Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 4  |  Page : 283-290

Comparing the efficacy of a combination of artificial lymphatics in the form of silicone tube and compressive therapy versus compressive therapy only in upper limb lymphedema following axillary lymph node dissection in breast cancer patients: A randomized controlled trial


1 Department of Surgical Disciplines, AIIMS, New Delhi, India
2 Department of Nuclear Medicine, AIIMS, New Delhi, India
3 Department of Biostatistics, AIIMS, New Delhi, India

Date of Submission15-Sep-2019
Date of Acceptance21-Oct-2019
Date of Web Publication20-Dec-2019

Correspondence Address:
Dr. Adarsh Pratap Singh
Department of Surgical Disciplines, AIIMS, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_73_19

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  Abstract 


Objectives of this Trial: The objectives of this trial were to compare the treatment of lymphedema by creating artificial pathways along with standard compressive therapy versus standard therapy alone in Stage 2 and 3 lymphedema. Materials and Methods: A total of 18 patients were randomized into two groups. Silicone group (n = 8) received the placement of fenestrated silicone tubes subcutaneously from the hand to scapular region along with standard compression therapy, and the control group (n = 10) received standard compression therapy only. Follow-up was for 6 months. Results: A mean reduction of limb volume in the silicone group was 887 ml (25%), whereas in the control group, it was 250 ml (8%) (P = 0.01). All patients, 8 (100%) of silicone group and only 4 (40%) of control group, had ≥10% limb volume reduction at the end of 24 weeks with P = 0.013. More number of patients in the silicone group had a mean reduction in limb circumference of ≥2 cm as compared to the control group at almost all points of measurements along the limb with P < 0.05. There was a significant improvement in the quality of life, especially the functional domain in the silicone group with a P = 0.01. Improvement in pain-free range of motion in all major joints was observed in both the groups. No serious complications were reported. Postoperative ultrasonography and lymphoscintigraphy have shown patency of tubes, lymphatic fluid flow in silicone tubes. Postoperative indocyanine green lymphography showed decreased dermal backflow compared to preoperative. Conclusion: Combination of artificial lymphatics in the form of silicone tubes and standard care leads to a more significant reduction in the limb volume and limb circumference with improved quality of life with no serious complications.

Keywords: Artificial lymphatics, breast cancer, silicone tube, upper limb lymphedema


How to cite this article:
Singh AP, Dhar A, Srivastava A, Kumar R, Pandey R M. Comparing the efficacy of a combination of artificial lymphatics in the form of silicone tube and compressive therapy versus compressive therapy only in upper limb lymphedema following axillary lymph node dissection in breast cancer patients: A randomized controlled trial. Indian J Vasc Endovasc Surg 2019;6:283-90

How to cite this URL:
Singh AP, Dhar A, Srivastava A, Kumar R, Pandey R M. Comparing the efficacy of a combination of artificial lymphatics in the form of silicone tube and compressive therapy versus compressive therapy only in upper limb lymphedema following axillary lymph node dissection in breast cancer patients: A randomized controlled trial. Indian J Vasc Endovasc Surg [serial online] 2019 [cited 2020 Feb 20];6:283-90. Available from: http://www.indjvascsurg.org/text.asp?2019/6/4/283/273602




  Introduction Top


Breast cancer is one of the most common cancers in women across the world. Surgery is the mainstay of treatment. Every patient is at lifelong risk for development of lymphedema, and the incidence increases with time period after surgery[1],[2] Women treated for breast cancer face a lifetime risk for developing lymphedema in up to 40% of this population.[3] The most common risk factors are the extent of axillary lymph node removal, i.e., number of lymph nodes removed, locoregional adjuvant radiotherapy to chest wall, and axillary area, and others risk factors include adjuvant chemotherapy, postoperative surgical site infection, prolonged seroma, obesity, sedentary life, and diabetes mellitus.[4],[5],[6]

Most patients suffer from psychological distress related to lymphedema, including depression and lifelong anxiety affecting their quality of life. Rarely, long-standing lymphedema may be associated with an increased incidence of malignancies, lymphangiosarcoma (Stewart–Treves syndrome), Kaposi sarcoma, or lymphoma.[7],[8] Lymphedema is still an incurable disease, and at present, complete decongestive therapy (CDT) is the gold standard treatment.[9] Various surgical methods have been used for its management, but none has shown promising results. Lymphovenous anastomosis and vascularized lymph node transfer are limited in the early stage of lymphedema with no long-term follow-up available. Recently, Prof. Olszewski explored the drainage of lymphatic fluid by the placement of artificial lymphatics in the form of silicone tube along with compression therapy in both upper and lower limb lymphedema as case series showed promising results. Patients of lymphedema are predisposed for recurrent episode of dermatolymphangioadenitis (DLA). Injection benzathine penicillin G 1.2 million units every 3 weeks by intramuscular (IM) route shown decreased rate of DLA episodes.[10] Since there is a lack of evidence of benefit of silicone tubes through randomized trials, the present study shall compare both groups, i.e., the group that received surgical placement of silicone tubes in affected limb along with CDT followed by injection benzathine penicillin G 1.2 MU every 3 weeks with the group receiving only CDT and injection benzathine penicillin G.


  Materials and Methods Top


After the Institutional Ethics Clearance, the study was conducted at our Institute in the departments of surgical disciplines, radiodiagnosis, nuclear medicine, and microbiology. The study duration was from August 2017 to May 2019. Patients of Stage 2 and 3 (Clinical staging by Prof Olszewski et al.) upper limb lymphedema included and patients with deep-vein thrombosis, peripheral arterial disease, acute infection and known allergy to injection penicillin, and not giving consent were excluded from the study. Patients who gave consent to participate in the study were randomized into two groups of study by computer-generated codes, namely silicone group receiving standard therapy plus silicone tube placement and control group received standard therapy only. Eighteen patients were included after the inclusion and exclusion criteria. The primary objective was to study the reduction of upper limb volume, girth, and improvement in pain-free range of motion in the upper limb in both the groups. The secondary objectives were to observe the change in quality of life and assessment of lymphatic fluid to find out the organism responsible for lymphedema by the culture method. Detailed clinical history and examination were done. Limb Volume measurement was done with water displacement technique, limb circumference measurement was done with measuring tape at intervals of 5 cm, pain-free range of motion measured with goniometer at all major joints of upper limb. Vascular Doppler, Technetium99 lymphoscintigraphy, indocyanine green (ICG) lymphography, and quality of life (LYMQOL-Arm) assessment were done of all patients pre- and postintervention. All patients received DLA prophylaxis with injection benzathine penicillin G 1.2 mu deep IM 3 weekly after antibody sensitivity test. Control group received daily skincare and limb elevation whenever possible, shoulder and chest wall stretch exercises, manual lymph drainage (MLD) with Vodder technique everyday 30–45 min 5 days/week, and short stretch multilayered compression bandaging [Figure 1] round the clock for initial 2 weeks after that compression garments in daytime and bandaging during night. The silicone group received standard therapy along with placement of fenestrated silicone tube. Surgery was performed under general anesthesia in the lateral position. Three small incisions of 2 cm were made: first 2 cm above the carpal-metacarpal joint, second incision on the internal aspect of the arm above the elbow joint medially, and the third incision at the scapular region. A 1.5 cm wide and 100 cm long metallic tunneler was passed subcutaneously from dorsum of hand to the elbow incision and from elbow to scapular region under manual guidance. The silicone tubes were passed through the tunneler, no fixation of the tube to the surrounding tissue is required. Skin wounds were closed with nonabsorbable suture (Prolene 2–0), and occlusive dressing was applied. Short-stretch compression bandages with 50% overlap were applied in operation theater only. The average duration of surgery was 45 min; all steps are shown in [Figure 2]. Follow-up was done at week 1, 2, 4, 12, and 24.
Figure 1: Technique of compression bandaging, two-layered short-stretch compression bandaging

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Figure 2: Technique of silicone tube placement (a) Lateral position of the patient, (b) Creating fenestrations in silicone tubes with Mayo's scissor, (c) making a subcutaneous tunnel with tunneler, (d) placement of silicone tubes with the help of tunneler, (e) Placement of silicone tubes with forceps, (f) dressings

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  Results Top


Eighteen patients were randomized into two groups of the study (eight in silico ne group and ten in control group), as shown in the consort diagram [Figure 3]. The basic characteristics of patients of both the groups were similar with P > 0.05 [Table 1]. Common risk factors identified were Level 3 ALND, adjuvant radiotherapy, adjuvant chemotherapy, and body mass index more than 25 [Figure 4]. All patients were presented with a complaint of arm swelling, and other companies were pain, inflammation, stiffness, and numbness [Figure 5]. Two-thirds of patients were of Stage 3 and one-third were of Stage 2 of lymphedema. Vascular Doppler of all patients was normal.
Figure 3: Consort diagram of the study

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Table 1: Basic characteristics of patients of both the groups

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Figure 4: Bar diagram shows the prevalence of common risk factors in the present study for developing upper limb lymphedema

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Figure 5: Bar diagram shows the frequency of symptoms at presentation

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In both the group of patients, there was a significant mean volume reduction. In silico ne group, mean (standard deviation [SD]) volume reduction was from 3462 (565.5) ml to 2575 (514.7) ml, that is, 887 ml (25%), whereas in the control group, mean (SD) volume was reduced from 2950 (846.2) ml to 2700 (795) ml, that is, 250 ml (8%) at the end of 24 weeks with (P = 0.001). Maximum reduction of volume was observed in silico ne group at the interval of 1 week, as shown in [Figure 6] and [Table 2]. In silico ne group, mean volume was continuing to show decreasing trend, whereas in control group, mean volume achieved plateau at 12 weeks, which was statistically significant. Clinical photographs preoperative and postoperative are shown in [Figure 7]. All patients 8 (100%) of silicone group had ≥10% limb volume reduction, and in control group, only 4 (40%) had ≥10% limb volume reduction at the end of 24 weeks (P = 0.013). As there was incidental mean baseline difference between the groups due to lesser sample size, so results were compared after adjusting baseline using ANCOVA analysis. There was volume reduction of 588 ml more in silico ne group compared to control group (P = 0.01).
Figure 6: Mean volume reduction in both the groups over the 24 weeks of follow-up

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Table 2: Change in the mean volume of the limb in both the groups over the follow-up of 24 weeks

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Figure 7: Clinical photographs (a) preoperative left limb lymphedema (b) postoperative reduced edema, (c) right limb lymphedema preoperative, (d) reduced edema of right limb postsilicone tube placement

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Limb circumference changes were in the same trend like limb volume. There was a reduction in circumference from 34.6 (4.4) cm to 30.9 (3.1) cm in silico ne group and in control group from 32.6 (3.7) to 31.7 (3.9) cm, which is statistically significant in both the groups (P = 0.001 and P = 0.004), respectively, at the end of 24 weeks at measurement point 10 cm above the elbow joint [Figure 8] and [Table 3]. Silicone group had progressive decrease in circumference, whereas control group achieved plateau. Similar changes were observed at other points of measurements along the limb except mid palm, wrist, and highest point of arm because there was very less baseline difference from normal arm at these points.
Figure 8: Line diagram showing change in mean circumference at 10 cm above the elbow joint between the groups

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Table 3: Mean limb circumference at 10 cm above the elbow joint (C) in both the groups over 24 weeks

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There was a statistically significant improvement in pain-free range of motion observed at all joints in both the silicone and control group at the end of 24 weeks (P< 0.05) [Table 4] and [Table 5]; however, the difference between the groups was not statistically significant.
Table 4: Improvement in pain-free range of motion of the upper limb in silicone group

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Table 5: Change in pain-free range of movement in control group over 24 weeks

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There was an improvement in all the domains of quality of life and overall quality of life postintervention in both the groups. There was a significant improvement in functional domain from 1.8 (0.4) to 1.3 (0.4) (P = 0.01) in silico ne group, as shown in [Table 6] and [Table 7]. Patients had significant improvement in their household activities. As the weight of limb reduces and range of pain-free motion improves overall functionality increases in the silicone group, whereas in the control group, this improvement in the quality of life was not statistically significant.
Table 6: Change in quality-of-life scores in the silicone group at the end of 24 weeks

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Table 7: Change in quality-of-life scores in the control group at the end of 24 weeks

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Postoperative lymphoscintigraphy showed decreased dermal backflow and visualized tubes with radiotracer activity in draining silicone tubes. Dermal backflow decreased due to drainage of lymphatic fluid through the tubes [Figure 9] and [Figure 10].
Figure 9: Lymphoscintigraphic images (a) preoperative lymphoscintigraphy showing no lymphatic flow, (b) postsilicone tube placement, lymphatic fluid draining through tube (Arrow showing dye is going through the patent silicone tubes)

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Figure 10: (a) preoperative lymphoscintigraphy showing dermal backflow (b) postsilicone tubes placement, decreased dermal backflow (Arrow)

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In unaffected limb with the normal lymphatic drainage system, there was normal transit of tracer with normal visualization of axillary lymph nodes at 30 min, whereas on the affected arm, axillary lymph nodes were not visualized till delayed 4 h images.

After silicone tube placement, the dye is visualized in the shoulder region after 30 min in most patients. There was a decrease in dermal backflow observed in ICG lymphography which is suggestive of improvement in severity of lymphedema at the end of 30 min postdye injection [

[Figure 11].
Figure 11: Indocyanine green lymphography. (a) preoperative (b) postoperative showing dye reaching till scapular region

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Ultrasound showed patent tubes with lymphatic fluid in the lumen and the area surrounding the tubes [Figure 12]. There were no serious complications observed; however, in silico ne group, two patients developed seroma in the dorsum of the hand which resolved within 2 weeks of compressive dressing, one patient developed ecchymosis over the shoulder, which resolved after 1 week of antibiotic course, one patient had wound dehiscence of wrist incision, the wound was resutured and healed well, and none of the patients develop DLA. While in control group, one patient develops DLA. None of the patients had a foreign-body reaction to the subcutaneously placed silicone tube and needed removal of tubes.
Figure 12: Postoperative ultrasonic visualization of the silicone tubes filled with lymphatic fluid

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  Discussion Top


The present study is probably the first randomized controlled trial comparing the silicone tubes placement plus standard therapy versus standard therapy only. Following previous studies in the form of case series on silicone tube placement as artificial lymphatics in secondary lymphedema of the upper and lower limb are shown in [Table 8].
Table 8: Studies done on silicone tube placement in the upper and lower limb lymphedema

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In silicone group, mean (SD) volume reduction was from 3462 (565.5) to 2575 (514.7) ml that is 887 ml (25%) at the end of 24 weeks, which is comparable to the study by Olszewski and Zaleska[11] in 2015 where 700 ml (17%) volume reduction was achieved. Maximum reduction was observed at 1 week of interval. While in the control group, mean (SD) volume reduction was from 2950 (846.2) ml to 2700 (795) ml, that is, 250 ml (8.5%) at the end of 24 weeks. There was a significant reduction in both the groups with P = 0.001. More number of patients in silico ne group had reduction in circumference of ≥2 cm as compared to control group (P< 0.05). At elbow joint, 10 cm above and 10 cm below the elbow joint, all patients of silicone group had reduction of ≥2 cm as compared to control group with P values (0.004, 0.004, and 0.001), respectively. The reduction was 14%, 10.6%, and 12.8%, respectively, in silico ne group, which is comparable to the study by Olszewski et al., which was ranging from 10% to 15%. Comparing to control group where reduction of these points was 3, 2.7, and 2.5%, respectively (P< 0.05).

Comparing to other standard therapy studies, randomized controlled trials, and meta-analysis, none of the surgical treatment was without giving compression therapy in the various forms, including compression bandages, compression sleeves, and sequential pneumatic compression. All advised long-term maintenance with compression therapy. A systemic review including 20 studies on various surgical methods of lymphedema treatment by Janice N. Cormier in 2012 was done.[12] Excisional surgery (n = 8) was performed in advanced stage of lymphedema; lymphatic reconstruction (n = 8), and vascularized lymph node transfer (n = 4) were performed in the early stage of lymphedema. Studies used inconsistent and nonstandardized techniques and lack long-term follow-up. Excisional technique included 155 patients and achieved 91.1% reduction in volume. Lymphatic reconstruction involves lympholymphatic bypass and lymphovenous anastomosis; it included 990 patients and showed 54.9% reduction in volume, whereas in study on vascularized lymph node transfer, where 47.6% volume reduction was seen. On long-term follow-up, volume reduction was variable from 118% to 13%. Each surgical treatment had some limitations such as excisional surgeries which have highest volume reduction but had the high incidence of complications, including hematoma, flap necrosis, infections, chronic wound, deep-vein thrombosis, poor cosmesis, destruction of residual lymphatics, recurrence, and loss of limb function. Excisional surgeries required long-term intense compression therapy in all the patients. Lymphatic reconstructions are time-consuming, involve microsurgical skills, and can be done effectively in the early stage of lymphedema only.

Comparison between individual and combination of different components of CDT was studied. A study by Johansson et al. in 2002 compared MLD and sequential pneumatic compression and found 15% volume reduction, but there was no significant difference between the groups.[13] A randomized controlled trial by Dini et al. in 2002 of eighty patients on pneumatic compression versus placebo and self-care found 25% reduction in pneumatic group and 20% volume reduction in placebo group with no benefit of pneumatic compression; however, combination of pneumatic compression, compression bandages, and MLD showed favorable results.[13] Anderson et al. in 2000 compared MLD with standard physiotherapy alone and found overall reduction of 43% from baseline. In Phase I 43% reduction and Phase II 66% reduction in volume in MLD with standard physiotherapy group. There with no significant difference in volume reduction between the groups. Furthermore, there was no difference in improvement in range of motion and subjective sensation between the groups. In this study by Anderson, compression garments were used instead of compression bandages. In a meta-analysis by Ezzo et al. in 2015 which included six trials comparing MLD with other components in combination. Anderson compared MLD plus standard physiotherapy with physiotherapy alone, which showed improvement in both the groups, but there was no significant difference between groups in percentage reduction of volume. Two trials by Trials by Ezzo et al. compared MLD plus compression therapy, with compression therapy alone showed significant reduction of 30%–38.6% for compression bandaging alone and an additional 7.11% reduction for MLD. Subgroup analysis showed that participants with mild-to-moderate lymphedema were better responder to MLD than were moderate-to-severe lymphedema participants. Three trials compared MLD plus compression therapy with non-MLD plus compression therapy.[14] Sitzia et al. in 2002 compared MLD plus compression bandage with simple lymphatic drainage plus compression bandages, found volume reduction of 33.8% and 22%, respectively, with a difference of 11.8% which was not statistically significant.[15] Williams et al. in 2002 compared MLD plus compression sleeves with simple lymphatic drainage plus compression sleeves, found reduction of 4% and 6.4%, respectively, with difference of −2.4%.[16] Another trial by Johansson et al. in 1998 compared MLD plus compression sleeves with pneumatic compression plus compression sleeves, the percentage volume reduction was 15% and 7%, respectively, with borderline significant difference.[13] All of these trials were small ranging from 24 to 45 patients.

Studies by Anderson et al. and Sitzia et al. in 2002 assessed the improvement of range of motion and found improvement in both the groups with or without MLD, but there was no significant difference between the groups. Volume reduction along with guided exercises leads to improvement in pain-free range of movement in all joints of the upper limb.

Quality of life assessed by Anderson et al. and Johansson et al. found improvement in emotions domain of patients. However, there was no significant difference between with or without MLD.[13] Hence, with this study, we observed that the combination of standard therapy with silicone tube placement is more efficacious in reducing limb volume and girth, improving range of motion and quality of life with no serious complications.

Financial support and sponsorship

The study was financially supported by the Department of Surgery.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Petrek JA, Senie RT, Peters M, Rosen PP. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis. Cancer 2001;92:1368-77.  Back to cited text no. 3
    
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International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 consensus document of the International Society of Lymphology. Lymphology 2013;46:1-11.  Back to cited text no. 9
    
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Olszewski WL, Zaleska M. Treatment of postmastectomy lymphedema by bypassing the armpit with implanted silicone tubings. Int Angiol 2017;36:50-8.  Back to cited text no. 10
    
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Olszewski WL, Zaleska M. A novel method of edema fluid drainage in obstructive lymphedema of limbs by implantation of hydrophobic silicone tubes. J Vasc Surg Venous Lymphat Disord 2015;3:401-8.  Back to cited text no. 11
    
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Ezzo J, Manheimer E, McNeely ML, Howell DM, Weiss R, Johansson KI, et al. Manual lymphatic drainage for lymphedema following breast cancer treatment. Cochrane Database Syst Rev. 2015 May 21;(5):CD003475.  Back to cited text no. 12
    
13.
Johansson K, Lie E, Ekdahl C, Lindfeldt J. A randomized study comparing manual lymph drainage with sequential pneumatic compression for treatment of postoperative arm lymphedema. Lymphology 1998;31:56-64.  Back to cited text no. 13
    
14.
Dini D, Del Mastro L, Gozza A, limoneto R. The role of pneumatic compression in the treatment of post mastectomy lymphedema: A randomised controlled trial Ann onco 1998;9:187-90.  Back to cited text no. 14
    
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Sitzia J, Sobrido L, Harlow W. Manual lymphatic drainage compared with simple lymphatic drainage in the treatment of post-mastectomy lymphoedema: A pilot randomised trial. Physiotherapy 2002;88:99-107.  Back to cited text no. 15
    
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Williams AF, Vadgama A, Franks PJ, Mortimer PS. A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema. Eur J Cancer Care (Engl) 2002;11:254-61.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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