Staging laparoscopy in esophagogastric junction cancer: Systematic review and meta-analysis

Table 1 Variables assessed to investigate the secondary objectives

Characteristics	Classification
Study characteristics	Year
	Country
	Study design
	Study period
Patient characteristics	Number of patients
	Sex
	Mean age
	Reported comorbidities and scoring systems (e.g., ASA, Charlson Comorbidity Index, Clinical Frailty Scale, POSSUM, etc.)
Siewert classification type
Indication for staging laparoscopy (T, N)
Technical description	Number of surgical ports used
	Camera angle employed
	Pneumoperitoneum pressure
	Quantification of carcinomatosis, if present
	Abdominal regions inspected
	Sites of peritoneal lavage sampling
	Timing of lavage
	Lavage volume instilled and aspirated
	Duration of the procedure
	Use of intraoperative ultrasound
	Conversion to laparotomy
Postoperative assessment	Presence of complications
	Sources used to evaluate complications
	Use of complication classification/scoring systems
	Follow-up duration
	Postoperative hospital stay
	Readmission
	Interval between SL and initiation of neoadjuvant therapy or definitive surgery

ASA: American Society of Anesthesiologists; POSSUM: Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity; SL: Staging laparoscopy.

Table 2 Number of patients included in the studies, with details on whether the different variables analyzed were or were not specified

Characteristics	Specified		Not specified
	n	Population	n	Population
Comorbidities	0	0	18	1591
Indications for laparoscopy (based on T and N)	1	41	17	1550
TNM version used	5	540	13	1051
Siewert type considered for inclusion	7	668	11	923
Method of tumor localization for Siewert classification	11	911	7	680
Patient position during procedure	2	84	16	1507
Type of access to peritoneal cavity	3	234	15	1357
Number of surgical ports	14	1258	4	333
Type of camera	4	347	14	1244
Pneumoperitoneum pressure	1	43	17	1548
Substance used for peritoneal lavage	8	766	4	418
Volume of lavage fluid	8	766	4	418
Timing of peritoneal lavage during surgery	4	237	8	947
Use of intraoperative ultrasound	7	399	11	1192
Carcinomatosis measured with scores or indices	0	0	18	1591
Study design	14	1385	4	206
Study period specified (months)	15	1255	3	336
Regions inspected	9	567	9	1024
Regions sampled for lavage	2	117	10	1067
Volume of aspirated lavage	1	81	11	1103
Surgical time	4	309	14	1282
Positive macroscopic carcinomatosis	15	1453	3	138
Positive hepatic metastases	6	434	12	1157
Positive ascites	1	43	12	1184
Cytology performed on lavage	9	826	3	358
Conversion to open surgery	0	0	18	1591
Data recording methodology	8	1052	10	539
Evaluation of complications	5	381	13	1210
Use of complication scoring system	0	0	18	1591
Postoperative length of stay	0	0	18	1591
Performed as outpatient surgery	0	0	18	1591
Follow-up duration	0	0	18	1591
Readmissions	0	0	18	1591
Days from surgery to oncological treatment	0	0	18	1591

TNM: Tumor-node-metastasis.

Table 3 Main characteristics of the studies and their most relevant results

Ref.	No. of patients	Study type	Country	Inspection areas	Peritoneal lavage areas	Positive in macroscopic carcinomatosis	Positive in liver metastases	Positive in ascites cytology	Positive in peritoneal lavage	Positive peritoneal malignancy	Patients who became unresectable
Halle-Smith et al[13], 2024	396	R	United Kingdom	NS	NS	29	NS	NS	29	58	58
Mitchell et al[14], 2023	79	R	United States	NS	NS	NS	NS	NS	NS	NS	12
Strandby et al[15], 2020	81	P	Denmark	NS	1, 2	6	NS	NS	4	10	10
Mirza et al[16], 2016	212	R	United Kingdom	2, 3, 4, 9, 10	NS	27	NS	NS	NS	27	27
Strandby et al[17], 2016	171	R	Denmark	NS	NP	9	4	NP	NP	9	13
Simon et al[18], 2016	41	R	France	1, 2, 3, 4, 11, 12, 13	NS	NS	NS	NS	NS	NS	5
Bhatti et al[19], 2014	60	R	Pakistan	NS	NS	5	NS	NS	12	17	17
Munasinghe et al[20], 2013	36	R	United Kingdom	4, 5, 8, 11, 12, 13, 14	1, 2, 3	2	NS	NS	3	5	5
Nath et al[21], 2008	48	P	United Kingdom	NS	NS	3	NS	NS	4	7	7
Sarela et al[22], 2006	105	NS	United States	NS	NS	40	NS	NS	NS	40	40
Clements et al[23], 2004	45	NS	United Kingdom	NS	NP	4	NS	NP	NP	4	4
Menon and Dehn[24], 2003	43	P	United Kingdom	4, 8, 9, 15	NP	6	5	1	NP	7	12
Nieveen van Dikjum et al[25], 1999	36	NS	Netherlands	4, 13, 14	NS	11	NS	NS	NS	11	11
Romijn et al[26], 1998	20	NS	Netherlands	4, 5, 9, 16, 17	NP	4	2	NP	NP	4	6
Stein et al[27], 1997	72	P	Germany	4, 7, 8, 13, 17, 18	NS	8	13	NS	12	20	33
O´brien et al[28], 1995	39	P	Ireland	NS	NP	8	1	NP	NP	8	8
Dagnini et al[29], 1986	89	R	Italy	4, 5, 6, 16, 19	NP	27	15	NP	NP	27	42
Bemelman et al[30], 1995	18	P	Netherlands	4, 8, 17	NS	NS	NS	NS	0	NS	5

R: Retrospective; P: Prospective; NP: Not performed; NS: Not specified; 1: Right upper abdominal quadrant; 2: Left upper abdominal quadrant; 3: Pelvis; 4: Liver; 5: Primary tumor region; 6: Douglas pouch; 7: Diaphragmatic hiatus; 8: Lesser sac (omental bursa); 9: Greater omentum; 10: Lesser omentum; 11: Treitz angle; 12: Foramen of Winslow; 13: Hepatoduodenal ligament; 14: Transverse mesocolon; 15: Left gastric artery; 16: Diaphragm; 17: Celiac lymph nodes; 18: Lesser curvature of the stomach; 19: Gastrohepatic ligament.

Table 4 Evaluation of the risk of bias in the studies included using the Risk of Bias in Non-randomised Studies of Interventions tool

Ref.	Design	Participant selection	Intervention classification	Missing data	Outcome measurement	Selective reporting	Overall risk
Mitchell et al[14], 2023	Retrospective	Moderate	Moderate	Moderate	Low	Moderate	Moderate
Halle-Smith et al[13], 2024	Prospective	Low	Low	Low	Low	Low	Low
Strandby et al[15], 2020	Prospective	Low	Low	Low	Low	Low	Low
Strandby et al[17], 2016	Retrospective	Moderate	Moderate	Moderate	Moderate	Moderate	Moderate
Mirza et al[16], 2016	Retrospective	Moderate	Moderate	Moderate	Moderate	Moderate	Moderate
Simon et al[18], 2016	Retrospective	Moderate	Moderate	Moderate	Moderate	Moderate	Moderate
Bhatti et al[19], 2014	Retrospective	Moderate	Moderate	Moderate	Moderate	Moderate	Moderate
Munasinghe et al[20], 2013	Prospective	Low	Low	Low	Low	Low	Low
Nath et al[21], 2008	Prospective	Low	Low	Low	Low	Low	Low
Sarela 2006[22]	Retrospective	Moderate	Moderate	Moderate	Moderate	Moderate	Moderate
Clements et al[23], 2004	Retrospective	Moderate	Moderate	Moderate	Moderate	Moderate	Moderate
Menon and Dehn[24], 2003	Prospective	Low	Low	Low	Low	Low	Low
Nieveen van Dikjum et al[25], 1999	Prospective	Low	Low	Low	Low	Low	Low
Romijn et al[26], 1998	Prospective	Low	Low	Low	Low	Low	Low
Stein et al[27], 1997	Prospective	Low	Low	Moderate	Low	Low	Low
O´brien et al[28], 1995	Prospective	Low	Moderate	Moderate	Low	Low	Low
Bemelman et al[30], 1995	Prospective	Low	Low	Low	Low	Low	Low
Dagnini et al[29], 1986	Retrospective	High	High	High	Moderate	High	High

Table 5 Quality assessment of studies’ diagnostic accuracy (quality assessment of diagnostic accuracy studies-2)

Ref.	Patient selection	Index test (laparoscopy)	Reference standard	Flow and timing
Mitchell et al[14], 2023	Low	Low	Low	Low
Halle-Smith et al[13], 2024	Low	Low	Low	Low
Strandby et al[15], 2020	Low	Low	Low	Low
Strandby et al[17], 2016	High	Low	Unclear	Unclear
Mirza et al[16], 2016	High	Low	Unclear	Unclear
Simon et al[18], 2016	Low	Low	Low	Low
Bhatti et al[19], 2014	High	Low	Low	Unclear
Munasinghe et al[20], 2013	Low	Low	Low	Low
Nath et al[21], 2008	Low	Low	Unclear	Unclear
Sarela et al[22], 2006	High	Low	Unclear	Unclear
Clements et al[23], 2004	High	Low	Unclear	Unclear
Menon and Dehn[24], 2003	Low	Low	Low	Low
Nieveen van Dikjum et al[25], 1999	Low	Low	Low	Low
Romijn et al[26], 1998	Low	Low	Low	Low
Stein et al[27], 1997	Low	Low	Low	Low
O´brien et al[28], 1995	Low	Low	Low	Low
Bemelman et al[30], 1995	Low	Low	Low	Low
Dagnini et al[29], 1986	High	Low	Unclear	Unclear

Table 6 Number of articles, patients, and stage iv confirmation in cancers of the gastroesophageal junction

Description	Number of studies	Patients (n)	Positive		Negative
			n	%	n	%
Total patients with staging laparoscopy identifying disseminated disease	18	1591	315	19.8	1276	80.2
Studies specifying positive peritoneal metastases	15	1453	254	17.5	1199	82.5
Studies specifying positive peritoneal carcinomatosis	15	1453	189	13	1264	87
Studies specifying positive peritoneal washing cytology	7	711	64	9	647	91
Studies specifying hepatic metastases detected	6	434	40	9.2	394	90.8

Table 7 Relationship between staging laparoscopy results and Siewert type (non-parametric Mann-Whitney U test)

Variable	Siewert 1								Siewert 2								P value
	n	mean	SD	Min	Max	p50	p25	p75	n	mean	SD	Min	Max	p50	p25	p75
Macroscopic carcinomatosis	3	14.67	10.69	8	27	9	8	27	2	3.5	0.71	3	4	3.5	3	4	0.200
Hepatic metastases	2	8.5	6.36	4	13	8.5	4	13	0	-	-	-	-	-	-	-	-
Peritoneal malignancy	3	12.67	12.9	2	27	9	2	27	2	5.5	2.12	4	7	5.5	4	7	0.800
Staging changes	4	19.5	12.79	5	33	20	9	30	3	7.67	4.04	4	12	7	4	12	0.228

Min: Minimum; Max: Maximum.

Table 8 Relationship between laparoscopy findings and number of inspected areas (non-parametric correlation coefficient: Spearman’s Rho)

Variable	Number of inspected areas
	Correlation coefficient	P value
Staging changes	0.316	0.684
Peritoneal malignancy	-0.632	0.135
Macroscopic carcinomatosis	0.316	0.684
Hepatic metastases	0.316	0.684

Table 9 Relationship between peritoneal malignancy results and the use of peritoneal lavage, non-parametric Mann-Whitney U test

Peritoneal lavage performed	n	mean	SD	Min	Max	p50	p25	p75	P value
Not performed	6	9.83	8.66	4	27	7.5	4	9	0.999
Performed or not specified	9	14.67	18.24	1	58	7	4	17

Min: Minimum; Max: Maximum.

Table 10 Relationship between laparoscopy findings and volume of lavage used

Variable	Lavage volume
	Correlation coefficient	P value
Peritoneal malignancy	0.559	0.248
Staging changes	0.067	0.886

Non-parametric correlation coefficient, Spearman’s Rho.

Table 11 Relationship between laparoscopy findings and the use of intraoperative ultrasound, non-parametric Mann-Whitney U Test

Ultrasound performed	n	Mean	SD	Min	Max	p50	p25	p75	P value
Yes	3	5.67	4.73	2	11	4	2	11	0.700
No	3	8	1	7	9	8	7	9

Min: Minimum; Max: Maximum.

Table 12 Summary of meta-analysis and sensitivity analysis

Variable	Number of studies	Global effect size (%)	Heterogeneity (I2)
Overall diagnostic performance of the staging laparoscopy	18	22 (95%CI: 17-27)	88.3%
Positive peritoneal malignancy	15	19 (95%CI: 14-24)	83.6%
Positive peritoneal carcinomatosis	18	13 (95%CI: 10-17)	82.8%
Hepatic metastatic disease	6	9 (95%CI: 4-14)	81.7%
Diagnostic performance - Siewert I	4	18 (95%CI: 8-28)	93.7%
Diagnostic performance - Siewert II	3	13 (95%CI: 8-18)	0%
Positive peritoneal malignancy - Siewert I	3	7 (95%CI: 1-12)	84.4%
Positive peritoneal malignancy - Siewert II	2	11 (95%CI: 5-18)	0%

CI: Confidence interval.

Table 13 Certainty of evidence assessment (Grading of Recommendations, Assessment, Development and Evaluation)

Outcome	Number of studies	Patients (n)	Estimated effect	Certainty of evidence (GRADE)	Comments
Positive peritoneal carcinomatosis	18	1591	13% (95%CI: 10-17)	Low	High heterogeneity (I2 > 80%), moderate risk of bias
Hepatic metastatic disease	6	434	9% (95%CI: 4-14)	Low	High heterogeneity, small number of studies
Positive peritoneal malignancy	15	1453	19% (95%CI: 14-24)	Low	Variable results, wide confidence intervals, potential publication bias
Overall diagnostic performance of staging laparoscopy	18	1591	22% (95%CI: 17-27)	Low to moderate	High I2, majority observational studies, moderate risk of bias
Diagnostic performance - Siewert I	4	-	18% (95%CI: 8-28)	Low	High heterogeneity, one outlier study
Diagnostic performance - Siewert II	3	-	13% (95%CI: 8-18)	Moderate	Consistent results across studies, no heterogeneity
Positive peritoneal malignancy Siewert I	3	-	7% (95%CI: 1-12)	Low	Very heterogeneous, low frequency of events, wide CI
Positive peritoneal malignancy Siewert II	2	-	11% (95%CI: 5-18)	Moderate	Few studies, but consistent and homogeneous results

CI: Confidence interval; GRADE: Grading of Recommendations, Assessment, Development and Evaluation.

Table 14 Tumor classification systems used in included studies

Ref.	Siewert classification	AJCC classification
Halle-Smith et al[13], 2024	No	No
Mitchell et al[14], 2023	Yes	Yes
Strandby et al[15], 2020	No	Yes
Mirza et al[16], 2016	yes	Yes
Strandby et al[17], 2016	Yes	Yes
Simon et al[18], 2016	Yes	No
Bhatti et al[19], 2014	No	Yes
Munasinghe et al[20], 2013	No	No
Nath et al[21], 2008	Yes	No
Sarela et al[22], 2006	No	No
Clements et al[23], 2004	Yes	No
Menon and Dehn[24], 2003	No	No
Nieveen van Dikjum et al[25], 1999	No	No
Romijn et al[26], 1998	No	No
Stein et al[27], 1997	Yes	yes
O´brien et al[28], 1995	No	No
Dagnini et al[29], 1986	No	No
Bemelman et al[30], 1995	No	No

Siewert classification and/or the American Joint Committee on Cancer. AJCC: American Joint Committee on Cancer.