Accepted Manuscript No need to cut the nerve in LD reconstruction to avoid jumping of the breast - A Prospective Randomized Study Minna Kääriäinen , MD, PhD Salvatore Giordano , MD Susanna Kauhanen , MD, PhD Mika Helminen , MSc Hannu Kuokkanen , MD, PhD PII:

S1748-6815(14)00207-1

DOI:

10.1016/j.bjps.2014.04.029

Reference:

PRAS 4174

To appear in:

Journal of Plastic, Reconstructive & Aesthetic Surgery

Received Date: 25 November 2013 Revised Date:

14 March 2014

Accepted Date: 29 April 2014

Please cite this article as: Kääriäinen M, Giordano S, Kauhanen S, Helminen M, Kuokkanen H, No need to cut the nerve in LD reconstruction to avoid jumping of the breast - A Prospective Randomized Study, British Journal of Plastic Surgery (2014), doi: 10.1016/j.bjps.2014.04.029. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT No need to cut the nerve in LD reconstruction to avoid jumping of the breast A Prospective Randomized Study

Minna Kääriäinen, MD, PhD¹, Salvatore Giordano, MD², Susanna Kauhanen, MD, PhD3, Mika

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Helminen, MSc4, Hannu Kuokkanen, MD, PhD¹

Department of Plastic Surgery, Tampere University Hospital, Tampere, Finland

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Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland

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Department of Plastic and Reconstructive Surgery, Helsinki University Hospital, Helsinki, Finland

4

Science Center, Pirkanmaa Hospital District and School of Health Sciences, University of

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Tampere, Finland

Minna Kääriäinen, MD, PhD

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Corresponding author and reprint requests to:

Department of Plastic and Reconstructive Surgery,

PO BOX 2000,

Finland

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33521 Tampere,

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Tampere University Hospital,

E-mail: [email protected] Phone: +358331165008 Fax: +358331169730 Mobile phone: +358505687096

Presented at the 21st European Association of Plastic Surgeons (EURAPS), Manchester, United 1

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th

Kingdom, May 27-29 2010.

Clinical trial has been registered in public trials registry. Trial registry name is "The significance of latissimus dorsi flap innervation in delayed breast reconstruction". Registration number is

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NCT01239524 and URL is https://register.clinicaltrials.gov.

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ACCEPTED MANUSCRIPT Summary Background: It has been shown, that the myocutaneous latissimus dorsi flap volume and consistency remain mainly the same regardless the nerve is cut or not in breast reconstruction. It is controversial how big impact the flap innervation has on the muscle activity of the flap. The aim of

functional and aesthetic outcome of delayed breast reconstruction.

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the study was to prospectively evaluate the influence of latissimus dorsi flap innervation on the

Methods: Between 2007-2008, 28 breast reconstructions were performed and randomly divided to

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denervation group (surgical denervation by excision of 1 cm of proximal thoracodorsal nerve, n=14) and innervation group (thoracodorsal nerve saved intact, n=14). Patients were clinically evaluated

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and a questionnaire considering functional and esthetical outcome was filled 1 year after operation. Muscular twitching, pain, tightness, shape and symmetry of the breasts were evaluated. In addition, the mobility of the shoulder joint on the operated side was evaluated and the patients self-estimated the activities of daily living.

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Results: There was no significant difference in latissimus dorsi flap twitching, pain and tightness of the breast and symmetry and shape of the breasts between denervated and innervated groups. The shoulder joint mobility was not found to be changed significantly in either of the groups and there

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were no limitations in activities of daily living.

Conclusions: Thoracodorsal nerve division or preservation does not significantly affect muscle

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contraction activity of the latissimus dorsi flap and distortion of the breast, when latissimus dorsi muscle humeral insertion is also detached. Therefore, both cutting and saving the nerve is justified in latissimus dorsi flap breast reconstruction depending on whether the humeral insertion of the muscle is preserved intact or divided and the flap islanded. The study shows that there is no tangible benefit in dividing the nerve when the flap is islanded Key words: latissimus dorsi muscle, flap, breast reconstruction, innervation, denervation, muscle activity

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ACCEPTED MANUSCRIPT Introduction Breast reconstruction with a pedicled myocutaneous latissimus dorsi (LD) flap is a widely used safe reconstruction method with minimal donor-site morbidity. [1-11] It is an appropriate method for a wide group of patients including very thin women where abdominal tissue is not available, or for

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patients with co-morbidities such as diabetes and smoking that present a higher risk for abdominal flap procedures. It has been found that, patients generally express a preference for autologous material and an excellent aesthetic result when choosing the type of breast reconstruction. [12]

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However, autologous tissue combined with an implant has been found less popular than autologous tissue alone. Short operation time has been preferred over a long operation. Short-term and long

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term complications rates are also found important by the patients. Based on these findings, extended latissimus dorsi flap reconstruction, for example, offer the advantages of autologous tissue, while operation times are shorter than those of free flap breast reconstruction and long-term complications

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associated with the use implant material are avoided.

It is controversial if surgical denervation by transecting the thoracodorsal nerve should be performed or not. Some surgeons consider that resection of the thoracodorsal nerve may lead to

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pedicle injury, especially in delayed breast reconstruction. [9,13,14] It has been assumed that after denervation the latissimus dorsi muscle will significantly atrophy and, thus, lose its volume. [7,14-

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16] In a previous study, we have showed that denervation of the LD-flap causes more significant myofiber atrophy than if the flap is innervated. [17] However, marked atrophy was also observed in the innervated flaps, which can be explained by the inactivity of the muscle. The completely detached LD muscle is no longer stretched between the origin and insertion. Interestingly, it was also shown that there was no significant difference in the LD-flap thickness between the denervated and innervated groups. This was explained by more pronounced fatty tissue infiltration in denervated flaps. It seems, that the volume and consistency of the flap remain more or less the same regardless of whether the thoracodorsal nerve is cut or not. Currently, some surgeons believe that 4

ACCEPTED MANUSCRIPT the discomforting signs and symptoms from muscle contraction can be avoided if surgical denervation is performed. [3,6,13,18]

In this prospective, randomized study, the aim was to examine the functional and aesthetic effect of

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both innervation and denervation of the LD flap, in association with complete division of the LD tendon, in delayed reconstruction.

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Materials and Methods Patients

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Delayed unilateral breast reconstructions with a pedicled myocutaneous LD-flap were performed during the years 2007-2008. The research protocol was accepted by the ethical committee of Tampere University Hospital. Written informed consent was obtained from the patients.

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Twenty-eight patients were randomized into two groups: denervated group (n=14) and innervated group (n=14). The average age of the patients was 53 years (range 41-62 years). Average time after primary mastectomy was 2.8 years (range 1-10 years). Sentinel node biopsy was done for 8 patients

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(6 in denervated group and 2 in innervated group) and axillary node clearance for 20 (8 in denervated group and 12 in innervated group) patients. Eight patients (2 in denervated group and 6

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in innervated group) underwent post-operative radiation after the initial mastectomy, 18 (6 in denervated group and 12 in innervated group) had chemotherapy and 17 (8 in denervated group and 9 in innervated group) additional hormonal medication.

Surgical technique The surgical technique for extended latissimus dorsi flap harvest was used. [2-4,19] Muscle was completely transected both at the origin (the humeral insertion) and the distal insertion. In the denervated group, 1 cm of proximal thoracodorsal nerve was excised through a dorsal approach. In 5

ACCEPTED MANUSCRIPT the innervated group the nerve was saved intact. The back wound was closed in two layers and no quilting sutures were used. The insertion of the flap was fixed to the lateral border of the pectoralis major muscle when shaping the breast. A silicone implant was inserted if extra volume was needed (8 in denervated group and 5 in innervated group). Implant was located on top of the pectoralis

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major muscle and covered totally or partially with the LD-flap.

Questionnaire

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Patients filled in a questionnaire considering the functional and aesthetic outcome 12 months after the operation. [6] Patients were asked to evaluate (A) the twitching of the breast (1= no twitching at

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all, 2= minor twitching, 3= substantial twitching), (B) pain of the breast (1= no pain at all, 2= little pain, 3= a lot of pain) and (C) tightness of the breast (1= no tightness at all, 2= little tightness, 3= a lot of tightness). Both the patient and the physician evaluated (A) the shape of the breast and (B) the

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symmetry of the breasts (1= good, 2= moderate, 3= poor).

In addition, patients made a subjective evaluation on the mobility of their shoulder joint on the operated side. Weakness (1= no, 2= minor, 3= moderate and 4 = serious weakness) in abduction,

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adduction, internal rotation, external rotation and anterior and posterior elevation were evaluated. The activities of daily living (ADL) were self-estimated on a scale from 1 to 10 (1= no limitation,

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10= cannot be done).

Statistical analysis

Differences between denervated and innervated group in twitching, pain, tightness, shape and symmetry of the breasts was evaluated with Fisher test. A p-value less than 0.05 was considered as statistically significant. Statistical analysis has been performed using a SPSS statistical software (SPSS 16.0.1., Chicago, Illinois 60606, U.S.A). A post-hoc statistical power of 11.4% was calculated for discrete variables. 6

ACCEPTED MANUSCRIPT Results The results of patients´ evaluation of the twitching, pain and tightness of the breast 12 months after LD-flap breast reconstruction are presented in Table 1. In the innervated group, seven patients had

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minor twitching and seven had no twitching at all. Those patients, who had minor twitching, did not find it discomforting. In addition, they did not feel that the breast was markedly distorted because of the muscle contractions. Several patients in the innervated group mentioned that the breast had been

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twitching in the early period after the operation but twitching had gradually diminished or disappeared over time. Surprisingly, muscle activity was also found in the denervated group. Five

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patients in that group had minor twitching. There was no significant difference between the results regarding twitching of the breast in denervated and innervated group (p=0.70). In addition, there was no significant difference between the denervated and innervated group regarding pain (p=1.00)

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and tightness (0.65) of the reconstructed breast.

The results of patients´ and physicians´ evaluation of the shape and symmetry of the breast 12 months after LD flap breast reconstruction are presented in Table 2. Shape of the breast was mostly

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found good by the physician and the patient in both denervated and innervated group. There was no significant difference between the groups (p=0.60). The symmetry of the breasts was found good

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according to ten and seven of the patients in denervated and innervated groups. The physician found the symmetry of the breasts good for ten of the patients in denervated group and for eight in innervated group. There was no significant difference between denervated and innervated group regarding both patients´ and physician´s evaluation of the symmetry of the breasts (p=0.24, p=0.83).

Patients made a subjective evaluation on the mobility of their shoulder joint on the operated side. One patient in denervated group experienced minor weakness in abduction and two patients in denervated group experienced minor weakness in anterior elevation. Otherwise, the shoulder joint 7

ACCEPTED MANUSCRIPT mobility was found normal in abduction, adduction, internal rotation, external rotation and anterior and posterior elevation. All the patients evaluated that all activities of daily living (ADL) could be

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done without limitations.

Discussion

The treatment of thoracodorsal nerve during breast reconstruction with LD-flaps has been discussed

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and there are opinions both in favour of and against transecting the nerve. Some authors prefer leaving the thoracodorsal nerve intact in order to preserve flap volume and maintain long term

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symmetrical results, particularly when the LD muscle is raised extended with surrounding fat tissue [16,17,20,21] or following radiotherapy. [22] However, it has been shown histologically, immunohistochemically and in magnetic resonance images that innervation of the LD-flap does not significantly effect on the preservation of the flap volume compared to the denervated flaps. [17] In

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that study the atrophy of the muscle was significant in both groups. In the innervated group, this could be explained by the disuse atrophy of the completely detached latissimus dorsi muscle. The atrophy of the muscle was more severe in the denervated group, but the atrophied muscle was more

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replaced by fat tissue compared to the innervated group. Therefore, the consistency of the flap remained mainly the same whether the nerve was cut or not. Considering the volume preservation

not.

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and consistency of the flap in LD-flap reconstruction, the thoracodorsal nerve can either be cut or

Cutting the thoracodorsal nerve can prevent adverse effects, such as painfulness and breast animation, increasing patients' overall satisfaction compared when the nerve is preserved. [18,23,24] Some surgeons leave the nerve intact and recommend secondary delayed nerve cutting if patient have symptoms. [13] However, secondary procedure may be challenging. [10,24,25] LD muscular contraction deformities and distortion can also be treated with botulinum toxin type A, but 8

ACCEPTED MANUSCRIPT the results are temporary and difficult to predict. [14]

Some authors recommend primary nerve cutting because they have found that muscle activity causes marked disfiguring distortion in the reconstructed breast. [23,24] Interestingly, we found that

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cutting or saving the nerve does not make a significant difference in muscle twitching between denervated and innervated group. Furthermore, there was no significant difference between denervated and innervated groups regarding pain and tightness of the breast. The patients with some

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muscle activity in both groups did not find it uncomfortable. We believe that cutting the insertion of the muscle is reason for that. We find transposing the flap into anterior side easier when cutting the

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insertion. In addition, the insertion can be fixed to the lateral border of the pectoralis majos muscle to avoid any extra bulking in the axillary fold.

Technical differences in proximal muscle insertion dissection seem to have effect on the muscle

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activity if the nerve is left intact. Some surgeons cut the thoracodorsal nerve but do not transect the LD muscle insertion [18,21,24], others transect it partly or totally. [4,7,15,16,11,13] If the thoracodorsal nerve is saved and the muscle insertion is not transected, muscle contraction may

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cause a discomforting movement of the flap towards the axilla. If muscle is transected at both ends of the flap and the nerve saved, muscle loses both points of attachment and therefore the muscle

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activity can no longer cause major movement. Indeed, muscle atrophy is more severe when muscle is immobilized in shortened position compared to neutral and lengthened position. [26,27] We previously showed significant disuse myofiber atrophy in the innervated flaps, supporting this theory. [17] If an experienced surgeon performs the procedure we do not consider the risk of pedicle injury significant and it can be minimized by fixing the tendon to the pectoralis muscle.

One must also keep in mind that reinnervation of the denervated muscle, aberrant regeneration from adjacent nerves or technical error by transecting the nerve too distally may be possible and thus can 9

ACCEPTED MANUSCRIPT compromise the denervation result in a patient with an intact muscle insertion. [17,24,28,29] In fact, few patients in the denervated group noticed little twitching of the breast. This finding together with some immunohistochemical findings, support the reinnervation option. [17] Technical error in our study was avoided by transecting the nerve as proximal as possible through dorsal approach and by

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excising 1 cm of the nerve. Paolini et al. [24] showed in cadaver studies that thoracodorsal nerve takes origin from fibers arising from C6 to C8 roots, exiting the posterior cord of the brachial plexus at the medial apex of the axilla. It was found that usually, the nerve runs as a single trunk in its

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proximal course emerging medially in the axilla in between the subscapular nerves; along the lateral border of the subscapularis muscle and then turns laterally in its middle course passing over teres

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major to join the thoracodorsal vascular pedicle on top of LD muscle and finally enters the LD in its distal course after the serratus branching. Subsequently, it divides intramuscularly following the thoracodorsal artery course into a vertical and a transverse branch. However, in 20 % of the cases a presence of a proximal branch of the thoracodorsal nerve dividing before the muscle neuromuscular

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hilus was found. This branch was found to enter the LD surface separately. That is why Paolini et. al [23] found proximal nerve resection through axillary approach the most successful LD-flap

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denervation method.

If extra volume was needed, an implant was inserted. The implant can be placed underneath the

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partially transected pectoralis major muscle and the flap. Another option is to place the implant on top of the pectoralis major muscle and cover it totally or partially with the flap as we did in this study. We believe that locating the implant underneath the pectoralis major muscle and the flap can cause more distortion of the breast or lateralization of the implant during muscle contraction. Transecting the LD muscle at both ends and inserting the implant when needed only underneath the flap may be crucial technical choices to minimize the effect of muscle contraction on breast shape and twitching when the thoracodorsal nerve is saved.

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ACCEPTED MANUSCRIPT Our data also showed that the shape and symmetry of the breast are not dependent on the transecting or saving the thoracodorsal nerve. In addition, patients in both denervated and innervated groups did not find significant changes in shoulder joint mobility or any difficulties in

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activities of daily living.

In summary, our data suggests that in delayed LD-flap breast reconstruction, if the LD tendon is completely divided, there is no significant difference in reconstructed breast muscle activity, pain,

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tightness, shape or symmetry regardless of whether the thoracodorsal nerve is cut or not. Therefore,

Conflict of interest/Funding statement

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both cutting and saving the nerve is justified in LD-flap breast reconstruction.

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None of the authors have a financial interest to declare in relation to the content of this article.

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ACCEPTED MANUSCRIPT References 1. Sternberg EG, Perdikis G, McLaughlin SA et al. Latissimus dorsi flap remains an excellent choice for breast reconstruction. Ann Plast Surg 2006;56;31-35. 2. Chang DW, Youssef A, Cha S et al. Autologous breast reconstruction with the extended

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latissimus dorsi flap. Plast Reconstr Surg 2002;110;751-759. 3. Hammond DC. Latissimus dorsi flap breast reconstruction. Clin Plast Surg 2007;34;75-82. 4. Losken A, Nicholas CS, Pinell XA, Carlson GW. Outcomes evaluation following bilateral

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breast reconstruction using latissimus dorsi myocutaneous flaps. Ann Plast Surg 2010;65;17-22.

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5. Clough KB, Louis-Sylvestre C, Fitoussi A et al. Donor site sequelae after autologous breast reconstruction with an extended latissimus dorsi flap. Plast Reconstr Surg 2002;109;19041911.

6. Adams WP Jr, Lipschitz AH, Ansari M, et al. Functional donor-site morbidity following

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latissimus dorsi muscle flap transfer. Ann Plast Surg 2004;53;6-11. 7. Munhoz AM, Montag E, Feis K, et al. Outcome analysis of breast-conservation surgery and immediate latissimus dorsi flap reconstruction in patients with T1 and T2 breast cancer.

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Plast Reconstr Surg 2005;116;741-752.

8. Randolph LC, Barone J, Angelats J et al. Prediction of postoperative seroma after latissimus

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dorsi breast reconstruction. Plast Reconstr Surg 2005;116;1287-1290. 9. Giordano S, Kääriäinen K, Alavaikko J, Kaistila T, Kuokkanen H. Latissimus dorsi free flap harvesting may affect the shoulder joint in long run. Scand J Surg 2011;100(3);202-207. 10. Button J, Scott J, Taghizadeh R, Weiler-Mithoff E, Hart AM. Shoulder function following autologous latissimus dorsi breast reconstruction. A prospective three year observational study comparing quilting and non-quilting donor site techniques. J Plast Reconstr Aesthet Surg 2010; 63(9):1505-1512. 11. Fatah F. Extended latissimus dorsi flap in breast reconstruction: Operative techniques in 12

ACCEPTED MANUSCRIPT plastic and reconstructive surgery 1999; 6(1): 38-49. 12. Damen TMC, de Bekker-Grob EW, Mureau MAM et. al. Petients`preferences for breast reconstruction: A discrete choice experiment, J Plast Reconstr Aesthet Surg 2011;64:75-83. 13. Halperin TJ, Fox SE, Caterson SA et al. Delayed division of the thoracodorsal nerve. Ann

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Plast Surg 2007;59;23-25. 14. Figus A, Mazzocchi M, Dessy LA et al. Treatment of muscular contraction deformities with botulinum toxin type A after latissimus dorsi flap and sub-pectoral implant breast

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reconstruction. J Plast Reconstr Aesthet Surg 2009;62(7);869-875.

15. Hao L, Clarke CP. Persistent twitching of the latissimus dorsi muscle after a posterolateral

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thoracotomy. ANZ J Surg 2002;72:680-681.

16. Lee JW, Chang TW. Extended latissimus dorsi musculocutaneous flap for breast reconstrucion: experience in Oriental patients. Br J Plast Surg 1999;52;365-372. 17. Kääriäinen M, Giordano S, Kauhanen S et.al. The significance of latissimus dorsi flap

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innervation in delayed breast reconstruction: a prospective randomized study-magnetic resonance imaging and histologic findings. Plast Reconstr Surg 2011; Dec;128(6);637e645e.

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18. Szychta P, Butterworth M, Dixon M, Kulkarni D, Stewart K, Raine C. Breast reconstruction with the denervated latissimus dorsi musculocutaneous flap. Breast 2013 Oct;22(5);667-672.

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19. Delay E, Gounot N, Bouillot A, Zlatoff P, Rivoire M. Autologous latissimus breast reconstruction: a 3-year clinical experience with 100 patients. Plast Reconstr Surg 1998; Oct;102(5);1461-1478. 20. Lundberg J. Extension or combination of an autologous latissimus dorsi flap in breast reconstruction. Scand J Plast Reconstr Surg Hand Surg 2009;43(1);16-21. 21. Branford OA, Kelemen N, Hartmann CE, Holt R, Floyd D. Subfascial harvest of the extended latissimus dorsi myocutaneous flap in breast reconstruction: a comparative analysis of two techniques. Plast Reconstr Surg 2013 Oct;132(4);737-748. 13

ACCEPTED MANUSCRIPT 22. Thomson HJ, Potter S, Greenwood RJ et al. A prospective longitudinal study of cosmetic outcome in immediate latissimus dorsi breast reconstruction and the influence of radiotherapy. Ann Surg Oncol 2008; Apr;15(4);1081-1091. 23. Hammond DC. Discussion: the significance of latissimus dorsi flap innervation in delayed

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breast reconstruction: a prospective randomized study-magnetic resonance imaging and histologic findings. Plast Reconstr Surg 2011; Dec;128(6);646e64-8e.

24. Paolini G, Longo B, Laporta R, Sorotos M, Amoroso M, Santanelli F. Permanent Latissimus

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Dorsi Muscle Denervation in Breast Reconstruction. Ann Plast Surg 2013; 71:639-642. 25. Kakinuma S, Sasabe F, Nogaki H, Negoro K, Morimatsu M. A case of painful involuntary

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contraction of the left latissimus dorsi muscle, successfully treated with left thoracodorsal nerve resection. Rinsho Shinkeigaku 1994; Oct;34(10);1018-20. 26. Talmadge RJ. Myosin heavy chain isoform expression following reduced neuromuscular activity: potential regulatory mechanisms. Muscle Nerve 2000; 23;661-679.

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27. Rantanen J, Hurme T, Kalimo H. Calf muscle atrophy and achilles tendon healing following experimental tendon division and surgery in rats. Comparison of postoperative immobilization of the muscle-tendon complex in relaxed and tensioned positions. Scand J

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Med Sci Sports 1999; 9;57-61.

28. Kuwabara S, Fukutake T, Kasahata N, Shimoe Y, Yamanaka I, Hirayama K. Associated

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movement as a sequel to thoracotomy: aberrant regeneration to the latissimus dorsi muscle. Mov Disord 1995; Nov;10(6);788-790. 29. Rantanen J, Ranne J, Hurme T, et al. Denervated segments of injured skeletal muscle fibers are reinnervated by newly formed neuromuscular junctions. J Neuropath Exp Neurol 1995;54;188-194.

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ACCEPTED MANUSCRIPT Tables Table 1. Patients´ evaluation of the twitching, pain and tightness of the breast 12 months after LDflap breast reconstruction. Pain of the breast

Tightness of the breast

(number of the patients)a

(number of the patients)a

(number of the patients)a

No

Minor

Substantial

No pain

Little

A lot of

twitching

twitching

twitching

at all

pain

pain

at all 9

5

0

12

2

7

7

0

13

1

A lot of

tightness

tightness

tightness

0

4

0

2

0

10

0

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group a

Little

at all

group innervated

No

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denervated

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Twitching of the breast

There was no significant difference between denervation and innervation groups regarding twitching, pain and

tightness of the breast, p=0.70/ p=1,00/ p=0.65, Fisher test.

Table 2. Patients´ and physicians´ evaluation of the shape and symmetry of the breast 12 months

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after LD- flap breast reconstruction.

group

innervation group a

patient/physician evaluationa

patient/physician evaluationa

(number of the patients)

(number of the patients)

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Symmetry of the breast:

Good

Moderate

Poor

Good

Moderate

Poor

13/ 13

1/ 1

0/ 0

10/ 10

3/ 3

1/ 1

11/ 11

3/ 3

0/ 0

7/ 8

7/ 5

0/ 1

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denervation

Shape of the breast:

There was no significant difference between denervation and innervation groups regarding both patients´ and

physician´s evaluation of the shape and symmetry of the breasts, p=0.60/ 0.60 and p=0.24/ 0.83, Fisher test.

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No need to cut the nerve in LD reconstruction to avoid jumping of the breast: a prospective randomized study.

It has been shown that the myocutaneous latissimus dorsi flap volume and consistency remain mainly the same regardless the nerve is cut or not in brea...
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