Total three-dimensional laparoscopic radical resection for Bismuth type IV hilar cholangiocarcinoma

Yang-Sui Liu,Dun-Feng Qi,Jun Zhang,Huan-Song Li,Xin-Cun Jiang,Long Cui

Department of Hepatobiliary Surgery, Xuzhou Central Hospital, Xuzhou 221009, China

Hilar cholangiocarcinoma (HCCA) (also known as Klatskin tumor) has a poor prognosis worldwide,and accounts for more than half of cholangiocarcinoma cases. HCCA originates from epithelium and often arises from the confluence of the bile ducts or the right or left hepatic ducts [ 1,2 ]. Because of its aggressiveness and refractory biological characteristics,the median survival time of patients with unresectable HCCA is less than 1 year. Radical resection is the most effective treatment for HCCA. Surgery for Bismuth type IV HCCA requires radical lymphadenectomy,corresponding hemihepatectomy combined with caudate lobectomy,resection of extrahepatic bile duct,and hepaticojejunostomy for biliary reconstruction to achieve long-term patient survival [ 3,4 ]. Due to the diffi-cult surgical procedure and specific malignant biological behaviors of HCCA,laparoscopic radical resection of HCCA has been implemented only in specific and highly selective cases [5–8] . However,surgeons work in a three-dimensional (3D) space under the guidance of traditional two-dimensional (2D) laparoscopy,which lacks true depth perception and spatial orientation,potentially increasing the risk of surgical complications and the duration of surgery.The development of 3D high-definition laparoscopy for surgical application offers surgeons a better and clearer depth of surgical field and improves hand-eye coordination. Some studies have reported that 3D laparoscopy can effectively reduce performance errors,operative time,and intraoperative and postoperative complications and shorten the time required for surgical novices to learn new surgical procedures compared with 2D laparoscopy [9–11] . We recently first implemented 3D laparoscopy radical resection for Bismuth type IV HCCA for selected patients into our daily routine,and the results were encouraging. In this report,we documented the use of 3D high-definition laparoscopy in radical Bismuth type IV HCCA surgery in a patient and assessed the patient’s recovery over a 3-month follow-up period.

The patient was a 54-year-old woman who experienced yellowing skin and sclera for 7 days and was admitted to the Department of Hepatobiliary Surgery of our hospital. The patient had a body mass index (BMI) of 25.39 kg/m2. Clinical examination revealed mild upper abdominal tenderness and no other abdominal abnormalities. Routine blood examination and coagulation function were within normal ranges. Hepatic function examination and tumor marker analyses showed the following results:alanine aminotransferase (ALT): 352.0 U/L; aspartate aminotransferase (AST): 236.0 U/L; total bilirubin (TBIL): 302.9μmol/L; direct bilirubin (DBIL): 231.1μmol/L; alkaline phosphatase (ALP): 365.0 U/L;γ-glutamate aminotransferase (γ-GT): 1695.0 U/L; carbohydrate antigen 19-9 (CA19-9): 107.20 U/mL; carcinoembryonic antigen (CEA): 1.97 ng/mL; and alpha-fetoprotein (AFP): 3.10 ng/mL.Preoperative enhanced computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) scanning showed that intrahepatic cholangiectasis occupied space above the hilar biliary tree and invaded the left and right hepatic ducts ( Fig. 1 ). The patient was diagnosed with type IV HCCA based on the Bismuth-Corlette classification. It was necessary to specify that it was adenovoHCCA and not a cholangiocarcinoma in the setting of primary sclerosing cholangitis (PSC) because the patient did not have a history of PSC. Percutaneous transhepatic biliary drainage (PTBD) of the right anterior intrahepatic biliary duct was performed on the second day after admission ( Fig. 2 ). The patient was scheduled for total 3D laparoscopy resection at day 26 after PTCD,which was expected to achieve R0 resection. Analysis of preoperative liver function and tumor markers showed the following results: ALT: 83.0 U/L; AST: 52.0 U/L; ALP: 179.0 U/L;γ-GT: 287.0 U/L; TBIL: 43.7 mmol/L; DBIL: 34.7 mmol/L; CA19-9: 24.03 U/mL; and CEA: 1.3 U/mL. Positron emission tomography/computed tomography (PETCT) showed HCCA without intrahepatic or distant metastasis. Preoperative 3D image reconstruction of the liver parenchyma,intrahepatic and extrahepatic vessels,and dilated bile duct as well as a true reflection of the degree of infiltration of the tumor into adjacent organs were performed based on the 2D CT images using Beijing Jingzhen Technology software (Jingzhentech,Beijing,China)( Fig. 3 ),which can better assess the liver parenchyma resection range and the effective residual liver volume [12] . The future effective remaining left liver volume was 400 mL,accounting for 39% of the standard liver volume,which was enough considering an indocyanine green retention rate at 15 minutes (ICG-R15) of 5.6% [13] .This study was approved by the Ethics Committee of Xuzhou Central Hospital,and informed consent was obtained from the patient before surgery.

Fig. 1. CT ( A ) and MRCP ( B ) scanning showed the tumor (green arrow) and dilated bile duct (red arrow). CT: computed tomography; MRCP: magnetic resonance cholangiopancreatography.

Fig. 2. PTBD angiography scanning showed the tumor (green arrow) and dilated bile duct (red arrow). PTBD: percutaneous transhepatic biliary drainage.

Fig. 3. Reconstructed 3D images showed the tumor,intrahepatic and extrahepatic vessels,dilated bile duct,and adjacent organs. 3D: three-dimensional.

In this case,the surgical procedure was completed under total 3D laparoscopy. Briefly,after general anaesthesia,the patient was placed in a supine position with legs split and the ability to be tilted during the operation. A 10-mm camera port was placed in the left subumbilical region. Pneumoperitoneum was established and maintained between 11-14 mmHg. The remaining ports were placed as shown in Fig. 4 . First,the hepatoduodenal ligament and hepatic hilar tissue were isolated. This included identifying various histological structures in the hilar region,such as the common hepatic artery,the left and right hepatic arteries,the common and left hepatic ducts,the portal vein,and the right branch of the portal vein ( Fig. 5 ). Intraoperative frozen sections of the lymph nodes anterior to the common hepatic artery (Station 8)and the lymph nodes adjacent to the hepatoduodenal ligament(Station 12) showed no tumor invasion (N0). Retroduodenal lymph nodes (Station 13) were only intraoperatively explored without being resected in this case. After transection and ligature with the distal common bile duct,the right hepatic artery and the right branch of the portal vein,a right hemihepatectomy was performed using the middle hepatic ischemia line as a marker ( Fig. 6 A).As a standard procedure,laparoscopic Pringle ’ s manoeuvre was only performed when needed during liver parenchymal transection. An ultrasound scalpel (Ethicon Endo-Surgery,LLC,Guaynabo,PR,USA) was used to separate and enter through the liver and fatty parenchyma ( Fig. 6 B). Blood vessels below 2 mm were directly coagulated by the ultrasound scalpel,whereas blood vessels above 2 mm needed to be clamped or sutured if necessary to achieve hemostasis. Biliary structures were clipped or ligated before transection. After the left hepatic duct was transected,a frozen section was obtained from the hepatic duct of the sector,showing a tumor-free parenchymal resection margin. Similarly,the distal resection margin of the resected common bile duct was treated in the same way. To avoid local tumor implantation,the biliary structure of the resected specimens is usually ligated after transection.The caudate lobe was removed during resection of a Bismuth type IV HCCA for anatomic reasons. After mobilization of the caudate lobe,the right hepatic vein was transected using a laparoscopic vascular stapler (Ethicon Endo-Surgery,LLC). The resected specimen was placed in a plastic bag and removed through an extended incision of the upper abdomen trocar access. After transection of the proximal jejunum at 40 cm from the Treitz ligament,biliary reconstruction was performed with a Roux-en-Y retro colonic elevated jejunal segment. Hepaticojejunostomy was performed with 4-0 unidirectional barbed running sutures (Stratafix,Ethicon Endo-Surgery,LLC) ( Fig. 6 C). The gastrointestinal tract was anastomosed using a distal stapler (Ethicon Endo-Surgery,LLC) end-to-side jejunojejunostomy 40 cm from the site of the hepaticojejunostomy( Fig. 6 D). The surgery procedure was completed within 600 minutes. The total blood loss was no more than 400 mL,and no intraoperative or postoperative transfusion was needed. The patient was discharged at postoperative day 12,and there were no intraoperative or postoperative complications. Postoperative pathological examination of the surgical specimens ( Fig. 7 ) revealed the following results: moderately to poorly differentiated HCCA; an approximate tumor size of 1.5 cm × 2.0 cm,invading the left hepatic bile duct,the right anterior and posterior bile ducts,and the extra biliary fibrous adipose tissue; the presence of nerve infiltration; no tumor in the lymph nodes of Stations 8 and 12 (0/14); and no tumor in the gallbladder and liver. The patient was followed up for 3 months without any discomfort and planned to receive postoperative adjuvant chemotherapy after the final histopathologic grading of a G 2-3 adenocarcinoma,T3 N0 (0/14) M0,R0.

Fig. 4. Trocar placement in 3D laparoscopic radical resection for Bismuth type IV HCCA. HCCA: hilar cholangiocarcinoma; 3D: three-dimensional.

Fig. 5. After dissection of the hepatoduodenal ligament and hepatic hilar tissue,the proper hepatic artery (a),common hepatic artery (b),gastroduodenal artery (c),common bile duct (d),portal vein (e),right hepatic artery (f),right branch of the portal vein (g) and lymph nodes (h) were identified.

Fig. 6. A : The ischemic line (red arrow) can be used as a landmark structure for anatomic hepatectomy; B : right hemihepatectomy was performed; C : intraoperative view of the hepaticojejunostomy (green arrow); D : the flow of bile into the small bowel was restored by jejunojejunostomy (yellow arrow).

Fig. 7. A : Postoperative pathological examination of the surgical specimens showed moderately to poorly differentiated HCCA,an approximate tumor size of 1.5 × 2.0 cm,invading the left hepatic bile duct,the right anterior and posterior bile ducts and the extrabiliary fibrous adipose tissue; the presence of nerve infiltration; no tumor in the lymph nodes of Stations 8 and 12 (0/14); no tumor at the cutting edge of the left hepatic bile duct and common bile duct; and no tumor in the gallbladder and liver. B :Hematoxylin and eosin stain demonstrated moderately to poorly differentiated cholangiocarcinoma (H&E stain,original magnification × 40). HCCA: hilar cholangiocarcinoma.

Due to their atypical early clinical symptoms,most patients with HCCA are diagnosed with advanced disease,which is often accompanied by vascular involvement and intrahepatic or extrahepatic metastasis and cannot be treated by radical surgery [ 1,2 ].The preoperative assessment of HCCA is very important. The cornerstone of preoperative radiological evaluation is enhanced CT,which can accurately assess the local spread,vascular invasion,lymph node involvement,and metastasis of HCCA and predict the intrabiliary spread of tumor tissue in dilated bile ducts [14] . MRI coupled with MRCP also has ideal sensitivity and accuracy (92%and 76%,respectively) in identifying HCCA,and this approach has the advantage of better visualization of the bile duct tree [15] .PET-CT has a limited application in detecting tumor extension due to its low sensitivity,but it plays a significant role in the detection of metastatic lymph nodes,distant metastasis,and differential diagnosis,which might be necessary when making surgical decisions [16] . Endoscopic retrograde cholangiopancreatography(ERCP) and PTBD can directly provide anatomical information about the biliary tree,but invasive examination is accompanied by the risks of complications such as infection,bleeding,and biliary fistula. The roles of ERCP and PTBD have gradually evolved from radiological diagnostic tools to interventional procedures aimed at preoperative biliary drainage [17] . ERCP was recommended as the first choice for the preoperative drainage of biliary tract cancers by Japanese clinical practical guidelines [18] . In contrast,Wang et al. [19] recently compared the efficacy and safety of PTBD and ERCP in patients with resectable HCCA and showed that PTBD might be the preferred preoperative drainage method for HCCA because of its low incidence of pancreatitis and cholangitis. Thus far,how to define optimal methods remains controversial. The present study used PTBD as a preoperative drainage method and it significantly reduced the preoperative serum bilirubin levels. Additionally,there was no intraoperative or postoperative complications.

Laparoscopic radical resection of HCCA has been implemented in specific and highly selective cases around the world [5–8] and has achieved good short-term clinical results in some medical centers. The main problem associated with laparoscopic HCCA resection is the lack of direct palpation of the hilar structures,which makes it difficult to implement bilioenteric anastomosis,especially for patients with Bismuth type IV HCCA [20] . In the surgical treatment of Bismuth type IV HCCA,there are multiple biliary stumps after hemihepatectomy that are irregular and at different angles,which results in very difficult bilioenteric anastomosis. Combined with our laparoscopic surgery,laparotomy,and some literature reports [21],our experience is as follows: (1) the adjacent multiple biliary stumps are integrated into a bile duct as much as possible and then anastomosed with the jejunum. (2) If the distance between the multiple biliary stumps is great,it is difficult to perform orthopaedic operations,and anastomosis should be performed separately. (3) If there are multiple biliary stumps with small diameters,single-layer continuous sutures can be used to suture the posterior wall of the multiple biliary stumps and the sheath with the connective tissue of the Glisson pedicle between the bile stumps as the posterior layer of the anastomosis [22] . Additionally,we inserted a polyvinyl chloride tube into each bile duct stump as a stent insert. To prevent sutures from cutting into tissue,the suture lines should be tightened individually after the procedure. (4)The abdominal drainage tube is routinely placed behind the bilioenteric anastomosis and near the liver section. (5) In cases where the nature of the surgical margin or complete bilioenteric anastomosis cannot be determined under laparoscopy,laparotomy should be performed in time to achieve radical R0 resection. When the tumor cannot be radically resected,liver transplantation can provide a new therapeutic option for patients. Recently,Cambridge et al.summarized survival after liver transplantation for unresectable HCCA,and this summary included 428 patients from 20 studies that were eligible for analysis [23] . The pooled 1-,3-,and 5-year overall survival rates following orthotopic liver transplantation with neoadjuvant therapy were 82.8%,65.5%,and 65.1%,respectively. However,considering the limited donor resources and the acceptable long-term prognosis of patients with R0 radical resection,radical resection will remain the standard therapy for HCCA.

Patients with Bismuth type IV HCCA usually require radical lymphadenectomy,corresponding hemihepatectomy combined with caudate lobectomy,resection of extrahepatic bile duct and hepaticojejunostomy for biliary reconstruction to achieve longterm patient survival [1–4] . The complex anatomic features largely increase the difficulty of the surgery,and high postoperative morbidity and mortality remain a problem [4] . The latest laparoscopic 3D vision system is a dual-lens system that has two separate lenses and two cameras within a single laparoscope. Images are captured by each camera and then specially processed and displayed synchronously on the same monitor. This approach does not require larger ports but rather a 1.0-cm port similar to a 2D laparoscope [24] . 3D laparoscopy allows for a deeper field of view,more comprehensive tissue definition,and better anatomical precision than the 2D system [9–11] . For example,when used for hemihepatectomy,this 3D laparoscopy technology was shown to be better than traditional 2D laparoscopy in terms of higher accuracy,higher tissue clarity and deeper vision [25] . Similar results were reported for gastric cancer and colorectal cancer [ 10,11 ],and these results have shown that 3D laparoscopic surgery can improve the spatial location and depth of operation,increase accuracy,reduce mistakes,and save time,especially for complex laparoscopic surgery.In this report,we first demonstrated the use of 3D laparoscopy for the treatment of Bismuth type IV HCCA. During surgery operation,the 3D laparoscopy offered clearer anatomic structure views of the hepatic hilum tissue,increasing blood vessel protection,reducing the risk of wounds during operation,and decreasing the possibilities of the associated postoperative complications. The procedure was completed within 600 minutes,and no intraoperative or postoperative transfusion was necessary. There were no intraoperative or postoperative complications. These results suggest that 3D laparoscopy may gradually replace 2D techniques in HCCA surgery.

In summary,for patients with HCCA,3D laparoscopy provides a clearer depth of field for the surgeon,increases the accuracy of dissection,and improves the success rate of the operation. However,further large sample studies and longer follow-up are needed.

Acknowledgments

None.

CRediT authorship contribution statement

Yang-SuiLiu:Data curation,Formal analysis,Investigation,Methodology,Writing - original draft.Dun-FengQi:Investigation,Methodology,Project administration,Validation,Visualization.JunZhang:Formal analysis,Investigation,Methodology,Resources.Huan-SongLi:Investigation,Methodology,Resources.Xin-Cun Jiang:Investigation,Methodology,Resources.LongCui:Conceptualization,Funding acquisition,Project administration,Supervision,Writing - review & editing.

Funding

This study was supported by a grant from the Xuzhou Science and Technology Project (KC19192).

Ethical approval

This study was approved by the Ethics Committee of Xuzhou Central Hospital (No. 2022-01). Written informed consent was obtained from all participants.

Competing interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.