Risk Factors for Recurrence of Radically Resected Mucinous Colorectal Adenocarcinoma

Figures & data

Figure 1 Flow diagram showing patient selection and exclusion process.

Table 1 Clinical and Pathologic Information of 162 MAC

Clinical and Pathologic Information
Age	Median (range)	60(15–87)
Gender	Male/Female	76/86
Comorbidities	Yes/No	61/101
ASA score	I/II/III	73/68/21
Tumor location	Right/Left/Rectal	69/45/48
Tumor size (cm)	Mean±SD	4.4±12.1
CA199 (U/mL)	Mean±SD	57.5±152.6
CEA (ng/mL)	Mean±SD	16±42.1
Adjuvant chemotherapy	Yes/No	114/48
Number of LNs	Median (range)	17(5–53)
T stage	T1/T2/T3/T4	1/12/74/75
N stage	N0/N1/N2	76/36/50
TNM stage	I/II/III	11/65/86

Abbreviations: ASA, American Society of Anesthesiology; CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; LN, lymph node; SD, standard deviation.

Table 2 Surgical and Prognosis Outcome of 162 MAC

Surgical and Prognosis Outcome
Surgical method	LAP/OPEN	83/79
Operative time (min)	Mean±SD	211±78.3
Blood loss (mL)	Mean±SD	130.7±108.3
Multivisceral resection	Total (%)	14(8.64)
	Abdominal wall (%)	2(1.23)
	Small bowel (except duodenum) (%)	5(3.09)
	Urinary organs (%)	1(0.62)
	Gynecologic organs (%)	3(1.85)
	Gallbladder (%)	3(1.85)
Postoperative complication	Total (%)	26(16.05)
The frequency of appearance	Anastomotic Hemorrhage (%)	3(1.85)
	Intraabdominal bleeding (%)	2(1.23)
	Leakage (%)	5(3.09)
	Gastroplegia (%)	2(1.23)
	Infection (incision and abdomen) (%)	12(7.41)
	Pulmonary infection (%)	6(3.7)
	Obstruction (%)	9(5.56)
	Renal insufficiency (%)	1(0.62)
Local recurrence	Total (%)	38(23.46)
	Recurrent abdominal or pelvic masses (%)	13(8.02)
	Peritoneal dissemination (%)	12(7.41)
	Recurrent enlarged LNs (%)	5(3.09)
	Recurrent masses and Peritoneal nodules (%)	8(4.94)
Distant metastasis	Total (%)	33(20.37)
	Liver metastasis (%)	13(8.02)
	Lung metastasis (%)	8(4.94)
	Bone metastasis (%)	6(3.7)
	Liver and Lung metastasis (%)	4(2.47)
	Liver, Bone and Brain metastasis (%)	1(0.62)
	Brain metastasis (%)	1(0.62)

Abbreviations: LAP, laparoscopic surgery group; OPEN, open surgery group; LN, lymph node; ^asome patients have multiple postoperative complications.

Figure 2 (A) Log Rank (Mantel-Cox) test=1.371, P=0.504. Five-year DFS rates of MAC, colonic MA, and rectal MA were 62.0%, 65.8%, and 51.7%, respectively. Figure 2 (B) Log Rank (Mantel-Cox) test=14.290, P=0.001. Five-year DFS rates of TNM stage I, TNM stage II, and TNM stage III were 100%, 71.2%, and 47.81%, respectively.

Table 3 Univariate Analysis of the Risk Factors for Local Recurrence of MAC

Variable (MAC)		Local Recurrence N=38	No Local Recurrence N=124	95% CI	OR	P-value
Age	Median (range)	59(15–82)	60(24–87)	0.97–1.02	0.992	0.510
Gender	Male/Female	19/19	67/57	0.41–1.76	0.851	0.663
Comorbidities (%)	Yes	14(36.8)	47(37.9)	0.45–2.03	0.956	0.906
ASA score	I(R)	16(42.1)	57(46.0)	-	-	0.180
	II	20(52.6)	48(38.7)	0.69–3.18	1.484
	III	2(5.3)	19(15.3)	0.08–1.78	0.375
CA199 (U/mL)	Mean±SD	65.6±127	55.1±160	0.998–1.003	1.000	0.709
CEA (ng/mL)	Mean±SD	15.3±32.5	16.2±44.7	0.99–1.008	0.999	0.908
Tumor location	Colonic/Rectal	26/12	88/36	0.51–2.48	1.128	0.764
Tumor size (cm)	Mean±SD	4.1±1.7	4.5±2.2	0.75–1.09	0.907	0.305
LAP and OPEN		17/21	66/58	0.34–1.48	0.711	0.361
Operative time (min)	Mean±SD	213.9±80.2	210.12±78.06	0.996–1.005	1.001	0.795
Blood loss (mL)	Mean±SD	178.7±138.5	116±93	1.00–1.01	1.005	0.004*
Transfusion (%)	Yes	10(26.3)	8(6.5)	1.87–14.32	5.179	0.002*
Multivisceral resection (%)	Yes	2(5.3)	12(9.7)	0.11–2.43	0.519	0.404
Complications (%)	Yes	7(18.4)	19(15.3)	0.48–3.24	1.248	0.649
Number of LN resected	Median (range)	15(5–47)	18(6–53)	0.93–1.02	0.973	0.205
T stage	T1-T2	0	13(10.5)	-	-	0.093
	T3 (R)	13(34.2)	61(49.2)	-	-
	T4a+T4b	25(65.8)	50(40.3)	1.09–5.05	2.346
N stage	N0 (R)	11(28.9)	65(52.4)	-	-	0.000*
	N1	5(13.2)	31(25.0)	0.31–2.98	0.953
	N2	22(57.9)	28(22.6)	1.99–10.85	4.643
TNM stage	I	0	11(8.9)	-	-	0.062
	II(R)	10(26.3)	55(44.4)	-	-
	III	28(73.7)	58(46.8)	1.18–5.97	2.655
Adjuvant chemotherapy	Yes	27(71.1)	86(69.4)	0.49–2.41	1.085	0.842

Table 4 Subgroup Analysis of the Risk Factors for Local Recurrence of Colonic MA

Variable (Colonic MA)		Local Recurrence N=26	No Local Recurrence N=88	95% CI	OR	P-value
Age	Median (range)	60.5(15–82)	61(24–85)	0.96–1.02	0.991	0.508
Gender	Male/Female	13/13	50/38	0.32–1.83	0.760	0.540
Comorbidities (%)	Yes	9(34.6)	36(40.9)	0.31–1.91	0.765	0.565
ASA score	I(R)	10(38.5)	38(43.2)	-	-	0.412
	II	14(53.8)	36(40.9)	0.58–3.75	1.478
	III	2(7.7)	14(15.9)	0.11–2.79	0.543
CA199 (U/mL)	Mean±SD	75.3±150.1	60.5±182.6	0.998–1.003	1.000	0.706
CEA (ng/mL)	Mean±SD	18.5±38.7	17±41	0.99–1.01	1.001	0.868
Tumor location	Right/Left	14/12	55/33	0.59–3.46	1.429	0.429
Tumor size (cm)	Mean±SD	4.2±1.7	4.9±2.2	0.66–1.06	0.837	0.137
LAP and OPEN		11/15	45/43	0.29–1.7	0.701	0.430
Operative time (min)	Mean±SD	202.7±54.6	199.3±67.3	0.99–1.01	1.001	0.813
Blood loss (mL)	Mean±SD	181.5±135	112.6±87.1	1.00–1.01	1.006	0.008*
Transfusion (%)	Yes	5(19.2)	5(5.7)	1.05–14.93	3.952	0.043*
Multivisceral resection (%)	Yes	1(3.8)	11(12.5)	0.03–2.28	0.280	0.234
Complications (%)	Yes	5(19.2)	13(14.8)	0.44–4.29	1.374	0.585
Number of LN resected	Median (range)	16.5(7–47)	18(6–53)	0.94–1.03	0.985	0.510
T stage	T1-T2	0	7(8.0)	-	-	0.029*
	T3 (R)	7(26.9)	47(53.4)	-	-
	T4a+T4b	19(73.1)	34(38.6)	1.42–9.92	3.752
N stage	N0 (R)	8(30.8)	49(55.7)	-	-	0.004*
	N1	4(15.4)	22(25.0)	0.31–4.1	1.114
	N2	14(53.8)	17(19.3)	1.8–14.12	5.044
TNM stage	I	0	7(7.9)	-	-	0.077
	II(R)	7(26.9)	43(48.9)	-	-
	III	19(73.1)	38(43.2)	1.16–8.1	3.071
Adjuvant chemotherapy	Yes	20(76.9)	58(65.9)	0.63–4.75	1.724	0.292

Table 5 Subgroup Analysis of the Risk Factors for Local Recurrence of Rectal MA

Variable (Rectal MA)		Local Recurrence N=12	No Local Recurrence N=36	95% CI	OR	P-value
Age	Median (range)	55(43–78)	57(29–87)	0.95–1.05	0.996	0.882
Gender	Male/Female	6/6	17/19	0.3–4.13	1.118	0.868
Comorbidities (%)	Yes	5(41.7)	11(30.6)	0.42–6.26	1.623	0.481
ASA score	I(R)	6(50.0)	19(52.8)	-	-	0.799
	II	6(50.0)	12(33.3)	0.41–6.06	1.583
	III	0(0)	5(13.9)	-	-
CA199 (U/mL)	Mean±SD	44.8±48.3	41.8±82.9	0.99–1.01	1.001	0.906
CEA (ng/mL)	Mean±SD	8.6±7.7	14.4±53.5	0.98–1.02	0.996	0.719
Tumor size (cm)	Mean±SD	3.8±1.6	3.3±1.6	0.79–1.78	1.184	0.417
LAP and OPEN		6/6	21/15	0.19–2.65	0.714	0.615
Operative time (min)	Mean±SD	238.2±118	236.6±95.5	0.99–1.01	1.000	0.962
Blood loss (mL)	Mean±SD	172.5±151.8	124.4±106.9	1.00–1.01	1.003	0.242
Transfusion (%)	Yes	5(41.7)	3(8.3)	1.51–40.81	7.857	0.014*
Multivisceral resection (%)	Yes	1(8.3)	1(2.8)	0.18–55.19	3.182	0.427
Complications (%)	Yes	2(16.7)	6(16.7)	0.17–5.77	1.0	1.0
Number of LN resected	Median (range)	13(5–30)	17.5(7–44)	0.85–1.03	0.935	0.172
T stage	T1-T2	0	6(16.7)	-	-	0.981
	T3 (R)	6(50.0)	14(38.9)	-	-
	T4a+T4b	6(50.0)	16(44.4)	0.23–3.34	0.875
N stage	N0 (R)	3(25.0)	16(44.0)	-	-	0.102
	N1	1(8.3)	9(25.0)	0.05–6.57	0.593
	N2	8(66.7)	11(30.6)	0.84–17.97	3.879
TNM stage	I	0	4(11.1)	-	-	0.742
	II(R)	3(25.0)	12(33.3)	-	-
	III	9(75.0)	20(69.0)	0.41–7.99	1.8
Adjuvant chemotherapy	Yes	7(58.3)	28(77.8)	0.1–1.61	0.4	0.197

Note: *P<0.05.

Abbreviations: ASA, American Society of Anesthesiology; CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; OR, risk ratio; R, reference group; LAP, laparoscopic surgery group; OPEN, open surgery group; LN, lymph nodes.

Table 6 Univariate Analysis of the Risk Factors for Local Distant Metastasis of MAC

Variable (MAC)		Distant Metastasis N=33	No Distant Metastasis N=129	95% CI	OR	P-value
Age	Median (range)	61(24–82)	60(15–87)	0.98–1.04	1.01	0.452
Gender	Male/Female	23/10	63/66	1.06–5.46	2.41	0.035*
Comorbidities (%)	Yes	13(39.4)	48(37.2)	0.5–2.4	1.097	0.817
ASA score	I(R)	13(39.4)	60(46.5)	-	-	0.438
	II	17(51.2)	51(39.5)	0.68–3.47	1.538
	III	3(9.1)	18(14.0)	0.2–3.0	0.769
CA199 (U/mL)	Mean±SD	141.9±244.3	35.9±109.8	1.0–1.01	1.004	0.011*
CEA (ng/mL)	Mean±SD	33.9±62.2	11.5±34	1.0–1.02	1.010	0.020
Tumor location	Colonic/Rectal	22/11	92/37	0.55–2.82	1.243	0.602
Tumor size (cm)	Mean±SD	4.3±2.4	4.4±2	0.82–1.19	0.991	0.928
LAP and OPEN		17/16	67/62	0.41–1.87	0.871	0.723
Operative time (min)	Mean±SD	225.5±77.5	207.3±78.4	1.0–1.01	1.003	0.240
Blood loss (mL)	Mean±SD	171.2±117.5	120.4±103.8	1.00–1.01	1.004	0.022*
Transfusion (%)	Yes	6(18.2)	12(9.3)	0.75–6.29	2.167	0.155
Multivisceral resection (%)	Yes	3(9.1)	11(8.5)	0.28–4.09	1.073	0.918
Complications (%)	Yes	5(15.2)	21(16.3)	0.32–2.65	0.918	0.875
Number of LN resected	Median (range)	19(7–45)	17(5–53)	0.96–1.04	1.001	0.973
T stage	T1-T2	0	13(10.1)	-	-	0.007*
	T3 (R)	8(24.2)	66(51.2)	-	-
	T4a+T4b	25(75.8)	50(38.8)	1.72–9.91	4.125
N stage	N0 (R)	10(30.3)	66(51.2)	-	-	0.018*
	N1	6(18.2)	30(23.3)	0.44–3.97	1.32
	N2	17(51.5)	33(25.6)	1.4–8.25	3.4
TNM stage	I	0	11(8.5)	-	-	0.126
	II(R)	9(27.3)	56(43.4)	-	-
	III	24(72.7)	62(48.1)	1.03–5.62	2.409
Adjuvant chemotherapy	Yes	23(69.7)	90(69.8)	0.43–2.29	0.997	0.994

Table 7 Subgroup Analysis of the Risk Factor of Distant Metastasis of Colonic MA

Variable (Colonic MA)		Distant Metastasis N=22	No Distant Metastasis N=92	95% CI	OR	P-value
Age	Median (range)	67(24–82)	60(15–85)	0.99–1.05	1.018	0.291
Gender	Male/Female	16/6	47/45	0.92–7.11	2.553	0.073
Comorbidities (%)	Yes	9(40.9)	36(39.1)	0.42–2.78	1.077	0.878
ASA score	I(R)	8(36.4)	40(43.6)	-	-	0.504
	II	12(54.5)	38(41.3)	0.58–4.29	1.579
	III	2(9.1)	14(15.2)	0.14–3.77	0.714
CA199 (U/mL)	Mean±SD	165.1±283.3	39.6±128.5	1.00–1.01	1.003	0.022*
CEA (ng/mL)	Mean±SD	46.5±73.2	10.3±22.9	1.01–1.03	1.017	0.004*
Tumor location	Right/Left	15/7	54/38	0.25–1.78	0.663	0.415
Tumor size (cm)	Mean±SD	4.8±2.5	4.7±2.1	0.81–1.25	1.009	0.932
LAP and OPEN		9/13	47/45	0.26–1.7	0.663	0.393
Operative time (min)	Mean±SD	208±67.0	198.2±64	1.00–1.01	1.002	0.522
Blood loss (mL)	Mean±SD	147.7±113.6	123.7±101.1	1.00–1.01	1.002	0.333
Transfusion (%)	Yes	3(13.6)	7(7.6)	0.45–8.1	1.917	0.376
Multivisceral resection (%)	Yes	2(10.5)	10(10.9)	0.17–4.04	0.820	0.807
Complications (%)	Yes	4(18.2)	14(15.2)	0.36–4.21	1.238	0.732
Number of LN resected	Median (range)	18.5(7–45)	17(6–53)	0.95–1.05	1.000	0.998
T stage	T1-T2	0	7(7.6)	-	-	0.022*
	T3 (R)	5(22.7)	49(53.3)	-	-
	T4a+T4b	17(77.3)	36(39.1)	1.56–13.71	4.628
N stage	N0 (R)	5(22.7)	52(56.5)	-	-	0.006*
	N1	5(22.7)	21(22.8)	0.65–9.45	2.476
	N2	12(54.5)	19(20.7)	2.04–21.12	6.568
TNM stage	I	0	7(7.6)	-	-	0.019*
	II(R)	4(18.2)	46(50.0)	-	-
	III	18(81.8)	39(42.4)	1.66–17.01	5.308
Adjuvant chemotherapy	Yes	14(63.6)	64(69.6)	0.29–2.03	0.766	0.592

Table 8 Subgroup Analysis of the Risk Factor of Distant Metastasis of Rectal MA

Variable (Rectal MA)		Distant Metastasis N=11	No Distant Metastasis N=37	95% CI	OR	P-value
Age	Median (range)	56(42–76)	57(29–87)	0.95–1.05	0.994	0.804
Gender	Male/Female	7/4	16/21	0.57–9.22	2.297	0.241
Comorbidities (%)	Yes	4(36.4)	12(32.4)	0.29–4.87	1.19	0.808
ASA score	I(R)	5(45.5)	20(54.1)	-	-	0.826
	II	5(45.5)	13(35.1)	0.37–6.38	1.538
	III	1(9.1)	4(10.8)	0.09–11.03	1.000
CA199 (U/mL)	Mean±SD	95.5±137.8	26.8±31.9	1.00–1.03	1.013	0.050*
CEA (ng/mL)	Mean±SD	8.8±9.5	14.2±52.7	0.98–1.02	0.996	0.743
Tumor size (cm)	Mean±SD	3.4±2	3.5±1.5	0.65–1.53	0.994	0.977
LAP and OPEN		7/4	20/17	0.37–5.96	1.487	0.575
Operative time (min)	Mean±SD	260.5±88.3	230.0±103.7	1.00–1.01	1.003	0.382
Blood loss (mL)	Mean±SD	218.2±115.82	112.2±111.2	1.00–1.01	1.007	0.027*
Transfusion (%)	Yes	3(27.3)	5(13.5)	0.47–12.22	2.400	0.292
Multivisceral resection (%)	Yes	1(9.1)	1(2.7)	0.21–62.8	3.600	0.380
Complications (%)	Yes	1(9.1)	7(18.9)	0.05–3.92	0.429	0.453
Number of LN resected	Median (range)	19(9–24)	15(5–44)	0.93–1.1	1.007	0.861
T stage	T1-T2	0	6(16.2)	-	-	0.309
	T3 (R)	3(27.3)	17(45.9)	-	-
	T4a+T4b	8(72.7)	14(37.8)	0.72–14.57	3.238
N stage	N0 (R)	5(39.6)	14(37.8)	-	-	0.579
	N1	1(20.8)	9(24.3)	0.03–3.12	0.311
	N2	5(39.6)	15(37.8)	0.24–4.24	1.000
TNM stage	I	0	4(10.8)	-	-	0.660
	II(R)	5(45.5)	10(27.0)	-	-
	III	6(54.5)	23(62.2)	0.13–2.12	0.522
Adjuvant chemotherapy	Yes	9(81.8)	26(70.3)	0.35–10.28	1.904	0.454

Note: *P<0.05.

Abbreviations: ASA, American Society of Anesthesiology; CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; OR, risk ratio; R, reference group; LAP, laparoscopic surgery group; OPEN, open surgery group; LN, lymph nodes.

Table 9 Multivariate Analysis of the Significant Independent Predictors for Local Recurrence of MAC

Variable (MAC)	95% CI	OR	P -value
Blood loss (mL)	1.00–1.01	1.002	0.305
Transfusion	1.07–16.30	4.175	0.04*
N2 stage	2.13–13.13	5.291	0.000*

Table 10 Multivariate Analysis of the Significant Independent Predictors for Local Recurrence of Colonic MA

Variable (Colonic MA)	95% CI	OR	P-value
Blood loss (mL)	1.00–1.01	1.005	0.124
Transfusion	0.09–8.97	0.914	0.939
T4 stage	0.95–7.81	2.729	0.061
N1 stage	0.26–4.12	1.033	0.963
N2 stage	1.15–11.27	3.592	0.028*

Table 11 Multivariate Analysis of the Significant Independent Predictors for Local Recurrence of Rectal MA

Variable (Rectal MA)	95% CI	OR	P -value
Transfusion	1.51–40.81	7.857	0.014*

Table 12 Multivariate Analysis of the Significant Independent Predictors for Distant Metastasis of MAC

Variable (MAC)	95% CI	OR	P-value
Male sex	1.01–6.88	2.63	0.049*
CA199 (U/mL)	1.00–1.01	1.003	0.02*
CEA (ng/mL)	1.00–1.02	1.005	0.322
Blood loss (mL)	1.00–1.01	1.004	0.053
T4 stage	1.47–10.94	4.006*	0.007*
N1 stage	0.22–3.19	0.832	0.789
N2 stage	0.79–5.73	2.13	0.134

Notes: *P<0.05. The risk ratio (OR) of T4 stage is relative to T3 stage. The risk ratio (OR) of N1 or N2 stage is relative to N0 stage.

Abbreviations: CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; OR, risk ratio; CI, confidence interval.

Table 13 Multivariate Analysis of the Significant Independent Predictors for Distant Metastasis of Colonic MA

Variable (Colonic MA)	95% CI	OR	P-value
CA199 (U/mL)	1.00–1.01	1.002	0.273
CEA (ng/mL)	1.00–1.03	1.013	0.113
T4 stage	1.04–12.66	3.627*	0.043*
N stage	-	-	0.41
TNM stage	-	-	0.999

Table 14 Multivariate Analysis of the Significant Independent Predictors for Distant Metastasis of Rectal MA

Variable (Rectal MA)	95% CI	OR	P -value
CA199 (U/mL)	1.00–1.03	1.011	0.11
Blood loss (mL)	1.00–1.01	1.006	0.091

*P<0.05. The risk ratio (OR) of T4 stage is relative to T3 stage. The risk ratio (OR) of N1 or N2 stage is relative to N0 stage.

Abbreviations: CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; OR, risk ratio; CI, confidence interval.