Genetic testing vs microforceps biopsy in pancreatic cysts: Systematic review and meta-analysis

Table 1 Characteristics of studies of molecular analysis included in the analysis

Ref.	Type of study	Number of genes/DNA quantity, ng/microL	Diagnosis	Sample size	Technical success	Adverse events	Diagnostic yield	Surgical cohort	Mean cyst size and range (mm)	Cysts < 3 cm	Cyst location	Specific Cyst Diagnosis	Specific Cyst Diagnosis	High risk cysts	Mucinous low-risk cysts	Benign cysts	Specific cyst type (MA/surgical pathology)
	(study period)	(mean and interval)		(all patients in the study)	(successful molecular analysis)	(major/minor)	(patients with DNA mutations detected)				(H/B/T)Cysts with mutations	(MA/all patients)	(MA/surgical pathology)	(MA/surgical pathology)	(MA/surgical pathology)	(MA/surgical pathology)	IPMN-ADC	IPMN-HG	IPMN-LG	MCN-HG	MCN-LG	SCA	Pseudocyst	NET	Other4
Jones et al[45], 2015	Prospective (Mar 2013-Feb 2014)	39/12.3 (0-1283)	Pathology or cytology	86	79 (only 3 due to NGS failure)	NA	46	10	NA	NA	NA	72/92	5/10	1/6	4/4	0/0	1/4	0/2	4/4	0/0	0/0	0/0	0/0	0/0	0/0
Singhi et al[46], 2016	Retrospective (Jan 2014-May 2015)	6/NA	Pathology or clinicopathologic	225	225	NA	118	41	2.8 (8-115)	152	95/81/49	130/225	32/41	10/14	12/13	10/14	9/92	1/22	12/12	0/0	0/1	2/2	8/8	0/2	0/53
Rosenbaum et al[32], 2016	Retrospective (Mar 2013-Jun 2015)	9/NA	Pathology or clinicopathologic	105	105	NA	67	25	NA	NA	NA	67/1131	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Singhi et al[47], 2017	Prospective (Jan 2014-Ju 2017)	11/6.93 (0.01-248)	Pathology or cytology	642	595	NA	335	102	2.7 (8-210)	NA	320/B+T=306	357/626	77/102	17/29	41/47	19/26	13/13	4/43	39/39	0/2	2/8	2/3	17/17	0/9	0/73
				1058	1004	NA	566 (54%)	178	2,7(8-210)	152		828/965 (86%)	114/153 (74%)	28/49 (62%)	57/64 (89%)	29/40 (73%)	23/26	5/8	55/55	0/2	2/9	4/5	25/25	0/11	0/12

¹113 samples of 105 patients;

²TP53, PIK3CA, PTEN;

³1 ACC;

⁴includes: ACC, retention cyst, lymphoepithelial cyst, epidermoid cyst, and squamoid cyst. MA: Molecular analysis; NA: Non-available data; ACC: Acinar cell cyst; H/B/T: Head body and tail of the pancreas; ADC: Adenocarcinoma; HG: High-grade; LG: Low-grade; NET: Neuroendocrine tumor.

Table 2 Characteristics of studies of microforceps biopsies included in the analysis

Ref.	Type of study	Diagnosis	Sample size	Technical success	Adverse events	Diagnostic yield	Surgical cohort	Mean cyst size and range,(mm)	Cysts < 3 cm	Cyst location	Specific cyst diagnosis	Specific cyst	High risk cysts	Mucinous low risk cysts	Benign cysts	Specific cyst type (MFB/surgical pathology)
	(study period)		(all patients in the study)	(successful cyst puncture and biopsy)	(major/minor)	(histopathologic diagnosis available)				(H/B/T)	(MFB/all patients)	(MFB/surgical pathology)	(MFB/surgical pathology)	(MFB/surgical pathology)	(MFB/surgical pathology)	IPMN-ADC	IPMN-HG	IPMN-LG	MCN-HG	MCN-LG	SCA	Pseudocyst	NET	Other (ACC)
Mittal et al[18], 2018	Retrospective (Dec 2016-June 2017)	Pathology, cytology and cyst fluid analysis	27	27	0/0	24	4	38 (15-70)	20	14/B+T=13	24/27	2/4	1/1	1/3	0/0	0/0	0/0	12/3	-	NA	-	-	1/1	-
Zhang et al[20], 2018	Retrospective (Jan 2016- Set 2017)	Pathology, cytology and cyst fluid analysis	48	46	0/0	36	10	31 (12-60)	23	13/22/13	24/48	7/10	3/4	4/5	1/1	11/3	13/0	4/4	-	01/1	1/1	-	-	1/1
Basar et al[21], 2018	Retrospective (2015-2016)	Pathology, cytology and cyst fluid analysis	42	38	0/2	26	7	28 (12-60)	24	16/17/9	15/42	6/7	4/4	1/2	1/1	2/2	-	1/1	-	01/1	1/1	-	1/1	1/1
Kovacevic et al[19], 2018	Retrospective (Sep 2016-Oct 2017)	Pathology or multidisciplinary conference	31	27	1/2	22	4	34 (12-130)	14	NA/NA/NA	244/31	3/4	0/1	2/2	1/1	0/1	-	33/2	-	-	-	1/1	-	-
			148	138	1/4	108/148 (73%)	25	33 (12-130)	81		63/148 (42%)	18/25 (72%)	8/10 (80%)	8/12 (67%)	3/3 (100%)	3/6	1/0	8/10	-	0/2	2/2	1/1	2/2	2/2

¹1 nondiagnostic on MFB;

²2 nondiagnostic on MFB;

³1 false negative IPMN associated invasive carcinoma;

⁴2 cases with a suspicion of pseudocyst. MFB: Microforceps biopsy; NA: Non-available data; ND: Nondiagnostic; ACC: Acinar cystadenoma; H/B/T: Head body and tail of the pancreas; ADC: Adenocarcinoma; HG: High-grade; LG: Low-grade; NET: Neuroendocrine tumor.