HEPATOBILIARY SURGERY

Gallstones
Abeed H Chowdhury Dileep N Lobo

Abstract
Gallstones represent one of the commonest surgical problems in the developed world. Post-mortem studies have found gallstones in 12% of men and 24% of women of all ages. Gallstones may be symptomatic or found incidentally. Symptoms arise due to stones in the gallbladder, in the bile duct, or both. It is estimated that 10e30% of patients with gallstones develop symptoms, of which a majority eventually require endoscopic or surgical intervention. Complications of gallstone disease include acute cholecystitis, obstructive jaundice, acute pancreatitis, gangrene of the gallbladder and gallstone ileus. Laparoscopic cholecystectomy is currently the treatment of choice for symptomatic gallstone disease and common bile duct stones can be treated surgically or at endoscopic retrograde cholangiopancreatography.

Keywords Cholecystectomy; endoscopic retrograde cholangiopancreatography; gallbladder; gallstone ileus; gallstones

presence of specic local conditions with each type of stone having an epidemiological and genetic risk prole associated with it. Based on these conditions, two broad types of stone are encountered: cholesterol or pigment stones, with pigment stones further characterized as black or brown. Ethnicity is a major factor inuencing the prevalence of different stone types. In Western societies cholesterol stones are by far the most common, accounting for 80e90% of gallstones found at cholecystectomy. Black pigment stones, composed primarily of calcium bilirubinate, develop exclusively in the gallbladder and over 50% are radio-opaque. These are typically seen in patients with cirrhosis, cystic brosis or increased red cell destruction (e.g. haemolytic anaemia, splenomegaly, myeloproliferative disorders, etc.). Other associations include diseases of the terminal ileum or after ileocaecal resection, where the enterohepatic circulation of bilirubin is interrupted. Brown pigment stones arise in the gallbladder and bile ducts in association with biliary infection or bile stasis, and are common in Asia, with reported prevalence rates as high as 20% in some parts of China. It is thought that infection with b-glucuronidase-producing bacteria such as Escherichia coli and Bacteroides spp. and parasites such as Opisthorchis viverinni or Ascaris lumbricoides cause deconjugation of bilirubin and bile salts with subsequent precipitation into insoluble forms.

Introduction
Gallstones represent one of the commonest surgical problems in the developed world and impose a signicant economic burden on healthcare. Post-mortem studies in adults have found gallstones in 12% of men and 24% of women. Prevalence of gallstones varies in different populations, and in Europe ranges from 6e22%, with an annual incidence of one in 200. It is estimated that 10e30% of patients with gallstones develop symptoms, of which a majority eventually require endoscopic or surgical intervention. Each year more than 50,000 cholecystectomies are performed in the UK, with approximately 700,000 being performed in the USA. Common bile duct stones are found in approximately 12% patients before or at the time of cholecystectomy, indicating a need for over 6000 duct clearance procedures per year in the UK.

Risk factors
North American Indians have a higher risk of developing cholelithiasis, as do rst-degree relatives of patients with known gallstones, indicating a heritable component to the condition. Whilst the presence of supersaturated bile is undoubtedly a prerequisite for cholesterol gallstone formation, other factors contribute to individual gallstone susceptibility. These include impaired gallbladder motility and the presence of pro-nucleating factors. Risk factors for the development of cholesterol stones are shown in Box 1.

Risk factors for cholesterol gallstone formation

C C

Types of gallstone
The process of gallstone formation involves the precipitation of substances found in bile, including cholesterol, calcium bilirubinate, and calcium salts of phosphate, carbonate and palmitate. The exact composition of stones is dependent on the

C C C C C C C C

Abeed H Chowdhury BSc MRCS is a Specialist Registrar in the Division of Gastrointestinal Surgery at Nottingham University Hospitals, Queens Medical Centre, Nottingham, UK. Conict of interest: none. Dileep N Lobo MS DM FRCS FACS is Professor of Gastrointestinal Surgery in the Division of Gastrointestinal Surgery at Nottingham University Hospitals, Queens Medical Centre, Nottingham, UK. Conict of interest: none to declare.

C C C C C

Age Female sex Family history Race Pregnancy Parity Obesity Oral contraceptives Diabetes mellitus Cirrhosis Prolonged fasting Rapid weight loss Total parenteral nutrition Ileal disease or resection Impaired gallbladder emptying

Box 1

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Mechanisms for cholesterol stone formation

The secretion of bile salts, phospholipids and cholesterol from hepatocytes is carefully regulated by a series of adenosine triphosphate-binding (ATP-binding) cassette transmembrane pumps (ABC transporters), which are, in turn, under transcriptional regulation by a small number of nuclear receptors. In normal circumstances cholesterol is secreted by hepatocytes as small unilamellar vesicles (40e200 nm diameter), which are converted to smaller micelles (40e100  diameter) by the A detergent action of bile salts (Figure 1). As the circulating bile salt pool is relatively small, excess cholesterol soon overwhelms its emulsifying capacity, remaining in bile as vesicles, which have a greater propensity for cholesterol crystal precipitation. Recent murine investigations have uncovered genetic inuences which may increase susceptibility to stone formation. Multiple candidate genes, many with orthologs in humans, have now been identied following the recognition of the lithogenic genes Lith1 and Lith2. In the normally non-lithogenic mouse strain AKR/J, the presence of alleles from the lithogenic strain C57L/J in both Lith1 and Lith2 chromosome regions promotes the gallstone-forming phenotype. Another gene offering a possible therapeutic target encodes the farnesoid X receptor (Fxr), which in normal circumstances increases biliary bile salt and phospholipid concentrations. Feeding of synthetic Fxr ligands to gallstone susceptible mice confers a non-lithogenic phenotype mediated by an increased expression of several bile salt transport pumps. Although specic gene products for all Lith genes are yet to be fully characterized, candidate products include hepatic lipid transporters, lipid regulatory enzymes, transcription factors and hormone receptors.

Natural history
The vast majority of patients with gallstones are asymptomatic and remain so following diagnosis, usually made after ultrasonography or cross-sectional imaging for the investigation of other conditions. Symptoms, which develop in 10% of patients by 5 years and in 20% by 20 years, are common to a number of upper gastrointestinal disorders and typied by upper abdominal pain, so called biliary colic and dyspepsia. Cholecystectomy results in the relief of symptoms in 92% of patients with biliary colic, 72% with upper abdominal pain and 56% with dyspepsia. There has been much debate concerning the management of patients with asymptomatic gallstones although prospective studies show that following diagnosis the risk of developing symptoms remains low, equating to 1e4% per year, with only 10% and 20% developing symptoms within 5 years and 20 years respectively. Although gallbladder cancer is undoubtedly associated with the presence of gallstones, studies suggest that the incidence is very low compared with the prevalence of gallstones. For these reasons, routine cholecystectomy is not currently advocated for patients with asymptomatic gallstones. The risk of complications is much higher in symptomatic patients, with an annual incidence of 14% for acute cholecystitis and 5% for both obstructive jaundice and acute pancreatitis. Rare but serious complications of gallstones include gallstone ileus, gallbladder empyema and perforation.

Clinical presentation
Gallstones may be symptomatic or found incidentally. Symptoms arise due to stones in the gallbladder, in the bile duct, or both.

Symptomatic gallstones

Secretion of bile constituents from the hepatocyte luminal membrane

Phospholipids Cholesterol Bile salts

ABC G5

ABC G8

ABC B4

ABC B11

Cytosol Lumen

Unilamellar vesicles

Micelles

Biliary colic Gallstones obstructing the outlet of the gallbladder at Hartmanns pouch can cause biliary colic, triggered by contraction of the gallbladder against a closed orice. Experienced by about 20% of patients with gallstones, the pain usually starts abruptly and rapidly reaches a peak, from which it is constant before eventually subsiding, usually within hours, as the stone either falls back into the gallbladder or passes into the common bile duct (Figure 2). Fluctuations are rare, and in this respect, the term colic may be regarded as a misnomer. Pain is commonly, but not exclusively post-prandial, usually experienced in the right upper quadrant, and often radiates to the right scapula or shoulder. A commonly reported feature is an inability to assume a comfortable position to lessen the pain. Two-thirds of patients presenting with their rst attack of biliary colic will have a further attack within 2 years, rising to 90% at 10 years, which explains in part the current recommendation for cholecystectomy in patients with symptomatic gallstones. Acute calculous cholecystitis Inammation of the gallbladder can result from prolonged gallstone obstruction of the cystic duct. As indicated previously the risk of cholecystitis is much higher for those who experience symptoms, but for all patients with gallstones this risk equates to roughly 1e3%. Obstruction increases intraluminal pressure with subsequent venous congestion, reduced arterial ow and

Bile salts, phospholipids and cholesterol are actively secreted by specific ATP-binding cassettes (ABCs) on the luminal membrane. Secreted cholesterol initially forms relatively large unilamellar vesicles with membrane phospholipids. The presence of bile salts, which contain a hydrophobic head and hydrophilic tails, results in fat emulsification and micelle formation, dramatically increasing the surface area of cholesterol available for attack by pancreatic lipase

Figure 1

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Pain typically experienced during an attack of biliary colic

Intensity

Plateau

Rapid rise

classied into two types. Type I is caused by a stone in Hartmanns pouch compressing the adjacent common bile duct. Type II is caused by erosion of such a stone into the common bile duct leading to a cholecystocholedochal stula. Diagnosed only in twothirds of cases preoperatively, there is an increased risk of bile duct injury during cholecystectomy when present. Of note, 6e23% of patients diagnosed with Mirizzis syndrome preoperatively, have a nal diagnosis of gallbladder carcinoma. Intra operative frozen section histological examination is therefore recommended for these patients as radical cholecystectomy rather than interval re-operation is associated with improved outcomes. Gallstone ileus Intestinal obstruction can occur when gallstones occlude the intestinal lumen. This clinical entity results most commonly from the presence of a cholecystoduodenal stula, but rarely the cause is a cholecystocolonic stula. Responsible for 1% of all small bowel obstructions, patients present with intermittent intestinal obstruction as the gallstone impacts and disimpacts, usually at the terminal ileum and clear features of intestinal obstruction are present in only 50e70% of patients, which can introduce diagnostic delay. Radiographic clues to the diagnosis include evidence of intestinal obstruction with a transition point and the presence of air in the biliary tree, present in 40% of cases. Other causes of pneumobilia can include endoscopic sphincterotomy or bilioenteric anastomoses but in the absence of previous instrumentation, air in the biliary tree should be considered pathological. Treatment is surgical, though in selected cases endoscopic or minimally invasive treatment may be possible. Enterolithotomy is the essential procedure to relieve the obstruction. If possible the stone should be milked proximally from the site of impaction and extracted through an enterotomy in healthy bowel wall, the latter being then closed transversely. It is mandatory to examine the entire bowel carefully, as multiple stones have been reported in 3e40% of cases, and if missed, can cause recurrent gallstone ileus. Cholecystectomy and repair of the cholecystoenteric stula may be considered in t patients, either simultaneously, or as a second-stage procedure. Acalculous cholecystitis Although rare, accounting for only 2e15% of cases of acute cholecystitis, acute acalculous cholecystitis is recognized as an important surgical emergency owing to an increased risk of serious complications. Risk factors which also contribute to a mortality of 30% include intercurrent illness, recent major surgery or trauma, burns, diabetes and total parenteral nutrition. Other known associations include the dissemination of microorganisms from a remote or systemic source of sepsis. Typical infections include candidiasis, leptospirosis, typhoid, malaria, cholera and tuberculosis. Serious complications are more common than with calculous cholecystitis and include gangrene, empyema and perforation. Although poorly understood, the aetiological mechanisms include bile stasis and ischaemia. Bile stasis is thought to alter the composition of bile leading to increased viscosity and subsequent increased risk of bacterial overgrowth. Although histologically, there is little to distinguish acalculous cholecystitis from that caused by gallstones, arteriography often reveals multiple arterial occlusions and minimal venous lling suggesting that microcirculatory abnormalities are central to the

Time
Reproduced with permission from Moser A, Roslyn J. Gallbladder and biliary tree. In: Corson J, Williamson R, eds. Surgery, 1st edn. London: Harcourt International, 2001

Figure 2

impaired lymphatic drainage. Inammatory mediators, in particular the prostaglandins I2 and E2, are released in response to mucosal ischaemia leading to inammatory cell inltration and oedema of the gallbladder wall. Patients present with abdominal pain localized to the right upper quadrant and systemic signs of inammation, such as pyrexia. An acute abdomen is revealed on examination and a positive Murphys sign aids the differentiation from biliary colic. Progressive inammation can lead to focal necrosis, gangrene and in rare instances perforation. Superadded infection with gram-negative organisms may result in empyema. The role of prostaglandins in the clinical course of acute cholecystitis is further highlighted by the effect of indomethacin, a non-selective inhibitor of cyclooxygenase 1 and 2. In a randomized placebocontrolled study, patients treated with indomethacin had significant improvements in pyrexia, pain and white blood cell count on day 1 of treatment as well as shorter hospital stay. Chronic cholecystitis Repeated low-grade obstruction can give rise to a picture of chronic inammation of the gallbladder, with progressive granulation and collagen deposition within the gallbladder wall. Patients typically present with post-prandial fullness, belching, nausea and right upper quadrant discomfort. Symptom proles vary widely and can even be identied in 12e13% of patients without gallstones. Clinical examination is usually unhelpful. Ultrasound may demonstrate the presence of a contracted gallbladder with gallstones, but often the gallbladder is normal. Symptom persistence and the demonstration of cholelithiasis ensure that many patients undergo laparoscopic cholecystectomy, and whilst the gallbladder may be normal on histology, most patients appear to benet from surgery, at least in the short term. Mirizzis syndrome Very occasionally, stones in the gallbladder may cause obstructive jaundice, eponymously termed Mirizzis syndrome, which is

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pathophysiological process. Often challenging, diagnosis can be made using ultrasonography, which in the presence of gallbladder wall thickening to 3.5 mm, has a sensitivity of 80% and specicity of 98.5%. Computed tomography has comparable diagnostic value and may be favoured for patients in whom the aetiology of clinical features is unclear. Due to the high risk of gangrene and perforation the treatment of choice is laparoscopic cholecystectomy but in patients who are unt to undergo anaesthesia and surgery, percutaneous cholecystostomy is a viable primary treatment strategy.

Management considerations in patients with cholecystolithiasis

Ultrasound As only 10% of gallstones are radio-opaque (Figure 3), transabdominal ultrasound is the main diagnostic modality used for gallbladder disease. Gallstones are usually seen as sonodense lesions with posterior acoustic shadowing (Figure 4). Thickening of the gallbladder wall and the presence of pericholecystic uid suggest acute cholecystitis and an ultrasonic Murphys sign may be elicited. Dilatation of the biliary tree implies duct obstruction and common bile duct stones may sometimes be visible, although the lower end of the bile duct is sometimes obscured by bowel gas. Dissolution therapy, lithotripsy and pharmacological targets Non-surgical options have been utilized in patients with symptomatic gallstones, but this course of treatment plays a limited role in comparison to laparoscopic cholecystectomy. Oral therapy with bile salts (chenodeoxycholate and ursodeoxycholate) is suitable in only 15% of symptomatic patients with cholesterol gallstones. In this subgroup of patients with favourable proles (small stones,
Figure 4 Transabdominal ultrasound demonstrating a sonodense gallstone with posterior acoustic shadowing.

radiolucency and functioning gallbladder) gallstone dissolution is effective, but success is slow to achieve. Side effects are common and recurrence rates approach 50% after 10 years. Lithotripsy has been attempted with only partial successes. Indeed it has been estimated that almost half of the patients undergoing lithotripsy require subsequent cholecystectomy. Even in patients in whom successful fragmentation is achieved, recurrence rates approach 50% at 5 years. Novel pharmacological targets for the prevention of gallstones have recently emerged. Data from animal and epidemiological studies, suggest that statins (competitive inhibitors of 3-hydroxy3-methylglutaryl coenzyme A), reduce the frequency of gallstone formation. Patients who took statins for at least 1e1.5 years had a reduced risk of developing gallstones and undergoing subsequent cholecystectomy by one-third compared to matched control patients, in whom statin use was absent. In rodent studies, blocking the intestinal absorption of cholesterol with the Niemanne Pick C1-like 1 protein inhibitor, ezetimibe, lowered biliary cholesterol secretion and in human studies the same treatment led to bile desaturation and reduced cholesterol crystallization. Although these pharmacological agents offer a potential role in the prevention of gallstones, especially for patients at high risk of gallstone development, further evaluation in clinical studies will be required before this role can be established. Laparoscopic cholecystectomy Laparoscopic cholecystectomy (Figures 5 and 6) has developed into the mainstay for treatment of symptomatic gallstones and in the developed world, is now the most commonly performed elective abdominal procedure. Previous abdominal surgery, pregnancy, cirrhosis and coagulopathy are no longer considered contraindications for laparoscopic surgery which can in many cases be undertaken safely as a day case procedure. Accordingly, perioperative mortality is low lying between 0 and 0.3%, as is the frequency of complications. The reported incidence of bile duct injury is one in 200e300 cases and the conversion rate 1e5%. Other complications requiring re-operation include major bowel or vessel injury during trocar insertion (0.02%), bile leak (0.1e0.2%), peritonitis (0.2%), post operative bleeding (0.1%e0.5%) and intra-abdominal abscess (0.1%). Recent advances in laparoscopic technology have seen the introduction of single incision laparoscopic cholecystectomy

Figure 3 Plain abdominal X-ray showing radio-opaque gallstones.

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a reduction in gallstone-related complications during a shortened waiting period. Other advantages include a reduction in hospital stay, recuperation time and economic cost. Fears over the safety of early intervention are unfounded with no increase in the frequency of complications in comparison with the delayed procedure. However, unless dedicated operating lists are made available for these procedures, delay caused by competition with other emergency operations is unlikely to result in a reduction in hospital stay or costs.

Common bile duct stones (choledocholithiasis)

Common bile duct stones may occur due to passage of a stone from the gallbladder, or arise de novo in association with biliary strictures, infection, duodenal diverticula or foreign material (i.e. suture material). Pain is not generally regarded as a feature due to a lack of smooth muscle within wall of the common bile duct, although some authors believe that spasm of the sphincter of Oddi may contribute to pain which is typically experienced in the right upper quadrant. Common duct stones may be asymptomatic, or manifest as a number of well-dened clinical entities, as outlined below. Asymptomatic common bile duct (CBD) stones When routine cholangiography is performed at laparoscopic cholecystectomy, common duct stones are found in 8e20% of patients. Of these over 90% have pre operative indicators such as a history of pancreatitis, cholangitis or jaundice, a dilated common bile duct on ultrasonography (USS), or abnormal liver function tests (LFTs). Less than 10% are believed to have silent CBD stones, of which approximately one-third are believed to pass spontaneously. Very small stones less than 5 mm in size are believed to pass with even greater frequency. Obstructive jaundice Jaundice is usually detectable clinically when the serum bilirubin exceeds 50 mmol/litre. Gallstones are a common cause, leading to persistent jaundice in cases of gallstone impaction at the ampulla (Figure 7), or uctuant jaundice due to ball-valving of common duct stones. Abdominal ultrasonography is the rst-line investigation of choice, but its sensitivity in detecting CBD stones varies between 23% and 80% depending on body habitus and operator experience. Common bile duct dilatation is commonly used as a soft marker for the presence of CBD stones, but is associated with low sensitivities. A normal CBD diameter is, however, a strong negative predictor for the presence of CBD stones. The introduction of magnetic resonance cholangiopancreatography (MRCP) has greatly improved the detection of common duct stones (Figure 8), with a reported diagnostic accuracy of over 90%, equivalent to endoscopic retrograde cholangiopancreatography (ERCP). The technique is performed easily, non-invasive and obviates the need for intravenous contrast, but it cannot be combined with therapeutic intervention and depends on local availability and radiological expertise for interpretation. Its main advantage is that it reduces the number of unnecessary ERCPs performed, with obvious benets in terms of patient morbidity. However, whilst there are proponents of routine pre-operative MRCP, most clinicians utilize MRCP selectively, often as part of stratication tools designed to predict individual risk of harbouring common duct stones.

Figure 5 It is essential to dissect Calots triangle prior to clipping any structure. This initial dissection shows that there are only two structures crossing Calots triangle (the cystic artery and the cystic duct).

(SILC) with early reports suggesting no difference in postoperative pain, blood loss or conversion rates to the conventional 4 port approach. In the only randomized controlled trial comparing SILC with 4 port laparoscopic cholecystectomy involving 83 patients, similar pain and satisfaction scores were obtained for SILC compared to the standard four-port approach. Although there are obvious benets in terms of cosmesis, long term data on umbilical hernia and complication rates have yet to be reported. Acute versus interval laparoscopic cholecystectomy for acute cholecystitis The traditional strategy for scheduling operative intervention after acute cholecystitis included a waiting period of several weeks to allow the process of inammation to settle in the belief that this reduced the risk of bile duct injury. A number of systematic reviews have provided evidence to refute this belief. An advantage for early laparoscopic cholecystectomy (within 1 week of symptom onset) has been demonstrated owing to

Figure 6 After further dissection to skeletonize the structures, the cystic artery has been clipped and divided. The cystic duct is ready for application of clips.

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Figure 7 Endoscopic photograph showing a stone impacted at the papilla. The stone was extracted at ERCP, revealing a patulous papilla.

Ascending cholangitis Stasis of bile within the common bile duct increases the risk of ascending infection from the gut. Typical organisms include E. coli, Klebsiella pneumoniae and Enterococcus faecalis. Established ascending cholangitis e typied by Charcots triad of obstructive jaundice, fever and rigours e is a surgical emergency mandating prompt biliary drainage. The development of shock and mental obfuscation in ascending cholangitis (Reynolds pentad) is a grave sign associated with a high mortality. ERCP (Figure 9) is the management of choice following appropriate resuscitation, administration of broad-spectrum antibiotics and

correction of clotting abnormalities. If ERCP fails options include percutaneous transhepatic biliary drainage or surgery. In general, because patients are often severely unwell, external biliary drainage is preferred to surgery, although the decision is dependent upon the availability of local radiological expertise. Acute pancreatitis Gallstones which pass through the common bile duct can obstruct the pancreatic duct either transiently as they pass into the duodenum or for prolonged periods if they are large enough to impact at the sphincter of Oddi. An increase in pancreatic duct pressure can cause proenzyme activation leading to autodigestion and acute pancreatitis, for which gallstones are the most common cause, carrying a mortality between 3% and 10%. The rst-line investigation of choice is abdominal ultrasonography, which may identify gallbladder stones, a dilated common duct, or occasionally a common duct stone. It is worth appreciating that because the limit of resolution of abdominal ultrasonography is approximately 4 mm, smaller stones responsible for acute

Figure 8 An MRCP image demonstrating gallstones within the gallbladder and common bile duct, with associated ductal dilatation.

Figure 9 ERCP in a patient with acute cholangitis demonstrating multiple stones in a dilated common bile duct (left). An endoscopic sphincterotomy was performed and a double pigtail stent was inserted to facilitate drainage (right).

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pancreatitis may be missed. Repeat ultrasound, MRCP and endoscopic ultrasound (EUS) all have evolving roles in the detection of microlithiasis in patients with a provisional diagnosis of idiopathic pancreatitis. In patients with established severe gallstone pancreatitis who are jaundiced or have a suspicion of cholangitis, early ERCP has been shown to reduce both morbidity and mortality. However, in the absence of cholangitis, early endoscopic sphincterotomy does not reduce pancreatic complications or mortality and should not be considered as denitive treatment of common bile duct stones. Patients with acute gallstone pancreatitis are at increased risk of further pancreatitis as well as other gallstone related complications and should, therefore, undergo laparoscopic cholecystectomy and intra operative cholangiogram (IOC) once the patients clinical course permits.

Management considerations in patients with CBD stones

Routine versus selective intra operative cholangiography The possibility of overlooking occult common bile duct stones has prompted some surgeons to advocate routine IOC at laparoscopic cholecystectomy, yet this remains controversial. Proponents argue that routine operative cholangiography not only identies silent CBD stones, but also reduces the risk of signicant bile duct injury. There is no doubt that IOC is associated with a lower rate of common bile duct injuries compared with cases where IOC is not performed, but the evidence is weaker when routine IOC and selective IOC are compared. In perhaps the best study of its kind, Snow et al. retrospectively compared results of routine IOC and selective IOC at a single institution. Unsuspected CBD stones were discovered in 2.8% at routine IOC, with residual symptomatic CBD stones identied in only 0.3% of those in the selective IOC. In particular there were no differences in bile duct injuries among the groups, suggesting that careful patient selection can reduce the number of unnecessary intra operative cholangiograms performed. IOC is indicated in patients with a history of abnormal liver function tests, jaundice, gallstone pancreatitis or duct stones and/or dilatation on imaging. Management considerations when CBD stones are identied intra operatively A properly performed intra operative cholangiogram is associated with low false-positive rates of less than 5%. When CBD stones are identied, the options are four-fold:  open exploration of the common bile duct  laparoscopic exploration of the CBD (transcystic or via choledochotomy)  on-table ERCP  post operative ERCP. The optimal management of CBD stones found at laparoscopic cholecystectomy remains elusive, and is the subject of much debate. Open exploration allows for excellent access to the CBD, albeit at the expense of increased morbidity, post operative stay and recuperation time. Transcystic exploration utilizes small calibre endoscopes or radiologically-guided wire baskets to access the common duct via the cystic duct. Stones are then retrieved via the cystic duct. The technique allows for easy closure of the cystic duct with clips, obviating the need for intra-corporeal suturing, but is associated with failure rates of 30e40%. Laparoscopic choledochotomy allows for easy access to the common duct in

a majority of patients, and is particularly useful in patients with failed transcystic exploration, large or multiple stones, and patients with failed or contraindications to ERCP. The only absolute contraindication to laparoscopic choledochotomy is a small common duct (<8 mm diameter), which predisposes an increased risk of complications following endoscopic exploration. Once duct clearance has been established the choledochotomy is sutured and a subhepatic drain placed. Where doubt exists over the adequacy of duct clearance, the cystic duct may be decompressed with either a T-tube or an antegrade biliary stent. This manoeuvre also allows access for post operative ductal cholangiogram via the T-tube. ERCP can be performed intra operatively, but is more commonly performed post operatively. It is associated with duct clearance rates of 90e95%, but is technically not feasible in approximately 5e10% of patients. Major complications including pancreatitis, cholangitis, haemorrhage and retroduodenal perforation occur in 10% of patients, with a procedure-related mortality of less than 1%. Ultimately the choice of procedure for intra operatively detected CBD stones depends upon local expertise and availability of resources. Management considerations when CBD stones are identied pre operatively When CBD stones are identied on radiological imaging, an attempt at duct clearance is considered mandatory. Stone removal can be achieved surgically or at ERCP. Primary ERCP is considered preferable to surgery in post-cholecystectomy patients and those too frail or unt to undergo surgery, although a careful anaesthetic assessment of such patients should be made, as up to 47% of patients will develop further acute biliary episodes when the gallbladder is left in situ. Electrocautery sphincterotomy to enlarge the biliary sphincter is performed using a bowed sphincterotome and this manoeuvre allows up to 90% of CBD stones to be retrieved by basket or balloon catheter. Complications occur in 4e10%, the most frequent being pancreatitis in 5.4% and bleeding in 2%. An evaluation of clotting function should be performed prior to ERCP for patients with liver disease, those taking anticoagulants or with a family history of coagulation disorders. ERCP is associated with a failure to clear the common duct in 5e10% of cases. Reasons for ERCP failure are shown in Box 2. In

Reasons for ERCP failure in patients with choledocholithiasis

C C C C C C C C C C

Billroth II reconstruction Duodenal stricture Duodenal diverticulum Ampullary stenosis Bile duct tortuosity Biliary stricture Stone impaction Multiple stones Stone >15 mm Intrahepatic stone

Box 2

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such cases, surgical exploration is necessary. For some, preoperative ERCP is the chosen method of duct clearance, whereas others advocate laparoscopic CBD exploration and cholecystectomy for all-comers. A recent prospective, multicentre randomized controlled trial compared combined ERCP/ interval cholecystectomy with single-stage CBD exploration and cholecystectomy for patients with CBD stones. Identical efcacy for stone removal was shown, with similar rates for morbidity and mortality. Because patients in the ERCP group required two hospital admissions, the single-stage laparoscopic approach was the more cost-effective of the two options. There are some cases in which ERCP or the laparoscopic approach has either failed or is not feasible; the open approach is reserved for such patients.

Summary
Although asymptomatic for the majority of patients, gallstones represent one of the commonest causes for acute hospital admission. The risk of developing complications is increased for symptomatic patients, providing the rationale for laparoscopic cholecystectomy which remains the treatment of choice. Common bile duct stones can be the cause of obstructive jaundice, acute cholangitis or pancreatitis and can be managed with ERCP or open surgery. A

FURTHER READING Di Ciaula A, Wang DQ, Wang HH, Bonfrate L, Portincasa P. Targets for current pharmacologic therapy in cholesterol gallstone disease. Gastroenterol Clin North Am 2010; 39: 245e64. viiieix. Gurusamy K, Samraj K, Gluud C, Wilson E, Davidson BR. Meta-analysis of randomized controlled trials on the safety and effectiveness of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 2010; 97: 141e50. Lobo DN, Jobling JC, Balfour TW. Gallstone ileus: diagnostic pitfalls and therapeutic successes. J Clin Gastroenterol 2000; 30: 72e6. Macafee DA, Humes DJ, Bouliotis G, Beckingham IJ, Whynes DK, Lobo DN. Prospective randomized trial using cost-utility analysis of early versus delayed laparoscopic cholecystectomy for acute gallbladder disease. Br J Surg 2009; 96: 1031e40. Marschall HU, Katsika D, Rudling M, Einarsson C. The genetic background of gallstone formation: an update. Biochem Biophys Res Commun 2010; 396: 58e62. Moser A, Roslyn J. Gallbladder and biliary tree. In: Corson J, Williamson R, eds. Surgery. 1st edn. London: Harcourt International, 2001. Strasberg SM. Clinical practice. Acute calculous cholecystitis. N Engl J Med 2008; 358: 2804e11. Zaliekas J, Munson JL. Complications of gallstones: the Mirizzi syndrome, gallstone ileus, gallstone pancreatitis, complications of lost gallstones. Surg Clin North Am 2008; 88: 1345e68. x.

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