The incidence of asymptomatic cholelithiasis is on the rise due to easy availability and frequent use of ultrasonography for evaluation of most of the abdominal complaints. It accounts for 10-25% in the general population with majority i.e.70-80 % being asymptomatic at diagnosis and 10-20% out of the same becoming symptomatic or facing complications during lifetime. Laparoscopic cholecystectomy is considered as the gold standard for treating symptomatic gallstones while controversy continues to exist in managing asymptomatic cases. However, except under some special circumstances and few well defined at-risk individuals, expectant management is considered adequate for asymptomatic gallstones (AG).The study of natural history of gallstone disease and the life time risk of complications shows, prophylactic cholecystectomy for AG may be a too aggressive treatment. The aim of this article is to make the clinician and the patient aware of the available data regarding AG and thus decision making in its management.
KEY WORDS: Asymptomatic gallstones, Prophylactic cholecystectomy.
The occurrence of gallstones is very common and its incidence increases by 1% per year, so that 35% of women and 20% of men develop it by 75years and about 60% of both sexes by 80 years [1- 3]. Another study in United Kingdom shows the incidence as 8% of population over 40 years and 20% over 60 years of age. However 90% of the individuals are asymptomatic, yet cholecystectomy is the most commonly performed abdominal procedure . The incidence is greatly influenced by fat intake and Western type of diet. Several studies reveal rise in incidence in Saudi Arabia after adoption of Western diet where gallstones were virtually unheard 50years ago . AG is detected incidentally during ultrasound for other abdominal conditions or occasionally by palpation of gallbladder at operation. Symptomatic gallstones should be considered when patient gets biliary pain which is almost always episodic and infrequent [6, 7].It develops rapidly, is severe, steady and unrelieved by change of position or gas passage. Pain that frequently comes and goes, lasts less than 15minutes ,does not interfere with activity and symptoms of dyspepsia, epigastric discomfort, flatulence or nausea should not be attributable to gallstones as they often occur in general population with or without other gastrointestinal problems [8-14,16]. Symptomatic gallstones may arise due to movement or impaction of stone, stasis or infection. Studies on follow up of AG reveal biliary pain as commonest initial symptom in up to 90%  followed by acute cholecystitis and acute pancreatitis [16-18]. As studies have shown dyspepsia to occur with equal frequency with presence or absence of gallstone, hence gallstone dyspepsia is a myth [16, 19-21].
NATURAL HISTORY OF GALLSTONES: Prevalence of AG is 10-20% with higher incidence seen in women and as age advances. Mayo in 1904 quoted that ‘the innocent gallstone’ is a myth and warned of the consequences of silent stones in 1911, but today studies support the view that most of the gallstones are asymptomatic and incidentally found and continue to be as such throughout life and require no treatment [16, 19, 22-33]. About 70-90% of gallstones remain asymptomatic, biliary pain occur at the rate of 1-4% per year and usually one episode of it precedes onset of complication that occur at a rate of 0.2-0.8% per year[22,26,34-36]. A longitudinal follow up study of AG over 20years at the University of Michigan, showed development of biliary pain in 18% of the case and the mean yearly probability of development of biliary pain is 2%,1%,0.5% and 0% during first, second, third and fourth consecutive 5years respectively . Complications due to gallstones did not occur in anyone and none died due to gallstone disease [37, 38]. In about 30% of patients with biliary pain, had no further pain episodes. Hence natural history of AG is so benign that neither they necessitate treatment nor a regular follow up [35, 39].
SPONTANEOUS DISSOLUTION OF GALLSTONES:
Spontaneous dissolution of gallstones is a possibility especially with asymptomatic biliary sludge or stones referred as pseudolithiasis encountered in postoperative paediatric patients either treated with high doses of ceftriaxone or prolonged restriction of oral diet. Dissolution occur usually 2weeks to 4months of cessation of ceftriaxone and hence prompt cholecystectomy should be avoided [41, 42]. Incidence of biliary sludge and stones during pregnancy is 31% and 2% respectively, occurring during first trimester until post-partum and they usually disappear spontaneously over 5-10months.Sludge causes no pain though stones are associated with biliary pain in 28% and sludge dissolute faster than stones. AG can be classified as i) low risk groups with small stones 3-20mm in a functioning gallbladder, without comorbidities and ii) high risk groups with large stones >25mm or multiple tiny stones <3mm and obliterated cystic duct[43-45]. Korean study shows a 3 fold increase in risk of acute gallstone pancreatitis when number of stones are more than 20 and at least one of them is less than 5 mm . MANAGEMENT OF GALLSTONES: Medical management of symptomatic gallstones with Ursodeoxycholic acid (UDCA) takes longer time with potential for recurrence and GB cancer. Hence laparoscopic cholecystectomy is the preferred method. The risk of developing GB cancer in AG is <0.01% which is less than mortality associated with cholecystectomy. Hence prophylactic cholecystectomy is not necessary [37, 38, 47]. However, selected patients with AG demand special attention like diabetes, pregnancy, GB cancer, incidental during intra-abdominal surgery for unrelated condition, colon carcinoma, transplant surgery, cirrhosis of liver, CBD stone, hemolytic child and patient's choice. DIABETES MELLITUS AND GALLSTONES: In the past prophylactic cholecystectomy was advised in diabetics with gallstones because of higher incidence of symptoms and complications like infection, gangrene and perforation as associated autonomic neuropathy masks signs and symptoms and cause delay in diagnosis [11, 48, 49]. Several recent study reports have established that AG in diabetics do not carry added risk of morbidity and mortality compared to general population and early surgery is considered only for symptomatic cases . PREGNANCY AND GALLSTONES: Oral estrogen and pregnancy have been found associated with gallstone disease. Asymptomatic biliary sludge develop during pregnancy in 26-31% females and disappear spontaneously after delivery due to the effect of estrogens in enhancing bile lithogenicity and progesterone causing GB hypomotility . Hence females with AG should not be prescribed oral estrogen or hormone replacement therapy . AG may become symptomatic during pregnancy  and over 90% of the symptomatic cases resolves with conservative management and cholecystectomy is advised for non-resolving symptomatic or complicated cases [53, 54]. GALLSTONES AND GENETICS: Gallstone incidence varies greatly among world populations.Pima Indians of United States especially females , Chilean , North and South American, Indians and European-American Indians has a high incidence of gallstone disease and gallbladder cancer to the extent of 3-5% against the average incidence of about <0.01%.In India incidence rate in females in the north are very high as compared to the south . Indians are at higher risk for developing gallbladder carcinoma as shown by studies on migrants to UK, Australia, Fiji, Kuwait and Singapore has higher incidence and mortality than native population in those areas. Hence prophylactic cholecystectomy is justified for AG in those high risk populations . GALLSTONES AND GALLBLADDER CARCINOMA: GB carcinoma is found associated with gallstones in over 70% cases except rare condition of adenomatous polyps . The risk of gall bladder cancer in AG is <0.01% which is less than the mortality associated with cholecystectomy . Certain conditions where probability of GB carcinoma is more, prophylactic cholecystectomy is advocated like gallstone size >3cm that runs 10 times more risk than size <1cm, GB packed with stones, porcelain GB with wall calcification that runs a risk of cancer in 13-22% of patients, Children and young adults because of cumulative lifetime risk, GB wall thickness >3mm on USG as found associated with xanthogranulomatous cholecystitis in 50% cases , large sessile polyps, anomalous pancreaticobiliary ductal union, high parity and first childbirth before age of 25years [63,64] and the at risk racial group of people as discussed above.
AG becomes symptomatic on occasions in the postoperative period possibly due to stasis of bile causing cholecystitis [65-67]. USG abdomen should be routinely done in all cases of planned laparotomy to detect silent gallstones and prior counseling the patient before surgery [68-70].Hence it is considered safe to do cholecystectomy in women with AG undergoing major gynecological surgery if it does not add further life risk . So also concomitant cholecystectomy should be done along with laparoscopic antireflux surgery , splenectomy in sickle cell disease  and laparotomy done in patients on prolonged parenteral nutrition .
OTHER FACTORS FOR PROPHYLACTIC CHOLECYSTECTOMY:
Prophylactic laparoscopic cholecystectomy can be considered for recipients of solid organ transplant on cyclosporine as frequently associated with AG  and not justified before renal and cardiac transplantation[75,76]. Patients having AG and CBD stone should be put for endoscopic(ERCP) CBD stone removal with cholecystectomy in younger patient <50years and wait and watch policy for elderly patients with low risk as only 10% of such cases might return with further biliary complication . Patients with hemolytic anemias are at greater risk of symptomatic gallstones  thus favoring prophylactic cholecystectomy to avoid future confusion between biliary complication and vaso-occlusive crisis as both present similarly with nausea, abdominal pain, fever, leucocytosis and cholestatic jaundice. Gall stones occur in up to 57% in sickle cell disease (30% being asymptomatic) at a young age raising the life time risk of biliary complication thus favoring a prophylactic cholecystectomy along with splenectomy [79-81]. Similarly in hereditary spherocytosis and chronic hemolytic anemias prophylactic splenectomy and cholecystectomy renders quality adjusted survival advantages . Individuals with AG and young females concerned about cosmesis residing in remote places with lack of adequate emergency and skilled healthcare services can be considered for prophylactic cholecystectomy. CONCLUSION: Majority of patients with gallstones remain asymptomatic throughout life and symptomatic cases present for the first time usually after 2 years of stone formation at a rate of 2% per year for first 10 years following which it declines. Cancer risk in AG is <0.01% which is even less than due to mortality due to laparoscopic cholecystectomy. Hence a patient with AG should be well informed about the natural history of gallstones before making a decision to proceed for cholecystectomy and he/she should not dictate the management as future medico-legal issues arising out of complications of surgery which are very troublesome especially in situations where surgery was not indicated in the first place. All AG usually develop a bout of biliary colic before they present with complication and cholecystectomy done presently under better healthcare facilities does not put additional risk compared to prophylactic cholecystectomy. So AG should be left alone and a wait and watch principle to be followed except for certain high risk individuals and under special circumstances.
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