World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 16, Number 1, February 2025, pages 70-82

Effect of Whey Protein Supplementation on Postoperative Outcomes After Gynecological Cancer Surgery: A Randomized Controlled Trial

Figure 1. Participant flow diagram after randomization to either whey protein supplementation (WPS) or control group.

Figure 2. Kaplan-Meier survival estimates for length of hospital stay of participants categorized by whey protein supplementation (WPS) and control group.

Figure 3. Kaplan-Meier survival estimates for (a) time to first bowel sound, (b) time to first flatus, (c) time to first defecation, and (d) time to first ambulation of participants categorized by whey protein supplementation (WPS) and control group.

**Table 1.** Baseline Clinical Characteristics of Participants in WPS Group and Control Group
Characteristics	Total (n = 61)	WPS group (n = 30)	Control group (n = 31)	P-value
^aDissociative disorder and old pulmonary tuberculosis. ^bNormal nutrition: score 0 - 5; level 1: score 6 - 12; level 2: score 13 - 19; level 3: score 20 - 25. ^cP-value from Student’s t-test. ^dP-value from Fischer’s exact test. ^eP-value from Chi-square test. BMI: body mass index; kg: kilogram; n: number; m: meter; SD: standard deviation; RJ-SGA: Rajavithi Subjective Global Assessment; WPS: whey protein supplementation.
Age (years), mean ± SD	51.0 ± 11.8	48.8 ± 12.1	53.2 ± 11.3	0.151^c
BMI (kg/m²), mean ± SD	25.2 ± 6.5	25.9 ± 7.4	24.5 ± 5.5	0.372^c
Ethnicity, n (%)				0.514^d
Thai	56 (91.8)	29 (96.7)	27 (87.0)
Myanmar	3 (4.9)	1 (3.3)	2 (6.5)
Laos	2 (3.3)	0 (0.0)	2 (6.5)
Underlying disease, n (%)
None	51 (83.6)	26 (86.8)	25 (80.7)	0.731^d
Dyslipidemia	5 (8.3)	1 (3.3)	4 (12.9)	0.354^d
Asthma	2 (3.3)	1 (3.3)	1 (3.2)	1.000^d
Allergic rhinitis	1 (1.6)	1 (3.3)	0 (0.0)	0.492^d
Thyroid disease	1 (1.6)	0 (0.0)	1 (3.2)	1.000^d
Others^a	1 (1.6)	1 (3.3)	0 (0.0)	0.492^d
Menopausal status, n (%)				0.249^e
No	24 (39.3)	14 (46.7)	10 (32.3)
Yes	37 (60.7)	16 (53.3)	21 (67.7)
Previous surgery, n (%)				0.413^e
No	46 (75.4)	24 (80.0)	22 (71.0)
Yes	15 (34.6)	6 (20.0)	9 (29.0)
Smoking, n (%)				0.492^d
No	60 (98.4)	29 (96.7)	31 (100.0)
Yes	1 (1.6)	1 (3.3)	0 (0.0)
Nutritional status by RJ-SGA^b, n (%)				0.508^d
Normal nutrition	0 (0.0)	0 (0.0)	0 (0.0)
Malnutrition level 1	50 (82.0)	26 (86.7)	24 (77.4)
Malnutrition level 2	11 (18.0)	4 (13.3)	7 (22.6)
Malnutrition level 3	0 (0.0)	0 (0.0)	0 (0.0)

Table 1. Baseline Clinical Characteristics of Participants in WPS Group and Control Group

Characteristics

Total (n = 61)

WPS group (n = 30)

Control group (n = 31)

P-value

^aDissociative disorder and old pulmonary tuberculosis. ^bNormal nutrition: score 0 - 5; level 1: score 6 - 12; level 2: score 13 - 19; level 3: score 20 - 25. ^cP-value from Student’s t-test. ^dP-value from Fischer’s exact test. ^eP-value from Chi-square test. BMI: body mass index; kg: kilogram; n: number; m: meter; SD: standard deviation; RJ-SGA: Rajavithi Subjective Global Assessment; WPS: whey protein supplementation.

Age (years), mean ± SD

51.0 ± 11.8

48.8 ± 12.1

53.2 ± 11.3

0.151^c

BMI (kg/m²), mean ± SD

25.2 ± 6.5

25.9 ± 7.4

24.5 ± 5.5

0.372^c

Ethnicity, n (%)

0.514^d

Thai

56 (91.8)

29 (96.7)

27 (87.0)

Myanmar

3 (4.9)

1 (3.3)

2 (6.5)

Laos

2 (3.3)

0 (0.0)

2 (6.5)

Underlying disease, n (%)

None

51 (83.6)

26 (86.8)

25 (80.7)

0.731^d

Dyslipidemia

5 (8.3)

1 (3.3)

4 (12.9)

0.354^d

Asthma

2 (3.3)

1 (3.3)

1 (3.2)

1.000^d

Allergic rhinitis

1 (1.6)

1 (3.3)

0 (0.0)

0.492^d

Thyroid disease

1 (1.6)

0 (0.0)

1 (3.2)

1.000^d

Others^a

1 (1.6)

1 (3.3)

0 (0.0)

0.492^d

Menopausal status, n (%)

0.249^e

24 (39.3)

14 (46.7)

10 (32.3)

Yes

37 (60.7)

16 (53.3)

21 (67.7)

Previous surgery, n (%)

0.413^e

46 (75.4)

24 (80.0)

22 (71.0)

Yes

15 (34.6)

6 (20.0)

9 (29.0)

Smoking, n (%)

0.492^d

60 (98.4)

29 (96.7)

31 (100.0)

Yes

1 (1.6)

1 (3.3)

0 (0.0)

Nutritional status by RJ-SGA^b, n (%)

0.508^d

Normal nutrition

0 (0.0)

Malnutrition level 1

50 (82.0)

26 (86.7)

24 (77.4)

Malnutrition level 2

11 (18.0)

4 (13.3)

7 (22.6)

Malnutrition level 3

0 (0.0)

**Table 2.** Surgical Characteristics of Participants in WPS Group and Control Group
Characteristics	Total (n = 61)	WPS group (n = 30)	Control group (n = 31)	P-value
^aCellular fibroma, endometrial hyperplasia, endometrioid adenofibroma, metastatic adenocarcinoma, ovarian fibroma, mature cystic teratoma, and endometrioma. ^bTumor biopsy and peritoneal biopsy. ^cP-value from Chi-square test. ^dP-value from Fischer’s exact test. ^eP-value from Student’s t-test. ^fP-value from Mann-Whitney U test. BOT: borderline ovarian tumor; BSO: bilateral salpingo-oophorectomy; EBL: estimated blood loss; mL: milliliter; h: hour; n: number; PRC: packed red cell; SD: standard deviation; TAH: total abdominal hysterectomy; USO: unilateral salpingo-oophorectomy; WPS: whey protein supplementation.
Pre-operative diagnosis, n (%)				0.055^c
Suspected uterine cancer	27 (44.3)	17 (56.7)	10 (32.3)
Suspected ovarian cancer	34 (55.7)	13 (43.3)	21 (67.7)
Postoperative diagnosis, n (%)				0.178^d
Endometrial cancer	23 (37.7)	14 (46.7)	9 (29.0)
Ovarian cancer	20 (32.8)	9 (30.0)	11 (35.5)
BOT	10 (6.4)	2 (6.7)	8 (25.8)
Uterine sarcoma	1 (1.6)	1 (3.3)	0 (0.0)
Others^a	7 (11.5)	4 (13.3)	3 (9.7)
Surgical procedure, n (%)				0.591^d
USO/BSO	6 (9.8)	3 (10.0)	3 (9.7)
TAH with USO/BSO	53 (86.9)	27 (90.0)	26 (83.9)
Others^b	2 (3.3)	0 (0.0)	2 (6.4)
Lymphadenectomy, n (%)				0.906^c
Not done	24 (39.3)	11 (36.7)	13 (41.9)
Pelvic node	16 (26.3)	8 (26.7)	8 (25.8)
Pelvic and paraaortic node	21 (34.4)	11 (36.6)	10 (32.3)
Abdominal adhesiolysis, n (%)	20 (32.8)	9 (30.0)	11 (35.5)	0.648^c
Operative time (h), mean ± SD	2.45 ± 0.80	2.48 ± 0.82	2.49 ± 0.79	0.963^e
EBL (mL), median (range)	369.2 (20.0 - 1,600.0)	289.0 (20.0 - 800.0)	446.8 (50.0 - 1,600.0)	0.188^f
PRC transfusion, n (%)	13 (21.3)	3 (10.0)	10 (32.3)	0.059^d

Table 2. Surgical Characteristics of Participants in WPS Group and Control Group

Characteristics

Total (n = 61)

WPS group (n = 30)

Control group (n = 31)

P-value

^aCellular fibroma, endometrial hyperplasia, endometrioid adenofibroma, metastatic adenocarcinoma, ovarian fibroma, mature cystic teratoma, and endometrioma. ^bTumor biopsy and peritoneal biopsy. ^cP-value from Chi-square test. ^dP-value from Fischer’s exact test. ^eP-value from Student’s t-test. ^fP-value from Mann-Whitney U test. BOT: borderline ovarian tumor; BSO: bilateral salpingo-oophorectomy; EBL: estimated blood loss; mL: milliliter; h: hour; n: number; PRC: packed red cell; SD: standard deviation; TAH: total abdominal hysterectomy; USO: unilateral salpingo-oophorectomy; WPS: whey protein supplementation.

Pre-operative diagnosis, n (%)

0.055^c

Suspected uterine cancer

27 (44.3)

17 (56.7)

10 (32.3)

Suspected ovarian cancer

34 (55.7)

13 (43.3)

21 (67.7)

Postoperative diagnosis, n (%)

0.178^d

Endometrial cancer

23 (37.7)

14 (46.7)

9 (29.0)

Ovarian cancer

20 (32.8)

9 (30.0)

11 (35.5)

BOT

10 (6.4)

2 (6.7)

8 (25.8)

Uterine sarcoma

1 (1.6)

1 (3.3)

0 (0.0)

Others^a

7 (11.5)

4 (13.3)

3 (9.7)

Surgical procedure, n (%)

0.591^d

USO/BSO

6 (9.8)

3 (10.0)

3 (9.7)

TAH with USO/BSO

53 (86.9)

27 (90.0)

26 (83.9)

Others^b

2 (3.3)

0 (0.0)

2 (6.4)

Lymphadenectomy, n (%)

0.906^c

Not done

24 (39.3)

11 (36.7)

13 (41.9)

Pelvic node

16 (26.3)

8 (26.7)

8 (25.8)

Pelvic and paraaortic node

21 (34.4)

11 (36.6)

10 (32.3)

Abdominal adhesiolysis, n (%)

20 (32.8)

9 (30.0)

11 (35.5)

0.648^c

Operative time (h), mean ± SD

2.45 ± 0.80

2.48 ± 0.82

2.49 ± 0.79

0.963^e

EBL (mL), median (range)

369.2 (20.0 - 1,600.0)

289.0 (20.0 - 800.0)

446.8 (50.0 - 1,600.0)

0.188^f

PRC transfusion, n (%)

13 (21.3)

3 (10.0)

10 (32.3)

0.059^d

**Table 3.** Comparison of Pre- and Postoperative Serum Albumin Among WPS Group and Control Group
Serum albumin (g/L)	Total (n = 61)	WPS group (n = 30)	Control group (n = 31)	MD/RD (95% CI)	P-value
^aHypoalbuminemia defined as serum albumin less than 3.5 g/L.^bP-value from generalized linear mixed model analysis (GLMM). ^cP-value from Student’s t-test. ^dP-value from Fischer’s exact test. *Significant P-value < 0.05. CI: confidence interval; g: gram; L: liter; MD: mean difference; n: number; OR: odds ratio; RD: risk difference; SD: standard deviation; WPS: whey protein supplementation.

Pre-operative serum albumin, mean ± SD	4.04 ± 0.47	4.04 ± 0.47	3.82 ± 0.59	0.21 (-0.59, 0.49)	0.123^c
Postoperative serum albumin, mean ± SD	3.17 ± 0.48	3.31 ± 0.41	3.04 ± 0.51	0.27 (0.03, 0.51)	0.026*^c
Treatment effect, MD (95% CI)		0.24 (0.02, 0.46)	Ref.
P-value		0.031*^b	-
Hypoalbuminemia^a
Pre-operative, n (%)	11 (18.0)	3 (10.0)	8 (25.8)	-0.16 (-0.35, 0.03)	0.182^d
Postoperative, n (%)	42 (68.9)	16 (53.3)	26 (83.9)	-0.31 (-0.53, -0.08)	0.013^d*
Treatment effect, OR (95% CI)		0.38 (0.18, 0.80)	Ref.
P-value		0.011*^b	-

Table 3. Comparison of Pre- and Postoperative Serum Albumin Among WPS Group and Control Group

Serum albumin (g/L)

Total (n = 61)

WPS group (n = 30)

Control group (n = 31)

MD/RD (95% CI)

P-value

^aHypoalbuminemia defined as serum albumin less than 3.5 g/L.^bP-value from generalized linear mixed model analysis (GLMM). ^cP-value from Student’s t-test. ^dP-value from Fischer’s exact test. *Significant P-value < 0.05. CI: confidence interval; g: gram; L: liter; MD: mean difference; n: number; OR: odds ratio; RD: risk difference; SD: standard deviation; WPS: whey protein supplementation.

Pre-operative serum albumin, mean ± SD

4.04 ± 0.47

3.82 ± 0.59

0.21 (-0.59, 0.49)

0.123^c

Postoperative serum albumin, mean ± SD

3.17 ± 0.48

3.31 ± 0.41

3.04 ± 0.51

0.27 (0.03, 0.51)

0.026*^c

Treatment effect, MD (95% CI)

0.24 (0.02, 0.46)

Ref.

P-value

0.031*^b

Hypoalbuminemia^a

Pre-operative, n (%)

11 (18.0)

3 (10.0)

8 (25.8)

-0.16 (-0.35, 0.03)

0.182^d

Postoperative, n (%)

42 (68.9)

16 (53.3)

26 (83.9)

-0.31 (-0.53, -0.08)

0.013^d*

Treatment effect, OR (95% CI)

0.38 (0.18, 0.80)

Ref.

P-value

0.011*^b

**Table 4.** Postoperative Outcomes Categorized by WPS Group and Control Group
Outcome	WPS group (n = 30)	Control group (n = 31)	Mean difference (95% CI)	P-value
^aAdditional analgesic drugs defined as intravenous non-steroidal anti-inflammatory drug. ^bP-value from Student’s t-test. ^cP-value from Fischer’s exact test. *Significant P-value < 0.05. CI: confidence interval; MD: mean difference; n: number; SD: standard deviation; WPS: whey protein supplementation.
Primary outcomes
Length of hospital stay (h), mean ± SD	79.0 ± 16.7	93.3 ± 28.4	-14.3 (-26.3, -2.3)	0.021*^b
Secondary outcomes
Time to first bowel sound (h), mean ± SD	16.0 ± 4.3	17.4 ± 6.3	-1.4 (-4.2, 1.3)	0.309^b
Time to first passage of flatus (h), mean ± SD	27.0 ± 9.1	38.0 ± 14.0	-11.0 (-17.1, -4.9)	< 0.001*^b
Time to first defecation (h), mean ± SD	62.9 ± 13.7	74.2 ± 19.9	-11.3 (-20.1, -2.5)	0.013*^b
Time to first ambulation (h), mean ± SD	25.6 ± 4.9	29.9 ± 10.3	-4.3 (-8.4, -0.1)	0.043*^b
Additional analgesic drug^a, n (%)				0.425^c
No	28 (93.3)	26 (83.9)	-
Yes	2 (6.7)	5 (16.1)	-

Table 4. Postoperative Outcomes Categorized by WPS Group and Control Group

Outcome

WPS group (n = 30)

Control group (n = 31)

Mean difference (95% CI)

P-value

^aAdditional analgesic drugs defined as intravenous non-steroidal anti-inflammatory drug. ^bP-value from Student’s t-test. ^cP-value from Fischer’s exact test. *Significant P-value < 0.05. CI: confidence interval; MD: mean difference; n: number; SD: standard deviation; WPS: whey protein supplementation.

Primary outcomes

Length of hospital stay (h), mean ± SD

79.0 ± 16.7

93.3 ± 28.4

-14.3 (-26.3, -2.3)

0.021*^b

Secondary outcomes

Time to first bowel sound (h), mean ± SD

16.0 ± 4.3

17.4 ± 6.3

-1.4 (-4.2, 1.3)

0.309^b

Time to first passage of flatus (h), mean ± SD

27.0 ± 9.1

38.0 ± 14.0

-11.0 (-17.1, -4.9)

< 0.001*^b

Time to first defecation (h), mean ± SD

62.9 ± 13.7

74.2 ± 19.9

-11.3 (-20.1, -2.5)

0.013*^b

Time to first ambulation (h), mean ± SD

25.6 ± 4.9

29.9 ± 10.3

-4.3 (-8.4, -0.1)

0.043*^b

Additional analgesic drug^a, n (%)

0.425^c

28 (93.3)

26 (83.9)

Yes

2 (6.7)

5 (16.1)

**Table 5.** Postoperative Complications Categorized by WPS Group and Control Group
Outcome	Total (n = 61)	WPS group (n = 30)	Control group (n = 31)	P-value
^aP-value from Fischer’s exact test. n: number; SD: standard deviation; WPS: whey protein supplementation.
Fever, n (%)				1.000^a
No	60 (98.4)	30 (100.0)	30 (96.8)
Yes	1 (1.6)	0 (0.0)	1 (3.2)
Postoperative nausea/vomiting, n (%)				0.053^a
No	53 (86.9)	29 (96.7)	24 (77.4)
Yes	8 (13.1)	1 (3.3)	7 (22.6)
Wound infection on postoperative day 7, n (%)				1.000^a
No	59 (96.7)	29 (96.7)	30 (96.8)
Yes	2 (3.3)	1 (3.3)	1 (3.2)
Wound infection on postoperative day 14, n (%)				0.492^a
No	60 (98.4)	25 (96.7)	31 (100.0)
Yes	1 (1.6)	1 (3.3)	0 (0.0)
Readmission within 30 days, n (%)				1.000^a
No	59 (96.7)	29 (96.7)	30 (96.8)
Yes	2 (3.3)	1 (3.3)	1 (3.2)
Readmission cause, n (%)				1.000^a
Wound dehiscence	1 (1.6)	1 (3.3)	0 (0.0)
Gut obstruction	1 (1.6)	0 (0.0)	1 (3.2)

Table 5. Postoperative Complications Categorized by WPS Group and Control Group

Outcome

Total (n = 61)

WPS group (n = 30)

Control group (n = 31)

P-value

^aP-value from Fischer’s exact test. n: number; SD: standard deviation; WPS: whey protein supplementation.

Fever, n (%)

1.000^a

60 (98.4)

30 (100.0)

30 (96.8)

Yes

1 (1.6)

0 (0.0)

1 (3.2)

Postoperative nausea/vomiting, n (%)

0.053^a

53 (86.9)

29 (96.7)

24 (77.4)

Yes

8 (13.1)

1 (3.3)

7 (22.6)

Wound infection on postoperative day 7, n (%)

1.000^a

59 (96.7)

29 (96.7)

30 (96.8)

Yes

2 (3.3)

1 (3.3)

1 (3.2)

Wound infection on postoperative day 14, n (%)

0.492^a

60 (98.4)

25 (96.7)

31 (100.0)

Yes

1 (1.6)

1 (3.3)

0 (0.0)

Readmission within 30 days, n (%)

1.000^a

59 (96.7)

29 (96.7)

30 (96.8)

Yes

2 (3.3)

1 (3.3)

1 (3.2)

Readmission cause, n (%)

1.000^a

Wound dehiscence

1 (1.6)

1 (3.3)

0 (0.0)

Gut obstruction

1 (1.6)

0 (0.0)

1 (3.2)