Improvement in Breast Skin Sensibility After Breast Reconstruction: a Comparison of 3 Surgical Techniques (S-DIEP)

Sensory Restoration in DIEP Free Flaps for Post-Mastectomy Breast Reconstruction After Breast Cancer: Comparing Non-sensitized Standard Technique to Direct Nerve Suture and to Autograft: A Three-arm, Randomized, Double-blinded Superiority Trial

The goal of this clinical trial is to learn if nerve sutures in free flap breast reconstruction can optimize sensibility in the reconstructed breast in patients opting for DIEP flap breast reconstruction due to breast cancer or genetic conditions. Affected women 18 to 80 years old can be included. The main question is:

If a nerve suture was carried out, can pressure be felt better on the reconstructed breast after 12 months? If a nerve suture was carried out, will better sensibility and quality of life be felt and perceived (questionnaire) at 12 and 24 months after the initial operation ? Researchers will compare two different nerve suture techniques and no nerve suture to one another to see if and which nerve suture optimizes sensibility.

Participants will have regular visits and follow-up controls, during which

• their sensibility will be tested multimodally,
• they will fill out questionnaires
• skin biopsies will be taken.

Study Overview

• Status: Recruiting
• Conditions: Reconstruction Breast Surgery; Breast Cancer Surgery; Sensitization; DIEP Flap Breast Reconstruction
• Intervention / Treatment: Procedure: Nerve Suture

Detailed Description

Breast reconstruction with autologous tissue is one of the most important methods: The DIEP (deep inferior epigastric artery perforator) flap is today's workhorse in autologous reconstruction. Routinely, the arteries and veins of the donor- and recipient sites are connected, but not the nerves. The sensory recovery is an undervalued aspect despite the disadvantages of insensate flaps. Connection of the abdominal flap skin's nerves to the breast region's nerves allows sensitized reconstruction. The research project aims to make sensitized flap-based breast reconstruction the standard method by proving its superiority, using the sensory testing with Semmes-Weinstein-Monofilament (pressure threshold) as the primary outcome measured before surgery and 12 months post-surgery. Therefore, patients will be randomized in three groups:

1. sensitization with direct nerve suture or
2. autograft or
3. no sensitization. Moreover, no previous studies have analyzed the potential changes in flap skin with proteomics, thus justifying our secondary objective.

The hypothesis is that flaps with nerve suture(s) have better sensibility. The main outcome will be the sensory testing (pressure threshold). As secondary outcomes the questionnaire will show the patients' quality of life, and the proteomic analysis, should, according to our hypothesis, show that quantity and expression of the proteins of flap skin with nerve suture are closer to normal skin than without nerve suture.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patricia E Engels, MD; Phone Number: +41795537557; Email: patricia.engels@hug.ch
• Study Contact Backup: Name: Axelle Serre, MD; Phone Number: +41795538642; Email: axelle.serre@usb.ch

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • Recruiting
    • Geneva University Hospitals
    • Contact: Patricia E Engels, MD; Phone Number: +41795537557; Email: patricia.engels@hug.ch
    • Contact: Axelle Serre, MD; Phone Number: +41795538642; Email: axelle.serre@hug.de
    • Contact: Patricia E Engels, MD
    • Contact: Axelle Serre, MD
    • Contact: Stephanie N Schulz, MD
    • Contact: Srinivas Madduri, PhD
    • Contact: Daniel F Kalbermatten, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

A) Pilot study

Inclusion criteria:

• 18-80 years old
• having received DIEP flap breast reconstruction with a flap not completely buried
• having given written informed consent for participating in the study

Exclusion criteria:

• postoperative radiotherapy on the flap
• neurological conditions as diabetic neuropathy, alcoholism or any other severe underlying peripheral neuropathy including chemotherapy-induced neuropathy or neuropathy induced by other medications
• active smoking
• language barrier
• pregnancy or lactating women

B) Main study

Inclusion Criteria:

• 18 to 80 years old
• having given written informed consent for participating in the study
• receiving immediate or delayed unilateral DIEP breast reconstruction with a DIEP flap which will not be completely buried

Exclusion Criteria:

• autologous reconstruction where the flap is completely buried
• patients in need of both-sided reconstruction (double DIEP)
• postoperative radiotherapy on the flap
• neurological conditions as diabetic neuropathy, alcoholism, or any other severe underlying peripheral neuropathy including chemotherapy-induced neuropathy or neuropathy induced by other medications
• active smoking
• language barrier
• pregnancy at time of planned DIEP flap surgery and lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: no nerve suture; No nerve suture will be carried out.
Experimental: direct nerve suture; Epineural coaptation of one nerve of the flap to one nerve of the breast region	Procedure: Nerve Suture; Sensory nerve coaptations will be performed; either by suturing the donor to the recipient nerve immediately (1 coaptation); or by interposing an autograft originating from the zone of the flap to be discarded (2 coaptations). The anterior cutaneous branch (ACB) of the 3rd or 4th intercostal nerve (ICN) will be connected to the sensory branch of the 10th, 11th or 12th ICN of the flap.
Experimental: interposition of an autograft; Epineural coaptation intercostal nerve flap to autograft (from another intercostal nerve of the flap) to intercostal nerve of the breast = interposition of an autograft	Procedure: Nerve Suture; Sensory nerve coaptations will be performed; either by suturing the donor to the recipient nerve immediately (1 coaptation); or by interposing an autograft originating from the zone of the flap to be discarded (2 coaptations). The anterior cutaneous branch (ACB) of the 3rd or 4th intercostal nerve (ICN) will be connected to the sensory branch of the 10th, 11th or 12th ICN of the flap.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Semmes-Weinstein-Monofilament-Test	The results of one modality of the sensory testing, the Semmes-Weinstein-Monofilament-Test for pressure perception. The breast will be divided into 9 zones, which will all be measured with the Semmes Weinstein monofilament 20-piece full kit (unit: grams of force) at the given time (see time frame).	At 12-months-follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in breast sensation	Semmes-Weinstein monoflament The breast will be divided into 9 zones, which will all be measured with the Semmes Weinstein monofilament 20-piece full kit at the given times (see time frame). The resulting monofilament values (unit: grams of force) are examined over the various specified periods and the delta is determined.	day-1/1week/3/6/12/24 months postop
Sensory recovery to DIEP flap	2-point-discrimination, i.e. threshold distance between two points that are perceived as separate in millimeters. Instrument: Aesthesiometer. 9 zones of the breast.	12 months postop
Change in breast sensation	2-point-discrimination, i.e. threshold distance between two points that are perceived as separate in millimeters. Instrument: Aesthesiometer. 9 zones of the breast. Measurement at the specified times (see time frame), determination of the delta.	day-1/1week/3/6/12/24 months postop
Sensory recovery to DIEP flap	Vibration perception with tuning forks of 256 and 32 Hz. Binary: yes/no on 9 zones of the breast.	12 months postop
Change in breast sensation	Vibration perception with tuning forks of 256 and 32 Hz. 9 zones of the breast. Binary: yes/no Evaluation of the difference in the number of zones of the breast with perception of vibration, delta over different time points.	day-1/1week/3/6/12/24 months postop
Sensory recovery to DIEP flap	Temperature perception. Metal rods of 6°C and 37°C. Patients have to indicate which rod feels colder that the other. Capacity of differentiation of temperature: yes/no on 9 zones of the breast.	12 months postop
Change in breast sensation	Temperature perception. Metal rods of 6°C and 37°C. Patients have to indicate which rod feels colder that the other. Capacity of differentiation of temperature: yes/no on 9 zones of the breast. Testing at given time points (see time frame), Calculation of delta of number of zones with distinction.	day-1/1week/3/6/12/24 months postop
Sensory recovery to DIEP flap	Temperature surface. FLIR thermal camera, flap monitor versus whole breast and contralateral breast surface temperature, difference in temperature in degree Celsius.	12 months postop
Change in breast sensation	Temperature surface. FLIR thermal camera, flap monitor versus whole breast and contralateral breast surface temperature, difference in temperature in degree Celsius. Calculation of delta over given time points (see time frame)	day-1/1week/3/6/12/24 months postop
Sensory recovery to DIEP flap	Sharp/dull: Instrument system used: 18G needle / cotton swab, on nine areas of the breast.; Each area will be tested 3 consecutive times with both objects (i.e., 6 measurements per area); The distinction between prick and gentle pressure will be considered successful if the patient responds correctly 5 times out of 6 or 6 times out of 6 (distinction ability: yes/no)	12 months postop
Change in breast sensation	Sharp/dull: Instrument system used: 18G needle / cotton swab, on nine areas of the breast.; Each area will be tested 3 consecutive times with both objects (i.e., 6 measurements per area); The distinction between prick and gentle pressure will be considered successful if the patient responds correctly 5 times out of 6 or 6 times out of 6 (distinction ability: yes/no) Delta calculation over given time points (see time frame)	day-1/1week/3/6/12/24 months postop
Breast-specific health-related QoL	Breast-Q®	12 months postop
Breast-specific health-related QoL (change over time)	Breast-Q®, delta of points over time (see time frame)	Day -1, 12 &24 months postop
Operative time	Minutes for nerve coaptation(s)	At time of 1st operation
Changes to DIEP flap skin	Proteomics, neuroprotein quantification	A) Pilot study Postoperatively at any time of follow-up-interventions. B) Main study At time of 1st operation and at 6-months-follow-up
Sensory recovery to DIEP flap	2-point-discrimination, i.e. threshold distance between two points that are perceived as separate in millimeters. Instrument: Aesthesiometer.	12 months postop

Collaborators and Investigators

• Sponsor: Patricia Esther Engels
• Investigators: Principal Investigator: Patricia E Engels, MD, University Hospital, Geneva

Publications and helpful links

General Publications

• Puonti HK, Broth TA, Soinila SO, Hallikainen HK, Jaaskelainen SK. How to Assess Sensory Recovery After Breast Reconstruction Surgery? Clin Breast Cancer. 2017 Oct;17(6):471-485. doi: 10.1016/j.clbc.2017.04.011. Epub 2017 Apr 29.
• Blondeel PN, Demuynck M, Mete D, Monstrey SJ, Van Landuyt K, Matton G, Vanderstraeten GG. Sensory nerve repair in perforator flaps for autologous breast reconstruction: sensational or senseless? Br J Plast Surg. 1999 Jan;52(1):37-44. doi: 10.1054/bjps.1998.3011.
• Spiegel AJ, Salazar-Reyes H, Izaddoost S, Khan FN. A novel method for neurotization of deep inferior epigastric perforator and superficial inferior epigastric artery flaps. Plast Reconstr Surg. 2009 Jan;123(1):29e-30e. doi: 10.1097/PRS.0b013e3181905564. No abstract available.
• Bijkerk E, Beugels J, van Kuijk SMJ, Lataster A, van der Hulst RRWJ, Tuinder SMH. Clinical Relevance of Sensory Nerve Coaptation in DIEP Flap Breast Reconstruction Evaluated Using the BREAST-Q. Plast Reconstr Surg. 2022 Nov 1;150(5):959e-969e. doi: 10.1097/PRS.0000000000009617. Epub 2022 Aug 22.
• Shiah E, Laikhter E, Comer CD, Manstein SM, Bustos VP, Bain PA, Lee BT, Lin SJ. Neurotization in Innervated Breast Reconstruction: A Systematic Review of Techniques and Outcomes. J Plast Reconstr Aesthet Surg. 2022 Sep;75(9):2890-2913. doi: 10.1016/j.bjps.2022.06.006. Epub 2022 Jun 17.
• Ducic I, Yoon J, Momeni A, Ahcan U. Anatomical Considerations to Optimize Sensory Recovery in Breast Neurotization with Allograft. Plast Reconstr Surg Glob Open. 2018 Nov 7;6(11):e1985. doi: 10.1097/GOX.0000000000001985. eCollection 2018 Nov.
• Spiegel AJ, Menn ZK, Eldor L, Kaufman Y, Dellon AL. Breast Reinnervation: DIEP Neurotization Using the Third Anterior Intercostal Nerve. Plast Reconstr Surg Glob Open. 2013 Dec 6;1(8):e72. doi: 10.1097/GOX.0000000000000008. eCollection 2013 Nov.
• Beugels J, Cornelissen AJM, van Kuijk SMJ, Lataster A, Heuts EM, Piatkowski A, Spiegel AJ, van der Hulst RRWJ, Tuinder SMH. Sensory Recovery of the Breast following Innervated and Noninnervated DIEP Flap Breast Reconstruction. Plast Reconstr Surg. 2019 Aug;144(2):178e-188e. doi: 10.1097/PRS.0000000000005802.
• Hamilton KL, Kania KE, Spiegel AJ. Post-mastectomy sensory recovery and restoration. Gland Surg. 2021 Jan;10(1):494-497. doi: 10.21037/gs.2020.03.22.
• Bijkerk E, van Kuijk SMJ, Lataster A, van der Hulst RRWJ, Tuinder SMH. Breast sensibility in bilateral autologous breast reconstruction with unilateral sensory nerve coaptation. Breast Cancer Res Treat. 2020 Jun;181(3):599-610. doi: 10.1007/s10549-020-05645-y. Epub 2020 Apr 28.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: DIEP flap; breast reconstruction; free flap; sensory recovery; neurotization; autologous-based reconstruction; post-mastectomy sensation; autologous breast reconstruction
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SNCTP000006257; BASEC2024-02109 (Other Identifier: BASEC (Business Administration System for Ethics Committees) Switzerland)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No