Successful Outcomes of Single‐Port Insufflation Endoscopic Breast‐Conserving Surgery for Breast Cancer


 PurposeIn the surgical treatment of breast cancer, the goal of surgeons is to continuously create and improve minimally invasive surgical methods to increase the quality of life of the patient. Currently, routine breast-conserving surgery is performed using two obvious incisions. Here, we compare the clinical efficacy and aesthetic perspectives between a novel technique using one incision called single-port insufflation endoscopic breast-conserving surgery and conventional breast-conserving surgery in early stage breast cancer.MethodsA total of 180 patients with stage I or stage II breast cancer participated in this study. Single-port insufflation endoscopic breast-conserving surgery was performed on 63 patients, while conventional breast-conserving surgery was performed on 117 patients. The evaluation of the aesthetic outcome was carried out by the BREAST-Q scale. Logistic regression was conducted to assess the risk of local recurrence and metastasis.ResultsThere were significant differences between the two groups for chest well-being, psychological well-being, and adverse effects of radiation. The scores for satisfaction of breasts and sexual well-being showed no statistical differences between the two groups. There was no statistical significance in local recurrence or metastasis between the two groups. Single-port insufflation endoscopic breast-conserving surgery did not increase the risk of local recurrence or metastasis.ConclusionThe novel surgical technique, single-port insufflation endoscopic breast-conserving surgery, is a feasible and safe surgery and has advantages in terms of cosmetic outcome and psychological status.


Introduction
Breast cancer is the most common malignancy in women worldwide [1][2][3]. To surgically treat breast cancer, surgeons have continuously created and improved minimally invasive procedures such as breastconserving surgery, sentinel lymph node biopsy, and endoscopic surgery. Due to these advanced techniques, patients diagnosed with breast cancer increasingly adopt the minimally invasive breastconserving therapy over mastectomy. Multiple studies have observed a faster recovery and better body image satisfaction in women who chose breast-conserving therapy while also showing similar survival rates for breast-conserving therapy and mastectomy [4][5][6][7]. When surgery is indicated for treatment and the patient choses conventional breast-conserving surgery (C-BCS), the surgery is performed by creating two obvious incisions. One incision is used for local extended lumpectomy and the other for sentinel lymph node biopsy or axillary lymph node dissection. These obvious incisions can cause patient dissatisfaction and poor body image. Therefore, we designed a novel surgical technique called single-port insu ation endoscopic breast-conserving surgery (SIE-BCS), which combines the advantages of being minimally invasive and breast-conserving without an obvious incision on the breast. In this retrospective cohort study, we compare the clinical e cacy and aesthetic outcomes between SIE-BCS and C-BCS.

Ethics Statement
All of the surgical procedures and informed consent details were approved by the Ethics Committee of the  (Table 1). SIE-BCS was performed on 63 patients. C-BCS was performed on 117 patients. The following inclusive criteria were used: (1) diagnosis of stage I or II invasive breast cancer; (2) the tumor was constrained to the mammary gland (magnetic resonance imaging con rmed); (3) lesions ≤ 3 cm in diameter and the distance between the lesion and the nipple areola complex > 3 cm; (4) axillary lymph nodes were not signi cantly fused with the axillary vein or brachial plexus nerves; (5) patients with adequate glandular volume; (6) age between 18 and 70 years old; (7) Eastern Cooperative Oncology Group scoring grade from 0 to 2; and (8) normal function of the liver, kidney, and bone marrow.
The following exclusive criteria were used: (1) comorbidities including cardiovascular disease, myocardial infarction, and cerebrovascular disease; (2) patients who could not receive general anesthesia or surgical treatment; (3) tumor history within the past ve years; (4) pregnant or lactating women; (5) the tumor invaded the skin or subcutaneous tissue (con rmed by magnetic resonance imaging or physical examination); (6) widespread disease that cannot be incorporated by local excision of a single region or segment of breast tissue that achieves negative margins with a satisfactory cosmetic result; (7) unable to guarantee performance of radiological therapy after the operation; and (8) persistently positive pathologic margin.

Surgical procedures
All surgeries in both groups were performed by Dr. Xiang Qu. Patients were placed in the supine position with the ipsilateral arm in abduction at 90°. First, we injected 0.2 mL of methylene blue around the mammary areola to identify the sentinel lymph node. To endoscopically con rm the extent of tumor removal, we injected 5 mL of methylene blue 1 cm away from the tumor margin ( Fig. 1). After fteen minutes, a 2.5 cm single-port incision was made along the wrinkles in the axilla. Second, we performed the sentinel lymph node biopsy through this incision, and the intraoperative frozen pathology determined whether axillary lymph node dissection was necessary.

SIE-BCS procedure
A total of 63 cases were performed by the same team and the same surgeon (X. Qu). The laparoscopy equipment kit (Olympus Optical Co., Tokyo, Japan) included optic and endoscopic instruments and were reusable after disinfection. For SIE-BCS, we used the same short axillary incision that was used to perform the sentinel lymph node biopsy. First, we injected 0.5 mg of adrenaline mixed with 250 mL of 0.9% sodium chloride into the subcutaneous layer between the skin ap and the mammary gland to reduce blood loss. Second, we inserted a tunneler ( Fig. 2) into the subcutaneous layer to reveal the potential space between the skin ap and the mammary gland. Third, we created an adequate working space by insu ating 8 mmHg of pressure and 8 L of carbon dioxide per minute through the single-port insu ation kit (HTKD-Hang T Port, China) ( Fig. 3), which also had four plastic trocars on the surface. We inserted the laparoscopic tools from the single-port insu ation kit. Then, we dissected the Cooper's ligament with laparoscopic tissue scissors until the skin ap and the mammary gland were totally separated (Fig. 4). Next, we used electrocautery to vertically section from the surface of the mammary gland to the pectoral fascia. The excision range was determined via the prior methylene blue injection (Fig. 5). Finally, the retromammary space was separated with electrocautery, and the pectoral muscle fascia was removed laparoscopically. To prevent metastasis from the incision, the tumor and surrounding tissues were removed through the single-port insu ation kit (Fig. 6).
An intraoperative cryosection was performed around the edges of the specimen to con rm the extent of in ltration of the tumor. If the result implied residual tumor cells, then additional resection was performed until no residual tumor cells were found. If the cryosection pathology was positive more than twice, then a mastectomy was considered and performed immediately.
Titanium clips were placed around the incisal margin of the tumor for subsequent radiotherapy. A running suture of absorbable mono lament 3 − 0 barbed thread was used to close the residual cavity of the mammary gland. The surgical eld was irrigated, and one drainage was placed. The single axillary incision was sutured intradermally with a 4 − 0 absorbable suture. The 63 patients who received SIE-BCS also received postoperative radiotherapy according to the National Comprehensive Cancer Network guideline [8].

C-BCS procedure
In addition to the axillary incision, a second spindle-shaped incision on the surface of the tumor was created. The tumor and the surrounding glandular tissues within 1cm of the lesion were removed. An intraoperative cryosection of the incised margin around the tumor and the basal tissue of the tumor was performed. If the pathological ndings indicated the presence of residual tumor cells, then the resection was extended until the pathological results indicated the incised margin was negative. Titanium clips were placed in the residual cavity to locate the tumor area for postoperative radiotherapy. The surgical eld was irrigated, drainage was placed, and the incision was sutured layer by layer.

Cosmetic Evaluation and Patient Satisfaction
The aesthetic satisfaction of patients was evaluated by the BREAST-Q [9,10] scale six months after the operation. The BREAST-Q included questions about the patients' satisfaction with their breasts, psychosocial well-being, chest well-being, adverse effects of radiation, and sexual well-being. We compared the answers between the two groups.
Statistical Analysis Measurement data were described by mean ± standard deviation (normal distribution) or median (upper quartile, lower quartile) (non-normal distribution). Differences in patient age, tumor size, operative time, hospitalization days, incision length, cosmetic effect score, blood loss, the total ow, and drainage tube indwelling time were determined using the independent sample t-test (normal distribution) or the Mann-Whitney U nonparametric test (non-normal distribution). Count data, such as lesion site, tumor stage, and hormone receptor, were described in absolute numbers and percentages. Fisher's exact test was used to determine differences for the intraoperative cryosections, local recurrence, and metastasis between the two groups. Baseline data differences between the two groups were compared using the Chi-square test. The methods of operation, size, age, and HER2 status were analyzed by logistic regression. SPSS 22.0 statistical software was used for all statistical analyses. There was a signi cant difference when p < 0.05.

Results
No laparoscopic-related complications such as subcutaneous emphysema were observed. The mean incision length was 3.4 cm in the SIE-BCS group and 8.6 cm in the C-BCS group. The difference between the two groups was statistically signi cant (t = 19.59, p < 0.001) ( Table 2). The difference in mean operation time between the two groups was statistically signi cant (T = 8.788, p < 0.001) ( Table 2)     The patients were followed up until October 2020. Two patients in the SIE-BCS group had local recurrence (3.2%), while no patients in the C-BCS group had local recurrence (0%). One patient in the SIE-BCS group had metastasis (1.6%), while six patients in the C-BCS group had metastasis (5.1%) ( Table 2). The differences between the SIE-BCS group and C-BCS group for local recurrence (p = 0.121) and metastasis (p = 0.424) were not statistically signi cant.  (Table 4).

Discussion
Breast-conserving surgery is becoming the rst choice for patients when they are diagnosed with earlystage breast cancer [11,12]. However, traditional open breast-conserving surgery requires two obvious surgical incisions, which have a negative impact on postoperative aesthetics and quality of life for patients [13][14][15]. For this reason, patient quality of life and well-being after breast surgery are important factors to evaluate as clinical outcomes and to consider when developing diagnosis and treatment techniques. Due to the continuing development of laparoscopy in general surgery, surgeons have begun integrating the technology in breast-conserving surgery for the treatment of early breast cancer [16,17]. In this study, we developed and introduced SIE-BCS. We previously described a nonin atable laparoscopic breast-conserving surgery [18]. However, this novel use of the insu ation technique from this report allowed an increase in su cient surgical space and an increase in satisfactory exposure compared to our previous report.
All patients successfully completed endoscopic breast-conserving surgery, and there were no transfers to open surgery. Unexpectedly, when performing the intraoperative cryosection of the margin of the tumor, the residual tumor cell rates in both groups were low (0% in the SIE-BCS group and 1.7% in the C-BCS group). In addition, there were no residual tumor cells at the resection margin after postoperative pathology. This is in contrast to other studies [19,20] that found residual tumor cells at the resection margin in approximately 6.3% of cases. We hypothesize that the low positive residual tumor cell rate in our study was related to how our group determines the resection range. Before surgery, we palpate the tumor edge and then inject methylene blue around the tumor with a 1 cm margin that was used as the boundary for surgical resection. Postoperative gross pathology shows that palpation leads to a size larger than the actual tumor compared to other detection methods, such as ultrasound. Therefore, the method of palpation and adding a 1-cm border may explain the nonexistent residual tumor cell rate in both groups.
The SIE-BCS group had a signi cantly shorter incision length than the C-BCS group (3.4 cm vs 8.6 cm, respectively, p < 0.001). This novel single-port endoscopic surgical technique reduced the length of the incision and the number of incisions. Additionally, this single-port incision was created along the wrinkles of the axilla, which is then hidden by the upper limb and the axillary fossa (Fig. 7A). Routine breastconserving surgery typically requires two obvious incisions. The incision on the surface of the breast greatly reduces the aesthetic satisfaction of the patient (Fig. 7B). The mean operation time of C-BCS was signi cantly shorter than the operation time of SIE-BCS and C-BCS. When we compared the operation times of the lateral quadrant and the medial quadrant in each group, we found that there was no statistically signi cant difference. This indicates that the length of operation time was related to the operation method. It has been shown in other elds, such as gastrointestinal [21], hepatobiliary [22], and thyroid surgery [23], that the use of endoscopy increases the operation time when compared to conventional surgery.
The BREAST-Q scores at six months after the surgery showed that there were statistically signi cant differences in chest well-being and psychological well-being between the SIE-BCS group and the C-BCS group. This could be due to avoiding an incision on the breast surface. These results indicate that choosing SIE-BCS may bring a better psychological status and higher quality of life to the patient. We observed that there was no statistically signi cant difference breast satisfaction between the two groups. The reason may be that both groups received breast-conserving surgery. Surprisingly, we observed that the SIE-BCS group had a better score than the C-BCS group for adverse effects of radiation. By removing one incision for SIE-BCS, there is no longer a scar on the breast surface that may cause discomfort from scar contracture during radiotherapy. The reduction of side effects from radiotherapy and an improvement in chest well-being in SIE-BCS patients likely contributed to the improvement of psychological well-being.
Because the HER2 positivity rate was different between the two groups, logistic regression analysis was performed. HER2 positivity rate, method of operation, tumor size, and age were included in the analysis. The results showed that choosing SIE-BCS did not increase the risk of local recurrence or metastasis. HER2 positivity rate, tumor size, and age were not independent risk factors for local recurrence and metastasis in this study. However, other studies have found that HER2 status, tumor size, and age are risk factors for recurrence [24,25]. This inconsistency is likely due to a small sample size and short follow-up period in our report. A future prospective study has been designed to further clarify this nding.

Conclusion
In this study, we introduced a novel single-port endoscopic method of breast-conserving surgery called SIE-BCS that reduced the length and number of incisions. SIE-BCS patients reported signi cantly better scores for adverse effects of radiation, chest well-being, and psychological well-being compared to C-BCS patients. Logistic regression analysis showed that SIE-BCS did not increase the risk of local recurrence and metastasis. Because this study was a retrospective study with a short follow-up time, we have designed a prospective study to further prove the feasibility and success of this novel breast-conserving method.

Declarations
Abbreviations C-BCS Conventional breast-conserving surgery CI Con dence interval OR Odds ratio SIE-BCS Single-port insu ation endoscopic breast-conserving surgery Declarations