Asymptomatic Gallstones

Surprisingly, most patients with gallstones, about 65% to 80%, are asymptomatic (see Chapter 30). Studies of the natural history of silent gallstones have shown that symptoms develop in 1% to 2% of patients per year. Among patients with asymptomatic gallstones, about 10% develop symptoms in 5 years, and about 20% develop symptoms by 20 years. Additionally, most patients experience symptoms for some time before they develop a complication (National Institutes of Health [NIH] Consensus Statement Online, 1992; Stewart et al, 1989; Festi et al, 2010; McSherry et al, 1985). So, the majority of patients with asymptomatic gallstones can be observed, and surgical intervention (laparoscopic cholecystectomy) can be offered if symptoms develop.

Surgical treatment of asymptomatic gallstones is indicated in a number of patient populations for whom prophylactic cholecystectomy was once recommended. These populations comprise transplant patients and those with diabetes mellitus, chronic liver disease, sickle cell anemia or other chronic hemolytic anemia, patients undergoing bariatric or other gastrointestinal operations, and those with a potentially increased risk of gallbladder carcinoma (Table 37.1).

Table 37.1 Management of Asymptomatic Gallstones

Prophylactic cholecystectomy for asymptomatic cholelithiasis was previously recommended for patients with diabetes mellitus. Studies in the late 1960s reported a higher mortality following emergency cholecystectomy in diabetic patients. Subsequent meta-analysis revealed that diabetes was not an independent variable; instead, cardiovascular, peripheral vascular, cerebrovascular, or prerenal azotemia were associated with more severe acute cholecystitis (Stewart et al, 1989; Hickman et al, 1988). More recent series have shown similar complication rates for acute cholecystectomy among diabetic and nondiabetic patients. Diabetic patients with asymptomatic gallstones today are managed expectantly.

The incidence of gallstones is twice as high in patients with chronic liver disease. Most of these patients remain asymptomatic. Operative morbidity and mortality rates for patients with chronic liver disease are also significantly higher. Meta-analyses report no increase in mortality in asymptomatic patients with an expectant management approach (Stewart et al, 1989; NIH Consensus Statement Online, 1992).

Patients undergoing bariatric surgery have a higher incidence of cholelithiasis, because obesity is associated with cholelithiasis, and gallstones may form during rapid weight loss. Studies report a cholelithiasis incidence of 27% to 35% before bariatric operations and a 28% to 71% increase in gallstone formation following bariatric surgery (Wudel et al, 2002). Many surgeons utilize bile salt medications during periods of rapid weight to help prevent cholesterol gallstones. But even if gallstones form, most are asymptomatic, and elective cholecystectomy is safe for symptomatic disease (NIH Consensus Statement Online, 1992).

Several factors must be considered for potential transplant patients with asymptomatic cholelithiasis: cholelithiasis is common, immunosuppression may increase infectious morbidity, and morbidity and mortality may be increased with emergency surgery. This problem was examined with a recent decision analysis, using probabilities and outcomes derived from a pooled analysis of published studies (Kao et al, 2005). The authors recommended prophylactic posttransplantation cholecystectomy for cardiac transplant recipients with asymptomatic cholelithiasis. For pancreas and kidney transplant patients with asymptomatic cholelithiasis, however, expectant management was recommended.

Asymptomatic gallstones found at another gastrointestinal operation should generally be removed if exposure is adequate, if the cholecystectomy can be done safely. Studies of expectant management for patients with asymptomatic gallstones undergoing laparotomy for other conditions have shown a high (up to 70%) incidence of symptoms and/or complications from the biliary system, and a significant percentage (up to 40%) of patients require a cholecystectomy within 1 year of the initial operation. Further, no increase in morbidity is associated with concomitant cholecystectomy (Stewart et al, 1989; Klaus et al, 2002).

The management of patients with asymptomatic gallstones undergoing abdominal aortic aneurysm (AAA) repair has recently evolved, especially with the advent of endovascular aortic procedures. In the past, when AAA repair and cholecystectomy were open operations, concomitant cholecystectomy was recommended to prevent the higher morbidity associated with the development of acute cholecystitis in the postoperative period. Studies reported no increase in graft infection or morbidity when cholecystectomy was done following closure of the retroperitoneum; however, more recent data show similar mortality rates with or without concomitant cholecystectomy. Today, laparoscopic cholecystectomy is typically performed after endovascular AAA repair, without increased morbidity (Cadot et al, 2002).

Children with asymptomatic gallstones comprise two main etiologic groups: those with hemolytic anemia (sickle cell disease, β-thalassemia, hemoglobinopathies) and those whose cholelithiasis stems from some other cause (total parenteral nutrition, short bowel syndrome, cardiac surgery, leukemia, lymphoma). Expectant management for children with hemolytic anemia is associated with a significant increase in morbidity and postoperative hospital stay, so elective cholecystectomy is recommended (Curro et al, 2007). For patients with sickle cell disease and asymptomatic gallstones, elective cholecystectomy is advised, because expectant management yields more than a twofold increase in morbidity. Further, the diagnosis of acute cholecystitis can be difficult to differentiate from acute vasoocclusive sickle cell crisis (Curro et al, 2007). In contrast, children with asymptomatic gallstones caused by other etiologies can be safely managed expectantly. These gallstones even regress in 17% to 34% of cases.

Finally, gallstones have a proven association with gallbladder carcinoma (Tewari, 2006; see Chapter 49). In a review of 200 consecutive calculous cholecystitis specimens, Albores-Saavedra and colleagues (1980) reported that 83% exhibited epithelial hyperplasia, 13.5% atypical hyperplasia, and 3.5% carcinoma in situ. The risk of gallbladder carcinoma increases with larger gallstones: the relative risk rises from 2.4 for stones 2 to 2.9 cm in diameter to 10 for gallstones larger than 3 cm. Native Americans and patients with gallbladder calcification also have a higher incidence of gallbladder cancer. Elective cholecystectomy has been recommended in patients with gallstones greater than 3 cm in diameter, but no proof is available to support that such an approach is warranted from an oncologic standpoint.

Symptomatic Gallstones

Approximately 30% of patients with gallstones develop symptoms. Cholecystectomy is indicated to relieve suffering and to prevent complications of gallstones. The spectrum of severity characterizing symptomatic gallstones ranges from episodic pain to life-threatening infection and shock.

Cholecystitis

Acute cholecystitis occurs in about 20% of patients with symptomatic gallstones (see Chapter 31). The pathogenesis is prolonged calculous obstruction of the cystic duct with resulting inflammation. The inflamed gallbladder becomes dilated and edematous, manifested by wall thickening, and an exudate of pericholecystic fluid can develop. If the gallstones are sterile, the inflammation is initially sterile, which can occur in patients with cholesterol gallstones. In other cases, however, gallstone formation occurs as a result of bacterial colonization of the biliary tree, rendering pigmented gallstones containing bacterial microcolonies (Stewart et al, 2002). In these cases, obstruction of the cystic duct results in a contained infection of the gallbladder. Research on the pathogenesis of gallstone-associated infections has shown that patients with bacteria-laden gallstones have more severe biliary infections. In addition, acute cholecystitis can coexist with choledocholithiasis, cholangitis, or gallstone pancreatitis. In the general population, 5% of patients presenting with cholecystitis have coexisting common bile duct stones. In the elderly, however, this figure rises to 10% to 20% (Siegel & Kasmin, 1997).

The initial treatment for patients with acute cholecystitis is intravenous hydration, antibiotics, and bowel rest. Many patients should be offered early cholecystectomy, but others will benefit from delayed intervention, either following conservative therapy or percutaneous gallbladder drainage. Several factors govern the approach to patients with acute cholecystitis. One consideration is patient comorbidity; emergency cholecystectomy in patients with significant comorbidities can be associated with high morbidity (20% to 30%) and mortality (6% to 30%) rates. Guidelines for the management of acute cholecystitis and acute cholangitis were described at an international consensus meeting held in Tokyo in 2006 (Takada et al, 2007). The Tokyo Guidelines define three levels of severity for acute cholecystitis and serve as a useful tool in the management of acute cholecystitis (Table 37.2).

Table 37.2 Tokyo Guidelines for Acute Cholecystitis

Grade	Criteria
I Mild	Acute cholecystitis that does not meet the criteria for a more severe gradeMild gallbladder inflammation, no organ dysfunction
II Moderate	The presence of one or more of the following:1.  Elevated while blood cell count (>18,000/mm3)2.  Palpable tender mass in the right upper abdominal quadrant3.  Duration of complaints >72 h4.  Marked local inflammation (biliary peritonitis, pericholecystic abscess, hepatic abscess, gangrenous cholecystitis, emphysematous cholecystitis)
III Severe	The presence of one or more of the following:1.  Cardiovascular system: hypotension requiring dopamine >5 µg/kg/min or any dose of dobutamine2.  Nervous system: decreased level of consciousness3.  Respiratory system: Pao2/Fio2 ratio <3004.  Renal system: serum creatinine >2.0 mg/dL5.  Liver: PT-INR >1.56.  Hematologic system: platelet count <100,000/mm3

PT-INR, prothrombin time/international normalized ratio

Grade I Acute Cholecystitis

Patients presenting with mild grade I acute cholecystitis should be offered early cholecystectomy, performed laparoscopically if possible; numerous studies document a high success rate for laparoscopic cholecystectomy when the procedure is performed within 48 to 96 hours of onset of acute cholecystitis (Hadad et al, 2007). Further, a Cochrane review of five randomized trials showed a shorter hospital stay for early cholecystectomy patients and no significant difference in complication rates or conversion rates between early laparoscopic cholecystectomy (within 7 days) versus delayed laparoscopic cholecystectomy (6 to 12 weeks; Gurusamy & Samraj, 2006). Conversion rates, however, were 45% among patients randomized to the delayed group, those who required a cholecystectomy between 1 and 6 weeks. For patients with significant medical problems, cholecystectomy may need to be delayed to maximize medical therapy. Most patients with acute cholecystitis can be safely managed with antibiotics and bowel rest with resolution of their acute illness; they can then undergo an elective cholecystectomy once their medical problems have been addressed.

Grade II Acute Cholecystitis

Patients presenting with grade II acute cholecystitis are a more diverse group. Many will be well managed with early cholecystectomy; this is particularly true for cases with delayed presentation as their only grade II finding. In these cases, laparoscopic cholecystectomy should be performed if possible within 7 days of the acute illness. In cases with severe local inflammation, early gallbladder drainage (percutaneous or surgical) is recommended as the initial treatment of choice, followed by elective cholecystectomy once the acute inflammation resolves. The key is to identify which patients have such an inflammatory process. Several studies have correlated such findings as age older than 50 years, male sex, presence of diabetes, elevated bilirubin level (>1.5 mg/dL), and leukocytosis (while blood cell count >15,000 mm³) in the setting of gangrenous cholecystitis (Nguyen et al, 2004). These findings are also frequently associated with a severe inflammatory process. Other factors suggestive of an inflammatory process include symptoms of gastric outlet obstruction. Patients with such symptoms should have cross-sectional imaging, with either computed tomography (CT) or magnetic resonance imaging (MRI), to determine whether a severe inflammatory process is present (Fig. 37.1), followed by percutaneous cholecystostomy if such is found (Takada et al, 2007).

FIGURE 37.1 Computed tomographic scan demonstrating a severe inflammatory process in the setting of acute cholecystitis. This patient was treated with percutaneous cholecystostomy followed by elective laparoscopic cholecystectomy once the inflammatory process had resolved.

Grade III Acute Cholecystitis

Patients presenting with grade III acute cholecystitis have associated organ dysfunction, and they require intensive organ support and medical treatment. Because the source of their inflammatory (septic) response and organ dysfunction is the severe cholecystitis, percutaneous cholecystostomy is necessary to treat the severe infection as well as the associated organ dysfunction. Numerous studies have documented the success of percutaneous cholecystostomy in achieving control of the underlying infection within 24 to 48 hours (Howard et al, 2009). In rare cases, urgent cholecystectomy may be required, such as cases with biliary peritonitis as a result of perforation of the gallbladder; but in general, cholecystectomy in the acute phase of grade III acute cholecystitis should be avoided (Takada et al, 2007).

Choosing Laparoscopic Versus Open Techniques

For typical uncomplicated gallstone disease, laparoscopic cholecystectomy is the preferred method of removing the gallbladder (Keus et al, 2006). Since its debut, cholecystectomy rates have increased worldwide, reflecting patient acceptance of the laparoscopic technique. Because the technical aspects of this operation are covered in other chapters (see Chapters 33 and 34), this section will focus on concepts of feasibility and safety that relate to disease severity and the choice between laparoscopic and open cholecystectomy (Callery, 2006).

Laparoscopic cholecystectomy should be performed only by surgeons properly trained and proctored, and experience should be correlated to how difficult the operation may be based on disease severity. Laparoscopic cholecystectomy for severe acute and chronic inflammation is considerably more difficult and is an advanced operation. Less experienced surgeons must recognize this and seek the help they need during the operation, and conversion to open cholecystectomy may be necessary in some patients (Ishizaki et al, 2006). Biliary injuries are more likely to occur during difficult laparoscopic operations, no different than with open operations, but at a higher incidence (see Chapter 42A, Chapter 42B ). When laparoscopic cholecystectomy is performed for acute cholecystitis, biliary injuries occur three times more often than during elective laparoscopic cases and twice as often compared with open cholecystectomy for acute cholecystitis.

Today, the selection of open cholecystectomy may be difficult for some. Over the past 20 years, open cholecystectomy has been far less frequently performed. Trainees during this period presumably have received valid instruction and proctoring for laparoscopic cholecystectomy but have less experience with difficult open cases (Schulman et al, 2007). The experience needed to command the laparoscopic operation potentially reduces the level of comfort with the open technique. Finally, there is the pressure related to patient expectation for rapid recovery.

Behind these two very different techniques are scenarios that might subtly account in part for static biliary injury rates (Khan et al, 2007). Because of inexperience, the surgeon ignores or resists the sensible default option to convert to the open technique, does not, and causes injury. In other instances, the surgeon overextends laparoscopic experience when disease severity warrants conversion. What can help prevent this? First, during informed consent, patients need to be made fully aware that open cholecystectomy is always a possibility. If faced with acute or chronic cholecystitis at operation, the surgeon should seek help rather than persist on marginal laparoscopic or open cholecystectomy experience. Conversion from laparoscopic to open cholecystectomy is not a defeat but rather is reflective of caution and good judgment (Jenkins et al, 2007; Wolf, 2009).

Ideally, a surgeon would suspect the likelihood of conversion on clinical grounds. The anesthesia and operative teams should be so notified and prepared. Open-case instruments need to be readily available, and trocar stab incisions should be placed along a predrawn right subcostal incision line. Unless there is need to control bleeding, the surgeon enters the RUQ deliberately and is not stressed by the decision to convert. Everyone should be ready for what lies ahead, and it should be clear to all that it will be a difficult operation.

The difficult open cholecystectomy demands adequate exposure, retraction, and identification of anatomy by dissection in the anterior and posterior aspects of the triangle of Calot, followed by dissection of the gallbladder off the liver bed. The surgeon achieves conclusive identification of the cystic structures as the only two structures entering the gallbladder, eliminating the possibility of misidentification (Callery, 2006). As with the laparoscopic technique, once the critical view is attained, the cystic structures can be occluded with ligatures and divided. Failure to achieve this critical view should prompt cholangiography to define ductal anatomy. Avoidance of ductal injury in the liver bed depends upon a combination of patience and staying in the correct plane of dissection, with meticulous technique and experience. In some cases of acute cholecystitis, the gallbladder “shells out” relatively easily from its edematous hepatic bed. In other cases, and especially in chronic cholecystitis, the dissection of the gallbladder out of the liver bed can be tedious, frustrating, and bloody. Hemostasis can take time but must be achieved, with argon beam, cautery, packing, and topical hemostatics if necessary. Subtotal cholecystectomy is always a valid option, especially in patients with cirrhosis or in those with severe inflammation that obscures the anatomy within the porta hepatis. Surgeons should indicate in operative notes for open and laparoscopic cholecystectomy precisely how they identified the cystic structures for division. For conversions, they should specify the circumstances, stressing safety and surgical judgment.

Percutaneous Cholecystostomy (See Chapter 32)