A systematic review and meta-analysis of Harmonic technology compared with conventional techniques in mastectomy and breast-conserving surgery with lymphadenectomy for breast cancer

Figures & data

Table 1 Study and baseline characteristics for studies meeting inclusion criteria

Reference	Country	Interventions evaluated	n	Mean age ± SD or (range)	Surgery	Included end points
Anlar et al^Citation5	Turkey	UltraCision Harmonic scalpel Electrocautery Scalpel	39 41 40	52 (27–74)a 52 (24–82)a 51 (29–68)a	Modified radical mastectomy and axillary LN dissection	• Operating time • Intraoperative blood loss • Overall seroma • Hematoma • Wound infection • Necrosis • Ecchymosis
Bohm et al^Citation4	Germany	Harmonic FOCUS + electrocautery Scalpel and electrocautery with scissors	54 52	56.6±11.5 59.1±12.3	BCS (lumpectomy and segmentectomy) and axillary dissection (when indicated)	• Operating time • Postoperative drainage volume of chest wall • Postoperative hospital length of stay • Overall seroma • Hematoma
Damani et al^Citation32	Pakistan	Ultracision Harmonic scalpel Olympus electrocautery (monopolar diathermy)	25 25	43.8±6.7 43.9±7.1	Modified radical mastectomy	• Operating time • Intraoperative blood loss • Postoperative drainage volume of chest wall • Overall seroma • Hematoma • Wound infection • Necrosis
He et al^Citation6	People’s Republic of China	Harmonic FOCUS Electrocautery	64 64	48.5 (23–72)a	Axillary LN dissection for breast cancer with mastectomy or BC (lumpectomy) surgery	• Operating time • Intraoperative blood loss • Postoperative hospital length of stay • Overall seroma • Hematoma • Wound infection • Necrosis
Iovino et al^Citation7	Italy	Harmonic scalpel Traditional scalpel, scissors, ligations, electrocautery	30 30	61 (39–81)a 65 (42–78)a	Axillary LN dissection for breast cancer: conservative surgery (83%) and mastectomy (17%)	• Operating time • Intraoperative blood loss • Postoperative drainage volume of chest wall • Postoperative hospital length of stay • Overall seroma • Hematoma • Wound Infection
Khan et al^Citation30	Pakistan	J-Hook Harmonic scalpel Electrocautery	75 75	50±12.2 48.5±14.5	Modified radical mastectomy and axillary LN dissection	• Operating time • Intraoperative blood loss • Total complications • Overall seroma • Hematoma • Wound infection • Necrosis
Khater^Citation31	Egypt	Harmonic UltraCision shears Valley Lab Force FX Electrocautery	30 30	54.47±7.57 56.27±9.05	Modified radical mastectomy and axilia dissection	• Operating time • Intraoperative blood loss • Overall seroma • Hematoma • Necrosis
Kontos et al^Citation26	England	UltraCision Harmonic scalpel with curved blade or hook Valley Lab Force FX Electrocautery	15 17	60 (40–76)b 58 (32–86)b	Modified radical mastectomy with sentinel node biopsy, skin sparing mastectomy with immediate reconstruction and wide excision and axillary clearance as part of BCS	• Operating time • Total complications • Overall seroma • Hematoma • Wound infection • Necrosis
Kozomara et al^Citation33	Bosnia and Herzegovina	UltraCision Harmonic scalpel Olympus electrocautery (monopolar)	31 30	62±17 c	Modified radical mastectomy and LN dissection	• Operating time • Intraoperative blood loss • Overall Seroma • Wound infection
Lumachi et al^Citation28	Italy	UltraCision Harmonic scalpel Scalpel	38 38	55.1±11.8 c	Modified radical mastectomy or BC (lumpectomy) surgery with axillary LN dissection for breast cancer; no immediate breast reconstruction	• Postoperative hospital length of stay
Rohaizak et al^Citation8	Malaysia	UltraCision Harmonic scalpel Value Lab Diathermy Electrocautery	20 20	53.0±7.0 53.0±9.0	Modified radical mastectomy and axillary LN dissection	• Postoperative drainage volume of chest wall • Overall seroma • Wound infection • Necrosis
Yilmaz et al^Citation29	Turkey	UltraCision Harmonic scalpel Scalpel Olympus EUS 10 Electrocautery	29 27 26	52.0±9.5 50.2±9.3 48.5±9.8	Modified radical mastectomy and axillary LN dissection	• Operating time • Intraoperative blood loss • Overall seroma • Hematoma • Wound infection • Necrosis • Ecchymosis

Notes:

a Age reported as median (range).

b Age reported as mean (range).

c Only an overall age range was provided by the authors. Abbreviations: LN, lymph node; SD, standard deviation; BCS, breast-conserving surgery.

Figure 1 PRISMA diagram for the systematic literature review.

Abbreviations: BCS, breast-conserving surgery; LN, lymph node; RCT, randomized controlled trial.

Figure 2 Risk of bias assessment for studies meeting inclusion criteria.

Table 2 Qualitative risk of bias assessment summary

Study	Sequence generation	Allocation concealment	Blinding of personnel and participants	Blinding of outcomes	Incomplete outcome data addressed	Free of selective reporting	Free of other bias
Anlar et al^Citation5	Unclear	Unclear	Yes	Yes	Yes	Unclear	Yes
Bohm et al^Citation4	Yes	Unclear	Yes	Yes	Yes	Unclear	Yes
Damani et al^Citation32	Unclear	Unclear	Yes	Yes	Yes	Unclear	Yes
He et al^Citation6	Unclear	Yes	Yes	Yes	Yes	Unclear	Yes
Iovino et al^Citation7	Yes	Yes	Yes	Yes	Yes	Unclear	Yes
Khan et al^Citation30	Yes	Unclear	Yes	Yes	Yes	Yes	No
Khater^Citation31	Unclear	Unclear	Yes	Yes	Yes	Unclear	Yes
Kontos et al^Citation26	Yes	Yes	Yes	Yes	Yes	Unclear	Yes
Kozomara et al^Citation33	Unclear	Unclear	Yes	Yes	Yes	Unclear	Yes
Lumachi et al^Citation28	Unclear	Unclear	Yes	Yes	Yes	Unclear	Yes
Rohaizak et al^Citation8	No	No	Yes	Yes	Yes	Unclear	Yes
Yilmaz et al^Citation29	Unclear	Unclear	Yes	Yes	Yes	Unclear	Yes

Notes: Yes, low risk of bias; No, high risk of bias.

Table 3 Summary of primary and sensitivity analyses

Outcome	Primary analysis	% Decrease with Harmonic technology	Sensitivity analyses
			Exclusion of studies not randomizing device use in breast surgery^Citation28	Exclusion of studies not randomizing device use in LN dissection^Citation5,Citation29	Exclusion of studies requiring imputation^Citation4,Citation5,Citation7,Citation26	Exclusion of “lower” quality studies^8,30a
Operating time (minutes) (MD [95% CI]; P-value; I^2 value)	−5.07 [95% CI: −10.98 to 0.83]; P=0.09; I^2=83%	4.60	Same as primary analysis	−4.46 [95% CI: −10.92 to 2.00]; P=0.18; I^2=86%	−6.87 [95% CI: −13.78 to 0.04]; P=0.05; I^2=87%	−5.92 [95% CI: −12.13 to 0.30]; P=0.06; I^2=84%
Intraoperative blood loss (mL) (MD [95% CI]; P-value; I^2 value)	−87.54 [95% CI: −137.07 to −38.02]; P=0.0005; I^2=99%	37.59		−102.26 [95% CI: −157.68 to −46.84]; P=0.0003; I^2=99%	−109.57 [95% CI: −135.06 to −84.07]; P<0.00001; I^2=87%	−88.20 [95% CI: −143.05 to −33.36]; P=0.002; I^2=99%
Postoperative drainage volume of chest wall (mL) (MD [95% CI]; P-value; I^2 value)	−42.14 [95% CI: −65.90 to −18.39]; P=0.0005; I^2=87%	45.77		Same as primary analysis	−46.04 [95% CI: −78.11 to −13.97]; P=0.005; I^2=91%	−35.03 [95% CI: −56.91 to −13.15]; P=0.002; I^2=88%
Postoperative hospital length of stay (days) (MD [95% CI]; P-value; I^2 value)	−1.38 [95% CI: −2.38 to −0.38]; P=0.007; I^2=98%	22.44	−1.79 [95% CI: −3.07 to −0.51]; P=0.006; I^2=98%		−1.74 [95% CI: −3.16 to −0.33]; P=0.02; I^2=98%	Same as primary analysis
Total complications (RR [95% CI]; P-value; I^2 value)	0.48 [95% CI: 0.30–0.77]; P=0.002; I^2=0%	52	Same as primary analysis		Same as primary analysis	Too few studies to inform (<2)
Overall seroma (RR [95% CI]; P-value; I^2 value)	0.54 [95% CI: 0.43–0.69]; P<0.00001; I^2=25%	46		0.56 [95% CI: 0.41 to 0.76]; P=0.0002; I^2=30%		0.51 [95% CI: 0.39–0.68]; P<0.00001; I^2=43%
Hematoma (RR [95% CI]; P-value; I^2 value)	0.57 [95% CI: 0.30–1.10]; P=0.09; I^2=0%	43		0.44 [95% CI: 0.21 to 0.91]; P=0.03; I^2=0%		0.65 [95% CI: 0.33–1.28]; P=0.21; I^2=0%
Wound infection (RR [95% CI]; P-value; I^2 value)	0.71 [95% CI: 0.32–1.56]; P=0.39; I^2=0%	29		0.55 [95% CI: 0.21 to 1.44]; P=0.22; I^2=0%		0.78 [95% CI: 0.31–1.98]; P=0.60; I^2=0%
Necrosis (RR [95% CI]; P-value; I^2 value)	0.51 [95% CI: 0.28–0.96]; P=0.04; I^2=0%	49		0.33 [95% CI: 0.01 to 7.81]; P=0.08; I^2=0%		0.62 [95% CI: 0.31–1.25]; P=0.18; I^2=0%
Ecchymosis (RR [95% CI]; P-value; I^2 value)	0.67 [95% CI: 0.36–1.25]; P=0.21; I^2=0%	33		Too few studies to inform (<2)		Same as primary analysis

Notes:

a Lower quality study defined as: ≥4 “Unclear” OR one “No” listed in any risk of bias assessment category for Khan et al³⁰ and Rohaizak et al.⁸

Abbreviations: RR, risk ratio; CI, confidence interval; LN, lymph node; MD, mean difference.

Figure 3 Forest plot of meta-analysis results for intraoperative blood loss (mL).

Abbreviations: SD, standard deviation; CI, confidence interval; LN, lymph node; HT, Harmonic technology; Conv Tech, conventional techniques; IV, inverse variance.

Figure 4 Forest plot of meta-analysis results for postoperative drainage volume (mL) from chest wall.

Abbreviations: SD, standard deviation; CI, confidence interval; LN, lymph node; HT, Harmonic technology; Conv Tech, conventional techniques; IV, inverse variance.

Figure 5 Forest plot of meta-analysis results for postoperative hospital length of stay (days).

Abbreviations: SD, standard deviation; CI, confidence interval; LN, lymph node; HT, Harmonic technology; Conv Tech, conventional techniques; IV, inverse variance.

Figure 6 Forest plot of meta-analysis results for overall seroma.

Abbreviations: CI, confidence interval; LN, lymph node; HT, Harmonic technology; Conv Tech, conventional techniques; IV, inverse variance.

Figure 7 Forest plot of meta-analysis results for necrosis.

Abbreviations: CI, confidence interval; LN, lymph node; HT, Harmonic technology; Conv Tech, conventional techniques; M-H, Mantel–Haenszel.

Table S1 Secondary analysis of dichotomous outcomes using the OR, Mantel–Haenszel method with a fixed-effects model

Outcome	Secondary analysis (OR [95% CI]; I^2 value)	P-value
Total complications	0.34 [0.17–0.66]; 0%	0.002
Overall seroma	0.39 [0.27–0.57]; 0%	<0.00001
Hematoma	0.53 [0.26–1.08]; 16%	0.08
Wound infection	0.67 [0.29–1.58]; 0%	0.37
Necrosis	0.46 [0.23–0.91]; 0%	0.03
Ecchymosis	0.60 [0.27–1.34]; 0%	0.21

Notes: The analysis of outcomes with rare events (event rate <1%) was conducted using Peto OR. A P-value less than 0.05 (in bold) is considered statistically significant.

Abbreviations: OR, odds ratio; CI, confidence interval.

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