Clinical utility of a novel concentrated enteral formula in patients undergoing colorectal cancer surgery: A randomized controlled trial

Table 1 Ingredients per a 330 mL bottle of recovery K5

Component
Energy	400 kcal
Protein	20.0 g
Fat	10.7 g
Carbohydrates	60.4 g
Carbohydrate	52.4 g
Dietary fiber	8.0 g
Sodium equivalent	1.68 g
Sodium	660 mg
Potassium	540 mg
Calcium	280 mg
Magnesium	140 mg
Phosphorus	320 mg
Iron	3.2 mg
Zinc	4.8 mg
Copper	0.40 mg
Manganese	1.68 mg
Iodine	44 μg
Selenium	28 μg
Chromium	20.0 μg
Molybdenum	20 μg
Vitamin A	452 μg
Vitamin D	3.6 μg
Vitamin E	5.6 mg
Vitamin K	64 μg
Vitamin B1	0.88 mg
Vitamin B2	0.88 mg
Niacin	11.6 mg
Vitamin B6	0.80 mg
Vitamin B12	2.8 μg
Folic acid	152 μg
Pantothenic acid	4.40 mg
Biotin	29.2 μg
Vitamin C	80 mg
Water	264 g
Collagen peptide	4 g
Galactooligosaccharide	0.8 g
Chlorine	600 mg
Enterococcus faecalis (heat-sterilized bacteria)	240 billion pieces
L-carnitine	80 mg

Table 2 Clinical and pathological characteristics of the patients, n (%)

Parameter	Nutritional intervention group (n = 17)	Non-intervention group (n = 18)	P value
Gender, men/female	13/4 (76/24)	13/5 (72/28)	1.00001
Age, year, mean ± SD (median, range)	61.3 ± 7.3 (61, 44-73)	58.8 ± 11.4 (62, 34-73)	0.45662
BMI, kg/m2, mean ± SD (median, range)	22.1 ± 3.2 (22.7, 16.3-26.9)	23.6 ± 3.8 (22.9, 18.2-33.0)	0.21292
ASA			0.49513
1	1 (5.9)	2 (11.1)
2	15 (88.2)	12 (66.7)
3	1 (5.9)	4 (22.2)
Tumor location			0.60374
C	3 (17.6)	2 (11.1)
A	1 (5.9)	1 (5.6)
T	0 (0)	1 (5.6)
D	2 (11.8)	1 (5.6)
S	4 (23.5)	3 (16.7)
RS	3 (17.6)	2 (11.1)
Ra	1 (5.9)	6 (33.3)
Rb	3 (17.6)	2 (11.1)
Tumor size, mm, mean ± SD (median, range)	34.4 ± 19.9 (35, 11-75)	35.9 ± 18.0 (33, 0-77)	0.81902
UICC-TNM stage			0.83783
0	0 (0)	1 (5.6)
I	6 (35.3)	3 (16.7)
II	3 (17.6)	7 (38.9)
III	7 (41.2)	7 (38.9)
IV	1 (5.9)	0 (0)
T category			0.43663
T0	0 (0)	1 (5.6)
T1	5 (29.4)	1 (5.6)
T2	3 (17.6)	3 (16.7)
T3	7 (41.2)	12 (66.7)
T4	2 (11.8)	1 (5.6)
N category			0.43193
N0	9 (52.9)	11 (61.1)
N1	4 (23.5)	5 (27.8)
N2	4 (23.5)	2 (11.1)
M category			0.30353
M0	16 (94.1)	18 (100.0)
M1	1 (5.9)	0 (0)
Any comorbidity	9 (52.9)	12 (66.7)	0.49981
Hypertension	5 (29.4)	6 (33.3)	1.00001
Ischemic heart disease	0 (0)	2 (11.1)	0.48571
Arrhythmia	1 (5.9)	0 (0)	0.48571
Cerebrovascular disease	0 (0)	1 (5.6)	1.00001
Asthma	2 (11.8)	3 (16.7)	1.00001
COPD	1 (5.9)	0 (0)	0.48571
Diabetes mellitus	1 (5.9)	5 (27.8)	0.17741
Dyslipidemia	4 (23.5)	7 (38.9)	0.47051
Smoking	9 (52.9)	11 (61.1)	0.73801
Preoperative chemotherapy	3 (17.6)	6 (33.3)	0.44301
Operative time, minute, mean ± SD (median, range)	199.1 ± 89.3 (174.0, 117-453)	212.4 ± 57.5 (202.5, 115-328)	0.59942
Temporary loop ileostomy	2 (11.8)	5 (27.8)	0.40181
Postoperative stay, day, mean ± SD (median, range)	10.3 ± 4.6 (9, 8-27)	10.8 ± 3.5 (9, 8-18)	0.69602

¹Fisher exact test.

²t-test.

³Cochran-Mantel-Haenszel correlation test.

⁴Cochran-Mantel-Haenszel general association test.

BMI: Body mass index; ASA: American Society of Anesthesiologists; C: Colon; A: Ascending colon; T: Transverse colon; D: Descending colon; S: Sigmoid colon; RS: Rectosigmoid; Ra: Upper rectum; Rb: Lower rectum; UICC: Union for International Cancer Control; T: Tumor; N: Node; M: Metastasis; COPD: Chronic obstructive pulmonary disease.

Table 3 Odds ratio of surgical site infection occurrence in nutritional intervention group/non-intervention group (logistic model), n (%)

	SSI
Nutritional intervention group (n = 17)	1 (5.9)
Non-intervention group (n = 18)	6 (33.3)
Odds ratio	0.125
95%CI	0.013-1.181
P value	0.0695

SSI: Surgical site infection; CI: Confidence interval.

Table 4 The effect of actual oral calorie intake on the incidence of surgical site infections

	Nutritional intervention group (n = 17)			Non-intervention group (n = 18)			Comparison of odds ratio between groups
	Odds ratio	95%CI	P value	Odds ratio	95%CI	P value	P value
Oral intake pre-op-2	0.58	0.24-1.32	0.1849	1.06	0.81-1.40	0.6705	0.1637
Oral intake pre-op-1	0.78	0.57-1.06	0.1176	1.04	0.86-1.26	0.6562	0.0994
Oral intake pre-op-2 to-1	0.88	0.72-1.08	0.2228	1.00	0.91-1.13	0.6231	0.0955

CI: Confidence interval; Op: Operation.

Table 5 Changes in various parameters

	Nutritional intervention group (n = 17)			Non-intervention group (n = 18)			Comparison of difference from pre-op to post-op between groups
	Pre-op	Post-op	P value1	Pre-op	Post-op	P value1	P value
WBC, ×103/μL, mean ± SD	4.56 ± 1.42	6.71 ± 3.13	0.0041	5.67 ± 1.72	7.40 ± 2.36	0.0154	0.6685
Neutro, %, mean ± SD	69.2 ± 7.0	69.8 ± 9.2	0.8050	68.0 ± 6.4	71.0 ± 6.8	0.1703	0.4236
Lympho, %, mean ± SD	21.6 ± 6.6	19.0 ± 7.7	0.1673	22.7 ± 6.4	18.9 ± 5.6	0.0289	0.5453
Mono, %, mean ± SD	5.65 ± 1.87	5.81 ± 1.85	0.7246	6.29 ± 1.08	5.99 ± 1.23	0.4306	0.4213
Eosino, %, geo-mean (CV)	2.37 (41.6)	3.98 (35.9)	0.0058	1.96 (47.5)	2.94 (46.0)	0.0704	0.4393
Baso, %, mean ± SD	0.69 ± 0.39	0.67 ± 0.38	0.8978	0.63 ± 0.28	0.47 ± 0.21	0.0543	0.1971
RBC, ×106/μL, mean ± SD	3.83 ± 0.65	4.14 ± 0.63	0.0020	3.83 ± 0.59	4.10 ± 0.70	0.0048	0.7676
Hb, g/dL, mean ± SD	11.7 ± 1.8	12.6 ± 1.6	0.0038	11.7 ± 1.9	12.5 ± 2.2	0.0104	0.7380
HCT, %, mean ± SD	35.5 ± 5.2	38.0 ± 4.7	0.0052	35.4 ± 5.1	37.5 ± 5.9	0.0191	0.6707
PLT, ×103/μL, mean ± SD	197.6 ± 45.3	286.5 ± 69.4	< 0.0001	214.9 ± 74.3	306.0 ± 66.4	< 0.0001	0.9039
AST, U/L, geo-mean (CV)	15.4 (9.5)	20.2 (10.7)	0.0043	20.6 (14.0)	20.5 (12.4)	0.9598	0.0324
ALT, U/L, geo-mean (CV)	12.9 (15.8)	19.9 (19.9)	0.0041	18.4 (23.0)	21.4 (18.2)	0.2852	0.1556
ALP, U/L, mean ± SD	60.3 ± 18.6	76.5 ± 26.9	0.0005	64.8 ± 19.4	77.1 ± 24.2	0.0048	0.5161
CK, U/L, geo-mean (CV)	54.6 (9.5)	46.7 (14.7)	0.1557	68.0 (11.6)	43.1 (18.3)	0.0001	0.0558
Amylase, U/L, geo-mean (CV)	68.5 (9.8)	99.1 (18.5)	0.0038	47.8 (9.0)	55.5 (13.8)	0.2329	0.1966
Total bilirubin, mg/dL, mean ± SD	0.64 ± 0.28	0.52 ± 0.23	0.0341	0.73 ± 0.34	0.61 ± 0.27	0.0191	0.8955
Total cholesterol, mg/dL, mean ± SD	182.2 ± 38.0	189.4 ± 51.2	0.3596	161.2 ± 33.8	156.6 ± 30.4	0.3651	0.2008
LDL cholesterol, mg/dL, mean ± SD	114.1 ± 36.4	116.8 ± 35.2	0.7775	94.7 ± 26.0	89.9 ± 26.5	0.4003	0.4243
HDL cholesterol, mg/dL, mean ± SD	44.7 ± 13.7	39.6 ± 12.8	0.0015	44.2 ± 12.4	38.8 ± 9.8	0.0008	0.8211
Triglyceride, mg/dL, mean ± SD	117.4 ± 51.5	133.3 ± 40.0	0.0704	111.9 ± 64.7	135.0 ± 43.9	0.0628	0.9739
Na, mmol/L, mean ± SD	140.9 ± 2.4	139.9 ± 2.3	0.2099	142.1 ± 2.0	139.1 ± 3.7	0.0002	0.0595
Cl, mmol/L, mean ± SD	106.9 ± 4.6	102.2 ± 3.0	0.0001	108.1 ± 3.2	102.7 ± 4.2	< 0.0001	0.6757
K, mmol/L, mean ± SD	3.71 ± 0.45	4.19 ± 0.39	0.0002	3.89 ± 0.43	4.37 ± 0.35	0.0001	0.9770
BUN, mg/dL, mean ± SD	11.3 ± 2.7	12.2 ± 3.4	0.5041	11.4 ± 3.7	14.6 ± 6.2	0.0116	0.1776
Creatinine, mg/dL, mean ± SD	0.75 ± 0.15	0.80 ± 0.15	0.0846	0.76 ± 0.21	0.81 ± 0.21	0.1388	0.8287
Total protein, g/dL, mean ± SD	5.62 ± 0.59	6.44 ± 0.48	< 0.0001	5.68 ± 0.67	6.45 ± 0.77	< 0.0001	0.8087
Albumin, g/dL	3.37 ± 0.43	3.51 ± 0.52	0.2014	3.43 ± 0.43	3.59 ± 0.54	0.1197	0.8595
eGFR, mL/minute/1.73 m2, mean ± SD	79.1 ± 13.4	73.2 ± 11.8	0.0638	80.3 ± 19.4	74.7 ± 16.3	0.0686	0.9499
CRP, mg/dL, geo-mean (CV)	0.08 (-39.9)	1.11 (1161.8)	< 0.0001	0.11 (-56.3)	1.03 (3756.7)	< 0.0001	0.4785
Glucose, mg/dL, mean ± SD	103.8 ± 16.8	103.1 ± 20.8	0.8662	107.2 ± 12.3	107.1 ± 18.1	0.9623	0.9323
Prealbumin, mg/dL, mean ± SD	22.2 ± 4.9	20.0 ± 5.3	0.1799	21.1 ± 6.4	20.4 ± 8.5	0.5151	0.6254
NK cell activity, %, mean ± SD	31.5 ± 10.7	28.9 ± 12.7	0.4505	38.1 ± 14.4	30.9 ± 18.5	0.0314	0.2922
CD4, %, mean ± SD	44.1 ± 12.1	42.1 ± 7.9	0.2782	44.9 ± 9.5	45.9 ± 9.7	0.8166	0.3551
CD8, %, mean ± SD	35.9 ± 11.2	33.2 ± 10.6	0.0446	30.8 ± 8.0	29.7 ± 9.2	0.3464	0.4438
CD4/CD8 ratio, mean ± SD	1.47 ± 0.75	1.43 ± 0.67	0.7161	1.57 ± 0.61	1.74 ± 0.73	0.1822	0.2268
INF-γ, IU/mL, mean ± SD	0.10 ± 0.00	0.11 ± 0.02	0.7982	0.13 ± 0.12	0.11 ± 0.05	0.5087	0.5170
TNF-α, IU/mL, geo-mean (CV)	0.66 (-262.8)	0.93 (300.8)	0.0002	0.68 (-311.3)	0.93 (190.0)	0.0028	0.5537
Body composition analysis
BMI, kg/m2, mean ± SD	21.3 ± 3.4	20.8 ± 3.4	0.0010	23.6 ± 3.9	22.8 ± 3.8	< 0.0001	0.4039
Weight, kg, mean ± SD	59.7 ± 13.1	58.4 ± 12.7	0.0010	65.6 ± 12.9	63.1 ± 12.3	< 0.0001	0.4015
Muscle mass, kg, mean ± SD	42.8 ± 8.2	42.4 ± 7.6	0.4376	44.6 ± 8.8	43.1 ± 9.5	0.0989	0.5402
Lean body mass, kg, mean ± SD	45.3 ± 8.6	44.9 ± 8.0	0.4543	47.2 ± 9.2	45.7 ± 9.9	0.1363	0.6074
Body fat, kg, mean ± SD	14.3 ± 6.6	13.5 ± 6.6	0.1630	18.4 ± 6.9	17.4 ± 6.2	0.1255	0.9494
Skeletal muscle mass	24.7 ± 5.2	24.4 ± 4.9	0.3361	25.9 ± 5.7	25.0 ± 6.2	0.1338	0.7156
Skeletal muscle index	6.91 ± 1.14	6.81 ± 0.95	0.4287	7.24 ± 1.13	6.93 ± 1.19	0.0753	0.4861
CONUT score	4.1 ± 2.5	3.6 ± 2.6	0.4145	3.7 ± 1.9	3.4 ± 2.1	0.7999	0.6870

¹Comparison between pre-operation and post-operation.

WBC: White blood cell; RBC: Red blood cell; Hb: Hemoglobin: HCT: Hematocrit; PLT: Platelet; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase: CK: Creatine kinase; LDL: Low density lipoprotein; HDL: High density lipoprotein; BUN: Blood urea nitrogen; eGFR: Estimated glomerular filtration rate; CRP: C-reactive protein; NK: Natural killer; INF-γ: Interferon gamma; TNF-α: Tumour necrosis factor alpha; BMI: Body mass index; COUNT: Controlling Nutrition Status.

Table 6 Odds ratio of surgical site infection occurrence in colon group and rectum group (logistic model), n (%)

	SSI
RS-Rb (n = 17)	6 (35.3)
C-S (n = 18)	1 (5.6)
Odds ratio	9.273
95%CI	0.979-87.870
P value	0.0522
Ra-Rb (n = 12)	5 (41.7)
C-RS (n = 23)	2 (8.7)
Odds ratio	7.498
95%CI	1.180-47.660
P value	0.0328

SSI: Surgical site infection; RS-Rb: Rectosigmoid, upper rectum and lower rectum; C-S: Colon, ascending colon, transverse colon, descending colon, and sigmoid colon; CI: Confidence interval; Ra-Rb: Upper rectum and lower rectum; C-RS: Colon, ascending colon, transverse colon, descending colon, sigmoid colon and rectosigmoid.