DISEASES
BILIARY
ATRESIA
Biliary atresia (BA) remains an enigmatic disease that challenges hepatobiliary specialists as well as clinical and basic researchers. Today, thanks to remarkable improvement in medical care, over 90% of biliary atresia patients survive in the mid- and long-term. However, every attempt to completely cure BA or identify the state of the disease has thus far failed. Sequential surgery such as portoenterostomy and optional liver transplantation (LTx) represents nothing more than a symptomatic approach, that does not target the origin or pathomechanism of the ongoing and devastating inflammatory process. In most cases, the deterioration of the liver function is inevitable and the replacement of the liver remains the only option, being tantamount to lifelong immunosuppression and a risk of the development of post- transplant lymphoproliferative disorders (PTLD). In short, over the course of the last 50 years, the overall outcome of BA-patients has been continually improved; however, a fundamental breakthrough has yet to be achieved.
Assuming the hypothesis that against a background of a hereditary predisposition, BA is probably an (auto)immunological process, it is not surprising that the worldwide incidence of this disease differs. Isolated BA occurs most frequently in the Eastern world; e.g., in one in 5000 life births in Japan versus one in 15,000–19,000 births in Europe and North America. However, in any case, biliary atresia is a rare disease that hides behind the common phenomenon of neonatal jaundice. The challenge for pediatricians, family doctors, and midwives is to identify those babies that present with neonatal cholestasis and, as such, require further diagnostics. Herein, time matters, because early diagnosis and surgical treatment of BA is correlated with a better outcome.
Beside professional and non-professional information campaigns, today, the implementation of stool cards is the method of choice when early detection of BA is our common objective. In 2004, a pilot study took place, in which, stool cards were integrated into the child health booklet of each baby born in Taiwan. Early evaluation of this strategy demonstrated that timely operative intervention (before 60 days of age) increased from 60 to 74% and the jaundice free (< 34 μmol/l) survival rate was nearly 60% instead of 37%, which demonstrates that the stool card system can be effective. There are plans to launch similar initiatives in other countries, while stool cards are already introduced in Switzerland and Germany. Implementing nationwide screening tools should become an objective of the international community, while unification of stool cards and protocols should feature on the global agenda.
INCIDENCE AND
SCREENING
DIAGNOSTIC
Beside early detection, the crucial point in diagnosing BA is to define a clear and consistent diagnostic algorithm in neonatal cholestasis to distinguish those patients who are at a high risk of developing BA from all others. Considering that neonatal jaundice can be observed in nearly 50% of all neonates, differentiation of bilirubin is obligatory when clinical signs of cholestasis persist longer than 2 weeks. Patients with elevated direct bilirubin at that point in time should be referred to pediatric liver units. Herein, a pediatric hepatologist will take action to rule out other causes of conjugated hyperbilirubinemia, such as alpha-1-antitrypsin deficiency, cystic fibrosis and infections with hepatotropic viruses. In parallel to laboratory work-up, hepatobiliary secretion can be evaluated by hepatobiliary scintigraphy, while imaging usually starts with sonography followed by magnetic resonance cholangiography (MRCP) and becomes more invasive with the use of endoscopic retrograde cholangio(pancreatico)graphy (ERCP). According to respective in-house guide- lines, the relevance of liver biopsies is weighted differently. However, the main problem is that BA is characterized by an ongoing inflammatory process of the entire biliary tree, although the disease is defined as an irreversible closure/ atresia of the extrahepatic bile ducts. This means that visualization of the extra- and intra-hepatic bile ducts is the key to excluding or confirming biliary atresia. In other words, if none of the above-mentioned diagnostic tool provides evidence for any other diagnosis but BA, visualization of the extrahepatic bile ducts is inevitable and should be performed in a timely manner. The gold standard approach for this procedure remains the intraoperative cholangiography, which is performed by laparotomy or via minimally invasive access. In some places, ERCP is the method of choice, although this procedure requires general anesthesia and is technically demanding [30]. In our center, the following diagnostic algorithm has been developed: at the same time as laboratory investigations are underway, sonography is conducted to identify gallbladder abnormalities and the so-called triangular sign. During the synopsis of the initial results, an interdisciplinary decision is made as to whether ERCP is indicated or not. When this investigation reveals patency of the bile ducts, which occurs in about 25% of our patients, a liver needle biopsy is taken, and further diagnostics are scheduled. If the findings confirm the suspicion of BA, the patient is forwarded to surgery.
The current intermediate status on how to diagnose biliary atresia best is that, until now, no evidence-based protocol or algorithm has been validated. Each liver unit insists emphatically on its particular preferences without proving its superiority. Elaborating a generally accepted diagnostic flow-chart is mandatory and should be feasible within the near future.
SURGERY
For as long as the etiology of BA is unknown, surgery remains the only option for the treatment of patients with this devastating disease. Until the early 1960s, only cases presenting as so-called “correctable” form of BA were scheduled for bilodigestive anastomosis. Therein, cystic forms of BA, which might sometimes be confused with form fruste choledochal cysts [4], showed irreversible obstruction of the distal common bile duct together with prestenotic dilatation into the porta hepatis and a patent intrahepatic biliary tree. It was thanks to Morio Kasai that the “uncorrectable” became “correctable”, when he made a significant step beyond the established surgical limits. He meticulously dissected the porta hepatis and achieved bile drainage in those patients, who otherwise would have died within the 1st year of their lives. He published a paper about this ingenious technique in the late 1950s but it took time until Kasai’s portoenterostomy became the gold standard for BA surgery. However, the new technique was not always successful because mid- and long-term survival with their own liver occurred only in a minority of the patients involved. Most of them suffered from deterioration of their liver function and ultimately required liver transplantation. In subsequent years, several attempts were made to modify the original technique, to improve the rate of successful Kasai procedures. Based on the assumption that ascending cholangitis originates from intestinal reflux after Rouxen-Y-anastomosis, numerous surgeons changed the length of the afferent limb or created antirefluxive valve mechanisms. Another suggestion was related to the extent of dissection. Ando proposed dividing the Arantius’ canal to increase the number of draining bile ducts. Unfortunately, the overall outcome did not change as a result of such action and none of these modifications prevailed. Today, essential recommendations as to how to perform the Kasai portoenterostomy remain close to the original procedure, which is, until now, the obligatory first step in the sequential surgical treatment of BA. Another issue concerns whether redo procedures in obviously failing Kasai procedures make sense or not. In general, no study has ever demonstrated better bile flow after redo Kasai, provided that the first operation was performed in accordance with the standardized and correct technique. This position was recently supported by the series from Japanese centers. Exceptions to this statement are patients with initial good bile flow, who develop bile leakage or mechanical obstruction of the Rouxen-Y-loop. Since liver transplantation became routine in small children, the overall survival of BA patients is higher today, at around 90%. LTx is the second, but numerically most important, step in the treatment protocol, which is scheduled according to the parents’ preference and the availability of donor organs. Living related LTx gains increasing importance because split liver procedures also depend on the limited pool of donor organs. One key problem in BA-related surgical therapy is that it is not universally accepted that the Kasai procedure and LTx are separate, but sequential steps in a unique therapeutic algorithm. Bypassing Kasai and choosing LTx as the primary option deprives 20–30% of BA patients of the chance of long-term survival with their own liver. Another point that needs further attention is that there are no general criteria in existence to evaluate the timing and indication for LTx in patients with ongoing deterioration of their liver function. This topic should be addressed by interdisciplinary discussions and proposals. After minimally invasive surgery (MIS) became routine in neonates, some surgeons have also applied this elegant technique to BA patients. They presumed that it would allow them to secure better visual access to the porta hepatis, reduce the surgical trauma and induce lesser abdominal adhesions, facilitating redo procedures, at which point LTx would become necessary. However, preliminary results were contradictory. The authors of the initial series judged the MIS procedures to be feasible but reported diverging patient outcomes. On the one hand, MIS-performed Kasai was found to be superior to any open procedure, while on the other hand, a prospective series was stopped on the basis of ethical reasons because the short-term outcome in terms of survival with native liver were obviously worse. The crucial point in this technical discussion is that, until now, no studies have proven that MIS-Kasai delivers any tangible advantage over open surgery. Therefore, the ques-tion as to whether this particular point deserves closer attention as long as all other fundamental and unsolved problems are yet to be addressed, remains open. If one asks about adjuvant therapy after the Kasai procedure, most surgeons would agree that patients should be offered hypercaloric nutrition with medium-chain triglycerides as well as the substitution of fat-soluble vitamins and antibiotic prophylaxis for an indeterminate period. However, the question as to whether postoperative treatment protocols should include corticosteroids remains a matter of discussion. Assuming that inflammation is part of the BA pathomechanism, steroids are frequently used, while treatment protocols are diverging in terms of onset, dosage, and duration. Numerous outcome studies, published on a low evidence level, failed to significantly demonstrate any beneficial effect of their protocols. Only two studies meet the criteria of a prospective and placebo-controlled design. However, even under optimum conditions, a higher survival rate with native liver could not be achieved in those patients who received reasonable steroid dosages over an adequate period after the Kasai procedure. In conclusion, it remains debatable as to whether any effort should be addressed in this direction or whether we accept that treating BA with corticosteroids might be of help for the surgeons’ inner voice but not for the patients’ outcome. Another topic that is of fundamental interest concerns the timing and indication for liver transplantation in post-Kasai patients who exhibit an ongoing deterioration of their liver function. It is imperative that consensus is achieved on this matter because LTx-related algorithms usually depend on individual and in-house experience and preference.
OUTLOOK
Biliary atresia is a good example of transition and transla- tional research that bridge patients from pediatric surgery and hepatology to transplant surgery and hepatology in general. In 2016, this became a reality, when the ERN initiative of the European commission for rare diseases (European networks of reference for rare diseases) approved the net- work “Rare Liver”. However, interdisciplinary cooperation beyond national and continental borders will be critical to achieving fundamental change in favor of patients with biliary atresia and related disorders. Another step towards unity in diversity is to combine the knowledge and resources of multidisciplinary clinicians and researchers. This can be achieved by organizing periodical interdisciplinary single topic conferences and international partnerships on clinical and basic research.
Cited, updated and adapted from Pediatr Surg Int (2017) 33:1255–1261
ALLAGILLE
SYNDROME
Alagille syndrome (ALGS) is a genetic disorder that affects primarily the liver and the heart. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 30,000 to 1 in every 40,000 live births. It is named after the French pediatrician Daniel Alagille, who first described the condition in 1969. Children with Alagille syndrome live to the age of 18 in about 90% of the cases.
SYMPTOMS
The severity of the disorder can vary within the same family, with symptoms ranging from so mild as to go unnoticed, to severe heart and/or liver disease that requires transplantation. It is uncommon, but Alagille syndrome can be a life-threatening disease with a mortality rate of 10%. The majority of deaths from ALGS are typically due to heart complications or chronic liver failure. Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itching (pruritus), pale stools (acholia), an enlarged liver (hepatomegaly), an enlarged spleen (splenomegaly) and deposits of cholesterol in the skin (xanthomas). A liver biopsy may indicate too few bile ducts (bile duct paucity). Bile duct paucity results in the reduced absorption of fat and fat-soluble vitamins (A, D, E and K), which may lead to rickets or a failure to thrive. Cirrhosis and eventual liver failure is fairly common among ALGS patients, and 15% of those with severe hepatic manifestations require a liver transplant. Hepatocellular cancer has been reported in a small number of cases, but it is extremely rare. Other presentations of Alagille's syndrome include butterfly vertebrae, ophthalmic defects, and distinct facial structures. The butterfly vertebrae can be detected with an x-ray, but there typically are no symptoms from this abnormality. Other skeletal defects common in ALGS patients are spina bifida and the fusion of vertebrae. Most of the ophthalmological defects affect the anterior chamber of the eyeball, including Axenfeld's anomaly and Rieger anomaly, but retina pigment changes are also common. These anomalies can be beneficial in diagnosing Alagille syndrome. Many people with ALGS have similar facial features, including a broad, prominent forehead, deep-set eyes, and a small pointed chin. While these distinct facial features are often presented in ALGS patients, the features are presumably not due to Alagille syndrome, but they are characteristic of patients with intrahepatic cholestatic liver disease. So while these facial characteristics are extremely common in ALGS patients, it is because many patients experience extreme liver complications or liver failure, but it is not caused by the disease itself.
DIAGNOSIS
Alagille syndrome can be extremely difficult to diagnose. While people are born with ALGS, it is almost always diagnosed later during childhood. The diagnosis can be difficult because the severity of the disease varies widely among patients. Some common clinical tests that are run in order to diagnose the disease include vertebral x-rays, heart exams to detect any defects such as a heart murmur, and a liver biopsy to detect liver disease or any precursors. If a patient presents with multiple symptoms such as jaundice, heart murmur, and the characteristic facial features discussed above (deep set eyes, broad brow, etc.), they are likely to be diagnosed with Alagille syndrome. A more calculated and specific diagnosis can be done with genetic testing. Next-generation sequencing can be utilized to detect single nucleotide polymorphisms (SNPs) in the affected gene(s). Multiplex ligation-dependent probe amplification (MLPA) can detect large deletions and/or insertions and microarray comparative genomic hybridization is used to improve the accuracy of MLPA.
TREATMENT
Early treatment is possible once the disease is diagnosed. Treatments of Alagille syndrome typically involve medications, therapies, and/or surgical procedures. All treatments aim to improve bile excretion from the liver, reduce pain caused by the disease, and help improve nutritional deficiencies. Diet can also be a crucial factor in improving quality of life when living with ALGS.
MEDICATION
Several medications are used to improve bile flow, including ursodiol (Actigall or Urso). These medications differ in their rates of success. Certain drugs may be used to reduce itching (pruritus), such as cholestyramine and rifampin. While these medications can reduce pruritus, the itching often is reduced when bile flow is improved via ursodiol or liver transplant. Many patients with Alagille syndrome have nutritional and/or malabsorption issues which often hinders normal growth. Patients benefit from vitamin A, D, E, and K supplements because the reduced bile flow makes it difficult to absorb and utilize these vitamins. A high-calorie diet is very important, and often requires a gastrostomy tube to maintain the high caloric intake. A new approach is the treatment by intestinal bile acid transport (IBAT) inhibitors, e.g Maralixibat (Livmarli), wich was approved for medical use in the United States in September 2021.
SURGERY
Surgery is common in more severe cases on Alagille syndrome, especially for patients with liver disease or end-stage liver failure. Liver transplants can either be a complete liver transplant from a deceased organ donor, or a partial transplant from a living donor. Partial biliary diversion has been used to significantly reduce pruritus, jaundice, and xanthoma caused by poor bile flow in patients with bile duct paucity. A portion of the bile produced by the liver is directed through a surgically created stoma into a plastic pouch on the patient's lower right abdomen. The pouch is periodically drained as it fills with bile. Patients with biliary atresia may require a Kasai procedure to improve bile drainage; however, later liver transplantation is still often necessary. Cited and adapted from https://en.wikipedia.org/wiki/Alagille_syndrome (July, 24, 2024)
Bile is essential in order to break down fats and is produced in the liver. In PFIC patients, the transport of bile from the liver to the intestine is disrupted. Therefore, bile acids and in some cases, other metabolites such as bilirubin accumulate in the liver and in the blood. This can lead to a build up and to cholestasis, driving damage to the liver cells and inflammation. As a result, scar tissue is formed in the liver (fibrosis) and bile acids can circulate throughout the body and contribute to the stressful itching. PFIC is most often diagnosed in infants and in toddlers. In milder cases, it occurs in school-age children, adolescents and only rarely in adults. Only one in 50,000 to 100,000 children is affected by PFIC. The cause is a group of rare genetic defects. So far, we know of three main types of PFIC and their causative genetic defects, but more rare subtypes have been discovered. All those genes carry information for proteins which are somehow involved in the transport of bile ingredients from the liver cells to the bile ducts. The severity of symptoms and the course of disease vary among individuals. Many patients experience severe itching, others experience this along with other symptoms such as jaundice and failure to thrive. Jaundice is also a sign of disruption in liver function: bilirubin, a waste product of red blood cells, which is normally excreted with the bile, accumulates in the blood. This can lead to yellow discoloration of the skin and mucous membranes. Growth disorders and vitamin deficiencies can occur because fat and the fat-soluble vitamins A, D, E and K are less easily absorbed due to reduced levels or a lack of bile. In severe cases, the fibrosis (still potentially reversible) progresses to cirrhosis (scarring, rarely reversible). High blood pressure may develop in the portal vein. This may lead to the spleen increasing in size and to swelling of the blood vessels in the lower oesophagus or stomach which, upon rupture, can lead to significant blood loss and vomiting of blood. In some children, the final stage of liver failure is reached before the age of 10, which makes a liver transplant necessary.
PROGRESSIV FAMILIAL INTRAHEPATIC CHOLESTASIS (PFIC)
DIAGNOSIS
Due to the variety of symptoms and their severity, there are several treatment options. Current drugs are primarily intended to alleviate the symptoms and slow disease progression. For some patients, the only chance of complete recovery is through liver transplantation. There is potential for gene therapy in the future. In many cases, there are delays in diagnosing PFIC disease. The European Reference Network on Hepatological Diseases (ERN RARE-LIVER) with its > 30 centres across Europe is working to shorten this period significantly leading to earlier diagnosis and treatment initiation. As a first diagnostic step, blood is taken from the child or adult patient to carry out liver function tests (bilirubin, enzyme GGT and others, coagulation values, albumin). These tests are also repeated as part of recurring routine checks. Imaging techniques such as ultrasound can determine the sizes of liver and spleen and monitor the blood flow to the liver. X-rays may be used to determine whether bone density has decreased due to vitamin D deficiency. In many cases, the treating physician will also suggest a liver biopsy. This procedure is brief and carried out under anaesthesia or conscious sedation combined with pain control. The skin and underlying tissue on the right side are punctured to sample a very small cylinder of liver tissue. Specialists then examine this sample under the microscope. The risks of the procedure are low for the vast majority of patients. Families, parents and patients receive detailed information about liver biopsy in advance if this procedure is recommended. To confirm PFIC and determine the subtype, a genetic test (analysis of the affected parts of the genetic information located on the DNA) is carried out in most cases. The blood of the parents may also be required for this. The genetic test takes two weeks or sometimes longer
MANAGMENT
Once the diagnosis has been made, therapy is determined. The choice of medication for PFIC ultimately depends on the type and severity of the symptoms. The main purpose of these drugs is to relieve the symptoms and to help slow down disease progression. PFIC patients need to be monitored for liver cancer in the native liver all their lives as the risk is increased, even in younger children. A common treatment goal is to reduce the extremely stressful itching by alleviating cholestasis (lowering the concentration of bile acids in the blood). Ursodeoxycholic acid or rifampicin are often used in early stages to improve bile transport and metabolism. As no approved drugs for PFIC are available at this stage, doctors will frequently prescribe “off-label” drugs. New drugs are being tested in clinical trials for their potential future use in PFIC. If the growth and development of the child is impaired by the disease, doctors prescribe a formula diet whose energy and fat content is often adapted to the special needs of children with liver disease. To improve the vitamin status, fat-soluble vitamins are given as tablets or drops. Because they have difficulty absorbing fats, children with PFIC have a greater need for energy supplies from food, but their appetite is low. This means that a feeding tube may be required in some but exceptional cases. A surgical procedure called biliary diversion can also alleviate the symptoms in certain cases. The bile is partially drained or diverted via an external stoma on the right abdominal wall, or by an internal diversion from the gallbladder to the colon leading to a net loss of bile acids. To create this diversion, a short part of the small bowel is converted to function as a connection from the gallbladder to the abdominal wall or colon. Each option has its own advantages, but can also be associated with risks. Your or your child’s physician will provide comprehensive information before such a procedure. If the therapies outlined are not suitable or successful, the failing liver may need to be replaced. Different technical approaches offer a good prognosis for adults, older children or young children in need of such a procedure. One of them is the splitting of donor organs and the other is living donation of (a) liver segment(s) by parents. However, in all PFIC subtypes, this operation should only be performed after carefully weighing up the benefits and risks. Many children affected by PFIC after liver transplantation will have a good prognosis and regain good quality of life. However, the majority will require lifelong immune suppression which may come with disadvantages. Depending on the disease subtype, disease specific post-operative complications have to be considered. Families will receive detailed information on liver transplantation during the initial preparation phase and during all later phases should a liver transplant be deemed necessary.
ERN-rare-liver: https://rare-liver.eu/patients/understand-your-diagnosis/progressive-familial-intrahepatic-cholestasis-pfic/
CHOLEDOCHAL CYST
Choledochal cysts (CCs) are rare cystic dilations of the intrahepatic and/or extrahepatic bile ducts.1 Approximately 80% of CCs are diagnosed in childhood – most often presenting with a right upper quadrant mass, abdominal pain and jaundice. The greater use of cross-sectional imaging has increased detection of CCs among adults with the incidence of CCs being four-fold higher among females. Additionally, CCs occur more frequently in Asian versus Western populations with an incidence of 1 in 13,000 versus 1 in 150,000 people, respectively. We herein review the pathophysiology, diagnosis, and management of CCs. Todani and colleagues introduced the following classification: type I CCs are characterized by a fusiform dilation of the CBD with normal intrahepatic ducts, type II CCs are a focal supraduodenal diverticulum, and type III CCs, also known as choledochoceles, are intraduodenal cystic dilations of the CBD. Type IV CCs are characterized by intrahepatic and extrahepatic ductal dilation or multiple areas of extrahepatic dilation without involvement of the intrahepatic duct; type V CCs, also known as Caroli Disease, is characterized by variable degrees of intrahepatic bile duct dilation. Type I CCs are more often seen in children, while type IV are more prevalent in adults. Although the etiology of CCs is not well understood, most CCs likely develop as a result of an anomalous pancreaticobiliary duct union (APBDU). An APBDU is characterized by a long common channel (>10 mm proximal to the ampulla) of the pancreatic duct and CBD that predisposes to reflux of pancreatic fluid into the biliary tree leading to biliary duct inflammation, increased pressure, and, eventually, biliary ductal dilation. The CBD and pancreatic duct usually unite within the sphincter of Oddi to form a common channel with a normal length of 0.2–1.0 cm. An anomalous union creates an abnormal channel that allows pancreatic enzymes to enter the biliary tree weakening the CBD wall that facilitates cyst formation. In support of this theory, biliary manometry has documented high concentrations of pancreatic enzymes in CC fluid. Of note, while only 2% of individuals without CCs have an APBDU, up to 96% of patients with CCs have a documented APBDU. Presenting symptoms of CCs may include abdominal pain and jaundice. In a multi-institutional analysis of 394 patients who underwent resection of CCs, 84.5% of patients with CC presented with symptoms while 15.5% of individuals were asymptomatic. Adults were more likely to present with abdominal pain, while children were more likely to present with jaundice. Other CC-related symptoms may include cystolithiasis, cholecystitis, pancreatitis, liver abscess, and liver cirrhosis. Pancreatitis may be particularly common among patients with CCs with a prevalence of up to 70%. Pancreatitis may be secondary to the altered pancreaticobiliary ductal anatomy characterized by the long common channel, as well as the development of cystolithiasis. In particular, pancreatitis may be due to bile reflux into the pancreatic duct. Other clinical complications of CC include development of hepatolithiasis as a result of bile stasis or migration of intra-cystic stones, which can occur more often among patients with type IV CCs. Bouts of recurrent biliary obstruction and resultant cholangitis can lead to the development of intrahepatic abcesses. The most feared complication of CCs is malignant transformation. Among patients with CC, the incidence of malignant transformation has been reported to be around 3–5%. The true incidence of malignant transformation in CCs remains unknown, however. The risk of malignancy has been strongly linked with increasing age, as the risk of cancer – while not zero – is very low among the pediatric CC population. The association of age with malignancy risk has been postulated to be related to the long-term chronic exposure of the biliary epithelium to the pancreatic fluid, especially among patients with APUBD. The risk of CC malignancy is also higher among patients with type I or type IV CCs with a marked lower incidence among patients with type V CC; cancer has rarely been reported among patients with type II or III CCs. In a pooled analysis of 78 studies, the prevalence of malignancy was 7.5% (434 cancer diagnoses out of 5780 patients); cholangiocarcinoma and gallbladder cancer were the most common malignancies. In particular, adenocarcinoma is the most common histologic subtype comprising 73–84% of cancers; other histologies include anaplastic carcinoma (10%), undifferenced cancer (5–7%), and squamous cell carcinoma (5%).
DIAGNOSTICS
Radiological and endoscopic imaging is the cornerstone of CC diagnosis. The initial work-up for a patient suspected of having a CC generally begins with an ultrasound (US) or computed tomography (CT) scan. US is generally utilized more often in the pediatric population, while adults are more likely to undergo a CT. The key imaging feature of CCs on US, CT, or magnetic resonance imaging (MRI) is a bile duct in continuation with areas of cystic dilation.36 Communication with the biliary tree is important to differentiate a choledochal cyst from a mucinous cystic neoplasm (MCN) of the liver, as a MCN does not communicate with the biliary tree. Additionally, dilation of the bile ducts should not be associated with an identifiable mechanical obstruction. Use of a hepatobiliary contrast agent may assist in determining a possible connection with the biliary tree.
TREATMENT
Given the identification of increasing numbers of asymptomatic patients, indications and timing of surgery– especially among individuals at the extremes of the age spectrum – can be nuanced. For example, given that the risk of malignancy is relatively low, elderly patients who have multiple comorbidities may not benefit from operative intervention for CC. Clinicians that management is largely dictated by CC type, accurate imaging to determine CC extent and type is critical to determine treatment planning. In addition, when an operation is being considered accurate anatomic delineation of relationship of bile duct to the pancreatic duct is important. Aberrant biliary and pancreatic anatomy may be common and needs to be identified using preoperative imaging. Additionally, prior to surgical intervention, any underlying biliary infection should be controlled with either broad-spectrum antibiotics and/or endoscopic or percutaneous drainage procedures. The treatment of choledochal cysts should include complete cyst excision with Roux-en-Y hepaticojejunostomy (HJ). If the CC extends into the pancreatic head, pancreaticoduodenectomy (PD) may sometimes be needed to remove the CC completely, however “coring out” the entire CC behind the pancreatic head can often be accomplished. The risk of leaving residual CC should always be balanced against the increase morbidity of performing a PD. Biliary reconstruction typically involves a standard HJ. Hepaticoduodenostomy (HD) had previously been considered an option as it provides the advantage of access to the biliary tract via endoscopy for future interventions if needed. The ability to perform a HD may be limited, however, by the mobility of the duodenum and the inability to perform a tension-free anastomosis. In addition, some data suggest that HD may be associated with increased risk of gastric and biliary cancers, as using an operative approach that allows for continued exposure of the biliary tree to pancreatic fluid is counterintutive. As such, HD has largely been abandoned. Rather, complete cyst excision and HJ reconstruction is considered the treatment of choice for CC. In addition to the traditional open approach, minimally invasive surgery (MIS) using laparoscopy or robotic techniques have been successfully utilized to treat CC. MIS may provide superior visualization of the hilar structures, yet requires advanced skills in both MIS and hepatobiliary surgery. Experienced MIS surgeons can, however, achieve good technical outcomes. MIS management of CCs is more common among pediatric patients. While sample sizes are generally small and data scant, the evidence would suggest that there is no difference in the incidence of post-operative complications among patients undergoing open versus minimally invasive CC management. Several studies have noted good technical outcomes with MIS cyst excision and reconstruction in adults with acceptable post-operative morbidity. Operative intervention for CC is generally well-tolerated, and similar to other hepato-biliary procedures. Early complications can include HJ leak, while HJ stricture can be a late complication, although both are uncommon. Overall, patients who undergo surgery for CC do well with a 95.5% five-year survival with no significant differences in survival or major post-operative morbidity between children and adults. Not surprisingly, patients who have a malignancy at the time of CC resection have a worse outcome. Cited, updated and adapted from HPB (Oxford). 2023 Jan;25(1):14-25.
