Comparison of safety, efficacy, and long-term follow-up between “one-step” and “step-up” approaches for infected pancreatic necrosis

Table 1 The definitions of primary endpoints and secondary endpoints

Endpoints	Definition
Primary endpoints
Composite endpoint consisting of mortality and severe complications (Clavien-Dindo ≥ IIIa)	There are five grades of Clavien-Dindo Classification: Grade I, any complication that deviates from the natural course after surgery; Grade II, medications other than those permitted for Grade I complications are required; Grade III, surgical, endoscopic, and radiotherapy are required, including Grade IIIa (no general anesthesia is required) and IIIb (need for general anesthesia); Grade IV, life-threatening complication, including Grade IVa (single organ dysfunction) and IVb (multi-organ dysfunction) that require intermittent monitoring or ICU treatment; Grade V, death
Secondary endpoints
New-onset organ failure	New-onset failure of one or more organs in the 24 h prior to the first intervention
Pulmonary failure	Partial pressure of oxygen (PO2) < 60 mmHg with or without partial pressure of carbon dioxide (PCO2) > 50 mmHg, or need for mechanical ventilation
Circulatory failure	Blood pressure < 90/60 mmHg, or need for inotropic catecholamine to maintain blood pressure
Renal failure	The level of creatinine (Cr) > 177 μmoL/L, or need for hemofiltration or hemodialysis
Postoperative intra-abdominal bleeding	Need for operation, radiological, or endoscopic intervention
Pancreatic fistula	Drainage fluid amylase level more than 3 times that of serum amylase
Enterocutaneous fistula	Intestinal contents, including intestinal fluids, food residues, and feces, break through the intestinal wall (small bowel or large bowel) and leak into the abdominal cavity or outside the body. It can also be confirmed by radiology or surgery
Viscera perforation	Need for operation, radiological, or endoscopic intervention
Endocrine insufficiency	Oral hypoglycemic drugs or insulin therapy for at least 6 mo, with no need to take these drugs before the onset of AP
Pancreatic enzyme	Clinical symptoms were improved by oral pancreatic enzyme use for more than 6 mo, with no need to take this drug before the onset of AP
Recurrent pancreatitis	A history of two or more episodes with and interval of at least 3 mo
Chronic pancreatitis	Patients experience abdominal pain, weight loss, diabetes, and fatty diarrhea. The condition is also confirmed by radiological and laboratory examinations. The symptoms did not occur before the onset of AP
Incisional hernia	Six months after discharge, the full-thickness abdominal wall is discontinuous and abdominal contents bulge, with or without obstruction
Pancreatic portal hypertension	AP causes splenic vein thrombosis, which causes obstruction of splenic venous return

AP: Acute pancreatitis; ICU: Intensive care unit.

Table 2 Baseline characteristics of infectious necrotizing pancreatitis patients who underwent necrosectomy

Groups	“One-step” approach (n = 61)	“Step-up” approach (n = 97)		P value
Baseline characteristics
Sex			0.61
Female	19	34
Male	42	63
Age (yr)	52.16 ± 11.51	50.57 ± 13.71	0.45
BMI (kg/m2)	26.20 ± 3.78	25.91 ± 3.91	0.73
Cause of AP			0.36
Gallstone	31	48
Alcohol	3	2
Hyperlipidaemia	15	34
Others	12	13
Concomitant disease			0.15
Cardiovascular disease	29	37
Pulmonary disease	8	13
Chronic renal insufficiency	4	21
Diabetes	13	16
Others	7	10
ASA score			0.42
I: Healthy status	30	58
II: Mild systemic status	30	38
III: Severe systemic status	1	1
APACHE-II score	13.9 ± 5.1	14.2 ± 5.4	0.71
CT severity index	6.65 ± 2.55	7.19 ± 2.18	0.18
Severity of AP			0.79
Moderately AP	27	45
Severely AP	34	52
Extent of pancreatic necrosis			0.07
< 30%	35	41
30%-50%	11	33
> 50%	15	23
Preoperative inflammatory indicators
White blood cells (109/L)	11.04 ± 6.31	11.33 ± 6.03	0.77
Neutrophil percentage (%)	80.86 ± 8.3	79.57 ± 8.9	0.36
C-reactive protein (mg/L)	115.3 ± 81.8	118.5 ± 85.7	0.81
Procalcitonin (ng/mL)	1.18 ± 1.0	1.08 ± 2.2	0.73
Interleukin 6 (pg/mL)	113 ± 91.8	116 ± 95.1	0.93
Organ failure			0.49
Single	10	14
Multiple	5	14
None	46	69
Time from onset of disease to admission (days)	32.20 ± 20.75	53.69 ± 38.14	< 0.001
Time from onset of disease to initial surgical treatment (days)	54.38 ± 10.46	76.58 ± 17.03	< 0.001
Tertiary referral (%)	56 (91.8%)	96 (98.9%)	0.06

CT: Computed tomography; AP: Acute pancreatitis; BMI: Body mass index.

Table 3 Comparison of perioperative clinical outcomes between the “One-step” approach and the “Step-up” approach

Group	“One-step” approach (n = 61)	“Step-up” approach (n = 97)		P value
Outcomes
Primary composite outcomes
Severe complications or death, n (%)1	11 (18)	20 (20.6)		0.69
Secondary outcomes
New-onset organ failure	10	18		0.73
Pulmonary	6	12
Cardiovascular	8	10
Renal	1	3
Single-organ failure	5	12		0.41
Multiple-organ failure	5	6		0.63
Death	8	12		0.89
Postoperative intraabdominal bleeding	2	5		0.58
Pancreatic fistula	16	28		0.72
Enterocutaneous fistula or Viscera perforation	3	5		0.95
Surgical approach				0.77
Trans-lesser sac	40	39
Retroperitoneal	17	20
Combined	4	6
Length of stay in ICU after operation (days)	10.9 ± 22.7	14.4 ± 26.1		0.18
Total length of ICU stay (days)	22.5 ± 30.1	25.7 ± 28.7		0.43
Total length of hospital stay (days)	52.76 ± 24.71	65.41 ± 28.14		0.02
Number of operations	2.89 ± 1.23	3.42 ± 1.69		0.65
Operation time (min)	82.19 ± 29.34	87.01 ± 30.12		0.92
Number of interventions	3.18 ± 1.39	4.26 ± 1.71		0.000
Blood loss during the operation (mL)	49.5 ± 58.3	55.5 ± 72.1		0.51
Number of drainage tubes	3.9 ± 1.0	4.43 ± 1.77		0.04

¹Severe complications defined as postoperative complications classified as higher than Grade IIIa according to the Clavien-Dindo Classification.

ICU: Intensive care unit.

Table 4 The changes of inflammatory indicators and vital signs between two surgical approaches during the perioperative period

Groups	“One-step” approach (n = 61)	“Step-up” approach (n = 97)	P value
Indicators
Preoperative inflammatory indicators
White blood cells (109/L)	11.04 ± 6.31	11.33 ± 6.03	0.77
Neutrophil percentage (%)	80.86 ± 8.3	79.57 ± 8.9	0.36
C-reactive protein (mg/L)	115.3 ± 81.8	118.5 ± 85.7	0.81
Procalcitonin (ng/mL)	1.18 ± 1.0	1.08 ± 2.2	0.73
Interleukin-6 (pg/mL)	113 ± 91.8	116 ± 95.1	0.93
Preoperative vital signs
Body temperature (℃)	38.5 ± 0.6	38.0 ± 0.8	0.94
Respiratory frequency (times/min)	25.8 ± 4.8	23.1 ± 4.9	0.67
Heart rate (times/min)	116.1 ± 14.2	107 ± 15.1	0.33
Inflammatory indicators on the 3rd postoperative day
White blood cells (109/L)	9.91 ± 4.5	10.1 ± 4.4	0.54
Neutrophil percentage (%)	78.9 ± 6.8	78.1 ± 7.2	0.97
C-reactive protein (mg/L)	91.6 ± 40.6	91.1 ± 53.3	0.92
Procalcitonin (ng/mL)	0.84 ± 0.6	0.79 ± 0.5	0.71
Interleukin-6 (pg/mL)	91.2 ± 60.2	94.7 ± 68.4	0.31
Vital signs on the 3rd postoperative day
Body temperature (℃)	38.1 ± 0.4	37.8 ± 0.7	0.49
Respiratory frequency (times/min)	23.8 ± 6.1	22.7 ± 4.3	0.86
Heart rate (times/min)	105.1 ± 21.9	100 ± 24.9	0.68
Inflammatory indicators on the 7th postoperative day
White blood cells (109/L)	7.51 ± 3.0	7.48 ± 2.4	0.96
Neutrophil percentage (%)	69.30 ± 6.1	65.14 ± 7.8	0.43
C-reactive protein (mg/L)	62.63 ± 25.6	68.05 ± 38.1	0.54
Procalcitonin (ng/mL)	0.37 ± 0.3	0.31 ± 0.2	0.94
Interleukin-6 (pg/mL)	46.3 ± 22.6	49.7 ± 27.4	0.48
Vital signs on the 7th postoperative day
Body temperature (℃)	37.0 ± 0.6	37.3 ± 0.4	0.95
Respiratory frequency (times/min)	19.4 ± 2.3	19.1 ± 2.8	0.83
Heart rate (times/min)	90.1 ± 13.7	85.2 ± 14.1	0.61

Table 5 The long-term complication between the two surgical approaches during the follow-up period

Groups	“One-step” approach (n = 40)	“Step-up” approach (n = 63)	P value
Long-term complications
New-onset endocrine insufficiency, n (%)
Number of patients	12 (30)	28 (45)	0.143
Oral medication	9 (75)	20 (71.4)
Insulin	5 (41.7)	13 (46.4)
Exocrine insufficiency, n (%)
Fecal elastase-1, mean value	254.1 ± 107.8	257.9 ± 93.3	0.85
Fecal elastase-1 < 200 μg/g, n (%)	14 (35)	21 (33.3)	0.86
Pancreatic enzyme, n (%)	8 (20)	11 (20.8)	0.93
Recurrent pancreatitis, n (%)	7(17.5)	13(20.6)	0.69
Chronic pancreatitis, n (%)	4 (10)	7 (11.1)	0.86
Incisional hernia, n (%)	9 (20.5)	4 (6.3)	0.03
Clinical symptoms, n (%)
Diarrhea	16 (40)	23 (36.5)	0.72
Bloating	21(52.5)	28(44.4)	0.43
Abdominal pain	10 (25)	13 (20.6)	0.60
Weight loss	31 (77.5)	47 (74.6)	0.74
Pancreatic pseudocyst, n (%)	2 (5)	5 (7.9)	0.56
Pancreatic portal hypertension, n (%)	2 (5)	3 (4.8)	0.96
Pancreatic cancer, n (%)	0	0	-

Table 6 Quality of life rating scale during the follow-up period every 6 mo after treatment of surviving acute pancreatitis patients with the “One-step” approach or “Step-up” approach

Groups	“One-step” approach (n = 40)	“Step-up” approach (n = 63)	P value
Rating scale
SF-36 physical health score1	40 ± 9	41 ± 7	0.61
SF-36 mental health score1	47 ± 13	49 ± 13	0.58
EQ-5D health status score2	75 ± 20	76 ± 18	0.76
Izbicki pain score3	23 ± 26	21 ± 24	0.87

¹SF-36, Short Form-36. The SF-36 physical and mental health scores range from 0 to 100. The higher the score, the better the quality of life.

²EQ-5D, EuroQol 5 dimensions. The scores also range from 0 to 100, and the higher the score, the better the health.

³The higher the Izbicki pain score, the more severe the discomfort. The Izbicki pain score scale includes four parts (ranging from 0 to 100 per part), the sum of the values of the four parts are divided by 4.

Table 7 The comparison of perioperative medical costs between two surgical approaches

Groups	“One-step” approach (n = 61)	“Step-up” approach (n = 97)	P value
Medical costs
Surgical costs1 (RMB)	18582.37 ± 5918.45	29641.63 ± 6795.11	< 0.001
ICU costs (RMB)	276812.39 ± 183417.12	281133.73 ± 193252.47	0.87
Perioperative medical total costs (RMB)2	529958.23 ± 171128.74	569768.07 ± 193184.68	0.34
Follow-up costs per year
Outpatient costs (RMB)	2040.79 ± 519.48	2169.08 ± 463.71	0.71
Auxiliary examination costs3 (RMB)	9751.96 ± 1012.37	9003.65 ± 1102.29	0.58
Drug costs4 (RMB)	2855.36 ± 318.12	2994.21 ± 372.95	0.82

¹Surgical costs include percutaneous drainage, necrosectomy, or disease-related drainage tube replacement.

²Perioperative medical total costs include surgical costs, intensive care unit costs, general ward costs, and auxiliary examination costs.

³Auxiliary examination costs include laboratory examination, microbiological examination, radiological examination, and endoscopic examination (except drainage).

⁴Drug costs include oral medicine or insulin for treating.

ICU: Intensive care unit.