Use of Microporous Polysaccharide Hemispheres in Breast Cancer Patients Undergoing Mastectomy

INTRODUCTION Breast cancer is one of the most frequently diagnosed neoplasms worldwide. The global incidence of breast cancer has been increasing during the past decades. It was estimated to affect approximately 2.3 million women globally in 2020, causing about 685,000 deaths, and its incidence is likely to increase in the years to come.

Locoregional therapy includes surgery to remove the tumour, which remains one of the key interventions in the management of breast cancer. However, different postoperative complications can arise, especially when axillary surgery is concomitantly performed. Among these, seroma formation is one of the most common, with a described incidence of up to 90%, defined as an accumulation of serous fluid under the skin. Although seromas are not usually considered a serious complication, their appearance can result in wound infection and delayed wound healing and might delay adjuvant treatments.

Different strategies are currently available, such as wound drainage, external compression dressings, glues, and drugs, to reduce postoperative seroma formation. Several meta-analyses have evaluated the use of these techniques however, some of these studies have highlighted the lack of the overall quality of the reviewed data.

In this context, hemostatic agents have emerged as an alternative in surgical procedures. Among these, a powder composed of plant-based microporous polysaccharide hemospheres (MPH)11 has been approved as an adjunctive hemostatic device. MPH functions as a sieve absorbing fluid and concentrating clotting factors and is absorbed within 24 to 48 hours. Over a decade ago, MPH showed a significant reduction in seroma volume after mastectomy and axillary dissection in an animal model. In addition, these authors demonstrated a reduction in seroma's total protein, albumin and lactate dehydrogenase levels and white blood cell count in animals receiving MPH, suggesting a reduced seroma formation after MPH application. More recent studies conducted in patients undergoing different surgical interventions have evaluated the potential of MPH in postoperative seroma formation. However, data on MPH effectiveness in reducing seroma formation are heterogeneous.

Considering the above, the main goal of the study was to evaluate the use of MPH in reducing postoperative seroma formation in patients with breast cancer undergoing mastectomy with or without axillary lymphadenectomy.

In addition, we aimed to assess the emergence of immediate postoperative complications (first 72 hours) and the number of visits to the emergency department, to identify clinical factors associated with seroma formation, and to determine the relation between the amount of MPH and seroma formation, drain output, lymphadenectomy, and body mass index (BMI).

OBJECTIVE This study aimed to evaluate the effects of MPH in reducing postoperative seroma formation in patients undergoing mastectomy, with or without associated lymphadenectomy.

METHODS Study design and population This prospective, controlled study was conducted at the Hospital Clínico Universitario de Valencia between 2020 and 2022. All patients ≥18 years old diagnosed with breast cancer undergoing mastectomy with or without axillary lymphadenectomy were consecutively invited to participate in the study. No exclusion criteria were applied. Written informed consent was obtained before the inclusion. During the intraoperative period, patients were randomized 1:1 to receive microporous polysaccharide hemispheres (AristaTM AH; MPH treatment arm) or not (control arm). Management of postoperative complications in both groups followed routine clinical practice.

The study was approved by the Ethics Committee for Research of the Hospital Clínico Universitario de Valencia (code 2024/118) and developed following the ethical standards of the Helsinki Declaration of 1975.

Surgical procedure The surgical procedure followed the standard protocol for this type of intervention. In most cases, the Stewart incision was adapted according to the location of the tumour and/or the necessity for skin resection. The axillary approach, whether for the sentinel lymph node biopsy or in cases requiring an axillary dissection, was performed through the same incision used for the mastectomy. After the resection of the mammary gland and/or axillary node dissection, the area of the surgical site was measured. The area was calculated in all cases by measuring the length of the surgical site from medial to lateral and cranial to caudal, multiplying these dimensions to obtain the area in cm². Following the mastectomy and measurement of the surgical site, the patient was randomized. If assigned to the Arista group, the product was applied to cover the entire surface, and the amount used was recorded in grams. In all cases, suction drains were placed, and a compressive bandage was applied to all patients in both groups. They were discharged on the same day as the surgery and were followed up in outpatient clinics 24-48 hours post-operation. Each patient was provided with a sheet to record the daily drainage output. During follow-up visits, the drain was removed when the output was less than 30 ml over 24 hours, and patients were monitored until the complete resolution of the seroma. In cases where a seroma developed, drainage was performed via puncture and aspiration.

Study variables Sociodemographic (sex, age), clinical (weight, height, obesity, body mass index, diabetes, previous breast cancer and surgery, cardiopathy, hypertension, chronic obstructive pulmonary disease, smoking status, use of antiplatelet drugs and anticoagulants) and breast cancer-related (affected breast, inflammatory carcinoma, diagnostic, molecular determination, adjuvant treatment, sentinel node affectation) characteristics were collected before the procedure. Variables related to the surgical procedure (lymphadenectomy, mastectomy, surgical intervention time, surgical area, intraoperative complications, drainage, antibiotic prophylaxis, dressing, hemostasia, bleeding risk) and patient follow-up (surgical wound infection and dehiscence, seroma, time with drainage, volume of drain output, seroma punctures, postoperative complications, hematoma, follow-up time, outpatient visits, hospital length of stay, death) were also collected.

Sample size calculation The sample size was estimated based on data from a previous review in which the percentage of seromas in mastectomy after a drain insertion was 46.21%19.

To find as statistically significant a proportion difference of ≥25% between treatment and control arms (estimated at 0.2121 and 0.4621 for the MPH and control group, respectively) and accepting a confidence level of 5% (alpha risk) and a power of 80% (beta risk) in a two-tailed test, a total sample size of 116 patients (58 per treatment arm) was estimated. A drop-out rate of 5% was anticipated.

Statistical analysis Quantitative variables were presented as mean and standard deviation (SD). For qualitative variables, relative and absolute frequencies were calculated. The normality of data distribution was tested with the Shapiro-Wilk test.

The association between MPH and qualitative variables was assessed using the Chi-square or Fisher's exact test, while the association between MPH and quantitative variables was evaluated using Student's t-test or Mann-Whitney U test. A univariate logistic regression model was also used to quantify the association between seroma formation and the MPH treatment arm. Results were presented as Odds Ratio (OR) and 95% confidence interval (95% CI). To evaluate the association between the quantity (cm2/g) of MPH used during surgery and the drain output, Pearson's correlation coefficient or Spearman's non-parametric correlation coefficient were used.

All analyses were performed using the STATA v.14 software. A p-value \< 0.05 was considered statistically significant for all statistical tests.