Highly cosmetic and safe breast-conserving surgery using a wave-like periareolar incision with sub-nipple and extensive subcutaneous dissection: a retrospective cohort study

Introduction

Breast-conserving surgery (BCS) is a common breast surgical method that allows breast preservation while maintaining oncologic outcomes. Milan, NSABP B-06, and EORTC 10801 trials showed that long-term survival in patients undergoing BCS followed by radiation therapy was comparable to mastectomy (1-3). As BCS has been more widely adopted, there is an increasing demand to improve breast cosmesis postoperatively. In conventional BCS, a skin incision is often placed over the tumor (tumor-surface incision) to allow direct access to the tumor and to ensure adequate margins. However, the tumor-surface incision often results in conspicuous scarring, which can lead to skin contracture and nipple displacement (4). In response, surgical approaches combining oncologic control with plastic surgery principles to prevent breast deformity, termed ‘oncoplastic surgery’, have been developed (5-7).

However, oncoplastic-BCS (OBCS) currently remains non-standardized, as conventional OBCS techniques vary according to tumor location, tumor size, and patient characteristics. Moreover, OBCSs occasionally require invasive procedures, such as adipofascial or myocutaneous flap reconstruction (8,9). These factors pose significant challenges to the broader implementation of OBCS. There is a growing need for a less invasive, standardized OBCS technique that can be applied to a wide range of patient and tumor characteristics.

We adopted a new OBCS technique combining a linear or wave-like periareolar incision with sub-nipple and extensive subcutaneous dissection. The use of a periareolar incision renders the scar tissue inconspicuous and prevents skin contracture. Moreover, sub-nipple and extensive subcutaneous dissection facilitate defect filling and prevent skin tension and nipple displacement. Our OBCS is considered to achieve superior esthetic quality across various patient and tumor characteristics with a single technique. This technique has been used at Keio University School of Medicine and is termed Keio-BCS (K-BCS).

We aimed to retrospectively compare K-BCS with tumor-surface incision surgery in terms of cosmetic outcomes, oncological and surgical safety. We used the BCCT.core computer software-based program for objective cosmetic evaluation (10,11). Moreover, we examined whether K-BCS could provide better esthetic results regardless of patient and tumor characteristics. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0299/rc).

Methods

Patients

We retrospectively reviewed patients who underwent BCS at Keio University School of Medicine between January 1, 2021, and December 31, 2023. During this period, 328 patients underwent BCS. These patients were consecutively identified to minimize selection bias.

The inclusion criteria comprised: (I) patients who consented to postoperative breast photography; (II) patients with a lesion that was unilateral and unifocal; (III) patients with no prior history of breast or axillary surgery at diagnosis; (IV) patients for whom the nipple-areolar complex (NAC) had been preserved postoperatively; and (V) patients whose surgical technique involved either K-BCS or a tumor-surface incision. In total, 197 patients met the inclusion criteria.

The exclusion criterion comprised patients whose photographs were deemed unsuitable for cosmetic evaluation. One patient in the K-BCS group and one in the tumor-surface incision group were excluded owing to postoperative hematomas sufficiently severe to have interfered with esthetic assessment. Finally, 195 patients were included in this study. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Keio University School of Medicine (approval No. 20150170) and individual consent for this retrospective analysis was waived.

Clinicopathological data in relation to the included patients [age at diagnosis, body mass index (BMI), tumor location, nipple-tumor distance (NTD), tumor size, excised specimen size, tumor and nodal status based on tumor-node-metastasis (TNM) classification, axillary surgery type, and preoperative therapy] were obtained from our retrospective database.

Surgical technique

Two techniques were compared in this study, namely, K-BCS and tumor-surface incision, as follows.

K-BCS

Marking of the tumor location and periareolar incision

Ultrasonography was used to mark the tumor location on the skin. We employed two types of periareolar incision: standard linear incision and wave-like incision (Figure 1A). In both designs, the periareolar incision typically extended along about half (180°) of the areolar circumference and never exceeded half. The choice between wave-like and linear designs was based on the balance of areolar size, NTD, and tumor size; the wave-like design was preferred for larger or more distant tumors, or when the resection area was large relative to the areolar size. The wave-like incision followed approximately five waves that traversed the areola border. This incision was derived from the W-plasty technique, which is widely practiced in plastic surgery (12-14). This incision design partially aligns with skin tension lines, reducing scar visibility; disperses the tension caused by skin stretching, lowering the risk of scar contracture; and expands like an accordion to provide a better visibility in the surgical field, allowing easier access to larger or more distant tumor from the nipple.

Figure 1 Surgical procedure and intraoperative findings in K-BCS. (A) Two types of periareolar incision were used: linear design or wave-like design which followed five waves crossing the boundary of areola. (B) A thicker skin flap was created at the beginning of subcutaneous dissection. (C) Extensive subcutaneous dissection was performed beyond the tumor. (D) Illustration of looped venous network beneath NAC, shown from surface (left) and cross-sectional (right) perspectives. (E) Sub-nipple dissection should maintain a tissue thickness of 5–10 mm to preserve the looped vein. (F) The tumor and surrounding mammary tissue were resected under clear surgical view using a wound retractor. (G) The post-resection defect was filled by suturing the remaining breast tissue. (H) The wound was closed in two layers: first the subcutaneous tissue and residual mammary tissue, followed by buried dermal sutures. These images are published with the patients’ consent. K-BCS, Keio-breast-conserving surgery; NAC, nipple-areolar complex.

Extensive subcutaneous dissection and sub-nipple dissection

A thicker skin flap was initially created to facilitate suturing with the mammary gland beneath the NAC during wound closure (Figure 1B). The thinner skin flap was subsequently made and widely dissected beyond the tumor, with a marking suture placed directly over it reaching the site (Figure 1C). The glandular tissue beneath the NAC was always transected, and the opposite side of the tumor was also extensively dissected. Extreme care was taken in the sub-nipple area, where the looped venous network lies within the fatty tissue (Figure 1D), as damage to this network can cause venous congestion and epidermal and nipple necrosis (15,16). To preserve vascular integrity, a certain adequate thickness should be maintained in this region (Figure 1E).

Resection of the tumor and defect filling

A wound retractor was used to protect the wound edges and to fully expose the entire resection area (Figure 1F). The breast tissue was excised in a cylindrical shape with an adequate margin. The surgical margin was examined using intraoperative frozen section assessment, and additional resection was performed if the margin was positive. Subsequently, the remaining breast tissue was appropriately mobilized to fill the defect (Figure 1G).

Wound closure for the prevention of nipple displacement

Wound closure was performed in two layers. To prevent nipple displacement, the residual breast tissue beneath the NAC was sutured to the opposite subcutaneous tissue (Figure 1H). Omission of this step may cause the nipple to shift toward the incision site postoperatively, resulting in improper nipple orientation and loss of forward projection. Finally, the skin was closed with buried dermal sutures.

Drain placement to prevent seroma or hematoma compromising nipple blood flow

Postoperative seroma and hematoma both delay wound healing and, in some cases, compromise nipple blood flow, leading to nipple discoloration or necrosis. If the subcutaneous dissection area or resection area was vast and seroma or hematoma was anticipated, a drainage tube was placed in the subcutaneous dissection area and sufficient compression was applied to ensure proper tissue adhesion.

Tumor-surface incision

The conventional BCS technique involved a linear or spindle-shaped incision directly over the tumor. The incision direction varied according to location. In the upper inner, lower inner, or lower outer quadrants, horizontal incisions along skin tension lines or radial incisions extending outward from the nipple were commonly used. In the upper outer quadrant, superolateral radial incisions extending toward the axilla were designed to perform axillary surgery. Subcutaneous dissection extended the planned resection line to facilitate defect filling. The breast tissue was excised in a cylindrical shape with an appropriate margin, with intraoperative frozen section assessment and additional resection if necessary. The surrounding glandular tissue was mobilized to fill the defect, and a drainage tube was placed when fluid accumulation was anticipated. Skin closure was completed with dermal buried sutures.

Drain removal timing and discharge

In both groups, patients without drains were discharged approximately on postoperative day (POD) 3 or 4. When a drain had been inserted, it was removed once the drainage volume was ≤20 mL, with discharge on the following day. When axillary lymph node dissection had been performed, hospitalization was extended to POD 7. Discharge was occasionally delayed at the patient’s request.

Operating surgeons and choice of surgical technique

All operations were performed by five breast surgeons (surgeons A to E), each with more than 15 years of clinical experience (29, 21, 18, 27, and 21 years, respectively). Surgeons A, B, and C used both K-BCS and the tumor-surface incision, selecting between the two on a case-by-case basis according to whether each surgeon judged that the tumor could be adequately accessed and resected through a periareolar incision (for example, tumors in the far outer or axillary region, too large for periareolar delivery, or requiring skin resection were treated with the tumor-surface incision). Per-surgeon case volumes were surgeon A: 82 K-BCS and 5 tumor-surface; surgeon B: 33 K-BCS and 23 tumor-surface; surgeon C: 12 K-BCS and 15 tumor-surface. Surgeons D and E used the tumor-surface incision exclusively (surgeon D: 10; surgeon E: 15). The per-surgeon case volume is shown in Table S1. Patient preference for cosmesis was not systematically consulted, but the surgeon’s clinical judgment may have influenced the choice; for example, K-BCS was sometimes favored in younger patients or those in whom cosmesis was considered particularly important.

Cosmetic evaluation

Breast esthetics were objectively evaluated using BCCT.core software, a validated tool for assessing cosmetic outcomes based on postoperative frontal photographs (10,11). The software analyzed various asymmetry indices (breast volume, nipple position, skin color, and scar visibility) and integrated them into an overall esthetic score using a four-point scale, as follows: excellent, good, fair, or poor. Photographs taken within 1 month postoperatively, prior to radiotherapy, for wound inspection were used. These photographs were taken in a frontal position with hands on hips, under the same source of lighting conditions, and at a standardized distance from the camera. The images were evaluated using BCCT.core (v.30) software, and the proportions of ratings classified as excellent, good, fair, or poor were compared between the two groups. Additionally, the ‘excellent’ rating using BCCT.core was defined as an ‘excellent’ evaluation, and we conducted subgroup analyses to compare ‘excellent’ evaluation between the two groups across various patient and tumor factors. Furthermore, logistic regression analysis was performed to examine whether a significant association existed between K-BCS and ‘excellent’ evaluation.

Oncological safety evaluation

As an outcome parameter reflecting oncological safety, we evaluated the rate of positive or close surgical margins in both frozen and permanent sections. In the permanent section, margins were evaluated for all specimens, including those obtained from additional resections. A positive margin was defined as the presence of a tumor at the edge of the specimen. A close margin was defined as the presence of a tumor within 2 mm of the specimen edge. This latter definition was based on previous studies in which a close margin is typically defined as a tumor within 1 or 2 mm of the specimen edge, and is associated with an increased risk of local recurrence (17,18).

Operative safety evaluation

We examined the parameters of perioperative management, including operative time, intraoperative blood loss, postoperative length of hospital stay, and drain insertion rate.

To assess surgical safety, we investigated the rate of surgical complications requiring treatment or intervention. Surgical complications included punctured seroma or hematoma, surgical site infection requiring antibiotic treatment or drainage, and nipple or skin necrosis managed with ointment or debridement.

Statistical analysis

Between-group differences were assessed using Fisher’s exact test or Student’s t-test, as appropriate. Logistic regression analysis was performed to identify factors independently associated with the ‘excellent’ evaluation in the univariate analysis. The factors identified in the univariate analysis or those considered clinically relevant were included in the multivariate analysis. All statistical analyses were conducted using R version 4.3.3 (The R Foundation for Statistical Computing, Vienna, Austria) software. Statistical significance was set at P<0.05.

Results

Patient and tumor characteristics

Among the 195 patients, 127 underwent K-BCS (incision design: wave-like, n=89; linear, n=38) and 68 underwent the tumor-surface incision. The median clinical follow-up was 33.5 months (range, 1.7–56.5 months). Significant differences in age and NTD were observed between the two groups (Table 1). Patients in the K-BCS group were younger than those in the tumor-surface incision group (mean age, 53.7±10.4 vs. 59.4±12.8 years, respectively; P=0.002). The mean NTD of the K-BCS group was smaller than that in the tumor-surface incision group (4.20±1.71 vs. 5.38±2.47 cm, respectively; P=0.001). This difference was likely because the periareolar incision was more commonly performed for tumors located closer to the NAC. No significant differences in other patient characteristics were observed between the two groups.

Cosmetic outcome

The K-BCS group exhibited significantly better esthetic outcomes than the tumor-surface incision group (esthetic outcomes: excellent, 57% vs. 34%; good, 37% vs. 47%; fair, 5% vs. 16%; poor, 1% vs. 3%, respectively; P=0.002; Figure 2).

Figure 2 Comparison of postoperative breast cosmetic outcomes evaluated using BCCT.core. The bar graph shows the proportions of four-point BCCT.core evaluations (excellent, good, fair, or poor) of postoperative cosmetic outcomes for the K-BCS group and the tumor-surface incision group. The proportions of the four-point scale evaluations between the two groups were assessed using Fisher’s exact test. K-BCS, Keio-breast-conserving surgery.

In the subgroup analysis, the K-BCS group showed superior cosmetic results compared with the tumor-surface incision group across all subgroups (Figure 3). In the upper inner and lower inner quadrants, the K-BCS group achieved significantly better esthetic outcomes than the tumor-surface incision group. In the upper inner quadrant, the rate of ‘excellent’ evaluation was 50.0% vs. 10.5%, respectively [odds ratio (OR) =8.50; 95% confidence interval (CI): 1.77–40.1; P=0.008]. In the lower inner quadrant, the rate of ‘excellent’ evaluation was 73.3% vs. 16.7%, respectively (OR =13.7; 95% CI: 1.21–157.0; P=0.04); however, the number of the patients in the tumor-surface incision group was low.

Figure 3 Subgroup analysis of ORs for ‘excellent’ evaluations between the K-BCS and tumor-surface incision groups. Subgroup analysis results and the corresponding forest plot for the ORs of ‘excellent’ evaluations between the K-BCS and tumor-surface incision groups are shown. An OR ≥1 indicates a higher likelihood of ‘excellent’ evaluations in the K-BCS group. BMI, body mass index; CI, confidence interval; K-BCS, Keio-breast-conserving surgery; NTD, nipple-tumor distance; OR, odds ratio.

In the univariate analysis of the logistic regression, operation type, age, BMI, tumor location, and NTD were associated with ‘excellent’ evaluation (Table 2). In the multivariate analysis, K-BCS was shown to be significantly associated with ‘excellent’ evaluation, even after adjusting for other factors (OR =2.58; 95% CI: 1.26–5.32; P=0.009).

Comparison between wave-like and linear designs within the K-BCS group

Within the K-BCS group, baseline patient and tumor characteristics did not differ significantly between the wave-like (n=89) and linear (n=38) incision designs (Table S2). There was no significant difference in cosmetic outcomes between the two designs (excellent, 60% vs. 53%; good, 35% vs. 42%; fair, 4% vs. 5%; poor, 1% vs. 0%, respectively; P=0.83; Table S3).

Oncological safety

No significant difference in the rate of positive or close surgical margins was observed between the K-BCS and tumor-surface incision groups (frozen section: 14.2% vs. 11.8%, P=0.83; permanent section: 0.79% vs. 2.94%, respectively, P=0.28; Table 3). K-BCS demonstrated comparable outcomes to the widely accepted tumor-surface incision, which is used to successfully achieve adequate surgical margins in BCS. No re-excision was performed in the entire cohort; all three patients with positive or close margins (all with a non-invasive component only) received a radiation boost instead, at the patients’ request.

Surgical safety

No significant differences between the K-BCS and tumor-surface incision groups were observed in operative time (118.8±28.9 vs. 121.7±31.5 min, respectively, P=0.52; Table 4) and intraoperative blood loss (16.5±11.2 vs. 19.2±11.5 mL, respectively, P=0.11). The K-BCS group had a higher drain insertion rate than the tumor-surface incision group (72.4% vs. 13.2%, respectively, P<0.001). Owing to the time required for drain removal, the postoperative length of hospital stay was longer in the K-BCS group (4.80±1.36 vs. 4.23±1.69 days, respectively, P=0.01).

No significant difference in the incidence rate of complications was observed between the two groups (15.0% vs. 19.1%, respectively, P=0.54; Table 4). The most common complication in both groups was seroma. Sub-nipple dissection was performed in all cases in the K-BCS group; however, no cases of nipple necrosis were observed.

Discussion

Breast esthetics following BCS is one of the most important concerns for patients. Although there were differences in patient and tumor characteristics between the two groups (younger age and shorter NTD in the K-BCS group), K-BCS yielded better esthetic outcomes than the tumor-surface incision. This superiority was preserved across all subgroup analyses, and multivariable adjustment confirmed K-BCS as an independent predictor of an ‘excellent’ outcome. Three reasons may explain why our approach contributed to improved esthetic outcomes across a variety of patient and tumor characteristics.

First, the wave-like incision design, predominantly used in the K-BCS group, achieves both surgical accessibility and inconspicuous scarring. In the tumor-surface incision, larger tumors and specimens require wider skin incisions, often leading to more conspicuous scars and higher risk of skin traction. In contrast, the wave-like incision expands like an accordion, facilitating access to and excision of large or distant tumors with the wider surgical field. In this study, specimens up to 8 cm en bloc were successfully removed and resected tumors were located as far as 10 cm from the nipple. Additionally, the wave-like incision has the advantage of unnoticeable scars. Although long-term outcomes were not analyzed in the present analysis, postoperative photographs (>12 months) are provided as illustrative examples, showing that this design becomes inconspicuous (Figure 4) and is often difficult to detect from a distant view (Figure 5). This favorable durable appearance reflects the design’s partial alignment with the natural lines of skin tension, which reduces scar formation (12-14).

Figure 4 Time-dependent changes in linear and wave-like periareolar incision designs. These clinical photographs show time-dependent changes to the periareolar incisions using either a linear or a wave-like design. These photographs were taken at four time points: preoperatively, immediately postoperatively, at 1 week postoperatively, and at 12 months postoperatively. Each row shows serial photographs of the same patient. Long-term observation showed favorable scar healing in both designs; these photographs are provided as illustrative examples of long-term postoperative appearance. These images are published with the patients’ consent.

Figure 5 Representative postoperative breast appearance in patients who underwent K-BCS. Representative distant-view (left) and close-up (right) clinical photographs of three patients who underwent K-BCS are shown as illustrative examples of long-term postoperative appearance. Bilateral breast photographs were taken >12 months postoperatively. Tumor locations are indicated by red circles. (A) A woman in her 70s with a tumor in the upper outer quadrant. (B) A woman in her 50s with a tumor in the lower outer quadrant. (C) A woman in her 60s with a tumor in the lower inner quadrant. These images are published with the patients’ consent. K-BCS, Keio-breast-conserving surgery.

Second, sub-nipple dissection enables more flexible reshaping of the breast in all quadrants without additional skin incisions or excisions. In conventional OBCS, surgical techniques are often modified based on tumor location—for example, V-mammoplasty for the lower inner quadrant and J-mammoplasty for the lower outer quadrant (19,20). Furthermore, additional skin incisions or excisions are frequently necessary to mobilize the glandular tissue. The impractical diversity of techniques and increased invasiveness have hindered the standardization of OBCS. To address these issues, we employed sub-nipple dissection, which allowed glandular tissue to move independently from the NAC and the overlying skin, and achieved symmetric reconstruction across all quadrants in most cases without additional incisions. Nipple displacement and skin retraction were rarely observed in K-BCS. Our approach substantially enhanced surgical flexibility and has the potential to reduce procedural variations as a single technique applicable across various patient and tumor characteristics.

Third, extensive subcutaneous dissection, in combination with sub-nipple dissection, improved the efficiency of defect filling. Breast reconstruction is generally challenging for large tumors or those located in the upper inner and lower inner quadrants where glandular volume is limited (20). In these areas, the tumor-surface incision tends to produce hypertrophic or prominent scarring owing to upward tension resulting from breast weight and proximity to the sternum. Deformity in this quadrant may compromise the natural contour of the décolleté and is highly noticeable (9). However, K-BCS achieved significantly better esthetic outcomes compared with the tumor-surface incision in these inner quadrants. This result is attributable to wide subcutaneous dissection, which allows redistribution of glandular tissue from other quadrants to compensate for volume deficiency. Achieving favorable cosmetic outcomes in these inner quadrants can be considered a significant advantage of K-BCS.

In K-BCS, the incision design (wave-like or linear) primarily determines surgical access and scar appearance, whereas the cosmetic reshaping benefit is driven by the sub-nipple and extensive subcutaneous dissection common to both designs; consistently, no significant difference in cosmetic outcomes was observed between the wave-like and linear designs, supporting grouping them as a single K-BCS technique. These techniques are within the routine skill set of breast surgeons and are expected to be readily acquired.

K-BCS showed oncological safety and an acceptable complication profile. No significant difference was observed in the rate of positive or close margins between the two groups. K-BCS ensured oncological safety similar to the tumor-surface incision, which is generally advantageous for obtaining adequate margins. Surgical complications were also comparable between the two groups. There were no cases of nipple necrosis in the K-BCS group, indicating that our sub-nipple dissection technique successfully preserved the looped venous network beneath the NAC. Prophylactic drain placement was intended to prevent seroma or hematoma from compromising nipple blood flow after K-BCS’s extensive dissection. This accounts for the higher drain insertion rate in the K-BCS group and, owing to drain removal timing, a longer hospital stay. Although drain insertion is often required in K-BCS, its preventive role and the modest extension of hospital stay are unlikely to hinder adoption.

K-BCS is not suitable for certain cases. First, when a tumor lies in the outer breast area near the serratus anterior muscle or axillary region, an incision along the mammary line provides better access. Second, a specimen too large to be removed through a periareolar incision renders this approach impractical. Third, when a tumor extends close to the skin and skin resection is required, tumor-surface incision is more appropriate. Fourth, K-BCS is not suitable for patients who desire lactation from the treated breast because it transects the glandular tissue beneath the NAC; in addition, postoperative radiotherapy itself substantially reduces lactation function (21).

This study had some limitations. It was a retrospective, single-center study with a small cohort, limiting generalizability. The choice of surgical technique may have introduced selection bias, indication bias, and surgeon-related bias from the partial surgeon–technique correlation; these biases cannot be fully excluded. K-BCS was performed disproportionately by a single surgeon (surgeon A: 64.6% of all K-BCS cases), and K-BCS adoption rates varied among surgeons who used both techniques (surgeon A: 94.3%; surgeon B: 58.9%; surgeon C: 44.4%), likely reflecting individual differences in clinical judgment regarding K-BCS feasibility. The primary cosmetic endpoint was assessed 1 month postoperatively, before adjuvant radiotherapy. Although this timing enables a matched-condition comparison between the two techniques and captures clinically meaningful early cosmesis, it does not capture the final long-term cosmetic outcome after completion of radiotherapy. Frontal-photograph assessment may not fully capture the three-dimensional breast shape or clinical impressions. Patient-reported outcomes and preoperative breast size were unavailable. Finally, oncologic safety was evaluated only using resection margins; long-term follow-up including survival analysis was not conducted in this study.

Conclusions

K-BCS showed better esthetic outcomes compared with the conventional tumor-surface incision across diverse patient and tumor characteristics in the early postoperative period. This novel oncoplastic method successfully balanced esthetic outcomes with oncological and surgical safety, and may serve as a promising and reproducible option within OBCS. Further studies are warranted to evaluate cosmetic outcomes after completion of radiotherapy, long-term oncological outcomes including survival, and patient-reported satisfaction.

Acknowledgments

We express our sincere gratitude to Jaime S. Cardoso, M. J. Cardoso, and the INESC Porto Breast Research Group for providing the BCCT.core software, which we used for the objective evaluation of breast cosmetic outcomes. We would like to thank Editage (https://www.editage.jp/) for English language editing. This work was presented in part at the 33rd Annual Meeting of the Japanese Breast Cancer Society and the 125th Annual Congress of the Japan Surgical Society.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0299/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0299/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0299/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0299/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Keio University School of Medicine (approval No. 20150170) and individual consent for this retrospective analysis was waived. All images presented in the figures of this article were used with permission obtained from the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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