Asymptomatic gallstones are being increasingly diagnosed today, mainly as a result of the widespread use of ultrasonography for the evaluation of patients for unrelated or vague abdominal complaints. Gallstones are now prevalent all over the world and about 10-20% of the adult population has gallstones.[1] In India, out of 800 million adult population, approximately 15% (120 millions) have gallstones. Asymptomatic gallstone disease has a benign natural course; the progression of asymptomatic to symptomatic is relatively low with about 2% become symptomatic each year.[1] The majority of patients rarely develop gallstone related complications without first having at least one episode of biliary pain (colic). Most common symptoms are upper abdominal pain, biliary colic, and dyspepsia. Biliary colic is defined as ‘‘a steady right upper quadrant abdominal pain lasting for more than half an hour’’, which may be associated with radiation to the back and nausea and may force patients to stop their activities. Dyspepsia is defined as the presence of three or more of the following symptoms: belching, flatulence, nausea, intolerance to fatty food, bloating of the abdomen, epigastric discomfort, and acid regurgitation. The complications of gallstones include acute cholecystitis (including empyema, when the gallbladder is filled with pus), acute gallstone pancreatitis, obstructive jaundice, and rarely small bowel obstruction (gallstone ileus).

The distinction between symptomatic and asymptomatic gallstones can be difficult because symptoms can be mild and varied. The annual incidence of complications of gallstones in asymptomatic patients is 0.3% acute cholecystitis, 0.2% obstructive jaundice, 0.04% to 1.5% of acute pancreatitis and rarely gallstone ileus.[2] Moderate and severe complications of gallstones have higher morbidity and mortality rates (close to 1%). Laparoscopic cholecystectomy though now commonly performed has a risk of 0.2% biliary injury and 0.05% mortality.[3,4] In the pre-laparoscopic era, open cholecystectomy was generally performed for symptomatic disease. Minimally invasive laparoscopic cholecystectomy has refuelled the discussion about the optimal management of asymptomatic gallstones.

In a country like India, where the population is large (1200 million), the magnitude of the problem is huge. A Markov model was prepared to understand the scope of the problem. (Figure 1), (Table1). [ 2,5,6]

Asymptomatic gallstones – extent of the problem

Asymptomatic cholelithiasis refers to the condition when gallstones are detected in the absence of gallstone related symptoms such as biliary pain or gallstone-related complications. Though complications are easy to diagnose, differentiating vague dyspeptic symptoms from biliary pain is not very easy. Therefore there is over-diagnosis of symptomatic stones, consequently providing no relief to some of the patients who undergo surgery. However the fact that patients with such non-specific symptoms sometimes benefit from cholecystectomy indicates that cholelithiasis to a certain extent contributes to vague clinical picture.

Natural history of gallstones

“There is no innocent gall stone” – William Mayo 1904. “It is unfortunate that so few appreciate from what small causes diseases come” – Charles Mayo 1902.

Though this was the dictum 100 years ago, now there is enough evidence that most incidentally discovered, clinically silent gallstones rarely have clinical significance. Most patients live and die with their gallstones having never caused pain or other medical problems. A longitudinal follow up study of asymptomatic gallstones showed that over 20 year period only 18% of patients developed biliary pain and mean yearly probability of development of 2% during first 5 years, 1% during second 5 years, 0.5% during third 5 years.[7]

In summary most studies indicate that the progression of asymptomatic to symptomatic disease is relatively low. The major concern is the possible development of a severe potentially life threatening complication, such as severe pancreatitis or acute suppurative cholangitis. In majority of patients these complications develop without any preceding episode of biliary colic. From a practical point of view, it would be very important for both the patient and physician if it is recognized which sub group of asymptomatic patients will become symptomatic, but this is not easily possible. Some authors have tried to classify patients into two groups: low risk group and high-risk group.[8]

This study plans to use clinical decision analysis and published data to compare the clinical effectiveness and cost of management strategies for asymptomatic gallstones.

Clinical starting points

The analysis applies to patients who are diagnosed with gallstones that are detected in the absence of related symptoms such as biliary pain or complications such as acute cholecystitis, acute pancreatitis or bile duct complications. The study also examines other significant co-morbidities.

Clinical strategies

Controversies surrounding routine cholecystectomy for asymptomatic gallstones are far from resolved. Four clinical strategies were evaluated. These included 1) expectant treatment for all and surgery if needed; 2) routine prophylactic laparoscopic cholecystectomy for all; 3) selective cholecystectomy for patients with factors predicting severe outcome and expectant for rest; 4) concomitantly during another intraabdominal operation for an unrelated pathologic condition.

Risk ratios and life expectancy

To evaluate further, one can use risk ratio and life expectancy as differing analytical techniques.22 Risk ratio was defined as the probability of dying of gallbladder surgery or disease if “wait and see” approach was chosen, divided by the probability of dying of gallbladder surgery if “operate now” modality was chosen. Life expectancy difference was defined as the life expectancy if the “operate now” approach was chosen minus the life expectancy with “wait and see” approach. The findings are compiled in (Table 2). It is evident that with intermediate symptom incidence the risk ratio strongly favored “prophylactic cholecystectomy” while other incidences favor a “wait and see” approach. Kottke[22] also stated that risk ratio can project a course of action that is different from that predicted by life expectancy analysis. He concluded that risk ratio and life expectancy are inadequate for clinical decisions and do not capture all information necessary for informed decisions. In a vast country like India the incidence of gallstone disease varies a lot. While north India, Uttar Pradesh and Bihar have a high incidence, south Indian states record low incidence of this condition. The type of gallstone disease is also variable, diabetes is rising rapidly and incidence of carcinoma of gallbladder is high in some areas. This information impacts decision-making for operating silent gallstones in specific populations.

Predictors of symptom development/persistence

Festi et al5 evaluated different predictors of symptom development/persistence such as age, sex, presence of comorbidities (diabetes, liver cirrhosis, peptic ulcer and inflammatory bowel disease), family history and characteristics of both gallstones (number and size) and the gallbladder (function, morphology). In patients who developed symptoms, only the presence of gallstones >1.5 cm was predictive of change in the clinical picture (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.19–2.71), while increasing age was the only observed predictor of the persistence of symptoms in patients with a stable clinical picture (OR = 0.96, 95% CI 0.93– 0.99). None of the variables could reliably predict the appearance of complications except for the presence of diabetes in patients with mild symptoms (OR = 8.8, 95% CI 1.2–63.8, p<0.03). In particular no relationship was documented between gallstone size and the risk of developing complications.

The health care implications for state run medical institutions will be colossal if routine prophylactic cholecystectomy were to be practiced for all asymptomatic cases of cholelithiasis. Every patient who is diagnosed with gallstones whether symptomatic or asymptomatic, would require to be worked up and operated for the same. In private sector, though the load on the system would be tremendous, the monetary implications would be positive. In contrast, government sector resources allocated to health care would have to be moderately increased to accommodate the added burden since a laproscopic cholecystectomy costs around $50-70 for the patient. However the healthcare personnel and their efforts have to be taken into account in public sector institution since most of the burden of surgery is borne by the state. The exact details of this monetary burden on the national infrastructure cannot be assessed due to differential rates of admission to the hospitals and since the charges are not billed to the patient. But it can be safely assumed that the added expenditure accrued to the state funds will be sizeable enough to warrant strong evidence of patient benefit to mandate its implementation.

In consideration of the current financial state of Indian health care facilities it is evident that prophylactic cholecystectomy for all asymptomatic patients will incur a much higher cost to the patients and health care infrastructure is therefore not advisable as a routine management strategy for these asymptomatic patients (Table 3,4). Selective cholecystectomy is good option to reduce higher costs of acute complications.

Comments

Over the years the incidence of reported asymptomatic gallstones has increased due to better investigations and diagnostic facilities. In last two decades minimally invasive surgery has reduced the morbidity (though mortality remains unchanged) of routine cholecystectomy. While laproscopic surgery is a simple and effective alternative with several advantages over open cholecystectomy, it has also resulted in broadening the indications of cholecystectomy and decreasing the “surgical threshold” for instituting surgical management in patients of asymptomatic cholelithiasis. However laparoscopy is expensive in a private sector hospital for an average Indian. In view of these observations it is pertinent to examine the scenario in the Indian setting. The Markov model presented here (Figure 1) outlines the scope of the problem and gives an idea about the need for treatment in such patients. According to most case series, patients appear to become symptomatic at the rate of 2-3% per year and require surgery in the approximate distribution as demonstrated in Figure 1.[18,22] The income of an average Indian is $85 per month. Every year 5-6% new patients are added to this pool of asymptomatic gallstones. This model has been created for first three years as an example, keeping in view the fact that majority of gallstones become symptomatic during early years and remain silent after 10-15 years. Diabetes is increasing in India and is likely to reach 60 million over the next 5 years. India has two contextual issues. The distribution of gallstone disease is regional: north Indian states have higher rate than the south Indian states. The type of stones also vary as per the region due to diet variations. Second issue is the endemicity of gallbladder cancer in some northern states. These issues impact the decision making for management of asymptomatic cases.

Based on previous studies[18,22,23] risk ratio and life expectancy were calculated. Expected operative mortality for elective cholecystectomy was 0.0005 for 25-year-old men and approximately doubled with each increasing decade. With the low incidence estimate life expectancy for men/ women with silent stones who chose to wait ranged from 40 to 7.25 years, declining with advancing age. The lifetime risk of death from gallbladder complications for men was initially 0.0129 for 25- year-old men, increased to 0.155 at the age of 45, and then decreased again at 75 years of age. This is an interesting pattern to study. In young patients the risk of surgery is low and hence risk ratio is higher. As age advances the risk of surgery escalates and incidence of developing complications lowers. Hence we see a ‘U’ pattern. On the ascending limb of this curve the risk of surgery is increasing faster than the life expectancy which is decreasing. On the descending limb life expectancy is decreasing faster than the surgical risk which is increasing. This has practical implications and one must consider laparoscopic surgery in young patients who have recently detected stones with doubtful symptoms. Surgery for elderly may be deferred if the stones are asymptomatic and have been there for longer period. Though these studies have not found single parameters as useful, this data can be used to undertake informed clinical decisions based on risks, life expectancy and complication patterns.

Selective cholecystectomy appears to be a good strategy in India. Routine prophylactic cholecystectomy can be advocated in endemic areas and in young patients based on clinical and sonographic predictors of severity. Factors such as multiple stones, large size and calcified and thickened gallbladder can be used to decide upon prophylactic cholecystectomy.

Cost analysis in India – India has less than adequate state funding for health (2% of GDP). Hence, most patients have to pay out of their own pockets for their treatment. The insurance sector is also poorly developed in our country, with only 3% patients being covered under health insurance. The cost of prophylactic cholecystectomy would thus be much higher in India as compared to expectant treatment. Therefore, there is a case for expectant treatment based on cost-benefit analysis.

To conclude routine prophylactic cholecystectomy for asymptomatic gallstones is not recommended. Based on our Markov model decision and cost analysis selective and concomitant cholecystectomy are recommended for special indications like hemolytic disorders, gallstones in endemic areas etc. Expectant management should be adopted in all others. Figure 1 depicting the model explains the magnitude of target patient population being considered here. Routine prophylactic cholecystectomy would amount to additional surgeries in excess of 4 million at the end of 3 years and 5000 patients suffering complications of those surgeries at an accepted complication rate of 1/1000. The magnitude of these statistics overwhelms the available expertise of laparoscopic surgery in our country and also present a significant strain on resources which will widen the deficit in the healthcare sector. The evolution of laparoscopy should not alter the indications of cholecystectomy. Because more than 90% patients with asymptomatic gallstones remain clinically “silent” routine laparoscopic cholecystectomy is not indicated for the vast majority of subjects with asymptomatic cholelithiasis. Laparoscopic cholecystectomy though has become safer, is associated with potential morbidity and mortality. The risks of the operation outweigh the complications if stones are left insitu. However, laparoscopic cholecystectomy should be performed selectively or concomitantly in select subgroup of patients. Patients should be counseled about the natural history and available management options, their advantages and disadvantages and should be part of the decision making process.

Acknowledgement

Author thanks Dr. Gaurav V. Kulkarni for his assistance in preparing this manuscript.

References