Systematic review of cystic duct closure techniques in relation to prevention of bile duct leakage after laparoscopic cholecystectomy

Table 1 Characteristics of included comparative studies, descending in year of publication

Study, year, country	Study design	Intervention	Control	Aim study
Jain[27], 2011, India	RCT	Ultrasonic shears	Electrocautery	To test the benefit of ultrasonic shears in LC
Redwan[13], 2010, Egypt	RCT	Harmonic shear (Olympus Keymed Sono surg version G2 220–240V 3A)	Titanium clips	To demonstrate the efficiency and safety of the harmonic scalpel
Kandil[14], 2010, Egypt	RCT	Harmonic scalpel (Harmonic ACE, Ethicon Endo-Surgery)	Metal clips	To compare metal clips vs the harmonic scalpel on safety and efficacy in LC
Bessa[15], 2008, Egypt	RCT	Harmonic scalpel (Harmonic ACE, Ethicon Endo-Surgery)	Clip and cautery	To compare the safety and efficacy of the harmonic scalpel vs clip and cautery in LC
Seenu[16], 2004, India	RCT	Absorbable ligature (Vicryl1, Ethicon)	Titanium clips (Ligaclip, Ethicon)	To compare postoperative outcomes after occlusion of the cystic duct with tied knots vs titanium clips
Singal[19], 2018, India	PS	Non-absorbable ligature (Filasilk, Meril)	Titanium clips (Ligaclip, Ethicon)	To study safety and efficacy of silk ligatures compared to clips of closure of the cystic duct
Schulze[17], 2010, Denmark	PS	LigaSure (ForceTriad system, Valleylab)	Titanium clips	To evaluate the safety of the LigaSure system in cholecystectomy
Hüscher[18], 2003, Italy	PS	Harmonic shears (Ultracision, Ethicon Endo-Surgery)	Harmonic shears and absorbable endo-loop	To verify the advantages if ultrasonic dissection
Yang[21], 2014, China	RS	One absorbable clip	Titanium clips	The effectiveness and safety of electrocoagulation after occlusion of the cystic duct and artery with an absorbable clip
Wills[22], 2013, USA	RS	Harmonic scalpel (Harmonic ACE, Ethicon Endo-Surgery) in pts with a cystic duct > 5 mm	Single surgical clip in pts with cystic duct < 5 mm	The comparison of the Harmonic scalpel vs surgical clips in the occlusion of the cystic duct
Matsui[20], 2012, Japan	RS	Locking absorbable clips (Laproclip 8 mm, 12mm, Tyco Healthcare) Locking non-absorbable clip (Hem-o-lok XL, Teleflex Medical)	Endo-loop (SURGITIE, Tyco Healthcare) Suture Metallic clip (ENDO CLIP III, Tyco Healthcare)	To evaluate the effect of locking clips on the leakage from the cystic duct in cholecystectomy
Wu[26], 2011, China	RS	Ultrasonic shears (Harmonic ACE, Ethicon Endo-Surgery)	Clips	To compare conventional LC to SILC
Gelmini[23], 2010, Italy	RS	Harmonic scalpel (Harmonic- Ethicon Endo Surgery)	Clips	To demonstrate that the harmonic scalpel is safe in LC
Rohatgi[24], 2006, United Kingdom	RS	Absorbable locking clips (Laproclip, USS-DG, Tyco)	Titanium clips (Ligaclip, Ethicon)	To compare the efficacy of the locking absorbable clip vs clips in LC
Yano, 2003, Japan[25]	RS	Locking absorbable clips (Laproclip, Davis and Geck)	Ligaclip (metal clip, Ethicon)	To assess if locking clips are safer and less invasive than metal Ligaclips

RS: Retrospective studydesign; RCT: Randomized controlled trial; PS: Prospective study design; LC: Laparoscopic cholecystectomy.

Table 2 Patient and operative characteristics of included comparative studies

Study, year, country	No. of patients	No. of complicated cases	Failure of technique in intervention group	Operating time	Hospital stay
Harmonic scalpel/ shears vs metal clips
Wills[22], 2013, United States	57 vs 148	NR	3	NR	NR
Wu[26], 2011, China	100 vs 100	0 (exclusion criterium)	NR	Mean in minute (SD) 49.2 (13.8) vs 53.3 (24)	NR
Redwan[13], 2010, Egypt	80 vs 80	NR	NR	Mean in minute (SD) 20 (6.8) vs 45 (6.5)	Mean in days (SD) 1 (0.0) vs 1.5 (0.51)
Kandil[14], 2010, Egypt	70 vs 70	NR	NR	Mean in minute (SD) 33.2 (9.6) vs 51.7 (13.8)	Mean in hours (SD) 23.4 (2.29) vs 267.0 (8.94)
Gelmini[23], 2010, Italy	95 vs 90	28 vs 22	17	Median in minute (range) 60 (20-140) vs 80 (45-130)	Median in days (range) 2 (1-16) vs 2 (1-12)
Bessa[15], 2008, Egypt	60 vs 60	0 (exclusion criterium)	NR	Median in minute (range) 32 (18-75) vs 40 (21-85)	NR
Absorbable vs non-absorbable clips
Yang[21], 2014, China	635 vs 728	545 vs 626	NR	Mean in minute (SD) 41.6 (16.5) vs 58.9 (19.4)	2.6 (0.4) vs 2.7 (0.6)
Locking vs non-locking clips
Matsui[20], 2012, Japan	907 vs 110	85 (unknown in which group)	5	NR	NR per group
Rohatgi[24], 2006, United Kingdom	346 vs 148	NR	2	NR	NR
Yano, 2003, Japan[25]	328 vs 444	8 vs 9	0	Mean in minute (SD) 84.6 (1.6) vs 112.7 (2.3)	Mean in days (SD) 7.9 (0.2) vs 8.0 (0.1)
Other
Singal[19], 2018, India	70 silk ligature vs 70 titanium clips	0 (exclusion criterium)	0	NR	NR in detail (“similar”)
Schulze[17], 2010, Denmark	101 Ligasure vs 113 titanium clips	Only elective surgery	NR	NR	NR
Seenu[16], 2004, India	53 absorbable ligature vs 52 titanium clips	NR	NR	Mean in minute 78 vs 66	NR
Hüscher[18], 2003, Italy	331 harmonic shears vs 130 harmonic shears + endoloop	109 vs 68	NR	Mean in minute 76.8 vs 97.5	Mean in days 4.3 vs 5.1

NR: Not reported.

Table 3 Clinical outcomes of included comparative studies

Study, year, country	No. of patients	Leakage of the cystic duct	Bile duct injury	Biloma	Intra-abdominal abcess
Harmonic scalpel/shears vs metal clips
Wills[22], 2013, United States	57 vs 148	1 vs 1	1 (D) vs 0	1 vs 0	0 vs 0
Wu[26], 2011, China	100 vs 100	0 vs 1	0 vs 0	0 vs 0	0 vs 0
Redwan[13], 2010, Egypt	80 vs 80	0 vs 1	0 vs 0	0 vs 0	0 vs 0
Kandil[14], 2010, Egypt	70 vs 70	0 vs 1	0 vs 0	NR	NR
Gelmini[23], 2010, Italy	95 vs 90	0 vs 0	0 vs 0	NR	2 vs 0
Bessa[15], 2008, Egypt	60 vs 60	0 vs 0	0 vs 0	NR	NR
Locking absorbable vs locking non-absorbable clips
Yang[21], 2014, China	635 vs 728	0 vs 7	NR	NR	1 vs 2
Locking vs non-locking clips
Matsui[20], 2012, Japan	907 vs 110	0 vs 0	NR	NR	NR
Rohatgi[24], 2006, United Kingdom	344 vs 146	0 vs 3	NR	2 vs 2	NR
Yano[25], 2003, Japan	328 vs 444	1 vs 2	2 vs 4 (severity not reported)	NR	NR
Other
Singal[19], 2018, India	70 silk ligature vs 70 titanium clips	0 vs 0	NR	NR	NR
Schulze[17], 2010, Denmark	101 Ligasure vs 113 titanium clips	0 vs 0	0 vs 0	NR	NR
Seenu[16], 2004, India	53 absorbable ligature vs 52 titanium clips	2 vs 2	NR	NR	NR
Hüscher[18], 2003, Italy	331 harmonic shears vs 130 harmonic shears + endoloop	7 vs 3	1 (D) vs 0	NR	0 vs 1

Amsterdam classification was used to identify the severity of the bile duct injuries: B: Major bile duct leaks with or without concomitant biliary strictures; C: Bile duct strictures without bile leakage; D: Complete transection of the duct with or without excision of some portion of the biliary tree.

Table 4 Outcomes of non-comparative studies

Study, year, country	Study design		Intervention	No. of patients	No. of complicated cases	CDL	Biloma/abcess	BDI	Failure of technique
Harmonic scalpel/ shears /stapler
Jain[27], 2011, India	RCT5		Harmonic shears	100	0 (exclusion criterium)	0	0	NR	NR
Ramos[44], 2015, Brazil	PS		Harmonic shears	125	0 (exclusion criterium)	0	NR	NR	NR
Patel[45], 2010, United Kingdom	PS		Harmonic scalpel (LCS-5, Ethicon)2	100	NR	1	NR	1 (D)	NR
Westervelt[46], 2004, United States	PS		Harmonic scalpel (unknown)	100	NR	0	NR	NR	2
Power[47], 2000, Ireland	PS		Harmonic scalpel (Ultracision, Ethicon Endo-Surgery) and clip	282	101	2	NR	NR	NR
Lee[28], 2011, South Korea	RS		Endo-GIA (US Surgical Corp.)1	921	90	0	NR	4 (D)	NR
Tebala[29], 2006, Italy	RS		Harmonic shears (Ultracision, Ethicon Endo- Surgery)	100	0 (exclusion criterium)	0	1/NR	0	2
Ligature
Shah[48], 2010, Nepal	PS		Intracorporeal single ligation	80	19	0	NR	NR	NR
Carvalh[49], 2009, Brazil	PS		Surgical knots (2-0 polyester)4	1000	NR	0	NR	0	NR
Talebpour, 2007, Iran[50]	PS		Absorbable sutures and intracorporeal knots	200	25	0	NR	1 (B)	18
Suo[36], 2013, China	RS		Absorbable thread (VICRYL_ W9215, Ethicon)	1096	296	0	NR /0	0	NR
Golash[37], 2008, Oman	RS		Intracorporeal ligation (3/0 Vicryl)	1000	NR	0	NR	NR	0
Fullum[38], 2005, United States	RS		Two 2–0 PDS Endoloops (Ethicon Endo-Surgery)	105	22	0	NR	NR	NR
Locking clips
Leung[39], 1996, Hong Kong	RS		PDS-clip (Ethicon Endo-surgery)	272	94	3	4 intra-peritoneal collections	NR	45 (30 in complicated group)
Clips
Sinha[40], 2012, India		RS	Ligaclip (titanium clip, Ethicon)4	756	NR	4	NR	NR	NR
Agresta[41], 2011, Italy		RS	Titanium clips4	932	123	1	NR	NR	NR
Feroci[32], 2011, Italy		RS	Polymeric absorbable clip	664	NR	0	0	NR	NR
Ou[42], 2009, China		RS	Clips	10000	NR	6	NR	0	NR
Ojima[35], 2007, Japan		RS	Clips	1127	NR	3	NR	23	NR
Lee[33], 2004, Taiwan		RS	Clips4	1009	78	5	NR/1	2 (D)	NR
Dolan[43], 1999, Nothern Ireland		RS	Titanium clips	303	18	0	1 / 0	NR	0
Wise Unger[30], 1996, United States		RS	Clips	22165	NR	58	NR	NR	NR
Feussner[31], 1991, Germany		RS	Clips	178	28	1	NR	NR	NR
Other
Lewandowski[34], 2006, Poland	RS		LigaSure (Valleylab)	129	NR	0	NR	2 (1B, 1D)	NR

Amsterdam classification was used to identify the severity of the bile duct injuries: B: Major bile duct leaks with or without concomitant biliary strictures; C: Bile duct strictures without bile leakage; D: Complete transection of the duct with or without excision of some portion of the biliary tree.

¹Only in patients with an inflamed an dilated cystic duct (> 1.0 cm);

²Only in patients with an cystic duct < 5 mm; ³severity unknown;

⁴In patients undergoing MLC (mini LC: three ports) or SILC;

⁵Method of closure not described in one study arm, therefore not used as comparative cohort. CDL: Cystic duct leakage; BDI: Bile duct injury; RS: Retrospective study design; PS: Prospective study design; CD: Cystic duct; LC: Laparoscopic cholecystectomy.