Gall Stone
Content
HEPATOBILIARY SURGERY
Gallstones
presence presence of specific specific local conditions conditions with each type of stone stone having having an epidemiol epidemiologica ogicall and genetic genetic risk profile associated 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. Ethnic Ethnicity ity is a major major factor factor influen influencin cing g the preval prevalenc encee of different stone types. In Western societies cholesterol stones are by far the most common, accounting for 80 e90% 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 fibrosis or increased red cell destruction (e.g. haemolytic anaemia, anaemia, splenome splenomegaly, galy, myeloprol myeloprolifer iferative ative disorders disorders,, etc.). 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 associ associati ation on with with biliar biliary y infect infection ion or bile bile stasis stasis,, and are common in Asia, with reported prevalence rates as high as 20% in some some part partss of Chin China. a. It is thou though ghtt that that infe infect ctio ion n with 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.
Abeed H Chowdhury Dileep N Lobo
Abstract Gallstone Gallstoness represen representt one of the commonest commonest surgica surgicall problems 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 10 e30% of patients with gallstones develop symptoms, of which a majority eventually require endoscopic scopic or surgica surgicall interven intervention tion.. Complica Complication tionss of gallstone gallstone disease include include acute acute cholecys cholecystitis titis,, obstruct obstructive ive jaundice, jaundice, acute acute pancrea pancreatiti titis, s, 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 Cholecys Cholecystect tectomy; omy; endoscop endoscopic ic retrogra retrograde de cholangio cholangiopan pan-creatography; gallbladder; gallstone ileus; gallstones
Risk factors
Introduction
Nort North h Amer Americ ican an Indi Indian anss have have a high higher er risk risk of deve develo lopi ping ng cholelithiasis, as do first-degree relatives of patients with known gallstones gallstones,, indicatin indicating g a heritable heritable component component to the condition condition.. Whilst Whilst the presen presence ce of supers supersatu aturat rated ed bile bile is undoub undoubted tedly ly a prerequisite for cholesterol gallstone formation, other factors contribut contributee to individua individuall gallstone gallstone susceptib susceptibilit ility. y. These These include include impaired gallbladder motility and the presence of pro-nucleating factors. Risk factors for the development of cholesterol stones are shown in Box 1. 1.
Gallstones represent one of the commonest surgical problems in the developed world and impose a significant 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 which a majori majority ty eventu eventuall ally y requir requiree endos endoscop copic ic or surgic surgical al intervention. Each year more than 50,000 cholecystectomies are performed performed in the UK, with approximatel approximately y 700,000 700,000 being performed formed in the USA. Common Common bile bile duct duct stones stones are found 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 for cholesterol gallstone formation C
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Types of gallstone
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The process of gallstone formation involves the precipitation of substance substancess found in bile, bile, including including cholesterol, cholesterol, calcium calcium bilirbilirubinate, and calcium salts of phosphate, carbonate and palmitate. tate. The exact exact compos compositi ition on of stone stoness is depend dependent ent on the
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Abeed H Chowdhury BSc MRCS is a Specialist Registrar in the Division of Gastrointestinal Surgery at Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none.
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Dileep N Lobo MS DM FRCS FACS is Professor of Gastrointestinal Surgery in the Division of Gastrointestinal Surgery at Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none to declare.
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Age Female sex Family history Race Pregnancy Parity Obesity Oral contraceptives contraceptives Diabetes mellitus Cirrhosis Prolonged Prolonged fasting Rapid weight loss Total parenteral parenteral nutrition Ileal disease or resection Impaired gallbladder emptying
Box 1
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Mechanisms for cholesterol stone formation
Natural history
The secretion of bile salts, phospholipids and cholesterol from hepato hepatocy cytes tes is carefu carefully lly regula regulated ted by a series series of adenos adenosine ine triphosph triphosphate-b ate-bindin inding g (ATP-bin (ATP-binding) ding) cassette cassette transmemb transmembrane rane pumps (ABC transporters), which are, in turn, under transcriptional tional regula regulatio tion n by a small small number number of nuclea nuclearr recept receptors ors.. In normal circumstances cholesterol is secreted by hepatocytes as small unilamellar unilamellar vesicles vesicles (40e200 nm diamet diameter) er),, which which are conver converted ted to smalle smallerr micell micelles es (40e100 A diam diamet eter er)) by the the detergent action of bile salts (Figure ( Figure 1). 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 influences which may increase increase susceptibili susceptibility ty to stone formation. formation. Multiple candidate genes, many with orthologs in humans, have now been identified following the recognition of the lithogenic genes Lith1 and Lith2. In the normally normally non-lithog non-lithogenic enic mouse strain AKR/J, the presence of alleles from the lithogenic strain C57L/J in both Lith1 and Lith2 chromosome regions promotes the the gall gallst ston onee-fo form rmin ing g phen phenot otyp ype. e. Anot Anothe herr gene gene offe offeri ring ng a possible possible therapeutic therapeutic target target encodes encodes the farnesoid farnesoid X receptor receptor ( Fxr ), ), which in normal circumstances increases biliary bile salt and phosp phosphol holipi ipid d conce concentr ntrati ations ons.. Feedin Feeding g of synthe synthetic tic Fxr ligands ligands to gallstone gallstone suscepti susceptible ble mice confers a non-litho non-lithogenic genic phenotype mediated by an increased expression of several bile salt transport pumps. Although specific gene products for all Lith genes genes are yet to be fully fully charac character terize ized, d, candid candidate ate produc products ts include include hepatic hepatic lipid lipid transport transporters, ers, lipid lipid regulatory regulatory enzymes, enzymes, transcription factors and hormone receptors.
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 conditio conditions. ns. Symptoms, Symptoms, which which develop develop in 10% of patients patients by 5 years and in 20% by 20 years, are common to a number of upper gastrointestinal disorders and typified 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 manage managemen mentt of patien patients ts with with asympt asymptoma omatic tic gallst gallstone oness although prospective studies show that following diagnosis the risk of developing symptoms remains low, equating to 1 e4% per year, year, with with only only 10% 10% and 20% 20% develo developin ping g sympt symptoms oms within 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 obstructive jaundice and acute pancreatiti pancreatitis. s. Rare but serious serious complica complications tions of gallstones gallstones include gallstone 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 Biliary colic Gallstones obstructing the outlet of the gallbladder at Hartmann’s pouch pouch can cause biliary biliary colic, triggered triggered by contraction contraction of the gallbladder against a closed orifice. Experienced by about 20% of patients patients with gallstones 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). 2). Fluctuations are rare, and in this respect, the term ‘colic’ may be regarded as a misnomer. Pain is commonly, but not exclusiv exclusively ely post-pran post-prandial dial,, usually usually experienc experienced ed in the right upper upper quadra quadrant, nt, and often often radiat radiates es to the right right scapu scapula la or shoulder. A commonly reported feature is an inability to assume a comfortable position to lessen the pain. Two-thirds of patients prese presenti nting ng with with their their first first attack attack of biliar biliary y colic colic will will have have a further attack within 2 years, rising to 90% at 10 years, which explains in part the current recommendation for cholecystectomy cholecystectomy in patients with symptomatic gallstones.
Secretion of bile constituents from the hepatocyte luminal membrane Phospholipids
Bile salts
Cholesterol
ABC G5
ABC G8
ABC B4
ABC B11
Cytosol Lumen
Unilamellar vesicles
Micelles
Acute calculous cholecystitis Inflammation of the gallbladder can result from prolonged gallstone obstruction of the cystic duct. As indicated previously the risk of cholecys cholecystitis titis is much higher for those those who experience experience symptoms, but for all patients with gallstones this risk equates to roughly 1e3%. Obstruction increases intraluminal pressure with subseq subsequen uentt venous venous conges congestio tion, n, reduce reduced d arteri arterial al flow and
Bile salts, phospholipids and cholesterol are actively secreted 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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class classifie ified d into into twotypes. twotypes. Type Type I is causedby causedby a stone stone in Hartma Hartmann’ nn’ss pouch compressing the adjacent common bile duct. Type II is caused by erosion of such a stone into the common bile duct leading leading to a cholecyst cholecystocho ocholedo ledochal chal fistula. fistula. Diagnosed Diagnosed only in twothirdsof thirdsof cases cases preope preoperat rative ively,thereis ly,thereis an increa increasedriskof sedriskof bile bile duct duct injury during cholecystectomy when present. Of note, 6 e23% of patients diagnosed with Mirizzi’s syndrome preoperatively, have a final diagnosis of gallbladder carcinoma. Intra operative frozen section histological examination is therefore recommended for these these patients patients as radical radical cholecys cholecystect tectomy omy rather rather than interval interval re-operation is associated with improved outcomes.
Pain typically experienced during an attack of biliary colic
Plateau
Intensity
Rapid rise
Gallstone ileus Intestina Intestinall obstructi obstruction on can occur occur when gallstones gallstones occlude occlude the intestinal lumen. This clinical entity results most commonly from the presence of a cholecystoduodenal fistula, but rarely the cause is a cholecys cholecystoco tocoloni lonicc fistula. fistula. Responsi Responsible ble for 1% of all small bowel obstructions, patients present with intermittent intestinal obstruct obstruction ion as the gallstone gallstone impacts impacts and disimpact disimpacts, s, usually usually at the terminal terminal ileum and clear features of intestinal intestinal obstruction obstruction are present in only 50 e70% of patients, which can introduce diagnostic delay. Radiographic clues to the diagnosis include evidence of intest intestina inall obstru obstructi ction on with with a transi transitio tion n point point and thepresenceof thepresenceof air in the biliary tree, present in 40% of cases. Other causes of pneumobil pneumobilia ia can include include endoscop endoscopic ic sphincter sphincterotomy otomy or biliobilioenteric 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 fistula may be considered in fit patients, either simultaneously, or as a second-stage procedure.
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
impair impaired ed lymph lymphati aticc draina drainage. ge. Inflamm Inflammato atory ry mediat mediators ors,, in particular the prostaglandins I2 and E2, are released in response to mucosal mucosal ischaemi ischaemia a leading leading to inflammator inflammatory y cell infiltration infiltration and oedema of the gallbladder wall. Patients present with abdominal pain localized to the right upper quadrant quadrant and systemic systemic signs of inflammati inflammation, on, such as pyrexi pyrexia. a. An acute acute abdome abdomen n is reveal revealed ed on examin examinati ation on and a positive positive Murphy’s Murphy’s sign aids the different differentiatio iation n from biliary colic. colic. Progre Progress ssive ive inflamm inflammati ation on can lead lead to focal focal necros necrosis is,, 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.
Acalculous cholecystitis Although Although rare, accountin accounting g for only 2e15% of cases cases of acute acute cholecystitis, acute acalculous cholecystitis is recognized as an importantsurgicalemergenc importantsurgicalemergency y owingto an increasedrisk increasedrisk of serious serious complications. complications. Risk factors which also contribute to a mortality of 30% include intercurrent illness, recent major surgery or trauma, burns, burns, diabet diabetes es and total total parent parentera erall nutrit nutrition ion.. Other Other known 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. losis. Serious Serious complica complicationsare tionsare more common common than withcalculous withcalculous cholecystitis and include gangrene, empyema and perforation. Although Although poorly poorly understood understood,, the aetiologic aetiological al mechanis mechanisms ms include bile stasis and ischaemia. Bile stasis is thought to alter the compos compositi ition on of bile bile leadin leading g to increa increased sed viscos viscosity ity and subsequen subsequentt increased increased risk of bacterial bacterial overgrowth overgrowth.. Although Although histologically, histologically, there is little to distinguish acalculous cholecystitis cholecystitis from from that that caused caused by gallst gallstone ones, s, arteri arteriogr ograph aphy y often often reveal revealss multiple arterial occlusions and minimal venous filling suggesting that that microc microcirc ircula ulator tory y abnorm abnormali alitie tiess are centra centrall to the
Chronic cholecystitis Repeat Repeated ed low-gr low-grade ade obstru obstructi ction on can give give rise rise to a pictur picturee of chronic inflammation of the gallbladder, with progressive granulation lation and collagen collagen depositi deposition on within within the gallbladde gallbladderr wall. wall. Patients Patients typically typically present present with post-pran post-prandial dial fullness, fullness, belching, belching, nausea nausea and right upper quadrant discomfort. Symptom profiles vary widely and can even be identified in 12 e13% of patients without gallstones. stones. Clinical Clinical examinati examination on is usually usually unhelpful. unhelpful. Ultrasoun Ultrasound d 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 undergo laparosco laparoscopic pic cholecyst cholecystecto ectomy, my, and whilst whilst the gallbladd gallbladder er may be normal on histology, most patients appear to benefit from surgery, at least in the short term. Mirizzi’s syndrome Very occasion occasionally, ally, stones stones in the gallbladde gallbladderr may cause cause obstructi obstructive ve jaundice, eponymousl eponymously y termed termed Mirizzi’s Mirizzi’s syndrome, syndrome, which which is
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pathophysiological process. Often challenging, diagnosis can be made made using using ultras ultrasono onogra graphy phy,, which which in the presen presence ce of gallgallbladder wall thickening to 3.5 mm, has a sensitivity of 80% and specificity 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 unfit to undergo anaesthesia and surgery, percutaneo percutaneous us cholecys cholecystost tostomy omy is a viable viable primary primary treatment treatment strategy.
Management considerations in patients with cholecystolithiasis Ultrasound As only 10% of gallstones are radio-opaque ( Figure 3), 3), transabdominal ultrasound is the main diagnostic modality used for gallbladde gallbladderr disease. disease. Gallstone Gallstoness are usually usually seen as sonodense sonodense lesions with posterior acoustic shadowing ( Figure 4). 4). Thickening of the gallbladder wall and the presence of pericholecystic fluid suggest acute cholecystitis and an ultrasonic Murphy’s sign may be elicited. Dilatation of the biliary tree implies duct obstruction and common bile duct stones may sometimes be visible, although the lower lower end of the bile bile duct duct is someti sometimesobscu mesobscuredby redby bowel bowel gas. gas.
Figure 4 Transabdom Transabdominal inal 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 recently emerged emerged.. Data from animal and epidemio epidemiologi logical cal 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 1 e1.5 years had a reduced reduced risk risk of developi developing ng gallston gallstones es and undergoi undergoing ng subsequ subsequent ent cholecy cholecystec stectomy tomy by one-thir one-third d compare compared d to matched matched control control patients patients,, in whomstatinuse was absent.In absent.In rodent rodent studies studies,, blockin blocking g the intest intestina inall absor absorpti ption on of choles choleste terol rol with with the Nieman Niemann ne Pick Pick C1-li C1-like ke 1 protei protein n inhibi inhibitor tor,, ezetim ezetimib ibe, e, lowere lowered d bilia biliary ry cholesterol cholesterol secretion and in human studies the same treatment led to bile desatura desaturatio tion n and reduced reduced cholest cholesterol erol crystall crystallizat ization. ion. Although Although these these pharmaco pharmacologi logical cal agents offer offer a potentia potentiall role in the preventi prevention on of gallsto gallstones, nes, especially especially for patients patients at high risk of gallsto gallstone ne developm development, ent, further further evaluati evaluation on in clinica clinicall studieswill studieswill be required before this role can be established.
Dissolution therapy, lithotripsy and pharmacological targets Non-surgical options have been utilized in patients with sympgallstone ones, s, butthis courseof courseof treatm treatment ent plays plays a limite limited d role role tomatic gallst in compariso comparison n to laparosco laparoscopic pic cholecyst cholecystecto ectomy. my. Oral therapy therapy with bile salts salts (chenodeo (chenodeoxych xycholate olate and ursodeox ursodeoxycho ycholate) late) is suitable suitable in only 15% of symptomatic patients with cholesterol gallstones. In this subgroup of patients with favourable profiles (small stones,
Laparoscopic cholecystectomy Laparoscopic Laparoscopic cholecystectom cholecystectomy y (Fi Figures5and6 gures5and6)) has develop developed ed into the mainstay for treatment of symptomatic gallstones and in the developed world, is now the most commonly performed elective abdominal abdominal procedure. procedure. Previous abdominal surgery, pregnancy, pregnancy, cirrhosis and coagulopathy are no longer considered contraindications cations for laparosc laparoscopic opic surgery surgery which which can in many cases be undertaken undertaken safely as a day case procedure. procedure. Accordingly, perioperative ative mortal mortalit ity y is lowlying lowlying betwe between en 0 and0.3%,as is the the freque frequenc ncy y of complic complicatio ations. ns. The reporte reported d inciden incidence ce of bile bile ductinjuryis one in 200e300 300 casesand casesand the the conver conversio sion n rate rate 1e5%. Other complications complications requiring re-operation include major bowel or vessel injury during trocar insertion (0.02%), bile leak (0.1 e0.2%), peritonitis (0.2%), post post operativ operativee bleedin bleeding g (0.1% (0.1%e0.5%) and intra-abdominal intra-abdominalabsces abscesss (0.1%). Recent Recent advances advances in laparosco laparoscopic pic technology technology have seen the introduct introduction ion of single single incision incision laparosco laparoscopic pic cholecyst cholecystecto ectomy my
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 early interv intervent ention ion are unfoun unfounded ded with with no increa increase se in the freque frequency ncy of compli complicat cation ionss in compar compariso ison n with with the delaye delayed d 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) Commo Common n bile bile duct duct stone stoness may occur occur dueto passa passage ge of a stone stone from from the gallbladder, or arise de novo in association with biliary strictures, tures, infecti infection, on, duodena duodenall divertic diverticula ula or foreign foreign material(i.e. material(i.e. suture suture mater material ial). ). Pain Pain is notgeneral notgenerally ly regar regarde ded d as a featu feature re dueto a lack lack of smoothmusclewithinwall smoothmusclewithinwall of thecommonbile duct, duct, althoughsome althoughsome authors believe that spasm spasm of the sphincter sphincter of Oddi Oddi may contribute contribute to pain which is typically typically experienced experienced in the right upper quadrant. Commo Common n duct duct stones stones may be asymp asympto tomat matic ic,, or manif manifes estt as a number of well-defined clinical entities, entities, as outlined below.
Figure 5 It is essential to dissect Calot’s triangle prior to clipping any structure. This initial dissection shows that there are only two structures crossing Calot’s triangle (the cystic artery and the cystic duct).
(SILC) (SILC) with with early early report reportss sugges suggestin ting g no differ differenc encee in postpostoperative operative pain, blood loss or conversion conversion rates to the conventional 4 port approach. In the only randomized controlled trial compar comparing ing SILC SILC with with 4 port port laparo laparosco scopic pic cholec cholecyst ystec ectom tomy y involving 83 patients, similar pain and satisfaction scores were obtained for SILC compared to the standard four-port approach. Although there are obvious benefits in terms of cosmesis, long term data on umbilical hernia and complication rates have yet to be reported.
Asymptomatic common bile duct (CBD) stones When routine routine cholangiog cholangiography raphy is performed performed at laparosco laparoscopic pic cholecystectomy, common duct stones are found in 8 e20% of patients. Of these over 90% have pre operative indicators such as a histor history y of pancre pancreati atitis tis,, cholan cholangit gitis is or jaundi jaundice, ce, a dilate dilated d 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.
Acute versus inter val laparoscopic cholecystectomy for acute cholecystitis The traditiona traditionall strategy strategy for scheduli scheduling ng operative operative intervent intervention ion after acute cholecys cholecystitis titis included included a waiting waiting period period of several several weeks to allow the process of inflammation to settle in the belief that that this this redu reduce ced d the the risk risk of bile bile duct duct inju injury ry.. A numb number er of systematic reviews have provided evidence to refute this belief. An advantage advantage for early laparosco laparoscopic pic cholecyst cholecystecto ectomy my (within (within 1 week week of sympto symptom m onset) onset) has been been demons demonstra trated ted owing owing to
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), 7), or fluctuant jaundice due to ‘ball-valving’ of common duct stones. Abdominal ultrasonography is the first-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 with low sensi sensitiv tiviti ities es.. A normal normal CBD diamet diameter er is, howeve however, r, a strong negative predictor for the presence of CBD stones. The introduction of magnetic resonance cholangiopancreatography cholangiopancreatography (MRCP) (MRCP) has greatly greatly improved improved the detectio detection n of common common duct stones (Figure (Figure 8), 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 intravenous contrast, contrast, but it cannot 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 benefits in terms of patient morbidity. However, whilst there are proponents of routine pre-operative MRCP, most clinicians utilize MRCP selectively, often as part of stra strati tific ficat atio ion n tool toolss desi design gned ed to pred predic ictt indi indivi vidu dual al risk risk of harbouring common duct stones.
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 ascending infectio infection n from the gut. Typical Typical organisms organisms include include E. coli, Klebsiella pneumoniae and Enterococcus faecalis. Established lished ascendin ascending g cholangit cholangitis is e typifi typified ed by Charco Charcot’s t’s triad triad of obstructive jaundice, fever and rigours e is a surgical emergency mandating prompt biliary drainage. The development of shock and mental mental obfuscati obfuscation on in ascending ascending cholangiti cholangitiss (Reynold’ (Reynold’ss pentad) is a grave sign associated with a high mortality. ERCP (Figure 9) 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, becaus becausee patien patients ts are often often severe severely ly unwell unwell,, extern external al biliar biliary y drai draina nage ge is pref prefer erre red d to surg surger ery, y, alth althou ough gh the the deci decisi sion on is dependent upon the availability of local radiological expertise.
Acute pancreatitis Gallstones which which pass through the common bile duct can obstruct pancreati aticc duct duct either either transi transient ently ly as they they pass pass into into the the pancre 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 first-line investigat investigation ion of choice choice is abdominal abdominal ultrasonog ultrasonography raphy,, which which may identify gallbladder stones, a dilated common duct, or occasional sionally ly a common common duct duct stone. stone. It is worth worth apprec appreciat iating ing that that because the limit of resolution of abdominal ultrasonography is approx approxima imatel tely y 4 mm, small smaller er stone stoness respon responsib sible le for acute acute
Figure 9 ERCP in a patient with acute cholangitis demonstrating multiple stones in a dilated common bile duct (left). An endoscopic endoscopic sphincterotomy sphincterotomy wasperformed wasperformed anda double double pigtail pigtail stent stent was insertedto insertedto facilitat facilitate e drainage drainage (right).
Figure 8 An MRCP image demonstrating gallstones within the gallbladder and common bile duct, with associated ductal dilatation.
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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 early ERCP ERCP has been shown shown to reduce reduce both morbid morbidity ity and mortality. However, in the absence of cholangitis, early endoscopic sphincterotomy does not reduce pancreatic complications or mortality and should not be considered as definitive treatment of common common bile bile duct duct stones stones.. Patien Patients ts with with acute acute gallst gallstone one pancreatitis are at increased risk of further pancreatitis as well as other gallstone gallstone related related complica complications tions and should, should, therefore therefore,, undergo laparoscopic cholecystectomy and intra operative cholangiogram (IOC) once the patients’ clinical course permits.
a majority of patients, and is particularly useful in patients with failed failed transc transcys ystic tic explor explorati ation, on, large large or multip multiple le stones stones,, and patients with failed or contraindications to ERCP. The only absolute contraindication to laparoscopic choledochotomy is a small common common duct duct (<8 mm diameter), diameter), which which predispos predisposes es an increased increased risk of complica complications tions following following endoscopi endoscopicc explorati exploration. on. Once duct clearance clearance has been establish established ed the choledoc choledochotom hotomy y is sutured sutured and a subhepatic drain placed. Where doubt exists over the adequacy of duct duct cleara clearance nce,, thecystic thecystic duct duct maybe decomp decompres ressedwith sedwith either either a T-tube T-tube or an antegrade antegrade biliary biliary stent. stent. This manoeuvre manoeuvre also allows allows access for post operative ductal cholangiogram via the T-tube. ERCP ERCP can can be perf perfor orme med d intr intra a oper operat ativ ivel ely, y, but but is more more commonly performed post operatively. It is associated with duct clearance clearance rates of 90e95%, 95%, but is techni technical cally ly not feasib feasible le in approximately 5e10% of patients. Major complications complications including pancreatitis, cholangitis, haemorrhage and retroduodenal perforation ration occur occur in 10%of patien patients ts,, with with a proced procedure ure-re -relat lated ed mortal mortality ity of less less than than 1%. Ultimate Ultimately ly the choice choice of proced procedure ure for intra intra operative operatively ly detected detected CBD stones stones depends depends upon local expertise expertise and availability of resources.
Management considerations in patients with CBD stones Routine versus selective intra operative cholangiography The possibil possibility ity of overlooki overlooking ng occult occult common common bile duct stones stones has prompted some surgeons to advocate routine IOC at laparoscopic cholecyst cholecystecto ectomy, my, yet thisremains controver controversial sial.. Proponentsargue Proponentsargue that routine operative cholangiography not only identifies silent CBDstones, CBDstones, butalso reduce reducess therisk of signifi significan cantt bile bile duct duct injury 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 discovere discovered d in 2.8% at routine routine IOC,with residual residual symptomat symptomatic ic CBD stones identified in only 0.3% of those in the selective IOC. In partic particula ularr there there were were no differ differenc ences es in bile bile duct duct injuri injuries es among among the groups, suggesting that careful patient selection can reduce the number number of unnecessa unnecessary ry intra operative operative cholangio cholangiograms grams 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 identified pr e operatively When When CBD stone stoness are identi identifie fied d on radiol radiologi ogical cal imagin imaging, g, an attempt attempt at duct clearance clearance is consider considered ed mandatory. mandatory. Stone removal removal canbe achiev achieved ed surgi surgical cally ly or at ERCP. ERCP. Primar Primary y ERCP ERCP is consi consider dered ed preferable to surgery in post-cholecystectomy patients and those too frail frail or unfit unfit to underg undergo o surge surgery, ry, althou although gh a carefu carefull anaest anaesthet hetic ic assessment of such patients should be made, as up to 47% of patients patients will develop develop further further acute biliary episodes 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 balloo balloon n cathet catheter. er. Compli Complicat cation ionss occur occur in 4e10%, 10%, the the most most freque frequent nt being being pancre pancreati atitis tis in 5.4% 5.4% and bleedi bleeding ng in 2%. An evaluation evaluation of clotting clotting function function should should be performed 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. 2. In
Management considerations when CBD stones are identified intra operatively A properly performed intra operative cholangiogram is associated with low false-positive rates of less than 5%. When CBD stones are identified, the options are four-fold: open exploration of the common bile duct laparosco laparoscopic pic explorati exploration on of the CBD (transcys (transcystic tic or via choledochotomy) on-table ERCP post operative ERCP. The optimal management of CBD stones found at laparoscopic cholecyst cholecystecto ectomy my remains remains elusive, elusive, and is the subject subject of much debate. Open exploration allows for excellent access to the CBD, albeit at the expense of increased morbidity, post operative stay and recuperat recuperation ion time. time. Transcys Transcystic tic explorati exploration on utilizes utilizes small small calibre calibre endoscop endoscopes es or radiologic radiologically ally-guid -guided ed wire baskets baskets to access 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, clips, obviating obviating the need for intra-cor intra-corporea poreall suturing, suturing, but is associated with failure rates of 30 e40%. Laparoscopic choledocho edochotom tomy y allows allows for easy easy access access to the common common duct in
Reasons for ERCP failure in patients with choledocholithiasis
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Billroth II reconstruction Duodenal Duodenal stricture Duodenal Duodenal diverticulum diverticulum Ampullary stenosis Bile duct tortuosity Biliary stricture Stone impaction Multiple stones Stone >15 mm Intrahepatic Intrahepatic stone
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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 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 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.
such cases, surgical exploration exploration is necessary necessary.. For some, preoper operat ativ ivee ERCP ERCP is the the chos chosen en meth method od of duct duct clea cleara ranc nce, e, wherea whereass others others advoca advocate te laparo laparosc scopi opicc CBD explor explorati ation on and cholecyst cholecystecto ectomy my for all-comers all-comers.. A recent recent prospect prospective, ive, multimulticentre randomized controlled trial compared combined ERCP/ interval cholecystectomy with single-stage CBD exploration and cholecystectomy for patients with CBD stones. Identical efficacy 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 repres represent ent one of the common commones estt causes causes for acute acute hospit hospital al admission. The risk of developing complications is increased for symptomat symptomatic ic patients, patients, providing providing the rationale rationale for laparosco laparoscopic pic chol cholec ecys yste tect ctom omy y whic which h rema remain inss the the trea treatm tmen entt of choi choice ce.. Common bile duct stones can be the cause of obstructive jaundice, acute cholangitis or pancreatitis and can be managed with ERCP or open surgery. surgery. A
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presence presence of specific specific local conditions conditions with each type of stone stone having having an epidemiol epidemiologica ogicall and genetic genetic risk profile associated 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. Ethnic Ethnicity ity is a major major factor factor influen influencin cing g the preval prevalenc encee of different stone types. In Western societies cholesterol stones are by far the most common, accounting for 80 e90% 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 fibrosis or increased red cell destruction (e.g. haemolytic anaemia, anaemia, splenome splenomegaly, galy, myeloprol myeloprolifer iferative ative disorders disorders,, etc.). 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 associ associati ation on with with biliar biliary y infect infection ion or bile bile stasis stasis,, and are common in Asia, with reported prevalence rates as high as 20% in some some part partss of Chin China. a. It is thou though ghtt that that infe infect ctio ion n with 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.
Abeed H Chowdhury Dileep N Lobo
Abstract Gallstone Gallstoness represen representt one of the commonest commonest surgica surgicall problems 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 10 e30% of patients with gallstones develop symptoms, of which a majority eventually require endoscopic scopic or surgica surgicall interven intervention tion.. Complica Complication tionss of gallstone gallstone disease include include acute acute cholecys cholecystitis titis,, obstruct obstructive ive jaundice, jaundice, acute acute pancrea pancreatiti titis, s, 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 Cholecys Cholecystect tectomy; omy; endoscop endoscopic ic retrogra retrograde de cholangio cholangiopan pan-creatography; gallbladder; gallstone ileus; gallstones
Risk factors
Introduction
Nort North h Amer Americ ican an Indi Indian anss have have a high higher er risk risk of deve develo lopi ping ng cholelithiasis, as do first-degree relatives of patients with known gallstones gallstones,, indicatin indicating g a heritable heritable component component to the condition condition.. Whilst Whilst the presen presence ce of supers supersatu aturat rated ed bile bile is undoub undoubted tedly ly a prerequisite for cholesterol gallstone formation, other factors contribut contributee to individua individuall gallstone gallstone susceptib susceptibilit ility. y. These These include include impaired gallbladder motility and the presence of pro-nucleating factors. Risk factors for the development of cholesterol stones are shown in Box 1. 1.
Gallstones represent one of the commonest surgical problems in the developed world and impose a significant 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 which a majori majority ty eventu eventuall ally y requir requiree endos endoscop copic ic or surgic surgical al intervention. Each year more than 50,000 cholecystectomies are performed performed in the UK, with approximatel approximately y 700,000 700,000 being performed formed in the USA. Common Common bile bile duct duct stones stones are found 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.
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Types of gallstone
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The process of gallstone formation involves the precipitation of substance substancess found in bile, bile, including including cholesterol, cholesterol, calcium calcium bilirbilirubinate, and calcium salts of phosphate, carbonate and palmitate. tate. The exact exact compos compositi ition on of stone stoness is depend dependent ent on the
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Abeed H Chowdhury BSc MRCS is a Specialist Registrar in the Division of Gastrointestinal Surgery at Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none.
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Dileep N Lobo MS DM FRCS FACS is Professor of Gastrointestinal Surgery in the Division of Gastrointestinal Surgery at Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none to declare.
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Age Female sex Family history Race Pregnancy Parity Obesity Oral contraceptives contraceptives Diabetes mellitus Cirrhosis Prolonged Prolonged fasting Rapid weight loss Total parenteral parenteral nutrition Ileal disease or resection Impaired gallbladder emptying
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Mechanisms for cholesterol stone formation
Natural history
The secretion of bile salts, phospholipids and cholesterol from hepato hepatocy cytes tes is carefu carefully lly regula regulated ted by a series series of adenos adenosine ine triphosph triphosphate-b ate-bindin inding g (ATP-bin (ATP-binding) ding) cassette cassette transmemb transmembrane rane pumps (ABC transporters), which are, in turn, under transcriptional tional regula regulatio tion n by a small small number number of nuclea nuclearr recept receptors ors.. In normal circumstances cholesterol is secreted by hepatocytes as small unilamellar unilamellar vesicles vesicles (40e200 nm diamet diameter) er),, which which are conver converted ted to smalle smallerr micell micelles es (40e100 A diam diamet eter er)) by the the detergent action of bile salts (Figure ( Figure 1). 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 influences which may increase increase susceptibili susceptibility ty to stone formation. formation. Multiple candidate genes, many with orthologs in humans, have now been identified following the recognition of the lithogenic genes Lith1 and Lith2. In the normally normally non-lithog non-lithogenic enic mouse strain AKR/J, the presence of alleles from the lithogenic strain C57L/J in both Lith1 and Lith2 chromosome regions promotes the the gall gallst ston onee-fo form rmin ing g phen phenot otyp ype. e. Anot Anothe herr gene gene offe offeri ring ng a possible possible therapeutic therapeutic target target encodes encodes the farnesoid farnesoid X receptor receptor ( Fxr ), ), which in normal circumstances increases biliary bile salt and phosp phosphol holipi ipid d conce concentr ntrati ations ons.. Feedin Feeding g of synthe synthetic tic Fxr ligands ligands to gallstone gallstone suscepti susceptible ble mice confers a non-litho non-lithogenic genic phenotype mediated by an increased expression of several bile salt transport pumps. Although specific gene products for all Lith genes genes are yet to be fully fully charac character terize ized, d, candid candidate ate produc products ts include include hepatic hepatic lipid lipid transport transporters, ers, lipid lipid regulatory regulatory enzymes, enzymes, transcription factors and hormone receptors.
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 conditio conditions. ns. Symptoms, Symptoms, which which develop develop in 10% of patients patients by 5 years and in 20% by 20 years, are common to a number of upper gastrointestinal disorders and typified 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 manage managemen mentt of patien patients ts with with asympt asymptoma omatic tic gallst gallstone oness although prospective studies show that following diagnosis the risk of developing symptoms remains low, equating to 1 e4% per year, year, with with only only 10% 10% and 20% 20% develo developin ping g sympt symptoms oms within 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 obstructive jaundice and acute pancreatiti pancreatitis. s. Rare but serious serious complica complications tions of gallstones gallstones include gallstone 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 Biliary colic Gallstones obstructing the outlet of the gallbladder at Hartmann’s pouch pouch can cause biliary biliary colic, triggered triggered by contraction contraction of the gallbladder against a closed orifice. Experienced by about 20% of patients patients with gallstones 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). 2). Fluctuations are rare, and in this respect, the term ‘colic’ may be regarded as a misnomer. Pain is commonly, but not exclusiv exclusively ely post-pran post-prandial dial,, usually usually experienc experienced ed in the right upper upper quadra quadrant, nt, and often often radiat radiates es to the right right scapu scapula la or shoulder. A commonly reported feature is an inability to assume a comfortable position to lessen the pain. Two-thirds of patients prese presenti nting ng with with their their first first attack attack of biliar biliary y colic colic will will have have a further attack within 2 years, rising to 90% at 10 years, which explains in part the current recommendation for cholecystectomy cholecystectomy in patients with symptomatic gallstones.
Secretion of bile constituents from the hepatocyte luminal membrane Phospholipids
Bile salts
Cholesterol
ABC G5
ABC G8
ABC B4
ABC B11
Cytosol Lumen
Unilamellar vesicles
Micelles
Acute calculous cholecystitis Inflammation of the gallbladder can result from prolonged gallstone obstruction of the cystic duct. As indicated previously the risk of cholecys cholecystitis titis is much higher for those those who experience experience symptoms, but for all patients with gallstones this risk equates to roughly 1e3%. Obstruction increases intraluminal pressure with subseq subsequen uentt venous venous conges congestio tion, n, reduce reduced d arteri arterial al flow and
Bile salts, phospholipids and cholesterol are actively secreted 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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class classifie ified d into into twotypes. twotypes. Type Type I is causedby causedby a stone stone in Hartma Hartmann’ nn’ss pouch compressing the adjacent common bile duct. Type II is caused by erosion of such a stone into the common bile duct leading leading to a cholecyst cholecystocho ocholedo ledochal chal fistula. fistula. Diagnosed Diagnosed only in twothirdsof thirdsof cases cases preope preoperat rative ively,thereis ly,thereis an increa increasedriskof sedriskof bile bile duct duct injury during cholecystectomy when present. Of note, 6 e23% of patients diagnosed with Mirizzi’s syndrome preoperatively, have a final diagnosis of gallbladder carcinoma. Intra operative frozen section histological examination is therefore recommended for these these patients patients as radical radical cholecys cholecystect tectomy omy rather rather than interval interval re-operation is associated with improved outcomes.
Pain typically experienced during an attack of biliary colic
Plateau
Intensity
Rapid rise
Gallstone ileus Intestina Intestinall obstructi obstruction on can occur occur when gallstones gallstones occlude occlude the intestinal lumen. This clinical entity results most commonly from the presence of a cholecystoduodenal fistula, but rarely the cause is a cholecys cholecystoco tocoloni lonicc fistula. fistula. Responsi Responsible ble for 1% of all small bowel obstructions, patients present with intermittent intestinal obstruct obstruction ion as the gallstone gallstone impacts impacts and disimpact disimpacts, s, usually usually at the terminal terminal ileum and clear features of intestinal intestinal obstruction obstruction are present in only 50 e70% of patients, which can introduce diagnostic delay. Radiographic clues to the diagnosis include evidence of intest intestina inall obstru obstructi ction on with with a transi transitio tion n point point and thepresenceof thepresenceof air in the biliary tree, present in 40% of cases. Other causes of pneumobil pneumobilia ia can include include endoscop endoscopic ic sphincter sphincterotomy otomy or biliobilioenteric 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 fistula may be considered in fit patients, either simultaneously, or as a second-stage procedure.
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
impair impaired ed lymph lymphati aticc draina drainage. ge. Inflamm Inflammato atory ry mediat mediators ors,, in particular the prostaglandins I2 and E2, are released in response to mucosal mucosal ischaemi ischaemia a leading leading to inflammator inflammatory y cell infiltration infiltration and oedema of the gallbladder wall. Patients present with abdominal pain localized to the right upper quadrant quadrant and systemic systemic signs of inflammati inflammation, on, such as pyrexi pyrexia. a. An acute acute abdome abdomen n is reveal revealed ed on examin examinati ation on and a positive positive Murphy’s Murphy’s sign aids the different differentiatio iation n from biliary colic. colic. Progre Progress ssive ive inflamm inflammati ation on can lead lead to focal focal necros necrosis is,, 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.
Acalculous cholecystitis Although Although rare, accountin accounting g for only 2e15% of cases cases of acute acute cholecystitis, acute acalculous cholecystitis is recognized as an importantsurgicalemergenc importantsurgicalemergency y owingto an increasedrisk increasedrisk of serious serious complications. complications. Risk factors which also contribute to a mortality of 30% include intercurrent illness, recent major surgery or trauma, burns, burns, diabet diabetes es and total total parent parentera erall nutrit nutrition ion.. Other Other known 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. losis. Serious Serious complica complicationsare tionsare more common common than withcalculous withcalculous cholecystitis and include gangrene, empyema and perforation. Although Although poorly poorly understood understood,, the aetiologic aetiological al mechanis mechanisms ms include bile stasis and ischaemia. Bile stasis is thought to alter the compos compositi ition on of bile bile leadin leading g to increa increased sed viscos viscosity ity and subsequen subsequentt increased increased risk of bacterial bacterial overgrowth overgrowth.. Although Although histologically, histologically, there is little to distinguish acalculous cholecystitis cholecystitis from from that that caused caused by gallst gallstone ones, s, arteri arteriogr ograph aphy y often often reveal revealss multiple arterial occlusions and minimal venous filling suggesting that that microc microcirc ircula ulator tory y abnorm abnormali alitie tiess are centra centrall to the
Chronic cholecystitis Repeat Repeated ed low-gr low-grade ade obstru obstructi ction on can give give rise rise to a pictur picturee of chronic inflammation of the gallbladder, with progressive granulation lation and collagen collagen depositi deposition on within within the gallbladde gallbladderr wall. wall. Patients Patients typically typically present present with post-pran post-prandial dial fullness, fullness, belching, belching, nausea nausea and right upper quadrant discomfort. Symptom profiles vary widely and can even be identified in 12 e13% of patients without gallstones. stones. Clinical Clinical examinati examination on is usually usually unhelpful. unhelpful. Ultrasoun Ultrasound d 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 undergo laparosco laparoscopic pic cholecyst cholecystecto ectomy, my, and whilst whilst the gallbladd gallbladder er may be normal on histology, most patients appear to benefit from surgery, at least in the short term. Mirizzi’s syndrome Very occasion occasionally, ally, stones stones in the gallbladde gallbladderr may cause cause obstructi obstructive ve jaundice, eponymousl eponymously y termed termed Mirizzi’s Mirizzi’s syndrome, syndrome, which which is
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pathophysiological process. Often challenging, diagnosis can be made made using using ultras ultrasono onogra graphy phy,, which which in the presen presence ce of gallgallbladder wall thickening to 3.5 mm, has a sensitivity of 80% and specificity 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 unfit to undergo anaesthesia and surgery, percutaneo percutaneous us cholecys cholecystost tostomy omy is a viable viable primary primary treatment treatment strategy.
Management considerations in patients with cholecystolithiasis Ultrasound As only 10% of gallstones are radio-opaque ( Figure 3), 3), transabdominal ultrasound is the main diagnostic modality used for gallbladde gallbladderr disease. disease. Gallstone Gallstoness are usually usually seen as sonodense sonodense lesions with posterior acoustic shadowing ( Figure 4). 4). Thickening of the gallbladder wall and the presence of pericholecystic fluid suggest acute cholecystitis and an ultrasonic Murphy’s sign may be elicited. Dilatation of the biliary tree implies duct obstruction and common bile duct stones may sometimes be visible, although the lower lower end of the bile bile duct duct is someti sometimesobscu mesobscuredby redby bowel bowel gas. gas.
Figure 4 Transabdom Transabdominal inal 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 recently emerged emerged.. Data from animal and epidemio epidemiologi logical cal 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 1 e1.5 years had a reduced reduced risk risk of developi developing ng gallston gallstones es and undergoi undergoing ng subsequ subsequent ent cholecy cholecystec stectomy tomy by one-thir one-third d compare compared d to matched matched control control patients patients,, in whomstatinuse was absent.In absent.In rodent rodent studies studies,, blockin blocking g the intest intestina inall absor absorpti ption on of choles choleste terol rol with with the Nieman Niemann ne Pick Pick C1-li C1-like ke 1 protei protein n inhibi inhibitor tor,, ezetim ezetimib ibe, e, lowere lowered d bilia biliary ry cholesterol cholesterol secretion and in human studies the same treatment led to bile desatura desaturatio tion n and reduced reduced cholest cholesterol erol crystall crystallizat ization. ion. Although Although these these pharmaco pharmacologi logical cal agents offer offer a potentia potentiall role in the preventi prevention on of gallsto gallstones, nes, especially especially for patients patients at high risk of gallsto gallstone ne developm development, ent, further further evaluati evaluation on in clinica clinicall studieswill studieswill be required before this role can be established.
Dissolution therapy, lithotripsy and pharmacological targets Non-surgical options have been utilized in patients with sympgallstone ones, s, butthis courseof courseof treatm treatment ent plays plays a limite limited d role role tomatic gallst in compariso comparison n to laparosco laparoscopic pic cholecyst cholecystecto ectomy. my. Oral therapy therapy with bile salts salts (chenodeo (chenodeoxych xycholate olate and ursodeox ursodeoxycho ycholate) late) is suitable suitable in only 15% of symptomatic patients with cholesterol gallstones. In this subgroup of patients with favourable profiles (small stones,
Laparoscopic cholecystectomy Laparoscopic Laparoscopic cholecystectom cholecystectomy y (Fi Figures5and6 gures5and6)) has develop developed ed into the mainstay for treatment of symptomatic gallstones and in the developed world, is now the most commonly performed elective abdominal abdominal procedure. procedure. Previous abdominal surgery, pregnancy, pregnancy, cirrhosis and coagulopathy are no longer considered contraindications cations for laparosc laparoscopic opic surgery surgery which which can in many cases be undertaken undertaken safely as a day case procedure. procedure. Accordingly, perioperative ative mortal mortalit ity y is lowlying lowlying betwe between en 0 and0.3%,as is the the freque frequenc ncy y of complic complicatio ations. ns. The reporte reported d inciden incidence ce of bile bile ductinjuryis one in 200e300 300 casesand casesand the the conver conversio sion n rate rate 1e5%. Other complications complications requiring re-operation include major bowel or vessel injury during trocar insertion (0.02%), bile leak (0.1 e0.2%), peritonitis (0.2%), post post operativ operativee bleedin bleeding g (0.1% (0.1%e0.5%) and intra-abdominal intra-abdominalabsces abscesss (0.1%). Recent Recent advances advances in laparosco laparoscopic pic technology technology have seen the introduct introduction ion of single single incision incision laparosco laparoscopic pic cholecyst cholecystecto ectomy my
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 early interv intervent ention ion are unfoun unfounded ded with with no increa increase se in the freque frequency ncy of compli complicat cation ionss in compar compariso ison n with with the delaye delayed d 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) Commo Common n bile bile duct duct stone stoness may occur occur dueto passa passage ge of a stone stone from from the gallbladder, or arise de novo in association with biliary strictures, tures, infecti infection, on, duodena duodenall divertic diverticula ula or foreign foreign material(i.e. material(i.e. suture suture mater material ial). ). Pain Pain is notgeneral notgenerally ly regar regarde ded d as a featu feature re dueto a lack lack of smoothmusclewithinwall smoothmusclewithinwall of thecommonbile duct, duct, althoughsome althoughsome authors believe that spasm spasm of the sphincter sphincter of Oddi Oddi may contribute contribute to pain which is typically typically experienced experienced in the right upper quadrant. Commo Common n duct duct stones stones may be asymp asympto tomat matic ic,, or manif manifes estt as a number of well-defined clinical entities, entities, as outlined below.
Figure 5 It is essential to dissect Calot’s triangle prior to clipping any structure. This initial dissection shows that there are only two structures crossing Calot’s triangle (the cystic artery and the cystic duct).
(SILC) (SILC) with with early early report reportss sugges suggestin ting g no differ differenc encee in postpostoperative operative pain, blood loss or conversion conversion rates to the conventional 4 port approach. In the only randomized controlled trial compar comparing ing SILC SILC with with 4 port port laparo laparosco scopic pic cholec cholecyst ystec ectom tomy y involving 83 patients, similar pain and satisfaction scores were obtained for SILC compared to the standard four-port approach. Although there are obvious benefits in terms of cosmesis, long term data on umbilical hernia and complication rates have yet to be reported.
Asymptomatic common bile duct (CBD) stones When routine routine cholangiog cholangiography raphy is performed performed at laparosco laparoscopic pic cholecystectomy, common duct stones are found in 8 e20% of patients. Of these over 90% have pre operative indicators such as a histor history y of pancre pancreati atitis tis,, cholan cholangit gitis is or jaundi jaundice, ce, a dilate dilated d 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.
Acute versus inter val laparoscopic cholecystectomy for acute cholecystitis The traditiona traditionall strategy strategy for scheduli scheduling ng operative operative intervent intervention ion after acute cholecys cholecystitis titis included included a waiting waiting period period of several several weeks to allow the process of inflammation to settle in the belief that that this this redu reduce ced d the the risk risk of bile bile duct duct inju injury ry.. A numb number er of systematic reviews have provided evidence to refute this belief. An advantage advantage for early laparosco laparoscopic pic cholecyst cholecystecto ectomy my (within (within 1 week week of sympto symptom m onset) onset) has been been demons demonstra trated ted owing owing to
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), 7), or fluctuant jaundice due to ‘ball-valving’ of common duct stones. Abdominal ultrasonography is the first-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 with low sensi sensitiv tiviti ities es.. A normal normal CBD diamet diameter er is, howeve however, r, a strong negative predictor for the presence of CBD stones. The introduction of magnetic resonance cholangiopancreatography cholangiopancreatography (MRCP) (MRCP) has greatly greatly improved improved the detectio detection n of common common duct stones (Figure (Figure 8), 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 intravenous contrast, contrast, but it cannot 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 benefits in terms of patient morbidity. However, whilst there are proponents of routine pre-operative MRCP, most clinicians utilize MRCP selectively, often as part of stra strati tific ficat atio ion n tool toolss desi design gned ed to pred predic ictt indi indivi vidu dual al risk risk of harbouring common duct stones.
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 ascending infectio infection n from the gut. Typical Typical organisms organisms include include E. coli, Klebsiella pneumoniae and Enterococcus faecalis. Established lished ascendin ascending g cholangit cholangitis is e typifi typified ed by Charco Charcot’s t’s triad triad of obstructive jaundice, fever and rigours e is a surgical emergency mandating prompt biliary drainage. The development of shock and mental mental obfuscati obfuscation on in ascending ascending cholangiti cholangitiss (Reynold’ (Reynold’ss pentad) is a grave sign associated with a high mortality. ERCP (Figure 9) 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, becaus becausee patien patients ts are often often severe severely ly unwell unwell,, extern external al biliar biliary y drai draina nage ge is pref prefer erre red d to surg surger ery, y, alth althou ough gh the the deci decisi sion on is dependent upon the availability of local radiological expertise.
Acute pancreatitis Gallstones which which pass through the common bile duct can obstruct pancreati aticc duct duct either either transi transient ently ly as they they pass pass into into the the pancre 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 first-line investigat investigation ion of choice choice is abdominal abdominal ultrasonog ultrasonography raphy,, which which may identify gallbladder stones, a dilated common duct, or occasional sionally ly a common common duct duct stone. stone. It is worth worth apprec appreciat iating ing that that because the limit of resolution of abdominal ultrasonography is approx approxima imatel tely y 4 mm, small smaller er stone stoness respon responsib sible le for acute acute
Figure 9 ERCP in a patient with acute cholangitis demonstrating multiple stones in a dilated common bile duct (left). An endoscopic endoscopic sphincterotomy sphincterotomy wasperformed wasperformed anda double double pigtail pigtail stent stent was insertedto insertedto facilitat facilitate e drainage drainage (right).
Figure 8 An MRCP image demonstrating gallstones within the gallbladder and common bile duct, with associated ductal dilatation.
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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 early ERCP ERCP has been shown shown to reduce reduce both morbid morbidity ity and mortality. However, in the absence of cholangitis, early endoscopic sphincterotomy does not reduce pancreatic complications or mortality and should not be considered as definitive treatment of common common bile bile duct duct stones stones.. Patien Patients ts with with acute acute gallst gallstone one pancreatitis are at increased risk of further pancreatitis as well as other gallstone gallstone related related complica complications tions and should, should, therefore therefore,, undergo laparoscopic cholecystectomy and intra operative cholangiogram (IOC) once the patients’ clinical course permits.
a majority of patients, and is particularly useful in patients with failed failed transc transcys ystic tic explor explorati ation, on, large large or multip multiple le stones stones,, and patients with failed or contraindications to ERCP. The only absolute contraindication to laparoscopic choledochotomy is a small common common duct duct (<8 mm diameter), diameter), which which predispos predisposes es an increased increased risk of complica complications tions following following endoscopi endoscopicc explorati exploration. on. Once duct clearance clearance has been establish established ed the choledoc choledochotom hotomy y is sutured sutured and a subhepatic drain placed. Where doubt exists over the adequacy of duct duct cleara clearance nce,, thecystic thecystic duct duct maybe decomp decompres ressedwith sedwith either either a T-tube T-tube or an antegrade antegrade biliary biliary stent. stent. This manoeuvre manoeuvre also allows allows access for post operative ductal cholangiogram via the T-tube. ERCP ERCP can can be perf perfor orme med d intr intra a oper operat ativ ivel ely, y, but but is more more commonly performed post operatively. It is associated with duct clearance clearance rates of 90e95%, 95%, but is techni technical cally ly not feasib feasible le in approximately 5e10% of patients. Major complications complications including pancreatitis, cholangitis, haemorrhage and retroduodenal perforation ration occur occur in 10%of patien patients ts,, with with a proced procedure ure-re -relat lated ed mortal mortality ity of less less than than 1%. Ultimate Ultimately ly the choice choice of proced procedure ure for intra intra operative operatively ly detected detected CBD stones stones depends depends upon local expertise expertise and availability of resources.
Management considerations in patients with CBD stones Routine versus selective intra operative cholangiography The possibil possibility ity of overlooki overlooking ng occult occult common common bile duct stones stones has prompted some surgeons to advocate routine IOC at laparoscopic cholecyst cholecystecto ectomy, my, yet thisremains controver controversial sial.. Proponentsargue Proponentsargue that routine operative cholangiography not only identifies silent CBDstones, CBDstones, butalso reduce reducess therisk of signifi significan cantt bile bile duct duct injury 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 discovere discovered d in 2.8% at routine routine IOC,with residual residual symptomat symptomatic ic CBD stones identified in only 0.3% of those in the selective IOC. In partic particula ularr there there were were no differ differenc ences es in bile bile duct duct injuri injuries es among among the groups, suggesting that careful patient selection can reduce the number number of unnecessa unnecessary ry intra operative operative cholangio cholangiograms grams 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 identified pr e operatively When When CBD stone stoness are identi identifie fied d on radiol radiologi ogical cal imagin imaging, g, an attempt attempt at duct clearance clearance is consider considered ed mandatory. mandatory. Stone removal removal canbe achiev achieved ed surgi surgical cally ly or at ERCP. ERCP. Primar Primary y ERCP ERCP is consi consider dered ed preferable to surgery in post-cholecystectomy patients and those too frail frail or unfit unfit to underg undergo o surge surgery, ry, althou although gh a carefu carefull anaest anaesthet hetic ic assessment of such patients should be made, as up to 47% of patients patients will develop develop further further acute biliary episodes 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 balloo balloon n cathet catheter. er. Compli Complicat cation ionss occur occur in 4e10%, 10%, the the most most freque frequent nt being being pancre pancreati atitis tis in 5.4% 5.4% and bleedi bleeding ng in 2%. An evaluation evaluation of clotting clotting function function should should be performed 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. 2. In
Management considerations when CBD stones are identified intra operatively A properly performed intra operative cholangiogram is associated with low false-positive rates of less than 5%. When CBD stones are identified, the options are four-fold: open exploration of the common bile duct laparosco laparoscopic pic explorati exploration on of the CBD (transcys (transcystic tic or via choledochotomy) on-table ERCP post operative ERCP. The optimal management of CBD stones found at laparoscopic cholecyst cholecystecto ectomy my remains remains elusive, elusive, and is the subject subject of much debate. Open exploration allows for excellent access to the CBD, albeit at the expense of increased morbidity, post operative stay and recuperat recuperation ion time. time. Transcys Transcystic tic explorati exploration on utilizes utilizes small small calibre calibre endoscop endoscopes es or radiologic radiologically ally-guid -guided ed wire baskets baskets to access 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, clips, obviating obviating the need for intra-cor intra-corporea poreall suturing, suturing, but is associated with failure rates of 30 e40%. Laparoscopic choledocho edochotom tomy y allows allows for easy easy access access to the common common duct in
Reasons for ERCP failure in patients with choledocholithiasis
C
C
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C
C
C
C
C
C
Billroth II reconstruction Duodenal Duodenal stricture Duodenal Duodenal diverticulum diverticulum Ampullary stenosis Bile duct tortuosity Biliary stricture Stone impaction Multiple stones Stone >15 mm Intrahepatic Intrahepatic stone
Box 2
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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 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 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.
such cases, surgical exploration exploration is necessary necessary.. For some, preoper operat ativ ivee ERCP ERCP is the the chos chosen en meth method od of duct duct clea cleara ranc nce, e, wherea whereass others others advoca advocate te laparo laparosc scopi opicc CBD explor explorati ation on and cholecyst cholecystecto ectomy my for all-comers all-comers.. A recent recent prospect prospective, ive, multimulticentre randomized controlled trial compared combined ERCP/ interval cholecystectomy with single-stage CBD exploration and cholecystectomy for patients with CBD stones. Identical efficacy 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 repres represent ent one of the common commones estt causes causes for acute acute hospit hospital al admission. The risk of developing complications is increased for symptomat symptomatic ic patients, patients, providing providing the rationale rationale for laparosco laparoscopic pic chol cholec ecys yste tect ctom omy y whic which h rema remain inss the the trea treatm tmen entt of choi choice ce.. Common bile duct stones can be the cause of obstructive jaundice, acute cholangitis or pancreatitis and can be managed with ERCP or open surgery. surgery. A
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