Nomographic predictive models for complications after minimally invasive esophagectomy: Current status and future perspectives

Table 1 Difference in post operative outcomes between minimally invasive and open esophagectomy

Ref.	Sample size	Blood loss (mL)	Operative time (minutes)	Length of stay (days)	Respiratory morbidity	Anastomotic leak rate	In-hospital mortality	Lymph node retrieval	3-year overall survival
Smithers et al[61]	446	Lower in MIE (300 vs 600), P = 0.017	Shorter in OE (330 vs 300), P = 0.01	Shorter in MIE (11 vs 14), P = 0.03	NSD	NSD	NSD	NSD	NSD
Nagpal et al[62]	1284	Lower in MIE, P < 0.001	Shorter in OE, P < 0.001	Shorter in MIE, P = 0.004	Lower in MIE, P = 0.04	Lower in MIE, P = 0.02	NSD	NSD	NR
Yibulayin et al[6]	15790	Lower in MIE, P = 0.05	Shorter in OE, P < 0.05	Shorter in MIE, P < 0.05	Lower in MIE, P < 0.05	NSD	Lower in MIE, P < 0.05	NS	NR
Sihag et al[63]	3780	NR	Shorter in OE (443 vs 312), P < 0.001	Shorter in MIE (9 vs 10), P < 0.001	NSD	NSD	NS	NR	NR
Xiong et al[64]	488	Lower in MIE, P = 0.001	Shorter in MIE, P < 0.001	Shorter in MIE, P < 0.001	Lower in MIE, P < 0.001	NSD	NSD	NSD	NR
Yoshida et al[65]	24233	Lower in MIE, P < 0.001	Shorter in MIE, P < 0.001	NR	Lower in MIE (16% vs 18%), P = 0.001	NSD	Lower in MIE (1.7 vs 2.4), P < 0.001	NR	NR
Akhtar et al[66]	13269	Lower in MIE, P < 0.001	Shorter in MIE, P < 0.001	Shorter in MIE, P < 0.001	Lower in MIE, P < 0.001	NR	NR	NR	NR
Ofuchi et al[67]	459	NR	NR	NR	Lower with MIE (28% vs 40%)	NR	NSD	NSD	NSD
Randomized control trials
Biere et al[5]	115	Lower in MIE (200 vs 475), P < 0.001	Shorter in OE (329 vs 299), P = 0.002	Shorter in MIE (11 vs 14), P = 0.044	Lower in MIE (12% vs 34%), P = 0.005	NSD	NSD	NSD	NR
Mariette et al[15]	207	NR	NSD	NSD (14 days vs 14 days)	Lower with MIE (18% vs 30%)	More in MIE (11% vs 7%)	NSD	NSD	NSD
van der Sluis et al[16]	112	Lower with MIE (120 mL vs 200 mL)	Longer in RAMIE (60-70 minutes more)	NSD (14 days vs 16 days)	Lower with MIE (32% vs 58%)	NSD (22% vs 20%)	NSD	NSD (27 vs 25)	NSD
ROMIO study group[68]	533	NR	NR	NSD (10 days vs 11 days)	NSD	NSD (8% vs 8%)	NSD	NR	NR

MIE: Minimally invasive esophagectomy; OE: Open esophagectomy; NSD: No significant difference; NS: No significant; NR: Not reported; RAMIE: Robot assisted minimally invasive esophagectomy.

Table 2 List of complications post minimally invasive esophagectomy

Timing	Category	Complications
Intraoperative		Bleeding
		Anesthesia related complications
		Adjacent visceral injury
Post-operative	Medical	Pulmonary morbidity
		Atelectasis
		Aspiration
		Bronchopneumonia
		Respiratory failure
		ARDS cardiac morbidity
		Cardiac arrest
		MI
		Angina
		Thromboembolism
		Arrhythmias
	Major surgical immediate	Anastomotic leak
		Conduit necrosis
		Chyle leak
		Recurrent laryngeal nerve palsy
	Surgical long term	Anastomotic stricture
		Delayed gastric emptying
		Gastro-esophageal reflux
		Malabsorption and nutritional deficiencies

MI: Myocardial infarction; ARDS: Acute respiratory distress syndrome.

Table 3 Published series reporting the incidence of major complications associated with minimally invasive esophagectomy

Ref.	Technique	n (cases)	Pulmonary complication (%)	Cardiac arrhythmia (%)	Anastomotic leak (%)	Conduit necrosis (%)	Chylothorax (%)	RLNP (%)
Xie et al[69]	IL	106	4.7	2.8	4.7	3.8	3.8	-
Sihag et al[63]	IL	600	12.8	-	13.8	-	-	4.3
van Workum et al[70]	IL	561	27.8	17.1	14.4	-	8.7	0.5
Naffouje et al[71]	IL	161	11.8	-	13	-	-	-
Lorimer et al[72]	IL	200	17	23	8.5	-	-	-
van der Sluis et al[73]	RM	108	33.3	8.3	18.5	-	17.6	9.3
Park et al[23]	RM	140	8.8	-	9.3	0	-	25
van der Sluis et al[16]	RM	54	27.8	22.2	24.1	-	31.5	9.3
Zhang et al[74]	RIL	76	6.6	-	9.2	1.3	1.9	6.6
Meredith et al[75]	RIL	147	6.8	11.6	2.7	-	-	3.4
Wang et al[76]	TME	194	6.2	3.6	4.6	-	-	4.6
Fujiwara et al[77]	TME	60	6.7	-	15	-	0	33.3
Kinjo et al[78]	M	106	16	9.4	10.4	0.9	-	19.8
Chen et al[79]	M	142	9.2	2.8	6.3	0.7	2.8	5.6
Li et al[80]	M	89	7.9	7.9	21.3	1.1	-	20.2
Tanaka et al[81]	M	59	13.6	11.9	6.8	0	-	22
Seesing et al[18]	M	121	36.4	19.8	26.4	33.9	-	7.4
Koterazawa et al[82]	M	162	14.8	-	17.9	-	-	19.8
van Workum et al[70]	M	226	24.8	26.1	26.5	-	13.3	9

RLNP: Recurrent laryngeal nerve palsy; IL: Ivor Lewis; RM: Robotic-assisted McKeown; RIL: Robotic-assisted Ivor Lewis; TME: Transmediastinal esophagectomy; M: McKeown.

Table 4 Risk factors found associated with morbidity in minimally invasive esophagectomy

Category	Risk factor	Association with higher morbidity
Patient related	Age	> 65 years[83]
	Gender	Male gender associated with more pulmonary and overall morbidity[48]
	Body habitus and BMI	Underweight/sarcopenic or morbid obesity[84]
	Performance status	ASA and ECOG score more than 1
	Nutritional status	Malnutrition (low albumin, hemoglobin level), weight loss, sarcopenia[48,84]
	Addictions	Smoking has higher risk[85-87]
	Pre-existing co-morbidities	Diabetes, COPD, cardiac disease and higher Charlson index[83,88]
Disease related	Tumor size	Tumour size > 4 cm[4]
	Tumor stage	T3 and higher tumours[4]
	Tumor location	Cervical and upper thoracic tumours[4]
Treatment related	Neo-adjuvant CRT	Standard of care but mixed evidence regarding slightly higher morbidity with CRT[89]
	Surgical approach (MIE/hybrid/open)	Open approach[5,15,16]
	Patient position (prone/semi-prone)	Semi-prone is associated with inferior outcomes in terms of pulmonary morbidity[17,81]
	Lymphadenectomy (standard or total two field/three field)	Three field and total two field have higher morbidity rates[82]
	Conduit type	Non gastric > gastric conduit[90]
	Anastomotic level	Cervical > intrathoracic anastomosis[91]
	Anastomotic technique	Overall similar for stapled and hand sewn technique. Semi-mechanical has better reported outcomes

BMI: Body mass index; ASA: American Society of Anesthesia; ECOG: Eastern Cooperative Oncology Group; COPD: Chronic obstructive pulmonary disease; CRT: Chemoradiotherapy; MIE: Minimally invasive esophagectomy.

Table 5 List of risk predictive nomograms developed for prediction of post esophagectomy morbidity

Ref.	Study size and period	Procedure	Morbidity predicted using nomogram	Risk factors influencing morbidity	Statistical significance
Yu et al[92], 2021	604 (2018-2020)	Open esophagectomy (53%) + MIE (47%)	Anastomotic leak	Smoking index, ASA score, anastomosis level (chest/neck, anastomotic technique, prognostic nutrition index	AUC = 0.766
Tong et al[93], 2022	969 (NS)	MIE	Pulmonary complications	Age, high BMI, smoking, FEV1/FVC, chemoradiotherapy, blood loss, general anesthesia, operative time, conversion to thoracotomy	C index = 0.654
Jin et al[94], 2022	609 (2015-2019)	MIE	Post operative pneumonia	Age, gender, abdominal phase approach, thoracic operative time, duration of chest tube placement, anastomotic leakage, RLN palsy	C index = 0.77
					AUC = 0.66
Su et al[95], 2023	308 (2018-2022)	MIE	Anastomotic leak	Age, post operative delirium, pleural adhesions, post operative pulmonary complication, raised TLC, low lymphocyte	C index = 0.96
					AUC = 0.96
Chen et al[9], 2022	285 (NS)	MIE (McKeowns esophagectomy)	Anastomotic leak	Aortic calcification, preexisting heart disease, obesity, low FEV1	C index = 0.67
Xi et al[96], 2020	119 (2019-2020)	Open esophagectomy (15%) + MIE (85%)	Post operative morbidity	BMI, ASA score, diabetes, eSAS (blood loss, lowest MAP, lowest HR)	C index = 0.903 (internal validation) 0.967 (external validation)
Zhong et al[50], 2025	747 (2019-2024)	MIE	Serious adverse events	Age, alcohol consumption, COPD, neoadjuvant radiotherapy, tumour size, FEV1, calcium, hemoglobin, albumin	AUC = 0.793

A C index (Concordance index) more than 0.7 suggests good discriminative capacity of the predictive model. A value less than 0.5 indicates discrimination by random chance and a value of 1.0 represents perfect discrimination. MIE: Minimally invasive esophagectomy; ASA: American Society of Anesthesia; AUC: Area under the curve for receiver operating characteristic curve; BMI: Body mass index; FEV1: Forced expiratory volume in 1 second; FVC: Forced vital capacity; RLN: Recurrent laryngeal nerve; TLC: Total leucocyte count; eSAS: Esophageal surgical Apgar score; MAP: Mean arterial pressure; COPD: Chronic obstructive pulmonary disease; HR: Hazard ratio.

Table 6 Currently available risk prediction models developed using artificial intelligence and machine learning for predicting esophagectomy related complications

Ref.	Study size	Study design	Objective	Results
Bolourani et al[97], 2021	2037	Retrospective	ML-based prediction model for early readmissions within 30 days following esophagectomy	ML model for clinical decision AUC: 0.72
				ML model for quality review of esophagectomy AUC: 0.74
van Kooten et al[98], 2022	4288	Retrospective	ML methods for predicting postoperative complications following esophagectomy and development of a predictive model for anastomotic leakage and cardiopulmonary complications	The AUC of 0.619 for anastomotic leakage and 0.644 for pulmonary complications
Jung et al[99], 2023	604	Retrospective	ML-based methods for predicting Clavien–Dindo grade IIIa or greater complications following esophagectomy	The AUC of neural network was 0.672 for overall Clavien-Dindo grade IIIa or higher morbidity, 0.695 for medical complications, and 0.653 for surgical complications
Klontzas et al[55], 2024	471	Retrospective	ML model combining CT and clinical variables for predicting anastomotic leakage following esophagectomy	The model achieved an AUC of 0.792

ML: Machine learning; AUC: Area under the curve for receiver operating characteristic curve; CT: Computed tomography.

Table 7 A hypothetical nomogram model for prediction of post minimally invasive esophagectomy complications proposed by the authors (needs predictive performance validation)

Risk factor	Criteria	Score
Age	< 65 years	0
	> 65 years	1
Gender	Female	0
	Male	1
ASA score	≤ Grade 2	0
	> Grade 2	1
ECOG status	≤ 1	0
	1-2	1
	> 2	3
Diabetes or cardiac co-morbidities	No	0
	Yes	1
BMI	18.5-25	0
	> 25	1
Smoking/tobacco use	No	0
	Yes	1
Hemoglobin levels	> 8 g/dL	0
	< 8 g/dL	1
Serum albumin	> 3.5	0
	< 3.5	1
Tumour size	< 4 cm	0
	> 4 cm	1
Tumour location	Middle or lower thoracic esophagus	0
	Cervical or upper thoracic esophagus	1
Tumour T stage	≤ 2	0
	> 2	1
Neoadjuvant chemoradiotherapy	No	0
	Yes	1
Surgical approach	Minimally invasive	0
	Open	1
Lymphadenectomy type	Standard or extended 2 field	0
	Total 2 field/3 field	1
Conduit type	Gastric	0
	Non-gastric	1
Anastomosis level	Intrathoracic	0
	Cervical	1

ASA: American Society of Anesthesia; ECOG: Eastern Cooperative Oncology Group; BMI: Body mass index.