Gallbladder and Biliary Tree

NATURAL HISTORY OF CHOLELITHIASIS

The first description of incidental gallstones probably dates back to the 14th century, a relatively recent observation in the grand scheme of pathologic observations. This has been attributed to the relative rarity of gallstone formation before modern diets. These postmortem findings preceded the first descriptions of symptomatic gallstones by about 200 years, perhaps a testament to their frequently asymptomatic nature. Without the benefits of modern ultrasonography, open cholecystectomy became the preferred treatment modality for symptomatic gallstone disease throughout the early 1900s, and it was not until the 1980s that incidental, asymptomatic cholelithiasis became a very common clinical problem.

The decreased morbidity of laparoscopic cholecystectomy introduced considerable interest in surgery for the treatment of asymptomatic gallstones. With increasing availability of and expertise with laparoscopic cholecystectomy throughout the 1990s, the surgical approach to asymptomatic gallstones became increasingly heterogeneous. This ultimately resulted in the National Institutes of Health convening of a Consensus Development group that set forth now-familiar guidelines recommending cholecystectomy only for symptomatic or otherwise complicated cholelithiasis in 1992. This guidance is the basis of the prevailing expectant approach to patients with silent gallstones for the past 30 years.

Since that time, both the natural history of gallstones and the outcomes associated with laparoscopic cholecystectomy have been better described ( Fig. 1 ). Asymptomatic cholelithiasis is quite common. In a large, prospective, cross-sectional study of 11,229 asymptomatic gallbladders with ultrasonography, Festi and colleagues demonstrated an incidental cholelithiasis rate of 7.1% among Italian adults. This probably underestimates the incidence in the United States, where smaller cross-sectional studies show an incidence closer to 15%. In certain ethnic groups and geographic locations in the United States, the rate exceeds 20%, implicating a familiar myriad of demographic and environmental factors in formation of gallstones (estrogen, age, obesity, Hispanic, and Native American). Regardless of their exact incidence, asymptomatic gallstones remain a common dilemma for referring physicians and surgeons alike, and the surgical management of asymptomatic cholelithiasis should ultimately be individualized based on the risk of progression to symptomatic disease and the estimated morbidity associated with expectant management. To thoughtfully approach this predicament, a general understanding of the relative risks of expectant management versus cholecystectomy is crucial.

RISK OF PROGRESSION TO SYMPTOMATIC CHOLELITHIASIS

Gallstone disease is generally thought of as a sequence from asymptomatic to symptomatic cholelithiasis (i.e., stone formation initially with subsequent development of pain, infection, pancreatitis, or cancer), although the time between development of stones and symptoms is not currently estimable. Through a combination of cross-sectional and longitudinal studies, it has been demonstrated that only a minority of patients with asymptomatic gallstones will ultimately develop symptoms. In their large, longitudinal investigation of 673 European subjects with asymptomatic cholelithiasis and a median follow-up of nearly 20 years, Shabanzadeh and colleagues found that only 20% of gallstones were ultimately found to cause any disease, which has been reiterated by smaller studies. The majority of disease was uncomplicated (i.e., biliary pain without acute cholecystitis, choledocholithiasis, or pancreatitis).

There are some demographic and ultrasonographic characteristics that are associated with increased risk of symptoms, especially with complicated presentation. Female sex, immobility of stones, numerous stones, and large (>10 mm) or small (<5 mm) stones all are independently associated with increased incidence of symptoms and complicated presentation ( Fig. 2 ).

Over about 20 years’ follow-up, Shabanzadeh and colleagues found that about 8% of their subjects with asymptomatic gallstones ultimately presented with acute cholecystitis, choledocholithiasis, or gallstone pancreatitis. None of the patients developed carcinoma of the gallbladder or cholangiocarcinoma during the study period. Festi et al. found a single case of gallbladder carcinoma in follow-up of their 856 patients with asymptomatic gallstones (0.12%).

These longitudinal studies may reflect some inherent bias toward identification of patients who will not develop symptoms, as only patients who were asymptomatic at the time of ultrasound were included, and the duration of cholelithiasis at the time of diagnosis was not known. Regardless, both studies clearly demonstrate that only a minority of patients with asymptomatic gallstones will have complicated gallbladder disease during their lifetime and therefore would have benefited from cholecystectomy at the time of asymptomatic gallstone identification.

MORBIDITY ASSOCIATED WITH LAPAROSCOPIC CHOLECYSTECTOMY VERSUS EXPECTANT MANAGEMENT

A modern discussion of the management of asymptomatic gallstones should include a modern appraisal of the risks associated with laparoscopic cholecystectomy in comparison to potential benefits. It is worthwhile to note that consensus guidelines that recommend reserving cholecystectomy only for symptomatic or complicated gallstone disease originate from an early era of laparoscopy, which may consider additional morbidity due to the early learning curve in adopting the procedure. The overall mortality and bile duct injury rates for modern laparoscopic cholecystectomy are less than 0.1% and 0.3%, respectively. Overall significant morbidity of laparoscopic cholecystectomy is about 5%, including hernia formation, bowel obstruction, and both deep and superficial surgical site infections. In the absence of acute inflammation, the morbidity associated with elective laparoscopic cholecystectomy performed for asymptomatic gallstones may be even lower, although there are no large, controlled studies addressing the question since cholecystectomy is so rarely performed prophylactically. Conversely, the ready availability of and low morbidity associated with procedures to treat the potential complications of cholelithiasis (endoscopic retrograde cholangiopancreatography [ERCP] for choledocholithiasis, for example) mean that complications of contemporary expectant management may also be less morbid.

Given that the rate of any symptom development after identification of incidental gallstones is about 20%, complicated disease development is about 8%, and major morbidity of laparoscopic cholecystectomy is roughly 5%; decisions regarding the approach to asymptomatic gallstones should be individualized to the patient, with careful consideration of the potential consequences of complicated gallbladder disease versus operative morbidity and fitness at the time of diagnosis.

SPECIFIC PATIENT POPULATIONS

Cancer Risk Reduction

Although gallbladder cancer is very uncommon in the United States (about 1 in 100,000 US adults) and only one patient in the two largest longitudinal studies of asymptomatic cholelithiasis developed this malignancy, there is undeniably a connection between gallstones and cancer. Between 75% and 90% of patients with gallbladder cancer have cholelithiasis, and many of the risk factors for gallbladder carcinoma are identical to those for gallstone formation. Therefore, the relative rarity of this malignancy in the United States probably precludes prophylactic cholecystectomy for risk reduction in the otherwise average-risk patient with gallstones. Special consideration should be given to patients who are at higher risk for this cancer, and an understanding of the risk factors for gallbladder cancer beyond silent gallstones will help inform decision making.

Mural calcification, or porcelain gallbladder, has traditionally been an indication for cholecystectomy to reduce the risk of malignancy ( Fig. 3 ). Early reports demonstrated 30% to 60% lifetime cancer risk associated with this finding. However, reexamination of malignancy risk in this special population has demonstrated much lower (but still elevated) risk of approximately 5%. There is no consensus on the management of this unusual radiographic finding in the absence of symptoms, and the approach should again be individualized to the patient, their overall condition, and risk of malignancy.

Finally, very large (>3 cm) gallstones have demonstrated a small but significant increase in the risk for malignancy. Given that these stones have a higher risk of lifetime symptom development as well, special consideration should be given to cholecystectomy in otherwise appropriate patients with very large gallstones.

SUMMARY

Asymptomatic cholelithiasis remains a common clinical dilemma, and the lifetime risk of complicated disease from initially silent gallstones is low but not negligible (estimated at 8%). Although the relative morbidity of laparoscopic cholecystectomy continues to decline since its advent in the 1980s, there is still occasional major morbidity associated with the procedure (roughly 5%, with the majority being infectious complications). Therefore, a thorough understanding of the relative risks of the procedure versus conservative management are foundational to individualizing surgical treatment recommendations for each patient.

EPIDEMIOLOGY

Biliary dyskinesia is a rare diagnosis. However, up to 20% of the cholecystectomies performed annually in the United States are for a diagnosis of functional gallbladder disorder. The incidence in the United States has risen from 43 cases/million to 89 cases/million in the decade between 1991 to 2001. This is in stark contrast to the 25 cases/million noted in countries outside of the United States. This increase has been most prominent in the pediatric patient population with a sevenfold increase between 1997 and 2010. It is unclear if the discrepancy noted in incidence between the United States and other countries represents a difference in patient population or overdiagnosis.

CLINICAL PRESENTATION, EVALUATION, AND DIAGNOSIS

Patients presenting with biliary dyskinesia often have vague abdominal complaints centered around recurrent episodes of abdominal pain. Biliary dyskinesia is a diagnosis of exclusion and more common causes of episodic abdominal pain should be excluded before intervention, such as irritable bowel syndrome, peptic ulcer disease, gastroesophageal reflux disease, chronic constipation, costochondritis, muscular skeletal disorders, coronary artery disease, or liver capsular pain in patients with cirrhosis. If these other more common entities are excluded, then biliary dyskinesia can be considered if specific pain symptoms are present as outlined in the Rome IV diagnostic criteria ( Box 1 ). These criteria have been designed by expert consensus to establish an accepted definition of biliary pain such that patients must have epigastric or right upper quadrant pain that (1) builds up to a steady level and lasts for 30 minutes or longer, (2) occurs at different intervals (not daily), (3) are severe enough to interrupt the patient’s daily activity or lead to an emergency room visit, (4) are not significantly related to bowel movements, and (5) are not related to postural changes or acid suppression. Additional supportive criteria include pain associated with nausea or vomiting, radiation of pain to the back or to the right infrasubscapular area (Boas’ sign), or pain that wakes the patient from sleep.

To be diagnosed as having a functional gallbladder disorder patients must meet all the biliary pain criteria previously mentioned and have the absence of gallstones or other structural pathology based on either imaging or laboratory analysis suggesting biliary obstruction. Supportive diagnostic criteria can be a low calculated gallbladder ejection fraction (GbEF). It is important to emphasize that cholescintigraphy is recommended only to support the diagnosis and not to make the diagnosis. When considering the use of cholescintigraphy, it is necessary to understand the history of this test. The highest level of data suggesting GbEF is useful in making treatment decisions for biliary dyskinesia is based on a study of 21 patients with abnormal cholescintigraphy randomized to either surgery or observation. This study suggested that abnormal GbEF was predictive of symptom improvement postcholecystectomy. However, these data must be interpreted cautiously as it was underpowered and did not compare surgery to medical management. A subsequent pilot study attempted to address this by randomizing patients with low GbEF to surgery or medical management with amitriptyline and found that the feasibility of a larger trial is doubtful given high crossover to the surgical arm due to clinician bias and lack of a “gold-standard” medical treatment. Reliance on GbEF to predict clinical response to cholecystectomy is problematic when considering up to 80% of patients with functional biliary pain and normal GbEF still have symptom relief after cholecystectomy.

The definition of an abnormally low GbEF can also be a moving target as reported cutoffs have ranged from <35% to <50% depending on how the test is done. Most modern series will use <35% as a cutoff, defining hypokinesis as described in a 2019 Cochran review based on standardized techniques. However, GbEFs of <35% have been reported in up to 25% of asymptomatic patients. Multiple confounders may artificially lower GbEF such as exercise, hormone replacements, anticholinergics, and proton pump inhibitors. Much of the variability in this test can be attributed to nonstandardized administration. An attempt to curb irregular test execution was undertaken by the Society of Nuclear Medicine, which defined practice guidelines to “assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of hepatobiliary scintigraphy in adults and children”. Their recommendations rely on the use of synthetic cholecystokinin for stimulation of GbEF as the use of fatty meals or other stimulants are nonstandardized. However, a subsequent national shortage of synthetic cholecystokinin led to a reevaluation of this recommendation and found that use of fatty meals may be adequate. These disparate recommendations again add variability to interpretation. A study looking at the reproducibility of an abnormally low GbEF when repeated a month later found that half of patients will normalize when using a standardized method ( Fig. 1 ). These many caveats are cautionary that a low GbEF should only be considered as supporting the diagnosis of biliary dyskinesia and not be utilized to make the diagnosis.

If a patient presents with symptoms of biliary colic by Rome criteria, has no other diagnosis that can explain the symptoms, and supporting data are considered carefully, only then can biliary dyskinesia can be diagnosed by exclusion. Patients meeting this recommendation are more likely to have an improvement in symptoms following cholecystectomy. The operative description of a laparoscopic cholecystectomy utilizing the “critical-view of safety” technique is described in the previous chapter. On pathologic examination there should be no evidence of gallstones or microlithiasis (i.e., sludge) if the correct diagnosis was made. Interestingly, 80% of resected specimens will show signs of chronic inflammation microscopically.

For some patients, the alternative approach of observation can be considered given this is a benign process. The natural history of biliary dyskinesia is not well studied, and it is unclear how many of these patients will improve with watchful waiting. To date, only one study has randomized patients to surgery versus observation and found that cholecystectomy was more likely to improve symptoms. However, many other retrospective series have reported outcomes in patients undergoing nonoperative therapies. An analysis of these studies showed an average of 50% of patients will improve without an operation if given time. It should be noted that the smallest improvement reported in this meta-analysis was in the aforementioned randomized study. While these limited data are hard to interpret, it is likely that we can expect some patients to improve with observation. Further work is needed to correctly identify those patients who would most benefit most from observation or cholecystectomy.

INTRODUCTION

Cholecystolithiasis is estimated to be present in 10% of the population, with one-third of those developing symptoms. Acute cholecystitis (AC) is most commonly a result of gallstone-mediated obstruction of the cystic duct, although acalculous cholecystitis can occur in low-perfusion states or biliary stasis in critically ill patients. Obstruction of the cystic duct by gallstones leads to mucosal inflammation and edema, distension of the gallbladder wall, and eventual ischemia. Not infrequently, untreated AC results in perforation with abscess formation or, more rarely, diffuse peritonitis.

The diagnosis of AC is based on a combination of clinical signs and symptoms with confirmatory imaging. Signs and symptoms include right upper quadrant (RUQ) pain/tenderness lasting more than 4 to 6 hours, associated nausea/vomiting, and fevers. On physical examination, patients are tender in the RUQ and/or epigastrium. Exacerbation of pain by palpating the right subcostal location in conjunction with deep inspiration may be elicited (Murphy’s sign). Abdominal ultrasound (US) of the RUQ is often performed in patients with characteristic presentations to confirm pericholecystic fluid, gallstones, and gallbladder wall thickening. Abdominal CT scans are not infrequently obtained, especially in patients presenting via the emergency room and/or with presentations that are not quite classic. Ultrasound has a higher sensitivity in visualizing gallstones and can be used to assess for pain directly overlying the gallbladder (“sonographic Murphy’s sign”). Standard treatment in low medical risk patients is early, same-admission laparoscopic cholecystectomy. Patients with equivocal presentations/imaging, or those with significant medical comorbidities, are approached with medical management and delayed cholecystectomy once the diagnosis is confirmed or the medical situation stabilized. Resolution of AC with intravenous antibiotics alone is quite common. Percutaneous cholecystostomy is performed in nonoperative patients when antibiotics alone fail. When performing laparoscopic cholecystectomy for AC, anatomic difficulties such as high body mass index (BMI) or variant ductal anatomy can be exacerbated by a severe inflammatory response. Therefore, surgeons should be proficient and prepared for conversion to open cholecystectomy or utilizing bailout options described later.

Robotic cholecystectomy is becoming increasingly popular. The robot is a tool, just as laparoscopic instruments are, but it allows for more fine motor control and 3D visualization. Indocyanine green (ICG) cholangiography is also being reported more frequently. It allows for real-time anatomic verification, which may improve efficiency when used in conjunction with the “critical view of safety” technique.

CLINICAL PRESENTATION, EVALUATION, AND DIAGNOSIS

Patients presenting with AC experience symptoms of upper abdominal pain (RUQ and/or epigastric) that lasts more than 4 to 6 hours. Often, careful history taking can elicit prior episodes of similar symptoms of shorter duration and less severe pain. Nausea and vomiting are often concomitant symptoms. Fever may also be present but objectively occurs less frequently. The patient may have a known history of gallstones from prior episodes or incidentally from prior imaging, allowing some focus in diagnostic workup.

The most common physical examination finding is RUQ tenderness to palpation; an inflammatory mass may also be palpated depending on body habitus and this finding often portends very difficult dissection. A classic physical finding is Murphy’s sign: inspiratory arrest with palpation over the gallbladder. This is often reported during diagnostic US as a “sonographic Murphy’s sign.” Despite these classic signs and symptoms, the presentation can be highly variable, especially in patients who are obese, diabetic, advanced in years, or immunosuppressed from various causes. There is also significant symptom overlap with other intraabdominal or thoracic causes.

The most important differentiation a surgeon makes is determining AC from other biliary disease, such as biliary colic or choledocholithiasis. AC needs immediate diagnosis, evaluation, and treatment to prevent progression of disease, while biliary colic can often be managed with symptom control and outpatient cholecystectomy. Choledocholithiasis is covered elsewhere, but treatment often initially involves other treatment modalities before laparoscopic cholecystectomy. Although not typical, some patients present with both AC and common duct complications (cholangitis, pancreatitis). Many patients with chronic biliary colic arising from cholecystolithiasis may have a thickened gallbladder without other manifestations of AC. In general, such patients should undergo elective cholecystectomy unless medical comorbidities dictate otherwise. As mentioned earlier, a number of other intraabdominal processes have overlapping symptom presentations including pancreatitis, peptic ulcer disease, hepatitis, mesenteric ischemia, colitis, and perforated appendicitis. Extraabdominal diseases with symptom overlap include myocardial ischemia and pneumonia. History taking and physical exam should focus efforts on ruling out other sources of symptoms as well as guide laboratory and imaging studies.

There are no pathognomonic laboratory studies for AC. Mild leukocytosis is common. Leukocytosis over 18,000 per mm ³ may be a predictor of severe inflammation. Liver transaminase (AST and ALT) and alkaline phosphatase levels are often normal or slightly elevated. Serum bilirubin is generally normal. Markedly elevated alkaline phosphatase and bilirubin levels should prompt consideration of common bile duct (CBD) pathology (cholangitis, choledocholithiasis), whereas profound elevations of liver transaminase levels may reflect intrinsic liver issues (hepatitis). Serum amylase and lipase are sent to evaluate for pancreatitis.

The optimal choice of imaging depends on the likelihood of cholecystitis as well as study sensitivity, availability, and cost of the study. US, CT, hepatobiliary iminodiacetic acid (HIDA) scan, and magnetic resonance cholangiopancreatography (MRCP) are all capable of diagnosing AC, each with advantages and weaknesses. For patients with a typical presentation of AC, US is the diagnostic test of choice. It is inexpensive, widely available, and has adequate sensitivity/specificity. Findings on US that suggest AC include pericholecystic fluid, gallbladder wall thickness over 4 mm, gallbladder distension, a gallstone lodged in the cystic duct/neck of the gallbladder, and a sonographic Murphy’s sign. Although US is 90% sensitive at diagnosing gallstones, it is only 60% to 70% sensitive for identification of objective signs of AC. It is common for a patient to present with classic history and laboratory findings of AC and an US showing gallstones but with no other objective findings. In this setting, abdominal CT may be useful to rule out other abdominal conditions, although for surgically low risk patients, proceeding straight to laparoscopy with anticipation of cholecystectomy is appropriate. It is not uncommon for surgeons to be consulted after CT imaging has already been obtained. CT is more sensitive than US at evaluating objective signs of AC including pericholecystic fluid, inflammation, and gallbladder thickening. If the CT scan has characteristic findings of AC, then it is not necessary to perform an US even when stones are not radiographically visible.

Another common scenario is the patient with an atypical presentation and US findings without clear evidence of cholecystitis. A full review of the patient and available data are needed, and the surgeon must decide whether there is significant likelihood of an alternate diagnosis not involving the biliary tract; at this point, CT of the abdomen and pelvis can be obtained to rule out other intraabdominal pathology and potentially rule in AC. It should be noted, however, CT scan is less sensitive in milder disease of the gallbladder and should not be used as the initial/gold standard study in uncomplicated AC.

In the unusual case where US and CT imaging are inconclusive, an HIDA scan may be informative. An HIDA showing nonvisualization of the gallbladder is consistent with cholecystitis from an obstructing gallstone, but it should be noted that false positives are possible in fasting patients. HIDA imaging is highly sensitive and specific for cholecystitis but provides no useful information for other sources of symptoms in the event of a negative study. We use HIDA very rarely, most commonly in patients with atypical presentations, significant comorbidities, and inconclusive US and CT scans. MRI is highly sensitive for AC but is more expensive and less expeditious. MRI/MRCP is typically reserved for patients with significant elevations in either bilirubin or alkaline phosphatase levels to rule out choledocholithiasis and malignancy, which may necessitate significantly different treatment approaches.

SURGICAL MANAGEMENT

Laparoscopic cholecystectomy is the standard treatment for AC. Early, index admission cholecystectomy in most patients has been proven to be clinically advantageous. Surgery treats the current episode of complicated gallstone disease, and potential subsequent episodes of AC or biliary tract complications related to gallstones are eliminated or minimized, respectively. All patients diagnosed with AC should be started on appropriate antibiotics at diagnosis. Antibiotics are directed to treatment of common pathogens in bile cultures including E. coli, Klebsiella, Enterobacter , and Bacteroides species.

The decision regarding the appropriate treatment strategy, surgery or medical management depends on the overall medical condition of the patient plus the severity and duration of symptoms. Patients with minimal medical comorbidity presenting early in the disease process should generally be managed with surgery. Those with significant, optimizable comorbidities but mild cholecystitis may merit a trial of medical therapy or “cool down” period followed by cholecystectomy after 6 to 12 weeks. Those who are critically ill or with severe comorbidities and severe AC are often best managed with early percutaneous cholecystostomy tube placement in conjunction with antibiotics and delayed cholecystectomy once their medical condition is satisfactory.

It is widely accepted that cholecystectomy should be completed as soon as feasible following diagnosis during the index hospitalization. No demonstrable difference is found in mortality rate, major bile duct injury, postoperative pain, or other significant complication in patients treated with early or delayed cholecystectomy. Multiple studies have shown the safety and efficacy of early, same-admission cholecystectomy in the management of cholecystitis. The practice of “cooling off” until there is an opening in the operating room convenient for the surgeon is specifically unwarranted as is a general practice of treating with antibiotics to facilitate discharge and surgery in an elective setting. These approaches serve only to extend hospitalization unnecessarily and place patients at risk for ongoing symptoms or complications from their stone burden. While laparoscopic cholecystectomy is the procedure of choice, surgeons must be familiar with laparoscopic and open approaches as the average conversion rate in AC is 10%.

Robotic cholecystectomy, as an extension of the laparoscopic toolset, is preferred by some surgeons. Robotic port placement and technique is theoretically equivalent to laparoscopic cholecystectomy, as the robot is a laparoscopic device. Three-dimensional visualization and wristed instrument movement are described as advantages by frequent robotic users. Additionally, the latest iterations of the DaVinci robot have fluorescent cholangiography (FC) capability.

ICG cholangiography during minimally invasive cholecystectomy allows for real-time identification of biliary structures during cholecystectomy and in the current era is straightforward to perform. Selective intraoperative intraluminal contrast cholangiogram (IOC) can also be useful in confirming difficult anatomy, and its timing of use is discussed later.

Indocyanine Green Use in Cholecystectomy

ICG is a green dye injected by the intravenous route preoperatively and is excreted exclusively in the bile. The standard dose of ICG at our institution is 7.5 mg administered IV at least 45 minutes, and up to 3 hours, before incision. Protein-bound ICG fluoresces when illuminated with NIR light and allows for FC. FC offers a potential detailed anatomic mapping of extrahepatic biliary structures and can be a useful adjunct to the critical view of safety technique. As the NIR light is built into the laparoscopic or robotic camera and processor equipment, FC can be performed without the need for additional equipment, supplies, or personnel in the operative theater. It has the added benefit of not requiring cannulation of the biliary tree, such as with IOC. No substantial contraindication for use of ICG exists, and it has been used safely in patients with iodine allergy. Anaphylactic reaction has been reported at a rate of 0.003%. Our group avoids use of ICG dye in patients with a history of anaphylactic reaction to shellfish or iodine out of an abundance of caution.

Although current firm recommendations are limited by published sample size, early data suggest both reduced operative time and conversion to open surgery in FC cases for both inflamed and noninflamed pathology. Whether FC significantly moves the needle on reducing major CBD injury remains to be confirmed with further collation of data and use in practice. Our institution routinely uses ICG in laparoscopic cholecystectomy. Examples of ICG use in practice are seen in Figures 1 and 2 .

MEDICAL MANAGEMENT

Patients with moderate to severe medical comorbidities (ASA>3, CCI>6) and mild cholecystitis may be managed medically with possible interval cholecystectomy. Antibiotics should empirically cover the most common organisms: enteric gram-negatives (E. coli, Klebsiella, Enterobacter), anaerobes (Bacteroides, Clostridium), enterococci, and streptococci. Duration of antibiotics is generally 7 to 14 days. Analgesia is also needed during the inflammatory response; regimens include aggressive multimodal nonnarcotic medications (acetaminophen, nonsteroidal antiinflammatory drugs) and opiates as needed. Supportive IV fluids are used until pain is controlled, laboratory tests begin to show improving trends, and the patient tolerates a diet. When patients clinically worsen or do not improve within 72 hours, percutaneous drainage should be considered. An 85% response rate to medical therapy is observed in AC, with most patients not experiencing recurrent issues in short term follow-up.

PERCUTANEOUS DRAINAGE

Percutaneous cholecystostomy is reserved for patients who do not respond to medical therapy, are clinically unstable with multiple comorbidities, have comorbidity that precludes general anesthesia, have atypical prolonged duration of symptoms (over 4 days), or already have associated abscess.

Cholecystostomy is 90% effective in alleviating symptoms and is performed under local anesthesia or light sedation by interventional radiology. Minor complications, such as catheter dislodgement or blockage, occur in 15% of cases and may require repeat IR intervention. Serious complications such as bleeding or bile leak are rare. If the patient is a surgical candidate, we leave the drain in place and perform interval cholecystectomy in 6 to 12 weeks. If comorbidities preclude surgery, IR cholecystogram is performed after a minimum of 6 weeks; if there are no stones present and cystic duct is patent, the tube can be removed or sequentially capped, symptoms monitored, and then removed. A more detailed description of cholecystostomy tube management can be found elsewhere in this book.

ENDOSCOPIC THERAPY

Endoscopic management of cholecystitis is rare but can be helpful in highly select patients. There are limited reports of treating AC via ERCP with placement of a transampullary stent into the gallbladder via the cystic duct. Transmural drainage can also be performed by puncturing the gallbladder via the duodenum under endoscopic US guidance, dilation of the tract, and placing a stent. This may be a long-term solution in the case of a patient who is not a surgical candidate, although it is used very rarely.

SPECIAL CONSIDERATIONS

INTRODUCTION

Gallstone disease is one of the most common gastrointestinal disorders encountered by general surgeons. Moreover, older patients who have severe cholecystitis and associated physiologic decompensation resulting from comorbidities and gallbladder pathology are increasingly more common. Ultimately, the preferred definitive treatment for patients with acute cholecystitis is laparoscopic cholecystectomy. However, there are situations in which emergent cholecystectomy is not always safe, including when cholecystitis leads to sepsis and hemodynamic instability, when cholecystitis causes acute decompensation of underlying comorbid illnesses, or when underlying comorbid conditions increase the patient’s surgical morbidity risk (e.g., severe cardiac disease, severe pulmonary disease, and/or metastatic malignancies). In these cases, cholecystostomy tube insertion should be considered as a less invasive treatment that avoids general anesthesia and provides infectious source control.

INDICATIONS FOR CHOLECYSTOSTOMY TUBE PLACEMENT

Despite moving toward early cholecystectomy in all patients presenting with acute cholecystitis, there remain patients with high surgical risk either because of severe cholecystitis, the advanced nature of their comorbid conditions, or both. It is in these subsets of patients that cholecystostomy tube placement may be indicated.

The decision to forgo cholecystectomy and perform a cholecystostomy tube placement is mainly driven by two factors, namely gallbladder pathology and patient-related factors. Gallbladder pathology is primarily described by (1) the presence or absence of gallstones (calculous or acalculous cholecystitis), (2) the severity of inflammation (with or without gangrene), (3) the duration of symptoms, (4) the presence of sepsis and/or hemodynamic instability, and (5) the presence of underlying intraabdominal malignancy. Patient-related factors are a combination of objective and more subjective factors including, but not limited to, underlying neurologic, cardiac, respiratory, renal, hepatic, and other systemic diseases that increase surgical risk. Such comorbid conditions, in the setting of otherwise manageable acute cholecystitis, may lead to physiologic decompensation. As a result, cholecystostomy tube placement is generally performed in critically ill, debilitated, and/or high–surgical risk patients with acute cholecystitis.

GALLBLADDER PATHOLOGY FACTORS

Calculous or Acalculous Cholecystitis

Acute cholecystitis is most often related to gallstones. Complications from gallstones include acute calculous cholecystitis, choledocholithiasis, cholangitis, and gallstone pancreatitis. The pathophysiology of acute cholecystitis results from obstruction of the cystic duct by an impacted gallstone, which then leads to transmural gallbladder edema and inflammation with potential necrosis. When indicated, cholecystostomy tube placement allows for gallbladder decompression in the setting of cystic duct obstruction and can be performed under ultrasound guidance with local anesthetic and minimal sedation. Decompression of the gallbladder reduces the inflammatory process, allowing the patient to recover from the infection and any underlying systemic inflammatory response. Further, cholecystostomy tube placement may provide a bridge to definitive therapy with interval cholecystectomy in selected patients.

In contrast to cholecystitis associated with cholelithiasis, acalculous cholecystitis primarily occurs in patients who are critically ill and cannot tolerate surgical intervention. Given the lack of gallstones, this is not considered an obstructive process. Numerous studies have reported cholecystostomy tube placement in patients with acalculous cholecystitis ( Table 1 ). But, given the fact that acalculous cholecystitis often occurs in already critically ill patients, mortality remains relatively high, with 30-day and in-hospital mortality rates ranging from 9% to 21% following percutaneous cholecystostomy tube placement. Despite lower morbidity rates of cholecystostomy tube placement versus cholecystectomy in this patient population, mortality rates were reported to be similar in a large retrospective study of 1725 patients with acalculous cholecystitis undergoing cholecystostomy tube placement or cholecystectomy. Although these data propose cholecystostomy tube placement as definitive treatment for patients with acalculous cholecystitis who cannot tolerate cholecystectomy, one-third of these patients eventually underwent definitive treatment with cholecystectomy ( Table 2 ).

TABLE 1

Studies Primarily Reporting Outcomes in Patients with Acalculous Cholecystitis Who Undergo Percutaneous Cholecystostomy Placement

Study	Total AAC (N)	Study Design	Outcomes
Horn (2015)	278	Retrospective	30-day mortality was 4.7%; 54.7% of patients were definitively treated with PC with a follow-up of 5 years; 23.5% of patients were readmitted for recurrently cholecystitis; 28% underwent an LC at some point in the study period.
Kirkegard (2015)	56	Observational	30-day mortality was 10.7%, with 80.4% being definitively treated with PC; 9% underwent LC at some point in the study period.
Anderson (2014)	4329	Retrospective	Decreased mortality in patients undergoing cholecystectomy versus PC (hazard ratio, 0.29, P < .001).
Simorov (2013)	704	Retrospective	Compared with LC and OC, those who underwent PC had decreased LOS, morbidity, ICU stay, and cost. No difference in mortality.
Chung (2012)	57	Retrospective	In-hospital mortality was 21%, and 49% were managed nonoperatively; 31% underwent cholecystectomy; 7% had recurrent cholecystitis.

ICU, Intensive care unit; LC, laparoscopic cholecystectomy; LOS, length of stay; OC, open cholecystectomy; PC, percutaneous cholecystostomy.

TABLE 2

Tube-Related Complications, Readmission, and Cholecystectomy Rates Associated with Cholecystostomy Tube Placement

Study		Total (N)		Tube-Related Complications (%)		Readmission Rates (%)		Recurrent Cholecystitis (%)		Cholecystectomy (%)
Kim (2017)		144		21.4		NR		9.7		27.9
Papis (2017)		39		0		15.4		15.4		30.7
Boules (2016)		380		NR		3.7		NR		32.9
Pang (2016)		71		28		NR		NR		45
Wang (2016)		279		NR		NR		9.2		33
Bala (2015)		257		31		15		NR		63.4
Jang (2015)		93		3.2		NR		19.3		33
Khasawneh (2015)		245		NR		NR		NR		83
Cha (2014)		82		NR		0		0		54.8
Chang (2014)		60		9.8		NR		11.7		5
Al-Jundi (2012)		30		9		NR		NR		36.7
Horn (2014)		278		35.2		23.5		23.5		28.4
Hsieh (2012)		166		16.3		NR		13.8		31.9
Joseph (2012)		106		5		NR		NR		27
McKay (2012)		68		14.7		41		41		30
Kortram (2011)		27		3.7		NR		19.7		16
Nasim (2011)		62		1.6		NR		9.7		37
Saeed (2010)		41		25		NR		NR		22
Wisemen (2010)		86		21		NR		NR		54.6
Paran (2006)		54		33		19 *		NR		51.8
Basaran (2005)		18		5.6		NR		NR		42.8
Byrne (2003)		45		2		NR		NR		37.8
Hatzidakis (2002)		63		5		NR		NR		25
Spira (2002)		55		16		19.2		19.2		56.4
Berber (2000)		15		13		NR		NR		80 †

* Percent of patients who had a percutaneous cholecystostomy and never underwent surgery because they were deemed unfit

† Unknown denominator. NR , Not reported.

Severity of Inflammation and Duration of Symptoms

In recent years, consensus recommendations have been created to provide formal guidelines regarding the diagnosis and management of cholecystitis. The Tokyo Guidelines (TG) were developed in 2007 (TG07) and subsequently revised in 2013 (TG13) and 2018 (TG18). The TG07 and TG13 created a classification system for the severity of cholecystitis ( Table 3 ). Based on this, an algorithm for cholecystostomy tube placement was derived. Earlier versions of the Tokyo Guidelines recommended utilization of cholecystostomy tubes for (1) patients with grade II cholecystitis who have symptoms lasting more than 72 hours and fail to respond to antibiotic therapy, or (2) patients with grade III cholecystitis ( Fig. 1 ). The updated TG18 guidelines now recommend percutaneous cholecystostomy tube placement in cases of grade II and grade III cholecystitis in high–surgical risk patients following failure of antibiotics and supportive care ( Fig. 2 ).

TABLE 3

Tokyo Guidelines Definition of Acute Cholecystitis Based on Disease Severity

Grade	Definition
I (Mild)	No findings of organ dysfunction and acute cholecystitis (does not meet criteria for grades II–III) Cholecystectomy is deemed low risk and safe Duration of symptoms <72 hours
II (Moderate)	Degree of inflammation is likely associated with operative difficulty if cholecystectomy is to be undertaken Associated with any one of the following: Elevated white blood cell count (>18,000/mm 3 ) Palpable tender mass in the right upper quadrant Symptoms >72 hours Marked local inflammation (i.e., gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary peritonitis, emphysematous cholecystitis)
III (Severe)	Cholecystitis with associated organ dysfunction to include any of the following: Circulatory failure (hypotension requiring treatment with dopamine >5 µg/kg/min, or any dose of norepinephrine Neurologic disturbance (decreased level of consciousness) Respiratory failure (partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio <300) Renal failure (oliguria, creatinine >2.0 mg/dL) Hepatic failure (international normalized ratio >1.5) Thrombocytopenia (platelet count <100,000/mm 3 )

Sepsis and/or Hemodynamic Instability

In some cases, the degree of inflammation in cholecystitis can worsen and thereby lead to sepsis, septic shock, and hemodynamic instability. For patients who present with severe cholecystitis, mortality rates in some studies have been shown to be as high as 35%. Along with supportive care and broad antibiotic therapy, early source control is crucial and has been demonstrated to be a major factor for reducing mortality in this population. However, hemodynamic instability and/or shock may preclude operative interventions, including cholecystectomy, as a viable option for source control. Cholecystostomy tube placement in patients with severe cholecystitis is easy to perform, effective, and provides adequate source control for patients with cholecystitis.

Underlying Intraabdominal Malignancy Precluding Definitive Surgical Intervention

A small subset of patients with underlying malignancies, such as pancreatic adenocarcinoma or cholangiocarcinoma, may develop acalculous cholecystitis from an obstructive process secondary to either the malignancy or a therapeutic intervention (e.g., biliary stenting to relieve a common bile duct obstruction). In both situations, the tumor and/or stent can occlude the cystic duct leading to cholecystitis. However, the underlying malignancy may preclude a safe cholecystectomy; therefore cholecystostomy tube placement can be offered if antibiotics are insufficient at treating the cholecystitis. Consistent with this approach, multiple case reports and one retrospective series have shown that the use of a cholecystostomy tube allows patients to recover more quickly and potentially proceed or return to their cancer therapy. In these cases, cholecystostomy tube management requires a multidisciplinary approach because patients may not be able to undergo definitive interval cholecystectomy. In contrast, for patients with resectable cancers, the gallbladder can be addressed at the time of definitive surgical intervention.

PATIENT-RELATED FACTORS

Multiple studies in the United States have evaluated the utilization of cholecystostomy tube decompression in the setting of acute calculous cholecystitis ( Table 4 ). As discussed earlier, although gallbladder pathology is an important factor when cholecystostomy tube placement is considered, these studies demonstrated that the primary indications for tube placement are independent of the severity of cholecystitis, and rather are largely based on patient-related factors including patient comorbidities that make the risk of anesthesia and an operation prohibitive (see Table 4 ). Some studies are nonspecific, simply recommending cholecystostomy in “poor surgical candidates” without clear definition. Others report specific patient-related factors as indications for cholecystostomy tube placement. In a retrospective analysis of 424 cholecystostomy tube patients published in 2017, Boules et al. reported that it was at the attending surgeon’s discretion whether a patient was considered a high-risk surgical candidate; review of the data identified six risk factors driving cholecystostomy tube placement: (1) cardiac surgery within 2 months of symptom onset, (2) pulmonary infection, (3) end-stage liver disease (ESLD) with cirrhosis, (4) new diagnosis of pulmonary embolism (PE), (5) use of systemic anticoagulation, and (6) hemodynamic instability. Other retrospective reviews have reported cholecystostomy tube indications such as terminal stage IV cancer and coronary artery disease.

The 2018 Tokyo Guidelines (TG18) attempted to further define high-risk patients for early operative intervention by including the Charlson Comorbidity Index (CCI) and American Society of Anesthesiologists’ (ASA) Physical Status Classification System. In addition, the TG18 guidelines established predictive factors that have been associated with increased surgical mortality risk on multivariate analyses, including jaundice (total bilirubin ≥2 mg/dL) with coexisting neurologic dysfunction or respiratory dysfunction.

• 1

  For grade II cholecystitis, TG18 recommends cholecystostomy tube placement in patients with CCI ≥ 6 and/or ASA class ≥ III, as well as local inflammation resistant to systemic antibiotic therapy.

• 2

  For grade III cholecystitis, TG18 recommends cholecystostomy tube placement in patients who, (1) fail supportive care with antibiotics, (2) are jaundiced and have neurologic or respiratory dysfunction, and (3) have organ system failure not rapidly reversible with therapy. However, even when antibiotics and supportive care are effective, as well as when cardiovascular and/or renal organ system failure are reversed in grade III disease, a cholecystostomy tube is still recommended if the patient has a poor performance status (CCI > 4 and/or ASA class ≥ III) (see Fig. 2 ).

ROLE OF CHOLECYSTOSTOMY TUBE PLACEMENT IN COVID-19 PATIENTS

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 pandemic has had a major impact on emergent and elective surgical services. Half of patients with perioperative SARS-CoV-2 infection develop pulmonary complications, which are associated with high mortality. In addition, multicenter studies have shown that COVID-19 is associated with an increased risk for serious perioperative morbidity and mortality. Moreover, a substantial number of patients with COVID-19 are not identified until after surgery.

At the start of the pandemic, the American College of Surgeons recommended nonoperative management of surgical diseases, including cholecystitis, when possible, for patients who had confirmed or suspected SARS-CoV-2 infection. Because of the morbidity and mortality risks associated with SARS-CoV-2 infection, the possibility of transmission to hospital staff, and resource shortages caused by the pandemic, many centers transitioned to conservative and nonoperative management of acute cholecystitis. Published data for treatment of SARS-CoV-2–positive patients with acute cholecystitis comes from only a few single-institution retrospective studies. Although based on limited data, some studies suggest that percutaneous cholecystostomy is safe and effective compared with laparoscopic cholecystectomy in the setting SARS-CoV-2 infection. However, other studies have raised concerns about this approach, with approximately 35% of patients who underwent cholecystostomy tube placement experiencing a complication and up to 43% requiring readmission. Thus, each treatment recommendation must be thoroughly discussed with patients with COVID-19 and their other comorbidities in mind.

APPROACHES TO CHOLECYSTOSTOMY TUBE PLACEMENT

The majority of cholecystectomy tubes are placed via a percutaneous approach. However, these tubes can also be surgically placed via an open or laparoscopic approach. Success rates of tube placement exceed 90% in most studies.

Percutaneous Approach

Percutaneous cholecystostomy is most often performed by interventional radiologists but can also be placed by a surgeon trained in the procedure. After localization by computed tomography (CT) or ultrasound ( Figs. 3 and 4 ), the gallbladder is accessed percutaneously with radiologic guidance via either a transhepatic or transperitoneal approach. Traditionally, the transhepatic approach is preferred to prevent bile spillage or bile leakage, especially in the setting of severe cholecystitis and a potentially necrotic gallbladder wall. In practice, however, there is the possibility of hepatic abscess and transient bacteremia with the transhepatic approach because of the direct connection with hepatic sinusoids. The transperitoneal approach is an alternative method that works best when the gallbladder wall is extremely inflamed and thickened because it is more likely to seal and more likely to tolerate a coiling wire without rupturing.

Under image guidance, a long, hollow Yeah sheathed needle is placed through the liver and into the gallbladder until bile is aspirated ( Fig. 3C,D ). In many cases, the cystic duct is obstructed, and this fluid will be clear secondary to resultant hydrops. Once the gallbladder is accessed, a wire (short 75-cm Amplatz or Rosen curved tip wire) is placed through the needle and into the gallbladder lumen ( Fig. 3C,D ). A dilator is placed over the wire, and an 8-Fr pigtail catheter is then advanced and coiled in the gallbladder lumen using the Seldinger technique ( Fig. 3E and Fig. 4D–F ). At the end of the procedure, CT and/or ultrasound should be utilized to confirm the proper position of the drainage tube ( Fig. 4D–F ). The catheter is then secured to the skin by a suture or proprietary adhesive device.

COMPLICATIONS OF CHOLECYSTOSTOMY TUBE PLACEMENT

Although cholecystectomy tube placement is often not difficult and allows for poor surgical candidates to avoid an operation, both immediate and long-term complications can occur. Data on complications are largely derived from single-institution retrospective studies.

LONG-TERM MANAGEMENT OF CHOLECYSTOSTOMY TUBES

The management of cholecystostomy tubes after initial treatment remains somewhat controversial. There are no broadly accepted guidelines regarding definitive tube management. Across studies, 5% to 63% of patients eventually undergo definitive cholecystectomy, but this is not well defined. However, the TG18 recommends delayed cholecystectomy after tube placement, regardless of initial grade of the cholecystitis. In the literature, several authors have proposed different algorithms for the management of cholecystostomy tubes, many of which involve cholangiography to assess the patency of the cystic duct and biliary tree. In a study by Cha and colleagues, patients underwent a cholangiogram through the cholecystostomy tube to evaluate for patency of the cystic duct and biliary tract once the patient’s symptoms and clinical status improved. This was done during the index hospitalization. If patency was demonstrated via contrast emptying into the duodenum, the catheter was clamped. If patients developed recurrent cholecystitis after clamping, worsening laboratory values (e.g., leukocytosis, hyperbilirubinemia, transaminitis), or worsening symptoms, the catheter was placed back to external drainage for 7 days, after which patients were reassessed. If the patient tolerated clamping and had continued clinical improvement, the cholecystostomy tube was removed during the initial admission. If the cystic duct was not patent, patients were discharged with the cholecystostomy tube placed to an external drainage bag. Zarour and colleagues reviewed outcomes of 119 patients who underwent cholecystostomy tube placement for acute cholecystitis. In their study, all patients who underwent tube placement were discharged with the tube in place and draining externally. Follow-up cholangiogram was performed 2 to 3 weeks later; if the duct was patent and the patient was deemed an appropriate surgical candidate, the tube was clamped and left in place, and the patient subsequently underwent interval cholecystectomy. In patients who were not deemed fit but had biliary tract patency, the tube was removed.

In the absence of prospective data, (1) the duration of recommended tube drainage, (2) the need for definitive cholecystectomy, (3) the timing of tube removal, and (4) the timing of cholecystectomy remain topics of debate. The reported median length of time that the tube remained varies widely in the literature and depends on whether definitive cholecystectomy was performed. Times ranged from 10 days in those who eventually underwent cholecystectomy to 70 days in patients who did not undergo definitive treatment with cholecystectomy. Most studies recommend drainage for 3 to 6 weeks because this allows a tract to develop. Others recommend earlier removal and early definitive cholecystectomy. In contrast, separate studies recommend a longer period of tube drainage in patients with uncontrolled diabetes, persistent infection, malnutrition, and/or those on steroids because these conditions may hinder the healing process.

Ultimately, tube removal is dependent on resolution of the patient’s symptoms, the presence or absence of cystic duct obstruction, and whether the patient is a candidate for cholecystectomy. This is determined on a case-by-case basis through evaluation of laboratory values, abdominal examination, and the patient’s report of resolved abdominal pain.

In our opinion, if the patient’s acute cholecystitis has resolved and he or she is a candidate for cholecystectomy, tube evaluation is not necessary. Cholecystectomy should be scheduled, and the tube should be left in situ and draining externally until the operation is performed. This can be done laparoscopically or open, though conversion rates in this setting are higher than normal and should not be unexpected. If the patient’s clinical status improves and he or she is not a candidate for cholecystectomy, the patient should undergo a tube cholangiogram, and tube removal should only be considered if there is patency of the patient’s cystic duct. This is because the likelihood of recurrent episodes of cholecystitis is extremely high if the cystic duct remains obstructed. The timeline in which a cholangiogram is done in these patients varies in the literature, but we recommend 3 to 6 weeks to allow for a track to form before tube removal. If a cholangiogram demonstrates a patent cystic duct, the next step is clamping of the cholecystostomy tube, with removal in the absence of recurring symptoms after clamping. It is important to note that the criterion of cystic duct patency does not necessarily apply to patients with acalculous cholecystitis as the pathophysiology is different from calculous cholecystitis. But patients should at least undergo clamping trials before removal to reduce the risk of having recurrent symptoms after tube removal that may lead to an additional procedure.

DEFINITIVE TREATMENT WITH CHOLECYSTECTOMY

Cholecystectomy remains the only definitive treatment for patients with acute cholecystitis. In individuals who undergo cholecystostomy tube placement, the TG18 recommend delayed-interval cholecystectomy after tube placement (see Figs. 1 and 2 ), except for patients with initial grade III disease, poor performance status, and limited predicted life expectancy. These recommendations apply to calculous cholecystitis, but other reports on patients with acalculous cholecystitis agree that cholecystectomy may not be necessary. The recurrence of acute cholecystitis in those who do not undergo definitive therapy ranges from 11% to 41%. Therefore, definitive therapy should be considered if the patient’s clinical status allows.

Despite the recommendation for cholecystectomy in the Tokyo guidelines, cholecystectomy rates vary widely, with 15% to 80% of patients undergoing cholecystectomy after cholecystostomy tube placement across many retrospective series. Ideally, cholecystectomy should be performed in the elective setting after the patient’s clinical status has improved. Cholecystectomy may be needed more urgently if cholecystostomy tube placement fails to control local inflammation and systemic sepsis or if inflammation recurs acutely. However, data from Medicare beneficiaries undergoing cholecystostomy tube placement for grade III cholecystitis demonstrate that only one-third of these patients undergo definitive treatment with a delayed cholecystectomy.

The timing for delayed cholecystectomy is also a topic of deliberation. In a study by Hung et al., there is some evidence that optimal timing for laparoscopic cholecystectomy is 9 to 10 weeks after placement of a cholecystostomy tube. In another retrospective study by Woodward et al., increased complications occurred when interval cholecystectomy was performed less than 1 month after cholecystostomy tube placement. However, patients with tubes in place for greater than 8 weeks demonstrated higher rates of tube-related complications, leading the authors to suggest that the most favorable timing for interval cholecystectomy is between 4 and 8 weeks after cholecystostomy tube placement. A retrospective analysis of the New York SPARCS database involving 9728 patients suggested that early cholecystectomy (≤8 weeks after cholecystostomy tube placement) was associated with a higher risk of complications and longer hospital length of stay. Ultimately, the timing of delayed cholecystectomy should be delayed at least 4 to 6 weeks after tube insertion, but there are no prospective analyses to determine this timing.

PROPOSED ALGORITHM FOR CHOLECYSTOSTOMY TUBE PLACEMENT AND MANAGEMENT

The proper use of cholecystostomy tubes includes temporary treatment for patients with calculous or acalculous cholecystitis who cannot tolerate surgery according to the TG18 guidelines. The severity of cholecystitis and the duration of symptoms are not absolute contraindications for cholecystectomy, and they do not mandate cholecystostomy tube placement in isolation. Potential reasons for a patient’s inability to tolerate surgery include severe systemic disease, including cardiovascular disease, underlying terminal malignancy, and/or any condition that precludes general anesthesia.

The TG18 algorithm for management of patients with acute cholecystitis (see Fig. 2 ) notes that initial evaluation should include assessment of the patient’s clinical status and the severity of the gallbladder disease. If patients are hemodynamically stable and able to tolerate a general anesthetic, cholecystectomy should be performed as soon as possible during the index admission, regardless of the Tokyo grade. Cholecystostomy tubes should be reserved for patients who are not candidates for cholecystectomy because of underlying comorbidity and/or physiologic decompensation resulting from acute illness and for those who do not rapidly respond to antibiotics and supportive care. In cases of grade III disease, if a patient improves with antibiotics and organ support, reevaluation should be undertaken during the index hospitalization for possible cholecystectomy. If not performed on the index admission, then delayed or elective cholecystectomy should be performed in patients who have a life expectancy of greater than 1 year as cholecystitis recurrence rates are high. As with all interventions, surgeons must consider the risks and benefits of this procedure and its long-term consequences with each individual patient in mind.

EPIDEMIOLOGY

The true incidence of CBDS in the general population is poorly known, as most cases are asymptomatic. CBDS are present in 10% to 15% of patients undergoing evaluation for cholelithiasis and are identified in 10% to 12% of intraoperative cholangiograms (IOC) when performed routinely during cholecystectomy (CCY). Similarly, the incidence of CBDS is approximately 10% to 20% in patients undergoing CCY for symptomatic cholelithiasis or acute cholecystitis.

PATHOPHYSIOLOGY AND PRESENTATION

Classification of CBDS by their point of origin is important for understanding their recurrence. The majority of CBDS in the Western population are secondary stones originating in the gallbladder and indicate the need for CCY to prevent recurrence. Primary CBDS, by contrast, form in bile ducts and are more common in Asian populations and patients with abnormal ducts. Primary CBDS recur after endoscopic CBD clearance in 4% to 24% of patients, and subsequent CCY may, in fact, increase risk of CBDS recurrence in Asian populations, possibly by increasing CBD stasis in the absence of periodic flushing of the CBD from gallbladder contractions.

Symptomatic CBDS typically present with episodes of epigastric or right upper quadrant (RUQ) abdominal pain. CBDS may cause biliary obstruction and subsequent jaundice, typically with pain, unlike neoplastic causes of jaundice. As intraductal pressure increases, disruption of epithelial tight junctions leads to cholangiovenous reflux as bacteria or endotoxins translocate from the biliary to the vascular system. Obstruction resolves with stone passage into the duodenum in more than half of patients but may lead to ascending cholangitis with Charcot’s triad of fever, RUQ pain, and jaundice in 15% to 20% of patients or even progress to septic shock with altered mental status, comprising Reynold’s pentad, and requiring emergent biliary decompression. In addition, biliopancreatic reflux from impacted distal CBDS or ampullary edema from passing CBDS is a cause of 30% to 50% of cases of acute pancreatitis.

DIAGNOSIS

The initial evaluation of patients with suspected symptomatic cholelithiasis, acute pancreatitis, or cholangitis includes transabdominal ultrasound (TAUS) and a liver panel, but the accuracy of TAUS and a liver panel for the diagnosis of asymptomatic CBDS is low. Factors associated with CBDS include clinical symptoms of cholangitis, dilation of the cystic and CBDs, and elevated serum bilirubin, alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). A patient with several of these factors has a high pretest probability for CBDS ( Fig. 1 ) and warrants preoperative ERCP or preparedness for intraoperative management with IOC and/or CBDE. A patient with none of these factors and no CBDS seen on imaging has a very low probability of CBDS and can proceed simply to CCY. Patients with intermediate CBDS probability require additional imaging (e.g., magnetic resonance cholangiopancreatography [MRCP] or endoscopic ultrasound EUS]) or IOC/IOUS during CCY. The sensitivity and specificity of common diagnostic tests for CBDS are listed in Table 1 .

MANAGEMENT

Surgical CBD Clearance

Surgical clearance of CBDS and CCY may also be done with a single- or two-stage approach. Single-stage CBD clearance (CCY + CDBE) offers shorter length of hospitalization and is likely cost-effective, while sharing similar morbidity and mortality with the two-stage approach (isolated CCY with pre- or post-CCY ERCP). The choice is up to the surgeon and based on available resources, expertise, and logistics. A minimally invasive surgery CBDE (MIS-CBDE) shares the same contraindications as any other MIS. CDBE should be avoided in patients with a small (<3 mm) CBD. Additionally, the single-stage approach is contraindicated in patients with suspected malignant process, unless appropriate staging workup has been completed, the case has been discussed in a multidisciplinary tumor-board setting, and the surgeon is prepared for an oncologically sound operation. Otherwise, patients should be referred to a surgeon with the relevant expertise.

Equipment and materials used for IOC/IOUS/MIS-CDBE include a fluoroscopy-compatible operating table, a fluoroscopic system, 3- to 5-Fr cholangiocatheters, Olson or Kumar or similar cholangiography clamps, water-soluble contrast, a hydrophilic 0.035” guidewire, 8-mm × 40-mm over-the-wire dilation balloon with high-pressure inflation capability, nitinol wire basket, Fogarty balloon catheters, and a choledochoscope (pediatric ureteroscopes and disposable bronchoscopes work well). Depending on available expertise, mechanical, electrohydraulic, or laser lithotripsy may be used for fragmentation of large CBDS.

Intraoperative Imaging

IOC or IOUS is a key step in any patient undergoing CCY and suspected of having CBDS at the time of operation. IOC is particularly useful as part of an MIS-CDBE ( Fig. 2 ). IOUS compares favorably to IOC but is best done before dissection, as dissection may obscure otherwise clear sonographic windows. After obtaining a critical view of safety, IOC may be done via the gallbladder, the CD, or, as a last resort, the CBD. Commonly, the CD is dissected, a locking clamp placed on the gallbladder for retraction, and another locking clamp or clip is placed on the CD cholecystad to the planned ductotomy to prevent filling of the gallbladder with contrast. A transverse 1- to 2-mm ductotomy is performed, and stones and debris are milked from the duct. A cholangiocatheter is passed through midclavicular port or via a 14- to 16-gauge, transabdominal, sheath trocar placed in the RUQ, and secured, ideally with an Olson or Kumar clamp, to the ductotomy. Digital subtraction on the C-arm and holding respirations may both improve image quality. A live, real-time (as opposed to still-image) cholangiogram is ideal. Contrast may be used full-strength, or, more commonly, diluted 50/50 in saline, as full-strength contrast is more likely to obscure small filling defects. The number and size of filling defects should be noted (the 5-mm diameter of the cholangiogram clamp may be used as a size reference). Smaller (≤3 mm) stones have a higher chance of being flushed into the duodenum, which is facilitated by administration of 1 mg to 2 mg intravenous glucagon to relax the sphincter of Oddi. Once the location, number, and size of stones, as well as CBD diameter, are determined, an optimal treatment strategy may be selected. To confirm the biliary tree free of stones by IOC, it is essential to visualize contrast opacification of both the duodenum and the intrahepatic biliary tree, both right and left sides.

Minimally Invasive Surgery CBDE

MIS-CBDE may be performed transcystic and transcholedochal. The transcystic approach is a reasonable initial choice, particularly with a large (>5 mm) nontortuous CD, a lateral insertion into the CBD, and small CBDS. The transcystic approach is contraindicated with multiple (>5–8) or large (>∼7 mm) stones or stones hepatad of the CD insertion to the CBD.

Transcystic Approach

In patients with a long and tortuous CD, a ductotomy closer to the CD–CBD junction may be made with care. If CBDS cannot be cleared during IOC by flushing, then MIS-CDBE may proceed by fluoroscopically advancing a soft-tipped, 0.035”, hydrophilic guidewire through the CD, the CBD, and well into the duodenum. The introduction catheter is removed and exchanged over the wire for a 12-Fr introducer sheath to provide better support and facilitate instrument exchange.

The CD is dilated to facilitate passage of instruments through the spiral valves and extraction of stones ( Fig. 3 ). This may be performed with an 8-mm × 40-mm (5-Fr), over-the-wire, dilation balloon filled with half-strength contrast under fluoroscopy, over 2 to 3 minutes, using an inflation device. Care should be taken to not overdilate the CD.

Stone clearance can be achieved by nitinol baskets or Fogarty-balloon catheters. The basket is passed collapsed beyond the target stones, deployed, and slowly withdrawn ( Fig. 4 ). Baskets, as opposed to balloon catheters, are less prone to cause inadvertent migration of CBD stones proximally into the common hepatic duct. It is important to advance and withdraw instruments along the CBD axis. If available, a flexible choledochoscope (see earlier) may be used for direct visualization of CBD and controlled retrieval of stones. The choledochoscope should ideally have video with an integrated light source and picture-in-picture capabilities. With available expertise and equipment, MIS-CDBE may be coupled with mechanical, electrohydraulic, or laser lithotripsy. An endoscopic retrieval bag and/or gauze sponge close to the ductotomy may facilitate collection of debris.

After a satisfactory completion IOC, the CD is transected and closed, preferably with an endoscopic loop. If a transcystic approach fails to achieve CBD clearance or is otherwise inappropriate, the surgeon may proceed with a transcholedochal MIS-CBDE, convert into open CBDE (OCBDE), or plan for postoperative ERCP or PTBD.

Transcholedochal Approach

Unlike a transcystic CBDE, transcholedochal CBDE provides access to both the CBD and the hepatic ducts. However, transcholedochal CDBE is associated with a higher risk of biliary strictures and postoperative bile leaks, and is contraindicated when CBD diameter is <7 mm and with hostile porta hepatis, as may occur with severe inflammation.

After exposing the anterior surface of the CBD, a ∼10-mm, longitudinal choledochotomy is made sharply. Fine-needle aspiration or indocyanine green cholangiography may be done to confirm the identity of the CBD if needed. Stay sutures on either side of the choledochotomy are useful to elevate the duct and maintain easy access to the ductotomy but are not used by all surgeons. The CBD is flushed via a cholangiocatheter, and stones are evacuated with a grasper, if possible. If not, CBDS may be retrieved with baskets and balloon catheters.

The choledochotomy is closed longitudinally with interrupted or running fine (4-0 or 5-0), absorbable suture on a tapered needle. An additional 5-mm port may be placed in the right-to-midabdomen to facilitate choledochotomy closure. Historically, it was standard practice to close the choledochotomy over a T-tube, which allows sustained access to the biliary tree, reliable decompression, and stenting of the CBD to possibly reduce risk of stricture. However, recent literature has supported primary closure instead, which has the advantage of avoiding tube-related discomfort and complications, with apparently similarly favorable outcomes. If a T-tube is left ( Fig. 5 ), it should fit loosely, not snugly, and the ductotomy should be closed hepatad of the tube to prevent tension on the suture line upon removal. The T-tube should remain for at least 3 weeks to allow maturation of the tract, to avoid bile leakage upon removal, after a normal tube cholangiogram. Typically, with or without a T-tube, a closed-suction drain is left near, but not touching, the ductotomy and removed after a few days if no bile is present in the drain. Before closure, a completion IOC should be performed.

Because papillary edema is not uncommon after MIS-CDBE, some surgeons prefer to leave a plastic biliary stent across the ampulla before choledochotomy closure to assure decompressed biliary tree and to decrease risk of postoperative bile leak from the choledochotomy.

Open CBDE

The proportion of patients with CBDS managed with OCBDE has decreased over the last decade from 30% to 5%. OCBDE is now performed mainly when less invasive techniques have failed or are not available. OCBDE may also be performed for patients with significant inflammation in Calot’s triangle or the porta or when the patient requires open CCY for other reasons. The CBD diameter for OCBDE should be >5 mm, and it is contraindicated if the CBD diameter is ≤3 mm.

The abdomen is entered through an upper midline or right subcostal incision, and the liver is retracted superiorly. An IOC should be performed before CBDE. After IOC and characterization of the CBD and contents, the duodenum is Kocherized and all portions of CBD are gently palpated. IOUS may be useful to identify CBDS. Stay sutures are placed and a stab choledochotomy is made between them with an #11 blade at the level of cystic duct insertion, slightly to the left of the longitudinal CBD midplane. Once the direction of CBD is determined by gentle probing, the choledochotomy is extended to ∼15 mm with Potts scissors. The stay sutures are retracted, and CBDS are gently milked or flushed out through the ductotomy. Fogarty balloons and Randall stone forceps are useful to sweep or grasp stones, respectively, in either direction, but care should be taken not to mistake the hepatic duct confluence for CBDS when using forceps. If a balloon is used, it should be passed through the ampulla and seen or palpated in the duodenum, at which point it should be inflated, pulled back until apposed to the ampulla, deflated enough to traverse the ampulla, then reinflated and withdrawn to extract stones and sludge. Evaluation by choledochoscopy is recommended. A completion cholangiogram or choledochoscopy should be obtained. Similar to MIS-CDBE, in OCBDE the ductotomy can be primarily closed with or without transpapillary temporary stent or closed over a T-tube.

Severely impacted stones are best managed with fragmentation by lithotripsy guided by choledochoscopy. If lithotripsy is not available, a biliary stent can be placed across the papilla or the CBD drained via T-tube and the patient transferred to a center with available expertise. Procedures such as transduodenal sphincteroplasty have been used for distally impacted CBDS but are rarely performed currently.

INTRODUCTION

Acute cholangitis is a clinical syndrome first described by Jean-Martin Charcot in 1877 characterized by abdominal pain, fever, and jaundice from stasis and infection in the biliary tract. In 2006, the Tokyo International Consensus Meeting consolidated literature about acute cholangitis into evidence-based guidelines, which were most recently updated in 2018.

EPIDEMIOLOGY

Acute cholangitis most commonly occurs in the fifth through seventh decades of life with equal prevalence in men and women. The most common causes of acute cholangitis include choledocholithiasis (40%–70%), malignancy (10%–60%), or benign stricturing (5%–30%). Cholangitis can also occur after instrumentation from either endoscopic retrograde cholangiopancreatography (ERCP) (1%–7%) or placement of biliary stents and indwelling biliary drains.

PATHOPHYSIOLOGY

The primary issue in acute cholangitis is obstruction of the common bile duct. Under physiologic conditions, bile remains sterile due to continuous flow, secretion of immunoglobulin A in the biliary tree, and the presence of bacteriostatic bile salts. In addition, the sphincter of Oddi acts as a barrier against ascending infection from duodenal reflux. The causes of acute cholangitis can therefore be conceptualized as related to stasis from biliary obstruction or to direct seeding of the biliary tree ( Table 1 ).

In the setting of acute inflammation, increased biliary pressure causes increased permeability of biliary ductules and translocation of bacteria from the portal venous system into the biliary tract. As a result, infection in acute cholangitis is typically polymicrobial and most commonly includes gram-negative rods of colonic origin. The most common bacteria identified in biliary cultures are Escherichia coli (25%–50%), Klebsiella (10%–20%), Enterococcus (10%–30%), and Enterobacter (5%–10%). Anaerobes such as Bacteroides and Clostridia are more commonly seen in patients with recurrent infections or biliary instrumentation.

The underlying permeability of the biliary system facilitates bacterial translocation from the biliary tract to the portal and systemic venous systems, leading to sepsis in severe cases.

DIAGNOSTIC WORKUP

Imaging Studies

The initial imaging study of choice is an abdominal ultrasound to evaluate for biliary dilation, cholelithiasis, or gallbladder sludge ( Fig. 1 ). Ultrasound is 40% sensitive but nearly 100% specific for acute cholangitis with findings of common bile duct dilation and choledocholithiasis. Although ultrasound is noninvasive, expedient, and easily accessible, it remains highly operator-dependent. Ultrasound also has difficulty detecting small stones and often results in false-negative reads in the setting of acute obstruction before the bile ducts dilate.

An abdominal CT scan is very effective in identifying the presence of biliary dilation or stenosis and the location of biliary obstruction, as well as local sequelae like liver abscess and portal vein thrombosis. However, it has low sensitivity for detecting choledocholithiasis and exposes the patient to radiation.

Magnetic resonance cholangiopancreatography (MRCP) is the best noninvasive imaging modality for identifying causes of biliary obstruction, characterizing biliary strictures, and detecting choledocholithiasis. MRCP is 90% sensitive and 95% specific in detection of choledocholithiasis, although its sensitivity decreases significantly with small stones <6 mm. As a result, it is increasingly becoming the imaging of choice when available. However, it is an expensive test and requires additional expertise for interpretation. Given its limited accessibility, routine use of MRCP is not universally recommended unless diagnosis is difficult despite abdominal ultrasound and CT.

Endoscopic ultrasound (EUS) is better able to identify bile duct stones and characterize the level of obstruction along the biliary tree. Given its invasive nature, it is only used for workup of cholangitis patients who are high risk for ERCP and cannot undergo MRCP.