Surgical Techniques to Prevent Delayed Gastric Emptying After Esophagectomy With Gastric Interposition: A Systematic Review Ronald D. L. Akkerman, BS, Leonie Haverkamp, MD, Richard van Hillegersberg, MD, PhD, and Jelle P. Ruurda, MD, PhD Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
Delayed gastric emptying is observed in 10% to 50% of patients after esophagectomy with gastric interposition. The effects of gastric interposition diameter, pyloric drainage, reconstructive route, and anastomotic site on postoperative gastric emptying were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Most studies showed superior passage of the gastric tube compared with the whole stomach. Pyloric drainage is not
significantly associated with the risk of developing delayed gastric emptying after esophagectomy. For reconstructive route and anastomotic site, available evidence on delayed gastric emptying is limited. Prospectively randomized studies with standardized outcome measurements are recommended.
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article. The search sensitivity was checked by crossreferencing the included articles. Pooling of data was performed for studies that provided DGE or gastric outlet obstruction as a dichotomous variable. Meta-analyses on other outcomes could not be performed because of the considerable heterogeneity in outcome reporting. The search results and screening selection are summarized in a flowchart (Fig 1).
sophagectomy is a complex operation, and many factors can contribute to its functional outcome [1, 2]. Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy. Clinical manifestations are observed in 10% to 50% of patients after esophagectomy with gastric interposition [3]. The optimal method for gastric interposition after esophagectomy remains controversial. This systematic review aims to assess the effects of various surgical aspects regarding gastric interposition on DGE after esophagectomy.
Material and Methods REVIEW
Study Selection This review was performed according to the Preferred Reporting Items for Systematic Reviews and MetaAnalyses guidelines [4]. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library for studies published before June 1, 2014. The databases were searched for all published comparative studies investigating four surgical variables. The variables included gastric interposition diameter (gastric tube versus whole stomach), pyloric drainage (yes or no), route (retrosternal versus posterior mediastinal), and the anastomotic site (cervical versus intrathoracic). Titles and abstracts were searched for “esophagectomy” AND (“gastric interposition diameter” OR “pyloric drainage” OR “route” OR “anastomotic site”) along with their synonyms. Duplicate publications were excluded. Authors were contacted by e-mail in case full-text articles were not available; this yielded one additional full-text Address correspondence to Dr Ruurda, Department of Surgery, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2014;98:1512–9) Ó 2014 by The Society of Thoracic Surgeons
Eligibility Criteria All published comparative studies reporting on gastric emptying were included. A broad range of definitions and terms used for DGE were considered for inclusion. Outcomes related to DGE included subjective eating abilities, changes in body weight, and the presence of reflux. Also, results from quality-of-life questionnaires were analyzed. No studies were excluded on the basis of time of publication. Language of articles was limited to English. Nonsystematic review articles, experimental studies, case series, and case reports were excluded.
Assessment of Methodological Quality The methodological quality of studies was assessed according to the Oxford Centre for Evidenced-Based Medicine (CEBM) levels of evidence [5]. In all randomized, controlled trials (RCTs), the risk of bias was assessed using the Oxford CEBM Critical Appraisal Skills Programme appraisal sheet for RCTs [6]. All cohort studies were scored with the use of the Newcastle-Ottawa quality assessment scale [7]. In case study quality was poor (ie, absence of both baseline comparability and identification of confounders), studies were graded down a level. Only studies with a level of evidence of at least 3 were selected for further analysis. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.06.057
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Results Methodological Quality A total of 50 studies were identified for critical appraisal. Level of evidence ranged between 2 and 4 (Tables 1, 2). The method of randomization was frequently not described. Moreover, it was often unclear whether the patients and outcome assessors were blinded for treatment allocation. Cohort studies generally lacked baseline comparability or reliable and standardized methods for measuring DGE. A total of 30 studies with a level of evidence of at least 3 were selected for further analysis.
Gastric Tube Versus Whole Stomach A total of two RCTs and five cohort studies were analyzed [8–14]. Gastric tube reconstruction was associated with a significantly reduced risk of DGE after esophagectomy when compared with the whole stomach (relative risk, 0.34; 95% confidence interval, 0.12 to 0.97; Fig 2). In RCTs, the gastric tube was created by serial applications of a linear-cutting stapling device parallel to and at a
distance of 3 to 4 cm from the greater curvature. In one RCT, the dissection started 2 to 3 cm proximal to the pylorus at the crow’s foot (preserving the right gastric artery). In the whole stomach group, the stomach was mobilized and an anastomosis was created between the proximal stump of the esophagus and the fundus of the stomach [8]. In the other RCT, the dissection started at 5 cm proximal to the pyloric ring. This RCT compared the gastric tube with a subtotal stomach in which the proximal half of the lesser curvature and cardia were resected [9]. It was shown that patients with a gastric tube had better quality of life and reflux scores during the first postoperative year compared with patients with a whole stomach for reconstruction [8]. The incidence of DGE was 6% in both groups. The other RCT reported on nutritional status but did not show significant differences up to 12 months after surgery [9]. The included cohort studies did not provide a detailed description of the tubulization of the stomach. The reported diameter varied from 2 to 6 cm. Superior early and late results in patients with gastric tube reconstruction
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Fig 1. Flowchart search. A total of 50 studies were included in this review. Some studies were allocated to multiple subgroups. After critical appraisal, 30 studies were selected for further analysis. (DGE ¼ delayed gastric emptying; RCT ¼ randomized controlled trial.)
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Table 1. Critical Appraisal Randomized Controlled Trialsa
Reference Diameter Zhang et al. [8] Tabira et al. [9] Pyloric drainage Kao et al.[15] Chattopadhyay et al. [16] Fok et al. [17] Manell et al. [18] Gupta et al. [19] Cheung et al. [20] Reconstructive route Khiria et al. [28] van Lanschot et al. [29] Gawad et al. [30] Anastomotic site Okuyama et al. [33] Walther et al. [34]
Blinding
IntentionTo-Treat Analysis
Same Treatment, Follow-Up and Data
Similar Groups
Follow-Up
▫
. .
3 2 2 2 2 2
▫
▫ ▫ ▫ ▫
. . . . . .
▫
▫ ▫
▫
2009 1999 1999
2 2 2
▫ ▫
. . .
▫
2007 2003
2 2
▫ ▫
. .
Year
Level of Evidence
Random Allocation
2011 2004
2 2
1994 1993 1991 1990 1989 1987
a
The critical appraisal of randomized controlled trials according to the Oxford CEBM Critical Appraisal Skills Programme appraisal sheets for randomized controlled trials.
¼ consistent with criteria, low risk of bias; k of bias; . ¼ not applicable.
¼ partly consistent with criteria, unknown risk of bias;
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were shown [10, 11]. The incidence of DGE was significantly lower in patients who underwent a gastric tube reconstruction when compared with patients who underwent reconstruction with the whole stomach [10]. The incidences of intrathoracic stomach syndrome (defined as the presence of palpitations or chest discomfort after eating) and reflux esophagitis at 6 months after surgery were significantly lower in patients with a gastric tube reconstruction [11]. Gastric emptying studies did not show significant differences in amount of time required to lose one half of the radioactivity in the gastric interposition [12, 13]. Only one study supported the use of the whole stomach for reconstruction [14]. The motility of the gastric interposition was studied by manometry during the fasting and postprandial period. The fasting and postprandial motility indexes were significantly reduced in patients with a gastric tube when compared with patients with a whole stomach. In conclusion, most of the available studies on gastric function after esophagectomy preferred the gastric tube reconstruction compared with the whole stomach.
Pyloric Drainage A total of six RCTs and seven cohort studies concerning pyloric drainage versus no drainage were included [15–27]. Pyloric drainage did not influence the incidence of DGE after esophagectomy (relative risk,: 0.91; 95% confidence interval, 0.57 to 1.43; Fig 3). Whole stomach reconstruction was used in the RCTs, whereas cohort studies used a gastric tube for reconstruction. Different techniques were used for pyloric drainage and included pyloroplasty,
▫ ¼ not consistent with criteria, high ris-
pyloromyotomy, and intrapyloric Botox injection. Definitions of DGE varied across the pooled studies. In some studies, DGE was defined as symptoms of gastric stasis combined with a delay on a barium swallow or gastric conduit dilatation on radiography [23, 27]. In other studies, only symptoms of gastric stasis (postprandial fullness, vomiting, regurgitation) were reported as DGE [17, 18]. In two studies, gastrointestinal passage was analyzed by a Gastrografin swallow and DGE was defined as Gastrografin stasis in the gastric conduit [25, 26]. One study defined DGE as the presence of prolonged gastric emptying time compared with that of normal volunteers [15]. Two recent cohort studies demonstrated that pyloric drainage was associated with an insignificant trend for increased DGE [24, 28]. In another study, gastric outlet obstruction was present in 28% of patients who underwent a pyloric drainage procedure compared with 18% of patients with no pyloric intervention (p ¼ 0.01) [23]. In addition, pyloric drainage was associated with significantly more reflux and its sequelae [22, 25, 27]. Only one cohort study assessed the effect of intrapyloric Botox injection on gastric emptying [26]. When compared with no drainage, intrapyloric Botox injection was associated with significantly less early DGE. Furthermore, intrapyloric Botox injection was associated with decreased respiratory complications, a shorter hospital stay, and reduced late biliary reflux when compared with the other drainage procedures. Unfortunately, the need for reintervention was not reported in this study. In conclusion, results regarding the benefit of pyloric drainage procedures on gastric function remain contradictory, but do not support its routine use.
Adequately Outcome Nonexposed Standardized Adequate Adequate Dealt With No Selective Reliable Representativeness Selected Ascertainment of Interest Outcome Level of Loss to Outcome Measurement Short-Term Long-Term Baseline From Same of Exposure Not Present Confounders of Exposed From Start? Identified? Comparability? Assessment? of Outcomes? Follow-Up? Follow-Up? Follow-Up? Reporting? Evidence Reliable? Population? Cohort? Year
References Diameter Shu et al. [11]
2013
1
1
1
0
0
1
0
0
1
1
.
1
3
Maffettone et al. [12]
2007
1
1
1
0
0
0
1
0
.
1
1
1
3
Lee et al. [13]
2005
1
1
1
0
0
0
1
0
1
1
.
1
3
Collard et al. [14]
1998
1
1
1
0
0
0
1
0
1
1
.
1
3
Collard et al. [44]
1995
1
1
1
0
0
0
0
0
1
1
1
1
4
Bemelman et al. [10]
1995
1
1
1
0
0
1
0
0
1
.
1
1
3 3
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Table 2. Critical Appraisal of Cohort Studiesa
Pyloric drainage van der Schaaf et al. [21] 2013
1
1
1
0
1
1
0
1
1
1
1
1
Mehran et al. [45]
2011
1
1
1
0
0
0
0
1
.
1
.
1
4
Lanuti et al. [22]
2011
1
1
1
0
1
0
0
0
1
1
.
1
3
Nguyen et al. [23]
2010
1
1
1
0
1
0
1
0
.
1
.
1
3
Yajima et al. [24]
2009
1
1
1
0
1
0
0
1
.
1
.
1
3
Cerfolio et al. [25]
2009
1
1
1
0
1
1
1
0
1
1
.
1
3
Palmes et al. [26]
2007
1
1
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0
1
1
0
0
1
1
.
1
3
2007
1
1
1
0
1
0
0
0
1
1
1
1
3
1995
1
1
1
0
0
0
0
0
1
1
1
1
4
Hill et al. [47]
1993
1
1
1
0
0
0
1
0
.
1
.
1
4
Wang et al. [48]
1992
1
1
1
0
0
0
1
0
1
0
0
1
4
Bemelman et al. [49]
1990
1
1
1
0
0
0
0
0
1
.
.
1
4
Reconstructive route Wang et al. [31]
2011
1
1
1
0
1
1
1
1
1
1
1
1
3
Chan et al. [50]
2011
1
1
1
0
0
0
0
1
1
1
1
1
4
Yajima et al. [24]
2009
1
1
1
0
1
0
0
1
.
1
.
1
3
Nakajima et al. [51]
2007
1
1
1
0
0
0
0
1
.
1
.
1
4
Katsoulis et al. [32]
2005
1
1
1
0
0
1
1
0
.
1
.
1
3
Shiraha et al. [52]
1992
1
1
1
0
0
0
1
0
.
1
.
1
4
Anastomotic site van der Schaaf et al. [21] 2013
1
1
1
0
1
1
0
1
1
1
1
1
3
Chang et al. [35]
2013
1
1
1
1
1
0
0
1
1
1
1
1
3
Berry et al. [53]
2010
1
1
1
0
0
0
0
0
1
.
1
1
4
D’Journo et al. [54]
2009
1
1
1
0
0
0
0
0
1
1
.
1
4
Egberts et al. [36]
2008
1
1
1
1
0
1
0
1
1
1
0
1
3
Schmidt et al. [37]
2004
1
1
1
0
0
1
0
1
.
0
1
1
3
Shibuya et al. [55]
2003
1
1
1
0
0
0
0
0
.
1
.
1
4
Johansson et al. [56]
1999
1
1
1
0
0
0
0
0
1
1
0
1
4
Johansson et al. [57]
1999
1
1
1
0
0
0
1
0
1
1
.
1
4
Finley et al. [46]
1995
1
1
1
0
0
0
0
0
1
1
1
1
4
de Leyn et al. [58]
1992
1
1
1
0
0
0
0
0
1
1
.
1
4
Critical appraisal of cohort studies according to the Newcastle-Ottawa quality assessment scale. Only studies with a level of evidence of at least 3 were selected for further analysis.
1 ¼ yes;
0 ¼ no or unclear;
. ¼ not applicable.
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Fig 2. Gastric tube versus whole stomach. The application of a gastric tube is associated with a lower risk of developing delayed gastric emptying after esophagectomy compared to the whole stomach reconstruction (relative risk, 0.34; 95% confidence interval [CI], 0.12 to 0.97).
Reconstructive Route
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A total of three RCTs and three cohort studies comparing the retrosternal and posterior mediastinal route were included [24, 28–32]. In all studies, a gastric tube was pulled up to the neck. No pyloric drainage procedure was performed. One RCT did not show significant differences for reflux, dysphagia, aspiration, and weight loss at 6 months of follow-up [28]. Another demonstrated that gastric emptying was similar in both groups [29]. In another RCT, it was shown by means of gastric emptying scintigraphy that the mean retention index 30 seconds after ingestion was significantly higher in the retrosternal group when compared with the posterior mediastinal group. However, symptom scores for nausea and vomiting, regurgitation, and dysphagia were similar in both groups [30]. Cohort studies showed contradictory results. One small cohort study favored the retrosternal route, as this was associated with less duodenogastric reflux at 3 to 6 months of follow-up [32]. However, a different cohort study demonstrated that the retrosternal route is associated with an insignificant trend for increased reflux esophagitis in the cervical remnant [24]. Moreover, a recent cohort study showed that scores for eating problems and dysphagia were significantly higher in the retrosternal group when compared with the posterior mediastinal group at 2 weeks of follow-up [31]. At 24 weeks, however, scores for eating problems and dysphagia were similar in both groups. Inversely, reflux scores were similar in the early
postoperative period. At 24 weeks, however, the reflux scores in the posterior mediastinal group were higher than in the retrosternal group, indicating more severe symptoms. In conclusion, the retrosternal route was associated with less (biliary) reflux in the late postoperative period, whereas gastric emptying results are similar compared with the posterior mediastinal route.
Anastomotic Site A total of two RCTs and four cohort studies comparing cervical with thoracic anastomosis were included [21, 33–37]. The RCTs report similar symptom scores (dysphagia, heartburn, regurgitation, and abdominal fullness) and changes in body weight during the first postoperative year for cervical and thoracic anastomosis [33, 34]. This finding is also supported by two large prospective cohort studies that reported on reflux in patients who underwent esophagectomy with gastric tube reconstruction [21, 36]. In one study, differences in occurrence of reflux were not significant at 6 months and 3 years of follow-up [21]. The other study reported similar reflux scores at 3, 6, 12, and 24 months after surgery [36]. Another prospective cohort study did not show any association between anastomotic site and esophageal-specific aspects of quality of life assessed by the EORTC QLQ-OES18 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for esophageal cancer) questionnaire during the first 6 months after surgery [35].
Fig 3. Pyloric drainage versus no drainage. Pyloric drainage is not significantly associated with the risk of developing delayed gastric emptying after esophagectomy (relative risk, 0.91; 95% confidence interval [CI], 0.57 to 1.43). The number of events in the study of Palmes et al. were calculated using a percentage bar graph.
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However, a small cohort study showed that reflux and vomiting scores in the late postoperative period were significantly higher in the thoracic anastomosis group when compared with the group with a cervical anastomosis [37]. In conclusion, intrathoracic or cervical anastomoses do not significantly influence DGE, except for one cohort study that favors a cervical anastomosis.
extent of lymphadenectomy during resection. When the tumor is located at the gastroesophageal junction, creating a gastric tube instead of the whole stomach may ensure radicality. In case of irradicality, the retrosternal route may be preferred as recurrence within the tract of reconstruction might be prevented [40]. The number of harvested lymph nodes may be lower with an intrathoracic anastomosis as periesophageal and paratracheal lymph nodes from the superior mediastinum remain in situ. The prognostic value of the extent of lymphadenectomy during surgery, however, remains controversial [41]. Improvement of gastric function may influence postoperative nutrition strategies. Commonly, a nil-by-mouth strategy is applied after esophagectomy as early oral intake would result in aspiration and complicate anastomotic leakages. Interestingly, one study showed that the risk of cervical anastomotic leak dramatically decreased after switching to a nil-by-mouth strategy until 15 days postoperatively [42]. Early enteral nutrition after upper gastrointestinal surgery, however, has been associated with a reduction of postoperative complications, length of hospital stay, and mortality [43]. The effect of these strategies on functional outcomes is a topic for future research. In conclusion, gastric function after esophagectomy with gastric interposition is an important outcome in the early and late postoperative period. The majority of best available evidence favors the use of the gastric tube over the whole stomach. Results regarding the benefit of pyloric drainage procedures remain controversial and do not support its routine use. Available evidence on the effect of reconstructive route and anastomotic site on DGE is not conclusive. Prospectively randomized studies with standardized outcome measurements are needed to clarify the optimal reconstructive techniques of gastric interposition after esophagectomy.
Comment This systematic review demonstrates that surgical factors influence DGE after esophageal resection. A gastric tube (instead of whole stomach) has superior disease-specific quality-of-life scores and significantly less reflux esophagitis. For pyloric drainage, contradictory results are seen between RCTs and recent cohort studies. Whereas omission of pyloric drainage probably leads to a reduction of biliary reflux in the long term, the effect on gastric emptying during the early postoperative period is controversial and of uncertain clinical relevance. Moreover, DGE can be managed by pyloric dilatation after surgery, and gastric motility appears to recover after several years [38]. Intrapyloric Botox injection can be seen as a promising alternative as it constitutes a transient effect during the early postoperative period when DGE may cause aspiration. Available evidence on the effect of reconstructive route and anastomotic site is limited. Overall, similar functional results were seen irrespective of reconstructive route and anastomotic site. Two cohort studies, however, demonstrated that the retrosternal route is associated with less reflux in the late postoperative period when compared with the reconstruction in the posterior mediastinum. Anastomotic site did not appear to influence DGE after esophagectomy. To our knowledge, this is the first systematic review that analyzed the effect of multiple reconstructive techniques on DGE in combination with a thorough assessment of methodological quality. This systematic review, however, has some important limitations. Heterogeneity in study populations, follow-up, and measurement of outcomes are points of concern. In addition, potential confounders, such as perioperative chemo(radio)therapy or the presence of relevant comorbidity (eg, diabetes mellitus), are often not reported. Also, the influences of antacid or motility agents were frequently not reported in included articles. Consequently, a strong recommendation regarding the method of reconstruction in gastric interposition after esophagectomy is not possible. Prospectively randomized studies are needed that measure DGE in a standardized method that combines gastric emptying scintigraphy with a validated questionnaire (eg, EORTC QLQ-OES18 [39]). Early and late follow-up is recommended, as gastric motility appears to increase up to 3 years after esophagectomy [14, 38]. Furthermore, the effect of reconstructive variables on the incidence and impact of other postoperative complications (eg, anastomotic leakage, stricture, pneumonia) should be thoroughly evaluated in future trials. Importantly, selection of the optimal reconstructive method should also take into account the radicality and the
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transhiatal oesophagectomy: a randomized controlled trial. Dig Liver Dis 2009;41:711–6. van Lanschot JJ, van Blankenstein M, Oei HY, Tilanus HW. Randomized comparison of prevertebral and retrosternal gastric tube reconstruction after resection of oesophageal carcinoma. Br J Surg 1999;86:102–8. Gawad KA, Hosch SB, Bumann D, et al. How important is the route of reconstruction after esophagectomy: a prospective randomized study. Am J Gastroenterol 1999;94:1490–6. Wang H, Tan L, Feng M, Zhang Y, Wang Q. Comparison of the short-term health-related quality of life in patients with esophageal cancer with different routes of gastric tube reconstruction after minimally invasive esophagectomy. Qual Life Res 2011;20:179–89. Katsoulis IE, Robotis I, Kouraklis G, Yannopoulos P. Duodenogastric reflux after esophagectomy and gastric pull-up: the effect of the route of reconstruction. World J Surg 2005;29:174–81. Okuyama M, Motoyama S, Suzuki H, Saito R, Maruyama K, Ogawa J. Hand-sewn cervical anastomosis versus stapled intrathoracic anastomosis after esophagectomy for middle or lower thoracic esophageal cancer: a prospective randomized controlled study. Surg Today 2007;37:947–52. Walther B, Johansson J, Johnsson F, Von Holstein CS, Zilling T. Cervical or thoracic anastomosis after esophageal resection and gastric tube reconstruction: a prospective randomized trial comparing sutured neck anastomosis with stapled intrathoracic anastomosis. Ann Surg 2003;238: 803–14. Chang YL, Tsai YF, Wu YC, Hsieh MJ. Factors relating to quality of life after esophagectomy for cancer patients in Taiwan. Cancer Nurs 2014;37:4–13. Egberts JH, Schniewind B, Bestmann B, et al. Impact of the site of anastomosis after oncologic esophagectomy on quality of life—a prospective, longitudinal outcome study. Ann Surg Oncol 2008;15:566–75. Schmidt CE, Bestmann B, K€ uchler T, Schmid A, Kremer B. Quality of life associated with surgery for esophageal cancer: differences between collar and intrathoracic anastomoses. World J Surg 2004;28:355–60. Nakabayashi T, Mochiki E, Garcia M, et al. Gastropyloric motor activity and the effects of erythromycin given orally after esophagectomy. Am J Surg 2002;183:317–23. Blazeby JM, Conroy T, Hammerlid E, et al; European Organisation for Research and Treatment of Cancer Gastrointestinal and Quality of Life Groups. Clinical and psychometric validation of an EORTC questionnaire module, the EORTC QLQ-OES18, to assess quality of life in patients with oesophageal cancer. Eur J Cancer 2003;39:1384–94. van Lanschot JJ, Hop WC, Voormolen MH, van Deelen RA, Blomjous JG, Tilanus HW. Quality of palliation and possible benefit of extra-anatomic reconstruction in recurrent dysphagia after resection of carcinoma of the esophagus. J Am Coll Surg 1994;179:705–13. Akutsu Y, Matsubara H. Lymph node dissection for esophageal cancer. Gen Thorac Cardiovasc Surg 2013;61:387–401. Iannetoni MD, Lynch WR, Parekh KR, McLaughlin KA. Kaizen method for esophagectomy patients: improved quality control, outcomes, and decreased costs. Ann Thorac Surg 2011;91:1011–8. Lewis SJ, Andersen HK, Thomas S. Early enteral nutrition within 24 h of intestinal surgery versus later commencement of feeding: a systematic review and meta-analysis. J Gastrointest Surg 2009;13:569–75. Collard JM, Tinton N, Malaise J, Romagnoli R, Otte JB, Kestens PJ. Esophageal replacement: gastric tube or whole stomach? Ann Thorac Surg 1995;60:261–7. Mehran R, Rice D, El-Zein R, et al. Minimally invasive esophagectomy versus open esophagectomy, a symptom assessment study. Dis Esophagus 2011;24:147–52. Finley RJ, Lamy A, Clifton J, Evans KG, Fradet G, Nelems B. Gastrointestinal function following esophagectomy for malignancy. Am J Surg 1995;169:471–5.
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47. Hill ADK, Walsh TN, Hamilton D, et al. Erythromycin improves emptying of the denervated stomach after oesophagectomy. Br J Surg 1993;80:879–81. 48. Wang LS, Huang MH, Huang BS, Chien KY. Gastric substitution for resectable carcinoma of the esophagus: an analysis of 368 cases. Ann Thorac Surg 1992;53:289–94. 49. Bemelman WA, Brummelkamp WH, Bartelsman JF. Endoscopic balloon dilation of the pylorus after esophagogastrostomy without a drainage procedure. Surg Gynecol Obstet 1990;170:424–6. 50. Chan ML, Hsieh CC, Wang CW, Huang MH, Hsu WH, Hsu HS. Reconstruction after esophagectomy for esophageal cancer: retrosternal or posterior mediastinal route? J Chin Med Assoc 2011;74:505–10. 51. Nakajima M, Kato H, Miyazaki T, et al. Comprehensive investigations of quality of life after esophagectomy with special reference to the route of reconstruction. Hepatogastroenterology 2007;54:104–10. 52. Shiraha S, Matsumoto H, Terada M, Noguchi J, Sankouji T, Hayashi M. Motility studies of the cervical esophagus with intrathoracic gastric conduit after esophagectomy. Scand J Thorac Cardiovasc Surg 1992;26:119–23.
53. Berry MF, Atkins BZ, Tong BC, Harpole DH, D’Amico TA, Onaitis MW. A comprehensive evaluation for aspiration after esophagectomy reduces the incidence of postoperative pneumonia. J Thorac Cardiovasc Surg 2010;140:1266–71. 54. D’Journo XB, Martin J, Rakovich G, et al. Mucosal damage in the esophageal remnant after esophagectomy and gastric transposition. Ann Surg 2009;249:262–8. 55. Shibuya S, Fukudo S, Shineha R, et al. High incidence of reflux esophagitis observed by routine endoscopic examination after gastric pull-up esophagectomy. World J Surg 2003;27:580–3. 56. Johansson J, Johnsson F, Groshen S, Walther B. Pharyngeal reflux after gastric pull-up esophagectomy with neck and chest anastomoses. J Thorac Cardiovasc Surg 1999;118:1078–83. 57. Johansson J, Sloth M, Bajc M, Walther B. Radioisotope evaluation of the esophageal remnant and the gastric conduit after gastric pull-up esophagectomy. Surgery 1999;125: 297–303. 58. De Leyn P, Coosemans W, Lerut T. Early and late functional results in patients with intrathoracic gastric replacement after oesophagectomy for carcinoma. Eur J Cardiothorac Surg 1992;6:79–85.
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Delayed gastric emptying is observed in 10% to 50% of patients after esophagectomy with gastric interposition. The effects of gastric interposition diameter, pyloric drainage, reconstructive route, and anastomotic site on postoperative gastric emptying were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Most studies showed superior passage of the gastric tube compared with the whole stomach. Pyloric drainage is not
significantly associated with the risk of developing delayed gastric emptying after esophagectomy. For reconstructive route and anastomotic site, available evidence on delayed gastric emptying is limited. Prospectively randomized studies with standardized outcome measurements are recommended.
E
article. The search sensitivity was checked by crossreferencing the included articles. Pooling of data was performed for studies that provided DGE or gastric outlet obstruction as a dichotomous variable. Meta-analyses on other outcomes could not be performed because of the considerable heterogeneity in outcome reporting. The search results and screening selection are summarized in a flowchart (Fig 1).
sophagectomy is a complex operation, and many factors can contribute to its functional outcome [1, 2]. Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy. Clinical manifestations are observed in 10% to 50% of patients after esophagectomy with gastric interposition [3]. The optimal method for gastric interposition after esophagectomy remains controversial. This systematic review aims to assess the effects of various surgical aspects regarding gastric interposition on DGE after esophagectomy.
Material and Methods REVIEW
Study Selection This review was performed according to the Preferred Reporting Items for Systematic Reviews and MetaAnalyses guidelines [4]. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library for studies published before June 1, 2014. The databases were searched for all published comparative studies investigating four surgical variables. The variables included gastric interposition diameter (gastric tube versus whole stomach), pyloric drainage (yes or no), route (retrosternal versus posterior mediastinal), and the anastomotic site (cervical versus intrathoracic). Titles and abstracts were searched for “esophagectomy” AND (“gastric interposition diameter” OR “pyloric drainage” OR “route” OR “anastomotic site”) along with their synonyms. Duplicate publications were excluded. Authors were contacted by e-mail in case full-text articles were not available; this yielded one additional full-text Address correspondence to Dr Ruurda, Department of Surgery, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2014;98:1512–9) Ó 2014 by The Society of Thoracic Surgeons
Eligibility Criteria All published comparative studies reporting on gastric emptying were included. A broad range of definitions and terms used for DGE were considered for inclusion. Outcomes related to DGE included subjective eating abilities, changes in body weight, and the presence of reflux. Also, results from quality-of-life questionnaires were analyzed. No studies were excluded on the basis of time of publication. Language of articles was limited to English. Nonsystematic review articles, experimental studies, case series, and case reports were excluded.
Assessment of Methodological Quality The methodological quality of studies was assessed according to the Oxford Centre for Evidenced-Based Medicine (CEBM) levels of evidence [5]. In all randomized, controlled trials (RCTs), the risk of bias was assessed using the Oxford CEBM Critical Appraisal Skills Programme appraisal sheet for RCTs [6]. All cohort studies were scored with the use of the Newcastle-Ottawa quality assessment scale [7]. In case study quality was poor (ie, absence of both baseline comparability and identification of confounders), studies were graded down a level. Only studies with a level of evidence of at least 3 were selected for further analysis. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.06.057
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Results Methodological Quality A total of 50 studies were identified for critical appraisal. Level of evidence ranged between 2 and 4 (Tables 1, 2). The method of randomization was frequently not described. Moreover, it was often unclear whether the patients and outcome assessors were blinded for treatment allocation. Cohort studies generally lacked baseline comparability or reliable and standardized methods for measuring DGE. A total of 30 studies with a level of evidence of at least 3 were selected for further analysis.
Gastric Tube Versus Whole Stomach A total of two RCTs and five cohort studies were analyzed [8–14]. Gastric tube reconstruction was associated with a significantly reduced risk of DGE after esophagectomy when compared with the whole stomach (relative risk, 0.34; 95% confidence interval, 0.12 to 0.97; Fig 2). In RCTs, the gastric tube was created by serial applications of a linear-cutting stapling device parallel to and at a
distance of 3 to 4 cm from the greater curvature. In one RCT, the dissection started 2 to 3 cm proximal to the pylorus at the crow’s foot (preserving the right gastric artery). In the whole stomach group, the stomach was mobilized and an anastomosis was created between the proximal stump of the esophagus and the fundus of the stomach [8]. In the other RCT, the dissection started at 5 cm proximal to the pyloric ring. This RCT compared the gastric tube with a subtotal stomach in which the proximal half of the lesser curvature and cardia were resected [9]. It was shown that patients with a gastric tube had better quality of life and reflux scores during the first postoperative year compared with patients with a whole stomach for reconstruction [8]. The incidence of DGE was 6% in both groups. The other RCT reported on nutritional status but did not show significant differences up to 12 months after surgery [9]. The included cohort studies did not provide a detailed description of the tubulization of the stomach. The reported diameter varied from 2 to 6 cm. Superior early and late results in patients with gastric tube reconstruction
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Fig 1. Flowchart search. A total of 50 studies were included in this review. Some studies were allocated to multiple subgroups. After critical appraisal, 30 studies were selected for further analysis. (DGE ¼ delayed gastric emptying; RCT ¼ randomized controlled trial.)
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Table 1. Critical Appraisal Randomized Controlled Trialsa
Reference Diameter Zhang et al. [8] Tabira et al. [9] Pyloric drainage Kao et al.[15] Chattopadhyay et al. [16] Fok et al. [17] Manell et al. [18] Gupta et al. [19] Cheung et al. [20] Reconstructive route Khiria et al. [28] van Lanschot et al. [29] Gawad et al. [30] Anastomotic site Okuyama et al. [33] Walther et al. [34]
Blinding
IntentionTo-Treat Analysis
Same Treatment, Follow-Up and Data
Similar Groups
Follow-Up
▫
. .
3 2 2 2 2 2
▫
▫ ▫ ▫ ▫
. . . . . .
▫
▫ ▫
▫
2009 1999 1999
2 2 2
▫ ▫
. . .
▫
2007 2003
2 2
▫ ▫
. .
Year
Level of Evidence
Random Allocation
2011 2004
2 2
1994 1993 1991 1990 1989 1987
a
The critical appraisal of randomized controlled trials according to the Oxford CEBM Critical Appraisal Skills Programme appraisal sheets for randomized controlled trials.
¼ consistent with criteria, low risk of bias; k of bias; . ¼ not applicable.
¼ partly consistent with criteria, unknown risk of bias;
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were shown [10, 11]. The incidence of DGE was significantly lower in patients who underwent a gastric tube reconstruction when compared with patients who underwent reconstruction with the whole stomach [10]. The incidences of intrathoracic stomach syndrome (defined as the presence of palpitations or chest discomfort after eating) and reflux esophagitis at 6 months after surgery were significantly lower in patients with a gastric tube reconstruction [11]. Gastric emptying studies did not show significant differences in amount of time required to lose one half of the radioactivity in the gastric interposition [12, 13]. Only one study supported the use of the whole stomach for reconstruction [14]. The motility of the gastric interposition was studied by manometry during the fasting and postprandial period. The fasting and postprandial motility indexes were significantly reduced in patients with a gastric tube when compared with patients with a whole stomach. In conclusion, most of the available studies on gastric function after esophagectomy preferred the gastric tube reconstruction compared with the whole stomach.
Pyloric Drainage A total of six RCTs and seven cohort studies concerning pyloric drainage versus no drainage were included [15–27]. Pyloric drainage did not influence the incidence of DGE after esophagectomy (relative risk,: 0.91; 95% confidence interval, 0.57 to 1.43; Fig 3). Whole stomach reconstruction was used in the RCTs, whereas cohort studies used a gastric tube for reconstruction. Different techniques were used for pyloric drainage and included pyloroplasty,
▫ ¼ not consistent with criteria, high ris-
pyloromyotomy, and intrapyloric Botox injection. Definitions of DGE varied across the pooled studies. In some studies, DGE was defined as symptoms of gastric stasis combined with a delay on a barium swallow or gastric conduit dilatation on radiography [23, 27]. In other studies, only symptoms of gastric stasis (postprandial fullness, vomiting, regurgitation) were reported as DGE [17, 18]. In two studies, gastrointestinal passage was analyzed by a Gastrografin swallow and DGE was defined as Gastrografin stasis in the gastric conduit [25, 26]. One study defined DGE as the presence of prolonged gastric emptying time compared with that of normal volunteers [15]. Two recent cohort studies demonstrated that pyloric drainage was associated with an insignificant trend for increased DGE [24, 28]. In another study, gastric outlet obstruction was present in 28% of patients who underwent a pyloric drainage procedure compared with 18% of patients with no pyloric intervention (p ¼ 0.01) [23]. In addition, pyloric drainage was associated with significantly more reflux and its sequelae [22, 25, 27]. Only one cohort study assessed the effect of intrapyloric Botox injection on gastric emptying [26]. When compared with no drainage, intrapyloric Botox injection was associated with significantly less early DGE. Furthermore, intrapyloric Botox injection was associated with decreased respiratory complications, a shorter hospital stay, and reduced late biliary reflux when compared with the other drainage procedures. Unfortunately, the need for reintervention was not reported in this study. In conclusion, results regarding the benefit of pyloric drainage procedures on gastric function remain contradictory, but do not support its routine use.
Adequately Outcome Nonexposed Standardized Adequate Adequate Dealt With No Selective Reliable Representativeness Selected Ascertainment of Interest Outcome Level of Loss to Outcome Measurement Short-Term Long-Term Baseline From Same of Exposure Not Present Confounders of Exposed From Start? Identified? Comparability? Assessment? of Outcomes? Follow-Up? Follow-Up? Follow-Up? Reporting? Evidence Reliable? Population? Cohort? Year
References Diameter Shu et al. [11]
2013
1
1
1
0
0
1
0
0
1
1
.
1
3
Maffettone et al. [12]
2007
1
1
1
0
0
0
1
0
.
1
1
1
3
Lee et al. [13]
2005
1
1
1
0
0
0
1
0
1
1
.
1
3
Collard et al. [14]
1998
1
1
1
0
0
0
1
0
1
1
.
1
3
Collard et al. [44]
1995
1
1
1
0
0
0
0
0
1
1
1
1
4
Bemelman et al. [10]
1995
1
1
1
0
0
1
0
0
1
.
1
1
3 3
Ann Thorac Surg 2014;98:1512–9
Table 2. Critical Appraisal of Cohort Studiesa
Pyloric drainage van der Schaaf et al. [21] 2013
1
1
1
0
1
1
0
1
1
1
1
1
Mehran et al. [45]
2011
1
1
1
0
0
0
0
1
.
1
.
1
4
Lanuti et al. [22]
2011
1
1
1
0
1
0
0
0
1
1
.
1
3
Nguyen et al. [23]
2010
1
1
1
0
1
0
1
0
.
1
.
1
3
Yajima et al. [24]
2009
1
1
1
0
1
0
0
1
.
1
.
1
3
Cerfolio et al. [25]
2009
1
1
1
0
1
1
1
0
1
1
.
1
3
Palmes et al. [26]
2007
1
1
1
0
1
1
0
0
1
1
.
1
3
2007
1
1
1
0
1
0
0
0
1
1
1
1
3
1995
1
1
1
0
0
0
0
0
1
1
1
1
4
Hill et al. [47]
1993
1
1
1
0
0
0
1
0
.
1
.
1
4
Wang et al. [48]
1992
1
1
1
0
0
0
1
0
1
0
0
1
4
Bemelman et al. [49]
1990
1
1
1
0
0
0
0
0
1
.
.
1
4
Reconstructive route Wang et al. [31]
2011
1
1
1
0
1
1
1
1
1
1
1
1
3
Chan et al. [50]
2011
1
1
1
0
0
0
0
1
1
1
1
1
4
Yajima et al. [24]
2009
1
1
1
0
1
0
0
1
.
1
.
1
3
Nakajima et al. [51]
2007
1
1
1
0
0
0
0
1
.
1
.
1
4
Katsoulis et al. [32]
2005
1
1
1
0
0
1
1
0
.
1
.
1
3
Shiraha et al. [52]
1992
1
1
1
0
0
0
1
0
.
1
.
1
4
Anastomotic site van der Schaaf et al. [21] 2013
1
1
1
0
1
1
0
1
1
1
1
1
3
Chang et al. [35]
2013
1
1
1
1
1
0
0
1
1
1
1
1
3
Berry et al. [53]
2010
1
1
1
0
0
0
0
0
1
.
1
1
4
D’Journo et al. [54]
2009
1
1
1
0
0
0
0
0
1
1
.
1
4
Egberts et al. [36]
2008
1
1
1
1
0
1
0
1
1
1
0
1
3
Schmidt et al. [37]
2004
1
1
1
0
0
1
0
1
.
0
1
1
3
Shibuya et al. [55]
2003
1
1
1
0
0
0
0
0
.
1
.
1
4
Johansson et al. [56]
1999
1
1
1
0
0
0
0
0
1
1
0
1
4
Johansson et al. [57]
1999
1
1
1
0
0
0
1
0
1
1
.
1
4
Finley et al. [46]
1995
1
1
1
0
0
0
0
0
1
1
1
1
4
de Leyn et al. [58]
1992
1
1
1
0
0
0
0
0
1
1
.
1
4
Critical appraisal of cohort studies according to the Newcastle-Ottawa quality assessment scale. Only studies with a level of evidence of at least 3 were selected for further analysis.
1 ¼ yes;
0 ¼ no or unclear;
. ¼ not applicable.
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a
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Lanuti et al. [27] Finley et al. [46]
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Fig 2. Gastric tube versus whole stomach. The application of a gastric tube is associated with a lower risk of developing delayed gastric emptying after esophagectomy compared to the whole stomach reconstruction (relative risk, 0.34; 95% confidence interval [CI], 0.12 to 0.97).
Reconstructive Route
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A total of three RCTs and three cohort studies comparing the retrosternal and posterior mediastinal route were included [24, 28–32]. In all studies, a gastric tube was pulled up to the neck. No pyloric drainage procedure was performed. One RCT did not show significant differences for reflux, dysphagia, aspiration, and weight loss at 6 months of follow-up [28]. Another demonstrated that gastric emptying was similar in both groups [29]. In another RCT, it was shown by means of gastric emptying scintigraphy that the mean retention index 30 seconds after ingestion was significantly higher in the retrosternal group when compared with the posterior mediastinal group. However, symptom scores for nausea and vomiting, regurgitation, and dysphagia were similar in both groups [30]. Cohort studies showed contradictory results. One small cohort study favored the retrosternal route, as this was associated with less duodenogastric reflux at 3 to 6 months of follow-up [32]. However, a different cohort study demonstrated that the retrosternal route is associated with an insignificant trend for increased reflux esophagitis in the cervical remnant [24]. Moreover, a recent cohort study showed that scores for eating problems and dysphagia were significantly higher in the retrosternal group when compared with the posterior mediastinal group at 2 weeks of follow-up [31]. At 24 weeks, however, scores for eating problems and dysphagia were similar in both groups. Inversely, reflux scores were similar in the early
postoperative period. At 24 weeks, however, the reflux scores in the posterior mediastinal group were higher than in the retrosternal group, indicating more severe symptoms. In conclusion, the retrosternal route was associated with less (biliary) reflux in the late postoperative period, whereas gastric emptying results are similar compared with the posterior mediastinal route.
Anastomotic Site A total of two RCTs and four cohort studies comparing cervical with thoracic anastomosis were included [21, 33–37]. The RCTs report similar symptom scores (dysphagia, heartburn, regurgitation, and abdominal fullness) and changes in body weight during the first postoperative year for cervical and thoracic anastomosis [33, 34]. This finding is also supported by two large prospective cohort studies that reported on reflux in patients who underwent esophagectomy with gastric tube reconstruction [21, 36]. In one study, differences in occurrence of reflux were not significant at 6 months and 3 years of follow-up [21]. The other study reported similar reflux scores at 3, 6, 12, and 24 months after surgery [36]. Another prospective cohort study did not show any association between anastomotic site and esophageal-specific aspects of quality of life assessed by the EORTC QLQ-OES18 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for esophageal cancer) questionnaire during the first 6 months after surgery [35].
Fig 3. Pyloric drainage versus no drainage. Pyloric drainage is not significantly associated with the risk of developing delayed gastric emptying after esophagectomy (relative risk, 0.91; 95% confidence interval [CI], 0.57 to 1.43). The number of events in the study of Palmes et al. were calculated using a percentage bar graph.
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However, a small cohort study showed that reflux and vomiting scores in the late postoperative period were significantly higher in the thoracic anastomosis group when compared with the group with a cervical anastomosis [37]. In conclusion, intrathoracic or cervical anastomoses do not significantly influence DGE, except for one cohort study that favors a cervical anastomosis.
extent of lymphadenectomy during resection. When the tumor is located at the gastroesophageal junction, creating a gastric tube instead of the whole stomach may ensure radicality. In case of irradicality, the retrosternal route may be preferred as recurrence within the tract of reconstruction might be prevented [40]. The number of harvested lymph nodes may be lower with an intrathoracic anastomosis as periesophageal and paratracheal lymph nodes from the superior mediastinum remain in situ. The prognostic value of the extent of lymphadenectomy during surgery, however, remains controversial [41]. Improvement of gastric function may influence postoperative nutrition strategies. Commonly, a nil-by-mouth strategy is applied after esophagectomy as early oral intake would result in aspiration and complicate anastomotic leakages. Interestingly, one study showed that the risk of cervical anastomotic leak dramatically decreased after switching to a nil-by-mouth strategy until 15 days postoperatively [42]. Early enteral nutrition after upper gastrointestinal surgery, however, has been associated with a reduction of postoperative complications, length of hospital stay, and mortality [43]. The effect of these strategies on functional outcomes is a topic for future research. In conclusion, gastric function after esophagectomy with gastric interposition is an important outcome in the early and late postoperative period. The majority of best available evidence favors the use of the gastric tube over the whole stomach. Results regarding the benefit of pyloric drainage procedures remain controversial and do not support its routine use. Available evidence on the effect of reconstructive route and anastomotic site on DGE is not conclusive. Prospectively randomized studies with standardized outcome measurements are needed to clarify the optimal reconstructive techniques of gastric interposition after esophagectomy.
Comment This systematic review demonstrates that surgical factors influence DGE after esophageal resection. A gastric tube (instead of whole stomach) has superior disease-specific quality-of-life scores and significantly less reflux esophagitis. For pyloric drainage, contradictory results are seen between RCTs and recent cohort studies. Whereas omission of pyloric drainage probably leads to a reduction of biliary reflux in the long term, the effect on gastric emptying during the early postoperative period is controversial and of uncertain clinical relevance. Moreover, DGE can be managed by pyloric dilatation after surgery, and gastric motility appears to recover after several years [38]. Intrapyloric Botox injection can be seen as a promising alternative as it constitutes a transient effect during the early postoperative period when DGE may cause aspiration. Available evidence on the effect of reconstructive route and anastomotic site is limited. Overall, similar functional results were seen irrespective of reconstructive route and anastomotic site. Two cohort studies, however, demonstrated that the retrosternal route is associated with less reflux in the late postoperative period when compared with the reconstruction in the posterior mediastinum. Anastomotic site did not appear to influence DGE after esophagectomy. To our knowledge, this is the first systematic review that analyzed the effect of multiple reconstructive techniques on DGE in combination with a thorough assessment of methodological quality. This systematic review, however, has some important limitations. Heterogeneity in study populations, follow-up, and measurement of outcomes are points of concern. In addition, potential confounders, such as perioperative chemo(radio)therapy or the presence of relevant comorbidity (eg, diabetes mellitus), are often not reported. Also, the influences of antacid or motility agents were frequently not reported in included articles. Consequently, a strong recommendation regarding the method of reconstruction in gastric interposition after esophagectomy is not possible. Prospectively randomized studies are needed that measure DGE in a standardized method that combines gastric emptying scintigraphy with a validated questionnaire (eg, EORTC QLQ-OES18 [39]). Early and late follow-up is recommended, as gastric motility appears to increase up to 3 years after esophagectomy [14, 38]. Furthermore, the effect of reconstructive variables on the incidence and impact of other postoperative complications (eg, anastomotic leakage, stricture, pneumonia) should be thoroughly evaluated in future trials. Importantly, selection of the optimal reconstructive method should also take into account the radicality and the
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