Hepatic or Cystic Artery Pseudoaneurysms Following a Laparoscopic Cholecystectomy Literature review of aetiopathogenesis , presentation , diagnosis and management

abstract: Pseudoaneurysms (PSAs) of the hepatic and/or cystic artery are a rare complication following a laparoscopic cholecystectomy (LC). Generally, PSA cases present with haemobilia several weeks following the procedure. Transarterial embolisation (TAE) is considered the optimal management approach. We report a 70-year-old woman who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2016 with massive hemoperitoneum two weeks after undergoing a LC procedure in another hospital. She was successfully managed using coil TAE. An extensive literature review revealed 101 cases of hepatic or cystic artery PSAs following a LC procedure. Haemobilia was the main presentation (85.1%) and the mean time of postoperative presentation was 36 days. The hepatic artery was involved in most cases (88.1%), followed by the cystic artery (7.9%) and a combination of both (4.0%). Most cases were managed with TAE (72.3%), with a 94.5% success rate. The overall mortality rate was 2.0%.

A laparoscopic cholecystectomy (LC) is the gold standard of treatment for symptomatic cholelithiasis due to its distinct advantages of reduced pain, early discharge and reduced wound complications. 1,2However, it is rarely associated with major complications, such as vascular complications (0.25%). 1,23][4][5] The mechanisms involved in the formation of a PSA may be multifactorial and include excessive use of cauterisation during the dissection of Calot's triangle, particularly if there are any abnormal anatomical variations of the vasculature. 2,64][5][6][7][8][9] This article describes a patient with a PSA of the hepatic artery originating in the cystic artery and then presents an extensive review of the scientific literature regarding the aetiopathogenesis, presentation, diagnosis and management of PSAs following LC procedures.
At presentation, the patient was hypotensive but responded to fluid resuscitation.She appeared pale and in severe pain.A physical examination revealed tenderness on the right side of the abdomen with abdominal guarding.Laboratory investigations revealed a haemoglobin level of 6.7 g/dL, haematocrit level of 0.26 L/L and raised lactate levels, with all other measurements within normal limits.A computed tomography (CT) scan of the abdomen with intravenous contrast showed multiple collections of fluid in the abdomen and pelvis with some reactionary changes to the bowel wall and no evidence of mesenteric ischaemia [Figures 1A and B].After receiving a blood transfusion, the patient was transferred to the operating room for a diagnostic laparoscopy, which revealed 1,500 mL of blood and clots with small bleeding points in the liver bed around the clips from the initial LC surgery.These bleeding points were subsequently clipped.There was no evidence of bile leakage.
Following the procedure, detailed examination of the CT scans suggested a PSA of the right hepatic artery (RHA) at the point of origin of the cystic artery [Figures 1C and D].Conventional angiography confirmed these findings and coil embolisation of the PSA in the RHA was carried out [Figure 2].The patient's liver function test findings remained normal during the postoperative period.However, the postoperative  Norman O. Machado, Adil Al-Zadjali, Anupam K. Kakaria, Shahzad Younus, Mohamed A. Rahim and Rashid Al-Sukaiti Review | e137 course was complicated by a hernia at the umbilical port site for which she underwent an open repair.She was discharged on the 12 th postoperative day.Six weeks later, during a follow-up appointment in the outpatient clinic, she appeared to be doing well.
Reasons for TAE failure included continuous growth of the PSA over a period of two months, persistent bleeding and other associated injuries, including to the portal vein. 6,7,42Among the cases treated with TAE, complications included liver abscesses (n = 10; 13.7%), post-embolisation syndrome and hepatic ischaemia (n = 9; 12.3%),postoperative bleeding for a month (n = 1; 1.4%) and erosion of the stent into the common bile duct (CBD; n = 1; 1.4%). 3,15,16,37,45The overall mortality rate was 2.0% (n = 2). 7,40One fatality was due to severe haemorrhagic relapse following repair of the PSA, resulting in irreversible hypovolaemic shock despite re-exploration and ligation. 40In the second case, the patient died from a concomitant injury to the portal vein. 7

Discussion i n c i d e n c e
The true incidence of PSAs in the cystic/hepatic arteries is difficult to determine as many cases are asymptomatic and thus never detected. 57Moreover, small subclinical PSAs may thrombose spontaneously or be too small to be observed, even on imaging. 57he reported incidence of PSAs involving the cystic or hepatic arteries following an LC procedure ranges from 0.06-0.6%. 3,63The incidence of haemobilia following an emergency LC for acute cholecystitis (within 72 hours) has been reported to be 0.001%, while it has been observed to be 0.0003% for those undergoing an elective LC. 31 A higher incidence of PSAs involving the hepatic artery has been reported in patients with a concomitant bile duct injury (4.5%). 441]57 Other involved sites include the cystic artery and, in some cases, the common hepatic and gastroduodenal arteries. 4,9,37,38,44,47,58e t i o pat h o g e n e s i s A PSA may arise due to multiple mechanisms of injury, including laceration, transection or occlusion of the blood vessels following a mechanical or thermal injury to the artery.6,37,51 This may occur when inappropriate energy (thermal/mechanical) is applied during dissection of the Calot's triangle or following dissection with a laser.5,37 A thermal injury could result from the direct transfer of heat to the vessel by cautery or indirectly via a metal clip in contact with the artery.3,18,31 Injury of the vessel could also be due to clip intrusion, bile leakage or infection.4,9,31 In numerous cases, the PSA has been found directly adjacent to a clip.31,43,46,51 1: Literature review of cases of pseudoaneurysm of the cystic and/or hepatic arteries following a laparoscopic cholecystectomy  Author and year of article    patients with bile leaks; this has been postulated to cause direct weakening and erosion of the vascular wall, leading to a PSA.4,18 In patients with bilomas, the resulting secondary infection may precipitate the development of a PSA. 4 Associations have also been reported between PSAs and intraoperative adhesions and anatomical variations of the ducts and cystic artery.16,41,57 Major anatomical variations include a doubled cystic artery (20%), a "caterpillar hump" formation of the RHA and the unusual course of the cystic artery anterior to the CBD or common hepatic artery.41,57 During a LC procedure, vessel injury can be avoided by adhering to basic surgical tenets, including performing the dissection in the plane closest to the gallbladder wall, retaining adequate view of the cystic artery and the duct entering the gallbladder before applying an energy source, freeing the infundibulum inferiorly to widen Calot's triangle (i.e.pediculisation) and ensuring meticulous dissection without bleeding so as to identify structures before applying the clips.1,57 In the event of bleeding, the blind application of clips or use of cautery may also enhance the risk of vascular injury. 1 Some researchers have recommended the use of bipolar cautery or ultrasonic dissection for a thickwalled gallbladder, particularly when the dissection penetrates deep into the liver-as in a buried gallbladder-because the potential carbonisation with the use of these tools is minimal in comparison to laser or monopolar cautery.31 The risk of a PSA rupture is related to its size, with a greater than 10-fold risk when the aneurysm is more than 5 cm. 7 In caes of rupture, bleeding can be either minimal or heavy, particularly in those presenting late.7,15 In such cases, a LC carried out for acute cholecystitis or concomitant ductal injury may be a difficult and prolonged procedure.4,6,18,30,31,37,41 p r e s e n tat i o n A PSA may present either in the initial days following a cholecystectomy or be delayed over weeks, months or, on rare occasions, years.31,41 A delay in presentation following a thermal injury could be due to charring of a vessel which gets detached weeks later, particularly in the presence of bile.31 Patients may present with gastrointestinal (GI) bleeding (i.e. haembilia) and/or hemoperitoneum, particularly when the PSA is large; in contrast, smaller PSAs may occasionally present with minimal abdominal discomfort.7 Haemobilia has been reported to be the most frequent presentation (90%), while abdominal pain (70%) and jaundice (60%) are other common presentations.3,31 The classical presentation of Quincke's triad (jaundice, abdominal pain and GI bleeding) may be seen in less than 40% of haemobilia cases.64 Rarely, an abdominal mass with a bruit may be noted.42 GI bleeding may present as haematemesis or melena, based on the rate of bleeding.63 During its natural course, a PSA will progressively grow in size before rupturing in 21-80% of cases. 30 The upture of a PSA into the peritoneal cavity may present with hypovolaemic shock or may be contained temporarily by the surrounding tissue-often referred to as "double rupture phenomenon", as the initial contained bleeding may be followed by secondary bleeding which is more severe.7 Erosion of a PSA into the cystic duct stump or GI tract forming a fistula between the two structures has been previously reported.5,9,23,24,35,40 This could involve the duodenum, leading to haematemesis, the jejunum, for example in a patient presenting with lower GI bleeding who had previously undergone Roux-en-Y reconstruction following a stomach carcinoma, or hepatic flexure in a patient presenting with hematochezia.23,24,35,40 In most patients (80%), the PSA usually presents approximately one month following the LC surgery; however, delayed PSA presentation as late as five years after the surgery has been reported.6,7

d i a g n o s t i c a n d t h e r a p e u t i c i n v e s t i g at i o n s
The diagnosis of a PSA can be confirmed by a combination of history-taking (i.e.37,53 Ultrasonography may lead to the detection of an aneurysm or fluid consistent with haemorrhage; however, the diagnostic accuracy of this option is directly related to the size of the PSA and the operator's experience. 13,16,25hree-dimensional (3D) CT reconstruction or catheter angiography can also help to define the aneurysm and its feeding vessels.With the advent of multidetector CT scans and advancements in 3D imaging software in the form of volume determination, CT is the preferred technique for primary vascular imaging among patients with suspected PSAs. 20Recent reports have discussed features of haemobilia on a CT scan, including the presence of a haematoma within the abdominal cavity and gallbladder fossae, high attenuation of blood clots within the bile duct, biliary dilatation, a PSA of the RHA, contrast extravasation, enhancement of the bile duct wall and hypoperfusion of the right lobe of the liver. 16,65theter angiography can be both diagnostic and therapeutic. 18,20,29,31Indications of a dilated cystic artery stump on an angiogram are considered ominous and may warrant embolisation, despite a lack of active bleeding during other investigations. 58evertheless, angiography has certain diagnostic Norman O. Machado, Adil Al-Zadjali, Anupam K. Kakaria, Shahzad Younus, Mohamed A. Rahim and Rashid Al-Sukaiti Review | e143 limitations which may be influenced by variable flow rate, intermittent bleeding at the time of investigation and hepatic artery abnormalities. 15Previous research has indicated that coeliac angiography can fail to identify PSAs subsequently detected via selective RHA angiography. 6,18However, angiography has been reported to detect vascular abnormalities in 90% of patients with significant haemobilia. 66r e at m e n t A diagnosis of PSA is considered an acute emergency and requires immediate and aggressive intervention, as a rupture could lead to life-threatening exsanguination; the rupture of a PSA in the hepatic artery has been associated with a mortality rate of 21-43%.17,18,22,33 Historically, PSAs were principally managed via surgery, which involved resectioning of the PSA and ligation of the cystic artery stump or RHA.6 However, due to significant advances in catheter-based therapies, PSAs are now primarily treated with TAE by occluding the sac or the feeding vessel with a variety of embolic agents, including gel foam, coils, N-butyl cyanoacrylate and thrombin, before ideally embolising the vessel distal and proximal to the PSA in order to prevent collateral filling of the PSA.5,6,[15][16][17][18][19]22,23,25,37,43 When coils are used, they can induce thrombosis; hence, in patients with significant coagulopathies, the vessel may still remain patent despite embolisation and the procedure may be ineffective in controlling bleeding.In small PSAs, glue may be used instead as the adhesive conforms to the shape of PSA.43,64 In addition, coil placement may be difficult in patients with a small PSA. 25 In some cases, both approaches may be used.25 Distinct advantages of TAE include the reduced risk of parenchymal injury, the use of local rather than general anaesthesia and rapid patient recovery following the procedure.However, in some instances, TAE may fail initially and the patient may require a further attempt at embolisation.6 Failure may be due to the difficulty in approaching the PSA in the presence of a thrombosed proximal vessel, such as the coeliac or tortuous hepatic arteries.5,11,24,36,48,55 In patients where cannulation is feasible, embolisation failure could be related to an inability to isolate the bleeding vessel, misidentification of the bleeding vessel or incomplete occlusion despite the disappearance of the sac or feeding vessel on post-embolisation angiography. 6,22 In addion, smaller vessels may feed the PSA and contribute to rebleeding, which may not be easily detected during angiography.42 Moreover, loosely packed coils can lead to recanalisation of the aneurysm.6 Failure to successfully embolise a PSA may require nonselective embolisation of the RHA or direct surgical exploration of the PSA.Nonselective embolisation of the RHA may also be required if there is bleeding from multiple sites.39 Recently, several researchers have reported the successful management of PSAs by injecting thrombin directly into the hepatic artery aneurysm.5,6,32 However, embolisation using this technique may be nonselective, resulting in potentially serious complications such as liver and bowel infarctions; injecting small aliquots of thrombin with real-time ultrasound and Doppler guidance may reduce this risk. 6On the other hand, angiographic embolisation may be associated with serious risks, including rupture of the PSA during coil embolisation, an extension of the thrombosis in the RHA, hepatobiliary necrosis, bleeding, abscess formation and CBD stricture due to ischaemia.3,4,22,37 A recent report found that post-embolisation syndrome occurred in nine out of 14 patients and was associated with the age of the patient and the time interval between the LC and TAE.16 In patients with liver cirrhosis or abscesses, some researchers have recommended assessment of adequate arterial and collateral flow prior to hepatic artery embolisation to avoid the risk of ischaemia.37 Others have advised use of a covered stent while treating the PSA in order to maintain blood flow to the liver and prevent complications related to reduced flow.33 Stents may also be used for patients with concomitant hepatic artery stenosis and PSAs.33 For small visceral vessels, the choice of stent is limited; one option is the JOSTENT ® GraftMaster ® graft (Abbott Vascular Inc., Chicago, Illinois, USA), which is 3-5 mm in diameter and 12-26 mm long.The placement of a stent for a PSA of the RHA is considered technically challenging due its distant location, smaller diameter and often complex or altered anatomy.33 The patency of the graft is generally better in arteries with larger diameters and high flow rates.Even though the hepatic artery has a smaller diameter, its high flow rate ensures good patency in most cases.33 In patients where an intra-arterial approach to the hepatic artery is not feasible, successful embolisation via a transhepatic approach has been reported.43 In one case, erosion of the TAE coil into the CBD was observed in a patient who presented two years after the LC procedure with acute pancreatitis.45 Surgical intervention is required if embolisation fails, for patients who lack the necessary haemodynamic stability to undergo a TAE procedure and for those with concomitant bile duct compression or injuries.4,15,22,57 The latter patient group may also require simultaneous biliodigestive anastomosis, although surgical repair can generally be delayed if the duct injury is detected later.2,8,12,19 Surgical intervention may also be mandatory when endovascular intervention facilities are not available and the patient is not stable enough to be transferred to a tertiary hospital.25,40 In cases whereby the PSA has continued to expand after initial control with TAE, subsequent surgical control has been reported in which an exploratory laparotomy and ligation of the feeding vessel resulted in a complete recovery.42 Surgical interventions for PSAs may involve excision of the PSA and ligation of the RHA, removal of a biliary obstruction or, in exceptional cases, a hepatectomy.4,6,20 Excision ensures that a PSA will not grow due to sustained arterial blood pressure; moreover, failure to excise the PSA may lead to its rupture as the aneurysm is often infected.Infection could also lead to a high risk of vascular suture rupture following ligation of the artery; in one report, a patient died 48 hours after having undergone surgical repair of a PSA due to fatal GI bleeding.40 Although in most cases a PSA is surgically treated using an open method, a recent report described the successful laparoscopic suture ligation of a PSA in the right posterior sector of the hepatic artery.21 The initial inspection and manipulation of the PSA led to severe bleeding, which was adequately controlled with a vascular clamp using the laparoscopic Pringle manoeuvre. With a clearer view of te surrounding anatomy, laparoscopic ligation was performed by taking some of the periarterial tissue to prevent ligature slippage.21 Following ligation of the RHA, the risk of a liver infarction is generally limited as blood flow is maintained by portal circulation.26 In addition, revascularisation of the right liver lobe occurs due to the rapid development within the hilar plate of an omega-shaped collateral arterial circulatory system, originating from the preserved branch of the hepatic artery.26 Some patients who present with haemobilia and obstructive jaundice may also require endoscopic retrograde cholangiopancreatography, transhepatic biliary drainage or CBD exploration to evacuate the clot if the jaundice does not improve.17,30,64 Embolisation has been reported as generally successful in 82% of cases, with surgery required for the remaining 18% of patients.7 Surgical management of massive haemobilia is reportedly successful for 90% of patients, with rebleeding and mortality rates of <5% and 10%, respectively.22 However, there have been reports of higher operative mortality rates (27-50%), particularly among haemodynamically unstable patients.36,67,68

Conclusion
A hepatic and/or cystic artery PSA following a LC procedure is an uncommon yet potentially lifethreatening complication.The often delayed presen-tation of this condition, which can occur weeks or months after the surgery, and its common manifestation with GI bleeding can easily result in misdiagnosis or delayed treatment.Hence, a high index of clinical suspicion is required for patients with unexplained GI bleeding following a LC procedure.A contrast CT scan or angiogram usually confirms the diagnosis and TAE is considered the gold standard of management, with a high success rate.However, surgical intervention is required for cases in which TAE is unfeasible or fails.Precautions should be taken to avoid vascular injury while performing a LC in order to reduce the risk of a PSA, particularly when the cholecystectomy procedure is difficult.

Figure 2 :
Figure 2: Selective angiograms of the hepatic artery of a 70-year-old woman two weeks after a laparoscopic cholecystectomy showing (A) focal outpouching from the right hepatic artery (RHA) at the site of origin of the cystic artery (arrow) and (B) complete obliteration of the pseudoaneurysm (arrow) following coil embolisation of the RHA.

Figure 1 :
Figure 1: Computed tomography (CT) images of a 70-year-old woman two weeks after a laparoscopic cholecystectomy.A: Non-contrast CT scan of the pelvis showing hyper-dense pelvic fluid (arrow).B: Non-contrast CT scan of the upper abdomen showing a small collection of fluid in the gallbladder fossa with layering hyper-dense contents (arrow).C: Arterial-phase CT scan showing a slight irregularity (arrow) in the right hepatic artery (RHA).D: Three-dimensional CT reconstruction confirming the irregularity and focal dilatation of the RHA (arrow).
Stent followed by a repeat stent and TAE (gel foam) Bleeding from the LHA after placement of the initial stent Good Abdalla et al.Machado, Adil Al-Zadjali, Anupam K. Kakaria, Shahzad Younus, Mohamed A. Rahim and Rashid Al-Sukaiti Review | e139 Kamani et al.