Biliary complications associated with weight loss, cholelithiasis and choledocholithiasis

Abstract

Biliary complications like cholelithiasis and choledocholithiasis are more common in bariatric surgery patients due to obesity and rapid weight loss. Patients with a body mass index > 40 face an eightfold risk of developing cholelithiasis. Post-bariatric surgery, especially after laparoscopic Roux-en-Y gastric bypass (LRYGB), 30% of patients develop biliary disease due to rapid weight loss. The aim of this review is to analyze the main biliary complications that occur after bariatric surgery and its management. A review of the literature was conducted mainly from 2010 up to 2023 with regard to biliary complications associated with bariatric patients in SciELO, PubMed, and MEDLINE. Patients undergoing LRYGB have a higher incidence (14.5%) of symptomatic calculi post-surgery compared to those undergoing laparoscopic sleeve gastrectomy at 4.1%. Key biliary complications within 6 to 12 months post-surgery include: Cholelithiasis: 36%; Biliary colic/dyskinesia: 3.86%; Acute cholecystitis: 0.98%-18.1%; Chronic cholecystitis: 70.2%; Choledocholithiasis: 0.2%-5.7% and Pancreatitis: 0.46%-9.4%. Surgeons need to be aware of these complications and consider surgical treatments based on patient symptoms to enhance their quality of life.

Key Words: Bariatric surgery, Complications, Choledocholithiasis, Cholelithiasis, Acute cholecystitis

Core Tip: Surgeons performing bariatric surgery should be vigilant about the increased risk of biliary complications in patients, particularly those with a body mass index over 40, as they have an eightfold higher risk of developing cholelithiasis. Monitoring for symptoms and considering individual risk factors can guide appropriate treatment, potentially improving patients' quality of life post-surgery.

INTRODUCTION

The most durable and effective treatment applied to obesity cases is bariatric surgery (BS), since it helps to reduce comorbidities associated with this disease, and consequently, it helps to lower morbidity rates in this population. However, the incidence of post-bariatric biliary complications, notably cholelithiasis and choledocholithiasis, surpasses that of the general population, particularly within the initial 6-month period post-surgery. This could be explained by the fact that individuals subjected to this surgery combine two risk factors, that is, obesity and rapid weight loss[1,2].

The recognized risk factors associated with cholelithiasis include age over 40, female gender, adiposity, fair complexion, and fertility (collectively referred to as the "5 Fs"). Additionally, dyslipidemia, prior upper gastrointestinal surgeries, and dietary patterns are acknowledged to elevate the risk of gallstone formation[3,4].

Biliary diseases are particularly significant to obese patients since individuals with a body mass index (BMI) of > 40 show eight times higher risk of developing cholelithiasis. It is known that 30% of patients undergoing BS, on average, mainly those undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB), end up developing biliary disease, particularly due to extremely rapid (> 1.5 kg/week) or excessive weight reduction (> 25% of the total body weight)[1,2,4].

This mechanism leads to mobilization of endogen cholesterol from fatty tissues, which increases the concentration of biliary cholesterol, the primary precursor of formation of gallstone (80% of them are formed by cholesterol, or mixed, while 20% are formed by calcium bilirubinate); therefore, the higher the weight loss amount and the shorter the weight loss time, the higher the likelihood of developing cholelithiasis after weight loss. Moreover, hypocaloric diet and duodenal exclusion in gastric bypass reduces secretion of cholecystokinin and, consequently, gallbladder motility. This may also be secondary to surgery manipulation and intraoperative injury to the hepatic branches of the vagus nerves or secondary to calorie restriction during the postoperative period (inefficient gallbladder emptying is associated with fat intake lower than 7 g–10 g per day). Other factors that contribute to formation of gallstone include increased secretion of calcium deriving from arachidonic acid, bile mucin (which enhances crystallization), enterohepatic circulation, and bile salt disorders, which may become imbalanced after weight loss[5,6].

Cholelithiasis is an alarming complication in need of close awareness following BS, with approximately 10% of patients undergoing RYGB or sleeve gastrectomy (SG) having to endure cholecystectomy postoperatively due to acute cholelithiasis[7].

Considering the significant rates of biliary complications associated with weight loss, cholelithiasis, and choledocholithiasis, the primary goal of this study was to conduct a literature review on the subject by searching SciELO, PubMed, and MEDLINE databases from 2010 onwards, selecting papers that are relevant to the subject with regard to symptoms, diagnostic tools, and current treatment options.

Various factors predisposing individuals to biliary complications post-BS are identified, including preoperative cholelithiasis, old age, female sex, diabetes mellitus, previous BS, BMI, and significant weight loss within the first six months after surgery. Genetic susceptibility, pregnancy, and dyslipidemia are also implicated (Table 1).

Table 1 Risk factors for biliary complications after bariatric surgery.

No.	Identified risk factors
1	Preoperative cholelithiasis
2	Old age
3	Female sex
4	Diabetes mellitus
5	Previous bariatric surgery
6	BMI
7	Significant weight loss in the first six months after surgery
8	Genetic susceptibility
9	Pregnancy
10	Dyslipidemia

BMI: Body mass index.

The type of bariatric procedure that is performed may have an impact on the incidence of formation of gallstones. Studies have shown that the susceptibility of developing symptomatic cholelithiasis is increased with each procedure. For instance, it is estimated that RYGB has a 6% to 50% incidence of gallstone formation compared to approximately 1% to 8% in laparoscopic SG and roughly 4% in laparoscopic gastric banding. In a recent prospective study, the incidence of gallstones was found to be 34% after RYGB and 28% after SG. The group of patients submitted to the SG procedure had a 35% lower rate of gallstone formation in a meta-analysis of eight cohort studies published in 2021 (in which 94855 SGs and 106844 RYGBs were performed). This clarifies that RYGB surgery is related to a major risk of formation of gallstone than other types of bariatric surgeries[5,8,9].

The following describes the incidence of the primary biliary complications from 6 to 12 months after surgery: Cholelithiasis (36%), biliary colic or dyskinesia (3.86%), acute cholecystitis (0.98%–18.1%), chronic cholecystitis (70.2%), choledocholithiasis (0.2%–5.7%), and pancreatitis (0.46%–9.4%)[1,2,10]

Simply put, obesity increases a patient’s risk of developing biliary complications, which indicates a poor prognosis for the course of the illness and makes managing these complications more challenging (Table 2).

Table 2 Incidence of the main biliary complications after bariatric surgery.

Type of complication	Incidence
Chronic cholecystitis	70.2%
Cholelithiasis	36%
Acute cholecystitis	0.98%-18.1%
Pancreatitis	0.46%-9.4%
Choledocholithiasis	0.2%-5.7%
Biliary colic or dyskinesia	3.86%

SYMPTOMATOLOGY

Symptoms associated with biliary complications in patients subjected to BS do not differ from those observed in patients who were not subjected to previous surgery. The primary complaints include hypochondrium or right epigastrium pain, intolerance to fatty foods, nausea and/or vomiting, dyspepsia, and flatulence. Patients with cholecystitis develop vesicular-origin inflammation and infection processes because calculi affect the infundibulum region. Conversely, patients with choledocholithiasis present jaundice in addition to the symptoms previously described, as a result of calculi affecting the bile duct; cholangitis results from jaundice progression in association with the infectious process known as biliary sepsis[5].

DIAGNOSIS

The diagnosis of biliary complications is based on clinical and imaging criteria. The diagnosis of cholecystitis follows the criteria proposed by the 2018 Tokyo Guidelines[10]. The following complementary exams can be requested for this purpose.

Abdominal ultrasound

This is the exam of choice for the diagnosis of biliary disorders. However, it is less accurate in obese patients than in the overall population, since these patients exhibit large amount of adipose tissue often associated with hepatomegaly, and it makes it more difficult to identify patients’ gallbladder through the transducer, missing the identification of 27%–36% of stones. Sometimes, it is necessary to require more sensitive diagnostic tests[5].

Computerized tomography of the abdomen

It can be used to diagnose biliary disorders or even complications of cholecystitis; using intravenous contrast helps increasing diagnosis sensitivity. Although it has not been verified in patients with a BMI of > 40, its performance in the overall population is lower than that of abdominal ultrasound (USG).

Magnetic resonance cholangiopancreatography

It is an alternative to the previously mentioned exams, but it is not often recommended. Since it is more sensitive to this specific finding, it has the potential to be useful in assessing lithiasis in cystic and bile duct.

Ecoendoscopy

It is a recent examination that combines traditional ultrasound images with endoscopy’s visual resources to get high-resolution images. This can be used to assess the hepatic biliary duct, the intrapancreatic portion of the bile duct, the Vater papilla, and the pancreatic duct. The upper portion of the hepatic biliary duct can be hard to assess. Calculi, tumors, and adjacent vascular invasion in the biliary tract can be detected with the use of endoscopic ultrasound.

Based on the current literature, the following topics of discussion on the impact of BS on biliary complications can be confirmed: The type of surgical procedure that was done, preferably the sleeve gastric bypass for its minor association with post-surgery cholelithiasis and choledocholithiasis; the use of ursodeoxycholic acid (UDCA), which is a helpful tool in preventing this condition post-BS; simultaneous cholecystectomy with BS or prophylactic cholecystectomy (PC) could be practiced in some cases without significant risks for individualized patients; and usefulness of endoscopic procedures as measures to resolve cholelithiasis, such as endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP).

USE OF UDCA TO PREVENT GALLSTONE FORMATION

There is consensus among most surgeons that the prophylactic use of ursodiol—also known as UDCA or ursodeoxycholic acid has significantly decreased the incidence of gallstone or sludge formation. The main effect of UDCA is the inhibition of the absorption of endogenous bile acids in the small bowel by competitive action[11].

UDCA is a naturally occurring bile acid that has been proven to manifest sufficient evidence to interfere in the formation of gallstones. UDCA works by decreasing the saturation of bile with cholesterol, reducing the risk of formation of cholesterol crystal and development of gallstone. In recent studies with promising results, the use of UDCA have been investigated for the prevention of formation of gallstones after BS.

Many randomized trials have recommended the use of UDCA that can successfully prevent the formation of gallstones, decreasing the risk of cholecystectomy after bariatric procedures. The beneficial daily dose of UDCA in each study varied from 500 to 1200 mg, and it might be considered at least during the period of rapid weight loss (during the first 3 to 6 months postoperatively) to reduce the frequency of symptomatic gallstones[4].

In a systematic review and meta-analysis conducted in 2023 that reunited 12 randomized controlled trials and involved 2767 patients who underwent diverse bariatric procedures, the total incidence of cholelithiasis was decreased in patients receiving UDCA, with a significantly lower frequency of gallstone formation following BS [the risk ratio (RR) was 0.13, P < 0.0001].

Subgroup analyses endorsed reduction of gallstone incidence at 3 months (P = 0.04), 6 months (P < 0.00001), and 1 year (P < 0.00001) with UDCA prophylaxis. The occurrence of symptomatic cholelithiasis was also lower in the UDCA group (RR 5.70; P < 0.00001), and cholecystectomy rates were significantly reduced (RR 3.05; P = 0.002).

Although the use of UDCA as a conservative management or performing cholecystectomy during BS only in the presence of symptomatic gallstones appears to be of higher efficiency, some authors in the current literature may support routine PC, in which there is still a debate over the best approach to prevent symptomatic cholelithiasis[12,13].

Thus far, the outcome of many clinical trials exhibit an advantageous tool of UDCA for preventing formation of gallstones after BS. Nevertheless, this practice still requires more studies for its standard use[4].

According to Sugerman et al[14], decrease in stone formation reached 32% in the group treated with UCDA, in comparison to values recorded for individuals in the placebo group (Figure 1)[14].

Figure 1 Flow diagram for decision-making processes based on the administration of ursodeoxycholic acid. UDCA: Ursodeoxycholic acid.

CONCOMITANT CHOLECYSTECTOMY DURING BS

Concurrent cholecystectomy after BS is no longer necessary in most cases, while it is still acceptable for patients who have previously experienced symptoms and whose image-based examination confirmed the incidence of calculi (Figure 2)[2,10,15].

Figure 2 Flow diagram for decision-making processes. ERCP: Endoscopic retrograde cholangiopancreatography.

Cholecystectomy is the treatment of choice for symptomatic gallstones, although there is ongoing discussion on the role of PC in the course of BS. PC was once recommended in the era of open surgery, but many studies have reported that PC is associated with an extended operative time and with an increased rate of complications, concomitantly increasing mortality. According to current studies, mutual laparoscopic cholecystectomy with SG or RYGB did not affect mortality or the risk of major complications, and it was associated with a 0.6% increased risk of post-surgical infection[4,16].

The two most effective treatment and preventive measures for cholelithiasis in patients who had BS are watchful waiting and prophylactic concomitant cholecystectomy. In watchful waiting, the physician stays watchful for symptomatic cholelithiasis and its development and only performs cholecystectomy if indicated. The advantage of conducting this condition in this manner includes avoiding a more invasive and possibly unnecessary operation; however, it could delay the treatment of cholelithiasis and it may cause more biliary complications, such as biliary colic, cholecystitis, cholangitis, choledocholithiasis, pancreatitis, obstructive cholestasis, fistula, and perforation[5,8,11,17].

Prophylactic cholecystectomies may be more challenging due to the resulting suboptimal trocar placement and visceral obesity, according to a 2022 study. Hence, the authors in that study did not recommend performing routine prophylactic cholecystectomies in all patients who had BS due to the lack of favorable evidence.

A 2023 case report stated that clinical evaluation should be the standard for identifying a patient’s indication for this procedure, individualizing the overall risk of developing symptomatic cholelithiasis by considering all of the factors involved with the patient[8].

Based on studies, the annual rate of cholecystectomy procedures applied to obese patients before surgery reaches 0.6%–0.7% and that this rate increases to 1.6%–2.0% between the first and the third year after LRYGB; it remains at 1.0% in subsequent years[18]. This procedure can be avoided or specifically recommended for symptomatic patients in the preoperative period, keeping in mind that it may add significant amount of time to the baseline procedure. This is because there is a low risk of postoperative biliary complications, primarily in patients treated with UDCA. Patients undergoing concurrent procedures experience longer procedure times—an average of 32 minutes—and a higher risk of complications[19].

Although many authors defended that this is an avoidable procedure, some still advocate for PC, in certain occasions. For example, Fobi et al[20] justified the PC with gastric bypass operation based on the frequent discovery of undetected cholelithiasis in the excised gallbladder and the risk of complications associated with gallstones migrating to the common bile duct[20].

It is worth emphasizing the extreme importance of performing intraoperative cholangiography in all patients who undergo cholecystectomy following LRYGB, since this is the final chance to quickly assess a patient’s bile duct. Intraoperative identification of lithiasis in the main bile duct requires washing it with saline solution and administering 1 mg glucagon to relax the sphincter of Oddi to help clearing distal obstruction.

Bleeding, infectious abscesses, biliary fistula (the most frequent one), the need of percutaneous drainage, intestinal perforation, and pancreatitis due to stones that were not observed in intraoperative cholangiography are the postoperative complications (incidence ranging from 1.8% to 5.56%)[1] of PC. After the gastric bypass surgery, the endoscopic access to the papilla becomes more difficult given the anatomical changes caused by such procedures, where the conventional endoscopic access to the papilla is no longer possible[5,6,21].

CHOLEDOCHOLITHIASIS

The risk of stone migration following LRYGB ranges from approximately 0.2% to 5.3%. ERCP remains the gold standard used to both diagnose and treat stone obstruction in the main bile duct. The rate of successful bile duct catheterization and papillotomy in patients with normal anatomy is close to 90%[22]. However, transgastric ERCP is currently one of the most widely used methods for treating choledocholithiasis in patients undergoing LRYGB[23].

ROLE OF LAPAROSCOPICALLY ASSISTED TRANSGASTRIC ERCP

Rapid weight loss after Roux-en-Y gastric bypass surgery could mean a major need for endoscopic management, such as ERCP intervention. The LA-ERCP is another endoscopic tool used in this case, which has the advantage of being capable of accessing the excluded stomach.

RYGB alters the normal gastrointestinal anatomy when excluding most of the stomach, duodenum, and proximal jejunum, which leads to rapid weight loss on a period of 12–18 months, resulting in complications such as cholelithiasis, choledocholithiasis, and gallstone pancreatitis. This supports the necessity of postoperative intervention, particularly the use of minimally invasive approaches.

However, the anatomy changes during this procedure, making it more difficult for patients who had RYGB to have conventional access to the pancreaticobiliary tract. This creates the opportunity for the emergence of alternative ERCP, for example, rotational and single- or double-balloon enteroscopy. However, these techniques are restricted because they cannot cannulate the desired ducts or reach the papilla.

LA-ERCP was first described in 2002 and its use is increasing annually. In a study published in 2023, 27 studies were included, with 1283 patients that went through 1303 LA-ERCP. The rate of concomitant cholecystectomy was 33.6%, and 90.9% of the procedures was a biliary indication. Technical success rate was 95.3%, while clinical success rate was 93.8%. The main complications identified were pancreatitis (6.8%), infection (6.1%), bleeding (3.4%), and perforation (2.5%). The rate of conversion to open laparotomy was 7%[24].

BALLOON ENTEROSCOPY-ASSISTED ERCP

Balloon enteroscopy-assisted ERCP is the second option to treat choledocholithiasis in these patients, with success rate ranging from 60% to 90%[20,25]. Its main advantage lies on the possibility of progressing within the small intestine to enable the endoscope to move forward in patients subjected to Roux-en-Y reconstruction. The primary disadvantage of this technique is the need of a more specialized endoscopic teams, which are not easily found. Therefore, it should not be taken into consideration as the first option to treat choledocholithiasis.

Finally, percutaneous biliary drainage can be used via USG-guided puncture of the intrahepatic bile duct, followed by cholangiography, in order to confirm the incidence, number, and size of stones. Cholangiography success rate reaches approximately 98% in patients with dilated ducts and 90% in patients without dilation[20]. After the procedure is over, a guidewire is inserted into the common bile duct, and the papilla is dilated with the aid of angioplasty balloon to enable to perform biliary drainage; 2–10 days later, the drainage pathway is consolidated[23-27]. Working through this pathway enables to push the stones into the duodenum or remove them through the hole in the skin. This process is made easier by the introduction of a balloon, as described several authors in the current literature[28-30]. Cholangiography is performed 24 h later to confirm unblocking of bile duct; once it is confirmed, the drain is removed. The success rate of this procedure ranges from 93% to 96%[20].

The following are the advantages of balloon-assisted papilla dilation over endoscopic sphincterotomy: It helps to prevent bleeding induced by sphincterotomy and preserve the biliary sphincter function. In addition, according to reports in the literature, papilla destruction can lead to malignant choledochal epithelium transformation, which increases the incidence of bile duct cancer. This factor turns balloon-assisted papilla dilation into an excellent option, mainly for young patients. Complications, such as hemobilia, pancreatitis, cholangitis, pleural effusion, and biliary peritonitis, take place in 4.7%–6.7% of cases[31].

CONCLUSION

The incidence of biliary complications, such as cholelithiasis and choledocholithiasis, is higher in patients subjected to BS than in the overall population, as well as 8 times higher in patients with a BMI of > 40. The primary risk factors for these complications include preoperative cholelithiasis, old age, female sex, diabetes, previous BS, BMI, and significant weight loss in the first six months after surgery. In order to diagnose these complications, ultrasound and computer tomography are the most common tests used; however, physicians can request other tests, whenever the aforementioned ones fail to confirm their suspicions. Because of its effectiveness in preventing biliary complications associated with BS, the use of UDCA is recommended. The surgical treatment applied to cholelithiasis, as well as to the other herein described complications, are reserved for symptomatic patients.