Incidence of Complications for Different Approaches in Gynecomastia Correction: A Systematic Review of the Literature

Background Gynecomastia is nowadays a very common disease, affecting a large cohort of patients with different ages. The aim of this literature review is to assess the incidence of complications with all proposed techniques and for combined procedures versus single approach procedures in gynecomastia correction. Materials and Methods A systematic review of the literature was performed to identify all reported techniques for gynecomastia correction covering a period from January 1, 1987 to November 1, 2020. For all selected papers, demographic data, proposed technique, and complications’ incidence have been recorded. Results A total number of 3970 results was obtained from database analysis. A final total number of 94 articles was obtained for 7294 patients analyzed. Patients have been divided into three groups: aspiration techniques, consisting in 874 patients (11,98%), surgical excision techniques, consisting in 2764 patients (37,90%), and combined techniques, consisting in 3656 patients (50,12%). Complications have been recorded for all groups, for a total number of 1407, of which 130 among “Aspiration techniques” group (14,87%), 847 among “Surgical excision techniques” group (30,64%), and 430 in “Combined techniques” group (11,76%). Conclusions Several techniques have been proposed in the literature to address gynecomastia, with the potential to greatly improve self-confidence and overall appearance of affected patients. The combined use of surgical excision and aspiration techniques seems to reduce the rate of complications compared to surgical excision alone, but the lack of unique classification and the presence of several surgical techniques still represents a bias in the literature review. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Introduction
Gynecomastia is defined as a benign enlargement of the mammary glands, commonly diffused among men. The prevalence of gynecomastia ranges from 38 to 64 percent in the male population [1]. Prevalence figures vary highly between age groups. Among male neonates, 60-90% have some amount of palpable breast tissue. The next chronological peak occurs during puberty with reported prevalence figures of 4-69% that decrease again by age 17 to approximately 10%. The third and last peak occurs in elderly men [2].
The etiology of gynecomastia is heterogeneous. More than 80% can be classified as idiopathic, since a wellestablished cause is not determined. Medical drugs, addictional drugs, and anabolic substance abuse, mostly among bodybuilders, have been identified as secondary causes for gynecomastia. The gynecomastia pathophysiology is due to a hormonal imbalance with decreased testosterone production, increased estrogen production, mainly from the peripheral conversion of androgens, and increased availability of estrogen precursors. In men, estrogen production results through aromatase activity to estradiol and estrone. In patients affected by gynecomastia, an increased local tissue sensitivity to estrogen metabolites is present [3]. Gynecomastia can affect normal self-esteem and sexual identity and often patients feel ashamed of their bodies during normal social activities.
Being a very popular item in the present literature, several surgical techniques have been proposed for gynecomastia correction. The aim of this systematic review is to assess the rate of reported complications with all proposed techniques and the evaluation of the complications' rate in combined procedures versus single procedures.

Literature Search
The searched databases included Medline, EMBASE, Cochrane and PubMed, covering a period from January 1, 1987 to November 1, 2020.
A detailed search was performed starting from the general topics to avoid overlooking the studies in the databases. Based on this, the keywords used for detailed investigation were ''gynecomastia,'' ''gynecomastia surgery,'' ''gynecomastia correction,'' ''gynecomastia surgical correction''.

Inclusion and Exclusion Criteria
Our predefined inclusion criteria included articles that included any age patients' cohort, including pediatric population; included surgical techniques for the correction of gynecomastia (defined as any enlargement of the breast tissue); were English-language articles; were published between 1987 and 2020. Exclusion criteria were as follows: article considering non-surgical or therapeutic treatment for gynecomastia; articles about pseudogynecomastia; noncomparative studies, systematic reviews, case reports, expert opinions, conference and abstracts, review, letters to editors, and non-English articles.

Data Extraction and Quality Assessment
Two authors independently reviewed the titles and abstracts to assess eligibility for potential inclusion. The full-text papers were reviewed by two authors and inclusion was made on a consensus basis. Disagreement was resolved through a discussion between the reviewers. Literature analysis is reported in Fig. 1.
All articles have been separately analyzed for the following data: Since not all articles included patients' satisfaction and gynecomastia's grades, the authors decided not to collect those data to avoid bias.
The accurate analysis of all selected papers was conducted by both authors simultaneously. Proposed techniques have been categorized into three major groups according to their characteristics: Complications have been statistically analyzed for all selected papers. In particular, the following complications have been recorded for each paper and grouped according to the proposed technique: hematoma, seroma, over-resection, under-resection, hypo-or hyperesthesia, wound dehiscence, infection, pathological scar, asymmetries, irregularities/redundant skin, NAC necrosis (partial or total)/abrasion and revision/recurrence.

Statistical Analysis
For each study, the overall complication rate and the rate of each complication type was calculated. The complication rate across all studies, grouped according to the technique, was then calculated. Chi-square tests were used to compare complication rates between the groups. Data are shown in Table 1.

Results
A total number of 3970 results was obtained from database analysis. A final total number of 94 articles was obtained, according to predefined inclusion and exclusion criteria, for a total number of 7294 patients analyzed .
Patients, according to previously mentioned criteria, have been divided into three groups:              From statistical descriptive analysis, we observe that using different techniques we obtain different percentages of patients with no complications and with the considered complications (Figs. 2 and 3).
Follow a statistical inference approach, we test, using Pearson's Chi-squared test, the null hypothesis of independence between technique and outcome; we observe a value of 760,49 for the test statistic with 24 degrees of freedom, with a very small p-value (p-value \ 2.2e-16). This suggests us to reject the null hypothesis, confirming that different techniques give different outcomes.

Discussion
Several techniques have been described throughout the years for treating gynecomastia. Aspiration techniques, including liposuction and its modern variations, base their principles on removing trough a minimal access to the redundant fatty and breast tissues by fragmentation and suction. Since gynecomastia in most cases is defined as mixed, aspiration of the gland cannot permit histopathological analysis and skin redistribution is limited. Moreover, these techniques do not permit a direct hemostasis [98][99][100][101].
Aspiration techniques vary according to the modality used for fat and glandular tissue removal. In suction-assisted liposuction, after tumescent solution infiltration, localized areas of unwanted fat are removed through the combination of a high-vacuum blunt-tipped cannula and longitudinal motion. In ultrasound-assisted liposuction, ultrasound frequencies produced by specific cannulas primarily affect tissues with the lowest density, such as fat tissues, whose density is further reduced by previous wetting with tumescent solution. Interactions between adipose tissue and ultrasound waves lead to adipocyte fragmentation trough cavitation and, therefore, this technique has a high degree of selectivity for fat cells resulting in a high degree of selectivity for fat cells, and thus reducing blood loss, postoperative edema, and ecchymosis and avoiding contour irregularities. In power-assisted liposuction, oscillating rotational and translational movements of cannula tip are produced, mimicking the motion of the operator's arm with lower amplitude and allowing an easier penetration of fibrous fat and glandular tissue, while generating no thermal energy and therefore reducing the risk of cutaneous burns. Laser lipolysis utilizes the principles of selective photothermolysis to preferentially lyse adipocytes while leaving surrounding structures unaffected. Different laser wavelengths may vary in their relative effectiveness in targeting substances present in the subcutaneous environment. Thus, lasers achieve their desired effect via photolysis of adipose cells, photocoagulation of small vessels, liberation of adipocyte lipases, and contraction of dermal collagen.
More challenging cases, such as male tuberous breast, can hardly be corrected only with aspiration techniques since an open excision is required to manage the deformity [102][103][104][105].
Open excision techniques base their principle on a direct view and management of the gland, through several types of surgical accesses according to the surgeon's preference and entity of the defect [106,107]. The main advantage of open excision is the direct control of the hemostasis and redundant skin control, with the main disadvantage of permanent scars, whose quality cannot be predicted. Furthermore, gland excision can permit histopathological analysis since male breast carcinoma, even if rare, can occur only in patients affected by gynecomastia [108].
Combined techniques are usually composed of an open excision phase followed by an aspiration phase: the combination of these techniques can permit a limited scar extension since, after open excision, the wide undermining   of the skin flap onto a larger area can often permit a sufficient skin redistribution [109][110][111][112].
Since gynecomastia represents a disease commonly diffused worldwide, an updated systematic review that focuses not only on the different types of proposed treatment but also on complications rate, is a useful tool for plastic surgeons [113]. Several biases can be found, mostly related to the high variations in proposed treatments and clinical classifications. In fact, several articles proposed specific treatments for graded gynecomastia patients, but the large variations of gynecomastia classifications cannot guarantee a statistical comparison and therefore only the type of surgical approach, despite the grade of the disease, have been considered [114][115][116]. Moreover, no comparison of patients' postoperative satisfaction has been performed because of the absence of evaluation in some papers and for the different used methods for evaluation [117][118][119][120][121]. Besides those biases, that are strictly relative to the large discussion on this topic in literature, this review, as previously stated, confirms that the combined approach with traditional surgical excision of glandular tissue combined with liposuction provides the lowest rate of complications, compared to aspiration techniques alone and surgical excision techniques alone . As an adjunctive element for discussion, authors retain that, despite its rare incidence, breast cancer in male affected by gynecomastia can occur, and therefore, histopathological analysis is mandatory and can be performed only with surgical excision  rather than with aspiration techniques [122,123]. Since psychological assessments have been largely discussed in literature, this aspect, even if fundamental, have not been included in this review. Focusing on surgical treatment, articles including medical treatment for gynecomastia have been excluded from this review. This review evidences the need for a single classification method, including also minor forms, and for a validated and universal method for the evaluation of satisfaction [124]. In this review, the male tuberous breast has not been included. Even if it presents peculiar clinical hallmarks, it is still poorly investigated in literature and often misdiagnosed with other forms of gynecomastia [125]. A general consensus on this condition, and its inclusion in gynecomastia classification, will help plastic surgeons in the diagnosis and management of this condition. To avoid bias, also pseudogynecomastia, due to massive weight loss, has not been included since its treatment and rate of complications differ from gynecomastia surgery [126,127]. We personally retain that the higher incidence of complications among patients who underwent surgical excision is strictly related to the high number of patients and to the fact that these techniques are often used to treat the most severe forms, compared to aspiration techniques and combined techniques [128]. Moreover, surgical excision techniques have been early described in the literature, and the evolution of techniques has reduced the complications rate.

Conclusion
Several techniques have been proposed in the literature to address gynecomastia, with the potential to greatly improve the self-confidence and overall appearance of affected patients. The combined use of surgical excision and aspiration techniques seems to reduce the rate of complications compared to surgical excision alone, but lack of unique classification and the presence of several surgical techniques still represents a bias in the literature review.

Declaration
Conflict of interest The authors have no financial interest or conflict of interest to declare in relation to the content of this article.
Statement of human and animal rights, or ethical approval This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent For this type of study, informed consent is not required.
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