PerfAct Study

Overview

This is a unique translational national, multicentre study aimed at understanding the issue of injury to the mastectomy skin flap caused by the retractors. A safe flap is an absolute essential during skin or nipple-sparing mastectomy with immediate breast reconstruction. The undue pressure from retractors, which can lead to potential loss of skin flap perfusion, remains a concern for the majority of reconstructive surgeons. However, to our knowledge, there are no studies in the literature that have attempted to explore and understand these issues objectively. This study, employing a translational approach, compares retractors versus non-retractors methods, aiming to provide initial evidence and generate ideas and innovations, including instrumentation, to maximise safety and achieve the best possible outcomes following breast reconstruction. It is funded by the UK Government's Research & Innovation Office for Technology Transfer, the Lead Centre’s charity (Addenbrooke's Charitable Trust), and, along with a generous supply of ICG, by Kimal Limited. It is sponsored by the Cambridge University Hospitals NIHR Biomedical Research Campus and managed by the Cambridge Clinical Trials Unit supported by the NIHR Research nursing team. 

Objectives

Complication rates associated with mastectomy and immediate reconstructions remain high; for example, with dominant implant reconstructions, up to 25% in the UK. Several risk factors have been identified for patient selection and during mastectomy. One dominant intraoperative risk is the use of retractors, which can cause mechanical damage to the skin flap's vascularity. In an EU survey, eighty per cent of EU breast surgeons believed that retractors were the leading cause of injury to breast skin during immediate reconstruction. The CI's online survey of UK breast surgeons revealed similar thinking. 

Hence, there is a need to understand and reduce issues due to tissue handling. The overall aim of the study is to collect clinical evidence to demonstrate the difference in trauma caused to the breast tissues due to current surgical practices in women undergoing bilateral mastectomy with immediate breast reconstruction. On one side, the surgeon exclusively uses retractors, and on the other side, uses splayed fingers (a gentler spread-apart technique) as long as possible, followed by retractors to complete the surgery. The skin flap perfusion as a consequence of the pressure is then measured objectively using ICG fluorescence. The baseline perfusion is compared to perfusion when the surgeon switches from fingers-only to retractors and at the end of mastectomy, with the following objectives:

Primary Objective: To determine if there is a difference in blood perfusion (Relative Value %) in the breast where the non-retractor technique is used versus the breast where the retractor technique is used. 

Secondary Objectives: To assess whether there are differences in the post-surgical complications, post-surgical recovery and post-surgical pain scores between the two sides. 

Exploratory (ergonomics) Objectives: To evaluate the surgeons’ experience of each different operative technique, retractors and non-retractors. 

Inclusion/exclusion criteria

Inclusion criteria:

• Female aged 18 years old or above.
• Needing bilateral mastectomy for either breast cancer or for risk reduction (due to pathogenic gene variation, high-risk family history, or previous mantle radiotherapy for lymphoma).
• Undergoing bilateral mastectomy concurrently with immediate breast reconstruction.
• Undergoing the same type of breast reconstruction on both sides.
• Adequate liver function where bilirubin is ≤1.5 x ULN.
• Adequate renal function with a serum creatinine ≤ 1.5 x ULN.

Exclusion criteria: 

• Locally advanced breast cancer with skin involvement.
• Previous unilateral breast radiotherapy (if mastectomy is for local recurrence).
• Previous significant unilateral breast surgery (such as reduction) judged by the recruiting/operating surgeon to have adversely affected breast supply on that side.
• Known allergies or hypersensitivity to indocyanine green (ICG) dye, sodium iodide or iodine or having experienced previous side-effects of ICG dye or its components.
• Patients with an overactive thyroid or benign tumours of the thyroid gland.
• Patients with severe renal insufficiency.
• Women who are pregnant, plan to become pregnant, or are lactating during the study period.

Planned sample size

It is a multicentre national study open to all centres within the UK ABS membership, provided they have the experience and availability of the Spy Phi perfusion measurement gadget with the QP software. As a feasibility study, the sample size is 30, with each partner centre anticipated to recruit up to five patients. 

Total number of sites planned

Based on the sample size and the known number of breast units using the said gadget, up to 5 centres were included in the funding. Participating centres were required to confirm the feasibility criteria supported by their CLRN and research and development team. 

Timeline

The study is approved until January 2026.