Current Operative Approaches to the Diseased Gallbladder. Diagnosis and Management Updates for General Surgeons

Abstract

Cholecystitis is a common diagnosis which requires management by general surgeons. Morbidity from cholecystitis is often life-threatening, especially in patients with underlying liver cirrhosis or other medical comorbidities. Diagnosis and management of this disease can vary among providers and hospitals. The decision to utilize a radiological or endoscopic temporizing maneuver in severe acute cholecystitis and the timing of later definitive cholecystectomy are relevant points of discussion within general surgery societies. In the last 5 years, the use of intraoperative ductal imaging by conventional vs fluorescence cholangiography had gained significant interest due to the widespread availability of indocyanine green. Finally, the operative strategies and how to manage intra-/postoperative complications are very important to optimizing patient outcomes. In this review paper, we discuss all treatment aspects of cholecystitis and provide updates in its management.

Initial Evaluation and Management

Acute cholecystitis is one of the most common surgical diseases managed by general surgeons. It is generally a result of cystic duct obstruction by a gallstone, followed by inflammation of the gallbladder and secondary bacterial infection. It is clinically manifested by a sharp right upper quadrant (RUQ) abdominal pain that lasts more than six hours and may radiate to the right flank. The pain may appear or worsen following consumption of a fatty meal and is frequently followed by nausea or vomiting. Additional findings include Murphy’s sign and fever. Blood tests usually show elevated white blood count (WBC) and C-reactive protein (CRP). Liver functions tests (LFTs) may be increased. It does not have a fixed pattern, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are often twice the normal laboratory values as well as a moderate increase in bilirubin and alkaline phosphatase (ALP). Ultrasound (US) is the preferred initial screening. ¹ Typical findings include gallbladder wall thickening (≥4 mm), distension of the gallbladder (long axis ≥8 cm, short axis ≥4 cm), and pericholecystic fluid. ² Hepatobiliary iminodiacetic acid (HIDA) scan is an effective modality in cases of clinically suspected acute cholecystitis with a nondiagnostic initial US, as it provides higher sensitivity and specificity. ³ Computed tomography (CT) scan is recommended when the differential diagnosis includes other potential intra-abdominal diseases or when local complications such as gangrenous cholecystitis, hepatic abscess, or biliary peritonitis are suspected. ⁴ Magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) MRI/MRCP is a useful adjunct to preoperatively assess the anatomy of the biliary system and to rule out presence of gallstones in the common bile duct (CBD).

According to the Tokyo Guidelines, acute cholecystitis can be classified into three categories—mild (grade I), moderate (grade II), and severe (grade III). ⁵ Mild acute cholecystitis is defined as one that does not meet the criteria of moderate or severe acute cholecystitis. Moderate disease includes one of the following: elevated WBC (>18,000/mm³), palpable tender mass in the right upper abdominal quadrant, duration of complaints >72 hours, or marked local inflammation—this includes gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary peritonitis, and emphysematous cholecystitis. Severe acute cholecystitis is associated with organ dysfunction and often requires treatment in an intensive care unit.

Early laparoscopic cholecystectomy is the treatment of choice for acute cholecystitis. Other alternatives include supportive treatment and percutaneous cholecystostomy, with/without delayed cholecystectomy.

Timing of Surgery

Several randomized controlled trials comparing early vs delayed intervention demonstrated similar results in terms of operative time, conversion rate, overall complication rate, and bile duct injuries, with the only clear benefits for early intervention being reduced total hospital stay and costs.^6–9 A large multicenter randomized control trial (RCT) comparing immediate intervention (<24 h of hospital admission) to delayed cholecystectomy (7-45 days after the initial admission), however, demonstrated a lower morbidity rate with the early intervention compared with the delayed approach (11.8% vs 34.4%, respectively). ¹⁰ In addition, a meta-analysis of 77 case-control studies showed significant reductions both in morbidity and mortality with the early cholecystectomy groups. ¹¹ Based on these results, early cholecystectomy should be the preferred approach for patients with acute cholecystitis. This approach is superior for most patients with mild to moderate disease, provided that their underlying medical condition allows them to undergo operation under general anesthesia. In patients with either moderate or severe disease and those who cannot tolerate general anesthesia due to systemic organ dysfunction, an alternative approach which includes supportive treatment, percutaneous cholecystostomy, and selective delayed surgery is recommended.

The definition of early cholecystectomy varies significantly between studies, ranging from 24 hours up to 10 days, either from presentation of symptoms or hospital admission. Several studies that have examined the optimal timing for early intervention suggest that it is ideal to perform early cholecystectomy within 2-3 days of symptoms onset or admission.^12–14 Patients may still benefit from an early intervention in cases where onset of symptoms was between 72 hours to 1 week. ¹¹

Percutaneous Cholecystostomy and Timing for Interval Cholecystectomy

Although early cholecystectomy is the preferred approach for most patients with acute cholecystitis, some patients would benefit from percutaneous cholecystostomy (PC) rather than immediate surgical intervention. According to the Tokyo Guidelines, patients with moderate or severe disease who cannot withstand surgery should be considered to undergo biliary drainage. ¹⁵ Previous RCT comparing PC to conservative treatment in high-risk patients demonstrated superior results of the PC group including early symptoms relief (within 24 hours), shorter hospital stay, higher success rate of interval cholecystectomy, and lower overall costs. ¹⁶ While there is a consensus regarding the advantages of biliary drainage in high-risk patients, the optimal timing for PC is also a controversial issue. In this RCT, PC was performed within 8 hours.^17-19

Regarding the techniques of performing PC, there are two approaches to drain the gallbladder: transhepatic and transperitoneal. The transhepatic route is used preferentially by most clinicians because it reduces the risk of biliary leak, allows the drain to be left in place for longer period, and it leads to a quicker maturation of the drainage tract. The most frequent complication of PC is drain dislodgment (7%-30%). Other possible complications include minor bleeding, sepsis, bile leak, digestive tract perforation, and pneumothorax. Recently, a novel approach of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) was suggested as an alternative to PC. ²⁰

There is no consensus on the optimal timing for interval cholecystectomy following PC and different studies report different results on the preferred timing.^21,22 Given these conflicting results, however, we recommend not to perform an interval cholecystectomy in less than 4 weeks from the PC insertion, and preferably to wait for at least 8 weeks. Earlier intervention may lead to a difficult operation under an inflamed surgical field that makes it difficult to identify the various structures, resulting in a higher complication rate.

Endoscopic Ultrasound-Guided Gallbladder Drainage. Review of Current Practice and Outcomes

Endoscopic gallbladder drainage had been described in the literature as a feasible and efficacious alternative to PC in the management of acute cholecystitis for high-risk individuals. ²⁰ When compared to the PC, endoscopic gallbladder drainage is not associated with external drain-related complications, including tube dislodgment, need for changes, and discomfort which limit its long-term use.^20–22 Endoscopic treatment via transpapillary gallbladder drainage and, more recently, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) have been developed and recommended by the American Gastroenterological Association in specific circumstances. Transpapillary drainage is achieved via endoscopic retrograde cholangiopancreatography (ERCP) by cannulating the cystic duct, allowing placement of a plastic stent into the gallbladder. Obstructing pathology, however, such as stone, stricture, or mass at or around the cystic duct may result in lower technical and clinical success rates when compared with EUS-GBD (84% vs 98% and 91% vs 97%, respectively). ²⁰

Endoscopic ultrasound-guided gallbladder drainage is undertaken by the placement of lumen apposing metal stents, which allows for spontaneous passage/endoscopic removal of gallstones and does not require stent exchanges. This technique essentially creates a controlled iatrogenic cholecystoduodenal fistula using an endoscopic technique. Under direct endoscopic ultrasonic visualization, a needle is advanced from the duodenum to the gallbladder. A guidewire is then placed across both the duodenal and gallbladder wall. Over the guidewire, a lumen apposing metal stent is then advanced into position, creating a watertight iatrogenic cholecystoduodenal fistula. The stent delivers radial and constant apposing force to avoid leak between the duodenal and gallbladder puncture site. A magnetic stent or device is not used in this technique. The stent allows for gallbladder decompression into the duodenum by allowing pus ± stones to leave the inflamed gallbladder and enter the duodenum. The patient receives a prophylactic periprocedural antibiotic to cover gram negative and anaerobic bacterias. This way, concerns for potential free abdominal contamination and development of deep organ space infection can be minimized. An accidental leak from the gallbladder and/or duodenum related to the endoscopic puncture is certainly possible, but significant complications are unlikely with precise technique and adequate case selection. Contraindications to the EUS-GBD include gallbladder perforation, biliary peritonitis, large-volume ascites, or significant coagulopathy. Discussion with the surgeon about potential future surgical candidacy is important to elucidate preference for preservation of normal biliary anatomy achieved with transpapillary drainage vs EUS-GBD, which would require fistula repair at the time of cholecystectomy.

Acute Calculous Cholecystitis in Liver Cirrhosis

Acalculous and calculus cholecystitis are conditions that occur also in patients with cirrhosis. Their impaired hepatic function causes a myriad of physiologic/systemic illnesses. The hepatic dysfunction causes impairment of bile composition and gallbladder function/motility, potentially leading to stone formation. The typical signs and symptoms of gallbladder disease may be masked by other systemic or local manifestations of hepatic dysfunction. The radiographic evaluation may be more challenging to interpret with later-stage liver disease, which can cause parenchymal fibrotic changes and ascites, making it more challenging to interpret gallbladder findings. In addition, the typical laboratory findings with gallbladder disease may also be challenging to interpret in the later stages of cirrhosis.

Predictors of outcome after treatment of acute cholecystitis in this population are determined by the stage of cirrhosis, coagulation status (platelet count and prolonged International Normalized Ratio), and the presence of other associated medical conditions. For staging of liver disease, either MELD (model for end-stage liver disease) or CTP (Child-Turcotte-Pugh) are widely used. Both are used as predictors of outcome, with the MELD score being more accurate. The higher the stage, the higher the risk of surgical morbidity and mortality. Low CTP stage, as well as low MELD score, has acceptable outcomes with surgical management. Complications include bleeding, wound complications, thromboembolism, intra-abdominal fluid collections, and cardiopulmonary complications. Operative factors such as operative time, blood loss, and transfusion requirements also contribute in predicting mortality and morbidity. Although the conversion rate to open cholecystectomy is higher than in the non-cirrhotic patients, laparoscopic cholecystectomy is the procedure of choice in patients with low-stage compensated liver disease. Open cholecystectomy, whether as an elective procedure or conversion from laparoscopic, is associated with increased complications over the laparoscopic approach.

Acute severe cholecystitis in the compensated cirrhotic should be treated with laparoscopic cholecystectomy with reasonable outcomes and an expected increase of complications, including increased conversion to open cholecystectomy. For acute severe disease in patients with decompensated liver disease, consideration should be given to waiting until the inflammatory condition has subsided, with medical management (+/- cholecystostomy tube) before definitive gallbladder removal.

Difficult Gallbladder and How to Avoid Injuring the Bile Duct

While cholecystectomy is usually a straightforward procedure, it can sometimes be a very challenging one, leading to a high risk of morbidity. The high variability in the level of complexity/technical difficulty is what makes this common procedure one that general surgeons should always treat with great respect. The most threatening complication is major bile duct injury due to misidentification of the common bile duct or the common hepatic duct that leads to a transection of one of these structures with or without bile leak. Other common injuries include cystic duct stump leak, thermal injuries with a late-term stricture or combined vasculobiliary injuries.

The first step in performing a safe cholecystectomy begins with a preoperative assessment and workup. Once a patient is considered an acceptable surgical candidate, the surgeon should evaluate all risk factors that are associated with a difficult gallbladder such as older age (>65 years), male gender, morbid obesity, prior upper abdominal surgery, previous episodes of biliary colic/acute cholecystitis, and cirrhosis. In the acute setting, duration of the symptoms more than 72-96 hours and high WBC (>18,000/mm³) leads to an increased risk of developing complications. ²³ The surgeon should review previous imaging, assess the anatomy of the gallbladder and the biliary system, and look for potential aberrant anatomy. If a difficult gallbladder is suspected, the surgeon may complete additional preoperative studies such as CT scan or MRCP to gather the most accurate preoperative anatomy. Alternatively, patients with a cholecystostomy tube can complete preoperative cholangiography to assess the patency of extrahepatic biliary tree and its potential anatomical variation.

During the procedure, the surgeon should attempt to achieve the critical view of safety (CVS). This common method includes dissection of the lower end of the gallbladder from the liver bed and clearing all adipose and fibrous tissue from the hepatocystic triangle to a point that only two structures are seen entering the gallbladder. Another way to try to minimize the risk and severity of bile duct injury is by performing intraoperative cholangiography (IOC). There is extensive debate on whether to perform this procedure routinely or only in select cases. Most studies, however, report a decreased rate of major bile duct injuries when IOC is used. ²⁴ When CVS cannot be achieved and the cystic duct cannot be identified, there are 3 main options: 1. Convert to open approach. 2. Perform a bail out procedure—fenestrated vs reconstituting cholecystectomy. 3. Place a drain and transfer the patient to a tertiary hepatobiliary center. Before making any of the above decisions, we recommend a simple and obvious action of calling for help or obtaining advice from an experienced surgeon, whenever one is available. This course of action is a useful method in preventing bile duct injury.

Intraoperative Cholangiography and Fluorescence Cholangiography

Intraoperative cholangiography is a well-known procedure during cholecystectomy that was initially described by Mirizzi in 1937. ²⁴ It includes dissection of the cystic duct, cannulation of it using a small feeding tube (5 French), and injection of contrast material while using fluoroscopy. Using this technique, the surgeon obtains a roadmap of the biliary tree and thereby potentially reduces the incidence of biliary injuries. This procedure also has the ability to identify or rule out the presence of CBD stones. As mentioned above, a debate exists regarding routine vs selective use of IOC. The main argument of the supporters of the routine IOC approach is that it reduces the rate of major biliary injuries. ²⁵ Its routine use, however, increases the operative time and expense, has a low yield of unsuspected CBD stones, and may increase the risk of false-positive rate, leading to unnecessary CBD exploration or endoscopic retrograde cholangiopancreatography (ERCP). Moreover, in the past two decades, the concept of CVS has become the recommended method for preventing bile duct injuries and therefore, the usage of IOC has gradually declined in most countries to only select cases. In fact, there are studies that claim that there is no clear benefit in using IOC to reduce bile duct injury (BDI). ²⁶ Most hepatobiliary surgeons believe that the main advantage of performing IOC is less of a prevention for BDI, but more of the ability to diagnose it once it has occurred. This way, appropriate actions can be taken by the operating surgeon and/or consultant(s) to manage it and certainly not to make it worse. The majority of surgeons do not find advantages using IOC in straightforward cases and therefore it is only recommended on a selective basis. In cases where CVS cannot be obtained, we do not see a clear benefit in performing IOC and performing IOC may itself cause biliary injury.

Fluorescent cholangiography (FC) is a novel approach to reduce biliary injuries that has gained popularity in the past decade. When FC is needed, the ICG is given intravenously approximately 30 minutes prior to the inspection of biliary tree (at the start of the cholecystectomy) since the emergence of fluorescence in the bile fluid is not instantaneous. Compared to IOC, operative time is reduced and there is no exposure to ionizing radiation. Several studies supporting FC had shown that this technique leads to superior common hepatic duct (CHD) visualization when compared to IOC. ²⁷ We believe that this newer approach will gradually replace the usage of conventional IOC with the exception of cases with suspected choledocholithiasis.

Bail Out Strategies—Fenestrated vs Reconstituting Cholecystectomy

CVS technique has been accepted as the best method in prevention of bile duct injury during cholecystectomy. In cases when CVS cannot be achieved due to significant inflammatory reaction over the hepatocystic triangle, an alternative approach should be used to complete the procedure both safely and effectively. A common bail out strategy is a subtotal cholecystectomy. This strategy is becoming more prevalent in the recent years, as most cholecystectomies are being undertaken with a minimally invasive approach. Subtotal cholecystectomy is further divided into “fenestrated” and “reconstituting” type. Subtotal fenestrated cholecystectomy includes a transverse incision across the body of the gallbladder and emptying the contents into a retrieval bag. The dissection continues all the way down to the base of the infundibulum, until the internal opening of the cystic duct is viewed. The cystic duct orifice can be left open or may be closed with a suture from the inside of the gallbladder lumen using purse-string technique. The mucosa of the posterior wall of the gallbladder can be ablated or excised. All the stones and gallbladder contents are removed prior to closure. A closed section abdominal drain is placed nearby. Subtotal reconstituting cholecystectomy involves a transection of the gallbladder in a similar fashion as the fenestrated approach. The dissection continues only partially along the body of the gallbladder, leaving a gallbladder remnant that is closed (reconstituted) with sutures or stapler. The fenestrated approach has the advantage of removing most of the gallbladder while having a higher risk of a bile leak. The reconstituting approach has a lower risk of bile leak, but the presence of a gallbladder remnant leads to future risks of complication such as recurrent cholecystitis, even years following the procedure. Given the fact that most of the bile leaks resolve spontaneously over a short period, the preferred approach is the fenestrated subtotal cholecystectomy. ²⁸ We recommend leaving a drain in the gallbladder bed, regardless of the surgical approach in cases of difficult gallbladder. When a surgeon feels that performing an operation via a minimally invasive approach will compromise the patient's safety or the quality of the procedure, he or she must convert to open approach without any hesitation. ²⁹

When to Open?

The decision when to convert from LC to open approach is a topic that has been under discussion for several decades. Multiple studies have reviewed the various risk factors for conversion to open, but no clear guidelines have been established. ³⁰ The most common indications for conversion are difficulty in identifying anatomy, technical issues leading to lack of progress, suspected biliary injury, and uncontrolled bleeding. One of the most crucial components of safe LC is avoidance of intraoperative complications, with biliary injury being the major one. Basically, whenever CVS cannot be obtained with laparoscopy, an acceptable step is to convert to open. ³¹ This generally allows the operating surgeon to complete the procedure safely with lower risk of biliary leak. Several factors, however, have reduced the use of this approach in recent years.

First, LC has become the standard of care for gallbladder disease over the past three decades, so that general surgeons today are more experienced with the laparoscopic approach. Moreover, most younger surgeons probably feel less comfortable performing open cholecystectomy than LC and therefore will try to complete the procedure with a laparoscopic approach, even in cases of difficult gallbladders. Second, by using IOC or FC the biliary tree can be well identified, even in cases where CVS has not been obtained, and thus avoiding the need of open conversion. Third, with the advent of bailout strategies such as subtotal cholecystectomy, the alternative of converting to open approach has become less attractive. Surgeons should also keep in mind that conversion to open procedure means higher postoperative complications including wound infection, incisional hernia and longer hospital stay. Beyond that, over the past decade, a new player has entered the arena of minimally invasive surgery. The robotic platform (Da Vinci, Intuitive) offers new and advanced capabilities for difficult dissection and fine suturing, which has been associated with reduced need for conversion. In a comparative study of ICG-aided robotic vs laparoscopic cholecystectomy by Gangemi et al, the rate of overall open conversion was reduced from 4.5% to .15% (P < .001) and open conversion in acute cholecystitis or gangrenous cholecystitis was reduced from 9.57% to .76% (P = .002) with the use of robotic system. We believe that robotic cholecystectomy will become the standard of care in the next decade for difficult cholecystectomies. Nevertheless, whenever a surgeon feels that proceeding with minimally invasive approach endangers the patient, either due to technical difficulties or unclear anatomy, the operation should be converted to open approach. Uncontrolled bleeding is another clear indication for conversion and we recommend use of a traditional right subcostal incision. In cases when biliary injury is suspected, it is best to consult with a hepatopancreatobiliary (HPB) surgeon before proceeding with conversion to open approach. The possibility of repairing BDI using minimally invasive Roux-en-Y hepaticojejunostomy (laparoscopic and robotic) is emerging with promising results. Several centers including ours are offering robotic biliary reconstruction routinely. To date, there have been no studies in the literature that compare the outcomes of robotic vs laparoscopic vs open bile duct injury repair.^32–34 In our opinion, the right thing to do in these situations today is to leave a drain in the surgical field and transfer the patient to a tertiary center that specializes in hepatobiliary surgery without the need for conversion.

Managing Acute Bile Duct Injuries

Bile duct injury is a complication with severe consequences that may result in significant morbidity and mortality. The various techniques described previously for performing a safe cholecystectomy are primary intended to prevent this serious complication. It occurs in .1%–.6% of all cholecystectomies. At the beginning of minimally invasive surgery, the rate of iatrogenic injuries was 2-3 times higher than that of open cholecystectomy. Recent reports, however, have demonstrated similar rates of open and laparoscopic approaches. ³² Strasberg’s classification is the widely accepted method to rate the severity of biliary injury. Classes A-D describe a minor duct injury or a partial injury to the CHD or CBD, while class E (E1-E5) is used to describe a major duct injury which means a complete transection of the CBD/CHD. Strasberg’s types A-D are usually managed by ERCP or percutaneous transhepatic cholangiography (PTC) with a stent placement while Strasberg’s E1-E5 are managed by surgical intervention with Roux-en-Y hepaticojejunostomy.

Important clinical factors in determining the appropriate treatment for BDI injury are the timing of recognition of the injury, the patient’s condition, presence of sepsis, and the presence of combined vascular injury. When BDI is suspected intraoperatively, further investigation should be done such as performing IOC. If a biliary injury has been found, a hepatobiliary surgeon should be consulted immediately, and an attempt should be done to repair the injury at the time of surgery. If there is no hepatobiliary surgeon available, the surgical field should be drained, and the patient should be transferred to a facility with a hepatobiliary surgeon as soon as possible. Previous studies have shown that repairing BDI by a hepatobiliary surgeon leads to better long-term results compared to a repair done by the primary operating surgeon. ³³

If the injury was diagnosed after the cholecystectomy, the priority of initial treatment is geared toward managing sepsis and achieving source control. This could be done by percutaneous drainage in cases of biloma or presence of intra-abdominal abscess, or diagnostic laparoscopy with lavage and drainage in cases of generalized bile peritonitis. PTC or ERCP may be used as well for biliary drainage and to perform cholangiography to obtain a roadmap for the upcoming biliary reconstruction. Additional workup should include either triple phase abdominal CT scan and/or MRI/MRCP. They should be used not only to view the biliary tree and presence intra-abdominal collection but also to view both the portal vein and the hepatic artery to rule out any concomitant vascular injury. This major vascular injury occurs in up to 25% of all BDIs with right hepatic artery being the most commonly injured vessel. It significantly affects the patient’s morbidity and may dramatically change the surgical plan and may even lead to a hepatectomy because of ischemia. ³⁵

The optimal timing of biliary repair remains controversial (early vs late intervention) and we believe it should be individualized depending on the patient’s clinical status, presence of sepsis, and the degree of inflammation of the biliary ducts or porta hepatis area. Basically, patients who are generally healthy and clinically stable without presence of sepsis can be repaired early (within 7 days of BDI), while in patients who have sepsis or other acute systemic conditions, the definitive biliary reconstruction should be delayed for at least 6-8 weeks. ³⁶ With time and proper drainage, the inflammation in the porta hepatis will subside and the level of bile duct ischemia will become more obvious.^37–43