How toTreat PULL-OUT SECTION

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INSIDE Aetiology Symptoms Management Cholecystitis Bile duct stones Related conditions

the authors

Dr Tony Speer gastroenterologist, Royal Melbourne Hospital and Western Hospital, Melbourne, Victoria.

Gallst nes Background

Professor Robert Gibson department of radiology, University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria.

Figure 1: Cholesterol stones.

GALLSTONES are common and are a leading cause of hospital admissions related to gastrointestinal disease. Since 1950, the number of cholecystectomies performed has increased markedly. It has further increased since 1989 when laparoscopic cholecystectomy was introduced. The prevalence of gallstone disease in adults is between 10 and 15%. About 75% of gallstones are cholesterol stones (figure 1), 20% are black pigment stones, containing insoluble bilirubin pigment polymer with calcium salts and cholesterol, and about 5% are brown pigment stones containing calcium bilirubinate and calcium palmitate and cholesterol. cont’d next page

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19 April 2013 | Australian Doctor |

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How To Treat – Gallstones Aetiology CHOLESTEROL stones form when three basic conditions coexist: cholesterol super saturation in bile, crystal nucleation and gall bladder stasis. Black pigment stones also occur in the gall bladder and are more frequent in the elderly. Deconjugation of the bile probably by bacterial enzymes leads to the formation of complex polymers of calcium bilirubin. Brown pigment stones are found most often within the bile duct and are associated with infection such as Clonorchis sinensis, Opisthorchis viverrini and Fasciola hepatica. Brown pigment stones are more common in Asia and are found in patients presenting with oriental cholangitis, which is a condition with multiple intrahepatic stones and strictures.

Risk factors for cholesterol stones Case–control studies comparing patients with gallstones and those without have confirmed gallstone

Cholesterol stone risk factors Increasing age High BMI Family history Female Diet

formation is influenced by a complex interaction between genes and environment (see box, right). Age is the most significant risk factor. Gallstones are rare in children but their prevalence increases with each decade to about 50% in those older than 80 years. A family history of stones increases risk fivefold. Several genes have been associated with gallstone disease, however no mode of simple

Mendelian pattern inheritance can account for most stones. Women are twice as likely to develop stones as men, although this difference narrows after menopause. Oestrogens increase cholesterol saturation in bile and progesterones act by impairing the gall bladder emptying. In pregnancy, new stones appear in about 30% of women. As hormone levels return to normal post-

partum, small gallstones often dissolve or pass spontaneously. Fertility is not an independent risk factor however the risk of gallstones increases with the number of pregnancies. Obesity increases the risk of stones. Women with severe obesity (ie, BMI greater than 32kg/m2) have a sixfold increased risk of stones. Rapid weight loss is also associated with stones, in particular the weight loss following bariatric surgery is associated with a 30-70% risk of developing gallstones. A Western diet high in refined carbohydrate and fat and low in fibre increases the risk of gallstones. Unsaturated fats, fibre and probably moderate intakes of coffee and

alcohol reduce the risk of stones. Increased physical activity, independent of its role in weight loss, reduces the incidence of stones. It has been suggested that 30 minutes of exercise five times a week will prevent gallstones from developing. Gallstones are more common in cirrhosis of the liver, possibly due to altered pigment secretion and increased oestrogen levels. Epidemiological studies suggest that the traditional textbook description of a typical at-risk patient as fair, fat, fertile, female and 40 is not fully supported by the evidence. Stones are certainly more common with higher BMI. However, it is parity not fertility that increases the risk of stones. Furthermore, while the incidence of cholecystectomy is greatest between 40 and 50 years of age, the prevalence of stones increases with each decade of age and is highest in those older than 80. Women are more likely to have stones than men but the prevalence is more equal after menopause.

Symptoms Asymptomatic STUDIES screening large populations with ultrasound have found that gallstones are asymptomatic in most patients (70-80%). The risk of developing symptoms is low, about 2-3% at one year, 10% by five years and plateaus at about 20% at 20 years.

Abdominal pain Stones cause pain when the gall bladder contracts, forcing the stone into the gall bladder neck or cystic duct, thereby obstructing drainage and increasing the intraluminal pressure. The stone often then falls back out of the cystic duct, the gall bladder empties and the pain resolves. Biliary colic is usually constant, not colicky, and lasts from 30 minutes to four hours. The pain is often right upper quadrant or epigastric and radiates through to the back but may also occur in the left upper quadrant. There may be associated nausea and vomiting and the patient often looks pale and sweaty. Prolonged pain, lasting more than 4-6 hours — especially if associated with fever

Biliary colic practice points Constant severe pain Not colicky Right upper quadrant/epigastric Duration ¼-4 hours Occurs infrequently, with weeks or months between episodes

— should arouse suspicion for acute cholecystitis rather than an attack of simple biliary colic.

Flatulent dyspepsia A variety of symptoms including bloating, fatty food intolerance, reflux and flatulence have been attributed to gallstones in the past. In 1908 Moynihan described gaseous eructation, flatulence, heaviness, epigastric pain of varying intensity and heartburn as the inaugural symptoms of gall bladder disease. This view became widespread and can still be found in recent textbooks and in some websites dealing with gallstone symptoms. About 40 years after Moynihan’s publication, physicians were less convinced gallstones caused

flatulent dyspepsia and surgeons found that cholecystectomy did not cure flatulent dyspepsia. Price performed an epidemiological study of 3000 patients in Edinburgh in 1963.1 Patients were interviewed and symptoms of flatulent dyspepsia were noted. An oral cholecystogram was performed to divide the group into those with and those without stones. Flatulent dyspepsia occurred in 22% of those with normal cholecystograms and in 25% of those with stones. More recent larger studies using ultrasound to screen for stones have found that flatulent dyspepsia and fatty food intolerance occur in 30-50% of both those with stones and those without. Dyspepsia is a common symptom in the normal population and is not associated with gallstones.

Investigation of symptoms Ultrasonography is the gold standard for diagnosing stones in the gall bladder (figure 2). Gallstones are mainly cholesterol with a small and variable amount of calcium salts. Fewer

Figure 2: Ultrasound. Single stone (arrow) in the gall bladder with a typical acoustic shadow (arrowheads).

than 10% can be seen on a plain abdominal X-ray. Ultrasound has a high sensitivity in excess of 95%. It has very few false positives and its false negative rate is 3-5% and most of these occur with larger patients and with small stones. Ultrasound is subject to operator performance variability and a repeat ultrasound may reveal stones if the initial study is negative. Occasionally it is difficult to dif-

ferentiate small gall bladder polyps and small stones, and the two may coexist. The ultrasound finding of gall bladder ‘sludge’ is usually not significant although its presence may obscure very small stones. CT has a low sensitivity (about 50%) for gall bladder stones. CT IV cholangiography (CT-IVC) and magnetic resonance cholangiopancreatography (MRCP) both are relatively insensitive for gall bladder stones.

complications guides the patient in the process of informed consent. Death and bile duct injury are possible major, but unlikely, adverse outcomes that should be discussed. The average perioperative mortality is reported to be between 0.1 and 0.6%. However younger patients undergoing elective surgery have a lower mortality than average. Mortality is higher in those older than 65-70, as cardiac and respiratory comorbidity is more common. Other comorbidities, particularly cirrhosis, also increase mortality. Bile duct injury, occurring in 0.10.3% of patients, can be devastating for a patient treated electively for

a benign disorder. Bile duct injury causes significant perioperative morbidity and mortality, reduced longterm survival and quality of life, with high rates of subsequent litigation. Cholecystectomy does not relieve the pain in all patients — pain recurs or persists in 20-30% of cases. Studies of post-cholecystectomy pain have found patient selection is the key to good outcomes. Abdominal pain is a common presenting symptom in general practice but only a small proportion of patients have pain due to gallstones. Muris et al. studied 578 patients with non-acute abdominal pain and cont’d page 28

Management Asymptomatic stones GALLSTONES may be detected in patients undergoing abdominal ultrasound for investigation of symptoms other than biliary colic. The term ‘asymptomatic’ implies that we know which pain is specific to gallstones, however, there is often some uncertainty. The decision to perform a prophylactic cholecystectomy depends on whether the benefits of a cholecystectomy outweigh the risks of surgery. The benefits are the prevention of later development of biliary pain, a biliary complication or carcinoma of the gall bladder. The probability of developing bil-

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iary pain in asymptomatic stones is reported as about 20% at 20 years. The probability of developing complications is between 0.2 and 0.8% annually in a Danish study and between 0.3 and 1.2% in an Italian study.2,3 Prevention of carcinoma of the gall bladder is an advantage of prophylactic cholecystectomy. However carcinoma of the gall bladder is a disease of the elderly, is rare at between 0.12% and 0.3% over 30 years and hence causes little loss of life expectancy. Prophylactic cholecystectomy is therefore not recommended for asymptomatic gallstones. An exception to conservative management

is the presence of asymptomatic stones in patients undergoing major abdominal surgery for other pathologies. Concomitant cholecystectomy along with a major abdominal procedure does not appear to significantly increase postoperative morbidity or hospital stay.

Symptomatic stones

Laparoscopic cholecystectomy Laparoscopic cholecystectomy is the treatment of choice in most patients who are fit for surgery. The procedure has a low morbidity and mortality and can be performed as a day case or an overnight stay. An appreciation of the possible www.australiandoctor.com.au

How To Treat – Gallstones from page 26 found that non-organic abdominal pain was the most common final diagnosis, and only 2% had pain due to gallstones.4 The factors that predict a good outcome after cholecystectomy are those that best describe biliary colic: severe right upper quadrant or epigastric pain, lasting 30 minutes to four hours and occurring infrequently, usually less than once a month. If symptoms are not typical, it is less likely that a successful outcome will be achieved from cholecystectomy. This should be discussed, to enable the patient to approach surgery with realistic expectations (see box, right). Bile acid therapy Gallstones form when bile becomes supersaturated with cholesterol. The administration of oral bile acids reduces cholesterol saturation in bile and has been used to dissolve cholesterol stones. Initially chenodeoxycholic acid was used but this was replaced with ursodeoxycholic acid (Ursofalk), which has fewer side effects. Only a small subgroup of symptomatic patients, about 15%, are suitable for oral bile acid therapy. Patients should be mildly symptomatic, have cholesterol gallstones

Realistic expectations of cholecystectomy Recurrent or persistent pain is common after cholecystectomy Mortality and bile duct injury are rare but significant possibilities Flatulent dyspepsia is common in normal people, is not caused by gallstones and is not cured by cholecystectomy

without any significant calcification and the gall bladder must function. The complete dissolution rate is a disappointing 37% but this increases to 48.5% with stones less than 10mm in diameter. Patients with very small stones, less than 5mm in diameter (about 3% of all patients) have a 90% chance of complete dissolution within six months. A significant drawback of bile acid therapy is gallstone recurrence, occurring at a rate of 10% annually, such that it is 50% by five years. Bile acid therapy is seldom used because of the long duration of therapy, low dissolution rates and high recurrence. Bile acid therapy, however, could be considered for an obese patient undergoing rapid weight loss particularly after bariatric surgery, as about one-third of these patients develop gallstones within a

few months of the operation. Oral prophylaxis with ursodeoxycholic acid 600mg a day prevents stone formation in these patients. When the weight loss stabilises the lithogenic tendency reduces and longterm stone recurrence may not be such a problem. Expectant management Is it reasonable to manage symptomatic patients expectantly and recommend surgery for biliary complications or persistent severe pain? Cholecystectomy is recommended to prevent the recurrence of biliary pain and to prevent biliary complications and death. With expectant management, further biliary pain is common, occurring in about 50% of patients in the first year, and 70% within two years. However, the probability of complications is only 1.3% annually. Ransohoff performed a quantitative analysis comparing expectant management with early surgery for patients with symptomatic gallstones and found there was little difference in survival between the two strategies.3 For a 30-yearold male, early cholecystectomy increased survival by 52 days over a lifetime. Ransohoff’s main message was that the risk of mortality from expectant management need

Treating gallbladder stones Asymptomatic — no treatment Symptomatic — laparoscopic cholecystectomy — most patients Expectant management — if shortterm comorbidity increases risks Cholecystostomy — for severe cholecystitis in patients who are high risks for surgery

not dominate the decision about therapy. He speculated that some patients and physicians would consider symptomatic gallstones a chronic disease that should receive intervention when a biliary complication occurs or when symptoms become sufficiently bothersome to the patient. In a real-life comparison, Vetrhus randomised patients to expectant management or early surgery with 51% of those randomised to expectant management undergoing cholecystectomy usually in the first few years for recurrent pain.5 There was a suggestion that in some patients symptoms abated after four years of follow-up. Expectant management is often considered for patients with comorbidities that increase the risk of surgery for a short period of time: pregnancy and a recent MI or major surgery are typical examples.

Special situations

Cirrhosis Gallstones are more common in cirrhosis and the risk of surgery is increased due to impaired liver function and portal hypertension with intra-abdominal venous collaterals. Recent studies have found that laparoscopic cholecystectomy can be performed in less severe cirrhosis (Childs A or B) with an operative mortality of up to 6.3%.6 Operations in more severe cirrhosis (Childs C) have a much higher morbidity and mortality and should only be performed by experienced hepatobiliary surgeons after review by a hepatologist.6 Pregnancy In the past, symptomatic gallstones have been managed conservatively during pregnancy and cholecystectomy reserved for severe or nonresolving symptoms. However recent studies have suggested laparoscopic cholecystectomy may be safer for the mother and fetus than previously considered. Cholecystectomy should be considered in selected patients, in particular those with symptomatic stones requiring hospital admission or those with other complications at least in the second trimester of pregnancy.

Cholecystitis IN patients presenting to the ED with abdominal pain, cholecystitis is the second most common cause after appendicitis, occurring in 3-10% of cases. Cholecystitis is a more common cause of pain in older patients, accounting for 21% of abdominal pain cases in those aged over 50 years compared with 6.3% in younger patients.7 The gallstone obstructs the neck of the gall bladder or cystic duct causing an increase in intraluminal pressure with gall bladder distension and wall oedema that may progress to ischaemia and necrosis. Bile is usually sterile in the early stages but secondary infection occurs in 20-75% of patients. Escherichia coli, Klebsiella and enterococci are commonly found in bile cultures. Patients usually present with abdominal pain and fever. The pain manifests in the right upper quadrant and may radiate through to the back. The pain is distinguished from biliary colic by its duration and the presence of Murphy’s sign (inspiration is inhibited by pain on palpation of the right upper quadrant). Blood tests show a raised WCC and raised inflamm-

Figure 3: Ultrasound — acute cholecystitis, thickened gall bladder wall with stone (arrow) in the gall bladder neck.

atory markers, particularly CRP. A WCC greater than 18 × 109/L, a palpable tender mass in the right upper quadrant and duration of pain greater than 72 hours are all markers of more severe disease.

Imaging of acute cholecystitis Ultrasound is the preferred initial modality for suspected acute cholecystitis with stones present in about 95% of cases (figure 3). The presence of a gallstone plus either tenderness localised on ultrasound to the gall bladder, or gall bladder wall thickening of more than 3mm yields a positive predictive value of about 95%. Ultra-

sound also has a high negative predictive value. CT has a lower sensitivity and specificity (positive and negative predictive value) than ultrasound. CT is, however, of more value if the clinical differential diagnosis is broader. CT can also be helpful when gall bladder ultrasound is technically difficult or suggests possible complications of perforation or emphysematous cholecystitis (figure 4). Hepatobiliary iminodiacetic acid (HIDA) scintigraphy is seldom used now, even though it has a high accuracy for diagnosis of acute cholecystitis. It is time-consuming and organ-specific, which limits its use.

Figure 4: Ultrasound and corresponding CT— perforation (arrows) in gall bladder wall with free fluid outside gall bladder.

Management Initial management includes fasting, IV fluid resuscitation, analgesia and IV antibiotics. Recent international guidelines suggest piperacillin/tazobactam or an extended-spectrum cephalosporin. The final choice depends on the likely organism, local antimicrobial susceptibilities, recent history of exposure to antibiotics and the severity of the illness. However it must be stressed that the optimal treatment for acute cholecystitis is surgery, not antibiotics. A key issue is the timing of surgery. About 20% of patients

require emergency surgery because of clinical deterioration or features suggesting complications such as peritonitis or perforation. For the remaining patients, randomised trials suggest that early surgery within days of admission is superior to delayed surgery, that is, surgery performed 6-8 weeks after admission. In a small group of patients with severe comorbidities or severe disease, the risks of surgery may outweigh the benefits. In these patients, ultrasound-guided percutaneous cholecystostomy provides drainage. Elective cholecystectomy can then be performed.

Bile duct stones PATIENTS with stones in the bile duct (choledocholithiasis) can be considered in two broad categories: gall bladder in situ and postcholecystectomy. Patients with their gall bladder in situ present with pain or cholecystitis and the question is whether there are stones in the bile duct as well as the gall bladder. Post-cholecystectomy patients present with pain and/or abnormal LFTs or imaging findings

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Figure 5: Ultrasound — gallstone (arrow) in the bile duct with typical acoustic shadow.

that raise suspicion. Patients in both groups may develop complications of the stone in the duct, such as pancreatitis or cholangitis. The likelihood of a stone in the duct can be predicted by consideration of clinical presentation, LFTs and bile duct diameter and confirmed with minimally invasive imaging.

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Imaging for choledocholithiasis

Ultrasound Ultrasound is the best initial imaging modality for choledocholithiasis (figure 5). Reports of the accuracy of ultrasound vary greatly with sensitivity ranging from 50 -80%, being better in jaundiced patients with dilated ducts. The positive predictive value is about 95%. That is, if ultrasound finds a stone in the duct, there is very likely a stone in the cont’d page 30

How To Treat – Gallstones Figure 7: CT-IVC — small stones (arrows) in a mildly dilated bile duct.

Figure 6: MRCP — two stones (arrows) in common bile duct.

from page 28 duct. If ultrasound does not find a stone in the duct this does not mean that there is not a stone in the duct as ultrasound fails to identify about 50% of stones in the bile duct in patients who are not jaundiced. Ultrasound also provides an accurate indicator of bile duct diameter. The probability of a stone in the duct increases with increasing duct diameter. This has been best studied in patients with their gallbladder in situ.8 Normal bile duct diameter is about 3mm in a 30-year-old and increases with age to about 5mm (and sometimes more) in an 80-yearold. The probability of a stone in a duct 4mm in diameter is only 4% and this increases to 50% for a duct greater than 10mm in diameter. Bile duct diameter is greater in the post-cholecystectomy population; a stone is unlikely if the duct diameter is less than 4mm but larger diameters do not carry the same predictive value as in patients with their gallbladder in situ. Unenhanced CT The sensitivity of unenhanced helical CT in identification of choledocholithiasis is only about 60% and hence is not an imaging modality of first choice for duct stones. Endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography (ERCP) was introduced over 30 years ago, initially as a primary method for diagnosing biliary and pancreatic diseases, and later used for their treatment. For diagnosis of choledocholithiasis, ERCP has been replaced by the safer and more available minimally invasive cholangiography. However, ERCP still has a major role in the treatment of duct stones. A side-viewing endoscope is passed into the second part of the duodenum, usually under sedation. The major papilla is visualised, a catheter is manoeuvred into the bile duct and contrast injected under X-ray fluoroscopy. Stones found in the duct are removed after performing a sphincterotomy. The sphincter at the lower end of the duct is cut with a diathermy wire built into a sphincterotome. The stone is pulled out through the enlarged opening with a basket or balloon. Sphincterotomy is safest if clotting is normal (normal INR and platelets). Antiplatelet agents such as clopidogrel should be stopped 7-10 days before elective sphincterotomy. Impaired clotting however is not a contraindication to urgent drainage in critically unwell patients (eg, in

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Cholangitis practice points Most is mild and self-limited Risk factors for severe cholangitis • Low platelet count • Increased serum bilirubin • Renal impairment • Low albumin • Increased age, comorbidities

Imaging bile duct stones — practice points Ultrasound detects up to 50-80% Ultrasound negative • If high probability, then ERCP and treat • If moderate to low probability, then MRCP or CT-IVC

patients with severe cholangitis and a low platelet count). Drainage can be performed by inserting a stent or nasobiliary drain without performing a sphincterotomy. Results of ERCP improve with the accumulation of experience and are better in high-volume centres. Cannulation of the bile duct is successful in about 85% of patients and sphincterotomy and stone extraction is successful in about 77%. Complications occur in about 7%, being mainly pancreatitis (2.7%) bleeding and perforation. Most complications occur within the first 24 hours of the procedure. However, bleeding may be delayed up to 10 days post-sphincterotomy and retroperitoneal perforation occasionally presents several days after discharge with abdominal pain and a mild fever. The average 30-day mortality for ERCP and sphincterotomy for stones is 1.5%. The mortality is lower in young fit patients (0.2%) and high in the elderly, being 2.4% in those older than 85 years. The mortality also increases with the severity of comorbidities, being 0.7% for patients with mild comorbidities and increasing to 13% for those with severe comorbidities. ERCP and sphincterotomy is the best management for choledocholithiasis post-cholecystectomy. It is also the best management for those with gall bladders in situ presenting with cholangitis or gallstone pancreatitis. ERCP and sphincterotomy is an alternate management to consider for choledocholithiasis before elective cholecystectomy. Minimally invasive cholangiography MRCP uses a rapidly alternating magnetic field to image the stationary fluid in the bile duct. The procedure can be performed with a

30-second breath hold and does not require IV contrast agents. MRCP accurately diagnoses bile duct stones (figure 6). Its weakness is a substantially lower sensitivity for detection of very small stones. CT-IVC combines helical CT with IV injection of a contrast agent, meglumine iotroxate (Biliscopin), to opacify the bile duct. The contrast agent does not usually opacify the duct if the serum bilirubin is greater than twice normal. CT-IVC is not useful in jaundiced patients. In a comparison with ERCP, CTIVC had a sensitivity and specificity for detection of duct stones of 96% and 94% respectively and is probably better than MRCP for detection of small stones less than 5mm in diameter (figure 7).9

Clinical scenarios

Gallbladder in situ — is there a stone in the duct? Choledocholithiasis is present in 7-20% of patients scheduled for laparoscopic cholecystectomy. If choledocholithiasis is suspected, the need for further investigation depends on the surgeon’s preference. Some surgeons prefer that bile duct stones are diagnosed preoperatively and removed at ERCP. Others prefer to assess the duct during surgery with an intraoperative cholangiogram and to manage any stone identified laparoscopically. Stones in the bile duct are more common in older patients when the gall bladder is in situ. They may be diagnosed on the initial ultrasound, or suspected because of abnormal LFTs and or an increased bile duct diameter. A recent history of cholangitis, and bilirubin elevated above twice normal are also good predictors. The choice of preoperative diagnostic imaging is determined by the probability of stones. Patients with a high probability of duct stones (stone seen in the duct on ultrasound, cholangitis or jaundice with a dilated duct), are best managed with ERCP and removal of the stone. Patients with a moderate or low probability of stones can be imaged with MRCP or CT-IVC. Post-cholecystectomy — is there a stone in the duct? Patients may have a stone in the bile duct not previously detected in the perioperative period or a stone forming de novo. After cholecystectomy, 2-4% of patients present with duct stones in the ensuing 10 years. There are several clinical presentations. www.australiandoctor.com.au

Pain Pain persists in about 20% of patients post-cholecystectomy and is often due to chronic pain unrelated to gallstones. Typical biliary colic suggests stones in the duct, and the differential diagnosis includes biliary spasm or a bile duct stricture. A bile leak usually occurs within the first few postoperative days but may occur up to two weeks later. Patients often complain of a right shoulder-tip pain. Abnormal LFTs A stone in the bile duct is always a possibility when investigating abnormal LFTs in a patient with previous cholecystectomy. A history of episodes of biliary colic increases the probability of a stone. Chronically elevated ALP and GGT may be seen. LFTs often flare during episodes of pain, with increases in the transaminases that return to normal over the following few days. The rapid fluctuations in LFTs with pain reflect intermittent obstruction by the stone and can also be seen in biliary spasm. Jaundice A recent Swedish study of patients presenting with jaundice (bilirubin greater than 100µmol/L) found the most common causes were bile duct stones (16%), malignancy (34%) and alcoholic liver disease (17%).10 The diagnosis of liver disease can usually be made from consideration of the history and LFTs. Stones and malignancy can often be distinguished on history. Patients with stones present with biliary colic, fever, fluctuating jaundice and a serum bilirubin less than 150µmol/L. Patients with malignancy usually present with progressive painless jaundice and serum bilirubin above 200µmol/L. Acute cholangitis Acute cholangitis due to stones in the bile duct is usually mild and self-limited, however it may present with severe sepsis, a life-threatening illness. Bile is normally sterile but may become colonised with bacteria in choledocholithiasis and biliary strictures. Acute obstruction of the bile duct increases intraductal pressure and facilitates spread of bacteria from the biliary canaliculi to the liver and blood stream. Thus the management of cholangitis involves the treatment of the sepsis and drainage of the biliary obstruction to reduce the intraductal pressure and to stop further release of bacteria into the liver. The diagnosis is made clinically, patients present with fever and or

rigors, jaundice and right upper quadrant pain. Treatment for sepsis is initiated and blood tests and imaging are performed to confirm the presence of biliary obstruction and exclude other causes of these symptoms such as acute cholecystitis or liver abscesses. Acute cholangitis is one of many causes of sepsis. The recent guidelines from the Surviving Sepsis Campaign advise early aggressive fluid resuscitation, blood cultures followed by intravenous antibiotic therapy that should be started as early as possible, preferably within the first hour of recognition of sepsis. The most commonly cultured bacteria in community acquired cholangitis are E. coli, Klebsiella and Enterobacter spp.7 In hospitalacquired cholangitis, Pseudomonas and vancomycin-resistant Enterococcus spp are also found. The choice of antibiotic therapy should be guided by the severity of the cholangitis, local susceptibility patterns and recent history of antibiotic treatment. Initially, broad-spectrum antibiotics are used empirically and these should be switched to narrower-spectrum agents once the susceptibility of the infecting bacteria is known. Recent international guidelines recommend the use of piperacillin/tazobactam or third- and fourth-generation cephalosporins with a wide microbial spectrum as the initial empirical treatment. All patients with cholangitis require drainage. Most patients respond to medical treatment. Drainage can then be performed semi-electively over the next 72 hours. Patients presenting with severe sepsis or failing to respond to medical treatment within 12-24 hours require urgent biliary drainage. ERCP with sphincterotomy and removal of stones or insertion of a biliary stent or nasobiliary drain is the treatment of choice for drainage. Randomised trials have confirmed endoscopic drainage has a lower morbidity and mortality than surgery. If endoscopic drainage is unsuccessful then percutaneous transhepatic drainage is the next best option. Several studies have identified risk factors for developing severe sepsis. They include increased age, comorbidities, a low and falling platelet count, renal impairment, low serum albumin and increased serum bilirubin. Patients with one or more of these risk factors should be considered for urgent endoscopic drainage.

Related conditions Acute pancreatitis

References Figure 8: Ultrasound — small polyps (arrows) adherent to gall bladder wall.

GALLSTONES are the most common cause of acute pancreatitis, however acute pancreatitis is an uncommon complication of gallstones. Pancreatitis is caused by a stone in the bile duct obstructing the pancreatic duct as it impacts in the papilla or passes out of the duct. Acute pancreatitis presents with persistent severe central abdominal pain, often radiating through to the back. The intensity of the pain almost always results in the patient seeking medical attention. The diagnosis of acute pancreatitis is suggested by typical abdominal pain, an amylase or lipase elevated above three times normal and characteristic findings on imaging, usually CT.11 A biliary aetiology is confirmed by finding gall bladder stones on transabdominal ultrasound and suggested by abnormal LFTs on admission.

on an abdominal ultrasound. Management is determined by the size and characteristics of the polyps on ultrasound (figure 8). Cholesterol polyps are the most common, accounting for 60% of all polyps. Adenomyomatosis

Gall bladder polyps Gall bladder polyps are less common than gallstones, occurring in about 5% of people. They are usually an incidental finding

accounts for 25% of polyp-like changes on ultrasound. These are benign hyperplastic lesions caused by proliferation of the surface epithelium, which leads to invagination into the muscularis. Inflammatory polyps are the next most common at 10% and true adenomas account for only 4% of all gall bladder polyps. Whether or not gall bladder adenomas progress to carcinomas is not clear. Several studies suggest this may be the case, however most gall bladder carcinomas probably do not arise from previous adenomas. Most polyps are asymptomatic, and the major consideration in management is the risk of malignancy. Most polyps are benign, however increasing diameter is associated with an increased probability of malignancy. Cholecystectomy traditionally has been recommended when polyps are greater than 10mm in diameter. Recent studies have suggested that polyps as small as 6mm in diameter could be malignant. Increasing age and the presence of gallstones also increase the probability of malignancy.

Author’s case studies Case 1 MR T, 58, has a past history of type 2 diabetes treated with metformin. He presented with five days of right upper quadrant pain, dark urine and malaise, followed by a conscious collapse at home. An ambulance was called. The ambulance paramedics found his temperature was elevated at 40ºC, his heart rate was 140 and his systolic blood pressure was 70. His respiratory rate was elevated at 46. A diagnosis of sepsis was made. Normal saline was given intravenously (3L an hour) at home and during transport to hospital An hour later, once he arrived at hospital, his heart rate was lower at 120 and his temperature was 38ºC. He also appeared jaundiced. A provisional diagnosis of biliary sepsis was made. He was resuscitated with IV normal saline. Blood was taken for cultures, biochemistry and clotting. The results were as follows: • Renal impairment, creatinine 195µmol/L. • Urea 11.1 mmol/L. • LFTs: albumin 30gm/L, ALP 361 IU/L, ALT 165 IU/L, bilirubin 152 µmol/L. • FBC: Hb 147 g/L WCC 7.9 × 109/L (with left shift) increasing to 25 × 109/ L five hours later, platelets 70 × 109/L falling to 35 × 109/L after 24 hours. • INR 1.7. Piperacillin/tazobactam was administered at a dose of 4.5g IV. An abdominal CT was done to exclude other pathology. It revealed a stone in a dilated bile duct. Mr T was given fresh frozen plasma to correct INR, and was started on inotropes to support blood pressure. About two hours later he was intubated because of his increasing respiratory failure. A decision was made to pro-

Figure 9: Mr T’s cholecystostomy, showing pus aspirated from catheter inserted percutaneously, under ultrasound guidance, into his gall bladder.

1. Price WH. Gall-bladder dyspepsia. British Medical Journal 1963; 2:138-41. 2. Ransohoff DF, et al. Prophylactic cholecystectomy or expectant management for silent gallstones. A decision analysis to assess survival. Annals of Internal Medicine 1983; 99:199-204. 3. Ransohoff DF, Gracie WA. Management of patients with symptomatic gallstones: a quantitative analysis. American Journal of Medicine 1990; 88:154-60. 4. Muris JWM, et al. Abdominal pain in general practice. Family Practitioner 1993; 10:387-90. 5. Vetrhus M, et al. Symptomatic, non-complicated gallbladder stone disease: Operation or observation. A randomized clinical study. Scandinavian Journal of Gastroenterology 2002; 37:834-39. 6. Overby W,et al. SAGES guidelines for the clinical application of laparoscopic biliary tract surgery. Surgical Endoscopy 2010; 24:2369-86. 7. Yusoff IF, et al. Diagnosis and management of cholecystitis and cholangitis. Gastroenterology Clinics of North America 2003; 32:1145-68. 8. Urquhart P, et al. Challenging clinical paradigms of common bile duct diameter. Gastrointestinal Endoscopy 2011; 74:378-79. 9. Gibson RN, et al. Accuracy computed tomographic intravenous cholangiography (CT-IVC) with iotroxate in the detection of choledocholithiasis. European Radiology 2005; 15:1634-42. 10. Bjornsson E, et al. Severe jaundice in Sweden in the new millennium: causes, investigations, treatment and prognosis. Scandinavian Journal of Gastroentology 2003; 38:86-94. 11. Banks PA, Freeman ML and the Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. American Journal of Gastroenterology 2006; 101:2379-2400.

Further reading

Figure 10: Mr T’s cholecystostomy, showing catheter in gall bladder. Contrast drains freely into duodenum. No stones in duct.

ceed to emergency ERCP, which showed the stone in the bile duct. After a sphincterotomy, the gastroenterologist successfully removed the stone. The following day, Mr T was

not improving, despite having had biliary drainage. A diagnosis of cholecystitis was made although the initial CT was not diagnostic. As he was too sick for cholecystectomy, a percutaneous cholewww.australiandoctor.com.au

cystostomy was performed under ultrasound guidance. This saw 20mL of pus drained from his gall bladder (figure 9). Contrast introduced via the cholecystostomy catheter confirmed free drainage (figure 10). After 18 days, Mr T was discharged home with a cholecystostomy tube in situ. At week 6, he had elective laparoscopic cholecystectomy with an overnight stay. Cholangitis is occasionally severe with rapid development of multiorgan failure. Mr T had most of the risk factors predicting severity: renal impairment, jaundice, WCC greater than 70 × 109/L, thrombocytopenia and diabetes as a comorbidity. There is a short window of opportunity after presentation to implement appropriate management — IV antibiotics, aggressive IV fluid resuscitation and urgent endoscopic drainage. Cholecystitis in patients at high risk for surgery is best managed with cholecystostomy. cont’d next page

All you need to know about gallbladder polyps: Gallahan WC, Conway JD. Diagnosis and management of gallbladder polyps. Gastroenterology Clinics of North America 2010; 39:359-67. Review of surgery: Gurusamy KS, Davidson BR. Surgical treatment of gallstones. Gastroenterology Clinics of North America 2010;39:229-24. Good recent review: Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut and Liver 2012;6:172-87. Recent study with a good review of literature. Advises taking a detailed history in selecting patients for cholecystectomy: Thistle JL, et al. Factors that predict relief from upper abdominal pain after cholecystectomy. Clinical Gastroenterology and Hepatology 2011;9:891-96. Detailed review of diagnosis and management: Williams EJ, et al. Guidelines on the management of common bile duct stones. Gut 2008; 57:1004-21.

19 April 2013 | Australian Doctor |

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How To Treat – Gallstones from previous page

Case 2 MRS A, a 28-year-old woman with three children presented with six months of recurrent biliary colic occurring once every month or two. Abdominal ultrasound demonstrated stones in her gall bladder and a bile duct diameter of 3mm. The management options were discussed. Mrs A preferred laparoscopic cholecystectomy and she was placed on the surgical waiting list. Before the operation could be performed she fell pregnant. Episodes of biliary colic became more frequent but were managed conservatively with the expectation of performing a cholecystectomy after delivery. At 24 weeks’ gestation Mrs A was admitted with a particularly severe episode of pain. Her LFTs were abnormal with an elevated bilirubin and mildly elevated transaminases. A stone in the bile duct was suspected. Abdominal ultrasound confirmed stones in the gall bladder. The bile duct was

4mm in diameter but no stones were seen in the duct. Abdominal ultrasound misses up to half of the stones in the duct. The typical pain and abnormal LFTs with a negative ultrasound and bile duct of 4mm diameter suggested a moderate probability of a stone in the duct. An MRCP demonstrated three small stones in a 4mm diameter duct. ERCP was performed with the fetus shielded by a lead skirt, a sphincterotomy performed and the stones were removed. Mrs A delivered a healthy baby at 40 weeks. Laparoscopic cholecystectomy was performed two months post-delivery. Expectant management for symptomatic gallstones is surprisingly safe but recurrent pain is common and complications are a possibility. Patients with a moderate probability of duct stones and a negative ultrasound are best investigated with minimally invasive cholangiography.

Conclusion GALLSTONES are common, with 80% of cases being asymptomatic. Asymptomatic stones should be managed conservatively. Symptomatic stones usually present with biliary colic — infrequent episodes of constant severe abdominal pain lasting from 30 minutes up to four hours. Ultrasound is the gold standard for diagnosing stones in the gall bladder with high sensitivity and few false positives. Symptomatic stones are best managed with laparoscopic cholecystectomy. Patients should understand the limitations and risks of surgery; there is a small risk of death or bile duct injury and pain is not relieved in 20% of cases. Patients presenting with typical biliary colic have the most successful relief of symptoms. Atypical symptoms are less likely to resolve after cholecystectomy. Bile duct stones present with pain, abnormal LFTs, cholangitis and pancreatitis. Abdominal ultrasound successfully diagnoses about 50% of duct stones. Patients with a negative ultrasound are best imaged with minimally invasive cholangiography, MRCP or CT-IVC, or ERCP if there is a high probability of stones. Cholangitis is usually mild and self-limiting but may be severe requiring aggressive fluid resuscitation, antibiotics, and urgent ERCP and drainage.

Instructions

How to Treat Quiz

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Gallstones — 19 April 2013 1. Which TWO statements are correct regarding the epidemiology and presentation of gallstones? a) Most gallstones (70-80% of cases) are asymptomatic with a low annual risk of developing symptoms in the first five years b) Gallstones are the underlying cause of more than 30% of abdominal pain presentations in general practice c) 30% of pregnant women will develop new gallstones d) Bariatric surgery is associated with an immediate improvement in the risk of developing gallstones and associated gall bladder disease 2. Which TWO statements are correct regarding clinical presentation of gallstones? a) A constant pain in epigastrium lasting for two hours cannot be biliary colic because the gall bladder is in the right upper quadrant and colicky pain is wavelike in nature b) The presence or history of an associated fever is a significant clinical flag of a complicated gallstone disease c) Flatulent dyspepsia (abdominal bloating and pain) is most likely due to gallstones d) A positive Murphy’s sign in a patient with a constant right upper quadrant pain for more than four hours will require active management 3. Which ONE statement is correct regarding investigation of gallstone disease? a) An abdominal CT will accurately pick up asymptomatic gallstones and allow for planning of gallstone removal at the same time

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b) An erect and supine abdominal X-ray is the first-line investigation for gallstones because it is cheap, easily accessible and has a good sensitivity c) Magnetic resonance cholangiopancreatography (MRCP), where readily available, is the first-line modality for the investigation of gall bladder disease d) Gall bladder ‘sludge’ found on ultrasound is usually not significant and does not usually require a referral to the hospital or the gastroenterologist 4. Which TWO statements are correct regarding prophylactic cholecystectomy for asymptomatic gallstones? a) The benefits of prophylactic cholecystectomy are the prevention of pain, weight reduction and improvement in dyspepsia b) The probability of asymptomatic gallstones developing complications is less than 1.2% c) Prophylactic cholecystectomy is recommended for asymptomatic gallstones in patients with a family history of cholecystitis d) Prophylactic cholecystectomy for asymptomatic gallstones may be considered concurrently for patients undergoing another major abdominal surgery 5. Which THREE statements are correct regarding cholecystectomy for symptomatic gallstones? a) Post-cholecystectomy, 20-30% of patients have recurrent or persistent abdominal pain for symptomatic gallstones b) The average perioperative mortality associated with laparoscopic cholecystectomy for symptomatic gallstones

is between 0.1% and 0.6% c) Healthy patients with uncomplicated gallstones should be given a trial of oral bile salts as the first-line therapy d) Cholecystectomy is recommended over expectant management to prevent the recurrence of biliary pain and to prevent biliary complications and death. 6. Which TWO statements regarding cholecystitis and its management are correct? a) The optimal definitive treatment for acute cholecystitis in an otherwise healthy patient is early cholecystectomy b) The choice of antibiotics for the medical management of acute cholecystitis are IV flucloxacillin and gentamicin c) Hepatobiliary iminodiacetic acid (HIDA) scintigraphy is the first-line modality for the investigation of cholecystitis d) Emergency percutaneous cholecystostomy can be performed under ultrasound with the view to an elective cholecystectomy later 7. Which THREE statements are correct regarding bile duct gallstones? a) Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line investigation for bile duct gallstones b) A negative ultrasound result does not rule out bile duct stones c) Jaundice caused by bile duct stones and malignancy can often be distinguished on history and bilirubin level d) In the 10 years post-cholecystectomy, 2-4% of patients may present with bile duct stones

8. Which TWO statements are correct regarding ERCP? a) ERCP is the investigation of choice for imaging known or suspected bile duct stones b) ERCP and sphincterotomy is safe, with a low 0.1-0.2% complication rate c) Patients can present with complications of ERCP and sphincterotomy in general practice after discharge d) Antiplatelet therapy should be stopped 7-10 days before elective ERCP and sphincterotomy if it is safe to do so 9. Which THREE statements are correct regarding acute cholangitis? a) Acute cholangitis due to bile duct stones is usually mild and self-limiting b) Acute cholangitis is usually diagnosed with an abdominal ultrasound c) Sepsis due to acute cholangitis should be treated within the first hour of the recognition of sepsis d) Risk factors for developing severe sepsis in acute cholangitis include increased age and comorbidities 10. Which TWO statements are correct regarding gall bladder polyps? a) Gall bladder polyps are pathological and require specialist intervention if found on abdominal ultrasound b) Gallstones are more common than gall bladder polyps, which are mostly asymptomatic c) Gall bladder adenomas are precursors to gall bladder carcinomas d) Cholecystectomy is recommended for polyps greater than 10mm in diameter

CPD QUIZ UPDATE The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2011-13 triennium. You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.

how to treat Editor: Dr Steve Liang Email: [email protected]

Next week Occupational contact dermatitis is a common occupational disorder, usually affecting the hands, although other exposed areas such as the face and arms may be affected. The next How to Treat discusses the types of occupational contact dermatitis, the risk factors, and how to investigate, treat and prevent this troubling condition. The authors are Dr Sarah Hannam, dermatology research fellow, Occupational Dermatology Research and Education Centre, Skin and Cancer Foundation, Melbourne; and Associate Professor Rosemary Nixon, dermatologist and occupational physician, director, Occupational Dermatology Research and Education Centre, Skin and Cancer Foundation, Melbourne, and clinical associate professor, Monash University and the University of Melbourne, Victoria.

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