Surgical Correction of Inverted Nipples.

Nipple inversion is a common pathologic condition affecting 2%-10% of women. Congenital inversions are the most common forms, while acquired inversions are less frequent. This condition can induce psychological discomfort, functional problems that could prevent adequate breast feeding, and cosmetic dissatisfaction, and create local irritation and infection. The aim of this article was to provide a comprehensive review of the literature about surgical treatment of inverted nipple.
METHODS: A literature search was conducted by using PubMed, Google Scholar, and Cochrane database using the following MeSH terms: "inverted nipple," "inverted nipple surgery," "inverted nipple treatment," and "inverted nipple management." Studies that described surgical treatment and included outcomes and recurrence rate were included.
RESULTS: Thirty-three articles were considered suitable, including 3369 inverted nipple cases. Eight studies described techniques with lactiferous ducts damaging, while 25 studies described techniques with lactiferous duct preservation using dermal flaps, sutures, or distractor systems. The average follow-up was 23.9 months. Overall, a satisfactory correction was reached in 88.6% of cases, and the recurrence rate was 3.89%.
CONCLUSIONS: To our knowledge, our review includes the largest sample size in the literature. The heterogeneity and subjectivity of outcomes make it more complicated to state which is the best surgical strategy to adopt to obtain satisfactory and stable results with minimal morbidity. This study highlights the need of a standardized method to evaluate outcomes, including aesthetic, functional and psychological results, while using objective and subjective measurement instruments.

INTRODUCTION

Nipple inversion was first described by Cooper in 1840[1] and is defined as a nonprojecting nipple[2] that lies below the plane of the areola. It affects 2%–10% of women.[3] This frequent pathologic condition can be congenital or acquired, unilateral or bilateral, and it can present different degrees of severity. Congenital inversions are the most common forms, and they depend on hypoplasia and the retraction of the lactiferous ducts produced by the presence of surrounding fibrous bands at the base of the nipple.[4,5] Acquired inversions can be secondary to mammary carcinoma, periductal mastitis, breast surgery, or breastfeeding.

The universally accepted classification of inverted nipple was proposed by Han and Hong,[6] and they classified the inversion into 3 grades:

- Grade I: the nipple can be easily pulled out by gentle palpation around the areola and maintains its projection quite well without any traction. Lactiferous ducts are normal.

- Grade II: the nipple is also pulled out by palpation but not as easily as in grade I and tends to retract. The nipple has medium fibrosis, and the lactiferous ducts are mildly retracted but do not need to be cut to release the fibrosis. Also, there are histologically rich collagenous stromata with several bundles of smooth muscle.

- Grade III: severe form in which inversion and retraction are important. Pulling the nipple out manually is really difficult, and a traction suture is needed to keep it protruded. Fibrosis beneath the nipple is severe and the soft tissue is insufficient. Histologically, the terminal lactiferous ducts and lobular units are atrophic and replaced with severe fibrosis.

Another classification proposed by Schwager et al[7] divides inverted nipples into 2 forms depending on the severity of the inversion: an “umbilicated” form (intermittently inverted) and an “invaginated” form (permanently inverted). Inverted nipple can induce psychological problems such as severe psychosexual discomfort.[8,9] Moreover, this condition can cause cosmetic and functional problems that prevent adequate breast feeding and can create local irritation and infection.

Generally, the nipple and areola can present in different size, color, and shape. The average height and diameter of the nipple are both about 1 cm, and the average diameter of the areola is about 3 cm.[10] Five normal shapes of nipples were identified: rectangular, omega, round, cup, and slanting.[11]

Since 1879, when Kehrer described the first surgical correction of nipple inversion, many surgical and nonsurgical corrective strategies have been proposed. Indeed, there is not a single technique adapted to all types of inverted nipples because of the heterogeneity of the clinical presentation. Ideally, the aim of every treatment should be to permanently recover normal projection and shape; to maintain a normal sensitivity; and finally to preserve the lactiferous ducts causing minimal scars. Nonoperative strategies, including manual traction, piercing, and vacuum therapy, can be used only in grade I inversion. The aim of this article was to provide a comprehensive review of the literature about surgical treatment of inverted nipples.

MATERIALS AND METHODS

A literature search was performed by using PubMed, Google Scholar, and Cochrane database according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)[12] guidelines to provide a comprehensive review of the literature about surgical treatment of inverted nipples.

The following MeSH terms were used: “inverted nipple,” “inverted nipple surgery,” “inverted nipple treatment,” and “inverted nipple management” (period: 1999–2020; last search on 22 March 2020). Two different reviewers performed double screening and data extraction. Abstracts were examined to identify qualified papers. Reference lists of relevant articles were screened for supplementary studies. A flowchart based on PRISMA guidelines is shown in Figure 1.

Fig. 1.

Flowchart according to PRISMA guidelines.

Inclusion and Exclusion Criteria

Articles were selected based on the following inclusion criteria: (1) Studies investigating surgical treatment of inverted nipples; (2) registration of outcomes after surgical treatment; (3) registration of recurrence rate after surgical treatment; and (4) full text availability in English.

The studies were excluded due to any one of the following criteria: (1) Articles reporting only on surgical technique and not surgical outcomes; (2) articles including <10 nipples; (3) <6 months follow-up; (4) review articles; (5) case report; (6) nonreferenced articles; and (7) expert opinion or comment (Level V).

Data Collection

Extracted data included author names, years of publication, number of nipples included, sex, mean age, etiology of nipple inversion, affected side (one or bilateral), Han-Hong grading,[6] surgical strategy (lactiferous ducts damaging or preservation), mean follow-up time, results (correction rate, nipple projection, nipple shape, and quality of scar), recurrence rate, nipple sensitivity, breast feeding, and postoperative complications.

Statistical Analysis

Statistical analysis was performed using SPSS statistical software (version 24.0; IBM Corporation, Somers, N.Y.).

RESULTS

One hundred and nine articles were identified after excluding duplicates. Two different authors screened all the records through titles and abstracts. Sixty full-text articles were examined for eligibility. Thirty-three articles[4-6,8,9,11,13-41] were considered suitable based on relevance, appropriateness, and actuality and were included in this systematic review (Fig. 1).

Among the 33 selected studies, 17 were retrospective studies, 16 were prospective studies, of which one was a randomized controlled trial. A total of 3369 inverted nipples were included in the review, and the sample size of each study ranged from 14 to 562 nipples. Nineteen of 35 articles reported the etiology of the nipple inversion including 794 nipples: in 93.9% of the cases, the inversion was congenital, and in 6.1% of the cases, the inversion was acquired. The acquired etiology has been referred to periductal mastitis, breast cancer, or previous mammoplasty. Regarding the laterality of the inversion, 16 articles described patients affected by bilateral nipple inversion (642 patients): of these patients, 66.97% were affected on both sides (430/642 patients). Seven studies included recurrence, amounting to 22 patients.

All the patients were women except 2. Twenty-four studies reported patients’ age expressed as mean or range or as both mean and range. The mean age of patients was 29.5 years (range 16–75).

Grading

Twenty-four studies reported a preoperative grading according to Han-Hong. Among them, 349 nipples were classified as grade I, 838 nipples were classified as grade II, and 562 nipples were classified as grade III. One study reported the classification proposed by Schwager et al.[7]

Surgical Strategies

Concerning surgical strategies, 4 studies described techniques with lactiferous ducts damaging (Table 1[15,18,29,31]), 25 described techniques with lactiferous ducts preservation and 4 studies included both (Table 2[6,13,16,41]) (Fig. 2). Surgical approaches without breastfeeding preservation are based on the section of the lactiferous ducts and the stabilization of the nipple’s eversion using Z-plasties and/or internal sutures (vertical suture, 5-point star suture, loop stitches with an arabesque-like shape) (Fig. 3).

Table 1.

Surgical Techniques with Lactiferous Ducts Damaging

Author/Year	Type	Sample Size	Grading	Surgical Technique	Follow-up	Results	Recurrence Rate	Nipple Sensitivity	Breastfeeding (BF)	Postoperative Complications
Lee et al/2003[15]	Prospective analysis (?)	17 nps	Grade I:0	Inferior periareolar incision (5–7 o’clock)	12 m	100% satisfactory correction	0	Not reported	Not reported	Not reported
			Grade II: 0	Two internal vertical sutures		100% patients satisfaction
			Grade III: 17	Without the use of dermal flaps Postoperative stent for 3 m
Serra-Renom et al/2004[18]	Retrospective analysis	12 ptsMean age 24 y (18–46)	—	Small periareolar incision (5–7 o’clock)	12 m	100% satisfactory correction	0	Not reported	Not possible	No major complications
				Section erector muscle and lactiferous canaliculi -5-point star stitches
Sapountzis et al/2011[29]	Prospective analysis	18 pts22 nps	Grade III	4 microincisions of about 0.5 cm at 12–3–6–9 o’clock	3–12 m	91% satisfactory outcome	2 npsEarly postoperative (loose knot)	Normal	Not possible	No major complications
		Mean age 26 y (20–37)		Erector muscle and lactiferous ducts dissected and sectioned			Required reoperation
				Loop stitch with an arabesque-like shape (between 3–9 and 6–12 o’clock)
				Donut dressing 1 w
Bracaglia et al/2012[31]	Retrospective analysis	19 pts	Grade I: 0	Periareolar incision in the lower quadrants	26 m (6 m–3 y)	97% satisfactory correction	1 case (3%)	One patient developed a temporary loss of sensibility	Not possible	No major complications
		35 nps	Grade II: 0	Ducts and the fibrous tissue section		97% patients satisfaction (shape and projection) Minimal scars
		All congenital	Grade III: 20 (+15 relapse)	Dermoglandular monolobed flap overturned under the nipple to fill the “dead space”
		15 recurrence Mean age 36 y (25–46)		No protective devices

Table 2.

Surgical Techniques with Lactiferous Ducts Damaging or Preservation

Author/Year	Type	Sample Size	Grading	Surgical Technique	Follow-up	Results	Recurrence Rate	Nipple Sensitivity	Breastfeeding (BF)	Postoperative Complications
Han and Hong/1999[6]	Retrospective analysis	60 pts	Grade I: 14	BF preservation	—	97.2% satisfactory correction	2.8% (3 nps)	Not reported	Not reported	1 hematoma; 3 sloughing
		107 nps	Grade II: 84Grade III: 9	Grade I: Nonincisional + purse-string suture						No necrosis; No infection
				Grade II: Release of fibrosis + purse-string suture
				No BF preservation
				Grade III: Release of fibrosis +cutting of ducts +dermal flaps+ purse-string suture
Sakai et al/1999[13]	Retrospective analysis	148 pts	Grade I: 23	Method I: 172 nps	—	Method I: 163 94.7% excellent results	8 npsMethod I = 5 recurrence	Not reported	24 nps (12 pts)	4 partial necrosis
		255 nps	Grade II: 88	No BF preservation: Vertical incision into the nipple, contracted tissue excision, Z-plasties on the neck of the nipple					Normal
			Grade III: 144				Method II: 3 recurrence
				BF preservation: Contracted tissues are released, Z-plasties on the neck of the nipple		Method II: 35 92.1% good results
				Method II: 38 nps
				BF preservation: Vertical incision contracted tissues are released and 2 dermal flaps are sutured in the center like a suspension bridge
Lee and Cho/2004[16]		11 pts	—	Modified Namba technique[16]	19.6 m (range 6–54)	Modified Namba technique	Modified Namba technique	Teimourian technique	Not reported	No major complications
		20 nps						Normal
		(9 bilat)		BF preservation			2 nps recurrence
		Mean age 35.4 y (24–47)		3 half–Z-plasties are designed		9 nps69.2% satisfactory outcomes
		All cong		Blunt subdermal dissection is made around the entire circumference of the nipple neck		3 loosing follow-up
				Triangular flaps are elevated and 2-cm depth of the breast parenchyma is vertically spread		Modified Teimourian technique: 100% satisfactory outcomes
				Protective covering for 3 weeks
				Modified Teimourian technique[4]
				No BF preservation
				Triangular flaps
Kalaaji et al/2019[41]	Retrospective analysis	86 pts	Grade I: 16	4 Techniques	14 m (2–57)	Patient satisfaction: 43 of 71 cases (61%) after the first operation	32 pts–55 nps after the first operation (6 pts–nps after the second operation, in 1 pt–1np after the third operation)	Not reported	Not reported	4 local infection
		161 nps	Grade II: 56	1. Central tunnelization of the retracted fibers/ducts (39 pts, 45%)						2 local irritation
		87% bilat	Grade III: 89
		Mean age 28.7 y (18–61)
				2. Partial incision of the center of the inversion through a tunnel (31 pts, 36%)		23 patients (93%) after the second operation,
				3. Total cut of the lactiferous ducts (16 pts, 19%)		3 patients after the third operation (97%).
				4. Fat grafting as support in 14 patients (26 nipples)		2 patients were not satisfied and 15 patients were not available for follow-up
				Postoperatively, nipples were suspended for 4 weeks using a manually reconstructed device

Fig. 2.

Surgical treatment of inverted nipples.

Fig. 3.

Techniques with lactiferous ducts damaging.

Techniques with breastfeeding conservation are based on the careful dissection of the fibrous bands by the lactiferous ducts, which therefore remain completely or partially preserved. Techniques with lactiferous ducts preservation were divided into 3 subcategories based on the use of dermal flaps, sutures, or distractor systems. Fifteen studies described the use of dermal flaps (Table 3 [5,8-9,11,14,17,21,24,26, 28,30,32,34,35,40]) with triangular, rhomboid, longitudinal, elliptical, or “diamond” shapes (Fig. 3). Six studies described several types of sutures (Table 4[4,19,25,36-38]), including peripheral circular stitches on the base of the nipple or internal sutures (Fig. 4). Finally, 4 authors reported the use of distractor systems (Table 5[20,23,27,39]). One author described an endoscopic technique with a dermal fat graft transfer from the groin to fill the base of the nipple.[22] Two authors reported the use of magnification to better visualize and dissect lactiferous ducts.[22,40]

Table 3.

Surgical Techniques with Lactiferous Ducts Preservation: Dermal Flaps

Author/Year	Type	Sample Size	Grading	Surgical Technique	Follow-up	Results	Recurrence Rate	Nipple Sensitivity	Breastfeeding (BF)	Postoperative Complications
Crestinu/2000[5]	Retrospective analysis	452 nps	—	Umbrella musculocutaneous flap	60 m	99.8% satisfactory correction	1 nps (0.2%)	Normal	Normal after 2–3 y	Not reported
				Blocking notch
				No special or bulky dressing
Huang/2003[14]	Retrospective analysis	25 pts	—	Three diamond-shaped inferiorly based dermofibrous flaps	6–60 m	100% satisfactory correction	0	Not reported	Not reported	5 nps sloughing of partial skin
		46 nps
				“Donut” dressing 6 m postoperatively		Minimal scar				No major complications
Kim et al/2003[9]	Prospective analysis	11 pts	Grade I: 0	Two triangular areolar dermal flaps	8.7 m (range, 3–12)	100% satisfactory correction	0	Normal	Not reported	No major complications
		16 nps	Grade II: 13
		Mean age: 27 (18–31)	Grade III: 9	No special or bulky dressing		100% patients satisfaction
		All congenital				Minimal scar
Ritz et al/2004[17]	Prospective analysis	11 pts	—	Two dermofibrous longitudinal flaps	27 m	16 nps	1 pt, 2 nps (Grade III)	1 pt decrease of nipple sensation	Reduced but possible (3 pts)	No major complications
		18 nps				88.8% satisfactory outcomes
		Mean age 31 y
Kim et al/2006[11]	Prospective analysis	15 pts	21 nps umbilicated type	Three diamond patterns, set at 120-degree intervals	14 m	100% satisfactory correction	0	Brush test 3 m after surgery: no disturbance was found in any of the patients.	Normal (5 pts)	No major complications
		29 nps (14 bilat)
		Mean age: 26 y (21–55)	8 nps invaginated type	Dermal flap
		All congenital		No special or bulky dressing
Burm and Kim/2007[21]	Prospective analysis	17 pts	Grade I: 0	Two-four diamond-shaped quadrangles	6.3 m (3–8)	96.5% satisfactory correction	3.5%	Normal (no permanent numbness)	Not reported	No major complications
		28 nps	Grade II: 19
		Age range (21–29)	Grade III: 9	Donut-type pad dressing for 2–3 m postoperatively		1 case (3.5%) unsatisfactory aesthetic projection
		26 congenital
		2 acquired (mastitis)
Wu et al/2008[24]	Prospective analysis	9 pts		Two triangular areolar dermofibrous flaps	3–18 m	100% patients satisfaction	0	No permanent sensory disturbance	Not reported	No major complications
		14 nps
		Mean age, 23 y (19–36)		“Donut” dressing		Nipples are relatively symmetric
		13 congenital		Continuous traction 2 weeks
		1 recurred
Min et al/2009[26]	Prospective analysis	46 pts	Grade I: 0	Triangular dermal flaps under the areolar skin (scar-free)	3–12 m	100% patients satisfaction	0	Not reported	Not reported	2 hypopigmentation over the areola with areolar flaps (resolved spontaneously)
		87 nps (41 bilat)	Grade II: 53
		Age range 22–49	Grade III: 34	Traction sutures for 3 days		Minimal scar
		All congenital
McG Taylor et al/2011[8]	Retrospective analysis	20 pts	Grade I: 0	2 Areolabased dermoglandular rhomboid flaps at 6 and 12 o’ clock	1–16 y (32 nps)	15 nps maintained complete eversion	5 nps	On specific questioning, no patients reported a reduction to nipple sensation following surgery	Normal (3 pts 4: 10–16 y post surgery)	3 superficial infection treated with oral antibiotics
		35 nps (15 bilat)	Grade II–III: 35				Early postoperatively (3 m follow-up)
		Mean age 35 y (16–48)
		34 congenital		Medial translation of the 2 flaps		13 nps variable
		1 acquired (mastitis) 2 recurred		No special or bulky dressing		100% patients satisfaction
						[(overall satisfaction score > 7/10)]
Persichetti et al/2011[28]	Retrospective analysis	52 pts	Grade I: 16	Vertical incision in the middle of the nipple, extended below the areola plane as deep as necessary to completely release the retracted ducts (interruption of central lactiferous ducts)	1–6 y	Patients and surgeon were asked to score nipple cosmetic outcome and their own satisfaction	1 nps	Preserved	3/5 normal (peripheral lactiferous ducts sparing	2 wound dehiscence
		53 nps (24 bilat)	Grade II: 20
		49 congenital	Grade III: 16				1 y (successfully treated with a second procedure)			1 partial scarring
		3 acquired
				Nipple is thus dissected into 2 dermoglandular flaps		Results were good considering projection, shape, and sensitivity
				2 V-Y advancement flaps		Minimal scar
				Syringe splint removed after 15–21 days
Zhou et al/2011[30]	Prospective analysis	36 pts	Grade I: 8 (pts)	2 rhomboid dermal flaps (pedicle located on the nipple base)	6 m–3 y (29 pts)	100% satisfactory correction	0	Normal	Among the 13 patients	Not reported
		64 nps
		Mean age 26 y (17–35)	Grade II: 19 (pts)						12 normal
		All congenital	Grade III: 9 (pts)	The 2 dermal flaps are filled crosswise through the tunnel and sutured to the opposite dermis as fixation					1 (grade III) ducts
									obstruction + pain
Taneda et al/2013[32]	Retrospective analysis	379 pts	—	Sakai technique	6–50 m	100% satisfactory outcomes	0	Not reported	Normal	No major complications
		562 nps		The choice between method I and method II was intraoperative based on the strength of the fibrous band at the base of the nipple
				Method I:
				Np splints in 2 flaps sutured between the inside base of the nipple
				Z-plasty to the base of the nipple
				Skin suture was only performed at the apex of the nipple and the bottom base of the nipple; raw surface remains on both sides of np to create a ball-shaped nipple
				Method II:
		25 recurrence		In method II, at both ends of the incision, the 2 areola dermal flaps were advanced and then fixed to act like a suspension bridge
		Age range 19-41				Slight changes in the results:
						Omega to round shape in 3 cases
						Omega to cup shape in 1 case
						Omega to slanting shape in 1 case
Durgun et al/2014[34]		16 pts	Grade II or III	2 triangular dermal flaps	16.5 m(8–24)	100% satisfactory outcomes	1 early recurrence on the 10th postoperative day→success after reoperation	Normal	Normal	No major complications
		28 nps		Traction 3 weeks
		15 congenital				100% patients satisfaction
		1 acquired
		Age range 17–35
Li /2016[35]	Retrospective analysis	Group A	Group A	Group A:	10.4 m (6–12)	16/25 satisfied Group A: 64% satisfaction (9 pts dissatisfied)	Group A:	Group A	Not reported	Group A
		(traditional technique):	Grade I: 9	3 periductal dermofibrous flaps according to the Huang technique			5 recurrence	6 insensitivity		6 obvious scar
		25 pts	Grade II: 23				Group B: 2 recurrence			1 nipple necrosis
		41 nps	Grade III: 9				(2 patients demanded removal of the traction device before the scheduled completion→ traction was reapplied with good outcome)			6 insensitivity
				Group B:						Group B
		(16 bilat)	Group B	5-ml single		Group B: 95% satisfaction (2 pts dissatisfied)				1 wire
		-Age range:19–38	Grade I: 16	Needle21 G 3–9 o’clock and 6–12 o’clock
		Group B (traction device):	Grade II: 34	Traction 2–4 m
		40 pts	Grade III: 24			Group A had significantly higher incidences of obvious scarring and lack of nipple sensitivity and significantly more patients who were dissatisfied with the outcome than did group B.
		74 nps
		Age range, 18– 46
		34 bilat
		2 recurrence
		All Congenital
Mathur et al/2018[40]	Retrospective analysis	60 pts	—	“Drawbridge” Flap	24 m	1. 100% satisfactory outcomes	0	Nipple sensation was preserved in 100% of cases	Lactation, although possible, was not reported in the duration of this study	1pt stitch abscess
		97 nps								1 pt epidermal cyst
		(37 bilat)		Vertical ellipse along the height of the nipple–areola at 6 o’clock position		2. Nipple projection: at 1 postoperative year 75,4% of the initial postoperative projection was maintained
		Mean age 37 (21–54)
		1 male
		Etiology:		Nipple component of the ellipse incision to raise a dermal flap from the tip of the nipple down to its base and lowered down in the manner of a drawbridge
		38 Congenital
		16 Hypoplastic
		6 Mastitis
		3 Mammaplasty				Minimal scar
		13 Recurrence
				Lactiferous ducts which are selectively divided under loupe magnification
				Dermal “drawbridge” flap interposition between the lactiferous ducts and sutured to the opposing side

Table 4.

Surgical Techniques with Lactiferous Ducts Preservation: Sutures

Author/Year	Type	Sample Size	Grading	Surgical Technique	Follow-up	Results	Recurrence Rates	Nipple Sensitivity	Breastfeeding (BF)	Postoperative Complications
Steven et al/2004[19]	Retrospective analysis	21 pts	—	Inferior periareolar incision	12 m	High patients satisfaction	0	Not reported	No patients have been known to attempt breastfeeding	Not reported
		38 nps
		2pts–4nps recurrence after surgery		Vertical spread preserving the ducts
				2 internal sutures (deep dermis to deep dermis) drawing together the opposite walls of the nipple, providing further stability + purse-string suture
				Traction maintained for 2–5 days
Kolker et al/2009[25]	Retrospective analysis	31 pts	Grade I: 18	Minimally invasive	22 m (8–69)	78% satisfactory correction (first procedure)	13/58 occurring between 3 days and 17 weeks 8/30 Grade II (27%)	Not reported	Not reported	No major complications
		58 nps	Grade II: 30
		27 bilat		18-gauge needle is inserted at the 6 o’clock position, using the tip to lyse the foreshortened subareolar fibro-ductal tissue
		All congenital	Grade III: 10
							5/10 Grade II (50%)
				Purse-string suture			11 (19%) corrected with a second procedure, 2 (3%) required a third procedure
				Two crossed 5-0 plain gut mattress sutures
Shiau et al/2011[4]	Prospective analysis	17 pts	Grade I: 0	Telescope method	11.4 m	78% satisfactory correction	0	Questionnaire + Cotton-swab brush test	3 pts normal breastfeeding	1 case of minor skin necrosis at the distal suture site of the wedge resection
		23 nps	Grade II–III: 23
		Mean age 30 (18–51)		One circular incision
		All congenital, 2 recurred		Dissection underneath the breast tissue through a reverse cone shape		Good projection (≥80% of original designed height) and circular shape with minimal scarring		No patient has complained of sensory disturbance during the postoperative cotton-swab brush test and survey
				Two small triangular wedge resections of the areolar skin at the 3 and 9 o’clock positions
				Three sutures between the deep stalk and outer subareolar breast tissue
				Purse-string suture
Jeong et al/2017[36]	Prospective analysis	46 pts	[Congenital = 63 nps]	Simultaneous augmentation mammoplasty in 9 pts	22.4 m (32 pts)	1. Nipple projection (mm) and determination of projection loss (%) at 1 y.	0	Normal	Not reported	2 cases of mild epidermolysis (wound healed with secondary intention, and there were no sequelae)
		75 nps					2 pts were not satisfied with the height of the eversion →additional operation to reinforce the original correction, and satisfactory results were achieved.
		29 bilat	Grade I: 0
		34 congenital	Grade II: 35	BF preservation
		12 acquired (implant-based reconstruction = 9 pts or reduction mammoplasty = 3 pts)	Grade III: 28
				3 slit incisions at 3, 9, and 12 o’clock		Mean projection loss
						Congenital Grade II: 31.4%
				Double-track sun-cross running suture
		Mean age 40.2 (16–75)				Grade III: 31.8%
						Acquired: 39.0%.
						2. Pts satisfaction: 32 pts as excellent
						2 pts as good
						100% satisfactory outcomes
						Minimal scar
Liang et al/2017[37]	Prospective analysis	30 pts	Grade I: 24	4 microincisions 3, 6, 9, 12 o’clock	6–12 m	1. 100% patient satisfaction	2 pts (preoperative severe inversion) projection was lost in both nipples	Brush test revealed that all postoperative nipples had retained sufficient sensory function to elicit a contraction response	Normal breastfeeding (4 pts)	No major complications
		55 nps	Grade II: 16
		25 bilat
		All congenital				2. Projection: 9.8 ± 0.9 mm, which had decreased to 8.0 ± 1.0 mm by the mean follow-up visit. In 30 of the cases, the postoperative nipple projection remained at 93%–100% of the nipple height achieved at the time of the operation
		2 pts (4nps) recurrence	Grade III: 15	Cut the fibrous tissue under the nipple (scissor tips were directed downward to the center→ duct preservation)
		Mean age 27 (22–32)					They were satisfied with the results after a second correction
				Cross vertical mattress suturing with basilar tightening
						3. Scar appearance: minimal
Dessena et al/2018[38]	Retrospective analysis	32 pts	Grade I: 0	Poliglecaprone spacer	12 m	100% satisfactory outcomes	0	Not reported	Not reported	1 case partial necrosis in a patient who underwent tumorectomy and radiotherapy
		41 nps	Grade II- III: 41
		11 bilat		Minimal incision (2–3 mm) at the 6 o’clock
		Mean age, 28 (17–44)				100% patients satisfaction
		27 pts congenital		Purse-string, closed with several knots to make a long ‘‘rope’’ of poliglecaprone suture. The ‘‘rope’’ is used as an absorbable filler		Minimal scar

Fig. 4.

Techniques with lactiferous ducts preservation: “dermal flaps.”

Table 5.

Surgical Techniques with Lactiferous Ducts Preservation: Distractors

Author/Year	Type	Sample Size	Grading	Surgical Technique	Follow-up	Results	Recurrence Rate	Nipple Sensitivity	Breastfeeding (BF)	Postoperative Complications
Teng et al/2005[20]	Prospective analysis	14 pts	Grade I: 6	Continuous elastic outside distraction	7.3 m (range, 3–12)	100% satisfactory correction	0	Analog scale using light touch and 2-point discrimination analysis	Not reported	No major complications
		26 nps	Grade II: 9	3–6 m for consolidation		100% patients satisfaction		Minimal or no difference between before/after surgery
		(12 bilat)	Grade III: 11
		Mean age: 24 yo (14–40)
		All congenital
Caviggioli et al/2008[23]	Prospective analysis	28 nps	Grade I: 0	Pitanguy’s technique (release of the fibrous tissue between the ducts with a direct approach)	12 m	Complete symmetry of the nipple–areola complex with no noticeable scars	0	Not reported	Not reported	No major complications
			Grade II: 28	Splint to allow the edges to overlap
			Grade III: 0	Splint in place for 3 weeks
Long et al/2011[27]	Prospective analysis	53 pts	Grade I: 0	Retractor	11.9 m (range, 8–18)	100% patient satisfaction	0	None of the patients suffered permanent paresthesia	Not reported	Rate: 5.26% (5/95)
		95 nps	Grade II: 75	10-ml (or 5-ml) syringe 6 m		Nipple height reduction 4.7 mm (range 3–7 mm) at 6 m postoperation.				Depigmentation (2.11%, 2/95),
		Mean age 25.6 yo (20–31)	Grade III: 20							Areolar ulcer (2.11%, 2/95)
										Wire dislocation (1.05%, 1/95)
Feng et al/2019[39]	Randomized controlled trial	230 pts who will breastfeed	Grade I: 196	Distracter was made using the distal end of a 10-ml syringe	19.5 m (8–55)	1. Aesthetic results evaluated by surgeons: good in 165/168 nps in the distractor group (98%).	Partial in 5 Grade II nipple (2–3 m after distractor removal).	Cotton-swab brush sensitivity	Distractor group: success rates 84.9% and 79.3% for Grade I and II nipples respectively.	Chapped nipples and mastitis was higher in the control nipples than in the distractor nipples P<0.05
			Grade II: 195
		391 nps
		Control group: 30 pts (48 nps)	Grade III: 0	6 m
			Distractor group: 168 nps	Women were taught exercises to loosen the adhesions of the nipple. The exercises had to be performed each morning for 6 m
		Mean age 27.7 (22–35)				2. Aesthetic results evaluated by pts by questionnaire:163 of 168 nps in the distractor group (97%)	However, the nipples had been converted from Grade II to Grade I.		Control group significantly lower (P < 0.05) 52.5% and 38.9% for Grade I and II nipples, respectively).	2 pts underwent a fistula excision after the breastfeeding period ended
		Nps were randomly assigned 1:1 to the distractor and control groups	Control group: 152 nps			3. Grade I and II nipples achieved increased height after the distractor was worn for 6 months and at 37 weeks of pregnancy, while the control nipples achieved only a marginal improvement at 37 weeks of pregnancy

Techniques with lactiferous ducts preservation: “sutures.”

Eleven authors explicitly described the placement of a temporary traction (3–30 days)[19,33,34,41] or a “donut” dressing to avoid a postoperative compression (2 weeks–6 months).[14,15,21,24,28,29]

Outcomes

Mean follow up was 23.9 months (range, 3–192 months). In most articles, results were expressed as the rate of satisfactory correction, which ranges between 64% and 100% (average, 88.7%). Nineteen studies reported that in 100% of the cases, the correction was effective and permanent.

Five studies evaluated nipple projection reporting:

Decrease of nipple height of 4.7 mm 6 months after surgery.[27]

An average projection loss of 31.4%, 31.8%, and 39% one year after surgery, respectively, in grade II, in grade III, and in acquired forms.[36]

Maintenance of nipple projection at 93%–100% of the nipple height achieved at the time of the operation (9.8 ± 0.9 mm, which had decreased to 8.0 ± 1.0 mm one year after surgery).[37]

Eleven studies utterly reported the quality of the scars referred as minimal in all cases except for 8 nipples.

Registration of recurrence rate was reported in all the studies being one of the inclusion criteria and resulted pair to 3.89% (131 nipples/3369) in this review. Recurrence rate was reported between 0% and 34.1%.

Satisfactory outcomes rate and recurrence rate in techniques that included lactiferous ducts damaging (91 nipples) were, respectively, 96.7% and 3.3%. Satisfactory outcomes rate and recurrence rate in techniques with lactiferous ducts preservation using dermal flaps (1594 nipples) were, respectively, 97.6% and 1.5%. Satisfactory outcomes rate and recurrence rate in techniques with lactiferous ducts preservation using corrective sutures (247 nipples) were, respectively, 90.6% and 6%. Satisfactory outcomes rate and recurrence rate in techniques with lactiferous ducts preservation using distractor systems (317 nipples) were, respectively, 98.4% and 1.5% (Table 4).

Sensitivity and Breastfeeding

Twenty-three articles reported data on postoperative nipple sensitivity. Sensitivity was evaluated using the brush test in 3 articles,[11,37,39] an analog scale considering light touch and 2-point discrimination analysis in 2 articles,[20,22] and a specific questionnaire[22] or a questionnaire combined with a cotton test in 2 articles.[4,39] In the other studies, the outcome measurement method was not specified. In 20 studies, nipple sensitivity results were normal in all patients, whereas in 3 studies, the nipple sensitivity results were temporarily or permanently altered (8 nipples).

Thirteen studies reported breastfeeding outcomes with good results in a small number of patients.

Postoperative Complications

Thirty-three studies mentioned postoperative complications, including 2885 nipples. Complication rate resulted in 1.7% (49/2885 nipples) of cases, and the most frequent problems were nipple sloughing (10 cases), areolar ulcer (8 cases), obvious scars (8 cases), superficial infection (7 cases), partial necrosis (3 cases), depigmentation (2 cases), wound dehiscence (2 cases), wire dislocation in case of retractor (2 cases), nipple necrosis (1 case), nipple insensitivity (1 case), stitch abscess (1 case), hematoma (1 case), and epidermal cyst (1 case).

DISCUSSION

Nipple inversion represents a common pathological condition with aesthetic, functional, and psychological consequences. To our knowledge, our review includes the largest sample in literature, analyzing 3369 inverted nipples.

Almost 70% of cases resulted were affected by a bilateral condition. More than 90% of patients were affected by a congenital nipple inversion, while the acquired etiology was less frequent, representing only 6.1% of cases. Periductal mastitis, breast cancer, or previous mammoplasties were the most common causes.

Twenty-four studies reported a preoperative grading according to Han-Hong. The Han and Hong[6] grading is the most recent and widespread inverted nipples classification system. This is based on the subjective quantification of the amount of effort required to allow an eversion of the nipple.

The pathogenesis of the congenital nipple inversion was recently clarified and seems to depend by the shortness of lactiferous ducts, the lack of supporting tissues, and the presence of fibrous bands that cause retraction at the base of the nipple.[4] Consequently, the different therapeutic strategies are all based on common cardinal assumptions: the dissection or the resection of the fibrous bands and the lactiferous ducts, the increase of volume below the nipple or the filling of the dead space created by the resection, and the tightening of the neck of the nipple.

In the current review, 4 studies described techniques with lactiferous ducts damaging, 25 studies described techniques with lactiferous ducts preservation, and 4 studies included both. Among studies describing techniques for lactiferous ducts preservation, different types of dermal flaps, sutures, or distractor system were used. For what postoperative management is concerned, 11 authors explicitly described the placement of a temporary traction (3–30 days) or a “donut” dressing to avoid compression (2 weeks–6 months) in postoperative.

Each surgical approach has its own advantages and disadvantages. Regardless of their conformation, local flaps certainly consent the stabilization of the nipple projection supporting the base of the nipple without compromising breastfeeding. Nevertheless, flaps required relatively extended operative time, multiple incisions, and subsequent scars. Moreover, the risk of these techniques is to provoke a distortion of the nipple–areolar complex, prejudicing the final aesthetic outcome. However, in our review, the 97.5% of patients who underwent a correction using dermal flaps reached satisfactory aesthetic results and presented a low rate of recurrence (1.5%).

Corrective techniques based on sutures present the main advantage to reduce scars on the nipple–areola complex skin. However, the suture offers a more precarious stability of nipple eversion when compared with flap’s placement. There are 2 different aims while performing sutures: tightening the neck of the nipple (purse-string sutures or 5-points star sutures), supporting the nipple eversion (internal sutures, Poliglecaprone “rope” suture), or both (double-track sun-cross running sutures). The attainment of the nipple neck’s tightening can be assisted also using Z-plasties or wedge excision of the nipple base.

These surgical approaches (flaps and sutures) are clearly always combined with lactiferous duct release using 1 or more incisions. Kalaaji et al[41] proposed a lactiferous duct release incision-free by the “central tunnel technique.” The latter consisted in the creation of a tunnel using a needle instead of a blade, the liberation of the lactiferous ducts of the central portion of the nipple, and the filler of the empty space with a fat graft.

Continual distraction represents a less invasive, safe, and easier technique that minimizes scars and reduces injury to the nipple–areola complex. The rationale of the distraction is to create a constant exterior traction on the fibrous bands and the hypoplastic lactiferous ducts to stretch their relative adhesion points. At the same time, the traction stimulates the growth of granulation tissue that works as support of the nipple base. However, this technique needs a long-lasting treatment requiring a very high degree of patient’s compliance. Indeed, the distraction can cause a disruption in daily life activities. In our review, the recurrence rate in case of outside distraction was very low (1.5%). Nevertheless, the low percentage of inverted nipples grade III and the short follow-up of 1 of the 4 studies must be considered as confounding factors.

In most articles, results were expressed as the rate of satisfactory correction, which ranges between 64% and 100% (mean 88.6%). In our opinion, the absence of a standard outcome measurement evaluating aesthetic, functional, and psychological results is one of the critical points of nipple-inverted treatment. Concerning aesthetic and functional outcomes, an objectively satisfactory result should comprehend an appropriate and stable nipple projection, an appropriate and stable nipple shape, a preserved sensitivity, a preserved lactation, and presence of minimal scars. Another considerable parameter should regard patient’s self-evaluation and patient satisfaction. Even if the Breast Q,[42] which is the most widespread method of measurement in breast surgery, contains a section dedicated to “nipple–areola complex”, to our knowledge, none of the published studies evaluated patient’s satisfaction using this specific questionnaire.

A study based on 600 nipple measurements in adult women described that the mean projection of a normal nipple is 0.9 cm.[43] Only 4 studies[4,27,36,37] reported an objective measurement and evaluation of stability of the nipple projection, showing in the first postoperative year different grades of projection decrease, which varies from 7% to 40%.

Kim et al[11] identified 5 normal nipple shapes (rectangular, omega, round, cup, and slanting). However, only 2 studies[13,32] explicitly mentioned outcomes about nipple shape referred to this classification.

Twenty-two articles reported data about postoperative nipple sensitivity. Sensory innervation of the nipple–areolar complex depends from a deep and a superficial plexus originating from the anterior cutaneous branches of the third, fourth, and fifth intercostal nerves and from branches of the lateral cutaneous nerves of the fourth and fifth intercostal nerves.[16,44]

The sensitivity measurement method is not specified in most of the studies. The few articles that reported sensitivity outcomes measurement methods adopted the brush test, an analog scale considering light touch and 2-point discrimination analysis and a questionnaire. Only 3 studies reported a temporary or permanent alteration of nipple sensitivity (8 nipples). Twelve studies reported data about breastfeeding with relatively good results but considering a very little sample of patients.

Similarly, the quality of scar is not expressed through a specific assessment scale. However, in just 8 among the >2800 cases, obvious scars are reported. Recurrence rate was one of the inclusion criteria, and the results were totally equal to 3.89% (131 nipples/3369) ranging between 0% and 34.1%.

To sum up, satisfactory outcome rate was, respectively, 96.7%, 97.5%, 90,6%, and 98.4% in techniques with lactiferous ducts resection, in techniques with lactiferous ducts preservation using flaps, sutures, or distractor. Recurrence rate was 3.3%, 1.5%, 6%, and 1.5%, respectively, in techniques with lactiferous ducts resection, in techniques with lactiferous ducts preservation using flaps, sutures, or distractor. However, according to us, the differences in terms of sample size, preoperative grading, methods of outcomes measurement and follow-up time impede to draw any conclusion about which is the best corrective technique. In our opinion, a minimal follow-up pair to 6 months should be considered to provide an acceptable recurrence rate.

Complications were relatively rare (rate, 1.7%), and the most frequent issues were nipple sloughing, areolar ulcer, superficial infection, partial or complete nipple necrosis, areolar depigmentation, wound dehiscence, and wire dislocation in case of retractor. As previously considered,[45] authors believed that the heterogeneity and subjectivity of surgical outcomes presentation make it extremely hard to perform a metanalysis of the included studies. However, this review offers a global view about preoperative evaluation, surgical strategies, and surgical outcomes in patients affected by nipple inversion. Moreover, our study outlines the need for a standardized method to evaluate outcomes, including aesthetic, functional, and psychological results using objective and subjective measurement instruments.

CONCLUSIONS

According to our research, our review includes the largest sample size in literature, analyzing 3369 inverted nipples and offering a global analysis about preoperative evaluation, surgical strategies, and surgical outcomes in patients affected by nipple inversion. However, the heterogeneity and subjectivity of outcomes presentation make it more complicated to state which is the best surgical strategy to obtain satisfactory and stable results with minimal morbidity. This study highlights the need of a standardized method to evaluate outcomes, including aesthetic, functional, and psychological results using objective and subjective measurement instruments. Prospective studies with a standardized outcome measurement method will be essential to better understand which is the ideal corrective strategy for patients affected by different grades of nipple inversion.

Table 6.

Surgical Strategies Outcomes and Recurrence Rate

Surgical Technique	Sample Size (Nipples)	Follow-up, mo	Satisfactory Outcomes, %	Recurrence Rate, %
Lactiferous ducts damaging	98	20 (6–62)	96.7	3.3
Lactiferous ducts preservation: dermal flaps	1589	28.2 (6–192)	97.5	1.5
Lactiferous ducts preservation: sutures	247	14.8 (6–69)	90.6	6
Lactiferous ducts preservation: distractors	317	12.6 (3–55)	98.4	1.5