Biliary sunrise - bile color as visible sign for hepatic ischemia after iatrogenic partial liver de-arterialization: A case report

Abstract

BACKGROUND

Bile duct injuries (BDI) present a serious complication of laparoscopic cholecystectomy. Additional arterial injuries, usually affecting the right hepatic artery (RHA), significantly worsen the prognosis. The combination of BDI and RHA injury is rare, but its occurrence is associated with a high risk of hepatic ischemia and necrosis.

CASE SUMMARY

A 72-year-old multimorbid patient was transferred to our tertiary center after laparoscopic cholecystectomy with combined complete transection of the common hepatic duct (Strasberg E4) and the RHA. Imaging showed delayed arterial contrast enhancement of the right hepatic lobe and biliary obstruction. During surgical revision, the right and left biliary systems were repaired with a combined hepaticojejunostomy and Roux-en-Y reconstruction. Three internal-external biliary Neuhaus drains were inserted into the right posterolateral, right anteromedial, and left bile ducts to splint the anastomosis. Postoperatively, there was a rapid decrease in serum bilirubin levels with no evidence of biliary leakage. A noticeable difference in the color of the drained bile between the individual liver areas was observed, correlating with the extent of regional liver ischemia. This characteristic pattern was referred to as “biliary sunrise”. Despite an initially stable course, the patient died as a result of septic multiple organ failure.

CONCLUSION

This case illustrates the pathophysiological consequences of a combined BDI and RHA injury. Segmental differences in biliary pigmentation can serve as a macroscopic indication of the extent of hepatic ischemia.

Key Words: Hepatic ischemia; Liver de-arterialization; Bile color; Bile duct injury; Ischemic cholangiopathy; Case report

Core Tip: Hepatic ischemia occurs after hepatic arterial occlusion with concomitant injury to collaterals, most importantly the peribiliary vascular plexus. This case of combined bile duct and right hepatic artery injury demonstrates that regional differences in bile color correlate with the extent of segmental hepatic ischemia. Darker, more concentrated bile originated from more ischemic areas, whereas lighter bile indicated preserved perfusion. Changes in bile color, although not studied extensively in recent years, might reflect underlying alterations in bile composition. These macroscopic changes provide a simple, real-time indicator of hepatobiliary functional impairment and offer interesting insights into the pathophysiology of ischemic cholestasis.

INTRODUCTION

Bile duct injury (BDI) during laparoscopic cholecystectomy presents a devastating surgical complication often requiring major revision surgery. Even with professional surgical repair it is associated with significant morbidity and mortality as well as long-term impact on quality of live[1,2]. In patients with concomitant hepatic artery injury, postoperative outcome is even less favorable[3,4]. Restricted arterial perfusion can lead to ischemia of the liver and bile ducts, resulting in distinct histopathological as well as functional changes of the hepatic parenchyma and biliary tree. This is particularly evident in cases of liver transplantation where impaired arterial supply leads to ischemic cholangiopathy and consecutive non-anastomotic biliary strictures[5]. Apart from liver transplantation, isolated hepatic arterial injury usually is tolerated without clinical consequences due to extensive arterial collaterals from the peribiliary vascular plexus to the liver. However, in cases of concomitant BDI these collaterals no longer provide arterial blood supply, resulting in higher risk of hepatic necrosis[4]. Simultaneous BDI and arterial injury most commonly affects the right hepatic artery (RHA). Herein, we present a case of combined BDI and RHA injury during laparoscopic cholecystectomy with consecutive surgical repair by proximal hepaticojejunostomy and anastomotic splinting through internal-external biliary drainage of liver regions with different degrees of ischemia.

CASE PRESENTATION

Chief complaints

A 72-year-old male patient with a previous history of advanced dementia was transferred to our tertiary surgical care facility for further management after sustaining a combined BDI and RHA injury during laparoscopic cholecystectomy at a peripheral hospital.

History of present illness

According to the medical records, the procedure was technically challenging due to extensive adhesions secondary to chronic cholecystitis.

History of past illness

The initial operation was performed three days earlier due to clinical signs of previous biliary colic.

Personal and family history

No relevant personal or family history was obtained.

Physical examination

In the postoperative course, progressive jaundice was observed.

Laboratory examinations

Laboratory investigations at that time showed a peak total serum bilirubin of 8.82 mg/dL.

Imaging examinations

An abdominal computed tomography scan with intravenous contrast demonstrated impaired arterial perfusion of the right hepatic lobe, suggestive of RHA injury, with associated intrahepatic biliary dilatation and non-visualization of the common bile duct within a postoperative hematoma. A magnetic resonance cholangiopancreatography was performed which also showed signs of BDI. In a subsequent endoscopic retrograde cholangiopancreatography the main bile duct could not be contrasted (Figure 1).

Figure 1 Contrast-enhanced computed tomography demonstrating delayed enhancement of the right hepatic lobe during the arterial phase and occlusion of the right hepatic artery.

FINAL DIAGNOSIS

Open revision surgery was indicated and performed 8 days after the primary operation. Intraoperatively, both a total main hepatic duct as well as RHA transection with surgical clips in place were identified. After removal of the surgical clip on the proximal hepatic duct, it was evident that the injury corresponded to a Strasberg type E4 without any remainder of bile duct wall between the right and left main hepatic ducts (Figure 2).

Figure 2 Intraoperative findings demonstrating iatrogenic transection and clipping of the main hepatic duct and right hepatic artery.

TREATMENT

Due to multimorbidity of the patient, the timeframe since the injury and some remaining collateralization from the left hepatic artery as assessed by intraoperative Doppler-sonography, a decision against arterial reconstruction was made. Since the preoperative laboratory tests showed no signs of significant liver necrosis and transaminase levels had normalized, resection of the right hepatic lobe was not performed in view of the patient’s general frailty. A duct-combining hepaticojejunostomy with Roux-en-Y reconstruction was initiated. Splinting of the anastomosis was achieved by insertion of three biliary Neuhaus drains providing an internal-external drainage. The three drains were directed into the biliary tree, corresponding to right posterolateral, right anteromedial and left bile ducts. Subsequently, they were brought to the jejunum and transfixed through the wall with consecutive creation of a Witzel channel as described by Strücker et al[6].

After creation of the hepaticojejunostomy, the three drains were brought to the surface and attached to draining bags. Two additional drains were placed in proximity to the anastomosis and the abdomen was closed (Figure 3).

Figure 3 Operative reconstruction. A: Intraoperative drain placement into the right posterolateral, right anteromedial and left bile duct; B: Percutaneous transfixed drains with external drainage.

OUTCOME AND FOLLOW-UP

Over the first postoperative days, the course was favorable. The total serum bilirubin decreased to 1.9 mg/dL on postoperative day two and there were no signs of biliary leakage in the extracted secrete of the perianastomotic drains. Interestingly, the color of the extracted bile differed in all three Neuhaus drains, reflecting the degree of liver parenchyma ischemia from most ischemic (right posterolateral duct), to relative ischemia in a transitional zone (right anteromedial duct) and virtually no ischemia (left bile duct). Since the extracted bile showed to be more concentrated and thus darker, coming from more ischemic areas, a characteristic pattern of biliary pigmentation was recognized. Due to its resemblance to the gradual color transition of the sky during dawn, this observation was termed the “biliary sunrise” (Figure 4).

Figure 4 The “biliary sunrise”. (Figure 4B was created by Adrian Stelzl using a professional graphic illustration software - Affinity Designer). A: Extracted bile demonstrating a gradient of biliary pigmentation from more ischemic to less ischemic liver regions. From left to right: 1: Right posterolateral duct; 2: Right anteromedial duct; 3: Left bile duct; B: Schematic illustration of Neuhaus drain positioning within the partially ischemic liver.

Unfortunately, over the next postoperative days the patient’s condition progressively deteriorated. He developed pneumonia with septic multiorgan failure. Because of the severe comorbidities and advanced dementia, recovery was deemed unlikely. In accordance with the patient’s family, a decision was made to withdraw life support and to commit to comfort terminal care. The patient passed away on postoperative day five with good symptom control.

DISCUSSION

BDI is a rare but serious complication of laparoscopic cholecystectomy, occurring in about 0.3%-0.7% of performed cases[7]. Although surgical repair is usually feasible, it results in a significant impact on long-term quality of live and an increased mortality of 8.8% compared to the expected age-adjusted death rate after 20 years[8]. For this reason, effective prevention of BDI is of utmost clinical importance. Currently used approaches include the critical view of safety as well as the use of bile duct imaging like intraoperative cholangiography or indocyanine green fluorescence cholangiography. In cases of unclear anatomy despite usage of these techniques, subtotal cholecystectomy should be considered as a bailout procedure[9]. Strasberg type E4 BDI represent a proximal transection at the level of the biliary confluence with no communication between left and right hepatic ducts[10]. These injuries are characterized by a high failure rate after surgical repair, frequently requiring hepatic resection or even liver transplantation[11]. When hepaticojejunostomy is performed, a combination anastomosis of separate bile ducts can be performed. In cases where the distance between right and left hepatic duct does not allow combination into one enterohepatic anastomosis, a double-barreled dual hepaticojejunostomy has been reported to effectively achieve biliary drainage[12].

Concomitant hepatic arterial injury aggravates the already serious prognosis of BDI even further. Depending on the anatomical location and distribution of the arterial injury consequences range from rapidly restored collateral arterial blood supply without clinical relevance to complete liver de-arterialization with consecutive hepatic or biliary necrosis[4]. Isolated injury to large branches of the hepatic artery is usually well tolerated due to preserved perfusion from collaterals, most importantly the peribiliary vascular plexus. However, in cases of concomitant injury to these collaterals, the de-arterialized liver can react with ischemic cholangiopathy which is characterized by BDI leading to cast formation, bile duct necrosis and strictures[13]. Ischemic cholangiopathy should be distinguished from a functional defect in bile formation during ischemia without structural bile duct changes due to impaired hepatocellular and cholangiocellular transport function which, in contrast to ischemic cholangiopathy, are theoretically reversible once perfusion is re-established[14,15]. While it is generally assumed that the blood supply of the bile ducts is exclusively arterial, some evidence suggests perfusion is to some degree additionally provided by portal venous branches or rather intrahepatic anastomosis of portal venous and arterial vessels[16,17]. This assumption is supported by the observation, that during liver transplantation, bleeding from the hepatic artery occurs after portal vein reperfusion[13]. Portal vein oxygen saturation seems not to be sufficient for proper physiologic function of the biliary system in complete de-arterialization. However, in desperate situations portal vein arterialization can provide adequate oxygen supply to maintain hepatobiliary viability[18,19].

In this case, the general frailty of the patient influenced the decision against right hepatic resection, which would have been an even more physiologically challenging procedure compared to hepaticojejunostomy. Also, since the left liver remnant proved to be functionally sufficient and there were no signs of relevant right hepatic necrosis as assessed biochemically and by imaging studies, there was no compelling indication for resection. For the same reasons, and in view of the timeframe since primary injury, arterial reconstruction was unreasonable. Although the patient passed away due to septic multiorgan failure secondary to postoperative pneumonia, there were no signs of complications related directly to the surgical site.

While the color of bile is primarily caused by excreted bile pigments, most importantly conjugated bilirubin created during hemoglobin metabolism[20], discoloration can result from various causes. Although recent reports are scarce, an older investigation examined the impact of different physiological and pathological influences on the amount and quality of excreted bile in dogs with surgically created biliary fistula. Darker, thus presumably more concentrated, bile was produced after various stressful incidents like heat, infections, operations and starvation[21]. The influence of ischemia on bile composition is complex. Although human investigations are scarce, it has been shown that there are alterations to the biliary metabolome after hepatic ischemia in a porcine liver model[22]. Further, certain bile acid compositions are associated with hepatic injury during ex-vivo liver perfusion after warm ischemia[23]. Changes in bile color during ischemia can be attributed to alterations in bilirubin concentrations. Experimental data shows that bilirubin concentration increases in both bile and serum after ischemia and consecutive reperfusion[24]. Furthermore, it is known that hepatic ischemia causes decreased bile flow that is restored after reperfusion[25,26], suggesting formation of a more concentrated yet less effective bile in terms of bilirubin excretion. Notably, changes in bile color can also be observed after kidney ischemia suggesting functional alterations of bile production induced by distant circulating factors like cytokines, chemokines, damage-associated molecular patterns and reactive oxygen species from another organ[27]. This questions whether the observed alterations in bile composition and discoloration after hepatic ischemia truly are primarily caused by lack of oxygen or an ischemia-induced inflammatory response causes down-regulation of associated enzymes and transporters[15].

This case illustrates the complex pathophysiologic consequences of iatrogenic partial liver de-arterialization. Separate percutaneous biliary drainage enabled direct observation of alterations in bile color, correlating with regions of severe ischemia, transitional ischemia, and preserved arterial perfusion, as demonstrated by intraoperative findings and imaging. However, the underlying mechanism of these color changes, whether caused by purely functional impairment of bile secretion or early structural BDI, cannot be definitively determined in this case. Some research proposes ischemia-induced formation of “toxic bile” involved in later structural bile duct damage, suggesting a continuous progression from functional to structural injury[28,29]. Unfortunately, due to rapid clinical deterioration of the patient, biochemical analysis of the bile composition was unfeasible. Further insights into the pathogenesis of cholestasis during hepatic ischemia might to lead novel therapeutic strategies to prevent non-reversible structural bile duct injuries[15].

CONCLUSION

Concomitant Strasberg E4 BDI and RHA injury present a devastating surgical complication after laparoscopic cholecystectomy. In this case, hepaticojejunostomy was feasible and anastomotic splinting with three separate Neuhaus drains was performed. The color of the excreted bile from areas with different degrees of ischemia (the “biliary sunrise”) reflected the extent of hepatobiliary functional impairment. Although early recognition and an individualized approach might allow successful surgical repair, the prognosis remains serious in patients with severe comorbidities.