Longitudinal evolution of low anterior resection syndrome in ultra-low rectal cancer: A trend analysis of a propensity-matched cohort

Table 1 Comparison of baseline characteristics in the pre-matched cohort (n = 403), n (%)

Characteristic	n	Ultra-low group (≤ 3 cm; n = 114)	Non-ultra-low group (> 3 cm; n = 289)	Test statistic	P value
Age (year)	403	57.24 ± 11.74	60.73 ± 10.87	t = -2.839	0.005
Gender
Female	168	42 (36.8)	126 (43.6)	χ2 = 1.535	0.215
Male	235	72 (63.2)	163 (56.4)
BMI (kg/m2)		23.67 ± 3.21	23.33 ± 3.02	t = 1.008	0.314
Blood type
A	130	38 (33.3)	92 (31.8)	χ2 = 0.326	0.955
AB	36	10 (8.8)	26 (9.0)
B	91	27 (23.7)	64 (22.1)
O	146	39 (34.2)	107 (37.0)
Diabetes
No	336	95 (83.3)	241 (83.4)	χ2 = 0.000	0.989
Yes	67	19 (16.7)	48 (16.6)
Hypertension
No	281	80 (70.2)	201 (69.6)	χ2 = 0.015	0.902
Yes	122	34 (29.8)	88 (30.4)
Tumor pathology
Adenocarcinoma	364	101 (88.6)	263 (91.0)	χ2 = 0.832	0.842
Mucinous adenocarcinoma	34	11 (9.6)	23 (8.0)
Neuroendocrine carcinoma	2	1 (0.9)	1 (0.3)
Signet ring cell carcinoma	3	1 (0.9)	2 (0.7)
TNM
0	28	14 (12.3)	14 (4.8)	χ2 = 18.288	0.001
I	89	35 (30.7)	54 (18.7)
II	114	22 (19.3)	92 (31.8)
III	115	26 (22.8)	89 (30.8)
IV	57	17 (14.9)	40 (13.8)
Postoperative complications
None	384	110 (96.5)	274 (94.8)	χ2 = 8.413	0.394
Anastomotic bleeding	9	2 (1.8)	7 (2.4)
Anastomotic leaks including invisible leaks	2	0 (0.0)	2 (0.7)
Stoma obstruction or intestinal obstruction	1	1 (0.9)	0 (0.0)
Incisional infection or incisional hernia	5	1 (0.9)	4 (1.4)
Other: e.g. high blood pressure, cardiac arrhythmia, deep vein thrombosis of the lower limbs	2	0 (0.0)	2 (0.6)
Neoadjuvant radiotherapy
No	287	47 (41.2)	240 (83.0)	χ2 = 69.738	< 0.001
Yes	116	67 (58.8)	49 (17.0)
Neoadjuvant chemotherapy
No	169	26 (22.8)	143 (49.5)	χ2 = 23.888	< 0.001
Yes	234	88 (77.2)	146 (50.5)

BMI: Body mass index.

Table 2 Comparison of baseline characteristics in the matched cohort (n = 220), n (%)

Characteristic	n	Ultra-low group (≤ 3 cm; n = 110)	Non-ultra-low group (> 3 cm; n = 110)	Test statistic	P value
Age (year)	220	58.08 ± 10.978	64.47 ± 11.242	t = 4.266	0.576
Gender
Female	95	41 (37.3)	54 (49.1)	χ2 = 3.131	0.077
Male	125	69 (62.7)	56 (50.9)
BMI (kg/m2)		23.75 ± 3.14	23.23 ± 2.99	t = -1.259	0.933
Blood type
A	74	37 (33.6)	37 (33.6)	χ2 = 1.530	0.675
AB	16	10 (9.1)	6 (5.5)
B	50	26 (23.6)	24 (21.8)
O	80	37 (33.6)	43 (39.1)
Diabetes
No	176	91 (82.7)	85 (77.3)	χ2 = 1.023	0.312
Yes	44	19 (17.3)	25 (22.7)
Hypertension
No	150	76 (69.1)	74 (67.3)	χ2 = 0.084	0.772
Yes	70	34 (30.9)	36 (32.7)
Tumor pathology
Adenocarcinoma	202	97 (88.2)	105 (95.5)	χ2 = 4.583	0.205
Mucinous adenocarcinoma	15	11 (10.0)	4 (3.6)
Neuroendocrine carcinoma	1	1 (0.9)	0 (0.0)
Signet ring cell carcinoma	2	1 (0.9)	1 (0.9)
TNM
0	27	13 (11.8)	14 (12.7)	χ2 = 25.940	< 0.001
I	82	32 (29.1)	50 (45.5)
II	57	22 (20.0)	35 (31.8)
III	33	26 (23.6)	7 (6.4)
IV	21	17 (15.5)	4 (3.6)
Postoperative complications
No	210	106 (96.4)	104 (94.5)	χ2 = 0.419	0.517
Yes	10	4 (3.6)	6 (5.5)
Neoadjuvant radiotherapy
No	136	46 (41.8)	90 (81.8)	χ2 = 37.283	< 0.001
Yes	84	64 (58.2)	20 (18.2)
Neoadjuvant chemotherapy
No	102	26 (23.6)	76 (69.1)	χ2 = 45.696	< 0.001
Yes	118	84 (76.4)	34 (30.9)

BMI: Body mass index.

Table 3 Univariate analysis of low anterior resection syndrome occurrence in the matched cohort (n = 220), n (%)

Time point and LARS occurrence	1 month		3 months		6 months		9 months		12 months
	Yes	No	Yes	No	Yes	No	Yes	No	Yes	No
Total	140 (63.6)	80 (36.3)	101 (45.9)	119 (54.1)	88 (40.0)	132 (60.0)	62 (8.2)	158 (71.8)	49 (22.3)	171 (77.7)
Ultra-low group	83 (75.5)	27 (24.5)	64 (58.2)	46 (41.8)	56 (50.9)	54 (49.1)	39 (35.5)	71 (64.5)	33 (30.0)	77 (70.0)
Non-ultra-low group	57 (51.8)	53 (48.2)	37 (33.6)	73 (66.4)	32 (29.1)	78 (70.9)	23 (20.9)	87 (79.1)	16 (14.5)	94 (85.5)
χ2	13.279		13.344		10.909		5.749		7.588
Coefficient of contingency	0.239		0.239		0.217		0.160		0.183
P value	< 0.001		< 0.001		0.001		0.016		0.006

LARS: Low anterior resection syndrome.

Table 4 Multivariable logistic regression analysis of risk factors for low anterior resection syndrome at 1 month postoperatively

	β	SE	Wald χ2	df	P value	Exp(B)	95%CI for Exp(B)
							Lower	Upper
Tumor location (> 3 cm)	0.824	0.367	5.055	1	0.025	2.280	1.111	4.678
Gender (female)	0.210	0.321	0.425	1	0.514	1.233	0.657	2.315
Age (< 61.28 years)	-0.483	0.331	2.127	1	0.145	0.617	0.322	1.181
Blood type (A)			1.964	3	0.580
AB	-0.582	0.417	1.952	1	0.162	0.559	0.247	1.264
B	-0.237	0.639	0.137	1	0.711	0.789	0.225	2.762
O	-0.270	0.365	0.544	1	0.461	0.764	0.373	1.563
BMI (< 23.42 kg/m2)	0.330	0.315	1.092	1	0.296	1.390	0.749	2.579
Diabetes (no)	0.232	0.401	0.334	1	0.563	1.261	0.575	2.765
Hypertension (no)	-0.224	0.339	0.436	1	0.509	0.799	0.411	1.553
Tumor pathology (adenocarcinoma)			1.270	3	0.736
Neuroendocrine carcinoma	19.502	40192.969	0.000	1	1.000	294868049.288	0.000
Signet ring cell carcinoma	19.821	28180.122	0.000	1	0.999	405570330.801	0.000
Mucinous adenocarcinoma	-0.820	0.728	1.270	1	0.260	0.440	0.106	1.834
TNM (0)			1.333	4	0.856
I	-0.127	0.522	0.059	1	0.808	0.881	0.317	2.449
II	-0.150	0.548	0.075	1	0.785	0.861	0.294	2.521
III	-0.356	0.633	0.315	1	0.574	0.701	0.203	2.424
IV	0.442	0.761	0.337	1	0.562	1.555	0.350	6.912
Postoperative complications (no)	-0.574	0.699	0.674	1	0.412	0.563	0.143	2.216
Neoadjuvant chemotherapy (no)	0.197	0.442	0.199	1	0.656	1.217	0.512	2.893
Neoadjuvant radiotherapy (no)	-0.177	0.460	0.149	1	0.700	0.838	0.340	2.062
Constant	1.273	0.928	1.883	1	0.170	3.572

Age and body mass index were converted into binary variables using the mean as the cutoff. Reference categories are shown in parentheses. BMI: Body mass index.

Table 5 Multivariable logistic regression analysis of risk factors for low anterior resection syndrome at 3 months postoperatively

	β	SE	Wald χ2	df	P value	Exp(B)	95%CI for Exp(B)
							Lower	Upper
Tumor location (> 3 cm)	1.166	0.362	10.398	1	0.001	3.21	1.58	6.52
Gender (female)	0.425	0.317	1.799	1	0.18	1.529	0.822	2.843
Age (< 61.28 years)	-0.217	0.323	0.451	1	0.502	0.805	0.427	1.516
Blood type (A)			1.618	3	0.655
AB	-0.251	0.402	0.389	1	0.533	0.778	0.354	1.712
B	-0.476	0.614	0.601	1	0.438	0.621	0.187	2.069
O	-0.424	0.356	1.416	1	0.234	0.654	0.326	1.316
BMI (< 23.42 kg/m2)	0.078	0.309	0.064	1	0.801	1.081	0.59	1.98
Diabetes (no)	0.214	0.386	0.308	1	0.579	1.239	0.582	2.637
Hypertension (no)	-0.309	0.334	0.858	1	0.354	0.734	0.382	1.412
Tumor pathology (adenocarcinoma)			0.357	3	0.949
Neuroendocrine carcinoma	-21.921	40192.97	0	1	1	0	0
Signet ring cell carcinoma	0.172	1.63	0.011	1	0.916	1.188	0.049	29.01
Mucinous adenocarcinoma	-0.324	0.611	0.282	1	0.595	0.723	0.218	2.393
TNM (0)			8.403	4	0.078
I	0.003	0.507	0	1	0.995	1.003	0.371	2.71
II	-0.522	0.534	0.954	1	0.329	0.594	0.208	1.691
III	-1.18	0.614	3.698	1	0.054	0.307	0.092	1.023
IV	-1.258	0.673	3.495	1	0.062	0.284	0.076	1.063
Postoperative complications (no)	-0.427	0.71	0.361	1	0.548	0.653	0.162	2.625
Neoadjuvant chemotherapy (no)	0.572	0.432	1.753	1	0.185	1.772	0.76	4.131
Neoadjuvant radiotherapy (no)	-0.407	0.435	0.873	1	0.35	0.666	0.284	1.562
Constant	-0.027	0.825	0.001	1	0.974	0.973

Age and body mass index were converted into binary variables using the mean as the cutoff. Reference categories are shown in parentheses. BMI: Body mass index.

Table 6 Multivariable logistic regression analysis of risk factors for low anterior resection syndrome at 6 months postoperatively

	β	SE	Wald χ2	df	P value	Exp(B)	95%CI for Exp(B)
							Lower	Upper
Tumor location (> 3 cm)	0.953	0.363	6.896	1	0.009	2.594	1.273	5.284
Gender (female)	-0.161	0.319	0.255	1	0.614	0.851	0.455	1.592
Age (< 61.28 years)	-0.097	0.323	0.09	1	0.764	0.908	0.482	1.71
Blood type (A)			2.487	3	0.478
AB	-0.118	0.409	0.083	1	0.773	0.889	0.399	1.981
B	0.891	0.623	2.048	1	0.152	2.438	0.719	8.264
O	0.114	0.357	0.102	1	0.749	1.121	0.557	2.257
BMI (< 23.42 kg/m2)	-0.194	0.313	0.384	1	0.535	0.824	0.447	1.52
Diabetes (no)	0.134	0.394	0.115	1	0.734	1.143	0.528	2.472
Hypertension (no)	-0.767	0.345	4.952	1	0.026	0.464	0.236	0.913
Tumor pathology (adenocarcinoma)			0.002	3	1
Neuroendocrine carcinoma	-21.827	40192.97	0	1	1	0	0
Signet ring cell carcinoma	-19.705	26717.346	0	1	0.999	0	0
Mucinous adenocarcinoma	-0.027	0.604	0.002	1	0.965	0.974	0.298	3.183
TNM (0)			2.583	4	0.63
I	0.042	0.5	0.007	1	0.933	1.043	0.391	2.779
II	-0.224	0.526	0.182	1	0.67	0.799	0.285	2.242
III	-0.285	0.598	0.228	1	0.633	0.752	0.233	2.426
IV	-0.88	0.683	1.66	1	0.198	0.415	0.109	1.582
Postoperative complications (no)	-0.351	0.759	0.213	1	0.644	0.704	0.159	3.118
Neoadjuvant chemotherapy (no)	-0.013	0.444	0.001	1	0.977	0.987	0.414	2.356
Neoadjuvant radiotherapy (no)	0.427	0.433	0.974	1	0.324	1.533	0.656	3.582
Constant	-0.485	0.822	0.348	1	0.555	0.616

Age and body mass index were converted into binary variables using the mean as the cutoff. Reference categories are shown in parentheses. BMI: Body mass index.

Table 7 Multivariable logistic regression analysis of risk factors for low anterior resection syndrome at 9 months postoperatively

	β	SE	Wald χ2	df	P value	Exp(B)	95%CI for Exp(B)
							Lower	Upper
Tumor location (> 3 cm)	0.859	0.386	4.958	1	0.026	2.362	1.108	5.032
Gender (female)	-0.027	0.337	0.006	1	0.937	0.974	0.503	1.883
Age (< 61.28 years)	0.083	0.348	0.057	1	0.811	1.087	0.55	2.148
Blood type (A)			2.662	3	0.447
AB	-0.629	0.443	2.018	1	0.155	0.533	0.224	1.27
B	0.155	0.614	0.064	1	0.8	1.168	0.351	3.89
O	-0.345	0.374	0.856	1	0.355	0.708	0.34	1.472
BMI (< 23.42 kg/m2)	-0.096	0.331	0.083	1	0.773	0.909	0.475	1.74
Diabetes (no)	0.566	0.405	1.959	1	0.162	1.762	0.797	3.893
Hypertension (no)	-0.383	0.361	1.122	1	0.289	0.682	0.336	1.384
Tumor pathology (adenocarcinoma)			0.003	3	1
Neuroendocrine carcinoma	-20.742	40192.97	0	1	1	0	0
Signet ring cell carcinoma	-19.65	27972.494	0	1	0.999	0	0
Mucinous adenocarcinoma	0.038	0.665	0.003	1	0.955	1.038	0.282	3.821
TNM (0)			1.483	4	0.83
I	-0.064	0.512	0.015	1	0.901	0.938	0.344	2.561
II	-0.486	0.555	0.766	1	0.382	0.615	0.207	1.827
III	-0.427	0.621	0.474	1	0.491	0.652	0.193	2.202
IV	-0.428	0.699	0.375	1	0.54	0.652	0.166	2.563
Postoperative complications (no)	0.107	0.75	0.02	1	0.886	1.113	0.256	4.845
Neoadjuvant chemotherapy (no)	-0.303	0.479	0.401	1	0.526	0.738	0.289	1.887
Neoadjuvant radiotherapy (no)	0.407	0.466	0.763	1	0.382	1.503	0.603	3.747
Constant	-0.911	0.886	1.056	1	0.304	0.402

Age and body mass index were converted into binary variables using the mean as the cutoff. Reference categories are shown in parentheses. BMI: Body mass index.

Table 8 Multivariable logistic regression analysis of risk factors for low anterior resection syndrome at 12 months postoperatively

	β	SE	Wald χ2	df	P value	Exp(B)	95%CI for Exp(B)
							Lower	Upper
Tumor location (> 3 cm)	1.077	0.425	6.41	1	0.011	2.935	1.275	6.756
Gender (female)	-0.038	0.368	0.011	1	0.918	0.963	0.468	1.981
Age (< 61.28 years)	0.004	0.38	0	1	0.992	1.004	0.476	2.115
Blood type (A)			5.134	3	0.162
AB	-0.934	0.52	3.222	1	0.073	0.393	0.142	1.09
B	0.616	0.638	0.933	1	0.334	1.851	0.53	6.459
O	-0.173	0.405	0.182	1	0.669	0.841	0.38	1.861
BMI (< 23.42 kg/m2)	-0.27	0.365	0.548	1	0.459	0.763	0.373	1.56
Diabetes (no)	0.466	0.449	1.081	1	0.299	1.594	0.662	3.841
Hypertension (no)	-0.438	0.396	1.226	1	0.268	0.645	0.297	1.401
Tumor pathology (adenocarcinoma)			1.239	3	0.744
Neuroendocrine carcinoma	-21.555	40192.97	0	1	1	0	0
Signet ring cell carcinoma	-19.393	28190.679	0	1	0.999	0	0
Mucinous adenocarcinoma	-0.73	0.655	1.239	1	0.266	0.482	0.133	1.742
TNM (0)			2.71	4	0.608
I	0.611	0.614	0.992	1	0.319	1.843	0.553	6.135
II	0.573	0.642	0.797	1	0.372	1.773	0.504	6.239
III	-0.157	0.739	0.045	1	0.832	0.855	0.201	3.635
IV	0.105	0.801	0.017	1	0.895	1.111	0.231	5.344
Postoperative complications (no)	-0.098	0.877	0.012	1	0.911	0.907	0.162	5.061
Neoadjuvant chemotherapy (no)	-0.35	0.518	0.458	1	0.499	0.705	0.255	1.943
Neoadjuvant radiotherapy (no)	0.494	0.503	0.964	1	0.326	1.638	0.611	4.39
Constant	-1.162	0.951	1.493	1	0.222	0.313

Age and body mass index were converted into binary variables using the mean as the cutoff. Reference categories are shown in parentheses. BMI: Body mass index.

Table 9 Summary of generalized estimating equation analysis for overall group, time, and interaction effects on low anterior resection syndrome

	Wald χ2	P value
Group effect	19.239	< 0.001
Time effect	86.309	< 0.001
Interaction effect	1.063	0.900

Table 10 Multivariable generalized estimating equation parameter estimates for predictors of low anterior resection syndrome occurrence over 12 months

	β	95%CI		Wald χ2	P value	Exp(B)	95%CI for Exp(B)
		Lower	Upper				Lower	Upper
	0.073	-0.301	0.447	0.145	0.703	1.075	0.74	1.563
Tumor distance from dentate line > 3 cm	0					1
Tumor distance from dentate line ≤ 3 cm	1.05	0.477	1.623	12.901	< 0.001	2.858	1.611	5.070
Post-operative time (month)
1	0					1
3	-0.752	-1.154	-0.35	13.456	< 0.001	0.471	0.315	0.704
6	-0.964	-1.417	-0.511	17.372	< 0.001	0.381	0.242	0.600
9	-1.403	-1.94	-0.866	26.237	< 0.001	0.246	0.144	0.421
12	-1.843	-2.465	-1.222	33.832	< 0.001	0.158	0.085	0.295

This generalized estimating equation model was adjusted for the following covariates: Age, sex, body mass index, neoadjuvant chemoradiotherapy, and TNM stage. The reference group for the “group” effect is the non-ultra-low group (> 3 cm). The reference time point for the “time” effect is 1 month postoperatively.