Compliance with enhanced recovery after surgery predicts long-term outcome after hepatectomy for cholangiocarcinoma

Table 1 Hepatic resection enhanced recovery program after surgery pathway

ERAS item	Goals
Preoperative counseling	Patients receive dedicated education, full care pathway, details of operation and associated complication, and estimated length of hospital stay with clear verbal and wriinstruction
Preoperative fasting and preoperative carbohydrates load	Preoperative fasting 6 h for solids and 2 h for liquids. Carbohydrate loading evening before the day of surgery and 2 h before induction of anesthesia
Pre-anesthetic anxiolytic	Short-acting anxiolytics prior to the induction of anesthesia
VTE prophylaxis	Low-molecular weight heparin or unfragmented heparin administration 2-12 h before surgery
Antimicrobial prophylaxis and skin preparation	Single dose intravenous antibiotics administration before skin incision and less than 1 h before hepatectomy
Prophylactic nasogastric intubation	No use of prophylactic nasogastric intubation
Preventing intraoperative hypothermia	Maintenance of perioperative normothermia using forced air blankets and controlling temperature of the operating room
Fluid management (CVP monitoring)	The maintenance of low CVP (below 5 cm H2O) with close monitoring during liver transection phase
Prophylactic abdominal drainage	None or minimize the use of prophylactic abdominal drainage
Early mobilization	Begin to walk around the ward at least 3 times a day
Postoperative glycemic control	Insulin therapy to maintain normoglycemia before full oral intake
Preventing PONV	Patients should receive PONV prophylaxis with 2 anti-emetic drugs until POD3
Multimodal analgesia	Multimodal analgesia combined with wound infusion analgesia or intrathecal opiates. Removal of epidural analgesia before POD3
Initial oral analgesic drug at POD1	Initial oral analgesic drug at POD1
Early NG tube removal at POD1	Removal of NG tube at POD1 unless there was > 400 mL/d drainage
Postoperative nutrition and early oral intake	Patients can eat soft diet at POD2
Removal of urinary catheter POD2	Removal of urinary catheter POD2

VTE: Venous thromboembolism; POD: Postoperative day; ERAS: Enhanced recovery program after surgery; PONV: Postoperative nausea and vomiting; NG: Nasogastric; CVP: Central venous pressure.

Table 2 Characteristics of the patients according to enhanced recovery program after surgery compliance

Variable	n (%) or mean (SD)				P value1
	ERAS < 50 (n = 102)		ERAS ≥ 50 (n = 14)
Age	62.1	7.9	61.8	11.0	0.905
Gender (male)	67	65.7	5.0	35.7	0.031
Location					0.027
Intrahepatic	40	39.2	12.0	85.7
Bismuth I	0	0.0	0.0	0.0
Bismuth II	2	2.0	0.0	0.0
Bismuth IIIA	38	37.3	1.0	7.1
Bismuth IIIB	17	16.7	1.0	7.1
Bismuth IV	5	4.9	0.0	0.0
Type of CCA					0.442
MF	10	9.8	2.0	14.3
PI/FN	31	30.4	2.0	14.3
IG/PP	61	59.8	10.0	71.4
Procedure					0.285
Right hepatectomy	38	37.3	9.0	64.3
Extended right hepatectomy	18	17.7	0.0	0.0
Right trisectionectomy	12	11.8	0.0	0.0
Left hepatectomy	25	24.5	4.0	28.6
Extended left hepatectomy	3	2.9	0.0	0.0
Left trisectionectomy	2	2.0	0.0	0.0
Other	4	3.9	1.0	7.1
Vascular resection	7	6.9	1.0	7.1	0.969
Vascular inflow occlusion	39	38.2	7.0	50.0	0.399
EBL (mL)	647.1	490.5	446.4	273.5	0.138
Preoperative laboratory investigation
TB	2.1	2.6	0.8	0.7	0.070
AST	365.9	359.0	215.8	122.7	0.139
ALT	253.6	250.6	166.0	96.0	0.216
ALP	141.3	106.0	84.8	39.4	0.060
Alb	2.8	0.7	3.0	0.6	0.257
Cholesterol	133.7	39.7	156.9	29.7	0.045

¹P < 0.05 by chi squared or t-test where appropriate.

MF: Mass-forming; PI: Periductal infiltrating; FN: Flat-nodular; IG: Intraductal growth; PP: Papillary polypoid; ERAS: Enhanced recovery program after surgery; CCA: Cholangiocarcinoma; EBL: Estimated blood loss; TB: Total bilirubin; AST: Aspartate aminotransferase; ALT: Alanine transaminase; ALP: Alkaline phosphatase; Alb: Albumin.

Table 3 Postoperative outcomes

Variable	n (%) or mean (95%CI)				P value1
	ERAS < 50 (n = 102)		ERAS ≥ 50 (n = 14)
Overall morbidity	51	50.0%	4	28.6%	0.132
Hepatobiliary complications					0.281
Post-hepatectomy liver failure	14	13.7%	0	0%
Bile leakage	4	3.9%	0	0%
Stricture/cholangitis	1	0.9%	0	0%
Transient hyperbilirubinemia	9	8.8%	0	0%
General complications
Wound complications	18	18.8%	0	0%	0.076
Pulmonary complications	9	8.8%	2	14.3%	0.513
Cardiac complication	5	4.9%	0	0%	0.397
Acute kidney injury	2	1.9%	0	0	0.597
Post-operative stay (d)	13.7	12.2-15.2	8.9	7.3-10.4	0.022
Cholesterol
Postoperative day 1	131.5	123.9-138.9	151.1	141.2-160.9	0.057
Postoperative day 3	107.3	101.5-113.1	127.7	116.7-138.7	0.013
Postoperative day 5	96.6	90.8-102.5	118.1	109.1-127.2	0.009
Serum albumin
Postoperative day 1	3.0	2.9-3.1	3.1	2.9-3.3	0.271
Postoperative day 3	2.9	2.8-2.9	3.0	2.9-3.2	0.224
Postoperative day 5	2.8	2.7-2.9	2.9	2.8-3.1	0.425
Total bilirubin
Postoperative day 1	3.2	2.4-3.9	1.6	1.1-2.2	0.142
Postoperative day 3	2.7	2.1-3.4	1.4	0.9-2.0	0.171
Postoperative day 5	2.8	2.0-3.5	1.3	0.9-1.6	0.157
Alanine aminotransferase
Postoperative day 1	294.9	242.6-347.2	231.1	166.9-295.3	0.376
Postoperative day 3	169.4	142.6-196.3	177.6	124.1-231.1	0.829
Postoperative day 5	89.7	74.5-104.9	97.1	72.5-121.8	0.726
Aspartate aminotransferase
Postoperative day 1	386.5	323.4-449.7	285.2	196.4-373.9	0.247
Postoperative day 3	169.4	142.6-196.3	177.6	124.1-231.1	0.829
Postoperative day 5	89.7	74.5-104.9	97.1	72.5-121.8	0.726
International normalized ratio (PT/INR)
Postoperative day 1	1.27	1.2-1.35	1.27	1.18-1.35	0.939
Postoperative day 3	1.42	1.37-1.47	1.34	1.24-1.45	0.293
Postoperative day 5	1.39	1.3-1.49	1.26	1.17 -1.35	0.295
Postoperative mortality
30 d	0	0%	0	0%
60 d	3	2.9%	0	0%
Survival (95%CI)					0.019
Median (d)	1257	853.2-1660.8	Not reached
1-yr survival	77.5%	63.1-89.1	100%
3-yr survival	50.9%	37.1-67.9	85.7	53.9-96.2

¹P < 0.05 by chi squared or t-test where appropriate.

ERAS: Enhanced recovery program after surgery; CI: Confidence interval; PT: Prothrombin time; INR: International normalized ratio.