Optimizing prediction models for pancreatic fistula after pancreatectomy: Current status and future perspectives

Table 1 Reported risk factors for postoperative pancreatic fistula after pancreaticoduodenectomy

Stage	Factors
Preoperative	(1) Sex, (2) age, (3) BMI, (4) weight, (5) weight loss, (6) smoking history, (7) hypertension, (8) diabetes mellitus, (9) history of acute pancreatitis, (10) history of abdominal surgery, (11) chronic steroid use, (12) ASA score, (13) preoperative biliary drainage, (14) preoperative chemotherapy, (15) albumin, (16) bilirubin, (17) alanine transaminase, (18) creatine, (19) tumor site, (20) MPD diameter, (21) MPD index1, (22) pancreatic thickness, (23) pancreatic density, (24) pancreatic texture, (25) relation with PV on CT, (26) pancreatic density index, (27) intra-abdominal fat thickness, (28) visceral adipose tissue, (29) total adipose tissue, (30) sarcopenic obesity, (31) L3 subcutaneous fat area, (32) pancreatic remnant volume, (33) stump area, (34) fat score, (35) atrophy score, (36) A/L ratio, (37) subcutaneous fat index, (38) radiomics score, (39) combined radiomics score, (40) liver density, (41) muscle attenuation, (42) PS SIratio, (43) PM SIratio, (44) fat mass at BIVA, (45) SWV value of pancreas, (46) MIPD experience, (47) preoperative diagnosis
Intraoperative	(A) MPD diameter, (B) pancreatic texture, (C) operating time, (D) estimated blood loss, (E) transfusion, (F) intraoperative colloid infusion, (G) surgical approach, (H) minimally invasive approach, (I) open conversion, (J) pancreatic anastomosis, (K) gastrojejunostomy, (L) extended lymphadenectomy, (M) venous resection, (N) nasojejunal feeding tube
Postoperative	(a) Postoperative DFA, (b) change of postoperative DFA, (c) WBC on POD1, (d) change of postoperative WBC, (e) neutrophil on POD3, (f) postoperative CRP, (g) temperature on POD3, (h) postoperative albumin, (i) albumin difference2, (j) postoperative CRP/albumin, (k) serum creatinine on POD1, (l) hyperamylasemia on POD1-2, (m) serum lipase on POD1, (n) DFL on POD1, (o) pathology, (p) PV invasion, (q) pancreatic fibrosis, (r) pancreatic steatosis, (s) deep surgical site infection, (t) DGE

¹Main pancreatic duct index indicates the ratio of main pancreatic duct diameter to pancreatic thickness at the transection site.

²Albumin difference indicates the difference of albumin level between preoperative and postoperative day 1.

A/L ratio: Arterial/late phase pancreas computed tomography attenuation value ratio; ASA: American Society of Anesthesiologists; BIVA: Bioimpedance vector analysis; BMI: Body mass index; CRP: C-reactive protein; CT: Computed tomography; DFA: Drain fluid amylase; DFL: Drain fluid lipase; DGE: Delayed gastric emptying; L3: The third lumbar vertebra; MIPD: Minimally invasive pancreaticoduodenectomy; MPD: Main pancreatic duct; POD: Postoperative day; PV: Portal vein; SWV: Shear wave velocity; PM SIratio: Signal intensity ratio of pancreas to muscle; PS SIratio: Signal intensity ratio of pancreas to spleen; WBC: White blood cell.

Table 2 Reported risk factors for postoperative pancreatic fistula after distal pancreatectomy

Preoperative	Intraoperative	Postoperative
(1) Age	(A) Epidural use	(a) CRP on POD1
(2) BMI	(B) Operating time	(b) DFA on POD1
(3) Diabetes mellitus	(C) Estimated blood loss	(c) DFA on POD3
(4) Coronary artery disease	(D) Transfusion	(d) Change of postoperative DFA
(5) ASA score	(E) Pancreatic texture	(e) Pathology
(6) Albumin	(F) Transection site
(7) MPD diameter	(G) Splenectomy
(8) Pancreatic thickness	(H) Vascular resection
(9) Pancreatic neck major diameter
(10) Pancreatic neck minor diameter
(11) Predicted pancreatic neck area

ASA: American Society of Anesthesiologists; BMI: Body mass index; CRP: C-reactive protein; DFA: Drain fluid amylase; MPD: Main pancreatic duct; POD: Postoperative day.

Table 3 Reported risk factors for postoperative pancreatic fistula after central pancreatectomy

Preoperative	Intraoperative	Postoperative
(1) Sex	(A) Operating time	(a) Pathology
(2) BMI	(B) Pancreatic texture
(3) Diabetes mellitus	(C) Transection site
(4) Cephalic MPD diameter	(D) Pancreatic anastomosis
(5) Distal MPD diameter
(6) Pancreatic thickness

BMI: Body mass index; MPD: Main pancreatic duct.

Table 4 Preoperative prediction models of postoperative pancreatic fistula after pancreaticoduodenectomy

Ref.	Year	Country	Center	Study period	Design cohort	CR-POPF (%)	Variables5	C-index/AUC (95%CI)	Validation
Wellner et al[13]	2010	Germany	Single	2006-2008	62	30.64	(2)(5)(6)(9)(47)		Internal
Yamamoto et al[14]	2011	Japan	Single	2004-2007	279	36.9	(1)(21)(25)(27)(47)	0.808 (0.757-0.860)	Internal
Roberts et al[15]	2014	United Kingdom	Single1	2007-2012	217	22.14	(3)(20)	0.832 (0.768-0.897)	Internal
Casadei et al[42]	2015	Italy	Single	2008-2012	2082	20.2	(3)(20)(47)
Zhang et al[43]	2018	China	Single		80	42.54	(38)	0.825 (0.736-0.913)	Internal
Shi et al[44]	2020	China	Multi	2009-2019	718	15.6	(20)(32)(33)(34)(35)	0.729 (0.678-0.775)	External
Yu et al[17]	2021	China	Single	2016-2018	124	25.8	(21)(23)	0.775 (0.687-0.862)	Internal
Lin et al[19]	2021	China	Single	2013-2019	175	21.1	(38)	0.801 (0.719-0.884)	Internal
							(39)	0.871 (0.816-0.926)
Tang et al[45]	2021	China	Single	2013-2019	239	19.7	(3)(20)(36)	0.823 (0.769-0.877)
Lapshyn et al[46]	2021	Germany	Single1	2012-2018	120	193	(1)(20)(22)	0.808 (0.726-0.874)	Internal
Perri et al[41]	2021	Italy	Multi	2017-2019	566	20	(3)(20)	0.70 (0.63-0.77)	External
Savin et al[47]	2021	Romania	Single	2015-2020	78	28.2	(20)(23)(32)	0.846 (0.694-0.941)
							(20)(32)(40)	0.774 (0.599-0.850)
Skawran et al[48]	2021	Switzerland	Single	2008-2018	62	27.4	(43)	0.75 (0.63-0.84)
Box et al[49]	2021	United States	Single	2013-2018	220	15.94	(3)(20)(37)	0.822
							(3)(20)(26)	0.757
							(3)(20)(26)(37)	0.844
Kolbinger et al[50]	2022	Germany	Single	2012-2021	195	28.7	(20)(24)(47)	0.82	Internal
							(20)(24)(32)(47)	0.83
Maqueda González et al[51]	2022	Spain	Single	2010-2019	103	30.1	(20)(29)	0.78 (0.68-0.87)
Zou et al[52]	2023	China	Single	2015-2021	125	17.6	(20)(28)(42)	0.903	Internal
Tian et al[53]	2023	China	Single1	2020-2021	1432	36	(20)(45)	0.866	Internal

¹Indicates prospective studies, others are retrospective studies.

²Surgical procedures included pancreaticoduodenectomy and distal pancreatectomy.

³The data is the CR-POPF rate of total cohort.

⁴The data includes biochemical leak.

⁵From Table 1.

AUC: Area under the curve; CI: Confidence interval; CR-POPF: Clinically relevant postoperative pancreatic fistula.

Table 5 Machine learning prediction models of postoperative pancreatic fistula after pancreaticoduodenectomy

Ref.	Year	Country	Center	Study period	Design cohort	CR-POPF (%)	C-index/AUC (95%CI)	Validation
Mu et al[54]	2020	China	Multi	2006-2019	359	15.6	0.85 (0.80-0.90)	Internal-external
Han et al[55]	2020	Korea	Single	2007-2016	1769	12.5	0.74
Skawran et al[48]	2021	Switzerland	Single	2008-2018	62	27.4	0.82 (0.74-0.89), 0.74 (0.63-0.89), 0.90 (0.84-0.95)	Internal
Giovinazzo et al[56]	2021	Multinational	Multi		1638	27	0.962 (0.940-0.984)
Shen et al[57]	2022	China	Single	2010-2021	2421	17.5	0.79-0.81	Internal
Long et al[58]	2022	China	Multi	2012-2021	618	18.1	0.897 (0.370-1.424)	Internal
Capretti et al[59]	2022	Italy	Single1	2011-2019	100	20	0.807, 0.749	Internal
Chen et al[60]	2022	United States	Nationwide	2014-2019	13940	14.4	0.746 (0.733-0.760)	Internal-external
Zheng et al[61]	2023	China	Single	2013-2021	2572	21.8	0.977	Internal
Ingwersen et al[22]	2023	Netherlands	Nationwide	2014-2020	4912	16.3	0.74 (0.73-0.74)
Verma et al[62]	2023	United States	Nationwide	2014-2018	8597	11	0.74 (0.72-0.76)	Internal-external
Ashraf Ganjouei et al[63]	2023	United States	Nationwide	2014-2019	8666	13	0.67-0.72	Internal
Ingwersen et al[64]	2023	Multinational	Multi	2013-2018	118	42.4	0.9 (0.71-0.99), 0.86, 0.81, 0.8	Internal-external

¹Indicates prospective studies, others are retrospective studies.

²Surgical procedures included open and laparoscopic pancreaticoduodenectomy.

AUC: Area under the curve; CI: Confidence interval; CR-POPF: Clinically relevant postoperative pancreatic fistula.

Table 6 Intraoperative prediction models of postoperative pancreatic fistula after pancreaticoduodenectomy

Ref.	Year	Country	Center	Study period	Design cohort	CR-POPF (%)	Variables5	C-index/AUC (95%CI)	Validation
Kim et al[67]	2013	Korea	Single	2003-2008	100	414	(A)(B)(M)	0.728 (0.630-0.812)	Internal
Chen et al[68]	2015	China	Single	2008-2013	921	9.7	(3)(A)(B)(D)(E)	0.812 (0.766-0.858)
Kantor et al[69]	2017	United States	Nationwide	2011-2012	1731	18.3	(1)(3)(16)(A)(B)	0.70 (0.65-0.74)	Internal-external
Li et al[70]	2019	China	Single	2011-2014	189	20.1	(15)(A)(B)(D)	0.821 (0.736-0.905)	Internal
Mungroop et al[37]	2019	Multinational	Multi	2007-2016	1924	124	(3)(20)(B)	0.75 (0.71-0.78)	Internal-external
Angrisani et al[21]	2020	Italy	Multi1	2016-2018	148	19.6	(44)(A)(B)(D)	0.774 (0.683-0.866)
							(44)(A)(B)	0.784 (0.680-0.888)
Zhang et al[16]	2021	China	Single	2012-2020	232	7.8	(7)(8)(10)(B)(K)	0.916
Mungroop et al[38]	2021	Multinational	Multi	2007-2017	9522	21	(1)(3)(20)(B)	0.75 (0.71-0.79)	External
Kolbinger et al[50]	2022	Germany	Single	2012-2021	195	28.7	(47)(A)(B)	0.82	Internal
Lucassen et al[18]	2022	Netherlands	Single	2009-2018	329	16.7	(20)(41)(B)	0.73 (0.68-0.79)
							(20)(28)(B)	0.81 (0.75-0.86)
							(20)(28)(41)(B)	0.81 (0.75-0.86)
Zheng et al[61]	2023	China	Single	2013-2021	257	21.8	(3)(20)(B)	0.743	Internal
Hayashi et al[71]	2023	Japan	Single	2010-2021	169	22.5	(30)(31)(B)	0.832
Ingwersen et al[22]	2023	Netherlands	Nationwide	2014-2020	4912	16.3	(1)(3)(5)(13)(16)(19)(A)(B)(G)(J)(M)(N)	0.73
Schuh et al[65]	2023	Multinational	Multi	2004-2019	55333	15.7	(A)(B)		External

¹Indicates prospective studies, others are retrospective studies.

²The surgical procedure was minimally invasive pancreaticoduodenectomy.

³The cohort is for validation.

⁴The data includes biochemical leak.

⁵From Table 1.

AUC: Area under the curve; CI: Confidence interval; CR-POPF: Clinically relevant postoperative pancreatic fistula.

Table 7 Postoperative prediction models of postoperative pancreatic fistula after pancreaticoduodenectomy

Ref.	Year	Country	Center	Study period	Design cohort	CR-POPF (%)	Variables6	C-index/AUC (95%CI)	Validation
Gaujoux et al[31]	2010	France	Single1	2004-2005	100	24	(3)(q)(r)	0.82
Callery et al[34]	2013	United States	Single1	2002-2007	233	13	(A)(B)(D)(o)	0.942	Internal
Xia et al[23]	2018	China	Single	2009-2017	225	17.8	(A)(B)(L)(h)	0.813 (0.737-0.889)	Internal
Xingjun et al[72]	2019	China	Multi	2014-2017	457	12.65	(A)(q)(r)	0.868	External
You et al[73]	2019	Korea	Single	2007-2016	1771	12.5	(1)(3)(12)(15)(A)(o)	0.709	Internal
Guo et al[74]	2020	China	Single	2012-2016	220	22.7	(A)(B)(o)(p)	0.793 (0.731-0.855)	Internal
Li et al[75]	2021	China	Single	2018-2020	176	21.1	(a)(e)(f)(g)(k)	0.814 (0.736-0.892)
Shen et al[76]	2021	China	Single	2016-2020	302	16.6	(3)(B)(a)(i)	0.87 (0.81-0.94)	Internal
Liu et al[77]	2021	China	Single	2016-2019	2514	7.6	(15)(18)(a)(j)	0.866 (0.737-0.996)
							(15)(18)(a)(j)	0.896 (0.814-0.978)
							(15)(18)(a)(j)	0.888 (0.806-0.971)
Huang et al[78]	2021	China	Multi	2010-2018	762	11.4	(3)(A)(a)	0.934 (0.914-0.950)	External
Guilbaud et al[79]	2021	France	Multi1	2017-2019	1823	21.2	(a)(f)	0.834 (0.769-0.900)
Honselmann et al[20]	2021	Germany	Single	2012-2017	182	16	(12)(A)(C)(c)(m)	0.903	Internal
							(12)(B)(c)(d)(m)	0.891
Suzuki et al[80]	2021	Japan	Single	2007-2012	349	17.5	(20)(B)(b)(n)
Al Abbas et al[81]	2021	United Sates	Nationwide	2014-2016	9867	13.9	(1)(2)(3)(7)(8)(A)(B)(o)	0.70 (0.69-0.71)	Internal
Yin et al[82]	2022	China	Single	2012-2016	662	16.3	(17)(A)(F)(M)(o)	0.667	Internal
							(A)(F)(a)(e)	0.809
Gu et al[24]	2023	China	Nationwide	2014-2017	36092	16.7	(4)(20)(B)(o)(s)(t)	0.855 (0.702-0.853)	External
Bannone et al[83]	2023	Italy	Single1	2016-2021	905	20.2	(A)(B)(D)(a)(o)	0.85 (0.82-0.87)
							(A)(B)(D)(a)(l)(o)	0.87 (0.84-0.89)
							(A)(B)(D)(a)(f)(l)(o)	0.90 (0.87-0.91)
Choi et al[84]	2023	Korea	Multi	2012-2020	4294	12.4	(12)(20)(46)(B)(E)(H)(I)(o)	0.739 (0.668-0.800)	Internal
van Dongen et al[85]	2023	Netherlands	Nationwide	2014-2018	3271	14.6	(1)(3)(8)(20)(o)	0.73	External
Raza et al[86]	2023	United Kingdom	Multi	2009-2019	187	12.8	(1)(a)(f)(h)	0.78	External
Mohamed et al[87]	2023	United Sates	Nationwide	2015-2018	5975	17	(1)(3)(14)(A)(B)(o)	0.72 (0.704-0.737)
Ahmad et al[88]	2023	United States	Nationwide	2014-2017	2417	12.6	(3)(11)(B)(C)(a)	0.720 (0.687-0.752)	Internal
							(3)(11)(B)(C)(a)(b)	0.758 (0.726-0.789)

¹Indicates prospective studies, others are retrospective studies.

²The study population was from the American College of Surgeons-National Surgical Quality Improvement Program database in the United States.

³Surgical procedures included pancreaticoduodenectomy and distal pancreatectomy.

⁴The surgical procedure was minimally invasive pancreaticoduodenectomy.

⁵The data is the clinically relevant postoperative pancreatic fistula rate of total cohort.

⁶From Table 1.

AUC: Area under the curve; CI: Confidence interval; CR-POPF: Clinically relevant postoperative pancreatic fistula.

Table 8 Postoperative pancreatic fistula prediction models after distal pancreatectomy

Ref.	Year	Country	Center	Design cohort	Study period	CR-POPF (%)	Variables3	AUC (95%CI)	Validation
Ecker et al[25]	2019	Multinational	Multi	2026	2001-2016	15.1	(1)(2)(6)(A)(G)(H)(e)	0.654 (0.620-0.688)
Guilbaud et al[79]	2021	France	Multi1	922	2017-2019	21.2	(a)(b)	0.762 (0.640-0.885)
Rollin et al[90]	2022	France	Single	103	2015-2019	32	(2)(8)(B)(c)	0.83 (0.75-0.92)
Nassour et al[91]	2022	USA	Nationwide	692	2014-2018	15.9	(1)(B)(D)(b)	0.731 (0.685-0.796)	Internal
							(1)(B)(b)(d)	0.791 (0.742-0.836)
Bonsdorff et al[89]	2022	Multinational	Multi	266	2013-2021	19.5	(3)(8)(F)	0.904 (0.855-0.949)	Internal-external
He et al[92]	2023	China	Single	115	2005-2020	33	(2)(6)(8)(E)	0.842 (0.762-0.921)
Pecorelli et al[26]	2023	Italy	Single	220	2016-2019	33.6	(2)(3)(4)(5)	0.651 (0.58-0.73)	Internal
							(2)(9)(10)(C)	0.725 (0.66-0.79)
							(5)(11)(C)	0.733 (0.64-0.80)
De Pastena et al[27]	2023	Multinational	Multi1	339	2014-2016	23	(7)(8)	0.731 (0.70-0.76)	Internal-external
							(2)(7)(8)(B)(E)	0.851 (0.80-0.90)	Internal

¹Indicates prospective studies, others are retrospective studies.

²Including patients underwent pancreaticoduodenectomy.

³From Table 2.

AUC: Area under the curve; CI: Confidence interval; CR-POPF: Clinically relevant postoperative pancreatic fistula.

Table 9 Postoperative pancreatic fistula prediction models after central pancreatectomy

Ref.	Year	Design cohort	Study period	CR-POPF (%)	Variables1	AUC (95%CI)
Ouyang et al[94]	2022	194	2009-2020	45.9	(2)(D)	0.678
Yang et al[95]	2023	115	2010-2022	30.4	(2)(4)(5)(6)	0.832 (0.751-0.895)
					(2)(4)(5)(6)(B)	0.827 (0.745-0.891)
					(1)(2)(4)(5)(6)(B)	0.828 (0.746-0.892)
					(1)(2)(3)(4)(5)(6)(a)	0.826 (0.744-0.890)
					(2)(4)(5)(6)(A)(B)	0.845 (0.766-0.906)
					(2)(4)(5)(6)(A)(B)	0.847 (0.768-0.907)
					(1)(2)(4)(5)(6)(A)(B)	0.823 (0.741-0.888)
					(1)(2)(3)(4)(5)(6)(A)(B)(a)	0.840 (0.760-0.902)
					(2)(3)(5)(6)(C)	0.758 (0.669-0.833)
					(2)(3)(5)(6)(B)(C)	0.748 (0.659-0.824)
					(1)(2)(3)(5)(6)(B)(C)	0.784 (0.698-0.855)
					(1)(2)(3)(5)(6)(C)(a)	0.750 (0.661-0.826)

¹From Table 3.

AUC: Area under the curve; CI: Confidence interval; CR-POPF: Clinically relevant postoperative pancreatic fistula.