0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

Gastric Bypass Why Roux-en-Y? A Review of Experimental Data FREE

Brendan J. Collins, MD; Tomoharu Miyashita, MD; Michael Schweitzer, MD; Thomas Magnuson, MD; John W. Harmon, MD
[+] Author Affiliations

Author Affiliations: Department of Surgery, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.


Arch Surg. 2007;142(10):1000-1003. doi:10.1001/archsurg.142.10.1000.
Text Size: A A A
Published online

Objective  To highlight the clinical and experimental rationales that support why the Roux-en-Y limb is an important surgical principle for bariatric gastric bypass.

Data Sources  We reviewed PubMed citations for open Roux-en-Y gastric bypass (RYGBP), laparoscopic RYGBP, loop gastric bypass, chronic alkaline reflux gastritis, and duodenoesophageal reflux.

Study Selection  We reviewed clinical and experimental articles. Clinical articles included prospective, retrospective, and case series of patients undergoing RYGBP, laparoscopic RYGBP, or loop gastric bypass. Experimental articles that were reviewed included in vivo and in vitro models of chronic duodenoesophageal reflux and its effect on carcinogenesis.

Data Extraction and Synthesis  No formal data extraction was performed. We reviewed published operative times, lengths of stay, and anastomotic leak rates for laparoscopic RYGBP and loop gastric bypass. For in vivo and in vitro experimental models of duodenoesophageal reflux, we reviewed the kinetics and potential molecular mechanisms of carcinogenesis.

Conclusions  Recent data suggest that laparoscopic loop gastric bypass, performed without the creation of a Roux-en-Y gastroenterostomy, is a faster surgical technique that confers similarly robust weight loss compared with RYGBP or laparoscopic RYGBP. In the absence of a Roux limb, the long-term effects of chronic alkaline reflux are unknown. Animal models and in vitro analyses of chronic alkaline reflux suggest a carcinogenic effect.

Figures in this Article

The obesity epidemic in the United States has brought about much interest in bariatric surgery. Data from the National Health and Nutrition Examination Survey (NHANES) suggest that 32% of adults in the United States are obese, with obesity defined as a body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 or greater.1 Most concerning is the observation that the number of overweight children in the United States has significantly increased in the past 6 years, from a prevalence of 14% (1999-2000 NHANES data) to 18% (2003-2004 NHANES data).1 The number of bariatric surgical procedures has dramatically increased during a similar time frame, from 13 000 in 1998 to 103 000 in 2003.2

Surgical procedures for the treatment of morbid obesity have undergone several iterations since loop gastroenterostomy was introduced by Mason and Ito in 1967.3 Prospective studies have demonstrated that Roux-en-Y gastric bypass (RYGBP), performed by either open or laparoscopic means, is an effective therapy for morbid obesity. Conventional RYGBP can be performed with minimal morbidity, allows for weight loss of approximately 60% of calculated excess body weight at 5 years, and can alleviate comorbid conditions such as diabetes mellitus, hyperlipidemia, hypertension, and obstructive sleep apnea.4,5

In the original laparoscopic loop gastric bypass only 1 anastomosis was performed, leading to a faster and perhaps safer procedure than the RYGBP. As shown in Figure 1, a laparoscopic loop gastric bypass involves the creation of a gastric pouch in the shape of a tube by dividing the stomach at the junction of the body and the antrum, parallel to the lesser curve.7 A loop of jejunum is then anastomosed to the gastric pouch. Rutledge and Walsh6 provide a 6-year follow-up of 2410 patients who underwent loop gastric bypass. These researchers report a mean preoperative body mass index of 46, a mean operative time of 37.5 minutes, and conversion to open mini–gastric bypass in 0.17% of cases. Their average length of stay was 1.4 days, and their anastomotic leak rate was 1.08%. The authors note that these data are comparable with those reported by other high-volume centers that perform laparoscopic RYGBP. For example, Higa et al4 provide data from their series of 1500 consecutive laparoscopic RYGBPs, reporting an average operating time of 60 minutes, a length of stay of 1.4 days, and no cases of anastomotic leak.

Place holder to copy figure label and caption
Figure 1.

Mini–gastric bypass. The stomach is divided vertically along the lesser curvature, against a 28F bougie. Loop gastrojejunostomy is then performed approximately 180 cm from the ligament of Treitz. Reprinted with permission from Obesity Surgery.6

Graphic Jump Location

Critics of loop gastric bypass call into question the effect of chronic alkaline reflux gastritis and cite previous complications associated with other loop gastrojejunostomies, such as Mason loop gastric bypass.8 Mason loop gastric bypass involves a pouch that is horizontal and contains a considerable amount of fundus. Proponents of loop gastric bypass defend the approach by citing data from Deitel et al,9 who examined the effect of vertical banded gastroplasty on lower esophageal sphincter tone. These authors found that vertical banded gastroplasty improved the resting pressure of the lower esophageal sphincter when patients were studied 13 weeks after surgery. Rutledge and Walsh6 drew a similar conclusion for their vertical gastric tube, although no data are provided that lower esophageal sphincter pressures have ever been seen in patients undergoing laparoscopic loop gastric bypass. Because patients with vertical banded gastroplasty typically develop gastroesophageal reflux months to years after their procedure, the durability of this effect on lower esophageal sphincter tone is questionable. Some patients who undergo loop gastric bypass develop symptomatic bile reflux gastritis and esophagitis, necessitating conversion to RYGBP.10 In addition, historical cohorts demonstrate an increased incidence of gastric cancer in patients with gastric and duodenal ulcers undergoing partial gastrectomy and loop gastrojejunostomy.11

Although loop gastric bypass seems to possess the attractive qualities of a successful weight loss operation, it is worrisome that the anatomical configuration of the bypass is similar to that in animal models of esophageal cancer. Much of our understanding of the pathogenesis of esophageal intestinal metaplasia and the subsequent development of adenocarcinoma is derived from rat models of surgically induced duodenoesophageal reflux. Attwood et al12 demonstrated that surgically induced duodenoesophageal reflux plus the ingestion of the carcinogen 2,6-dimethylnitrosomorpholine or methyl-N-amylnitrosamine in rats produced distal esophageal adenocarcinomas. Because the ingestion of these carcinogens in rats had previously been known to cause esophageal squamous carcinomas, the shift to adenocarcinomas in the presence of duodenal contents suggested an interesting role for bile in the pathogenesis of esophageal adenocarcinoma. Several research groups13,14 have subsequently demonstrated that esophageal reflux of duodenal contents alone, without any adjuvant carcinogens, is sufficient for the development of esophageal cancers. Miwa et al13 established duodenoesophageal reflux by means of an anastomosis between the duodenum and the forestomach, yielding distal esophageal cancers in 36% of animals after 50 weeks of observation. Fein et al14 similarly noted esophageal adenocarcinomas in 48% of rats 16 weeks after esophagojejunal anastomosis. Nishijima et al15 expanded on these observations by examining the protective effects of a Roux-en-Y esophagojejunal anastomosis in the pathogenesis of the progression of Barrett esophagus to invasive adenocarcinoma. As shown in Figure 2, biliary diversion with a Roux-en-Y anastomosis significantly prevents the development of esophageal adenocarcinoma in rats that had previously undergone esophagojejunostomy either 20 or 30 weeks earlier. In this study, none of the rats that underwent Roux-en-Y esophagojejunal anastomosis developed Barrett metaplasia or carcinoma.

Place holder to copy figure label and caption
Figure 2.

Biliary diversion (BD) with a Roux-en-Y esophagojejunal anastomosis (RY) prevents adenocarcinoma in a rat model of duodenoesophageal reflux. A, Animals underwent total gastrectomy, followed by either duodenoesophageal anastomosis (DER) or RY. Subsets of animals in the DER group were converted to RY at 20 and 30 weeks. B, Sixty percent of animals (18 of 30) exposed to duodenoesophageal reflux for 50 weeks developed esophageal adenocarcinomas, whereas no cancers were observed in animals protected with an RY (0 of 28). Reprinted with permission from Annals of Surgery.15

Graphic Jump Location

These well-described rat models of esophageal cancer demonstrate that reflux of duodenal contents is sufficient for producing esophageal cancer in rats. The exact pathogenesis is unclear, although it seems that the reflux of soluble bile acids in a neutral milieu results in severe esophagitis. Inflammation, ulceration, and hyperproliferative changes to the squamous epithelium of the esophagus precede the development of carcinoma.16 These cancers in the rat model were also shown to be phenotypically similar to human esophageal cancer at the histologic and molecular levels.17 Animal models of esophagojejunal reflux demonstrate up-regulation of the caudal-related homeobox gene Cdx2 in Barrett epithelium, a transcription factor that regulates intestine-specific protein expression.18 In vitro studies also demonstrate that the bile acids cholic and deoxycholic acid dose-dependently increase Cdx2 promoter activity and protein production in cultured rat esophageal keratinocytes. Forced expression in Cdx2 in this same cell line also drove the production of MUC2, an intestinal-type mucin. These data suggest an important role for bile acids in the pathogenesis of esophageal intestinal metaplasia. Experimental data also suggest a mitogenic role for bile salts in esophageal neoplasia. Numerous studies1921 demonstrate that bile salts activate proliferative and anti-apoptotic pathways in benign native esophageal epithelial explants, Barrett epithelial cell lines, and esophageal adenocarcinoma cell lines.

None of the published studies on rat models of esophageal cancer are identical to the anatomical configuration of loop gastric bypass. The various rat models of esophageal carcinoma described herein suggest that the presence of soluble bile acids in the esophageal refluxate is required for tumor formation. Although no data are available after loop gastric bypass, it is well described that bile acid content and the incidence of gastritis are much greater after loop gastroenterostomy for the management of morbid obesity. McCarthy et al22 performed endoscopy in 28 patients who had undergone loop gastroenterostomy, loop gastroenterostomy plus diverting enteroenterostomy between the afferent and efferent loops, or Roux-en-Y gastroenterostomy. Total bile acid levels in the gastric pouch were 2080.1 μg/mL (to convert to micromoles per liter, multiply by 2.448) in patients who had undergone loop gastroenterostomy alone compared with 165.0 μg/mL in patients who had undergone Roux-en-Y anastomosis. Moreover, the incidence of gastritis by endoscopy was only 13% in the Roux-en-Y group compared with 71% in the loop gastroenterostomy group. Whether this translates into a greater incidence of reflux esophagitis is unknown. Moreover, the chronic effects of esophageal bile reflux in this subset of patients are unknown because long-term follow-up data are not available.

The purpose of this review was to present the experimental data that support the importance of performing a biliary diversion procedure, such as Roux-en-Y, for a proximal gastroesophageal anastomosis. Just as the Food and Drug Administration would call into question any novel therapy that caused cancer in a preclinical animal model, we should proceed with the same degree of caution for any operation. Laparoscopic loop gastric bypass is technically easier than RYGBP because it requires only 1 anastomosis. However, there is a real risk of bile reflux due to the loop configuration that may have long-term damaging effects to the gastric pouch and possibly the distal esophagus. It may take years before clinically significant complications of bile reflux become apparent to the patient or the physician.

Correspondence: John W. Harmon, MD, Department of Surgery, Johns Hopkins Bayview Medical Center, 4940 Eastern Ave, A Building, Room 5C, Baltimore, MD 21224 (jharmon@jhmi.edu).

Accepted for Publication: April 27, 2007.

Author Contributions:Study concept and design: Collins, Miyashita, Schweitzer, Magnuson, and Harmon. Acquisition of data: Miyashita. Analysis and interpretation of data: Miyashita, Schweitzer, and Harmon. Drafting of the manuscript: Collins and Miyashita. Critical revision of the manuscript for important intellectual content: Collins, Schweitzer, Magnuson, and Harmon. Administrative, technical, and material support: Miyashita and Harmon. Study supervision: Collins, Schweitzer, Magnuson, and Harmon.

Financial Disclosure: Dr Harmon has a patent pending for a vaccine for esophageal cancer.

Ogden  CLCarroll  MDCurtin  LRMcDowell  MATabak  CJFlegal  KM Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006;295 (13) 1549- 1555
PubMed Link to Article
Santry  HPGillen  DLLauderdale  DS Trends in bariatric surgical procedures. JAMA 2005;294 (15) 1909- 1917
PubMed Link to Article
Mason  EEIto  C Gastric bypass in obesity. Surg Clin North Am 1967;47 (6) 1345- 1351
PubMed
Higa  KDHo  TBoone  KB Laparoscopic Roux-en-Y gastric bypass: technique and three year follow-up. J Laparoendosc Adv Surg Tech A 2001;11 (6) 377- 382
PubMed Link to Article
Buchwald  HAvidor  YBraunwald  E  et al.  Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292 (14) 1724- 1737
PubMed Link to Article
Rutledge  RWalsh  TR Continued excellent results with the mini-gastric bypass: six year study in 2,410 patients. Obes Surg 2005;15 (9) 1304- 1308
PubMed Link to Article
Rutledge  R The mini-gastric bypass: experience with the first 1,274 cases. Obes Surg 2001;11 (3) 276- 280
PubMed Link to Article
Fisher  BLBuchwald  HClark  W  et al.  Mini-gastric bypass controversy. Obes Surg 2001;11 (6) 773- 777
PubMed
Deitel  MKhanna  RKHagen  J  et al.  Vertical banded gastroplasty as an antireflux procedure. Am J Surg 1988;155 (3) 512- 526
PubMed Link to Article
Johnson  WHFernandez  AZFarrell  TM  et al.  Surgical revision of loop (“mini”) gastric bypass procedure: multicenter review of complications and conversions to Roux-en-Y gastric bypass. Surg Obes Relat Dis 2007;3 (1) 37- 41
PubMed Link to Article
Papachristou  DNAgnanti  NFortner  JG Gastric carcinoma after treatment of ulcer. Am J Surg 1980;139 (2) 193- 196
PubMed Link to Article
Attwood  SESmyrk  TCDeMeester  TR  et al.  Duodenoesophageal reflux and the development of esophageal adenocarcinoma in rats. Surgery 1992;111 (5) 503- 510
PubMed
Miwa  KSegawa  MTakano  Y  et al.  Induction of oesophageal and forestomach carcinomas in rats by reflux of duodenal contents. Br J Cancer 1994;70 (2) 185- 189
PubMed Link to Article
Fein  MPeters  JHChandrasoma  P  et al.  Duodenal esophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen. J Gastrointest Surg 1998;2 (3) 260- 268
PubMed Link to Article
Nishijima  KMiwa  KMiyashita  T  et al.  Impact of the biliary diversion procedure on carcinogenesis in Barrett's esophagus surgically induced by duodenoesophageal reflux in rats. Ann Surg 2004;240 (1) 57- 67
PubMed Link to Article
Byrnes  CKBahadursingh  AAkhter  N  et al.  Duodenal reflux produces hyperproliferative epithelial esophagitis: a possible precursor to esophageal adenocarcinoma in the rat. J Gastrointest Surg 2003;7 (2) 172- 180
PubMed Link to Article
Su  YChen  XKlein  M  et al.  Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett's esophagus. Lab Invest 2004;84 (6) 753- 765
PubMed Link to Article
Kazumori  HIshihara  SRumi  MAK  et al.  Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett's epithelium. Gut 2006;55 (1) 16- 25
PubMed Link to Article
Jaiswal  KLopez-Guzman  CSouza  RF  et al.  Bile salt exposure increases proliferation through p38 and ERK MAPK pathways in a non-neoplastic Barrett's cell line. Am J Physiol Gastrointest Liver Physiol 2006;290 (2) G335- G342
PubMed Link to Article
Tselepis  CMorris  CDWakelin  CD  et al.  Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro. Gut 2003;52 (2) 174- 180
PubMed Link to Article
Kaur  BSTriadafilapoulos  G Acid- and bile-induced PGE2 release and hyperproliferation in Barrett's esophagus are COX-2 and PKC-ε dependent. Am J Physiol Gastrointest Liver Physiol 2002;283 (2) G327- G334
PubMed
McCarthy  HBRucker  RDChan  EK  et al.  Gastritis after gastric bypass surgery. Surgery 1985;98 (1) 68- 71
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Mini–gastric bypass. The stomach is divided vertically along the lesser curvature, against a 28F bougie. Loop gastrojejunostomy is then performed approximately 180 cm from the ligament of Treitz. Reprinted with permission from Obesity Surgery.6

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Biliary diversion (BD) with a Roux-en-Y esophagojejunal anastomosis (RY) prevents adenocarcinoma in a rat model of duodenoesophageal reflux. A, Animals underwent total gastrectomy, followed by either duodenoesophageal anastomosis (DER) or RY. Subsets of animals in the DER group were converted to RY at 20 and 30 weeks. B, Sixty percent of animals (18 of 30) exposed to duodenoesophageal reflux for 50 weeks developed esophageal adenocarcinomas, whereas no cancers were observed in animals protected with an RY (0 of 28). Reprinted with permission from Annals of Surgery.15

Graphic Jump Location

Tables

References

Ogden  CLCarroll  MDCurtin  LRMcDowell  MATabak  CJFlegal  KM Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006;295 (13) 1549- 1555
PubMed Link to Article
Santry  HPGillen  DLLauderdale  DS Trends in bariatric surgical procedures. JAMA 2005;294 (15) 1909- 1917
PubMed Link to Article
Mason  EEIto  C Gastric bypass in obesity. Surg Clin North Am 1967;47 (6) 1345- 1351
PubMed
Higa  KDHo  TBoone  KB Laparoscopic Roux-en-Y gastric bypass: technique and three year follow-up. J Laparoendosc Adv Surg Tech A 2001;11 (6) 377- 382
PubMed Link to Article
Buchwald  HAvidor  YBraunwald  E  et al.  Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292 (14) 1724- 1737
PubMed Link to Article
Rutledge  RWalsh  TR Continued excellent results with the mini-gastric bypass: six year study in 2,410 patients. Obes Surg 2005;15 (9) 1304- 1308
PubMed Link to Article
Rutledge  R The mini-gastric bypass: experience with the first 1,274 cases. Obes Surg 2001;11 (3) 276- 280
PubMed Link to Article
Fisher  BLBuchwald  HClark  W  et al.  Mini-gastric bypass controversy. Obes Surg 2001;11 (6) 773- 777
PubMed
Deitel  MKhanna  RKHagen  J  et al.  Vertical banded gastroplasty as an antireflux procedure. Am J Surg 1988;155 (3) 512- 526
PubMed Link to Article
Johnson  WHFernandez  AZFarrell  TM  et al.  Surgical revision of loop (“mini”) gastric bypass procedure: multicenter review of complications and conversions to Roux-en-Y gastric bypass. Surg Obes Relat Dis 2007;3 (1) 37- 41
PubMed Link to Article
Papachristou  DNAgnanti  NFortner  JG Gastric carcinoma after treatment of ulcer. Am J Surg 1980;139 (2) 193- 196
PubMed Link to Article
Attwood  SESmyrk  TCDeMeester  TR  et al.  Duodenoesophageal reflux and the development of esophageal adenocarcinoma in rats. Surgery 1992;111 (5) 503- 510
PubMed
Miwa  KSegawa  MTakano  Y  et al.  Induction of oesophageal and forestomach carcinomas in rats by reflux of duodenal contents. Br J Cancer 1994;70 (2) 185- 189
PubMed Link to Article
Fein  MPeters  JHChandrasoma  P  et al.  Duodenal esophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen. J Gastrointest Surg 1998;2 (3) 260- 268
PubMed Link to Article
Nishijima  KMiwa  KMiyashita  T  et al.  Impact of the biliary diversion procedure on carcinogenesis in Barrett's esophagus surgically induced by duodenoesophageal reflux in rats. Ann Surg 2004;240 (1) 57- 67
PubMed Link to Article
Byrnes  CKBahadursingh  AAkhter  N  et al.  Duodenal reflux produces hyperproliferative epithelial esophagitis: a possible precursor to esophageal adenocarcinoma in the rat. J Gastrointest Surg 2003;7 (2) 172- 180
PubMed Link to Article
Su  YChen  XKlein  M  et al.  Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett's esophagus. Lab Invest 2004;84 (6) 753- 765
PubMed Link to Article
Kazumori  HIshihara  SRumi  MAK  et al.  Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett's epithelium. Gut 2006;55 (1) 16- 25
PubMed Link to Article
Jaiswal  KLopez-Guzman  CSouza  RF  et al.  Bile salt exposure increases proliferation through p38 and ERK MAPK pathways in a non-neoplastic Barrett's cell line. Am J Physiol Gastrointest Liver Physiol 2006;290 (2) G335- G342
PubMed Link to Article
Tselepis  CMorris  CDWakelin  CD  et al.  Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro. Gut 2003;52 (2) 174- 180
PubMed Link to Article
Kaur  BSTriadafilapoulos  G Acid- and bile-induced PGE2 release and hyperproliferation in Barrett's esophagus are COX-2 and PKC-ε dependent. Am J Physiol Gastrointest Liver Physiol 2002;283 (2) G327- G334
PubMed
McCarthy  HBRucker  RDChan  EK  et al.  Gastritis after gastric bypass surgery. Surgery 1985;98 (1) 68- 71
PubMed

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

1,398 Views
15 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs