewed the evidence for the effect of Roux‐en‐Y compared to Billroth‐I reconstruction after surgery for gastric cancer. We found eight studies.
Background
Gastric (stomach) cancer is one of the most common cancers worldwide. Recently, early detection rates of gastric cancer and treatment technology have improved. As a result, people can survive longer after surgery, and the importance of quality of life after surgery has been discussed. Billroth‐I and Roux‐en‐Y are both options for reconstruction of continuity of the gastrointestinal system after distal gastrectomy (removal of the lower part of the stomach).
However, there are no standards on which reconstructive procedure to select; guidelines do not describe which procedure should be a priority. It was therefore important to perform a review of the available evidence to aid decision making for people undergoing surgery, surgeons, physicians, medical staff, and policymakers.
Study characteristics
The evidence is current to 4 May 2021.
We identified eight trials including 942 participants with gastric cancer who underwent distal gastrectomy. The studies were conducted in four countries. One study included both cancer patients and patients with other diseases (such as stomach ulcers). Two studies compared Roux‐en‐Y, Billroth‐I, and Billroth‐II reconstruction, whilst the other studies compared Roux‐en‐Y and Billroth‐I directly. As for surgical approaches, open or laparoscopic (key‐hole) surgery, or both, were used in all studies; robotic surgery was not used. Six different scales were used to measure quality of life.
Key results
The evidence suggests that Roux‐en‐Y reconstruction may result in little to no difference in quality of life 12 months after surgery. However, these findings must be interpreted with caution because the study investigators measured quality of life in different ways. The evidence is very uncertain for the effect of the interventions on leakage through the reconstructed connection (anastomotic leakage).
Billroth‐I reconstruction may result in little to no difference in loss of body weight; probably increases bile reflux into the remnant stomach; and may reduce overall complications after surgery compared to Roux‐en‐Y reconstruction. The evidence is very uncertain for the effect of the procedures on length of hospital stay.
Certainty of the evidence
The certainty of the evidence for quality of life was low due to limitations in how the studies were designed and conducted, and because there are not enough studies to be certain about the results for this outcome. The certainty of the evidence for the other outcomes ranged from very low to moderate. Further research is needed to look at the effects of reconstruction methods over a longer time period.
Summary of findings
Summary of findings 1. Roux‐en‐Y compared to Billroth‐I after distal gastrectomy for gastric cancer.
| Roux‐en‐Y compared to Billroth‐I after distal gastrectomy for gastric cancer | ||||||
| Patient or population: people undergoing distal gastrectomy for gastric cancer Setting: operating room in a hospital Intervention: Roux‐en‐Y Comparison: Billroth‐I | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with Billroth‐I | Risk with Roux‐en‐Y | |||||
| Health‐related quality of life | ‐ | SMD 0.04 higher (0.11 lower to 0.18 higher) | ‐ | 695 (6 RCTs) | ⊕⊕⊝⊝ LOW1,2 | Regarding the effect size of the SMD, 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect (Cohen 1988). Converting an SMD of 0.04 into a global health status score of EORTC QLQ‐C30, Roux‐en‐Y may increase it by 0.56 points (95% CI −1.53 to 2.50) (Murad 2019). |
| Incidence of anastomotic leakage | 14 per 1000 | 9 per 1000 (2 to 36) | RR 0.63 (0.16 to 2.53) | 711 (5 RCTs) | ⊕⊝⊝⊝ VERY LOW3,4 | |
| Loss of body weight | The mean loss of body weight ranged from 8 to 9 percent. | The mean loss of body weight was 0.41% greater (0.77 smaller to 1.59 greater). | ‐ | 541 (4 RCTs) | ⊕⊕⊝⊝ LOW3,5 | Loss of body weight is expressed as a percentage (e.g. if a person of 50 kg becomes 40 kg, the loss of body weight is 20%). Weight loss can theoretically range from negative infinity to 100%, but weight gain is uncommon after gastrectomy, and weight loss of more than 50% is also uncommon. The observed values are therefore usually expected to fall within the range of 0 to 50%. |
| Incidence of bile reflux | 397 per 1000 | 159 per 1000 (99 to 250) | RR 0.40 (0.25 to 0.63) | 399 (4 RCTs) | ⊕⊕⊕⊝ MODERATE6 | |
| Length of hospital stay | The mean length of hospital stay ranged from 7 to 23 days. | The mean length of hospital stay was 0.96 days longer (0.16 to 1.76 days longer). | ‐ | 894 (7 RCTs) | ⊕⊝⊝⊝ VERY LOW3,7,8 | Length of hospital stay is expressed in days, and ranges from 1 to infinite. |
| Postoperative morbidity | 99 per 1000 | 146 per 1000 (101 to 209) | RR 1.47 (1.02 to 2.11) | 891 (7 RCTs) | ⊕⊕⊝⊝ LOW 3,9 | |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; EORTC QLQ‐C30: EORTC Core Quality of Life Questionnaire ‐ Core Questionnaire; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference | ||||||
| GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
1Downgraded one level due to imprecision; 95% CIs are compatible with both benefit and harm. 2Downgraded one level due to risk of bias; participants were not blinded despite this being a patient‐reported outcome. 3Downgraded one level due to risk of bias; surgeons were not blinded 4Downgraded by two levels due to imprecision; 95% CIs are wide due to rare events, with possibility of substantial harm and substantial benefit, suggesting very serious imprecision. 5Downgraded one level due to imprecision; small sample size — outcome included only four studies. 6Downgraded one level due to risk of bias; outcome assessors may not have been blinded. 7Downgraded one level due to risk of bias; incomplete reporting on the results indicating data are skewed. 8Downgraded one level due to inconsistency; substantial heterogeneity was observed. 9Downgraded one level due to inconsistency; possible inconsistencies in trial results due to different diagnostic criteria used to report complications.
Background
Description of the condition
In 2012, an estimated one million cases of gastric cancer occurred worldwide, making it the fifth most common malignancy and the third leading cause of cancer death in the world (IARC 2015). More than 70% of gastric cancer occurred in low‐ and middle‐income countries; geographically, half the total gastric cancer worldwide was seen in Eastern Asia, and 17% in Europe (IARC 2015).
Gastrectomy is a surgical procedure to treat gastric cancer. Standard gastrectomy for gastric cancer is defined as a principal procedure to be performed with curative intent involving resection of at least two‐thirds of the stomach with a D2 lymphadenectomy (JGCA 2017a), which can improve disease‐specific survival (Mocellin 2015). A sufficient resection margin should be ensured to determine the resection line. Generally, a distal gastrectomy can be performed if a resection margin of at least 3 cm can be obtained in advanced cancer. If not, a total gastrectomy should be considered (JGCA 2017a).
Due to improved early detection rates of gastric cancer and technological advances in treatments (ASGE 2002), a significant improvement in survival rates has been achieved amongst people with cancer undergoing gastrectomy (Roukos 1999). Early gastric cancer limited to the mucosa can be resected endoscopically, whilst preserving the stomach. For other types of early cancers (e.g. submucosal invasion) and advanced cancers, however, surgical resection is still the central treatment for gastric cancer (JGCA 2017a). Surgeons have been aware of the importance of postgastrectomy syndrome including fullness, delayed emptying, and cold sweat, etc., and several studies have investigated reconstructive procedures following distal gastrectomy from the viewpoint of achieving a good quality of life postsurgery (Lee 2012; Nakamura 2016; Nunobe 2007; Takiguchi 2012; Terashima 2014).
See Appendix 1 for a glossary of terms.
Description of the intervention
The four reconstructive procedures commonly employed after a distal gastrectomy are gastroduodenostomy (Billroth‐I (B‐I)); gastrojejunostomy (with or without Braun anastomosis (Billroth‐II (B‐II))); Roux‐en‐Y gastrojejunostomy; and jejunal interposition (JGCA 2017a). Billroth‐I reconstruction has been historically accepted as a common procedure after distal gastrectomy in Japan (Yoshino 2000). Roux‐en‐Y reconstruction has been more common in Western countries (Kumagai 2012; Schwarz 2015), although recently Billroth‐II reconstruction has also been performed (Lee 2012; Tran 2016). Billroth‐I is considered a simple procedure, as it requires only one anastomosis (Kanaya 2011), thus it remains the mainstay of reconstruction in Japan (Hoya 2009; Kumagai 2012). Nevertheless, Roux‐en‐Y reconstruction is gradually becoming more popular in Japan due to adverse events associated with Billroth‐I reconstruction, including bile reflux and ulcer in the remnant gastric segment (Kojima 2008).
How the intervention might work
Billroth‐I reconstruction may have a physiologic advantage of letting food pass through the duodenum (Kalmar 2006), and could potentially improve postoperative weight loss (Terashima 2014). However, based on the findings of an observational study, Roux‐en‐Y reconstruction has proven superiority over Billroth‐I and Billroth‐II (Fukuhara 2002), as it may be beneficial in preventing bile reflux into the gastric remnant if an appropriate length of the Roux limb is utilised. However, the possibility of a postoperative internal hernia occurring due to the nature of the Roux‐en‐Y reconstruction procedure, which causes mesenteric defects, cannot be neglected (Kelly 2013). Additionally, the possibility of Roux‐Y stasis, which shows nausea or vomiting worsened by eating either solids or liquids without mechanical obstruction, can dissuade surgeons from opting for a Roux‐en‐Y reconstruction (Kojima 2008). There has been no definitive and straightforward rationale for selecting a particular reconstructive procedure. The surgeon's experience, training received, and institutional policies of hospitals or facilities at which they work may dictate the choice of procedure. Furthermore, medical insurance and equipment, which differ amongst nations, may also affect preferences.
Why it is important to do this review
To date, there are no standard criteria regarding which reconstructive procedure to select. Existing guidelines do not describe which procedure should be prioritised as it is unclear if any one procedure is superior to others in terms of short‐ and long‐term efficacy and safety (JGCA 2017a; Smyth 2016). It was therefore important to perform a review of the available evidence and to establish a body of evidence for people undergoing surgery, surgeons, physicians, medical staff, and policymakers.
Objectives
To assess the evidence on health‐related quality of life and safety outcomes of Roux‐en‐Y and Billroth‐I reconstructions after distal gastrectomy for people with gastric cancer.
Methods
Criteria for considering studies for this review
Types of studies
As opposed to previously published reviews which included observational studies (Xiong 2013; Zong 2011), we included only randomised controlled trials (RCTs), with no restrictions on language. We included studies reported as full text, those published as abstract only, and unpublished data. We did not apply any restriction with respect to blinding status because blinding for surgeons and participants, which prevents detection and performance biases, is typically difficult in the case of surgical RCTs, although the degree of such biases is unknown (Probst 2016); however, the blinding status of assessors should be clarified (Speich 2017). We planned to include cluster‐RCTs when available. Clinical studies with a cross‐over design are impossible for the interventions in question.
Types of participants
We included adults aged 18 years and older with a diagnosis of gastric cancer who were undergoing robotic, laparoscopic, laparoscopy‐assisted, or open distal gastrectomy.
Types of interventions
We included studies comparing Roux‐en‐Y with Billroth‐I reconstruction. When a primary anastomosis was constructed, it could either be performed as an intracorporeal procedure (stapled or hand‐sewn) or an extracorporeal procedure (stapled or hand‐sewn). We did not specify types of stapling devices: we included both linear and circular stapling.
Types of outcome measures
We assessed the following outcomes. Reporting of the outcomes listed here was not considered as inclusion criteria for the review.
Primary outcomes
Health‐related quality of life after surgery (at time point closest to 12 months postoperatively), assessed by any generic and disease‐specific questionnaires on domains such as global health status and physical and mental well‐being.
Incidence of anastomotic leakage (defined as Clavien‐Dindo grade II or greater) (Clavien 2009; Dindo 2004), within 30 days after surgery.
Secondary outcomes
Loss of body weight, measured one year after surgery (range: 6 months to 24 months).
Incidence of bile reflux, including remnant gastritis or reflux oesophagitis (at time point closest to 12 months postoperatively).
Length of hospital stay (in days).
Postoperative morbidity (Clavien‐Dindo grade II or greater), within 30 days after surgery.
Search methods for identification of studies
Electronic searches
We conducted a literature search to identify all published and unpublished RCTs. We placed no restrictions on the language of publication when searching the electronic databases. We translated non‐English language papers and assessed them thoroughly for potential inclusion in the review, as necessary.
We searched the following electronic databases up to 4 May 2021.
The Cochrane Library databases, and the Cochrane Central Register of Controlled Trials (CENTRAL; to 2020 Issue 4; Appendix 2) (via Ovid).
MEDLINE (1946 to 4 May 2021; Appendix 3) (via Ovid).
Embase (1974 to 4 May 2021; Appendix 4) (via Ovid).
We also searched PubMed (www.ncbi.nlm.nih.gov/pubmed) before completing the review to obtain records that were not yet indexed in Ovid MEDLINE.
Searching other resources
We checked the reference lists of all primary studies for additional references that our original electronic searches may have missed. We searched clinical trials registers for unpublished data and planned to send a comprehensive list of relevant articles to the first author of reports of the included studies to enquire as to any further relevant studies (Higgins 2021). We also contacted manufacturers and experts in the field to ask if they knew of any ongoing and unpublished trials. We searched for errata or retractions from eligible studies on PubMed (www.ncbi.nlm.nih.gov/pubmed) and reported the date this was done in the review. We performed a citation search in the Web of Science to obtain articles citing the included studies.
We searched the following registers and grey literature sources up to 4 May 2021.
Grey literature databases
OpenGrey (www.opengrey.eu).
Clinical trial registers and trial result registers
We thoroughly searched various clinical trial registers/trial result registers.
US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov).
-
Current Controlled Trials metaRegister of Controlled Trials (mRCT; www.isrctn.com ):
active registers;
archived registers.
EU Clinical Trials Register (www.clinicaltrialsregister.eu).
World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch).
University Hospital Medical Information Network Clinical Trials Registry (UMIN‐CTR; www.umin.ac.jp/ctr).
We searched conference minutes of the following congress and annual meeting of societies for relevant abstracts.
American Society of Clinical Oncology (ASCO); searched up to 2019.
European Society of Medical Oncology (ESMO); searched up to 2018.
Japan Society of Clinical Oncology (JSCO); searched up to 2019.
Data collection and analysis
Selection of studies
Two review authors (DN and RG) independently screened the titles and abstracts of all studies identified by our search, coding them as 'retrieve' (eligible, potentially eligible, or unclear) or 'do not retrieve'. We retrieved the full text of study reports or publications, and two review authors (DN and RG) independently screened the full text, identified studies for inclusion, and recorded reasons for exclusion of ineligible studies. Any disagreements were resolved through discussion or by consulting a third review author (NW) when necessary. We identified and excluded duplicates and collated multiple reports of the same study so that each study, rather than each report, was the unit of interest in the review. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram and tabulated characteristics of excluded studies (Liberati 2009).
Data extraction and management
To determine study characteristics and outcome data, we used a standard data collection form that had been piloted on at least one study in the review. Two review authors (DN and RG) independently extracted the following study characteristics from included studies.
Methods: study design, number of study centres and location, study setting, withdrawals, date of study.
Participants: number, mean age, age range, gender, diagnostic criteria (for anastomotic leakage, bile reflux, and health‐related quality of life), inclusion and exclusion criteria.
Interventions: intervention, comparison.
Outcomes: primary and secondary outcomes specified and collected, time points reported.
Notes: funding for study, notable conflicts of authors participating in the study.
Two review authors (DN and RG) independently extracted outcome data from the included studies. We presented the characteristics of included studies in the ‘ Characteristics of included studies ’ tables, as well as whether data were reported in an unusable way. Any disagreements were resolved through discussion or by involving a third review author (NW) when necessary. One review author (DN) copied the data from the data collection form into the Review Manager 5 file (Review Manager 2020). We double‐checked that data had been entered correctly by comparing the study reports with the presentation of data in the review. A second review author (RG) spot‐checked study characteristics for accuracy against the study report.
Assessment of risk of bias in included studies
Two review authors (DN and RG) independently assessed the risk of bias of each study, according to the criteria in Table 8.5.d of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Any disagreements were resolved by discussion or by involving a third review author (NW) when necessary. We assessed the risk of bias based on the following domains.
Random sequence generation.
Allocation concealment.
Blinding of participants and personnel.
Blinding of outcome assessment.
Incomplete outcome data.
Selective outcome reporting.
Other potential bias (i.e. specific study design, deceptive study, co‐intervention, blinding of data assessors, baseline imbalance in participant characteristics, perioperative timing of randomisation, and the influence of funders).
We judged each potential source of bias as low, high, or unclear, and provided a quote from the study report and justification for our judgement in the risk of bias table.
We summarised the risk of bias judgements across studies for each of the domains listed. We considered blinding separately for different key outcomes where necessary (e.g. for unblinded outcome assessment, risk of bias for all‐cause mortality may be very different than for a participant‐reported health‐related quality of life scale). Where information on risk of bias related to unpublished data or correspondence with a trialist, we noted this in the risk of bias table.
We took into account the risk of bias for studies that contributed to a given outcome as part of the GRADE methodology when considering treatment effects.
Assessment of bias in conducting the review
We conducted the review based on the published protocol and reported any deviations from it in the Differences between protocol and review section of this review.
Measures of treatment effect
We analysed dichotomous data (incidence of anastomotic leakage, incidence of bile reflux, and postoperative morbidity) as a risk ratio (RR), and continuous data (health‐related quality of life, loss of body weight, and length of hospital stay) as a mean difference (MD) or standardised mean difference (SMD), using a 95% confidence interval (CI) in both cases. We ensured that higher scores for continuous outcomes had the same meaning for a particular outcome; explained the direction to the reader; and reported where the directions were reversed if this was necessary.
We deemed health‐related quality of life scores to be continuous (not arbitrarily categorised) and articulated them as SMDs with 95% CIs following the recommendations in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). We delineated a positive SMD as showing better effects for quality of life.
We undertook meta‐analyses only where this was meaningful, that is if the treatments, participants, and the underlying clinical question were similar enough for pooling to make sense. Considering substantial heterogeneity of surgical outcomes, we used the inverse‐variance random‐effects model unless the events were sparse.
Length of hospital stay is known to be skewed data in most cases. Although some studies ignored the skewness of data and reported mean and standard deviation (SD) for length of hospital stay, trials reporting medians and interquartile ranges (IQRs) only indicated the data were most likely to be skewed (Altman 1996). For studies that did not report mean and SD but did report median and IQRs, we assumed the median was similar to the mean, and IQRs were approximately 1.35 SDs (Higgins 2021). When median and range were reported, we calculated the mean and SD from the median, range, and sample size (Hozo 2005). We excluded these studies in a sensitivity analysis.
Unit of analysis issues
We planned to include cluster‐RCTs in the analysis along with individually randomised trials. We planned to adjust the sample sizes of cluster‐RCTs using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021), with an estimate of the intracluster correlation coefficient (ICC) derived from the trial if possible, or from a similar trial or a study of a similar population. If we used ICCs from other sources, we would report this and conduct a sensitivity analysis to investigate the effect of variation in the ICC. If we identified both cluster‐RCTs and individually randomised trials, we would synthesise the relevant information. We considered it reasonable to combine the results from both if there was little heterogeneity amongst the study designs, and interaction between the effect of intervention and the choice of randomisation unit was considered to be unlikely.
If we included multiple‐arm studies (e.g. comparison between Roux‐en‐Y, Billroth‐I and ‐II), we formed a pair‐wise comparison between Roux‐en‐Y and Billroth‐I reconstruction in the meta‐analysis, and excluded the other arms.
Dealing with missing data
We contacted investigators or study sponsors to verify key study characteristics and to obtain missing numerical data pertaining to outcomes as indicated (e.g. when a study was identified as abstract only). If we were unable to obtain information from investigators or study sponsors, we imputed the mean from the median (i.e. consider median as the mean) and the SD from the standard error, interquartile range, or P values, based on the recommendations in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). When only the median and range were reported, we imputed the mean and the SD calculated from the median, range, and sample size (Hozo 2005). We assessed the impact of including such studies in a sensitivity analysis and indicated our results. When we were unable to calculate the SD from any numerical data including standard error, IQR, range, or P values, we imputed SD as the highest SD in the remaining studies included in the outcome, as it appears safe to borrow SDs from other studies (Furukawa 2006; Higgins 2021), being mindful of the fact that this method of imputation decreases the weight of the studies in the meta‐analysis of MD and shifts the effect towards no effect for SMD.
Assessment of heterogeneity
We used the I² statistic to measure heterogeneity amongst studies in each analysis (Higgins 2003); we considered that an I² of 30% to 60% may represent moderate heterogeneity, and that an I² greater than 60% may represent substantial heterogeneity (Higgins 2021). Furthermore, we explored heterogeneity by prespecified subgroup analyses (Higgins 2021), regardless of the measurement of I² statistics. We additionally assessed heterogeneity by evaluating whether there was good overlap of CIs by visual inspection of the forest plots.
Assessment of reporting biases
If we are able to pool more than 10 studies, we would create and examine a funnel plot to explore possible publication biases. We planned to use Egger's test to determine the statistical significance of reporting bias (Egger 1997). We considered P < 0.05 to be a statistically significant reporting bias.
Data synthesis
We performed meta‐analyses based on the recommendations in the Cochrane Handbook for Systematic Reviews of Interventions using Review Manager 5 (Higgins 2021; Review Manager 2020). We used a random‐effects model for analysis as we considered that the different studies estimated different, yet related intervention effects (DerSimonian 1986), especially pertaining to surgical outcomes.
Subgroup analysis and investigation of heterogeneity
We planned to carry out the following subgroup analyses.
Open resection versus laparoscopic resection versus others.
Early clinical‐stage gastric cancer (stage I) versus others according to the 15th edition of Japanese Classification of Gastric Carcinoma (JGCA 2017b).
We chose two characteristics for subgroup analyses: surgical approach and clinical stage. The rationale for the choice of characteristics was as follows: i) difference of surgical approach may affect the outcomes (Best 2016; Vinuela 2012); and ii) the difference of clinical stage alters the extent of lymph node dissection (JGCA 2017a), which may affect the outcomes.
If the study included laparoscopic and laparoscopy‐assisted cases between 0% and 30%, 31% and 70%, 71% and 100%, and an unknown proportion, we classified them as 'open (laparotomy) study', 'mixed study', 'laparoscopic study', and 'unknown approach study', respectively. If the study included stage I cases between 0% and 30%, 31% and 70%, 71% and 100%, and an unknown proportion, we classified them as 'advanced stage study', 'mixed study', 'early‐stage study', and 'unknown stage study', respectively.
We planned to use the following outcomes in subgroup analyses. To avoid multiplicity issues, we focused on a total of three outcomes that included the two primary outcomes and one of the secondary outcomes.
Health‐related quality of life after surgery (12 months postoperatively).
Loss of body weight (6 to 24 months postoperatively).
Incidence of anastomotic leakage (within 30 days postoperatively).
We used the formal statistical test for subgroup differences to test for subgroup interactions as described in Section 9.6.6 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021).
Sensitivity analysis
We performed an a priori sensitivity analysis to assess the robustness of our conclusions that involved exclusion of studies with high risk of bias in random sequence generation, studies with high risk of bias in allocation concealment, and studies with high risk of attrition bias. We performed additional sensitivity analyses by excluding studies that contained stage IV participants for the outcomes of health‐related quality of life and loss of body weight. We also performed additional sensitivity analyses by excluding studies that reported only median and range in length of hospital stay; excluding studies with unclear usage of the Clavien‐Dindo classification in overall morbidity; and using a fixed‐effect model for the outcome with sparse events (anastomotic leakage).
Reaching conclusions
Our conclusions were only based on findings obtained from the quantitative or narrative synthesis of studies included in this review. We avoided making recommendations for practice. Our implications for research intended to give the reader a clear sense of the focus needed for future research and clarifications required for the uncertainties that remain in the field.
Summary of findings and assessment of the certainty of the evidence
We created a summary of findings table for the comparison Roux‐en‐Y versus Billroth‐I reconstruction with the following outcomes.
Health‐related quality of life (at the time point closest to 12 months postoperatively).
Incidence of anastomotic leakage (within 30 days postoperatively).
Loss of body weight (6 to 24 months after surgery).
Incidence of bile reflux (at time point closest to 12 months postoperatively).
Length of hospital stay (in days).
Postoperative morbidity (within 30 days after surgery).
We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of the body of evidence based on studies that contributed data to the meta‐analyses for each outcome, classifying it as high, moderate, low, or very low. We used the methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions, employing GRADEpro GDT software (GRADEpro GDT; Higgins 2011). Two review authors (DN, NH) independently assessed the certainty of the evidence. We justified all decisions to downgrade or upgrade the certainty of evidence in the footnotes, providing comments to aid the reader's understanding of the review where necessary. We considered whether there was additional outcome information that was not incorporated into the meta‐analyses, noted this in the comments, and stated if it supported or contradicted the information obtained from the meta‐analyses.
Results
Description of studies
Results of the search
Our initial search strategy conducted on 4 May 2021 yielded a total of 1559 articles, with one article identified from other sources (ASCO). Based on title and abstract screening, 17 articles appeared to meet the inclusion criteria and were obtained in full text. One article was written in Chinese, one in Italian, and the others in English. Two of the 17 full‐text articles were conference abstracts. Our check of the references of these 17 articles identified one article relevant to the current review. After full‐text screening, we excluded two articles and assessed one article as awaiting classification. We therefore included 15 articles on eight studies in the review (Figure 1).
1.
Study flow diagram.
We also contacted manufacturers of surgical equipment (Ethicon and Medtronic) to enquire as to whether they had data or literature, which revealed that they did not have this information. We found no grey literature in our search of OpenGrey. Searching other sources including ClinicalTrials.gov also revealed no relevant ongoing trials.
Included studies
See: Characteristics of included studies.
Design
All of the included trials employed randomisation at the level of the individual. We identified no cluster‐randomised studies.
Setting
Three studies were conducted in Japan (Ishikawa 2005; Nakamura 2016; Takiguchi 2012), three in South Korea (Choi 2017; Hur 2017; Lee 2012), one in China (Yang 2017), and one in Italy (D'Amato 1999). Six studies were single‐centre (Choi 2017; D'Amato 1999; Hur 2017; Ishikawa 2005; Lee 2012; Yang 2017), and two were multicentre (Nakamura 2016; Takiguchi 2012).
Participants
All of the included studies enrolled gastric cancer patients who underwent distal gastrectomy. Benign disease patients were also enrolled in one study (D'Amato 1999), and stage IV patients were enrolled in three studies (Ishikawa 2005; Takiguchi 2012; Yang 2017). The included studies enrolled a total of 942 participants.
Interventions
Two studies compared Roux‐en‐Y, Billroth‐I, and Billroth‐II reconstructions (D'Amato 1999; Lee 2012), whilst the remaining studies compared Roux‐en‐Y and Billroth‐I directly.
Surgical approaches
Open surgery (laparotomy), laparoscopic surgery, and robotic surgery are generally used in gastric cancer surgery. Open or laparoscopic approach was employed in all of the studies included in this review. Robotic approach was not employed.
Outcome measures
Health‐related quality of life
Six studies reported health‐related quality of life (HRQoL) (D'Amato 1999; Hur 2017; Lee 2012; Nakamura 2016; Takiguchi 2012; Yang 2017). One study did not report HRQoL, although HRQoL was prespecified in the study protocol (Choi 2017).
HRQoL was assessed using six scales, as follows.
EORTC Core Quality of Life Questionnaire ‐ Core Questionnaire (EORTC QLQ‐C30) (0 to 100 points, higher scores mean better quality of life (QoL)).
EORTC Quality of Life Questionnaire ‐ Gastric Cancer Module (EORTC QLQ‐STO22) (0 to 100 points, higher scores mean better QoL).
Functional Assessment of Cancer Therapy‐General (FACT‐G) (summation of raw scores; higher scores indicate better QoL).
Functional Assessment of Cancer Therapy‐Gastric (FACT‐Ga) (summation of raw scores; higher scores indicate better QoL).
Dysfunction After Upper Gastrointestinal Surgery 20 (DAUGS20) (0 to 100 points, lower scores mean better QoL).
Gastrointestinal Quality of Life Index (GIQLI) (0 to 144 points, higher scores mean better QoL) (Eypasch 1995).
EORTC QLQ‐C30 and FACT‐G are questionnaires in general for cancer patients, whilst EORTC QLQ‐STO22, FACT‐Ga, DAUGS20, and GIQLI are the specific modules for gastric cancer patients. EORTC QLQ‐STO22 is used to complement the EORTC QLQ‐30, and FACT‐Ga is used to complement the FACT‐G.
The included studies collected HRQoL at different time points, as follows:
every 3 months from preoperative baseline to 12 months after surgery (Yang 2017);
at baseline and six months after surgery, and reported the ratio of follow‐up QoL score to the baseline score (Hur 2017);
at baseline and 5 days, 6 months, and 12 months after surgery (Lee 2012);
at baseline, one year after surgery and three years after surgery, and reported the difference from baseline to follow‐up in the intervention and control groups (Nakamura 2016);
at three months after the last case had been registered (Takiguchi 2012).
One study did not report the time point of data collection (D'Amato 1999).
We contacted the trial authors of two studies because the original data were necessary for meta‐analysis (Hur 2017; Nakamura 2016), and were provided this information.
Incidence of anastomotic leakage
Seven studies reported incidence of anastomotic leakage (Choi 2017; Hur 2017; Ishikawa 2005; Lee 2012; Nakamura 2016; Takiguchi 2012; Yang 2017).
Loss of body weight
Patient's body weight was reported as body weight itself (Ishikawa 2005; Nakamura 2016; Takiguchi 2012), or as body mass index (Choi 2017). One study reported body weight change at six months after surgery (Ishikawa 2005); two studies reported body weight change one year after surgery (Choi 2017; Takiguchi 2012); whilst the last study reported body weight change three years after surgery but also measured body weight one year after surgery (Nakamura 2016). We contacted the author of this trial (Nakamura 2016), who provided us the data for body weight change one year after surgery.
Incidence and severity of bile reflux, including remnant gastritis and reflux oesophagitis
Seven studies performed endoscopic investigation after gastric surgery: two studies six months after surgery (Hur 2017; Ishikawa 2005), two studies 12 months after surgery (Lee 2012; Yang 2017), one study 36 months after surgery (Nakamura 2016), and one study at both 12 months and five years after surgery (Takiguchi 2012); the remaining study did not report the time of investigation (D'Amato 1999).
Bile reflux was assessed endoscopically by RGB (Residue, Gastritis, Bile) classification, Kubo 2002, in four studies (Hur 2017; Lee 2012; Nakamura 2016; Yang 2017).
Reflux oesophagitis was assessed endoscopically by Los Angeles classification in four studies (Ishikawa 2005; Lee 2012; Nakamura 2016; Takiguchi 2012).
Length of hospital stay
Seven studies reported length of hospital stay. Definition of 'hospital stay' differed amongst studies. Postoperative hospital stay was used in four studies (Ishikawa 2005; Nakamura 2016; Takiguchi 2012; Yang 2017), and hospital stay was used in three studies (Choi 2017; Hur 2017; Lee 2012).
Postoperative morbidity (Clavien‐Dindo grade II or greater), within 30 days after surgery
Seven studies reported postoperative morbidity. Only four studies used the Clavien‐Dindo classification (Choi 2017; Hur 2017; Nakamura 2016; Yang 2017). Three studies did not mention using the Clavien‐Dindo classification (Ishikawa 2005; Lee 2012; Takiguchi 2012); all the reported surgical complications in one of these studies could be deemed as Clavien‐Dindo grade II or greater (Ishikawa 2005); however, the other two studies might comprise complications equivalent to Clavien‐Dindo grade I (Lee 2012; Takiguchi 2012).
Excluded studies
We excluded two studies for which the randomisation process was conditional (Osugi 2004; Wang 2011). These studies compared Billroth‐I, Billroth‐II, and Roux‐en‐Y. However, randomisation was performed between Roux‐en‐Y and Billroth‐II only when Billroth‐I was impossible (Characteristics of excluded studies).
We assessed one study as awaiting classification as information regarding inclusion criteria and whether the study was appropriately conducted was lacking (Ren 2019). This study compared Billroth‐I, Billroth‐II, and Roux‐en‐Y. We contacted the trial author by email for further information, but received no response.
Risk of bias in included studies
Graphical presentations of risk of bias in the included studies are presented in Figure 2 and Figure 3. Any disagreements between the two review authors (DN and RG) on risk of bias assessment were resolved by discussion.
2.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See: Characteristics of included studies.
Allocation
Random sequence generation
All of the included studies were described as randomised studies. However, three studies did not mention the method of random sequence generation (D'Amato 1999; Hur 2017; Ishikawa 2005). The other studies employed appropriate methods for sequence generation.
Allocation concealment
Three studies adequately concealed allocation by sealed opaque envelopes or central allocations (Nakamura 2016; Takiguchi 2012; Yang 2017). The other five studies provided insufficient information about the method of concealment to make a judgement of low or high risk of bias.
Blinding
Blinding of participants and personnel
All of the included trials were at high risk of performance bias due to the nature of the intervention because surgeons cannot perform reconstruction without knowing the allocation. There was also no mention of efforts to keep the other clinical staff blinded to the treatment allocation in any of the included studies. As for blinding of participants, two studies clearly stated that participants were blinded (Choi 2017; Lee 2012). Three studies stated that no blinding for participants was done, although they focused on patient‐reported outcomes (Hur 2017; Nakamura 2016; Yang 2017). The other three studies did not report blinding status for participants (D'Amato 1999; Ishikawa 2005; Takiguchi 2012).
Blinding of outcome assessment
Since one of the primary outcomes in this review was patient‐reported, blinding for participants was directly linked to detection bias. We assessed four studies as at high risk of bias because participants were not blinded, although their outcomes were patient‐reported (Choi 2017; Hur 2017; Nakamura 2016; Yang 2017). One study that reported blinding for participants described in their study that "all medical documents were recorded without specifying the actual surgical approach" (Lee 2012). However, it would seem to be impossible to make medical records whilst concealing the procedures performed because surgeons generally make operative records. We therefore judged this study as at high risk of bias (Lee 2012). We assessed the other three studies as at unclear risk of bias because they did not report blinding status for outcome assessors or participants making a judgement (D'Amato 1999; Ishikawa 2005; Takiguchi 2012).
Incomplete outcome data
We judged two studies as at low risk of bias because they had a small number of dropouts and these were balanced in numbers and reasons (Choi 2017; Ishikawa 2005). We assessed one study as at unclear risk of bias because the reasons for attrition were not clearly described, although the reasons for exclusion were clearly stated, and the numbers of dropouts were small and well balanced in the intervention and control arms (Takiguchi 2012). We also judged the remaining five studies as at unclear risk of bias because they did not mention missing numbers or reasons for attrition (D'Amato 1999; Hur 2017; Lee 2012; Nakamura 2016; Yang 2017).
Selective reporting
Five studies had been registered in clinical trial databases before the commencement of trials (Choi 2017; Hur 2017; Nakamura 2016; Takiguchi 2012; Yang 2017). Of these, four studies reported outcomes adequately (Hur 2017; Nakamura 2016; Takiguchi 2012; Yang 2017), whilst one study did not report some prespecified outcomes and was therefore rated as at high risk of bias (Choi 2017).
Other potential sources of bias
The timing of randomisation is an important issue in surgical trials because preoperative randomisation allows surgeons to know allocation before resection, which may introduce an element of bias. Preoperative randomisation was used in three trials, which we deemed as at high risk of bias (Choi 2017; Hur 2017; Ishikawa 2005); intraoperative randomisation was used in three trials (Nakamura 2016; Takiguchi 2012; Yang 2017); and the other two trials did not report the timing of randomisation (D'Amato 1999; Lee 2012).
We suspected baseline imbalances in one study because stage IV patients were only included in the Roux‐en‐Y group, which may introduce an element of bias (Takiguchi 2012). Moreover, the acquisition method of HRQoL data in this study may have resulted in large variation in duration from surgery to the questionnaire survey, which could distort the outcome when attrition bias existed. We concluded that this variation was unclear, but considering baseline imbalances, we judged this study to be at high risk of bias (Takiguchi 2012).
In one study the proportion of participants who underwent postoperative chemotherapy differed between the Roux‐en‐Y group and the Billroth‐I group (Yang 2017). This may introduce co‐intervention bias, therefore we judged this study as at high risk of bias (Yang 2017).
There seemed to be little influence of funders in the included studies.
Effects of interventions
See: Table 1
Primary analysis
1.1 Primary outcomes
1.1.1 Health‐related quality of life
Six studies contributed to meta‐analysis (D'Amato 1999; Hur 2017; Lee 2012; Nakamura 2016; Takiguchi 2012; Yang 2017). Different scales were used to investigate HRQoL. We prioritised the use of scales to measure HRQoL including gastric cancer‐specific symptoms. If such a scale was not used, the scores for global health status were adopted. Lower scores indicate better quality of life in DAUGS20, whilst higher scores indicate better quality of life in FACT‐Ga, GIQLI, and global health status of QLQ‐C30. The timing of QoL acquisition in contributing studies was at six months after surgery in one study (Hur 2017), one year after surgery in three studies (Lee 2012; Nakamura 2016; Yang 2017), unknown in one study (D'Amato 1999), and at various time points after surgery in one study (Takiguchi 2012).
The evidence suggests that there is little to no difference in health‐related quality of life between Roux‐en‐Y and Billroth‐I reconstructions (standardised mean difference (SMD) 0.04, 95% confidence interval (CI) −0.11 to 0.18, P = 0.64, I² = 0%; 6 studies; 695 participants; low‐certainty evidence; Analysis 1.1) (Figure 4). We downgraded the certainty of the evidence by two levels due to study limitations (lack of blinding of participants and outcome assessment) and imprecision (95% CI overlapped no effect and was compatible both with benefit and harm).
1.1. Analysis.
Comparison 1: Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 1: Health‐related quality of life
4.
Forest plot of comparison: 1 Roux‐en‐Y versus Billroth‐I reconstruction, outcome: 1.1 Health‐related quality of life.
1.1.2 Incidence of anastomotic leakage
Five studies contributed to meta‐analysis (Hur 2017; Ishikawa 2005; Lee 2012; Nakamura 2016; Takiguchi 2012). Only five cases of anastomotic leakage were reported. Incidence was 0.6% and 1.4% in the Roux‐en‐Y and Billroth‐I groups, respectively. Two studies reported anastomotic leakage as zero (Choi 2017; Yang 2017). The evidence is very uncertain for the effect of Roux‐en‐Y and Billroth‐I reconstruction on incidence of anastomotic leakage (risk ratio (RR) 0.63, 95% CI 0.16 to 2.53, P = 0.51, I² = 0%; 5 studies; 711 participants; very low‐certainty evidence; Analysis 1.2) (Figure 5). We downgraded the certainty of the evidence by three levels due to risk of bias (lack of blinding) and imprecision (wide confidence interval because of rare events; a possibility of substantial harm and substantial benefit).
1.2. Analysis.
Comparison 1: Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 2: Incidence of anastomotic leakage
5.
Forest plot of comparison: 1 Roux‐en‐Y versus Billroth‐I reconstruction, outcome: 1.2 Incidence of anastomotic leakage.
1.2 Secondary outcomes
1.2.1 Loss of body weight
Four studies contributed to meta‐analysis (Choi 2017; Ishikawa 2005; Nakamura 2016; Takiguchi 2012). We chose the ratio of the postoperative body weight to the preoperative body weight as the outcome measure. Since one study did not report the precise value of SD (Ishikawa 2005), which was drawn as an error bar in the figure, we imputed the highest SD amongst the included studies in the analysis (Nakamura 2016), according to the method prespecified in the protocol. The evidence suggests that Billroth‐I reconstruction reduces loss of body weight by 0.41% compared to Roux‐en‐Y reconstruction, but it may increase loss of body weight by 0.77%, or reduce it by 1.59% (mean difference (MD) 0.41, 95% CI −0.77 to 1.59, P = 0. 50, I² = 0%; 4 studies; 541 participants; low‐certainty evidence; Analysis 1.3) (Figure 6). We downgraded the certainty of the evidence by two levels due to risk of bias (lack of blinding) and imprecision (small sample size).
1.3. Analysis.
Comparison 1: Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 3: Loss of body weight
6.
Forest plot of comparison: 1 Roux‐en‐Y versus Billroth‐I reconstruction, outcome: 1.3 Loss of body weight.
1.2.2 Incidence of bile reflux, including remnant gastritis or reflux oesophagitis
Incidence of bile reflux into remnant stomach
Four studies contributed to meta‐analysis (Hur 2017; Lee 2012; Nakamura 2016; Yang 2017). Roux‐en‐Y reconstruction probably reduces the incidence of bile reflux compared to Billroth‐I reconstruction (RR 0.40, 95% CI 0.25 to 0.63, P < 0.001, I² = 22%; 4 studies; 399 participants; moderate‐certainty evidence; Analysis 1.4). No substantial heterogeneity was observed. We downgraded the certainty of the evidence by one level because of study limitations (lack of blinding of outcome assessment and incomplete outcome data).
1.4. Analysis.
Comparison 1: Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 4: Incidence of bile reflux
Incidence of reflux oesophagitis
Four studies reported reflux oesophagitis using the Los Angeles classification (Ishikawa 2005; Lee 2012; Nakamura 2016; Takiguchi 2012). One study reported this outcome both one year and five years after surgery (Takiguchi 2012); we employed the result of one year after surgery. Heterogeneity was substantial (I² = 65%), and the CIs did not overlap well upon visual inspection. There was inconsistency in the direction of effect, and we judged that quoting an average value for the intervention effect could be misleading.
1.2.3 Length of hospital stay (days)
One study reported hospital stay in median and range as 11 days (range: 7 to 88 days) in the Roux‐en‐Y group and 11 days (range: 7 to 63 days) in the Billroth‐I group (Nakamura 2016). We calculated the mean and SD from the median, range, and sample size (Hozo 2005), and imputed them. Subsequently, seven studies contributed to the meta‐analysis (Choi 2017; Hur 2017; Ishikawa 2005; Lee 2012; Nakamura 2016; Takiguchi 2012; Yang 2017). Billroth‐I reconstruction may shorten hospital stay compared to Roux‐en‐Y reconstruction, but the evidence is very uncertain (MD 0.96, 95% CI 0.16 to 1.76, P = 0.02; 7 studies; 894 participants; very low‐certainty evidence; Analysis 1.5). There was moderate heterogeneity (I² = 56%). We downgraded the certainty of the evidence by three levels because of inconsistency and study limitations (lack of blinding and incomplete reporting on results which indicates the data are skewed).
1.5. Analysis.
Comparison 1: Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 5: Length of hospital stay
1.2.4 Postoperative morbidity (Clavien‐Dindo grade II or greater), within 30 days after surgery
Seven studies contributed to meta‐analysis (Choi 2017; Hur 2017; Ishikawa 2005; Lee 2012; Nakamura 2016; Takiguchi 2012; Yang 2017). Billroth‐I reconstruction may reduce postoperative morbidity within 30 days after surgery compared to Roux‐en‐Y reconstruction (RR 1.47, 95% CI 1.02 to 2.11, P = 0.04, I² = 0%; 7 studies; 891 participants; low‐certainty evidence; Analysis 1.6). We downgraded the certainty of the evidence by two levels because of the trial design (lack of blinding) and inconsistency. Details of the reported complications were summarised in Table 2.
1.6. Analysis.
Comparison 1: Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 6: Postoperative morbidity
1. Details of complications reported in included studies.
| Study | Roux‐en‐Y | Affected participants in Roux‐en‐Y | Billroth‐I | Affected participants in Billroth‐I |
| Choi 2017 | 1 Atelectasis 1 Bleeding |
2/20 | 1 Atelectasis 1 Complicated fluid |
2/20 |
| Hur 2017 | 3 Postoperative ileus 1 Pneumonia 1 Leakage 1 Wound seroma 1 Voiding difficulty |
6/58 | 1 Postoperative ileus 1 Pneumonia 1 Intra‐abdominal fluid 1 Cholecystitis 1 Voiding difficulty 2 Unknown fever |
7/56 |
| Yang 2017 | 10 Pulmonary complications 1 Acute cholecystitis 2 Superficial surgical site infection 2 Intra‐abdominal infection 1 Adhesive ileus 1 Acute urinary retention 1 Gastroplegia |
14/70 | 10 Pulmonary complications 1 Acute cholecystitis 1 Acute urinary retention 1 Gastroplegia |
11/70 |
| Nakamura 2016 | 4 Delayed gastric emptying 1 Pancreatic fistula 2 Anastomotic stricture 1 Pancreatic fistula 1 Postoperative bleeding |
9/59 | 1 Surgical site infection 2 Anastomotic leakage 1 Anastomotic stricture |
4/60 |
| Lee 2012 | 1 Anastomotic leakage 2 Gastorojejunostomy outlet obstruction 2 Intra‐abdominal abscess 1 Deep vein thrombosis |
6/47 | 2 Bleeding 1 Wound problem 1 Chyle leakage |
4/49 |
| Takiguchi 2012 | 3 Pancreatic fistula 3 Abdominal abscess 2 Bowel obstruction 2 Postoperative pancreatitis 2 Surgical site infection 2 Anastomotic stricture |
23/169 | 2 Pancreatic fistula 2 Anastomotic leakage 3 Abdominal abscess 1 Bowel obstruction 2 Postoperative pancreatitis 3 Surgical site infection 3 Anastomotic stricture |
14/163 |
| Ishikawa 2005 | 3 Gastric stasis 1 Intestinal obstruction 1 Pneumonia 2 Anastomotic stricture |
6/24 | 1 Leakage 1 Intestinal obstruction |
2/26 |
See Table 1 for the results of the primary analysis.
Secondary analysis
We categorised the included trials considering disease stages and surgical approaches for subgroup and sensitivity analysis, according to the prespecified methods. Regarding proportion of stage I patients included, we categorised four studies as 'early‐stage study' (Choi 2017; Hur 2017; Nakamura 2016; Takiguchi 2012); two studies as 'mixed‐stage study' (Ishikawa 2005; Yang 2017); and two studies as 'unknown‐stage study' (D'Amato 1999; Lee 2012).
Regarding surgical approach, we judged two studies as 'laparoscopic study' (Choi 2017; Hur 2017); two studies as 'mixed study' (Lee 2012; Nakamura 2016); two studies as 'open (laparotomy) study' (Takiguchi 2012; Yang 2017); and two studies as 'unknown study' (D'Amato 1999; Ishikawa 2005).
1.3 Subgroup analysis and investigation of heterogeneity
1.3.1 Health‐related quality of life
We judged two studies as open (laparotomy) studies (Takiguchi 2012; Yang 2017). If limited to open (laparotomy) studies, the estimated SMD was 0.15 (95% CI −0.05 to 0.34, P = 0.14), greater than the primary analysis. In contrast, the estimated SMD of the laparoscopic studies was −0.21 (95% CI −0.59 to 0.17, P = 0.28), and that of mixed and unknown studies was −0.07 (95% CI −0.35 to 0.22, P = 0.66). The SMD of laparoscopic studies had the opposite direction to that of the open studies (Analysis 2.1). The test for subgroup analysis did not show significant heterogeneity (I² = 39.9%).
2.1. Analysis.
Comparison 2: Subgroup analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 1: Health‐related quality of life based on surgical approach
We judged three studies as early‐stage studies (Hur 2017; Nakamura 2016; Takiguchi 2012). If limited to these three studies, the estimated SMD was −0.02 (95% CI −0.20 to 0.17, P = 0.87) (Analysis 2.3), which had the opposite direction to the primary analysis. Test for subgroup analysis did not show heterogeneity (I² = 0%).
2.3. Analysis.
Comparison 2: Subgroup analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 3: Health‐related quality of life based on cancer stage
1.3.2 Loss of body weight
We judged one study as an open (laparotomy) study (Takiguchi 2012); its estimated MD was 0.60 (95% CI −0.87 to 2.07, P = 0.42) (Analysis 2.2). Test for subgroup analysis did not show heterogeneity (I² = 0%). Regarding disease stage, we categorised three studies as early‐stage studies (Choi 2017; Nakamura 2016; Takiguchi 2012). If limited to these studies, the estimated MD was 0.37 (95% CI −0.86 to 1.59, P = 0.56) (Analysis 2.4).
2.2. Analysis.
Comparison 2: Subgroup analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 2: Loss of body weight based on surgical approach
2.4. Analysis.
Comparison 2: Subgroup analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 4: Loss of body weight based on cancer stage
1.3.3 Incidence of anastomotic leakage
Since the incidence of anastomotic leakage was sparse, we did not conduct the prespecified subgroup analysis.
1.4 Sensitivity analysis
1.4.1 Studies without selection and attrition bias
We judged no studies as at high risk of bias for random sequence generation, allocation concealment, or attrition bias.
1.4.2 Studies without stage IV patients
Three studies included stage IV cancer patients (Ishikawa 2005; Takiguchi 2012; Yang 2017), whose percentages were 2.0%, 1.5%, and 5.0%, respectively. Due to the small proportion of stage IV patients, we did not conduct the prespecified sensitivity analysis.
1.4.3 Studies without skewed data
In primary analyses, length of hospital stay (days) had a moderate amount of heterogeneity (I² = 56%). After excluding the study reporting only median value and range, Nakamura 2016, and the study under suspicion of being skewed with large SD (Ishikawa 2005), the I² statistic was 13% (Analysis 3.1).
3.1. Analysis.
Comparison 3: Sensitivity analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 1: Length of hospital stay in studies without skewed data
1.4.4 Studies without unclear usage of Clavien‐Dindo classification
In the primary analysis, three studies were unclear regarding the use of the Clavien‐Dindo classification. One study reported complications in detail (Ishikawa 2005), and all the events reported can be deemed Clavien‐Dindo grade II or greater. Although the other two studies did not report their events in detail (Lee 2012; Takiguchi 2012), we deemed their reported events as equivalent to the Clavien‐Dindo classification grade II or greater. As a sensitivity analysis, we excluded two studies (Lee 2012; Takiguchi 2012). As a result, the difference shown in the primary analysis did not remain statistically significant (Analysis 3.2). This sensitivity analysis was not prespecified in the protocol.
3.2. Analysis.
Comparison 3: Sensitivity analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 2: Postoperative morbidity in studies in which use of Clavien‐Dindo classification was not unclear
1.4.5 Anastomotic leakage with a fixed‐effect model
In the primary analysis, we used a random‐effects model to assess anastomotic leakage, although events were sparse. However, use of the random‐effects model for rare events should be avoided (Higgins 2021), therefore we performed a post hoc sensitivity analysis using a fixed‐effect model (Analysis 3.3). When the fixed‐effect model was used, the magnitude and the direction of the result did not change, whilst the confidence interval narrowed.
3.3. Analysis.
Comparison 3: Sensitivity analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 3: Incidence of anastomotic leakage with a fixed‐effect model
1.4.6 Studies without benign disease patients
One study included participants with benign disease, whose percentage was 55% (D'Amato 1999). The population in which participants with benign diseases were predominantly included may differ from that of only gastric cancer; hence, we performed a post hoc sensitivity analysis on health‐related quality of life. After excluding this study, the magnitude and the direction of the result did not change, whilst the confidence interval widened (Analysis 3.4).
3.4. Analysis.
Comparison 3: Sensitivity analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 4: Health‐related quality of life in studies without benign disease patients
1.4.7 Studies without patients with diabetes mellitus
All the participants in one study had type 2 diabetes mellitus (Choi 2017). Since the characteristics of participants may be different from those of the other included studies, we performed a post hoc sensitivity analysis on body weight loss. After excluding this study, the direction of the result did not change. Still, the magnitude of the result became larger in favour of Billroth‐I (Analysis 3.5).
3.5. Analysis.
Comparison 3: Sensitivity analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 5: Loss of body weight in studies not limited to diabetic patients
1.4.8 Studies without co‐intervention bias
In one study (Yang 2017), 62.9% of participants in the Roux‐en‐Y group underwent adjuvant chemotherapy, whilst 47.1% of the Billroth‐I group did. This imbalance may bring about co‐intervention bias, thus we performed a post hoc sensitivity analysis on health‐related quality of life. After excluding this study, the point estimate changed slightly toward favouring Billroth‐I, with a wider confidence interval (Analysis 3.6).
3.6. Analysis.
Comparison 3: Sensitivity analysis in Roux‐en‐Y versus Billroth‐I reconstruction, Outcome 6: Health‐related quality of life in studies without co‐intervention bias
Discussion
Summary of main results
This systematic review and meta‐analysis assessed the evidence on health‐related quality of life and safety outcomes of Roux‐en‐Y reconstruction for a short‐term phase compared with Billroth‐I reconstruction after distal gastrectomy for people with gastric cancer.
With regard to our primary outcomes, the evidence suggests that there is little to no difference between reconstruction methods for the outcome health‐related quality of life. The evidence is very uncertain regarding the effect of Roux‐en‐Y versus Billroth‐I reconstruction on incidence of anastomotic leakage. Subgroup analysis implied that the difference in surgical approaches might affect the direction of the effect for health‐related quality of life, although this was not statistically significant.
For our secondary outcomes, Billroth‐I reconstruction may reduce loss of body weight by 0.41% compared to Roux‐en‐Y reconstruction one year after surgery, but it may increase loss of body weight by 0.77%, or reduce it by 1.59%.
Roux‐en‐Y reconstruction probably reduces the incidence of bile reflux into the remnant stomach; however, the incidence of bile reflux into the remnant stomach was assessed only by endoscopic investigation, thus the difference might not be clinically relevant.
In contrast, Billroth‐I reconstruction may shorten length of hospital stay, but the evidence is very uncertain. Furthermore, Billroth‐I reconstruction may reduce overall morbidity. The sensitivity analyses suggested that the difference in length of hospital stay was robust, but the risk ratio in overall morbidity was not. Although not robust, the risk ratio was 1.47 in the primary analysis, which may be clinically meaningful. The average difference in length of hospital stay was 0.96 days, which may not be relevant to an individual patient. The value for such difference may differ amongst people and depend on the medical system of the individual country.
The certainty of the evidence was low for health‐related quality of life, moderate for incidence of bile reflux, very low for length of hospital stay and incidence of anastomotic leakage, and low for the other outcomes.
Overall completeness and applicability of evidence
Participants
Seven out of the eight included studies were conducted in East‐Asian countries. Hence, most of the participants in the current review could be Asian. This might weaken the applicability of the evidence.
Interventions
The current review includes eight studies conducted from 1995 to 2014. Surgical equipment and technique have changed over these 20 years. Recent studies tended to employ laparoscopic surgery. Moreover, methods for reconstruction varied amongst studies, as some trials employed hand‐sewn sutures, whilst others employed staplers. These differences might affect the applicability of the evidence.
Outcomes
Given that the Clavien‐Dindo classification was introduced in 2004 (Dindo 2004), some trials that started before 2004 did not employ this classification. The Clavien‐Dindo classification is currently the standard criteria for evaluating surgical complications (Clavien 2009). If appropriately used, Clavien‐Dindo grade II or greater precisely shows complications requiring additional treatment. When surgical complications are reported without use of this classification, complications may be overestimated because those that do not require additional treatment cannot be discriminated. In the current review, we included all studies reporting morbidity in the primary analysis. In the sensitivity analysis, we excluded two studies in which use of the Clavien‐Dindo classification was uncertain; the results were not statistically significant. Although the result of the primary analysis and the sensitivity analysis had the same direction, this led to downgrading of the certainty of the evidence.
Quality of the evidence
We summarised the certainty of the evidence of each outcome in the Effects of interventions section according to the GRADE approach.
Limitations in study design and implementation
Firstly, we assessed all of the included studies as at high risk of bias for blinding of personnel. This is unavoidable because surgeons cannot perform surgery without knowing the allocated procedure. Secondly, six studies measured and reported patient‐reported outcomes, but all six studies were not judged as at low risk of bias for outcome assessment. Patient‐reported outcomes should be assessed with adequate participant blinding. Thirdly, two studies reported their length of hospital stay using potentially skewed data.
Indirectness of the evidence
Firstly, bile reflux was assessed by endoscopic investigation. Roux‐en‐Y was significantly more effective in reducing the incidence of bile reflux into the remnant stomach. This evidence was based on endoscopic findings that are objective but could be trivial for patients without symptoms caused by bile reflux. Secondly, the study conducted in Europe comprised patients both with benign disease and with gastric cancer; almost 50% of participants in this study had gastric cancer, whilst the other studies included only patients with gastric cancer. This might affect the outcomes with regard to cancer‐specific symptoms.
Inconsistency of the results
We reviewed the incidence of reflux oesophagitis narratively since there was inconsistency in the results from each trial. This outcome could be affected by the missing of participants.
Imprecision of the results
Incidence of anastomotic leakage was sparse. When events are rare, the results of meta‐analysis can be biased (Higgins 2021). As described above, this led to downgrading of the certainty of the evidence.
Publication bias
We did not draw funnel plots, as we included fewer than 10 studies. We were unable to determine whether or not there was a publication bias. However, one study did not report QoL in the paper (Choi 2017), although the acquisition of QoL was stated in the protocol, which raises the suspicion of publication bias.
Potential biases in the review process
We followed Cochrane searching methodology. As a result of our initial search, we obtained non‐English reports as well as English‐language reports.
The strength of this review is the acquisition of unpublished data from trial authors, as recommended in the Cochrane Handbook for Systematic Reviews of Interventions. We obtained unpublished data for HRQoL and loss of body weight and performed data synthesis with this information.
The limitation of this review is that we included only eight studies.
Agreements and disagreements with other studies or reviews
Several reviews have been published recently investigating the efficacy of reconstruction methods. Xiong 2013 included RCTs and observational studies but assessed them separately. Their pooled analysis of RCTs had the same concept as ours but did not include newly published RCTs. Zong 2011 included observational studies and RCTs, which was different from our methodology. A newly published network meta‐analysis, Cai 2018, assessing Roux‐en‐Y, Billroth‐I, and Billroth‐II included only RCTs, but the results of the risk of bias assessment differed from our results. The newest review, Kim 2019, also assessed three reconstruction methods and included mainly observational studies. None of these reviews focused on health‐related quality of life. Since treatments should be evaluated not only by surgical outcomes or endoscopic findings but also by general functioning and quality of life, we focused our review on HRQoL as one of the primary outcomes, making our review different from the others.
Authors' conclusions
Implications for practice.
The evidence suggests that there is little to no difference between Roux‐en‐Y and Billroth‐I reconstruction for the outcome health‐related quality of life. However, the certainty of the evidence is low. Roux‐en‐Y probably prevents bile reflux into the remnant stomach. Billroth‐I may reduce overall morbidity. Billroth‐I may also shorten length of hospital stay, although the evidence for this outcome is very uncertain. The certainty of the evidence was low or very low for all of the outcomes in this review except incidence of bile reflux, for which the certainty was moderate. The results of this review should therefore be interpreted in consideration of this.
Implications for research.
In this review, health‐related quality of life was assessed only by disease‐specific scales, which are suitable for assessing health‐related quality of life with disease‐specific symptoms, but difficult for policymakers to use. The assessment with a preference‐based scale should also be discussed in future research. Moreover, a long‐term assessment of health‐related quality of life is needed.
We did not include an assessment of cost in the protocol because it was out of the scope of this Cochrane Review. None of the included studies reported the cost‐related outcome. Our review showed Billroth‐I reconstruction requires a shorter hospital stay than Roux‐en‐Y reconstruction. In the future, outcomes related to cost‐effectiveness should be assessed.
History
Protocol first published: Issue 4, 2018
Acknowledgements
We acknowledge the help and support of the Cochrane Gut Group. We thank Teo Quay (Managing Editor), Yuhong Yuan (Information Specialist and former Managing Editor), and Karin Dearness (former Managing Editor of Cochrane Upper Gastrointestinal and Pancreatic Diseases (now Cochrane Gut)) for providing administrative and logistical support for the conduct of the review.
The authors would also like to thank the following editors and peer referees, who provided comments to improve the protocol and the review: Grigorios Leontiadis (Co‐ordinating Editor), Sarah Rhodes (Editor), Takeshi Kanno (Editor), Hideaki Shimada (Peer Referee), Kouji Nakada (Peer Referee) and Alfretta Vanderheyden (Consumer Referee). The search strategies were designed and run by Yuhong Yuan (Information Specialist, Cochrane Gut). We thank Lisa Winer for copy‐editing this review.
We appreciate Sang‐Yong Son, Hoon Hur, and Sang‐Uk Han at Ajou University, and Masaki Nakamura at Wakayama Medical University Hospital for kindly providing us with their unpublished data.
The Methods section of this review is based on a standard template used by Cochrane Gut Group.
Appendices
Appendix 1. Glossary of terms
Anastomosis: the surgical connection between two structures, usually hollow, tubular ones, to maintain continuity, e.g. anastomosis of blood vessels, or organs of the gastrointestinal tract
Bile: a dark green to yellowish‐brown fluid produced by the liver that aids the digestion of lipids in the small intestine
Billroth‐I: an operation in which the pylorus is removed and the proximal stomach (or its remnant) is anastomosed directly to the duodenum
D2 lymphadenectomy: extended resection of lymph node basins around the stomach
Distal gastrectomy: a procedure in which the portion of the stomach distal to the antrum is excised
Duodenum: the first part of the small intestine (which follows after the stomach)
Endoscopically: using an endoscopy via mouth
Extracorporeal: occurring outside the body
Gastrectomy: a procedure where all or part of the stomach is surgically removed
Gastric: related to the stomach
Gastrojejunostomy: the surgical joining of the stomach and the jejunum to keep the continuity of the alimentary tract
Internal hernia: protrusions of the viscera through the peritoneum or mesentery, but remaining within the abdominal cavity
Intracorporeal: occurring within the body
Jejunal interposition: a reconstructive procedure whereby a section of the jejunum is put between the remnant stomach and the duodenum to replace the missing section of the stomach after resection of the distal side of the stomach
Lymphadenectomy: resection of the lymph node basin
Malignancy: malignant tumour
Mesenteric: related to mesentery (a tissue which attaches the intestines to the wall of the abdomen)
Mucosa: a moist membrane that lines various cavities in the body and surrounds internal organs
Physiologic: related to or characteristic of an organism's normal function
Postgastrectomy syndrome: uncomfortable symptoms including fullness, delayed emptying, and cold sweat, amongst others, occurring after gastrectomy
Reflux oesophagitis: inflammation of the distal oesophagus caused by bile which occurs after distal or total gastrectomy due to loss of valval function between the stomach and the oesophagus
Resection: surgical removal
Roux‐en‐Y: the surgical joining of the remnant stomach and the jejunum, which is divided to make an alternative pathway to divert bile flow away
Roux stasis: a symptom complex of postprandial fullness, nausea, vomiting, and abdominal pain occurring after a Roux‐en‐Y reconstruction without outlet stricture
Stasis: a stoppage or slowdown in the flow of body fluids
Ulcer: a discontinuity or breach in the continuity of a body membrane
Appendix 2. CENTRAL (via Ovid) search strategy
exp Stomach Neoplasms/
((gastric or gastro* or stomach) adj3 (cancer* or carcinoma* or malignan* or tumor* or tumour* or neoplas* or adenocarcinoma*)).tw,kw.
1 or 2
exp Gastric Bypass/
exp gastroenterostomy/
exp anastomosis, roux‐en‐y/
(Roux‐en‐Y or Roux‐Y).tw,kw.
((Stomch or gastric or gastro*) adj3 bypass).tw,kw.
(gastrojejunostom* or gastro‐jejunostom* or ((gastrojejunal or gastro‐jejunal or jejunogastric or jejunum‐gastric or jejuno‐gastric) adj2 (anastom* or fixation* or reconstruct*))).tw,kw.
(gastroenterostom* or gastro‐enterostom* or gastroduodenostom* or gastro‐duodenostom* or ((gastroduoden* or gastro‐duoden*) adj2 (anastom* or fixation* or reconstruct*))).tw,kw.
Billroth*.tw,kw.
or/4‐11
3 and 12
Appendix 3. MEDLINE (via Ovid) search strategy
exp Stomach Neoplasms/
((gastric or gastro* or stomach) adj3 (cancer* or carcinoma* or malignan* or tumor* or tumour* or neoplas* or adenocarcinoma*)).tw,kw.
1 or 2
exp Gastric Bypass/
exp gastroenterostomy/
exp anastomosis, roux‐en‐y/
(Roux‐en‐Y or Roux‐Y).tw,kw.
((Stomch or gastric or gastro*) adj3 bypass).tw,kw.
(gastrojejunostom* or gastro‐jejunostom* or ((gastrojejunal or gastro‐jejunal or jejunogastric or jejunum‐gastric or jejuno‐gastric) adj2 (anastom* or fixation* or reconstruct*))).tw,kw.
(gastroenterostom* or gastro‐enterostom* or gastroduodenostom* or gastro‐duodenostom* or ((gastroduoden* or gastro‐duoden*) adj2 (anastom* or fixation* or reconstruct*))).tw,kw.
Billroth*.tw,kw.
or/4‐11
3 and 12
randomized controlled trial.pt.
clinical trial.pt.
random*.ab.
placebo.ab.
trial.ab.
groups.ab.
or/14‐19
exp animals/ not humans.sh.
20 not 21
13 and 22
Note: Lines 14‐22, RCT filter, we used the Cochrane Handbook RCT filter ‐ sensitivity max version (2008 revision) . We made the following minor revisions: we used “random*” instead of “randomized.ab” or “randomly.ab.” to capture word variations such as “randomised, randomization, random”; we removed “drug therapy.fs.” from the above filter as this review is not related to drug therapy. “
Appendix 4. Embase (via Ovid) search strategy
exp stomach tumor/
((gastric or gastro* or stomach) adj3 (cancer* or carcinoma* or malignan* or tumor* or tumour* or neoplas* or adenocarcinoma*)).tw,kw.
1 or 2
exp gastroenterostomy/
exp gastroduodenostomy/
exp gastric bypass surgery/
exp gastrojejunostomy/
exp gastrectomy Billroth I/
(Roux‐en‐Y or Roux‐Y).tw,kw.
((Stomch or gastric or gastro*) adj3 bypass).tw,kw.
(gastrojejunostom* or gastro‐jejunostom* or ((gastrojejunal or gastro‐jejunal or jejunogastric or jejunum‐gastric or jejuno‐gastric) adj2 (anastom* or fixation* or reconstruct*))).tw,kw.
(gastroenterostom* or gastro‐enterostom* or gastroduodenostom* or gastro‐duodenostom* or ((gastroduoden* or gastro‐duoden*) adj2 (anastom* or fixation* or reconstruct*))).tw,kw.
Billroth*.tw,kw.
or/4‐13
3 and 14
random:.tw.
placebo:.mp.
double‐blind:.tw.
or/16‐18
exp animal/ not exp human/
19 not 20
15 and 21
Note: Lines 16‐19, Hedge Best balance of sensitivity and specificity filter for identifying "therapy studies"in Embase. hiru.mcmaster.ca/hiru/HIRU_Hedges_EMBASE_Strategies.aspx
Data and analyses
Comparison 1. Roux‐en‐Y versus Billroth‐I reconstruction.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1.1 Health‐related quality of life | 6 | 695 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐0.11, 0.18] |
| 1.2 Incidence of anastomotic leakage | 5 | 711 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.16, 2.53] |
| 1.3 Loss of body weight | 4 | 541 | Mean Difference (IV, Random, 95% CI) | 0.41 [‐0.77, 1.59] |
| 1.4 Incidence of bile reflux | 4 | 399 | Risk Ratio (M‐H, Random, 95% CI) | 0.40 [0.25, 0.63] |
| 1.5 Length of hospital stay | 7 | 894 | Mean Difference (IV, Random, 95% CI) | 0.96 [0.16, 1.76] |
| 1.6 Postoperative morbidity | 7 | 891 | Risk Ratio (M‐H, Random, 95% CI) | 1.47 [1.02, 2.11] |
Comparison 2. Subgroup analysis in Roux‐en‐Y versus Billroth‐I reconstruction.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 2.1 Health‐related quality of life based on surgical approach | 6 | 695 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐0.11, 0.18] |
| 2.1.1 Open studies | 2 | 404 | Std. Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.05, 0.34] |
| 2.1.2 Laparoscopic studies | 1 | 106 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.59, 0.17] |
| 2.1.3 Mixed and unknown studies | 3 | 185 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.07 [‐0.35, 0.22] |
| 2.2 Loss of body weight based on surgical approach | 4 | 541 | Mean Difference (IV, Random, 95% CI) | 0.41 [‐0.77, 1.59] |
| 2.2.1 Open studies | 1 | 332 | Mean Difference (IV, Random, 95% CI) | 0.60 [‐0.87, 2.07] |
| 2.2.2 Laparoscopic studies | 1 | 40 | Mean Difference (IV, Random, 95% CI) | ‐0.70 [‐4.48, 3.08] |
| 2.2.3 Mixed and unknown studies | 2 | 169 | Mean Difference (IV, Random, 95% CI) | 0.34 [‐2.01, 2.68] |
| 2.3 Health‐related quality of life based on cancer stage | 6 | 695 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐0.11, 0.18] |
| 2.3.1 Early stage studies | 3 | 490 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.20, 0.17] |
| 2.3.2 Mixed and unknown studies | 3 | 205 | Std. Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.13, 0.42] |
| 2.4 Loss of body weight based on cancer stage | 4 | 541 | Mean Difference (IV, Random, 95% CI) | 0.41 [‐0.77, 1.59] |
| 2.4.1 Early stage studies | 3 | 491 | Mean Difference (IV, Random, 95% CI) | 0.37 [‐0.86, 1.59] |
| 2.4.2 Mixed and unknown studies | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 0.90 [‐3.43, 5.23] |
Comparison 3. Sensitivity analysis in Roux‐en‐Y versus Billroth‐I reconstruction.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 3.1 Length of hospital stay in studies without skewed data | 5 | 722 | Mean Difference (IV, Random, 95% CI) | 0.62 [0.16, 1.09] |
| 3.2 Postoperative morbidity in studies in which use of Clavien‐Dindo classification was not unclear | 5 | 463 | Risk Ratio (M‐H, Random, 95% CI) | 1.39 [0.87, 2.24] |
| 3.3 Incidence of anastomotic leakage with a fixed‐effect model | 5 | 711 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.19, 1.93] |
| 3.4 Health‐related quality of life in studies without benign disease patients | 5 | 665 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐0.12, 0.19] |
| 3.5 Loss of body weight in studies not limited to diabetic patients | 3 | 501 | Mean Difference (IV, Random, 95% CI) | 0.53 [‐0.72, 1.77] |
| 3.6 Health‐related quality of life in studies without co‐intervention bias | 5 | 559 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.01 [‐0.18, 0.15] |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Choi 2017.
| Study characteristics | ||
| Methods | RCT, single‐centre, Seoul, South Korea Aim: "To investigate the impact of RY in distal gastrectomy, which can provide a longer bypass length of the proximal jejunum than BI and BII" Inclusion period: 35 months, from July 2011 to May 2014 Timing of randomisation: before surgery Registered ID: NCT01375738 |
|
| Participants | Number randomised: 44 Age: 20 to 80 Inclusion criteria: patients diagnosed with early gastric cancer and type 2 diabetes mellitus Exclusion criteria:
Stage: all participants were diagnosed as cT1N0 preoperatively, and stage IV patients were not included. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I Devices: linear staplers were used in each group. Approach: all participants underwent laparoscopic surgery. |
|
| Outcomes | Primary outcome: blood sugar stabilisation after gastrectomy at 3 months after surgery by comparing the difference between fasting blood sugar and postprandial blood glucose, blood sugar stabilisation after gastrectomy. Questionnaire for quality of life was listed as 1 of the outcomes in a translated protocol attached to the article. | |
| Notes | All participants received diabetic medication. Funding source was not stated; 1 of the authors acquired some funding, however the relationship of the funder to the author was unclear. Conflict of interest: the authors have declared that no competing interests existed. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "computer‐generated randomisation" Comment: done |
| Allocation concealment (selection bias) | Unclear risk | Comment: not mentioned |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "Neither patients nor investigators were masked to treatment assignment" |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: participants were not blinded for the outcome health‐related quality of life. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: there were 2/22 (9.1%) cases of loss to follow‐up in each group according to adjuvant chemotherapy, but numbers were balanced. |
| Selective reporting (reporting bias) | High risk | Comment: the study was registered before enrolment, but the prespecified outcome of quality of life was not reported. |
| Other bias | High risk | Comment: there is an unreported alteration for the timing of primary endpoint measure. Timing of randomisation was before surgery. |
D'Amato 1999.
| Study characteristics | ||
| Methods | RCT, single‐centre, Rome, Italy Aim: to evaluate which of the 3 techniques guarantees the best functional results Inclusion period: between 1990 and 1995 Allocation: 3 arms Timing of randomisation: no information provided. |
|
| Participants | Number randomised: 45 Age: not mentioned as inclusion criteria (observed range: 39 to 77) Inclusion criteria: benign diseases (whether peptic or duodenal ulcer) and malignant tumours in early stages (gastric carcinoma) Exclusion criteria: not mentioned Stage: amongst 45 participants analysed, 25 participants (55%) had benign diseases and 20 participants (45%) had early gastric carcinoma. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I vs Billroth‐II Devices: not mentioned Approach: not mentioned | |
| Outcomes | Gastro‐oesophageal reflux, dynamics of gastric emptying, and quality of life (GIQLI) | |
| Notes | Funding source: not mentioned Declaration of interests: no information provided. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Randomizzato e stratificato" and "patients were assigned randomly to 3 homogenous clusters" Comment: no further information provided. |
| Allocation concealment (selection bias) | Unclear risk | Comment: not mentioned |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: not mentioned in the study reports, but it is theoretically impossible for surgeons to perform reconstruction without knowing the allocation |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: not mentioned |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: missing participants were not described for quality of life. |
| Selective reporting (reporting bias) | Unclear risk | Comment: no information about study registration |
| Other bias | Unclear risk | Comment: insufficient information provided. |
Hur 2017.
| Study characteristics | ||
| Methods | RCT, single‐centre, Suwon, South Korea Aim: to assess the effect of R‐Y reconstruction on bile reflux as objectively as possible Inclusion period: 17 months, from July 2010 to November 2011 Allocation: parallel Timing of randomisation: before surgery Registered ID: NCT01142271 |
|
| Participants | Number randomised: 118 Age: 25 to 74 Inclusion criteria: patients with gastric adenocarcinoma located in the middle or distal portion of the stomach Exclusion criteria: pregnancy, synchronous malignancy, and uncontrolled systemic disease Stage: amongst 114 participants analysed, 99 participants (86.8%) were in stage I. Stage IV patients were not included. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I Devices: circular staplers (29 mm in diameter) were used in each group. Approach: 91.4% and 87.5% of participants underwent laparoscopic resection in Roux‐en‐Y and Billroth‐I groups, respectively. |
|
| Outcomes | Primary endpoint: reflux of bile content 6 months after surgery Secondary outcomes:
|
|
| Notes | Funding source: a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1320270) Declaration of interests: no potential conflicts of interest reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: the method of randomisation was not described. |
| Allocation concealment (selection bias) | Unclear risk | Comment: the method of concealment was not described. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "Surgeons and patients were not blinded" |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "Investigators and data collectors were blinded" Comment: however, the outcome HRQoL was judged to be at high risk of bias because participants were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: follow‐up rates between intervention groups were imbalanced, and the reasons for missing data were described only as "lost to follow‐up". |
| Selective reporting (reporting bias) | Low risk | Comment: the study was registered before enrolment, and the prespecified outcomes were reported. |
| Other bias | High risk | Comment: timing of randomisation was before surgery, which may have influenced the procedure. |
Ishikawa 2005.
| Study characteristics | ||
| Methods | RCT, single‐centre, Tokyo, Japan Aim: "To determine the clinical efficacy of Roux‐en‐Y reconstruction (RY) after distal gastrectomy" Inclusion period: 45 months, from January 2001 to September 2004 Allocation: parallel Timing of randomisation: preoperatively |
|
| Participants | Number randomised: 50 Age: not clearly mentioned Inclusion criteria: patients who underwent distal gastrectomy for gastric cancer Exclusion criteria: not mentioned Stage: amongst 50 participants analysed, 23 participants (46%) were in stage I, and 1 participant (2.0%) was in stage IV. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I Devices: a circular stapler (28 mm in diameter) was used in Roux‐en‐Y group, and hand‐sewn suture (Gambee fashion) was done in Billroth‐I group. Approach: not mentioned |
|
| Outcomes | Complications, intraoperative and postoperative course, postoperative nutritional status, and follow‐up endoscopy were evaluated. | |
| Notes | Funding source: not mentioned Declaration of interests: no information provided. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Randomized preoperatively" Comment: no further information provided. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "sealed envelop" Comment: no further information about opacity provided. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: not mentioned in the study report, but it is theoretically impossible for surgeons to perform reconstruction without knowing the allocation |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: no information provided. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: the proportion of missing participants was low. |
| Selective reporting (reporting bias) | Unclear risk | Comment: not registered |
| Other bias | High risk | Comment: intraoperative randomisation was not employed. |
Lee 2012.
| Study characteristics | ||
| Methods | RCT, single‐centre, Seongnam, South Korea Aim: "To evaluate what is the best reconstruction method after distal gastrectomy" Inclusion period: March 2006 to August 2007 Allocation: 3 arms Timing of randomisation: not mentioned |
|
| Participants | Number randomised: 159 Age: not mentioned as inclusion criteria Inclusion criteria: patients who were diagnosed preoperatively with distal gastric cancer and who underwent curative resection Exclusion criteria: duodenal invasion, gastric outlet obstruction, or the possibility of excessive tension on the anastomotic site, all conditions that precluded the possibility of performing the Billroth I procedure Stage: no information provided. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I vs Billroth‐II Devices: a circular stapler (25 mm in diameter) was used in Billroth‐I group, and hand‐sewn suture was done in Roux‐en‐Y group. Approach: amongst 149 participants analysed, 75 participants (50%) underwent laparoscopic surgery. Amongst 96 participants who were allocated to R‐Y or B‐I groups and analysed, 50 participants (52%) underwent laparoscopic surgery. |
|
| Outcomes | Primary endpoint: incidence of bile reflux according to reconstructive type after gastrectomy Secondary endpoint: differences in postoperative QoL and nutritional status of participants according to reconstruction type |
|
| Notes | Funding source: the study was supported by grant 02‐2006‐021 from Seoul National University Bundang Hospital. Declaration of interests: all authors declared that they had no conflicts of interest or financial ties to disclose. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Group allocation was determined by a computer‐generated random table" Comment: done |
| Allocation concealment (selection bias) | Unclear risk | Comment: not mentioned |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "The patient was also blinded to the type of operation performed" Comment: single‐blind |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "All medical documents were recorded without specifying the actual surgical approach" Comment: participants were blinded in answering patient‐reported outcome. However, it would seem to be impossible to make medical records whilst concealing the procedures actually performed (generally surgeons make surgical records). The blinding could have been broken, and the outcome measurement was likely to be influenced by lack of blinding. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: missing participants, and the reasons for the missing data were not clearly described; also, the analysed number of participants was not mentioned for some outcomes. |
| Selective reporting (reporting bias) | Unclear risk | Comment: the study was not registered before enrolment, and prespecified outcomes were unclear. |
| Other bias | Unclear risk | Comment: no information on the timing of randomisation |
Nakamura 2016.
| Study characteristics | ||
| Methods | RCT, multicentre, Wakayama, Japan Publication type: full report Aim: to investigate the optimal procedure for reconstruction after distal gastrectomy in patients who had a Billroth I or Roux‐en‐Y procedure, with respect to long‐term QoL Inclusion period: from January 2009 to September 2010 Allocation: parallel Timing of randomisation: intraoperatively Registered ID: NCT01065688 |
|
| Participants | Number randomised: 122 Age: 20 to 80 years Inclusion criteria:
Exclusion criteria:
Stage: amongst 122 participants randomised, 89 participants (73%) were in Stage IA or IB. Stage IV patients were not included. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I Devices: circular stapling devices were used in both group for anastomosis. Approach: amongst 122 participants randomised, 50 participants (41%) underwent laparoscopic resection. |
|
| Outcomes | Primary endpoint: FACT‐Ga total score at 36 months after surgery Secondary endpoints:
|
|
| Notes | Funding source: no information provided. Declaration of interests: the authors declared no conflict of interest. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Computer‐generated random number pattern (block size 4)" Comments: done |
| Allocation concealment (selection bias) | Low risk | Quote: "Central allocation by telephone" Comments: done |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "Patients were not blinded for the type of reconstruction" Comment: surgeons and participants were not blinded. |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "All data on postoperative outcomes were collected by a trained coordinator and discussed by at least three surgeons, who were not blinded to the allocation" Comment: quality of life was reported by participants, who were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: missing participants for the outcome QoL were well balanced, although reasons for missing data were not clearly stated. |
| Selective reporting (reporting bias) | Low risk | Comment: this study was registered before enrolment, and the prespecified outcomes were reported. |
| Other bias | Low risk | Comment: there was no concern about other bias. |
Takiguchi 2012.
| Study characteristics | ||
| Methods | RCT, multicentre, Osaka, Japan Aim: "to evaluate QOL and dysfunction following B‐I and R‐Y reconstructions after distal gastrectomy" Inclusion period: between August 2005 and December 2008 Allocation: parallel Timing of randomisation: intraoperatively |
|
| Participants | Number randomised: 332 Age: 20 to 90 years Inclusion criteria: histologically proven gastric cancer, ECOG performance status 0 to 1, and a lack of non‐curative surgical factors except for positive lavage of laparotomy Exclusion criteria: history of laparotomy, interstitial pneumonia, or pulmonary fibrosis, severe heart disease, liver cirrhosis or active hepatitis, chronic renal failure, severe diabetes (glycated haemoglobin >= 9.0%), severe reflux oesophagitis Stage: amongst 332 participants randomised, 263 participants (79%) were stage IA or IB. 5 participants (1.5%) were stage IV. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I Devices: hand‐sewn and automatic sutures were not regulated in this study. Approach: amongst 332 participants randomised, 62 participants (18.7%) underwent laparoscopic surgery. |
|
| Outcomes |
|
|
| Notes | Funding source: self‐funding (from registration data) Declaration of interests: none of the authors has financial or personal conflicts of interest to disclose. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Minimaization method" Comment: probably done |
| Allocation concealment (selection bias) | Low risk | Quote: "At the data centre at Osaka Unviersity" Comment: central registration |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: not mentioned in the study reports, but it would be theoretically impossible for surgeons to perform reconstruction without knowing the allocation |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: no information provided. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: missing data were balanced between groups, but the reasons for attrition were not clearly reported, although reasons for exclusion were described. |
| Selective reporting (reporting bias) | Low risk | Comment: all the expected outcomes including every domain of QoL were reported. |
| Other bias | High risk | Comment: baseline imbalances may influence the outcome, as all 5 participants with stage IV disease were included in the Roux‐en‐Y group. |
Yang 2017.
| Study characteristics | ||
| Methods | RCT, single‐centre, Chengdu, China Aim: to compare the quality of life of patients undergoing Billroth‐I versus Roux‐en‐Y reconstruction after curative distal gastrectomy for gastric cancer Inclusion period: 37 months: May 2011 to May 2014 Allocation: parallel Timing of randomisation: intraoperatively Registered ID: ChiCTR‐TRC‐10001434 |
|
| Participants | Number randomised: 140 Age: 20 to 80 years Inclusion criteria: patients with gastric adenocarcinoma with stages less than T4aN2M0 were included. The tumours were located at the lower third of stomach. Exclusion criteria: total gastrectomy, combined organ resection (except cholecystectomy), lymphoma or GIST, previous or synchronous malignancies, emergency cases, and neoadjuvant chemotherapy or radiotherapy Stage: amongst 140 participants randomised, 52 participants (37.1%) were in stage I and 7 participants (5.0%) were in stage IV. |
|
| Interventions | Roux‐en‐Y vs Billroth‐I Devices: circular staplers (25 mm in diameter) were used in each group. A total of 36 participants (25.7%) underwent laparoscopic resection. Approach: amongst 140 participants randomised, 36 participants (25.7%) underwent laparoscopic resection. |
|
| Outcomes | Primary endpoint: QoL (EORTC QLQ‐C30, EORTC QLQ‐STO22) Secondary endpoint: mortality, complication, and severity of postoperative gastritis |
|
| Notes | Funding source: (1) National Natural Science Foundation of China (No. 81301867, 81372344); (2) Sichuan Province Youth Science & Technology Innovative Research Team (No. 2015TD0009); (3) 1. 3. 5 project for disciplines of excellence, West China Hospital, Sichuan University; (4) Te Scientific Research Program of Public Health Department of Sichuan Province, China (No. 120196) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "random number table" |
| Allocation concealment (selection bias) | Low risk | Quote: "sealed in opaque envelop" Comment: probably done |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "patients, surgeons, staffs who collected data and analysed outcomes were not blinded" |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "Patients, surgeons, staffs who collected data and analysed outcomes were not blinded" Comment: patient‐reported outcome is at high risk of bias. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: missing outcome data were balanced, but 34% of participants were lost in assessment of bile reflux, with no reasons provided. |
| Selective reporting (reporting bias) | Low risk | Comment: the study was registered before enrolment, and the prespecified outcomes were reported. |
| Other bias | High risk | Comment: imbalance in the proportion of participants who underwent postoperative chemotherapy may affect the outcome. |
BI: Billroth‐I BII: Billroth‐II BMI: body mass index DAUGS20: Dysfunction After Upper Gastrointestinal Surgery 20 ECOG: Eastern Cooperative Oncology Group EORTC QLQ‐C30: EORTC Core Quality of Life Questionnaire ‐ Core Questionnaire EORTC QLQ‐STO22: EORTC Quality of Life Questionnaire ‐ Gastric Cancer Module FACT‐Ga: Functional Assessment of Cancer Therapy‐Gastric GIQLI: Gastrointestinal Quality of Life Index GIST: gastrointestinal stromal tumour HRQoL: health‐related quality of life QoL: quality of life RCT: randomised controlled trial R‐Y: Roux‐en‐Y
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Osugi 2004 | Randomisation process was conditional. |
| Wang 2011 | Randomisation process was conditional. |
Characteristics of studies awaiting classification [ordered by study ID]
Ren 2019.
| Methods | RCT, single‐centre, Wuhan, China Aim: to explore the efficacy of delta‐shaped Billroth‐I anastomosis in totally laparoscopic distal gastrectomy for digestive tract reconstruction Inclusion period: unknown Allocation: parallel Timing of randomisation: unknown Registered ID: unknown |
| Participants | Number randomised: 180 Age: not stated Inclusion criteria:
Exclusion criteria: preoperative chemotherapy or radiotherapy, patients with other severe liver or kidney dysfunction, and distant metastasis Stage: not reported |
| Interventions | Roux‐en‐Y vs Billroth‐I vs Billroth‐II Devices: delta‐shaped anastomosis using linear staplers was employed in Billroth‐I group. Hand‐sewn or using staplers was not regulated in Roux‐en‐Y group. Length from Treitz ligament to jejunojejunostomy was 15 cm, whilst length from jejunojejunostomy to gastrojejunostomy was approximately 50 cm. Approach: all participants underwent laparoscopic surgery. |
| Outcomes | Prespecified endpoints were not stated. Reported outcomes were as follows: length of hospital stay, operation time, volume of lymphatic drainage, intraoperative blood loss, time to anal exsufflation, hospitalisation length, distance between the proximal margin and the lesion, distance between the distal margin and the lesion, haemoglobin, pre‐albumin, total plasma protein, CD4, CD8, the CD4/CD8 ratio, incidence of postoperative infection, intestinal obstruction, anastomotic fistula, and reflux gastritis. |
| Notes | Study protocol was unavailable. The study was approved by the Institutional Review Board of the Ethics Committee in 2016. |
Differences between protocol and review
We changed the inclusion period for the assessment of body weight loss. We initially defined the period of 12 to 24 months after surgery, but changed it from 6 months to 24 months because we focused on the short‐term effect of reconstruction methods which may affect the dose of adjuvant chemotherapy. Also, we set an inclusion period for the assessment of bile reflux since this was not defined in the published protocol.
We included one study that had mixed populations of gastric cancer and benign disease (D'Amato 1999). We did not a priori state how to handle mixed populations in the protocol. However, we considered it appropriate to include this study rather than exclude it, in order to consider all gastric cancer patients. We also performed a sensitivity analysis by excluding this study.
Following the advice from the Cochrane audit, we changed i) the criteria for judgement of heterogeneity from the threshold of I² statistics to the range of I² statistics, and ii) added the rationale for subgroups.
We adopted the formula to calculate the mean and the standard deviation from the median, ranges, and sample size.
In subgroup analyses by surgical approaches, we used three subgroups (open surgery, laparoscopic surgery, and others) in the review, although only two subgroups (open surgery and others) were prespecified in the published protocol.
We only assessed the incidence of bile reflux in the review, not the severity of remnant gastritis, although severity of remnant gastritis was prespecified in the protocol: this was because we considered that alpha‐error would increase as the number of outcomes increased, and it would not be relevant for patients when the grade of the RGB (Residue, Gastritis, Bile) classification was an indicator of efficacy.
Since the incidence of anastomotic leakage was sparse, we decided not to conduct the prespecified subgroup analysis for this outcome.
We prespecified a sensitivity analysis by excluding studies with stage IV patients, but decided not to conduct this analysis because the proportion of stage IV patients included in each study was small.
We performed a sensitivity analysis on length of hospital stay by excluding the study with skewed data to confirm the robustness of the result, although this analysis was not prespecified in the protocol. We also performed a sensitivity analysis on overall morbidity by excluding the studies for which use of the Clavien‐Dindo classification was unknown, which was not prespecified in the protocol. Likewise, we performed post hoc sensitivity analyses as follows:
using a fixed‐effect model for anastomotic leakage;
excluding the study that included benign disease patients and the study with co‐intervention bias for health‐related quality of life; and
excluding the study that included only diabetic patients for body weight loss.
We did not note the criteria for defining disease stage in the published protocol; thus, we stated that we would use the 15th edition of the Japanese Classification of Gastric Carcinoma.
We noted who assessed the certainty of evidence in the review, as this information was not provided in the protocol.
Contributions of authors
All review authors contributed to the production of the protocol.
DN and RG identified studies for inclusion and checked the methodological quality of studies.
DN and RG extracted data and assessed risk of bias of the studies.
DN performed the analyses.
KO and DN contacted trial authors and manufacturers.
DN and NH performed the GRADE assessment.
NH, KH, KO, TAF, and YS provided general advice on the review.
NW supervised the conducting of the review.
DN wrote the final review, which was approved by the other authors.
Sources of support
Internal sources
No sources of support provided
External sources
No sources of support provided
Declarations of interest
DN: none known.
RG: none known.
NH has received writing fees from Igaku‐Shoin and Kanehara publishers.
KH has received grants for research from JSPS KAKENHI, Mitsubishi Foundation, Senko Medical, Kondo Memorial Foundation, and Japan Society of Laparoscopic Colorectal Surgery outside the submitted work. He has received lecture fees from Johnson & Johnson, Medtronic, and Otsuka Pharmaceutical Company outside the submitted work.
KO has received grants or research support from the Japan Agency for Medical Research and Development and the Japan Society for the Promotion of Science (JSPS KAKENHI). He has received grants from Taiho Pharmaceuticals, consultant fee from Ethicon, Stryker, Olympus, Medicaroid, Medtronic, and Intuitive Surgical, and payment for lectures from Ethicon, Covidien Japan, Intuitive Surgical, Taiho Pharmaceuticals, Chugai Pharmaceuticals, Tsumura Pharmaceuticals, Miyarisan Pharmaceuticals, EA Pharma, Otsuka Pharmaceuticals, Kaken Pharmaceuticals, Gunze Medical Japan, Medicon, Ono Pharmaceuticals, and Olympus.
TAF has received lecture fees from Eli Lilly, Janssen, Meiji, Mitsubishi‐Tanabe, MSD, and Pfizer and consultancy fees from Takeda Science Foundation, Mitsubishi‐Tanabe, Shionogi and SONY. He has received royalties from Igaku‐Shoin and Nihon Bunka Kagaku‐sha publishers. He has received research support from Mochida and Mitsubishi‐Tanabe and Shionogi. He has a patent 2020‐548587 concerning smartphone CBT apps pending, and intellectual properties for Kokoro‐app licensed to Mitsubishi‐Tanabe.
YS has received grants from Chugai, Taiho, Tsumura, Daiichi‐Sankyo, Yakult, Otsuka, Shionogi, and Sanofi, and payment for lectures from Chugai, Taiho, Tsumura, Johnson & Johnson, Covidien Japan, Striker Japan, Olympus, Takeda, and Terumo, outside the submitted work.
NW has received research funds from the Japanese Ministry of Health Labor and Welfare and the Japanese Ministry of Education, Science, and Technology. He has also received royalties from Sogensha and advantage Risk Management for writings. The results in the review are completely independent of the intention of these grants.
Affiliations of all members involved in this review have been unchanged for the past three years.
Nobody involved in this review is an investigator of a study that might be included in the review.
New
References
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