Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Clinical stage T1-2 N0M0 primary unilateral invasive breast cancer patients

The intervention (SLNB) is no different in the care of patients' in the study then in those who were not included in the past or will not be included after the trial terminates. SLNB is performed according to strict professional guidelines adopted by the National Institute of Oncology, Budapest, Hungary.

Sentinel lymph node biopsy (SLNB)

Zoltán Mátrai, MD, PhD, FEBS

Bence Dorogi, MD

Regional lymph node status is the most important prognostic factor for disease-free and overall survival in breast cancer. Accurate nodal staging can be achieved only by surgery. Today, in early-stage invasive breast cancers with clinically negative lymph nodes, minimally invasive sentinel lymph node biopsy (SLNB) is considered the gold standard of regional lymph node staging. To optimize the effectiveness of SLNB, precise pre-and intraoperative mapping of lymphatic drainage is important. The (SLNB) technique is not standardized. The most common and most accurate way of lymphatic mapping is performed with the combined application of a gamma-emitting isotope labeled substance and blue dye, the so-called double labeling technique. Functional lymphatic drainage of SLNB double staining in the mammary gland, skin and axilla present a number of uncertainties.

According to the axillary, lateral thoracic and thoracodorsal veins, Ibusuki et al. divided the axillary region into four subregions: brachial (lateral), pectoral (anterior), central and subscapular (posterior) zones. They revealed clear relationship between the anatomic location and status of the SLN, also confirmed by Gallowitsch et al. SLN was detected in Level I in 96% and in Level II in 4% by SPECT/CT.

Knowedge of relationships between the drainage of sentinel lymph node staining into the axillary subregions, location of the primary tumor, tumor size, SLN positivity and its location within the subregion are of particular importance in the decision making whether or not axillary lymphadenectomy (ALND) needs to be performed.

In the prospective randomized phase 3 trial by Giuliano et al. (ACOSOG Z-11) ALND was not performed in early breast cancer patients with clinically negative axilla and breast-conserving surgery, for 1-2 macroscopically positive SLNs (10). After an average follow-up of 6.3 years, data were compared to the traditional ALND group and no difference was detected in 5-year overall survival or disease-free survival at 5 years.

Aims of the investigation:

To examine the location of SLN in the axillary subregion (anterior, posterior, central, lateral, apical) in patients with early breast cancer (T \<5 cm).

To statistically assess correlations between the location, size, histological parameters of primary breast tumor and the subregion of the SLN.

To statistically assess SLN positivity and its location within the sbregion.

To statistically assess subregional localisation of positive SLN and the number of all positive regional lymph nodes, to predict a limited number of cases with lymph node metastasis, based on the test results of the ACOSOG Z-11 trial, by which ALND could be omitted.

Functional Anatomical Examination of Axillary Sentinel Lymph Node Drainage in the Axillary Subregions in Early Breast Cancer

National Institute of Oncology, Hungary

head of the Dept. of Breast and Sarcoma Surgery

Conventional physiotherapy program (joint movement exercises, local relaxation techniques, etc.) will be applied to the participants in this group.

In addition to the conventional physiotherapy program, manual lymphatic drainage (including upper limb extremity and anterior/posterior axillar-axillar anastomoses and axilla-inguinal anastomosis) will be applied to the participants in this group.

In addition to the conventional physiotherapy program, myofascial chain relasing techniques will be applied to the participants in this group.

In addition to the conventional physiotherapy program, manual lymphatic drainage (including upper limb extremity and anterior/posterior axillar-axillar anastomoses and axilla-inguinal anastomosis) and myofascial chain relasing techniques will be applied to the participants in this group.

A basic physiotherapy program consisting of shoulder exercises will be applied to the participants.

content of the physiotherapy program

* Shoulder passive/active abduction, flexion, internal and external rotation exercises
* Posture exercises
* Neck stretching exercises
* Pectoralis major stretching exercises
* Shoulder capsule stretching exercises
* Scapular Mobilization exercises

conventional physiotherapy

manual lymph drainage is a manual technique that is applied to the lymphatic system with a pressure of 40-50 mmHg and increases the working speed of lymphatic nodules/collectors. Manual lymph drainage will be made to the anterior axillar-axillar, posterior axillar-axillar and axilla-inguinal anastomosis collectors and the arm region (up to the elbow) lymph collectors.

Manual lymphatic drainage

it will be done with the thumb or 3rd finger from the acu points of the superficial arm-anterior myofascial chain. 6-8 seconds with thumb to these points. pressure will be applied and vibration will be given clockwise.

Myofascial relasing

Nilüfer Kablan, PhD

Gülser Cinbaz, MSc

Gülser Cinbaz

In breast cancer patients, limitation of shoulder joint movement occurs following mastectomy surgery. Studies have reported that damage to the fascia on the pectoralis major muscle during mastectomy surgery contributes to the development of the limitation. The aim of this study is to investigate the effect of release techniques applied to the fascia on the pectoralis major muscle and the fascial chain on the incerasing of shoulder joint range of motion.

After mastectomy, complications such as decreased range of motion and muscle strength in the shoulder joint, development of pain and tenderness, and formation of lymphedema are frequently observed. In addition to causing a significant decrease in the patient's daily life quality, shoulder limitation also negatively affects the treatment process by preventing the joint position required for radiotherapy. For this reason, it is a priority to prevent the development of shoulder joint limitations that may occur following surgery and to open the developing limitation immediately. This study was born from the idea that the relaxation techniques to be applied to regain the mobility of the fascial structure, which has been damaged and whose mobility has decreased due to breast surgery, should be performed by covering the entire myofascial chain. In addition, the investigators aim to prevent adhesions that will limit the mobility of soft tissue by minimizing scar tissue formation with early drainage of postoperative edema. The aim of this study is to investigate the effectiveness of myofascial chain relaxation techniques and manual lymphatic drainage applied to improve soft tissue mobility in the prevention and elimination of shoulder limitations after breast cancer surgery.

A total of 48 patients who agreed to participate in the study will be enrolled in the treatment program twice a week for 6 weeks. During the study, the same assessments will be applied to all patients and the cases will be evaluated 3 times (pre-treatment, post treatment, and one month post treatment). During the assessments, the physical evaluations of the patients on the shoulder region will be examined in detail using objective and subjective methods.

The Effect of Myofascial Chain Release Techniques on Shoulder Joint Range of Motion in Breast Cancer Survivors

The Effect of Myofascial Chain Release Techniques on Shoulder Joint Range of Motion Following Mastectomy Surgery in Breast Cancer Survivors

Stiffness values will be measured with myotonPro on centers of coordination located along the myofascial chain .

muscle tones will be measured with myotonPro on centers of coordination located along the myofascial chain

creep of tissue will be measured with myotonPro on centers of coordination located along the myofascial chain

The range of shoulder flexion, abduction, extension and external-internal rotation movements will be measured with a universal goniometer.

upper extremity daily living functional capacity of participation will be assessed with the Quick-DASH (Shortened Disabilities Arm, Shoulder and Hand Questionnaire). The scale consists of 11 items. In the scale, a 5-point Likert scale is evaluated and scored 1-5. The scores that can be obtained from the scale are between 0-100. Lower scores indicate better daily activity participation.

quality of life will be assessed using the Hospital Anxiety and Depression Scale (HAD). The scale consists of 14 items (7 items depression and 7 items anxiety). The scale is evaluated on a 4-point Likert scale and is scored 0-3. Depression and anxiety scores are calculated separately. While the score range that can be taken in the lower scales is 0-21, low scores are considered positive.

measurements will be taken from the area covering 3 cm of the surgical incision with a P45 thermographic camera with high thermal sensitivity (Flir Sistem, ThermaCAM, Sweden).

Pain will be evaluated by visual analog scale (VAS). In the scale, the patient is asked to mark the most appropriate pain intensity on a scale ranging from 0 (no pain) to 10 (tolerable pain). The higher the score, the greater the pain intensity.

Pain pressure threshold will be evaluated by a digital algometer (Algometer Commander, Jtech Medical, MM036_K, 2016).

The grip strength of both hand will be evaluated by "hand-held" dynamometer.

Istanbul Medeniyet University

Head of Department

Coagulants

All Drugs and Chemicals

Thrombin

After axillary lymph node dissection no surgical sealing patch (TachoSil®) is applied.

After axillary lymph node dissection, 3 large TachoSil® patches in the dissected axilla are positioned to cover as much of the axillary walls as possible.

TachoSil® is a sterile, ready-to-use, absorbable surgical patch and consists of an equine collagen sponge coated with human fibrinogen and human thrombin.

TachoSil® patches

Walter Weber, MD

Christoph Tausch, MD

Axillary lymph node dissection remains an integral part of surgical treatment of primarily node-positive invasive breast cancer. In order to reduce the incidence of clinically relevant seroma, a suction drain is routinely placed into the axillary cavity after axillary lymph node dissection (ALND) by a separate stab incision. The pathogenesis of seroma involves the collection of lymph fluid caused by dissection of lymph vessels and exudate. All coagulation and fibrinolytic factors are produced and secreted by lymphatic endothelial cells and are involved in the sealing of lymphatic capillaries. Local hemostyptic agents may therefore reduce postoperative secretion from lymphatic fistulas caused by ALND.

We propose to conduct a multicenter prospective randomized control trial in Switzerland to evaluate the impact of TachoSil®, a ready-to-use, absorbable surgical patch (consisting of an equine collagen sponge coated with human fibrinogen and human thrombin) on axillary drainage after ALND for breast cancer. We hypothesize that the use of TachoSil® significantly and relevantly reduces the volume and duration of axillary drainage after ALND. This has the potential to increase patients' quality of life, as well as to shorten the length of hospital stay and reduce hospital costs.

DISEASE BACKGROUND

In Switzerland, 5'500 women and 30 to 40 men are diagnosed with breast cancer every year. It accounts for one third of all cancer diagnoses among women, and causes approximately 1'350 deaths per year. Around 1'200 patients per year need axillary lymph node dissection (ALND) as part of their surgical treatment. ALND is indicated primarily for node-positive breast cancer. Patients are identified either by pre-operative evaluation of the axilla or by intraoperative sentinel lymph node biopsy (SLNB).

THERAPY BACKGROUND

During axillary lymph node dissection for breast cancer, standard techniques for prevention of leakage of dissected lymphatic vessels include the application of suture ligaments and the use of bipolar electrocautery. Seroma prevention after ALND is achieved by placement of a closed suction drain through the skin into the axillary cavity.

Closed axillary suction drains are archaic tools to prevent seroma after ALND by simple mechanical drainage at the cost of significant patient discomfort and increased length of hospital stay. The sealing agent TachoSil® (consists of an equine collagen sponge coated with human fibrinogen and human thrombin) allows a more nuanced approach to the management of axillary seroma prevention and may support ongoing and decades-old efforts of the professional breast cancer community to decrease the duration of axillary drainage and finally, to abandon the drain from routine clinical practice.

RATIONALE FOR PERFORMING THE TRIAL

Axillary lymph node dissection remains an integral part of surgical treatment of primarily node-positive invasive breast cancer. In order to reduce the incidence of clinically relevant seroma, a suction drain is routinely placed into the axillary cavity after ALND by a separate stab incision. Indeed, a recent meta-analysis of 6 randomized controlled trials (RCT's) on axillary drainage versus no axillary drainage and a similar meta-analysis of 6 RCT's on volume-controlled versus no/short-term drainage demonstrated a significant reduction of seroma risk with the use of axillary drainage. Importantly, however, the majority of patients in these trials did not develop seroma even in the absence of axillary drainage.

The reduction of seroma risk by axillary drainage in these trials was achieved at the expense of a prolonged hospital stay and significant patient discomfort caused by the drain. During the past 4 decades at least 50 RCT's have been performed on various interventions to reduce axillary drainage with the aim of abandoning the axillary drain from clinical practice. The interventions ranged from surgical dead space reduction, use of various surgical equipment, shoulder immobilization, compression dressing, to the application of somatostatin analogons and other medication. Due to the overall limited success of these trials axillary drainage is still standard of care after ALND.

The pathogenesis of seroma involves the collection of lymph fluid caused by dissection of lymph vessels and exudate. All coagulation and fibrinolytic factors are produced and secreted by lymphatic endothelial cells and are involved in the sealing of lymphatic capillaries. Local hemostyptic agents may therefore reduce postoperative secretion from lymphatic fistulas caused by ALND. However, the results of the trials on the use of fibrin sealant in the axillary cavity after ALND were conflicting. While some showed no favorable impact of fibrin sealant, others demonstrated promising results when using fibrin glue. Consequently, a meta-analysis of 11 RCT's with 632 patients showed no impact of the use of fibrin glues after ALND on the risk of seroma or the length of hospital stay, but revealed a trend toward less drainage volume (weighted mean difference - 117.7, 95 per cent confidence interval - 259.2 to 23.8 ml). In all these studies, however, the liquid form of fibrin sealant was used.

The use of TachoSil®, which is a non-liquid surgical patch, has been shown to strongly reduce the lymphatic drainage after lymphadenectomy in gynecologic and urologic procedures and prevented the development of chylothorax in patients who underwent heart surgery with intraoperative lymphatic leakage.

We propose to conduct a multicenter prospective RCT in Switzerland to evaluate the impact of TachoSil® on axillary drainage after ALND for breast cancer. We hypothesize that the use of TachoSil® significantly and relevantly reduces the volume and duration of axillary drainage after ALND. This has the potential to increase patients' quality of life, as well as to shorten the length of hospital stay and reduce hospital costs, and provides the rationale and the clinical relevance for the proposed RCT. If the proposed RCT shows a minimum of 33% relative drainage reduction, a follow-up trial is justified. The follow-up trial will be conducted with all patients receiving TachoSil® and randomization with versus without axillary drainage. Therefore, the final goal is the omission of axillary drainage after ALND in the future.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After ALND for Breast Cancer

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Lymph Node Dissection for Breast Cancer. A Multicenter Randomized Phase III Trial.

Total volume of axillary drainage in ml until drain removal.

Volume of axillary drainage per 24 hours in ml will be calculated as the total volume of axillary drainage in ml until drain removal divided by the total duration of axillary drainage in days

Total duration of axillary drainage in days will be calculated from the date of surgery to the date of axillary drain removal

Duration of postoperative hospital stay in days will be calculated from the date of surgery to the date of hospital discharge.

Clinically relevant seroma is defined as either causing discomfort or requiring aspiration.

Number of clinically relevant seroma aspirations until 24 weeks after surgery

Total volume of all clinically relevant seroma aspirations in ml until 24 weeks after surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Functional Anatomical Examination of Axillary Sentinel Lymph Node Drainage in the Axillary Subregions in Early Breast Cancer	NCT01804309	Breast Cancer	Sentinel lymph ...	18 Years -	National Institute of Oncology, Hungary
The Effect of Myofascial Chain Release Techniques on Shoulder Joint Range of Motion in Breast Cancer Survivors	NCT05386628	Breast Cancer S...	conventional ph... Manual lymphati... Myofascial rela...	30 Years - 60 Years	Istanbul Medeniyet University
Impact of a Surgical Sealing Patch on Lymphatic Drainage After ALND for Breast Cancer	NCT02311543	Breast Cancer	TachoSil® patch...	18 Years -	Swiss Group for Clinical Cancer Research

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