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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 33  |  Issue : 4  |  Page : 447-452

Comparative evaluation of the efficacy of co2 and diode laser in the treatment outcome of oral homogeneous leukoplakia


1 Department of Oral Medicine and Radiology, Mansarovar Dental College, Hospital and Research Center, Bhopal, Madhya Pradesh, India
2 Department of Oral Medicine and Radiology, D.Y. Patil School of Dentistry, Mumbai, Maharashtra, India
3 Department of Oral Medicine and Radiology, TPCT's Terna Dental College and Hospital, Mumbai, Maharashtra, India
4 Department of Oral Medicine and Radiology, Nair Hospital Dental College, Mumbai, Maharashtra, India

Date of Submission24-Feb-2021
Date of Decision23-Sep-2021
Date of Acceptance12-Nov-2021
Date of Web Publication27-Dec-2021

Correspondence Address:
Dr. Amrita Gupta
Mansarovar Dental College, Hospital and research center, Bhopal, Madhya, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.jiaomr_270_20

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   Abstract 


Background: “L.A.S.E.R” an acronym for “Light Amplification by Stimulated Emission of Radiation” works as an alternative to conventional surgical systems. It has many advantages and is widely used in the treatment of both oral hard and soft tissues. One of the most popular uses of lasers in the field of dentistry is in the treatment of precancerous lesions and conditions. Aim: This paper is based on the comparison of two laser techniques, carbon dioxide and diode lasers to assess the efficacy in the treatment outcome of oral homogeneous leukoplakia. Setting and Design: The study is a prospective pilot study and the study design is a hospital-based randomized clinical trial. Method and Material: The study compared two treatment groups; carbon dioxide laser on group A and diode laser on group B. The patients were assessed on the basis of postoperative signs and symptoms. Also, the rate of recurrence of oral homogeneous leukoplakia following two techniques was assessed. Statistical Analysis: One-way analysis of variance (ANOVA) test was applied and P value was measured. Study showed statistical significance with P value >0.05 for evaluation parameters such as pain, erythema, swelling, burning, and rate of recurrence. Result and Conclusion: The study concludes that carbon dioxide and diode lasers can be used as alternative treatment modalities for the excision of oral soft tissue lesions. Intraoperative and postoperative complications are rare, with minor bleeding being the only complication observed during the surgeries.

Keywords: CO2 laser, diode laser, oral homogeneous leukoplakia, postoperative complications, recurrence


How to cite this article:
Gupta A, Pagare SS, Bhatnagar S, Waghmare M, Vahanwala S. Comparative evaluation of the efficacy of co2 and diode laser in the treatment outcome of oral homogeneous leukoplakia. J Indian Acad Oral Med Radiol 2021;33:447-52

How to cite this URL:
Gupta A, Pagare SS, Bhatnagar S, Waghmare M, Vahanwala S. Comparative evaluation of the efficacy of co2 and diode laser in the treatment outcome of oral homogeneous leukoplakia. J Indian Acad Oral Med Radiol [serial online] 2021 [cited 2022 Jan 23];33:447-52. Available from: https://www.jiaomr.in/text.asp?2021/33/4/447/333872




   Introduction Top


The words “powerful,” “precise,” and “innovative” complement our conception of the world in terms of technology. In just one generation, lasers have moved out of the imagination into our day-to-day life. The word “Laser” procreates modern life. Ranking among the most significant laser applications is in the field of medicine and dentistry. Latest researches in laser technology and advancement have set the stage for a revolution and made the world of dentistry smarter.[1],[2] In this prospective pilot study, two different types of lasers, i.e., carbon dioxide and diode lasers were undertaken to evaluate the clinical efficacy and treatment outcome of oral homogeneous leukoplakia.

Aims and Objectives

  1. To assess the efficacy of Carbon dioxide (Co2) and Diode laser in the treatment outcome of oral homogenous leukoplakia.
  2. To assess the post-operative signs and symptoms in two groups of patients with oral homogenous leukoplakia associated with the habit of tobacco consumption in any form.
  3. To compare the rate of recurrence in two groups
  4. To assess whether such altered signs and symptoms in patients with oral homogenous leukoplakia can be used to compare two different treatment modalities.


Materials and Methods

The prospective pilot study was carried out in the department of Oral Medicine and Radiology, of a Dental college in Maharashtra, India. The study was approved by the Institutional Ethics Review Board (IERB), with reference No: IERB/2011/OMR/09 dated 07/09/2011) and followed all the recommendations of Helsinki Declaration. This study was conducted over a period of eight months from May 2013 to December 2013 and sample size of 20 patients were confirmed by the Institutional Ethics Review Board (IERB), considering the procedure to be invasive, time taking with longer follow ups. Also, the patient consent for the laser treatment and timely visits for the pre- and post-operative assessment of the lesion was needed. The patients were divided into two groups with a confirmed diagnosis of oral homogenous leukoplakia associated with the habit of tobacco consumption in any form. The clinical diagnostic criteria for oral leukoplakia by World Health Organization (WHO) was followed. The patients were kept under observation for 2 weeks after counselling, to notice any changes or reversal of lesions and to decrease the confounding bias caused due to tobacco cessation. The patients with no response were given the provisional diagnosis of oral leukoplakia. After the clinical diagnosis, incisional biopsy was performed to eliminate lesions with dysplastic changes. Pre-treatment diagnostic assessment was done for the clinical and histopathological staging (OLEP) of the disease [Table 1] and [Table 2]. Group A was subjected to Carbon dioxide laser surgery and Group B was subjected to Diode laser surgery. In both the groups, post-operative pain, swelling, burning sensation, paresthesia, erythema and recurrence of the lesion were evaluated.
Table 1: Classification of leukoplakia

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Table 2: Staging of leukoplakia

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Inclusion and exclusion criteria

New patients with clinically [Figure 1]a and histopathologically proven Oral Leukoplakia aged between 25 to 70 years, irrespective of the gender, with history of tobacco chewing and those who were willing to undergo laser therapy, were included in the study. Patients with persistent lesion even after counselling and tobacco cessation were included. Patients with history of any systemic disease or disorders were excluded from the study as it may alter the post-operative signs and symptoms. Patients who fail to give written consent were also excluded. Histopathological dysplastic changes, verrucous leukoplakia, speckled leukoplakia and nodular leukoplakia were excluded from the study. Patients who were previously treated for oral leukoplakia or potentially malignant disorders or had any oral potentially malignant disorders, oral cancer and white lesions like Candidiasis, Lichen planus were excluded from the study. Patients with lesions adjacent to sharp teeth were not included in the study as it may hinder the post-operative healing process and to eliminate further risk of malignant transformation. Oral Lesions present on the tongue, floor of the mouth, palate or any vascular region were excluded.
Figure 1: (a,b) Clinical appearance of leukoplakia, Leukoplakia after vital staining

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Methodology

Incisional Biopsy was performed after vital staining with toluidine blue [Figure 1]b to highlight potentially malignant oral lesions and the patients were rescheduled for the laser therapy after complete healing and histopathological diagnosis.Patients with non-dysplastic changes were taken. A confirmed diagnosis was achieved on the basis of histopathological report and Oral Leukoplakia (OLEP) classification was given to every patient.[1]

In Group A, the Co2 laser (Shailtec Model ULTIMA S-DC), at a wavelength of 10.6 microns was selected for excision with an average power of 2 W. The irradiation mode was noncontact and the spot size was about 0.44 mm. The entire lesion was evaporated by the laser in continuous mode by a sweeping motion about 1-2 mm above the surface accompanied by high vacuum suction. The total ablation site varies according to the size of the lesion. In Group B, the Diode laser unit (Wizer, doctor smile dental laser, LAMBDA SpA) at a wavelength of 980nm was selected for excision with an average power of 2 W. The irradiation mode was contact mode with the diameter of 0.2mm. The entire lesion was evaporated by the laser in continuous mode by a sweeping motion accompanied by high vacuum suction.

A 2mm safety margin was considered in both the groups. Post-surgical symptoms were assessed and patients were asked to mark the presence or absence of pain, swelling, burning sensation and numbness or none post surgically in the printed proforma for 7 consecutive days. Patients were recalled for follow up in 24 hrs, 72 hrs, 5 days, 7 days, 10 days, 15 days, 1 month, 2 months and 3 months [Figure 2] and [Figure 3].
Figure 2: (a) Preoperative picture of oral leukoplakia, (b) Post-operative picture after 24 hrs of Co2 laser therapy, (c) Postoperative picture after 1 month of Co2 laser therapy

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Figure 3: (a) Preoperative picture of oral leukoplakia, (b) Postoperative picture after 24 hrs of diode laser therapy, (c) Postoperative picture after 1 month of diode laser therapy

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Statistical analysis

The study subjects were then implied for the statistical analysis. The methods and formula used for data analysis were one-way classification of ANOVA analysis and the P value measures. The general rationale of ANOVA is that the total variance of all subjects in an experiment can be analysed into two sources, variants between groups and variance within groups. The ratio of these variances is called F ratio.


   Results Top


In the present study, the patients included were in the age group of 25 to 70 years; out of which, 20% were below 40 years, 55% were between 40 to 60 years, and 25% were above 60 years of age. This study showed that oral leukoplakia occurred in 100% of men over 40 years of age.[3] Out of 20 patients, 16 (80%) patients were chronic tobacco chewers and only four (20%) were cigarette/bidi smokers.[4] Of all the lesions, the buccal mucosa showed maximum incidence among the patients followed by labial mucosa, gingiva, alveolar ridge, and hard palate.[5] All the patients were counseled for tobacco cessation and were instructed to quit the habit before the laser treatment, though 17 out of 20 patients (85%) showed complete cessation before the treatment. However, three patients (15%) did not stop the habit. The first parameter evaluated was the postsurgery pain. Maximum subjects in both the groups complaint of pain at the end of day 2,[6] pain subsequently reduced from day 3, day 4, and day 5 [Graph 1]. The second parameter was postoperative swelling. Group A patients showed very minimal or no swelling at the end of day 2 but Group B patients consistently complained of swelling for almost a week [Graph 2]. Erythema was present in 100% of patients in both the groups at the end of day 5 [Graph 3]. At the end of day 2, only 40% of patients complain of burning sensation in group A, and 60% in group B, but at the end of day 5, 20% of patients from group A still complaint of burning as compared with group B where only 10% of patients complain of burning. Two patients did not quit the habit even after laser treatment and these two patients were from group B.[7] The collateral thermal damage zone on the borders of the excisional biopsies of oral mucosal lesions was significantly smaller with the CO2[8] laser as compared with the diode laser[9],[10] on histopathological index scores.[11]




   Discussion Top


Leukoplakia (Schwimmer, 1877), which comes under premalignant lesions,[12] are now redesignated as potentially malignant disorders because of the propensity to transform into malignancy at a higher rate when compared with other oral lesions.[13] According to Warnakulasuriya et al.,[14] the new concept of oral leukoplakia shall acknowledge white lesions with questionable risk of being an oral leukoplakia, being excluded any other pathologies or known disorders that do not present potential malignant risks such as candidiasis, lupus erythematosus, lichen planus, hairy leukoplakia, frictional keratosis, nicotinic stomatitis, and leukoedema.[15],[16],[17]

The estimated prevalence of oral leukoplakia worldwide is approximately 2%.[18] No strong gender predilection with an age prevalence of 30–40 years. The use of tobacco is an important etiological factor.[19] Oral leukoplakia is six times more common in smokers than in nonsmokers.[20] According to its clinical appearance [Table 1],[21] oral leukoplakia can be divided into two main clinical types: homogeneous (flat, thin, or wrinkled, uniform white) and nonhomogeneous (white or white-and-red- sometimes referred to as erythroleukoplakia,[22] either speckled, nodular, or verrucous). The first report of the use of laser appeared in 1965 when Leon Goldman applied two pulses of a ruby laser to the tooth of his brother.[23]

Depending on the wavelength of the laser device, the laser interaction with soft tissue can be seen in varying degrees like reflection, transmission, scattering, and absorption. Laser wavelengths have been shown to be absorbed by different components such as hemoglobin, melanin, water, and hydroxyapatite. A chromophore is a molecule or substance capable of absorbing specific laser wavelengths. Thermal relaxation can be defined as the time required for the irradiated tissue to cool by 50% of its original temperature immediately after the laser pulse.[24] The Co2 and diode laser can be used in various premalignant lesions and conditions.[25] The more used laser devices, in dental and stomatological fields, are the following models: Co2 Laser, Erbium Laser–Yag (Erbium: Yttrium Aluminium Garnet) Nd Lase–Yag (Neodimium Y Yttrium Aluminium Garnet), and Diode Laser.[26]

The first parameter evaluated was the postsurgery pain. A total of 90% of subjects in both the groups complaint of pain at the end of day 2 more or less similar to a study conducted by Raval et al.,[6] where 100% of patients showed postoperative pain. By the end of the first week, the pain subsequently reduced from day 3, day 4, and day 5 to 60%, 20%, and 10% in group A and 80%, 60%, and 10% in group B, respectively. In group A, only 20% of patients complain of pain at the end of day 4, as compared with 60% of patients in group B. The second parameter was postoperative swelling. Group A patients showed very minimal or no swelling at the end of day 2 but group B patients consistently complained of swelling for almost a week. In a study done on a diode laser, severe postoperative edema was present in 40% of the patients and by the end of the first-week edema disappeared only in 40% of the patients, whereas in our study only 20% of patients in Group B, complaint of swelling at the end of day 5, and group A patients were relieved at the end of day 5. The third parameter was erythema. It was present in 100% of patients in both groups at the end of day 5. After 1 week, postoperative erythema was not noted in 100% of subjects, whereas in group B 10% of subjects observed erythema till the end of 3 weeks. A study done by Lalabonova et al.[27] observed that all patients had erythema during the first day, which faded by the 7th day that was similar to our study.

While comparing burning sensations in both the groups, we found that at the end of day 2, only 40% of patients complain of burning sensation in group A, and 60% in group B, but at the end of day 5, 20% of patients from group A, still complain of burning as compared with group B where only 10% of patients complain of burning. According to the study by Chu et al.,[8] a recurrence of 10.8% was observed in the Co2 laser treatment of oral leukoplakia similar to our study. In both groups A and B, we found 20% recurrence after 1 month, two patients out of 10 from group A, and two patients out of 10 from group B. Out of these four patients, two patients did not quit the habit even after laser treatment and these two patients were from group B. The other two lesions of group A were on the hard palate, alveolar ridge, and gingiva. In a study by Raval et al.,[6] after 3 months of follow-up, 20% of patients complain of recurrence, unlike our study where the percentage was only 10%. According to Terezhalmy et al.[28] the annual malignant transformation rate varies from 0.13% to 15.7%. Suter et al.[11] studied collateral thermal damage zone on the borders of the excisional biopsies of oral mucosal lesions and found that it was significantly smaller with the Co2, laser for both settings tested compared with the diode laser regarding values in pm or histopathological index scores. The only intraoperative complication encountered was bleeding, which had to be controlled with electrocauterization. The Co2 laser seems to be appropriate for excisional biopsies of benign oral mucosal lesions. The Co2 laser offers clear advantages in terms of smaller thermal damage zones over the diode laser. In a study conducted by Cercadillo-Ibarguren et al.[9] on the porcine oral mucosa, the diode showed maximum thermal damage followed by Co2 laser. Co2 laser at 2W continuous mode and diode laser at 2W showed thermal effect of 35.1 μm and 38.9 μm, respectively, with the diode showing the highest scores in thermal damage extent parameter.

Limitations and future prospects

The pilot study provided us with many important insights but there is a need for a clinical study with a larger sample size for better appropriation of the results to a large population. A period of 3 months follow up seems to be inadequate and it is required that these patients are regularly monitored for a longer period of time in order to evaluate the maintenance of the treated areas and subsequent recurrence. Future studies are required at a histological and histochemical level to evaluate the activity and behavior of mucosa following the two procedures. Further investigations in comparison with standard treatment modalities with a prolonged follow up period will be necessary to confirm the efficacy of two lasers in the treatment of oral leukoplakia.


   Conclusion Top


Surgical excision of oral leukoplakia performed with a blade is precise, definite, and under control. With this technique, it is possible to appreciate the excised areas immediately and did not leave room for any residual pigments. However, this technique required the use of local anesthesia resulted in hemorrhage, and required great care while excising the epithelium in order not to expose the bone or to create gingival recession.

The CO2 and diode lasers can be used as alternative treatment modalities for the excision of oral soft tissue lesions. Intraoperative and postoperative complications are rare, with minor bleeding being the only complication observed during the surgeries.[29]

The present study did not show any significant difference in healing time and recurrence of the lesion in both the groups even though, with surgical excision technique, the healing is associated with mild pain and inflammatory changes as compared with laser technique. In both the procedures, evaluation on 10 days revealed restoration of normal features of mucosa without any scar formation. Thus, the healing of the wound was uneventful irrespective of techniques used. From the operator's point of view diode laser is easier to handle, although Co2 laser offers clean cutting.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Yalkinkaya SE, Dumlu A, Olgac V, Ozbarak S. Co2 laser management of leukoplakias: A clinical follow up. J Oral Laser Appl 2005;5:91-102.  Back to cited text no. 1
    
2.
Hamadah O, Thomson PJ. Factors affecting carbon dioxide laser treatment for oral precancer: A patient cohort study. Lasers Surg Med 2009;41:17-25.  Back to cited text no. 2
    
3.
Bokor-Bratic M, Za Stomatologiju K, Fakultet M, Sad S. Prevalence of oral leukoplakia. Med Pregl 2003;56:552-5.  Back to cited text no. 3
    
4.
Pindborg JJ, Kiler J, Gupta PC, Chawla TN. Studies in oral leukoplakia: Prevalence of leukoplakia among 10000 persons in lucknow with special reference to use of tobacco and betel nut. Bull World Health Organ 1967;37:109-16.  Back to cited text no. 4
    
5.
Ramesh S, Jincy T, Molrani P, Daniel VA, Sunila T, Vivek V. Frequency of leukoplakia in patients visiting a dental college located in a rural area of south Kerala. J Indian Acad Oral Med Radiol 2013;25:6.  Back to cited text no. 5
    
6.
Raval N, Raju DR, Athota A, Reddy TY. Diode laser and white lesion: A clinical study on postoperative recovery, depth control and wound healing. J Indian Acad Oral Med Radiol 2011;23:308-11.  Back to cited text no. 6
  [Full text]  
7.
Yang SW, Tsai CN, Lee YS, Chen TA. Treatment outcome of dysplastic oral leukoplakia with laser-emphasis on the factors affecting recurrence. J Oral Maxillofac Surg 2011;69:78-87.  Back to cited text no. 7
    
8.
Chu FW, Silverman S Jr, Dedo HH. Co2 laser treatment of oral leukoplakia. Laryngoscope 1988;98:125-30.  Back to cited text no. 8
    
9.
Cercadillo-Ibarguren I, Espana-Tost A, Arnabat-Dominguez J, Valmaseda-Castellon E, Berini-Aytes L, Gay-Escoda C. Histologic evaluation of thermal damage produced on soft tissues by Co2, Er, Cr:Ysgg And Diode Lasers. Med Oral Pathol Oral Cir Bucal 2010;15:912-8.  Back to cited text no. 9
    
10.
Kharadi UA, Onkar S, Birangane R, Chaudhari S, Kulkarni A, Chaudhari R. Treatment of oral leukoplakia with Diode laser: Apilot study on Indian subjects. Asian Pac J Cancer Prev 2016;16:8383-6.  Back to cited text no. 10
    
11.
Suter VG, Altermatt HJ, Sendi P, Mettraux G, Bornstein MM. CO2 and diode laser for excisional biopsies of oral mucosal lesions: A pilot study evaluating clinical and histopathological parameters. Schweiz Monatsschr Zahnmed 2010;120:664-71.  Back to cited text no. 11
    
12.
Talsania JR, Shah UB, Shah AI, Singh NK. Use of diode laser in oral submucous fibrosis with trismus: Prospective clinical study. Indian J Otolaryngology Head Neck Surg 2009;61:22-5.  Back to cited text no. 12
    
13.
Abidullah M, Kiran G, Gaddikeri K, Raghoji S, Ravishankar TS. Leuloplakia-Review of a potentially malignant disorder. J Clin Diag Res 2014;8:ZE01-4.  Back to cited text no. 13
    
14.
Warnakulasuriya S, Johnson NW, Vander Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Path and Med 2007;36:575-80.  Back to cited text no. 14
    
15.
Axell T, Pindborg JJ, Smith CJ, Van Der Waal I. Oral white lesions with special reference to precancerous and tobacco-related lesions: Conclusions of an international symposium held in Uppsala, Sweden, may 18–21 1994. J Oral Path and Med 1996;25:49-54.  Back to cited text no. 15
    
16.
Van Der Waal I, Schepman KP, Van Der Meij EH, Smeele LE. Oral Leukoplakia: A clinicopathological review. Oral Oncol 1997;33:291-301.  Back to cited text no. 16
    
17.
Villa A, Sonis S. Oral leukoplakia remains a challenging condition. Oral Dis 2018;24:179-83.  Back to cited text no. 17
    
18.
Petti S. Pooled estimate of world leukoplakia prevalence: A systematic review. Oral Oncol 2003;39:770-80.  Back to cited text no. 18
    
19.
Roed-Petersen B. Effect on oral leukoplakia of reducing or ceasing tobacco smoking. Acta Derm Venereol 1982;62:164-7.  Back to cited text no. 19
    
20.
Feller L, Lemmer J. Oral leukoplakia as it relates to HPV infection a review. Int J Dent 2012;1-7.  Back to cited text no. 20
    
21.
Yadav M, Bashir T, Chandel S, Krishnan V, Ahmad N, Pankaj. Review Article- Leukoplakia: A mysterious white patch. Int J Scientific Research and Education 2014;2:1824-30.  Back to cited text no. 21
    
22.
Greenbaum SS, Glogau R, Stegman SJ, Tromovitch TA. Carbon dioxide laser treatment of erythroplasia of Queyrat. J Dermatol Surg Oncol1989;15:747-50.  Back to cited text no. 22
    
23.
Miserendino LJ. Lasers in Dentistry. Quintessence Publication, USA; 1995.  Back to cited text no. 23
    
24.
Moritz A. Oral Laser Applications 2006.  Back to cited text no. 24
    
25.
Soliman M, ElKharbotly A, Saafan A. Management of oral lichen planus using diode laser (980 nm) a clinical study. Egypt Dermat Online J 2005;1:1-3.  Back to cited text no. 25
    
26.
Singh KP, Mohd. Mir GH, Jeelani U, Gupta S, Koul P, Kalsotra P. Carbon dioxide laser surgery in management of oral leukoplakia original research. Int J Contemp Med Res 2016;3:3565-67.  Back to cited text no. 26
    
27.
Lalabonova H, Peycheva S, Petrov P. Application of Nd–YAG laser treatment for oral leukoplakia. Journal of International Medical Association Bulgaria 2012;18(4):240-2.  Back to cited text no. 27
    
28.
Terezhalmy GT, Huber MA, Jones AC, Sankar V, Noujeim M. Physical Evaluation in Dental Practice. Ames, Iowa: Wiley-Blackwell; 2009. p. 170-1.  Back to cited text no. 28
    
29.
Romanos G, Nentwig GH. Diode laser (980nm) in oral and maxillofacial surgical procedures: clinical observations based on clinical applications. J Clin Laser Med Surg 1999;17:193-7.  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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