Laparoscopic Biliary Injuries (Part Two), prevention and presentation.

Prevention of biliary injuries

• Experience should be graded and difficult procedures should not be attempted until experience has been gained.


• Laparoscopic cholecystectomy is more difficult in the presence of acute inflammation, especially when the operation is delayed for several days and when leukocytosis is prominent.


• Biliary injury is more likely under these circumstances.

1. A previous attack of acute cholecystitis is also a significant contributing factor to operative difficulty.


2. It is also more difficult in the presence of chronic inflammation with a thick-walled gallbladder and


3. when the patients are
   • males,




• elderly, or


• when there have been repeated attacks of pain.

• These factors are additive.

Avoidance of misidentification of ducts

• Misidentification is due to failure to identify the cystic structures correctly


• The cystic duct and artery are the only structures which require division during a cholecystectomy, and the objective of dissection is to identify these structures.

During open cholecystectomy this could be achieved by a tentative identification of the cystic structures by dissection in the triangle of Calot, followed by dissection of the gallbladder off the liver bed.

• After complete detachment of the gallbladder, conclusive identification of the cystic structures, as the only two structures entering the gallbladder, could be made.

In 1995, Steven M. Strasberg et al introduced a technique for conclusive identification of the cystic structures at laparoscopic cholecystectomy based on a “critical view of safety”.

• In this technique the triangle of Calot is cleared of all fat and fibrous tissue.

• At this point only two structures are connected to the lower end of the gallbladder, and the lowest part of the gallbladder attachment to the liver bed has been exposed.


• The latter is an important step, which is equivalent to taking the gallbladder off the liver bed in the open technique.


• It is not necessary to see the common duct.


• Once the critical view is attained cystic structures may be occluded, as they have been positively identified.


• Failure to achieve the critical view is an absolute indication for conversion or possibly cholangiography to define ductal anatomy.

Some useful technical suggestions to aid clearing the triangle of Calot are

• to dissect the triangle of Calot from both its dorsal and ventral aspects,




• using a combination of pulling techniques,


• gentle spreading with forceps,


• and blunt dissection with a non activated spatula cautery tip or anchored pledgets


• The pouch of Hartman should be pulled laterally and inferiorly to open the anterior left side of Calot’s triangle and create an angle between the cystic duct and common bile duct ( fig. 1)


• The plane of dissection should always be maintained on the gallbladder or cystic duct.


• To do so, the gallbladder should be followed down to the presumed point of the infundibulum–cystic duct junction and dissection started there.

Anatomical identification by routine operative cholangiography (RIOC) is an alternative approach to dissection.

• There is now very strong evidence that RIOC can reduce biliary injury.


• A population study in Australia found that RIOC reduced the incidence of injury.


• This important study adjusted for confounding variables such as age, gender, hospital type, and severity of disease.


• Its conclusions have been supported by other more recent studies.


• Other studies suggest that the severity but not the incidence of biliary injury is reduced by RIOC.


• Operative cholangiography is best at detecting a misidentification of the common bile duct as the cystic duct, and will prevent excisional injuries of bile ducts, provided that the cholangiogram is interpreted properly.


• However, operative cholangiograms have been misinterpreted frequently in the presence of injury.


• The most common misinterpretation is the failure to recognize that the bile duct rather than the cystic duct has been incised and cannulated when only the lower part of the biliary tree is seen.


• Also an incisional injury of the common bile duct made to perform RIOC may not itself be innocuous.


• It will at the least require conversion and repair over a T-tube and at worst require biliary reconstruction.


• Furthermore, RIOC is very poor at detecting aberrant right ducts which unite with the cystic duct before joining the common duct.


• The aberrant duct appears to be the cystic duct visually and on X-ray since other right-sided ducts fill ( fig. 2)

Some authorities believe that meticulous dissection of the triangle of Calot, as was done during the open era, is the correct means of anatomical identification.

• The author’s view is that identification of the anatomy by the “critical view” technique is the method of choice for identification of biliary anatomy during laparoscopic cholecystectomy – but that if this method is not used, RIOC should be performed.


• It is also one view that the infundibular technique should not be used without cholangiography and that ductal identification by dissection to the cystic duct/common hepatic duct union ought not to be used as a routine technique of ductal identification during laparoscopic cholecystectomy because of the danger of injury to the common bile duct, especially when there is a parallel union of the cystic duct with the common hepatic duct.


• These issues are not resolved since even today the infundibular technique is an accepted form of surgical practice


• However, there are two points on which almost all authorities would agree;




• a method of conclusive identification should be used in all cholecystectomies and all methods are capable of failure under certain conditions.

The admonition that cystic structures be conclusively identified before transection means that an approved method of identification should be used and not that surgeons are capable of always identifying the structures correctly.

Avoidance of technical errors

• Clips should be placed so that the tips can be seen projecting beyond the duct, free of extraneous material.


• Clips should not be manipulated in the subsequent dissection.


• The new type “locking clip” may provide more secure closure.

• Clips should not be used when the cystic duct is thick.


• Instead, two preformed ligature loops should be applied and tightened to occlude the cystic duct.


• When the duct is very large a stapler may be used.




• Applying extra clips is not the answer and may lead to tenting injury.


• Tenting injury is also avoided by not pulling up on the gallbladder forcefully when applying clips and, most importantly, by direct observation that a piece of cystic duct remains below the clip applied closest to the common bile duct end of the cystic duct.

Avoidance of ductal injury in the liver bed depends upon

• staying in the correct plane of dissection.


• Use of the spatula dissector combined with irrigation to keep the field clear of blood is often helpful.


• The cautery scissors are also useful, but there is no substitute for meticulous technique and experience in this dissection.

Cautery should not be used, or used only with great care, in the triangle of Calot.

• Great care means low cautery settings, coagulation of small pieces of tissue at one time, and that tissue must be lifted off and be free of any adjacent tissue.


• Low cautery settings are mandatory, as higher settings may lead to arcing to ducts.


• Cautery should never be used to divide the cystic duct since this may lead to thermal necrosis of the cystic duct stump or adjacent bile duct.

Bleeding should never be controlled by blind application of clamps, clips, or cautery.

• Brisk bleeding is an indication for conversion.


• Lesser degrees of hemorrhage may appear more serious than they really are, because of the magnification of laparoscopy.


• The operating surgeon must use judgment in such cases as the bleeding often stops spontaneously or with direct pressure.

Presentation and investigation

• About 10% of type A injuries are identified intraoperatively; most of the rest are diagnosed in the first postoperative week.


• Type B injuries are infrequently diagnosed intraoperatively; often they are silent or become symptomatic with right-sided abdominal pain or jaundice months or years after he cholecystectomy.


• Type C and D injuries, which produce bilomas like type A injuries, tend to be diagnosed in the early postoperative period.


• The type of injury most likely to be identified during the procedures the type E;




• 25 to 40% of type E injuries are diagnosed intraoperatively according to most literature reports.


• Most of the remaining type E injuries are identified in the first 30 days after surgery with the remaining presenting months to years after the laparoscopic cholecystectomy.


• The preceding comments refer to the first presentation of injury.


• In large series, 30 to 40% of repairs are performed on patients who have had a prior repair at the institution where the injury occurred.

Intraoperative identification of injury may occur by recognition of bile in the field, indicating a cut bile duct, by cholangiography, or rarely by direct observation of a divided duct.

At other times the actual diagnosis of biliary injury is made after conversion for bleeding or inability to proceed in a difficult dissection.

Postoperative presentations are influenced by the type of injury and whether a drain has been left. Pathological processes leading to symptoms are:

• biloma,


• fistula,


• or bile ascites;


• partial or complete biliary obstructions;


• and superinfection.

These may occur in various combinations.

The commonest presentations are

1. pain with sepsis with or without jaundice,


2. and jaundice without other symptoms.


3. Biliary fistula is also a common presentation.


4. Some patients present only with distension and malaise.

There have been many papers written on the subject of investigation of symptoms developing after laparoscopic cholecystectomy, but there are no comparative trials of different algorithms.

Pain and sepsis

• This presentation usually occurs in injuries leading to bilomas, that is types A, C, and D.


• Most patients with type A injury present with the pain/sepsis symptom complex; jaundice is very uncommon but hyperbilirubinemia of (2 to 3 mg/dL) is often found, as is elevation of alkaline phosphatase level.


• Few of the more serious type E injuries present only with pain/sepsis.

The purpose of investigation in the pain/sepsis group is to determine whether there is a biloma or bile ascites, whether there is continuing bile leakage, and the site of the leakage from the biliary tree.

Computed tomography (CT) scan is performed first to localize fluid collections which may then be aspirated to determine if they are bilious.

In most cases a drain is placed in the biloma and an endoscopic retrograde cholangiopancreatography (ERCP) follows.

Magnetic resonance imaging (MRI) with magnetic resonance cholangiography (MRC)

• has the potential to replace these investigations with a single one,


• but MRC does not see collapsed ducts well,


• and is more likely to be useful when there is obstruction of the biliary tree than perforation with free drainage of bile into the peritoneal cavity.

Since most patients presenting with pain/sepsis have type A or D injuries, definitive treatment is possible at the time of ERCP.

• When bile ascites is found on CT, stable patients may be treated in the same manner with percutaneous drainage and ERCP,


• but laparotomy, lavage, and drainage may be advisable for unstable patients with generalized bile ascites.


• Another more circuitous approach when a collection is found is to perform a hepatobiliary iminodiacetic acid (HIDA) scan if bile is aspirated and proceed to drain placement and ERCP only if continuing leakage is demonstrated. The latter may be suitable for the minimally symptomatic patient.

Some patients presenting with pain and sepsis have more serious injuries.

• In these patients the ERCP will demonstrate occlusion of the bile duct or free communication with the peritoneal cavity.


• The next step to complete diagnosis of the extent of injury is by percutaneous transhepatic cholangiography (PTC),




• but the period immediately after drainage of bile collections is often a poor time to do so in this group of non jaundiced patients whose bile ducts are not dilated.


• Injection of drains at this time will frequently show a cloud of contrast and, as the bile ducts are not dilated, PTC as a primary step is difficult.


• One often wait for 2 to 3 weeks until the biloma is resolved and a tract forms around the drain.


• At this time injection of the drain will result in filling of the biliary tree, that is a fistulagram is possible.


• This permits diagnosis of the extent of the injury.


• Furthermore, once intrahepatic ducts can be filled with contrast, insertion of percutaneous tubes into intrahepatic bile ducts under fluoroscopy is possible.

It is critical that all intrahepatic ducts be accounted for.

• In type E1 to 3 injuries cannulation of any intrahepatic duct will result in filling of all intrahepatic ducts as they are in communication.

• In higher injuries this is not the case and more than one intrahepatic duct will require cannulation to identify all the intrahepatic ducts.

• It is not difficult to fail to appreciate that ducts from a particular volume of liver are not filling,




• but this has obvious, serious consequences if not recognized before repair is undertaken.

To avoid this problem the recommendation is to reconciliation between PTC studies and a CT scan of the liver.

• Livers are variably shaped and this type of reconciliation, which correlates the shape of the PTC volumes with the whole liver volume, provides confidence that all ducts are accounted for.


• The commonest problem is failure to appreciate that right posterior sectional ducts are absent on PTC in patients whose right liver descends inferiorly more than usual.

Jaundice

• The presence of jaundice strongly suggests that the patient has sustained a type E injury.


• Type E injuries present with jaundice in about 70% of cases, the other 30% presenting with pain/sepsis only as described above.


• Occlusions usually present with jaundice as the sole symptom, but transactions are often accompanied by pain and sepsis due to accumulation of bile in the peritoneal cavity.

ERCP is the first-line investigation today, although it may be supplanted by MRCP in the future.

MRCP is especially effective when the bile ducts are occluded.

• The bile-filled ducts show up well under these circumstances.


• On ERCP the duct may be found to be occluded often clips are seen at the point at which the dye column stops.


• Or it may be found to be transected, with loss of continuity to the upper biliary tract.


• If stenotic rather than occluded ducts are found, the entire extent of injury may be diagnosed by ERCP.


• When the upper ducts cannot be seen by ERCP, PTC is required.


• When the upper ducts are occluded and dilated, PTC is straightforward.


• When they are not the approach of delayed PTC as described under pain/sepsis is recommended.


• PTC also provides external drainage of bile.

The presence of bile collections may require percutaneous drainage as well.

Bile fistula

• About one-third of patients with type A injury present with bile fistula, but any injury in which there is a bile leak may do so.


• Since bile has egress, local collections or obstruction to bile flow are unlikely and sepsis and jaundice are usually absent.

The first-line investigation is a fistulagram. Subsequent management depends upon anatomical findings.

Vague symptoms

• A few patients present only with vague symptoms such as distension, malaise, anorexia, complaints of discomfort, or may require more than the usual amount of analgesia.


• These presentations are usually due to bile ascites, but hepatic bile is isotonic and has a low bile salt concentration compared to gallbladder bile and so may cause little irritation until infection occurs.

• The mild complaints are easy to overlook, but may be the only manifestations of a serious biliary injury and diagnostic delay is a key factor in stimulating litigation.

The suggested line of investigation is the same as for pain/ sepsis.

Hemobilia is a rare presentation of biliary injury and is due to pseudoaneurysm formation at the site of an associated arterial injury with subsequent erosion into the biliary tree.

Laparocopic Biliary Injuries (part one), classification and causes.

Introduction
Biliary injury is the most severe common complication of cholecystectomy.

It is always morbid, occasionally fatal, increases cost, and often results in litigation.

Bile duct injury has always been a risk of cholecystectomy but its incidence increased sharply when laparoscopic surgery for cholecystolithiasis was introduced.

• Not only has laparoscopic cholecystectomy led to more injuries, but certain types of injury, such as ductal lacerations, bile leaks, and aberrant duct injuries, are more common than they were previously.


• The causes of injury are becoming better understood and improved methods for preventing injury are available.


• When injury occurs, a high rate of permanent cure is possible using advanced techniques of reconstruction in specialized centers.

Classification of biliary injuries

Bismuth classified benign biliary strictures into five types based on the upper level of the stricture.

• This classification was used to stratify biliary injuries in the era of open cholecystectomy, but it became somewhat less useful as the injury pattern altered due to laparoscopic cholecystectomy.

In 1995, Steven M. Strasberg et al. introduced a classification that retained the essence of the Bismuth classification for major injuries, but broadened the classification to separately itemize injuries seen with increased frequency during laparoscopic cholecystectomy and this classification is based on anatomical location and on severity of injury and has found considerable acceptance. Other classification schemes not based on the Bismuth classification have been proposed by McMahon et al., Stewart and Way, and Schol et al.

Type A: bile leak from a minor duct retaining continuity with the common bile duct.

• These leaks are usually caused by a failure to adequately secure closure of the cystic duct or by an injury of a small bile duct in the liver bed.


• This type of biliary injury is the least serious, since major ducts are not involved and there is little chance of progression to a more serious form of injury.


• However, even these injuries can be quite morbid.


• They are usually lateral injuries to the biliary tract and therefore decreasing intrabiliary pressure by endoscopic sphincterotomy results in healing.

Types B and C: creation of a discontinuity of part of the biliary tree with occlusion (type B) or intraperitoneal leak (type C)

• These are end injuries which isolate a part of the biliary tree.


• They almost always result from injury to an aberrant right hepatic duct, although rarely an aberrant left ducts or a normally situated duct may be involved.


• About 2% of patients have an aberrant lowlying right duct which most commonly drains one or two segments of the right hemiliver.


• A key anatomical feature contributing to the likelihood of injury is that in some cases the cystic duct joins the aberrant duct, which then continues to join the main ductal system.


• The appearance of the junction of the aberrant duct with the hepatic duct may be identical to that of the junction of the cystic duct with the hepatic duct.


• As a result there is great potential for injury in these circumstances.
  When the injury is a ductal occlusion it is designated type B. When it is a transection without occlusion it is termed type C.


• The reason for the difference in classification is that presentation, management, and often prognosis are very different.

Occlusions are generally injuries of lesser severity.

• They are often asymptomatic, or if symptomatic may not cause symptoms such as cholangitis for months or years.


• The liver upstream from a type B injury atrophies and the remaining liver undergoes compensatory hyperplasia.

Transections without occlusion (type C) result in local intraperitoneal bile collections or bilious ascites and peritonitis.

• Type C injuries usually present in the early postoperative period and almost always require treatment.

Type D: lateral injury to major bile ducts

• D injuries are partial (<50%) transections of major bile ducts.


• When the transection involves >50% of the circumference of the duct, the injury should be considered an E type.


• Like the type A variant, they are lateral injuries and will often resolve after decompression by postoperative endoscopic sphincterotomy.


• Or if discovered at the time of surgery they may be corrected by simple suturing techniques and the placement of a t-tube.


• Type D injuries have the potential to evolve into more serious injuries, particularly if they are of thermal causation or associated with devascularization of the bile duct.


• Then they may progress to complete obstruction, that is a type E injury.


• Type D injuries may occur to other major ducts. Right hepatic duct injuries have been reported.


• Type C and type D injuries involving the right bile duct are very similar, but there are major therapeutic implications to complete transection (type C) versus lateral injury (type D).


• Inadvertent incision of the common bile duct instead of the cystic duct, when attempting to delineate ductal anatomy by operative cholangiography might be considered to be a type D injury.


• Cannulation of the bile duct, in order to protect it during abdominal surgery, is an accepted procedure and is not in itself considered a complication.

Type E: circumferential injury of major bile ducts (Bismuth class 1–5)

• These are circumferential injuries of major bile ducts.


• Sub classification into types E1 to E4 is based on the level of injury and, while type E5 is a combination of common hepatic duct and aberrant right duct injury.


• Type E injuries separate the hepatic parenchyma from the lower biliary tract, due to stenosis, simple occlusion, or transection.


• When occlusions or transections are present, resection of bile ducts may also have occurred.


• To classify the injury properly it must be stated which of these is present and if bile duct resection has occurred the length of excised duct should be given, for example “E2, simple total occlusion without resection” or “E3, 3-cm duct length excised, transection without proximal occlusion, distal occlusion present.” For purposes of repair the upper limit of injury is the key variable and this is given in the E type itself.

The incidence of laparoscopic biliary injury

• An increase in biliary injuries was an unforeseen accompaniment of laparoscopic cholecystectomy.


• The first indication of the problem was a sudden surge of referrals of biliary injuries to specialized hepatopancreaticobiliary units.


• To determine the true incidence of injury, large, accurate, representative studies were needed.


• Institutional or multi institutional studies, studies of fewer than several thousand cases, and studies with less than 100% reporting including mail surveys, fail to satisfy these conditions.


• Several excellent reports exist, including statewide evaluations from New York and Connecticut, a report from the armed services, and several from Europe.


• In all reports, an increase in the injury rate from 0.1% in the open era to 0.3 to 0.5% in the early laparoscopic era was noted.


• It is encouraging that two studies found that the injury rate is decreasing towards that in the open cholecystectomy era.


• All the early reports encompassed the period during which most surgeons were learning to perform the operation.


• As injury is more likely during the performance of the first fifty cholecystectomies, the injury rates reported in these studies are probably higher than current rates.


• Unfortunately, no study using reliable population techniques has defined the incidence in this decade and therefore it cannot be definitively stated whether injury rates remain above those before the introduction of laparoscopic cholecystectomy.


• However, based on available evidence, it seems that the incidence of the more serious type E injuries are moving towards rates seen in the open era but that type A to D injuries, which were rarely seen in the open era, are still more common today.

Risk factors for biliary injury Training and experience

• Early reports suggested that the high rate of injury was due mainly to inexperience in the procedure referred to as the “learning curve effect”.


• Unquestionably, experience did initially contribute to the high incidence of injury, but other factors are responsible for injury today.

Local operative risk factors

• As during open cholecystectomy, biliary injuries seem more likely to occur during difficult laparoscopic cholecystectomies.


• Russell, in a very large registry series from the State of Connecticut, reports that the incidence of injury when laparoscopic cholecystectomy is performed for acute cholecystitis (0.51%) is three time higher than that for elective laparoscopic cholecystectomy and twice as high as open cholecystectomy for acute cholecystitis.


• Thousand of patients are required to see this difference, and one should be wary of concluding that the procedure is as safe as elective cholecystectomy based on reports of a few hundred patients.


• Chronic inflammation with dense scarring, operative bleeding obscuring the field, or fat in the portal area are cited as contributing factors in 15 to 35% of injuries.


• Blood in the field hampers dissection more in laparoscopic than in open cholecystectomy, and gentle dissection is required, especially when inflammation is present, to avoid bleeding that then obscures vision.


• The role of obesity is difficult to evaluate, since it is so often present in patients with cholelithiasis.

Aberrant anatomy

• Aberrant anatomy is a well-described danger in biliary surgery.


• The aberrant right hepatic duct anomaly, referred to above under type B and type C injuries, is the most common anomaly associated with biliary injury.


• These injuries are probably under-reported since type B injuries may be asymptomatic.


• Isolated injuries to aberrant right ducts did occur before the advent of laparoscopic cholecystectomy, but such ducts appear to be particularly prone to injury during laparoscopic cholecystectomy.

Equipment

• Laparoscopic equipment must be well maintained.


• Thermal injuries to bile ducts or surrounding structures may occur due to focal loss of insulation on instruments used for cauterization.


• Also a charge may build up on laparoscopic instruments and cause arcing to surrounding structures.


• The incidence of such events must be extremely low, but specially shielded laparoscopic equipment and detectors are slowly becoming available to deal with the problem, although their use is not widespread.

Direct causes of laparoscopic biliary injury

• Biliary injury occurs either due to anatomical misidentification of the cystic duct or due to technical problems, especially the misuse of cautery.

Misidentification injuries

• Misidentification is the most common cause of serious injuries.

There are two scenarios.

In the first, the common duct is mistaken for the cystic duct, and is clipped and divided.

• To complete the excision of the gallbladder the bile ducts must be divided again.


• The type of injury produced varies from E1 to E4 and depends on the level of the second division of the biliary tree.


• Frequently, a “second cystic duct” or “accessory duct,” which is actually the common hepatic duct, is reported in the operative notes of these procedures, but just as often the second transection is not noted.


• High transections are probably associated with excessive traction on the gallbladder, an act which pulls the hepatic ducts down during transection of the biliary tree.


• Hepatic ducts may either be clipped or divided, resulting in either obstruction or bile leak.


• Injury of the bile duct is often associated with an injury to the right hepatic artery, with brisk bleeding that leads to conversion and diagnosis of biliary injury or simply to occlusion of the right hepatic duct.


• At the time of reconstruction there is often evidence of dissection on the left side of the common duct, even to the point of exposure of the portal vein.


• Sometimes one clip is placed on the cystic duct and the point of division is either the common duct or cystic duct.


• If the common duct is transected, bile drains from the cut end, sometimes leading to recognition of injury.


• However, equally often this is attributed, wishfully, to a second cystic duct and the full-blown injury evolves.


• The least harmful type of misidentification occurs when the cystic duct is divided, since if the injury is recognized by observation of bile in the field, the clip on the common bile duct may simply be removed.


• Bile leak will not occur if the cystic and common duct run in a common sheath and the clip is placed across both.


• Clip removal, balloon dilatation, or stenting of the clipped duct may occasionally resolve the injury even when the injury is recognized postoperatively but in other patients late stricture occurs after clip removal.

The second misidentification scenario leads to injury to an aberrant right hepatic duct, which is present in 2% of cases.

• The segment of the aberrant right hepatic duct, between where the cystic duct enters it and the point at which it joins the common hepatic, is thought to be the cystic duct.


• The misidentified segment is clipped and usually cut.


• In order to remove the gallbladder the aberrant duct must be cut again at a higher level.

Causes of misidentification injuries
The goal of dissection in laparoscopic cholecystectomy is positive identification of the cystic duct and artery as these are the structures to be divided. There are several methods used to identify the cystic duct –

1. intraoperative cholangiography,


2. the infundibular technique,


3. the critical view technique, and


4. identification by display of the cystic duct/common hepatic duct confluence to form the common bile duct.
   

The infundibular technique identifies the cystic duct by displaying the funnel-like (infundibulum = funnel) junction of the gallbladder and cystic duct.

• We have shown that the infundibular technique is prone to failure in the presence of severe acute or chronic infl ammation and when the cystic duct is hidden or effaced by a large stone, or hidden because of difficulty in retracting the gallbladder.


• These conditions tend to cause a visual deception when this technique is used.


• As a result, even when the technique is carried out properly, the common bile duct will be perceived as the cystic duct.


• This visual deception as a cause of injury in this operation has been focused in several reports .


• The approach to the problem by an analysis of operative notes came to the conclusion that a visual deception was most likely when the infundibular technique was used and the operative conditions listed above were present.
  


• Misidentification is also more common when adhesive bands tether the gallbladder to the common bile duct.


• Misidentification may lead to injury of the bile duct without division or clipping, since extensive dissection may cause devascularization especially if ductal arteries, thought to be the cystic artery, are divided.


• This type of injury may present later as a stricture.

Injuries due to technique

• The chief technical causes of laparoscopic ductal injury are failure to occlude the cystic duct securely, too deep a plane of dissection when taking the gallbladder off the liver bed, tenting injuries, and thermal injuries to the bile duct.


• The cystic duct is routinely occluded with clips.


• This method is less reliable than ligatures or suture ligatures, the standard methods of securing the cystic duct during open cholecystectomy.


• Retained stones in the bile duct may contribute to clip failure by raising biliary tract pressures, but the main cause is inappropriate use of clips instead of another occlusion device on a thick, rigid cystic duct.


• Clips may also “scissor” during application, resulting in faulty closure, or be loosened by subsequent dissection close to the clip.


• Injury to ducts in the liver bed is due to dissection in too deep a plane when excising the gallbladder.


• It usually occurs when the dissection is difficult such as when acute or severe chronic inflammation are present or when the gallbladder is intrahepatic.


• Tenting injury was well described in the open cholecystectomy era.


• There are few reports of this injury during laparoscopic cholecystectomy and it actually may be less common during laparoscopic cholecystectomy due to the excellent visualization of properly identified cystic ducts.


• In the tenting injury the junction of the common bile duct and hepatic bile duct is occluded when a clip is placed at the bottom end of the cystic duct while forcefully pulling up on the gallbladder.


• The tenting injury is more likely to occur when there is a parallel union of the cystic duct with the common bile duct, especially if ductal identification is attempted by dissection to the union of the cystic duct with the common hepatic duct.

Cautery-induced injuries are more likely to occur in the presence of severe inflammation, which may lead to the use of excessively high cautery settings to control hemorrhage.

• Misuse of cautery has led to some very serious bile duct injuries, characteristically type E injuries with loss of ductal tissue due to thermal necrosis.

Associated vascular injuries

• Vascular injuries may accompany ductal injuries, the commonest being injury to the right hepatic artery in association with an excisional injury of the common hepatic duct, due to the proximity of the artery to the duct.


• This association was noted by Meyers and his group in the early 1990s, and recent articles have expanded our knowledge of this complication.


• Vascular complications tend to be more common with higher levels of biliary injury.


• They are associated with a greater tendency to restricture, but this seems to be true only when bile ducts associated with vascular injuries are repaired in community hospitals rather than repaired after an interval in expert centers using the Hepp–Couinaud approach.


• There is a tendency to higher rates of mortality when an associated vascular injury has occurred.

Arterial injuries may involve the proper hepatic artery as well as the right hepatic artery, and portal vein thrombosis has also been reported.

• In severe vascular injuries the vascular component may become the predominant feature of the injury with necrosis of the intrahepatic biliary system, similar to that seen when the hepatic artery thromboses after liver transplantation, or even hepatic infarction.


• Infarction of the intrahepatic biliary tree requires transplantation, while hepatic infarction may lead to the need for hepatic resection or transplantation.


• Portal vein thrombosis may lead to cavernous transformation of the portal vein. This increases the difficulty of later repairs and may itself lead to bile duct compression.

CYSTIC DISEASES OF LIVER AND BILIARY TRACT (Part Two)

Cystic diseases of the biliary tract

Bile duct cysts may occur as solitary or multiple cystic dilatations throughout the entire biliary tree. Originally, these abnormalities were termed choledochal cysts, based on the frequent occurrence of cysts in the common bile duct.

• However, cystic dilatations may occur throughout the entire biliary tree and “bile duct cysts” or “cystic diseases of the biliary tract” are considered as more appropriate terms for this condition.
  
• When confined to the intrahepatic bile ducts, the term Caroli’s disease is generally used, whereas the term choledochal cyst is still frequently used for dilatations limited to the extrahepatic bile duct.
  
• In addition to these types of bile duct cysts, a rarer condition, characterized by multiple periductal cysts, has been identified.

Multiple periductal cysts

• Small cystic lesions of 1 to 2 mm are incidentally found within Glisson’s capsule along the large intra- or extrahepatic bile ducts.
  
• These rare cystic lesions have been referred to as mucinous hamartoma or periductal cysts.
  
• They usually occur in chronically diseased livers, but isolated presentations in otherwise normal livers have been reported as well.
  
• Occasionally, they are found in transplanted livers and are a cause of obstructive jaundice after liver transplantation.
  
• The cysts contain watery or mucoid material and have been considered as retention cysts, resulting from obstructed periductal glands.
  
• The inner lining consists of a mucinous epithelial lining and cysts are surrounded by a mild chronic inflammatory reaction.
  
• Although they are most frequently found in patients with severe chronic liver disease and portal hypertension, periductal cysts are usually asymptomatic and an incidental finding at autopsy
  
• When they occur in an otherwise normal liver and cause biliary obstruction, differentiation from a malignancy can be difficult and resection of the affected part of the liver can be indicated.

Caroli’s disease and Caroli’s syndrome

• Caroli’s disease is a developmental anomaly characterized by segmental dilatations of the large intrahepatic ducts, without an obstructive cause.
  
• Typical for this disease are localized and saccular dilatations of the large bile ducts, resembling a picture of multiple cyst-like structures of varying size.
  
• Two types of abnormalities have been described:
  

1. a type with bile duct abnormalities alone, and
   
2. a type with bile duct abnormalities in combination with periportal fibrosis, similar to congenital hepatic fibrosis.
   

• This combined type is also known as Caroli’s syndrome and has been reported more frequently than the pure type, or Caroli’s disease.

In Caroli’s disease, saccular dilatations of the large bile ducts are more frequently seen on the left side of the liver.

• In 30 to 40% of the cases, abnormalities are confined to one segment or sector of one side of the liver.
  
• Bilateral abnormalities are more frequently seen in the second type, or Caroli’s syndrome.
  
• The abnormal bile ducts are in continuity with the remaining normal bile tree, and therefore contain bile.
  
• Biliary stasis, leading to stone formation, is commonly seen in the dilated ducts and predisposes to the development of recurrent cholangitis and septicemia.

Other complications include amyloidosis and cholangiocarcinoma, the latter of which is found in 7 to 10% of the patients.

Caroli’s syndrome is associated with renal disorders: nephrospongiosis and renal cysts in 30 to 40% of the patients.

• Patients with Caroli’s disease donot have a higher incidence of renal disorders.
  
• Choledochal cysts, however, have been described in combination with both types.
  The disorder usually becomes symptomatic during childhood or early adult life, although initial symptoms may also be delayed until later ages.
• Males are slightly more affected than females.
  
• Typically, the clinical features are related to cholangitis and/or portal hypertension (in case of Caroli’s syndrome), and may include recurrent episodes of abdominal pain, chills, and fever.
  
• Jaundice may develop secondary to obstruction of the extrahepatic bile ducts by stones, which have migrated from the intrahepatic ducts.
  
• In the combination with congenital hepatic fibrosis (Caroli’s syndrome), symptoms from portal hypertension, such as hematemesis from bleeding esophageal varices, usually occur at an earlier age than cholangitis.
  • In this situation hepatomegaly and splenomegaly can be found during physical examination, whereas usually no abnormalities are found on physical examination in patients with Caroli’s disease.

Abnormal laboratory studies of liver function are usually not found, but will be compatible with obstructive cholestasis in patients with stones in the extrahepatic bile ducts.

The diagnosis is usually made by radiologic studies, such as ultrasonography or computed tomography, or by cholangiography during endoscopic retrograde cholangiopancreaticography (ERCP).

• Typical findings are saccular or cystically dilated intrahepatic ducts up to 5 cm in diameter, filled with stone material or sludge.
  
• Differential diagnosis includes
  
• • primary sclerosing cholangitis,
    
  • dilatations secondary to obstruction, and
  • Oriental cholangitis.
• Primary sclerosing cholangitis can usually be differentiated by the concomitant multiple strictures of the intra- and extrahepatic bile ducts in this disorder.
  
• In biliary obstruction due to a malignant tumor along the bile duct, the entire biliary tree proximal to the mass is dilated, including the small peripheral intrahepatic ducts.
  
• In the Asian population, differential diagnosis with recurrent pyogenic cholangitis or Oriental cholangitis can be difficult.

Oriental cholangitis usually occurs at an older age and is associated with a straightening and rigidity of the dilated large ducts, with acute peripheral tapering.

In uncomplicated cases, without signs of cholangitis or obstruction, conservative therapy with observation is indicated.

Medical treatment of complicated cases should focus on

• drainage of the obstructed or infected ducts and treatment of the bacterial cholangitis.
  
• In these cases surgical interventions are usually required in order to reduce the risk of
  • recurrent cholangitis and
    
  • formation of secondary biliary cirrhosis or
    
  • cholangiocarcinoma.

Surgical procedures may vary from

• drainage of the hepatic bifurcation via a hepaticojejunostomy, to a
  
• partial liver resection, with or without hepaticojejunostomy.
  
• Liver transplantation should be considered in selected patients with generalized disease or with concomitant liver fibrosis and portal hypertension(Caroli’s syndrome).

Choledochal cysts

• Choledochal cysts are relatively rare disorders, characterized by cystic dilatation of main bile ducts.
  
• The first classification, as proposed by Alonso-Lej in 1959, included three types, located in the extrahepatic bile duct.
  
• This classification was modified by Todani et al. In 1977, who identified two more types and included intrahepatic cystic dilatations of the large bile ducts, as found in Caroli’s disease.

Type I, a segmental or diffuse dilatation of the common bile duct, is most frequently found, accounting for 75 to 95% of all cases.

Type II represents a diverticulum of the common bile duct.

Type III has been identified as a choledochocele, which term represents a herniation of the distal end of the common bile duct into the duodenum, resulting in a cystic mass in continuity with the common bile duct.

Type IV has been recognized as a combination of cysts, either extrahepatic alone (type IVb) or as a combination of extra- and intrahepatic (Caroli-like) cysts (type IVa).

Multiple cysts of the large intrahepatic ducts (Caroli’s disease) were identified as type V.

Although there is no uniform definition of what size of the bile duct should be considered a cystic dilatation, a diameter above 1.5 to 2 cm is generally regarded as abnormal.

However, it should be realized that some widening of the common bile duct occurs with aging and is considered to be physiologic.

• The cyst wall is thickened and fibrotic, and the mucosa severely inflamed or even absent and replaced by granulation tissue.
  
• The classical classification scheme has recently been challenged and some investigators believe that type II (diverticula) and type III (choledochocele) are unrelated to the other types of cystic dilatation of the bile duct and should, therefore, not be considered as a subtype of choledochal cysts.

About 75% of the choledochal cysts occur in women and lesions are far more common in the Far East than in Western countries. The estimated prevalences vary from 1 : 1000 in Japan, to 1 : 13,000 live births in the US.

The etiology of choledochal cysts is unknown but several possible mechanisms have been proposed.

• One theory is based on the increased incidence of an anomalous pancreaticobiliary junction, which is seen in up to 85% of the patients with a choledochal cyst.
  
• This anomaly, which is also known as the “long common channel,” may represent failure of the embryological ducts to migrate fully into the duodenum.
  
• It has been suggested that this “long common channel” contributes to reflux of pancreatic secretions into the common bile duct, leading to damage of the wall and subsequent dilatation.

• Another theory proposes that choledochal cysts are part of the congenital fibropolycystic diseases, or ductal plate malformations.
  
• This theory is supported by the occasional finding of combinations of intrahepatic and extrahepatic bile disorders, with or without concomitant liver fibrosis.

Other factors that have been suggested to play a role in the pathogenesis of bile duct cysts are:

1. inadequate autonomic nerve innervation,
   
2. viral infections, and
   
3. abnormal function or dysmotility of the sphincter of Oddi.
   

• Probably, both congenital and acquired mechanisms can be involved in the pathogenesis of cystic dilatations of the bile ducts.

Most choledochal cysts become symptomatic during childhood.

• However, symptoms can be nonspecific, and the diagnosis can be missed until adolescence.
  
• The classic clinical triad of symptoms includes
  • intermittent upper abdominal pain,
    
  • jaundice, and a
    
  • palpable mass in the right upper quadrant of the abdomen.
• Occasionally, patients remain asymptomatic and the choledochal cyst is “incidentally” found during ERCP, computed tomography, or magnetic resonance cholangiopancreaticography (MRCP) performed for nonrelated symptoms.
  
• Secondary biliary cirrhosis is a rare complication in untreated patients in whom the diagnosis has been missed for several years.
  
• In infants, the disorder has to be differentiated from other diagnoses, which belong to the group of infantile obstructive cholangiopathies.
  
• In adults, differentiation between choledocholithiasis with secondary bile duct dilatation and a type I cyst in which stones have developed can usually not be made on the clinical symptoms alone.
  
• The definite diagnosis is usually made by radiologic imaging studies, similar to that discussed for Caroli’s disease above.

To treat or prevent complications, such as recurrent cholangitis and secondary cirrhosis, surgical treatment is generally indicated.

Another argument for surgical intervention is the risk of malignant degeneration, which has been reported in 2.5 to 30% of the patients in different series.

• Malignancies associated with choledochal cysts may arise within the cyst, but have also been described elsewhere within the liver or the biliary or pancreatic ducts.
  
• In fact, about one-third of the malignancies occur outside the bile duct cyst itself and they may even develop after cyst excision.

The current treatment of choice is a complete resection of the cyst and a hepaticojejunostomy, with a mucosa-to-mucosa anastomosis.

• If complete excision is not possible, partial cyst excision and a cystojejunostomy to an epithelial-lined portion of the cyst remnant is an acceptable second choice.

Endoscopic unroofing and sphincterotomy of the common bile duct has been successfully performed in patients with symptomatic small choledochoceles (type III choledochal cyst).

• The endoscopist, however, must be aware that an ampullary carcinoma may develop in a choledochocele, and complete surgical excision remains the treatment of choice in cases with large or “abnormal” looking choledochoceles.

A partial liver resection may be indicated in patients with cysts type IVa and type V (Caroli’s disease).

Liver transplantation should be considered in the more rare cases with concomitant diffuse intrahepatic abnormalities, such as congenital liver fibrosis or secondary biliary cirrhosis.

Simple drainage of the cyst alone, by a cyst-enterostomy, is generally regarded as an obsolete procedure, because of the high risk of late complications (anastomotic stricture formation, malignant degeneration).

• Especially in adults, how ever, the cyst wall is sometimes so adherent to the portal vein or the hepatic artery that a plane of dissection cannot be identified.
  
• In these cases, it has been recommended to enter the cyst and excise the entire mucosal lining, leaving the external wall attached to the adjacent structures.
  
• The mucosal lining of a choledochal cysts is currently considered as a precancerous condition, warranting complete excision.
  
• Although some investigators have found an increased risk for neoplasia to develop anywhere in the biliary tract, gallbladder, or pancreas in patients after resection of a choledochal cyst, others could not find malignant changes in the remnant proximal hepatic duct or terminal bile duct after a mean follow-up of 9.1 years.
  
• Prognosis in patients who have developed a cancer in the cyst is very poor, even after surgery.

Biliary cystadenoma and cystadenocarcinoma

Biliary cystadenomas are rare tumors, constituting about 2 to 5% of all intrahepatic tumors of biliary origin.

• Malignant degeneration into a cystadenocarcinoma is even less frequently seen.
  
• The size of biliary cystadenomas varies between 0.5 and 30 cm, with an average diameter of 10 cm.
• Usually they have a multilocular and multilobular aspect, with papillary foldings.
  
• The tumors arise from the intrahepatic, and rarely from the extrahepatic, bile ducts or gallbladder.

Cystadenomas are most frequently found in middle-aged females, but a nearly equal sex distribution has been found for cystadenocarcinomas.

• The inner lining of the cysts is formed by columnar epithelium with or without a densely cellular (“ovarian-like”) stroma.
  
• Cystadenocarcinomas surrounded by an “ovarian-like” stroma are exclusively found in females, whereas the ones without a distinctive cellular stroma are seen in males.
  
• The presence of a true epithelial lining distinguishes these cysts from infectious lesions and “pseudocysts.”
• Another distinguishing feature is the mucinous content of these cysts, compared to the more serous fluid content of simple cysts.

The etiology of biliary cystadenomas is largely unknown.

• It has been suggested that they develop from ectopic remnants of primitive foregut sequestered within the liver.
  
• According to this theory cystadenoma is a congenital, rather than an acquired, disorder.
• Cystadenocarcinomas are considered to result from malignant degeneration of cystadenomas.
  • A transition zone between benign and malignant parts is often encountered on histological examination of cystadenocarcinomas, supporting this theory.

The clinical presentation and symptoms are usually mild and atypical.

• Cystadenomas are slowly growing tumors, which usually remain asymptomatic until the second or third decade of life.
  
• In more than 80% of the patients, the presenting symptoms include
  • upper abdominal pain or discomfort,
    
  • nausea,
    
  • jaundice, and
    
  • a palpable mass.
• Less than 20% are discovered coincidentally. Complications are also seen in about 20% and include
  • cholangitis or sepsis secondary to compression of bile ducts,
    
  • hypertension due to portal vein compression,
    
  • bleeding, and
    
  • ruptureLaboratory studies usually reveal normal liver function tests and normal serum levels of alpha-fetoprotein and CEA. CA19-9 levels, however, are elevated in most cases and measurement can be helpful in making the diagnosis.

On ultrasonography and computed tomography, cystadenomas are usually recognized as multilobular cysts with internal septation and/or small polyps.

Cystadenomas need to be differentiated from simple cysts, with or without malignant degeneration, hydatid cysts, metastatic cystadenocarcinomas, primary or metastatic neoplasms with central necrosis, and post-traumatic cysts.

• Cystadenocarcinomas should be highly suspected when large papillary or solid parts are found inside the cyst on imaging studies.

Preoperative differentiation between a congenital cyst with malignant degeneration and a cystadenocarcinoma can be very difficult, if not impossible.

• Percutaneous aspiration of the cystic fluid and needle biopsy have been propagated to facilitate the diagnosis.
  
• However, these techniques may cause seeding metastasis of the needle track and therefore this procedure should be avoided.

The treatment of choice is a complete excision of the mass.

• This can be done either as a (anatomical or extraanatomical) liver resection or enucleation, depending on the size and localization of the tumor.
  
• Partial excision of cystadenomas is associated with a recurrence rate of 90%.
  
• Even after complete excision, recurrences are seen in 5% of the patients and therefore patients should be given a long follow-up.
  In general, however, the prognosis is good in patients with cystadenomas, if the tumor can be completely resected with free margins of normal liver tissue.
  
• Patients with cystadenocarcinomas accompanied by an “ovarianlike” stroma, who have been treated with radical excision also have a relatively good prognosis.
  
• However, cystadenocarcinomas lacking a distinctive (“ovarian-like”) surrounding stroma usually follow a more aggressive course and are more likely to result in the patient’s death.
  
• In one series, median survival for male patients with cystadenocarcinomas was 3 years, whereas no deaths were seen during these years of follow-up in 30 female patient with cystadenocarcinomas which were surrounded by a mesenchymal stroma.
  
• Distant metastases are rarely seen, but can occur in the liver, lungs, and bones.

CYSTIC DISEASES OF LIVER AND BILIARY TRACT (Part One)

Introduction

Cystic lesions of the bile ducts and liver can result from a variety of pathologic processes. They may be solitary or multiple.

• Cystic abnormalities occurring within the liver parenchyma, which are not in continuity with the biliary tree, are referred to as liver cysts.
  
• Cystic lesions which are in direct continuity with the intra- or extrahepatic bile ducts are considered as biliary cysts.
  

• Cystic lesions of the liver with an infectious origin (e.g. echinococcus or hydatid cysts, liver abscesses) and pseudocysts will not be discussed in this topic.

Cysts of the liver and bile ducts can occur as single entities, but are frequently found in various combinations of intra- or extrahepatic cystic abnormalities.

• Although the exact mechanisms underlying the origin of liver cysts are unknown, mutations in four distinct genes have been linked to various types of polycystic liver disease.
  
• Cystic abnormalities of the intra- and extrahepatic bile ducts have been historically classified as acquired entities; however, it is likely that other factors (i.e. genetic factors) also play a role in the pathogenesis of cystic diseases of the bile duct.
  
• In general, true or epithelialized liver and biliary cysts can be divided into two groups:

1. Neoplastic and
2. Non-neoplastic group.
   

• The neoplastic group primarily comprises:
  

1. Biliary cystadenoma and
   
2. Cystadenocarcinoma,

• The non-neoplastic group can be subdivided into:
  

1. Simple liver cysts,
   
2. Polycystic liver diseases,and
   
3. Bile duct-related cystic diseases.

Simple liver cysts

Simple hepatic cysts are also known as benign, nonparasitic, or solitary cysts, the latter being a poor name, since they are multiple in 50% of the cases.

• Although these cysts were traditionally considered as rare lesions, by the wider application of imaging modalities, such as the computed tomography (CT) scan, we now know that these cysts can be found rather commonly in asymptomatic patients.
  
• The exact pathogenesis of simple hepatic cysts is unknown, but it has been suggested that they develop from biliary microhamartoma or aberrant bile ducts, which have lost contact with other parts of the biliary system during the early embryological stages.
  

• Although simple hepatic cysts are not in direct continuity with the biliary tree, their presumed biliary origin, and the differential diagnosis with other types of hepatic and biliary cystic disorders, justifies a discussion of simple hepatic cysts in this topic

Simple cysts can be found at all ages, although the prevalence increases with increasing age and women are more often affected than men.

• Most cysts have a round or oval shape on cross-section and can vary in size from a few mm to more than 30 cm.
  
• They are usually asymptomatic and are found coincidentally during ultrasound or CT examination of the abdomen for unrelated symptoms or conditions.
  
• Occasionally, large cysts cause vague upper abdominal complaints or symptoms of partial bowel, secondary to compression of the gastrointestinal tract.
  
• Large cysts located in the hepatic hilum can cause obstructive jaundice or portal hypertension due to compression of the hepatic duct or portal vein.
  
• Compression of the inferior vena cava is a very rare complication, but it may lead to an inferior vena cava syndrome, characterized by symptoms related to venous congestion of the lower part of the body.
• Acute abdominal pain may result from rupture or bleeding into the cyst.
  
• Depending on the size and location within the liver, cysts can sometimes be found on physical examination.
• Serum values of the hepatic enzymes may be increased, but are usually within the normal range.

Histologically, the inner cystic lining is formed by a single layer of cuboidal or columnar epithelium that resembles biliary epithelium.

• The cystic fluid is usually clear yellow and serous, but may appear bloody or purulent under given circumstances.
  
• The presence of numerous microhamartomas in the surrounding liver, or the combination of multiple cysts should raise the possibility of autosomal dominant polycystic disease.
  
• Malignant degeneration, either to squamous cell carcinoma, adenocarcinoma, or a mixed type, is a rare but serious complication.

The diagnosis of simple cysts is usually made by ultrasonography or computed tomography .

• Differentiation with abscess, hematoma, and solid tumors is not difficult when using these radiological techniques.
  
• The differentiation between simple cysts and echinococcal (hydatid) cysts can be somewhat more difficult.
  
• Depending on the local prevalence of echinococcal infections, hydatid liver cysts may be mistaken for a simple liver cyst in up to 5% of the cases.
  
• Although simple cysts are always unilocular and never have calcifications, echinococcal cysts are usually septated and frequently have calcifications in the wall.

Serological studies will be helpful in discriminating the two conditions from each other.

Cysts with irregularities of the cystic wall or papillary projections into the cystic cavity should raise a very high suspicion for cystadenoma or cystadenocarcinoma.

• In these cases, carbohydrate antigen 19-9 (CA 19-9) or carcinoembryonic antigen (CEA) serum concentrations are usually elevated, where as this is not the case in simple cysts.
  
• Occasionally, metastasis from other tumors can present as cystic lesions due to central necrosis and cavity formation.

Treatment is not indicated in case of asymptomatic simple cysts.

For symptomatic cysts different approaches have been described.

Simple percutaneous puncture and aspiration of the cystic content is not effective and is immediately followed by refilling of the cysts.

• Percutaneous aspiration of the cyst followed by the injection of a sclerosing agent (95% alcohol or minocycline) has a higher success rate of up to 70%.
  
• However, for a long-term success, repeated procedures are usually required, which carry the risk of infection or sclerosing cholangitis.
  
• The use of alcohol can be complicated by pain, fever, or alcoholic intoxication.
  

Laparoscopic unroofing of the external part of the cyst, followed by transposition of an omental flap into the remaining cyst cavity, is currently considered to be the treatment of choice for symptomatic cysts.

Open surgery is indicated when cysts cannot be approached laparoscopically (e.g. the posterior segments VI and VII, and segment IVa), or when a potentially malignant disease cannot be excluded.

• If aspiration of the cystic contents, with precautions to avoid contamination of the abdominal cavity, provides evidence for a malignancy, a partial liver resection is indicated.
  
• Also, the incidental finding of a cystadenoma during or after laparoscopic fenestration of a liver cyst requires an open or laparoscopic enucleation of the cyst and in some cases hepatic resection.

Polycystic diseases of the liver

Multiple liver cysts can be identified in three different types of diseases:

1. Autosomal dominant polycystic kidney disease,
   
2. Autosomal dominant liver disease, and
   
3. Autosomal recessive polycystic liver disease (also known as congenital hepatic fibrosis).
   

The hepatic abnormalities in the first two types of polycystic liver disease are phenotypically similar, but mutations in distinct genes have been linked to these disorders.

Disease presentation in autosomal recessive polycystic liver disease is highly variable and may vary from biliary dysgenesis, resulting in congenital hepatic fibrosis, to intrahepatic bile duct dilatations.

Autosomal dominant polycystic diseases

The group of autosomal dominant polycystic diseases consists of genetically heterogeneous disorders with identified mutations in four distinct genes.

In the most common form, cystic manifestations are most prominent in the kidneys, and

• this disease is called autosomal dominant polycystic kidney disease (AD-PKD).
  
• Mutations in two different genes have been linked to AD-PKD: PKD1 and PKD2.
  
• Mutations in the PKD1 gene account for 85 to 90% of mutations in ADPKDfamilies; the remaining 10 to 15% are due to mutations in PKD2.
  
• PKD1 and 2 encode for proteins called polycystin-1 (PC-1) and polycystin-2 (PC-2), which have been characterized as membrane-bound proteins involved in cell–cell and cell–matrix interactions.
  
• Moreover, recent evidence demonstrates that PC-1 and PC-2 form the core of a mechanotransduction signaling complex within ciliated epithelium cells.

The three forms of polycystic liver disease are all characterized by the development of multiple liver cysts and are phenotypically indistinguishable.

The overall prevalence at autopsy studies is about 0.13%.

The natural history of the autosomal dominant forms of polycystic liver disease is strikingly similar, despite the variations in molecular and genetic background.

• Hepatic cysts are rarely observed before puberty.
  
• They tend to appear with increasing age, more commonly in women, especially after multiple pregnancies or the use of drugs containing sex hormones.
  
• In addition to liver and kidney cysts, patients with AD-PKD may also develop cysts in other organs, including the pancreas, spleen, ovaries, uterus, testes, thyroid, and mesenterium.
  
• Other associated disorders are colonic diverticula, vascular aneurysms, and inguinal hernias.
  
• Polycystic liver disease is considered to result from progressive dilatation of abnormal ducts in microhamartomas or von Meyenburg complexes, at the level of the small intrahepatic bile ducts.
  
• Apart from the initial gene mutation (“first hit”), a second loss-of-function muation in the functional gene copy (“second hit”) is believed to be responsible for initiation of cell proliferation and cyst formation.
  
• Expanding cysts detach from the intrahepatic bile duct, which explains the noncommunicating nature of the cysts in polycystic liver disease.
  
• On histological examination the cysts are very similar to simple hepatic cysts.
  
• The inner wall is formed by a single layer of more or less cuboidal epithelium, resembling biliary epithelium and they are surrounded by a thin fibrous wall.

Polycystic liver disease is usually asymptomatic and an incidental finding.

• Symptoms occur in 10 to 20% of the patients and usually not before the third decade.
  
• Most symptoms center around the massive hepatomegaly and include upper abdominal pain and discomfort, abdominal distention, and dyspnea.
  
• Hepatic function is well preserved in most cases and serum levels of liver enzymes are either normal or only slightly elevated.
  
• In symptomatic patients the liver can usually be felt on physical examination and may extend downwards into the pelvis.
  
• Complications may occur from infection, compression, bleeding, or rupture of the cysts.
  
• Infection of hepatic cysts occurs in up to 3% of patients with autosomal dominant polycystic disease who have end stage renal failure, but in less than 1% of such patients before end-stage renal failure.
  
• Compression of the bile ducts may result in jaundice.
  
• Isolated cases with compression of the inferior vena cava vein or portal vein, resulting in an inferior vena cava syndrome or portal hypertension, have been reported.
  
• Malignant degeneration is extremely rare and has been described only in a few case reports.
  
• Modern radiologic studies, such as ultrasonography, computed tomography, or magnetic resonance imaging (MRI) can be helpful in making the diagnosis or defining the cause of complications.

Diagnostic puncture and aspiration of the cyst content will facilitate in making the diagnosis when infection
of a cyst is suspected.

Most patients with polycystic liver disease do not require treatment.

• When kidney disorders are present, the abnormalities in kidney function, rather than the liver disease, define the long-term prognosis.
  
• Treatment of liver cysts is indicated in cases with serious complaints of pain or consequences of compression and/or infection.
  
• There is currently no specific medical treatment for polycystic liver disease.
  
• As with simple liver cysts, decompressing puncture alone does not provide long-term relief of symptoms.
  
• Chemical ablation is only indicated when one or two dominant cysts can be held responsible for the symptoms.
  

The indication for surgical interventions is less evident than for simple cysts.

Possible options are laparoscopic or open fenestration, partial liver resection, and liver transplantation.

• Relief of symptoms is often transient and the long-term effect of most surgical interventions is disappointing.
  
• Selected patients with severe symptomatic polycystic liver disease and favorable anatomy benefit from liver resection and open or laparoscopic fenestration with acceptable morbidity and mortality.
  
• The extent of hepatic resection and fenestration is important for the long-term effectiveness of this procedure.
  
• Some highly symptomatic patients with massive polycystic liver disease may benefit from combined hepatic resection and fenestration with acceptable risk.
  
• In general, the indication for surgical interventions in polycystic liver disease is limited and it should always be viewed in relationship with the risk of postoperative complications, such as infection or massive ascites production.
  
• In selected cases with diffuse bilobar polycystic disease and massive hepatomegaly, liver transplantation with or without combined kidney transplantation should be considered.

Autosomal recessive polycystic disease/congenital hepatic fibrosis

Autosomal recessive polycystic disease, also known as infantile polycystic disease, and congenital hepatic fibrosis are often seen in combination, and it has debated whether these entities are a different expression of the same underlying developmental disorder at the level of the intermediate or small intrahepatic bile ducts, rather than two distinct disorders.

• Both conditions are frequently associated with other liver malformations, such a Caroli’s disease and von Meyenburg complexes, but also with renal dysgenesis, such as polycystic renal disease, renal dysplasia, or nephronophthisis.
  
• The exact prevalence of autosomal recessive polycystic disease is not known, but estimates have suggested a frequency of 1 : 20,000 live births.
  
• Liver abnormalities are characterized by fibrous enlargements of the portal tracts containing numerous abnormally shaped and ectatic bile ducts.
  
• Macroscopically visible cysts are usually not present in the liver.
  
• Which term is used in an individual patient is mostly dependent on the amount of renal involvement, with the term autosomal recessive polycystic kidney disease preserved for those cases with renal involvement as the most prominent feature.
  
• Autosomal recessive polycystic kidney disease has been linked to mutations in the PKHD1 (polycystic kidney and hepatic disease 1) gene, encoding for fibrocystin, and located on chromosome 6p.
  
• Fibrocystin is a large protein and may have a receptor function.
  
• Recent evidence has linked the protein to the primary cilium of biliary epithelium cells.
  
• This localization is in common with that of other proteins that have been associated with other types of polycystic diseases.
  
• Cystic dilatations are not the main feature of these conditions.
• However, high mortality rates associated with this disorder make it an important cause of pediatric death.