1. Demographic and baseline before surgery
Details of the demographics and baseline before surgery are summarized in Table 1. There was no difference between LsRRH and LtRRH groups in gender, BWI, total and direct bilirubin, and preoperative biliary drainage manner. However, the mean age of patients in the LsRRH group was significantly younger than the LtRRH group (P<0.05), suggesting that patients with better condition and tolerance for pneumoperitoneum and prolonged anesthesia were selected for laparoscopic surgery. All patients with T-Bil >100μmol/L underwent PTBD except 6 patients who underwent ENBD in referral hospitals. Eight cases with T-Bil <100μmol/L in both groups did not undergo biliary drainage. A total of 5 patients in both groups did not experience bile reinfusion due to the resistance of the jejunal nutrient tube implement. No difference in mean biliary drainage time and ICG15% between the two groups were observed.
2. Preoperative assessment of tumor
Details of the preoperative assessment of the tumor are summarized in Table 2. Imaging-based assessment of tumor was emphasized on Bismuth classification, TNM stage, and vascular involvement to predetermine whether radical resection can be achieved. As shown in table 2, the proportion of Bismuth type Ⅰ in the LsRRH group was higher than in the LtRRH group. Type Ⅱ and Ⅲb were relatively comparable, while type Ⅲa and Ⅳ were less in the LsRRH group (p<0.05). In the LsRRH group, no patients had HA invasion, and 5 patients had PV involvement but not exceeding 180° of the vessel circumference. In the LtRRH group, 6 patients had HA invasion, and 13 had PV involvement. Among these 13 patients, 4 had an involvement exceeding 180° with required PV resection and reconstruction. Regarding the proportion of vascular invasion, HA and PV involvement in the LsRRH group was lower than in the LtRRH group (p<0.05), indicating that patients with a lower level of technique requirement were enrolled selectively for LsRRH.
3. Surgery strategy and intraoperative data
The surgery strategy for various Bismuth types of HCCA in our institution obeys the following principles. Bismuth type Ⅰ undergoes extrahepatic bile duct resection (EBDR). Bismuth type Ⅱ and Ⅲb undergo left hepatectomy (LHx) with total caudate lobectomy (TCL). Bismuth type Ⅲa undergoes right hepatectomy (RHx) with TCL. Bismuth type Ⅳ undergoes typical or extended LHx/RHx decided by the extent of tumor invasion to the left and right hepatic duct, residual liver volume, and ICG15%. In two patients with FLR, less than 40% received lobus quadratus resection (segment Ⅳb+Ⅴ) and TCL. Because of the high proportion of Bismuth type Ⅰ, the ratio of EBDR alone in the LsRRH group was higher than in the LtRRH group (p<0.05). And the proportion of type IIIa and type IV was lower in the LsRRH group, so the typical and extended RHx were less than in the LtRRH group (p<0.05). All cases were combined with hilar clearance of lymph nodes, adipose, and nerve tissue containing No.12, 13, 8, and 9 lymph nodes. Wedge resection and repair were performed for preserved PV invasion but not exceeding 180°; resection and end-to-end reconstruction were carried out for those exceeding 180°. One patient in the LsRRH group scheduled for wedge resection preoperatively was transferred to segmental resection and end-to-end anastomosis when involvement exceeded 180° intraoperatively. Intraoperative frozen sections of the proximal and distal residuals of the bile duct and vessel were made to guarantee negative margins. The TCL was routinely performed in Bismuth type Ⅱ, Ⅲ, and type IV patients. After excluding Bismuth type Ⅰ cases, the TCL ratio in the LsRRH group was higher than in the LtRRH group (p<0.05). The mean operation time was longer for LsRRH than LtRRH (p<0.05). The LsRRH group had less blood loss, fewer transfusion cases, and less transfusion volume (p<0.05). The details of surgery strategy and intraoperative data are summarized in Table 3.
4. Biliary-enteric reconstruction (BER)
The biliary residuals in the hepatic segment of the couinaud was the standard for counting. Depending on different surgery strategies, the residuals range from 1 to 6, with the most residuals presented in lobus quadratus resection. The average number of the residuals in the LsRRH and LtRRH groups was 2.54±1.62 and 2.47±1.46, respectively (p>0.05).
Cholangioplasty was performed to enlarge the diameter of the residuals to facilitate anastomosis and lessen the number of anastomoses. Distant biliary residuals out of plastic were subjected to choledochojejunostomy separately, and a scattered lobular duct on the liver section with a diameter less than 1mm was ligated directly. The choledochojejunostomy ranges from 1 to 4, with a mean of 2.04±1.27 and 2.57±1.33 in the LsRRH and LtRRH groups, respectively (p>0.05).
Retro-colic Roux-en-Y choledochojejunostomy is preferred for BER. For intrahepatic bile duct residuals diameters of 5 mm to 8 mm and below, end-to-end anastomoses were established with 5-0 absorbable monofilament sutures. And 4-0 was used for those with diameters above 8 mm. In complex cases with multiple residuals, small inner diameters, and thin duct walls that can neither be plastic nor anastomosed separately, a porto-jejunal anastomosis (also named as Kasai procedure[24] was used, which sutured the posterior intestinal wall to a duct or surrounding tissue of Glisson sheath and the anterior intestinal to hilar tissue. Alternatively, hepato-jejunostomy[25] intermittently sutured the anterior intestinal wall to liver tissue with a pouch needle.
As for the suture method, a continuous suture is suited for a long residuals with sufficient duct tissue, while an intermittent suture is done for a short residuals with scarce tissue. The discontinuous and continuous suture was performed randomly or in combination for anterior and posterior anastomosis walls depending on duct length and tissue volume. The average time of BER in the LsRRH and LtRRH groups was 65.67±21.53 min and 42.5±19.77 min, respectively (p<0.05), which accounted for 15.28±3.64% and 11.76±2.54% of the total operation time in each group (p<0.05). These illustrated that the time consumption ratio is significantly higher in the LsRRH group. The details of BER data are summarized in Table 4.
5. Complications related to BER
The details of complications related to BER are summarized in Table 5. Postoperative complications were totalized according to the definition and grade of bile leakage by the International Study Group of Liver Surgery (2011)[26]. There were 15 cases of postoperative bile leakage in the two groups. 6 (15.40%) were from the LsRRH group, including 4 grade A, 2 grade B, and 0 grade C. 9 (16.67%) were in the LtRRH group, including 5 grade A, 4 grade B, and also 0 grade C. All cases in grade A were cured by unblocking abdominal drainage and without additional treatment. Of the 6 grade B, 2 patients with limited perihepatic biliary effusion were from the LsRRH group, 3 patients with restricted perihepatic biliary flow, and 1 with diffuse cholestatic peritonitis was from the LtRRH group. They were cured by B-ultrasound or CT-guided percutaneous catheter drainage. No patient with bile leakage received second surgery. Statistical analysis showed no difference in the two groups incidence and grade of bile leakage (p>0.05).
The criterion for healing bile leakage is no abdominal fluid collection, and a drainage tube can be removed. Those who cannot remove the drainage tube with continuous bile drainage should be kept for 2~3 months until the sinus tract forms firmly and clamped the tube for seven days. Then the drainage tube can be removed after the patient has no effusion identified by CT and no abdominal pain or fever. The average healing time in LsRRH and LtRRH groups was 14±10.28d and 17±9.73d, respectively (p<0.05). The prolonged healing time was due to 1 case in the LsRRH group and 2 cases in the LtRRH group whose bile leakage was delayed and discharged with a draining tube. After excluding these three cases, the average healing time was 8±4.61d and 7±2.35d (p>0.05).
There was 1 case of biliary-enteric anastomotic stenosis in each group of LsRRH and LtRRH. The case in the LsRRH group was a Bismuth type Ⅲb who underwent LHx and TCL with two anastomoses of the right anterior and right posterior hepatic duct to the jejunum. On the 51st postoperative day, this patient presented fever with delayed jaundice, and MRCP confirmed right anterior anastomotic stenosis with stone formation. The stenosis and cholelithiasis were resolved by balloon expansion three times with percutaneous transhepatic choledochoscopy (PTCS). The case in the LtRRH group was Bismuth type IV HCCA who underwent LHx and dorsal segment of right anterior lobe and TCL with 3 anastomoses made of S5, S8, right posterior hepatic duct to the jejunum. This patient also presented fever with delayed jaundice on the 72nd postoperative day, and MRCP confirmed stenosis at S5 hepatic duct jejunostomy with stone formation. This patient was also resolved by balloon expansion twice through PTCS. There was no difference in the choice of anastomosis (cholangitis-/porto-/hepato-jejunostomy) between the LsRRH and LtRRH groups (Table 4) or in the anastomosis in which stenosis occurred.
No biliary hemorrhage occurred in either group. One patient in the LsRRH group died of hepatic failure within 72 hours after surgery. Another patient in the LtRRH group died on the 17th day after being discharged due to violent vomiting resulting in hemorrhage of the cardia mucosa tear. Therefore, no patient died from complications related to BER.