Combined and intraoperative risk modelling for oesophagectomy: A systematic review

Table 1 Development studies of combined and intraoperative multivariate models

Ref.	Period + number	Sample region	Operation	Characteristics	Source of data	Models tested	Outcomes tested
Janowak et al[26], 2015	2009-2013 (168)	United States	TT/TH/Hybrid/MIE	N: 93/168; H: N/A	Single centre	eSAS	Major morbidity
Yoshida et al[28], 2015	2005-2013 (365)	Japan	TT	N: 113/250; H: N/A	Single centre	Yoshida score	Morbidity +; Major morbidity
Stroyer et al[27], 2017	2011-2014 (234)	Denmark	TT	N: 188/234; H: N/A	Single centre	Modified eSAS, SAS, eSAS	Major morbidity
Xi et al[30], 2019	2015-2018 (194)	China	TT/Hybrid/MIE	N: 48/194; H: N/A	Single centre	eSAS nomogram	Major morbidity
Xi et al[29], 2020	2015-2017 (251)	China	TT/Hybrid/MIE	N: 56/251; H: N/A	Single centre	IPF nomogram	Major morbidity
Huang et al[31], 2020	2016-2018 (330)	China	TT/Hybrid/MIE	N: 41/330; H: 321SCC/9AC	Single centre	Huang nomogram	Anastomotic leak

TT: Transthoracic; TH: Transhiatal; MIE: Minimally invasive esophagectomy; N: Neoadjuvant status; H: Histopatholog; N/A: Not applicable; SCC: Squamous cell carcinoma; AC: Adenocarcinoma; eSAS: Esophagectomy surgical Apgar score; SAS: Surgical Apgar score; IPF: Intraoperative factors.

Table 2 Validation studies of combined and intraoperative models

Ref.	Period + number	Sample region	Operation	Characteristics	Source of data	Models tested	Outcomes tested
Zafirellis et al[36], 2002	1990-1999 (204)	United Kingdom	TT/TH	N: 39/204; H: 156AC/45SCC	Single centre	POSSUM	Major morbidity + Mortality
Lai et al[37], 2007	2001-2005 (545)	China	TT	N: N/A; H: 545SCC/0AC	Hong Kong (All)	POSSUM; O-POSSUM; P-POSSUM	Mortality
Lagarde et al[38], 2007	1993-2005 (663)	Netherlands	TT/TH	N: N/A; H: 476AC/187SCC	Single centre	O-POSSUM	Mortality
Baba et al[39], 2008	2000-2007 (142)	Japan	TT	N: 15/142; H: 142SCC/0AC	Single centre	E-PASS	Morbidity
Bosch et al[33], 2011	1991-2007 (278)	Netherlands	TT	N: 10/278; H: 235AC/43SCC	Single centre	ACCI; CCI; O-POSSUM; P-POSSUM	Mortality
Yoshida et al[40], 2013	2005-2012 (308)	Japan	TT	N: N/A; H: N/A	Single centre	E-PASS	Morbidity
Filip et al[34], 2014	2004-2013 (43)	Romania	TT/TH	N: 22/43; H: 33SCC/9AC	Single centre	ACCI; CCI; POSSUM; O-POSSUM; P-POSSUM	Mortality
Filip et al[32], 2015	2008-2012 (167)	Italy	TT/TH/MIE	N: 131/167; H: 105 AC/62SCC	Single centre	PNI-multivariate PNI; CCI; ACCI; O-POSSUM; P-POSSUM; Amsterdam score	Morbidity
Yamana et al[35], 2015	2005-2013 (251)	Japan	TT/MIE	N: 150/251; H: N/A	Single centre	GNRI; PNI; E-PASS; POSSUM	Respiratory complications
Xing et al[41], 2016	2008-2010 (189)	China	TT/TH	N: 7/189; H: 141SCC/45AC	Single centre	E-SAS	Major morbidity
Eto et al[42], 2016	2007-2015 (399)	Japan	Hybrid	N: 176/399; H: N/A	Single centre	SAS	Major morbidity
Nakagawa et al[43], 2017	2007-2017 (379)	Japan	TT/Hybrid/MIE	N: 129/379; H: 367SCC/12AC	Single centre	SAS	Major morbidity
Aoki et al[44], 2019	2011-2015 (246)	Japan	TT/Hybrid/MIE	N: 152/246; H: N/A	Single centre	E-SAS; Modified E-SAS	Major morbidity
Hayashi et al[45], 2019	2012-2016 (190)	Japan	TT	N: 115/190; H: N/A	Single centre	SAS	Major morbidity

TT: Transthoracic; TH: Transhiatal; MIE: Minimally invasive esophagectomy; N: Neoadjuvant status; H: Histopathology; N/A: Not applicable; SCC: Squamous cell carcinoma; AC: Adenocarcinoma; eSAS: Esophagectomy surgical Apgar score; SAS: Surgical Apgar score; IPF: Intraoperative factors; POSSUM: Physiological and operative severity score for the enumeration of mortality and morbidity; P-POSSUM: Portsmouth physiological and operative severity score for the enumeration of mortality and morbidity; O-POSSUM: Oesophagogastric physiological and operative severity score for the enumeration of mortality and morbidity; E-PASS: Estimation of physiologic ability and surgical stress; ACCI: Age adjusted charlson comorbidity index; CCI: Charlson comorbidity index; PNI: Prognostic nutritional index; GNRI: Geriatric nutritional risk index.

Table 3 Clinical credibility of combined and intraoperative models

Model	Ref.	Oesophageal specific	No thresholds	Timely data	Reliable data	Easy to generate	Understandable	Useful range	Total
POSSUM	Copeland et al[46], 1991	No	No	No	Yes	Yes	Yes	Yes	4
O-POSSUM	Tekkis et al[48], 2004	Partly	No	No	Yes	Yes	Yes	Yes	4.5
P-POSSUM	Prytherch et al[47], 1998	No	No	No	Yes	Yes	Yes	Yes	4
E-PASS	Haga et al[49], 1999	No	Yes	No	Partly	No	Partly	Yes	3
Yoshida score	Yoshida et al[28], 2014	Yes	No	No	Yes	Yes	Yes	No	4
Xi SAS nomogram	Xi et al[29], 2020	Yes	No	No	Partly	Yes	Yes	Yes	4.5
Xi IPF nomogram	Xi et al[30], 2019	Yes	No	No	Partly	Yes	Yes	Yes	4.5
Huang Model	Huang et al[31], 2020	Yes	No	No	Yes	Yes	Yes	Yes	5
SAS	Gawande et al[50], 2007	No	No	No	Partly	Yes	Yes	Yes	3.5
eSAS	Janowak et al[26], 2015	Yes	No	No	Partly	Yes	Yes	Yes	4.5
Modified eSAS	Stroyer et al[27], 2017	Yes	No	No	Partly	Yes	Yes	Yes	4.5

POSSUM: Physiological and operative severity score for the enumeration of mortality and morbidity; P-POSSUM: Portsmouth physiological and operative severity score for the enumeration of mortality and morbidity; O-POSSUM: Oesophagogastric physiological and operative severity score for the enumeration of mortality and morbidity; E-PASS: Estimation of physiologic ability and surgical stress; SAS: Surgical Apgar score; eSAS: Esophagectomy surgical Apgar score.

Table 4 Methodological quality (overall performance) for combined and intraoperative models

Model	Study participation (out of 8)	Measurements (out of 4)	Analysis (out of 8)	Total (out of 20)
POSSUM	7	3	5.5	15.5
O-POSSUM	8	4	8	20
P-POSSUM	7	3	7	17
E-PASS	7.5	3	6	16.5
Yoshida score	6	4	6	16.5
Xi SAS nomogram	8	4	7	19
Xi IPF nomogram	8	4	6	18
Huang model	7.5	4	6	16.5
SAS	8	4	7	19
eSAS	8	4	4	16
Modified eSAS	8	4	6	17.5

POSSUM: Physiological and operative severity score for the enumeration of mortality and morbidity; P-POSSUM: Portsmouth physiological and operative severity score for the enumeration of mortality and morbidity; O-POSSUM: Oesophagogastric physiological and operative severity score for the enumeration of mortality and morbidity; E-PASS: Estimation of physiologic ability and surgical stress; SAS: Surgical Apgar score; eSAS: Esophagectomy surgical Apgar score.

Table 5 Summary of the performance for each of the combined and intraoperative models

Predictive model (n)	Ref.	Discrimination	Calibration/other statistics	Outcome
POSSUM (5)	Zafirellis et al[36], 2002	0.55, 0.62	HL P < 0.001, 0.002	Morbidity + Mortality
	Lai et al[37], 2007	AUC = 0.776	O:E 0.367 (P = 0.001)	Mortality
	Filip et al[34], 2014	AUC = 0.826	O:E 1.11	Mortality
	Filip et al[32], 2015	AUC = 0.59	HL P value (0.08)	Morbidity
	Yamana et al[35], 2015	AUC = 0.601	Not reported	Resp complications
O-POSSUM (4)	Lai et al[37], 2007	AUC = 0.676	O:E 0.505 (P = 0.002)	Mortality
	Lagarde et al[38], 2007	AUC = 0.60	O:E 0.29 (P < 0.001)	Mortality
	Bosch et al[33], 2011	AUC = 0.756	HL P value (0.035)	Mortality
	Filip et al[34], 2014	AUC = 0.740	O:E 1.70	Mortality
P-POSSUM (3)	Lai et al[37], 2007	AUC = 0.776	O:E (P = 0.814)	Mortality
	Bosch et al[33], 2011	AUC = 0.766	HL P value (0.529)	Mortality
	Filip et al[34], 2014	AUC = 0.607	O:E 4.28	Mortality
E-PASS (3)	Baba et al[39], 2008	CRS > 1 (P < 0.001)	N/A	Morbidity
	Yoshida et al[40], 2013	CRS > 0.9 (P 0.029)	N/A	Morbidity
	Yamana et al[35], 2015	AUC = 0.659	N/A	Resp complications
Yoshida (1)	Yoshida et al[28], 2015	P value = < 0.001, 0.037	Not reported	Morbidity + Major morbidity
Xi SAS nomogram (1)	Xi et al[30], 2019	AUC = 0.903, 0.967	“Good”	Major morbidity
Xi IPF nomogram (1)	Xi et al[29], 2020	AUC = 0.921	“Sufficient”	Major morbidity
Huang (1)	Huang et al[31], 2020	AUC = 0.69	“Good”	Anastomotic leak
SAS (4)	Eto et al[42], 2016	AUC = 0.68	Cut off = 6 Pulm, SSI, AL	Major morbidity
	Stroyer et al[27], 2017	AUC = 0.561	All comp P = 0.148	Major morbidity
	Nakagawa et al[43], 2017	Not reported	Cut off > 5, P < 0.0001	Major morbidity
	Hayashi et al[45], 2019	Not reported	Cut off ≥ 6, P = 0.032	Major morbidity
eSAS (4)	Janowak et al[26], 2015	AUC = 0.614	Cut off = 6, Com P = 0.01	Major morbidity
	Xing et al[41], 2016	AUC = 0.62	Cut off > 7 LOS	Major morbidity
	Stroyer et al[27], 2017	AUC = 0.572	All comp P = 0.460	Major morbidity
	Aoki et al[44], 2019	Optimal cut-off 4 (Youden’s index = 0.069)	Major morbidity (P = 0.29)	Major morbidity
Modified eSAS (2)	Stroyer et al[27], 2017	AUC = 0.532	All comp P = 0.096	Major morbidity
	Aoki et al[44], 2019	Optimal cut-off 4 (Youden’s index = 0.180)	Major morbidity (P = 0.004)	Major morbidity

POSSUM: Physiological and operative severity score for the enumeration of mortality and morbidity; P-POSSUM: Portsmouth physiological and operative severity score for the enumeration of mortality and morbidity; O-POSSUM: Oesophagogastric physiological and operative severity score for the enumeration of mortality and morbidity; E-PASS: Estimation of physiologic ability and surgical stress; SAS: Surgical Apgar score; eSAS: Esophagectomy surgical Apgar score; N/A: Not applicable; IPF: Intraoperative factors; AUC: Area under the curve.

Table 6 Summary of the combination and intraoperative models across the five categories

Model	Ref.	Clinical credibility (out of 7)	Methodological quality (out of 20)	Model performance (overall utility)	External validation	Clinical effectiveness
POSSUM	Copeland et al[46], 1991	4	15.5	Mortality	Yes	No
O-POSSUM	Tekkis et al[48], 2004	4.5	20	No	Yes	No
P-POSSUM	Prytherch et al[47], 1998	4	17	Mortality	Yes	No
E-PASS	Haga et al[49], 1999	3	16.5	No	Yes	No
SAS	Gawande et al[50], 2007	4	16.5	No	Yes	No
eSAS	Janowak et al[26], 2015	4.5	19	No	Yes	No
Modified eSAS	Stroyer et al[27], 2017	4.5	18	No	Yes	No
Yoshida score	Yoshida et al[28], 2015	5	16.5	No	No	No
Xi SAS nomogram	Xi et al[29], 2020	3.5	19	Major morbidity	No	No
Xi IPF nomogram	Xi et al[30], 2019	4.5	16	Major morbidity	No	No
Huang	Huang et al[31], 2020	4.5	17.5	No	No	No

POSSUM: Physiological and operative severity score for the enumeration of mortality and morbidity; P-POSSUM: Portsmouth physiological and operative severity score for the enumeration of mortality and morbidity; O-POSSUM: Oesophagogastric physiological and operative severity score for the enumeration of mortality and morbidity; E-PASS: Estimation of physiologic ability and surgical stress; SAS: Surgical Apgar score; eSAS: Esophagectomy surgical Apgar score.