Although the relationship between obesity and

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1 Original Article / Biliary Hepatobiliary & Pancreatic Diseases International Gallstone-related complications after Roux-en-Y gastric bypass: a prospective study Rachid G Nagem, Alcino Lázaro-da-Silva, Rafael Morroni de Oliveira and Valter Garcia Morato Belo Horizonte, Brazil BACKGROUND: Gastric bypass is a widespread bariatric procedure that carries a high incidence of gallstone formation postoperatively. Controversy exists regarding the importance and consequences of gallstones in these patients. There are surgeons who consider gallstone-related complications after gastric bypass important enough to require routine removal of the gallbladder during gastric bypass (prophylactic cholecystectomy). However, this can lead to increased costs and risks. This study aimed to identify complications related to cholelithiasis after Roux-en-Y gastric bypass (RYGBP). METHODS: This is a prospective observational study of 40 morbidly obese patients free of gallbladder disease. The patients underwent open RYGBP at a public hospital in Brazil from February to October They were followed up clinically and ultrasonographically at 6 months and 1, 2, and 3 years after surgery. Of the patients, 38 patients were followed up for 3 years. RESULTS: Eleven patients (28.9%) developed cholelithiasis, four (10.5%) experienced biliary pain, and 2 suffered from acute biliary pancreatitis (5.3%). These patients had their gallbladders removed laparoscopically. No patient presented with acute cholecystitis, choledocholithiasis, or bile duct dilation during the follow-up period. There were no deaths. CONCLUSIONS: Gallstone-related complications after RYGBP were relatively common. Some of these complications, like acute pancreatitis, are known to have potentially severe outcomes. It seems reasonable to perform cholecystectomy during gastric bypass in the presence of cholelithiasis or after this procedure if gallstones develop. (Hepatobiliary Pancreat Dis Int 2012;11: ) Author Affiliations: Division of General Surgery, Ipsemg Hospital, Belo Horizonte, Brazil (Nagem RG, de Oliveira RM and Morato VG); Department of Surgery, Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil (Lázaro-da-Silva A) Corresponding Author: Rachid G Nagem, MD, Division of General Surgery, Ipsemg Hospital, Belo Horizonte, Brazil (Tel: ; Fax: ; rgnagem@yahoo.com.br) 2012, Hepatobiliary Pancreat Dis Int. All rights reserved. doi: /S (12) KEY WORDS: bariatric surgery; cholecystectomy; cholelithiasis; gallstones; obesity; gastric bypass Introduction Although the relationship between obesity and biliary lithiasis has been widely studied, some issues remain controversial. Roux-en-Y gastric bypass (RYGBP) is associated with gallstone formation, and the incidence of cholelithiasis after RYGBP ranges from 6.7% to 52.8%. [1-10] It is controversial whether cholecystectomy should be performed routinely during [11, 12] the gastric bypass, or only if cholelithiasis is present. [13-15] Some researchers have recently proposed gallbladder removal at the time of gastric bypass only in case of symptomatic cholelithiasis. [16-19] According to these authors, the risk of an asymptomatic gallstone patient developing complications after RYGBP is small, and there would be no need for cholecystectomy. However, the literature demonstrates a wide variation in the rate of cholelithiasis after RYGBP, and in its consequences in terms of symptoms and complications. [7, 11, 12, 18, 19] Previous studies have not prospectively assessed the relationship between gallstones and postoperative complications of RYGBP. Instead, these studies (retrospective in the majority of cases) have considered patients who underwent cholecystectomy after RYGBP to be symptomatic, regardless of the reason for gallbladder removal. It is reasonable to assume that a considerable number of gallstone patients are symptomatic but have not had their gallbladder removed for several reasons. Under these circumstances, it is understandably difficult to establish the best approach with respect to the gallbladder. This study was primarily designed to prospectively evaluate the development of gallstone-related complications after RYGBP. 630 Hepatobiliary Pancreat Dis Int,Vol 11,No 6 December 15,2012

2 Gallstone-related complications after RYGBP Methods This study was approved by the Research Ethics Committee of the Ipsemg Hospital (CAEE ) at Belo Horizonte, Brazil. All patients provided informed consent. From February to October 2007, a total of 50 consecutive patients underwent open RYGBP at the Department of Digestive Surgery, Ipsemg Hospital. All procedures were performed by the same surgeon and in accordance with the criteria of the Ministry of Health of Brazil for the management of morbid obesity (BMI 40 kg/m 2 or BMI 35 kg/m 2 with significant co-morbidities related to obesity). Each patient was evaluated with preoperative gallbladder, biliary tree, and liver ultrasonography. Patients who were found to have gallstones (in such cases, cholecystectomy was performed at the same time as RYGBP) and those who had undergone cholecystectomy before RYGBP were excluded. The remaining 40 patients free of gallbladder disease (defined as absence of gallstones or polyps on preoperative ultrasound and intraoperative gallbladder palpation) were prospectively followed up periodically in the outpatient clinic at 1 week, 6 months, and yearly thereafter for three years. Prophylactic postoperative bile salt therapy was not administered. The follow-up schedule included a complete clinical examination and biliary ultrasonography. was defined according to the World Gastroenterology Organization as constant pain at the right hypochondrium or epigastrium, often radiating to the right shoulder, forcing the patient to rest, and not relieved by bowel movement. Ultrasonography of the biliary tract was performed with Logiq P-Tech models (GE Medical Systems Korea, Sungnam-Shi, KS) by a team of four radiology specialists, each with at least 15 years of experience. The complaint of biliary pain (as defined) in two patients who had not formed gallstones raised the question of whether this symptom might be associated with RYGBP postoperative status itself, rather than with gallstones. Therefore, it was necessary to analyze the two groups regarding this variable. Six months after bariatric surgery, 6 of the 38 patients (15.8%) had developed cholelithiasis; 1 year after surgery, 9 patients had formed gallstones (23.7%); and 2 years after surgery, 11 of the 38 patients (28.9%) had presented with cholelithiasis. No additional patients developed cholelithiasis during the last year of follow-up. Two (5.3%) patients experienced acute biliary pancreatitis as the first manifestation of lithiasis (Figs. 1, 2). The disease was diagnosed by serum hyperamylasemia with ultrasonographic demonstration of microcalculi, and confirmed by computed tomography (CT). These patients showed an edematous form of the disease, which was not progressed to a severe form. They underwent cholecystectomy soon after the diagnosis. Perioperative cholangiography revealed no choledocholithiasis or dilation of the biliary tree. Fig. 1. Photograph of microcalculi and gallbladder removed from a patient with acute pancreatitis 3 months after RYGBP. Results Three (6%) of the 50 initial consecutive patients were excluded because of previous cholecystectomy. Seven patients (14%) with ultrasonographically-confirmed cholelithiasis had concomitant cholecystectomy at the time of RYGBP, and were also excluded from the study. Among the remaining 40 patients free of gallbladder disease, two (5%) were lost to a complete follow-up. Fig. 2. Photograph of microcalculi removed from a patient with acute pancreatitis 6 months after RYGBP. Hepatobiliary Pancreat Dis Int,Vol 11,No 6 December 15,

3 Hepatobiliary & Pancreatic Diseases International Fig. 3. Photograph of gallbladder and stone removed from a patient with one episode of biliary pain. The thickened gallbladder wall possibly secondary to inflammatory process. The patient underwent RYGBP 2 years before but the gallstone was formed within 1 year (date of last negative ultrasound). Fig. 4. Photograph of gallstones removed from a symptomatic patient. The patient underwent RYGBP 5 months before., as defined, was observed significantly more often in patients who exhibited lithiasis formation, and therefore may actually be considered a symptom of gallstones (P=0.0035, Fisher's exact test). Four (10.5%) patients manifested symptoms in the form of biliary pain (Figs. 3, 4). Three of these patients had no previous ultrasonographic diagnosis of cholelithiasis at followup and one received a cholelithiasis diagnosis and had been asymptomatic for 19 months until the appearance of symptoms. All of the four patients underwent elective cholecystectomy. Of the five asymptomatic patients with cholelithiasis, two were diagnosed with gallstones smaller than 5 mm. The risk of pancreatitis led to gallbladder removal in these patients before the end of the followup period, approximately 1 month after the diagnosis of microlithiasis. The remaining three asymptomatic patients had their gallbladders removed after the end of follow-up during abdominoplasty (2) and incisional hernia repair (1) (Table 1). All patients who underwent cholecystectomy had their gallbladders removed laparoscopically, with no conversions or significant complications. No patient presented with acute cholecystitis, choledocholithiasis, or bile duct dilation (Table 2). Discussion Table 1. Patient demographics Variables Data Men (n, %) 4 (10.5) Women (n, %) 34 (89.5) Mean age (yr) 43.16±10.11 Mean weight (kg) ±19.70 Mean BMI (kg/m 2 ) 47.86±4.92 BMI: body mass index. Table 2. Complementary information about patients with gallstonerelated complications after RYGBP Patient US diagnosis of cholelithiasis (months after RYGBP) US diagnosis of cholelithiasis (situation) Biliary complication 1 3 Urgency Cholelithiasis Acute pancreatitis 2 4 Urgency Cholelithiasis 3 6 Urgency Cholelithiasis Acute pancreatitis 4 6 Elective/ 5 6 Elective/ 6 6 Elective/ Cholecystectomy (months after RYGBP) Obesity is considered an independent risk factor for cholelithiasis, and a large proportion of the [7, 20] obese patients have gallstones. The prevalence of cholelithiasis in a given population is considered the sum of patients with proven cholelithiasis plus those with evidence of prior cholecystectomy. [21] The preoperative prevalence of cholelithiasis in the present study (20%) was similar to that reported elsewhere Cholelithiasis 7 Cholelithiasis 44 Cholelithiasis Urgency Cholelithiasis 8 11 Urgency Cholelithiasis 9 12 Elective/ Cholelithiasis Urgency Cholelithiasis Elective/ Cholelithiasis 41 RYGBP: Roux-en-Y gastric bypass; US: ultrasonography Hepatobiliary Pancreat Dis Int,Vol 11,No 6 December 15,2012

4 Gallstone-related complications after RYGBP [6, 8, 11-15, 20, 22-27] (13.6% to 47.9%). Cholelithiasis is common in obese patients because of elevated biliary cholesterol secretion, incremented nucleation factors, and impaired gallbladder contractility. [20] Furthermore, while patients with cholesterol gallstones form bile containing a relative excess of cholesterol, the mechanisms differ in nonobese and obese patients. The basic secretory defect in nonobese patients is not excess cholesterol secretion, but rather decreased bile salt and phospholipid secretion. Conversely, in obese patients, cholesterol secretion is greatly increased without any absolute reduction in bile salt or phospholipid secretion. [28] In addition, bariatric surgery is known to favor gallstone formation. Some of the mechanisms involved include increased bile cholesterol saturation, increased gallbladder secretion of mucin, and reduced gallbladder motility due to injury of the [13, 24] vagal nerve. The development of cholelithiasis after RYGBP ranges from 6.7% to 52.8%. [1-10] The incidence rate of 28.9% in the present study is within the range. The lowest incidence rate reported (6.7%) may be related to oral cholecystogram (which is less sensitive than ultrasonography [1] ) used as a diagnostic method. Similarly, the higher incidence rate reported (52.8%) may be due to the design of the study, which was retrospectively based on only 36 postoperative ultrasound examinations from a cohort of 103 patients. [7] Gallstone disease in the present study developed rapidly in the first six months after surgery. In this period, weight loss and cholesterol saturation of bile increased because of the reduced output of bile acids and phospholipids as well as the mobilization of cholesterol from adipose stores. [29] This phenomenon has enabled surgeons to use ursodeoxycholic acid (Ursodiol, Actigall ) in patients during the first 6 months after bariatric [5, 6, 8, 30] operations. Ursodeoxycholic acid is a bile acid that prevents lithiasis by acting on cholesterol and mucin levels in the bile (thereby decreasing the saturation [30, 31] of bile) and improving gallbladder emptying. This agent can reduce gallstone formation from 32% to 2% during the 6-month period after gastric bypass. [5] Another study that included more than 500 patients [31] reaffirmed the role of ursodeoxycholic acid in cholelithiasis prophylaxis after bariatric surgery. The agent reduced gallstone formation from 27.7% to 8.8% (P=0.01). However, patients in the present study did not use ursodeoxycholic acid because it is not sold in the Brazilian market. Taha et al [32] found a significant relationship between serum triglycerides, serum cholesterol, and percentage of weight loss during the first year after RYGBP and gallstone development. Few researchers prospectively studied gallstone formation after RYGBP, and used transabdominal ultrasonography to diagnose cholelithiasis. The results of these studies are not comparable to those of this method in obese individuals. Some researchers [33] used CT for this population with a specificity of 100% and a sensitivity of 91%. One major drawback of this method is the need for intravenous injection of cholecystograffin, which is associated with an increased incidence (25%) of adverse effects (nausea and vomiting). Other aspects to consider are the radiation and weight limitations of CT scanners. Others [34] correlated preoperative ultrasound and gallbladder pathological findings during gastric bypass, and reported only 35 discrepancies (1.1%). Hence, ultrasonography is an accurate diagnostic method for obese individuals since it is performed by ultrasound specialists. There was no increase in patients with gallstone 2 years after RYGBP in the present study. In fact, when weight maintenance is re-established at a lower level, cholesterol saturation of the bile is consistently reduced compared with the more obese state. Although patients are transient at increased risk for gallstone formation during active weight reduction, the chances of gallstone formation appear to be consistently reduced if a lower weight can be maintained. [29] The reported rates [2, 4, 6, 8, 13, 15, 16, 18, 19, 25] of symptomatic cholelithiasis after RYGBP vary from 6% to 13.3%, which are lower than those observed in the present study. Large surgical databases show that patients who undergo cholecystectomy after any bariatric operation are symptomatic. However, it is reasonable to assume that many symptomatic patients have not had their gallbladders removed for a multitude of causes, including unawareness of gallstone disease, fear of surgery, no clinical condition for surgery, gallstone-related symptoms assumed as secondary to bariatric surgery, or planning to combine cholecystectomy with plastic surgery. The literature shows a reduction in the performance of cholecystectomies in bariatric patients. The reduction is due to many reasons, including increased operative time, duration of hospitalization, potential complications, and surgeon's concern about removal of a normal organ. [13] Preoperative biliary ultrasound has been questioned because of the removal of a lithiasic gallbladder during RYGBP. [19] It is appropriate to emphasize that RYGBP causes exclusion of the duodenum from the alimentary tract, which complicates endoscopic access to the papilla of Vater. Although several approaches have been described to overcome this situation (joining endoscopy, Hepatobiliary Pancreat Dis Int,Vol 11,No 6 December 15,

5 Hepatobiliary & Pancreatic Diseases International laparoscopy and fluoroscopy), [35] they are hardly available in countries that lack technological resources (like Brazil), especially in the public health system. Thus, the patient is deprived of an important treatment option for biliary lithiasis: traditional endoscopic retrograde cholangiopancreatography (ERCP). Is RYGBP safe enough when it retains a lithiasic gallbladder while hindering entry to the biliary tree? It is worth noting that cholecystectomy adds approximately 15 minutes to the open RYGBP procedure [11] and 18 minutes to laparocopic gastric bypass. [13] The diagnosis of microlithiasis is not simple, and it is suspected that the incidence of cholelithiasis (as microcalculi) is higher than that reported. In conclusion, gallstone-related complications are relatively common after open RYGBP. Most of the patients with gallstones are symptomatic, and some have potentially severe conditions. If ursodeoxycholic acid is unavailable, it may be appropriate to perform cholecystectomy not only during RYGBP (if cholelithiasis is present), but also during the postoperative period if gallstones develop, even in the absence of symptoms. Laparoscopic cholecystectomy is effective and safe in the latter situation. Contributors: NRG proposed the study, performed research, collected and analyzed the data and wrote the first draft. LA, ORM and MVG contributed to the design and interpretation of the study and to further drafts. NRG is the guarantor. Funding: None. Ethical approval: The study was approved by the Research Ethics Committee (REC) of the Ipsemg Hospital (CAEE ). Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. References 1 Griffen WO Jr, Young VL, Stevenson CC. A prospective comparison of gastric and jejunoileal bypass procedures for morbid obesity. Ann Surg 1977;186: Wattchow DA, Hall JC, Whiting MJ, Bradley B, Iannos J, Watts JM. Prevalence and treatment of gall stones after gastric bypass surgery for morbid obesity. Br Med J (Clin Res Ed) 1983;286: Amaral JF, Thompson WR. Gallbladder disease in the morbidly obese. Am J Surg 1985;149: Shiffman ML, Sugerman HJ, Kellum JH, Brewer WH, Moore EW. Gallstones in patients with morbid obesity. Relationship to body weight, weight loss and gallbladder bile cholesterol solubility. Int J Obes Relat Metab Disord 1993;17: Sugerman HJ, Brewer WH, Shiffman ML, Brolin RE, Fobi MA, Linner JH, et al. A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss. Am J Surg 1995;169: Scott DJ, Villegas L, Sims TL, Hamilton EC, Provost DA, Jones DB. Intraoperative ultrasound and prophylactic ursodiol for gallstone prevention following laparoscopic gastric bypass. 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6 Gallstone-related complications after RYGBP in patients undergoing gastric bypass? Obes Surg 2007;17: Escalona A, Boza C, Muñoz R, Pérez G, Rayo S, Crovari F, et al. Routine preoperative ultrasonography and selective cholecystectomy in laparoscopic Roux-en-Y gastric bypass. Why not? Obes Surg 2008;18: Li VK, Pulido N, Fajnwaks P, Szomstein S, Rosenthal R, Martinez-Duartez P. Predictors of gallstone formation after bariatric surgery: a multivariate analysis of risk factors comparing gastric bypass, gastric banding, and sleeve gastrectomy. Surg Endosc 2009;23: Ellner SJ, Myers TT, Piorkowski JR, Mavanur AA, Barba CA. Routine cholecystectomy is not mandatory during morbid obesity surgery. Surg Obes Relat Dis 2007;3: Guadalajara H, Sanz Baro R, Pascual I, Blesa I, Rotundo GS, López JM, et al. Is prophylactic cholecystectomy useful in obese patients undergoing gastric bypass? Obes Surg 2006;16: Swartz DE, Felix EL. Elective cholecystectomy after Rouxen-Y gastric bypass: why should asymptomatic gallstones be treated differently in morbidly obese patients? Surg Obes Relat Dis 2005;1: Shaffer EA, Small DM. Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity. J Clin Invest 1977;59: Bennion LJ, Grundy SM. Effects of obesity and caloric intake on biliary lipid metabolism in man. J Clin Invest 1975;56: Miller K, Hell E, Lang B, Lengauer E. Gallstone formation prophylaxis after gastric restrictive procedures for weight loss: a randomized double-blind placebo-controlled trial. Ann Surg 2003;238: Uy MC, Talingdan-Te MC, Espinosa WZ, Daez ML, Ong JP. Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: a meta-analysis. Obes Surg 2008;18: Taha MI, Freitas WR Jr, Puglia CR, Lacombe A, Malheiros CA. Predictive factors for cholelithiasis in the morbidly obese submitted to Roux-en-Y gastroplasty. [Article in Portuguese] Rev Assoc Med Bras 2006;52: Neitlich T, Neitlich J. The imaging evaluation of cholelithiasis in the obese patient-ultrasound vs CT cholecystography: our experience with the bariatric surgery population. Obes Surg 2009;19: Oria HE. Pitfalls in the diagnosis of gallbladder disease in clinically severe obesity. Obes Surg 1998;8: Lopes TL, Baron TH. Endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y anatomy. J Hepatobiliary Pancreat Sci 2011;18: Received April 26, 2012 Accepted after revision September 27, 2012 Hepatobiliary Pancreat Dis Int,Vol 11,No 6 December 15,