Machine learning for modeling and identifying risk factors of pancreatic fistula

Table 1 Clinical parameters

Groups parameters	All patients	No fistula	No fistula and biochemical leak	Fistula B/C and biochemical leak	Biochemical leak	Fistula B/C
Qualitative disease and treatment parameters (%)
Blood vessel resection	15.3	19.8	16.8	3.3	7.1	0
Perineural invasion	46.9	55.6	52.6	23.3	14.3	31.3
Vascular invasion	48.7	59.3	54.7	20	14.3	25
Enterostomy	23.1	76.2	24.7	25	50	14.3
Roux anastomosis	36.3	87.9	37.7	20	0	28.6
Tumor morphology (%)
Benign tumor	2.02	1.4	2.3	4	10	0
Neuroendocrine cancer	10.1	6.8	9.5	20	30	13.3
Epithelial malignant tumor	87.9	91.9	88.1	76	60	86.7
Disease stage (%)
I	17	16.9	16.5	17.2	14.3	20
IIa	24	22.5	22.4	27.6	21.4	33.3
IIb	30	29.6	30.6	31	35.7	26.7
III	20	21.1	21.2	17.2	21.4	13.3
IV	9	9.9	9.4	6.9	7.1	6.7
Quantitative parameters, median (interquartile range)
Age	61 (53.75, 66)	62 (54.75, 68)	60.5 (54, 66)	56.5 (46, 62.75)	61 (50.75, 64.75)	54.5 (46, 59.5)
Blood amylase 3-5 days, mM	50 (29.5, 91.7)	44 (24, 70)	51 (30, 91.6)	81 (37, 138)	45.5 (32.5, 97.15)	91.8 (66.5, 246)
Drain amylase 3-5 days, mM	81 (17.75, 1243)	23 (13.5, 44.5)	81 (19.25, 1341)	2445 (628.2; 3725)	932.5 (370.25, 1653.75)	4065 (3707, 5000)
Leukocytes 2-3 days, 109/L	13.1(9.25, 17.45)	12.4 (9.225, 15.7)	12.8 (9.3, 17.2)	16.7 (11.85, 20.35)	16.7 (11.7, 20.8)	14.85 (12.1, 19.025)
Tumor size, mm3	12.5 (5.1, 32)	5 (3, 7.25)	12.5 (5.25, 36.26)	3 (2.5, 4.375)	3 (2.5, 3.75)	3 (2.95, 4.5)
BMI, kg/m2	25.26 (23.1, 28.21)	25.3 (23, 28.1)	25.3 (23, 28.1)	25.8 (23, 28.1)	24.5 (21.6, 27.5)	25.9 (23.9, 28.2)
Pancreatic duct diameter, mm	4.5 (2.5, 7)	5 (3, 7.25)	4.5 (2.5, 7)	3 (2.5, 4.36)	3 (2.5, 3.75)	3 (2.95, 4.5)

BMI: Body mass index.

Table 2 Correlation matrix

Correlated groups parameters	No fistula-0; biochemical leak-1; fistula-2		No fistula and biochemical leak- 0; fistula B/C-1		No fistula-0; biochemical leak and fistula B/C-1
	r value	P value	r value	P value	r value	P value
Age	-0.23	0.021a	-0.24	0.014b	-0.21	0.031a
Enterostomy	-0.05	0.637	-0.06	0.536	-0.04	0.676
Roux anastomosis	-0.2	0.064	-0.09	0.409	-0.22	0.04
Blood vessel resection	-0.13	0.226	-0.2	0.071	-0.12	0.288
Disease stage	-0.12	0.251	-0.11	0.3	-0.12	0.259
Blood amylase 3-5 days	0.25	0.017b	0.24	0.024a	0.24	0.02a
Drain amylase 3-5 days	0.74	8.37 × 10-9b	0.51	0.0004b	0.7	1.56 × 107b
Leukocytes 2-3 days	0.16	0.121	0.09	0.371	0.17	0.1
Tumor morphology	0.16	0.127	0.12	0.222	0.16	0.117
Tumor size, mm3	-0.01	0.934	-0.06	0.571	0.004b	0.975
Perineural invasion	-0.31	0.002b	-0.18	0.062	-0.33	0.001b
Vascular invasion	-0.32	0.001b	-0.17	0.088	-0.35	0.0003b
BMI	-0.04	0.239	0.001	0.672	-0.04	0.382
Pancreatic duct diameter	-0.08	0.437	0.03	0.743	-0.11	0.293

^aP < 0.05.

^bP < 0.0167 (Bonferroni correction, P < α/3).

BMI: Body mass index. The qualitative parameters were studied in numerical equivalent. For disease stages I, IIa, IIb, III, and IV the values were considered 1, 2, 2.5, 3, and 4, respectively. Tumor morphological types were divided into numerical classes by prognosis, from positive to negative: Benign tumor-0, neuroendocrine tumor-1, and adenocarcinoma-2[12,57].

Table 3 Quality of binary models, mean ± SD

Algorithm model	Logistic regression	Random forest	CatBoost
5-fold cross validation ROC AUC1
Pre- and intraoperative data model	0.71 ± 0.11	0.77 ± 0.08	0.74 ± 0.1
3-5 days after surgery	0.86 ± 0.09	0.8 ± 0.11	0.87 ± 0.07
5-fold cross validation ROC AUC2
Pre- and intraoperative data model	0.72	0.74	0.74
3-5 days after surgery	0.81	0.81	0.86

¹mean ± SD receiver operating characteristic area under the curve of each fold of cross-validation, n = 20% of the initial dataset.

²Integral receiver operating characteristic area under the curve calculated with all false positive rates obtained in 5-fold cross-validation. True positive rate was obtained from the initial dataset.

ROC: Receiver operating characteristic; AUC: Area under the curve.

Table 4 Quality of three-dimensional models, mean ± SD

Algorithm model	Logistic regression	Random forest	CatBoost
5-fold cross validation ROC AUC1
Pre- and intraoperative data model	0.71 ± 0.088	0.67 ± 0.09	0.68 ± 0.07
3-5 days after surgery	0.77 ± 0.145	0.726 ± 0.145	0.74 ± 0.16
5-fold cross validation ROC AUC2
Pre- and intraoperative data model: Fistula B/C vs other classes	0.77	0.73	0.85
3-5 days after surgery: Fistula B/C vs other classes	0.76	0.77	0.86
Pre- and intraoperative data model: Fistula B/C vs biochemical leak	0.73	0.45	0.74
3-5 days after surgery: Fistula B/C vs biochemical leak	0.39	0.44	0.47

¹mean ± SD receiver operating characteristic area under the curve of each fold of cross-validation, n = 20% of the initial dataset.

²Integral receiver operating characteristic area under the curve calculated with all false positive rates obtained in 5-fold cross-validation. True positive rate was obtained from the initial dataset. These metrics were calculated for the model’s ability to distinguish different classes.

ROC: Receiver operating characteristic; AUC: Area under the curve.