UOG1945 Ultrasound Obstet Gynecol 2005; 26: 000–000 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.1945
Two-dimensional and three-dimensional ultrasound imaging of suburethral slings EQ1
H. P. DIETZ*•, C. BARRY†, Y. N. LIM† and A. RANE† *Nepean Hospital and University of Sydney and †James Cook University and Townsville Hospital, Townsville, Australia
K E Y W O R D S: 3D ultrasound; IVS; SPARC; stress incontinence; suburethral slings; translabial ultrasound; TVT; volume ultrasound
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Suburethral• slings have become the most commonly performed anti-incontinence procedure in many developed countries. While there still is a relative lack of longterm follow-up data, the available information is very encouraging1 . It seems that one type of implant used in the surgical procedure, tensionless vaginal tape (TVT; Johnson & Johnson Ethicon •Gynecare, Somerville, NJ, USA), can deliver success rates equivalent to the previous ‘gold standard’ colposuspension2 . It is often assumed that similar success rates can be expected for the profusion of other techniques and materials used to produce a similar effect. TVT• is one of three types of implant which currently account for the vast majority of such surgery in Australia, the other two being suprapubic arc sling (SPARC; American Medical Systems, Minnetonka, MN, USA) and intravaginal sling (IVS; Tyco Healthcare, Mansfield, MA, USA). At the time of writing there had been no randomized controlled study directly comparing outcomes after these procedures. Currently, the available literature is limited to one randomized controlled trial comparing IVS to TVT3 . In a recent case control series, it was shown that SPARC insertion, when performed according to the originally published technique (i.e. with the use of a cough test under local or regional anesthesia), seemed to result in looser placement and consequently less voiding impairment as well as slightly increased objective recurrence of stress incontinence4 . Another case control series compared TVT and IVS, and showed a significantly higher rate of tape erosions after IVS5 .
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Methods In a prospective randomized controlled trial, 196 women were randomized to •TVT (n = 67), IVS (n = 64) or SPARC (n = 64). Thirteen women were excluded from the study due to incomplete preoperative data. Of the remaining 183 women, 146 (51 TVT, 48 IVS, 48 SPARC) were seen between 2 and 23 months after their procedure (80%). After an interview, two-dimensional (2D) and three-dimensional (3D) pelvic floor ultrasound was performed. 3D-volume analysis was carried out on a computer with the help of proprietary software (GE Kretz 4D View). Assessors of ultrasound data were blinded against group allocation.
INTRODUCTION
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Objective Suburethral slings have become the most commonly performed anti-incontinence procedures in many developed countries. Three types of implant account for the majority of such surgery in Australia: tensionless vaginal tape (TVT), suprapubic arc procedure (SPARC) and intravaginal slingplasty (IVS). The aim of this study was to determine differences in position and mobility of these implants, and to determine whether such differences explain variations in clinical outcome.
ultrasound, have comparable clinical and anatomical outcomes. Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd.
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ABSTRACT
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Results There were no significant differences in subjective cure/improvement of stress or urge incontinence or overall subjective cure/improvement. Symptoms, including those of voiding dysfunction, did not vary between groups. All tapes could be imaged by ultrasound. TVT and SPARC were highly echogenic, with the SPARC generally flatter and of wider weave. The IVS seemed narrower and less echogenic. Tape position and mobility were similar, with a trend towards greater distances between tape and symphysis pubis and greater horizontal tape mobility in the SPARC group.
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Conclusions The three types of suburethral sling, namely TVT, SPARC and IVS, investigated using 2D and 3D
Correspondence to: Prof. H. P. Dietz, Associate Professor in Obstetrics and Gynaecology, Western Clinical School, Nepean Campus, University of Sydney, Nepean Hospital, Penrith NSW 2750, Australia (e-mail:
[email protected]) Accepted: 25 April 2005
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd.
ORIGINAL PAPER
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Parameter
IVS (n = 45)
SPARC (n = 44)
56.9 2.5 20
58.1 2.8 12
58.3 2.6 10
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48
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0.79
0.82
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Age (years, mean) Vaginal parity (mean) Previous incontinence surgery (%) Preoperative urge incontinence (%) Preoperative detrusor overactivity on urodynamic testing (%) Follow-up time to ultrasound (years)
TVT (n = 47)
IVS, intravaginal sling; SPARC, suprapubic arc sling; TVT, tensionless vaginal tape.
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2D measurements for tape position and mobility11 were obtained supine and after bladder emptying, with the most effective of at least three Valsalva maneuvers used for numerical evaluation. Tape position was determined relative to bladder neck (urethrovesical junction) and inferoposterior symphyseal margin. The method has been shown to be highly •reproducible (ICC 0.85–0.93)11 . 3D analysis of volumes was carried out at a later date on a computer and with the help of proprietary software (Kretz 4D View 2000, GE Kretz Medizintechnik GMBH, Zipf, Austria). The use of this software for offline analysis results in measurements that are virtually identical to measurements taken live at the time of assessment12 . Assessors of ultrasound data were blinded against group allocation. All subjects gave written informed consent. The study was approved by the local Ethics Committee. For statistical analysis of continuous data we used analysis of variance and Tukey’s multiple comparisons after normality testing by the Kolmogorov–Smirnov test. P < 0.05 was considered significant.
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In a prospective randomized controlled trial, 196 women •were randomized to either TVT (n = 67), IVS (n = 64) or SPARC (n = 64). Thirteen women were excluded from analysis prior to or at the first postoperative clinical assessment (prior to the imaging assessment) due to incomplete preoperative and clinical data. Of the remaining 183 •women, 146 were seen for an interview and ultrasound imaging at 2–23 months after their procedure (80%). Ten of those were excluded from analysis as they had secondary procedures such as insertion of a second tape (n = 5), tape revision (n = 2), division, collagen injection or tape removal for infection (one each), which invalidated the imaging assessment. Consequently, data on 136 •women were analyzed for this study (47 TVT, 45 IVS, 44 SPARC). They had undergone a standardized interview, with particular emphasis on patient satisfaction and voiding function as well as free flowmetry with a weight transducer flowmeter. The flowmetry data were converted to maximum flow rate centiles according to the Liverpool nomogram8 , using a formula in Excel (Microsoft Corp., Redmond, WA, •USA) (= 100 * NORMSDIST((LN(Qmax) − (0.51136 + 0.50457 * LN (voided volume)))/0.33966). •Two-dimensional (2D) and three-dimensional (3D) pelvic floor ultrasound (translabial/transperineal) using a Philips ATL HDI 4000 system (Philips Medical Systems, Seattle, •USA) with a 7–4-MHz volume transducer. The methodology for 2D and 3D pelvic floor ultrasound has been published in detail elsewhere9,10 .
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd.
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Type of suburethral sling
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METHODS
Table 1 Effectiveness of randomization of three suburethral slings, TVT, IVS and SPARC, used for the surgical treatment of urodynamic stress •incontinence
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There are obvious differences between the three competitors •with regards to insertion mode (TVT and IVS from below upwards; SPARC from abdominally down through the space of Retzius) and the material itself, with TVT and SPARC being manufactured of wide-weave monofilament polypropylene mesh, and IVS of a much more narrowly woven multifilament polypropylene6 . As a consequence, IVS has distinctly different biomechanical characteristics, which result in greater tape stiffness compared to SPARC and TVT6 . While the material composition of TVT and SPARC are very similar, SPARC integrates a Vicryl suture, which limits distension of the tape on insertion; a modification which may paradoxically result in greater tape elasticity once the suture is cut or dissolved as it prevents ‘pretensioning’4 . The parent trial within which this imaging study was undertaken, the Suburethral Slingplasty Evaluation Study in North Queensland (SUSPEND), focused on clinical outcomes of peri- and early postoperative data that have been published elsewhere7 . The aim of this study was to determine whether there were any differences in position relative to bladder neck and symphysis pubis, and as regards mobility on Valsalva of these three implants. We also intended to examine whether any differences could explain potential variations in flowmetry data or subjective cure and satisfaction rates.
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RESULTS Randomization resulted in good matching for all significant preoperative parameters (age, parity, previous anti-incontinence or prolapse surgery, preoperative urge incontinence and detrusor overactivity, preoperative flowmetry indices). The same was true for intraoperative parameters such as concomitant surgery, and the length of follow-up (0.2–1.9 years, mean 0.85) (Table 1). Amongst the group whose imaging parameters were evaluated for this study there were no significant differences in subjective cure/improvement of stress incontinence (78–97%), subjective cure/improvement of urge incontinence (64–71%) or overall cure/improvement of bladder problems (79–93%) (Table 2). Reported symptoms, including those of voiding dysfunction, did not vary between groups (Table 2). Flowmetry indices also showed no significant differences
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Ultrasound of suburethral slings AQ2
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Table 2 Symptoms after surgical procedures with suburethral •slings Type of suburethral sling TVT (n = 47)
Symptom Cured/improved for stress incontinence (%) Cured/improved for urge incontinence (%) Overall cure/improvement (%) Voiding dysfunction* (%)
39 (83) 30 (64) 37 (79) 22 (47)
IVS (n = 45)
SPARC (n = 44)
35/45 (78) 32/45 (71) 37/45 (82) 19 (42)
42/44 (97) 30/44 (68) 41/44 (93) 15 (34)
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*Voiding dysfunction symptoms were hesitancy, straining to void, stop-start voiding and a poor stream. NS, non-significant. IVS, intravaginal sling; SPARC, suprapubic arc sling; TVT, tensionless vaginal tape.
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Table 3 Analysis of imaging parameters in patients with stress •incontinence
•Parameter
Bladder neck descent x y x–r y–r x–s y–s Horizontal tape mobility Vertical tape mobility Total tape mobility
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between groups, although there was a weak trend towards less reduction in maximum flow rate centiles in the SPARC group (−3.2, SD 28.9) vs. IVS (−5.7, SD 20.7) and TVT (−11.7, SD 24.4). Equally, there was no difference between groups for postoperative bladder neck mobility. All tapes could be imaged by translabial ultrasound, although appearances varied. TVT and SPARC are highly echogenic, with the SPARC generally seeming flatter and of wider weave. The TVT often assumes a ‘c’-shape on Valsalva, which is less marked with the SPARC. The IVS seemed smaller in craniocaudal dimensions, and it was generally less echogenic (Figure 1). Figure 2 shows appearances in the axial plane in which it is generally easier to locate the IVS. There were some differences regarding bladder neck descent or parameters of tape position and mobility between those 116 women who reported improvement/cure of stress incontinence and those 20 who did not, although the significance levels reached were low (Table 3). Failed tapes seemed to be more distal relative to the bladder neck (higher value for ‘x’) and the symphysis pubis, both at rest (lower ‘x-r’) and on Valsalva (lower ‘x-s’). The lower measurements for ‘y’, i.e. the horizontal distance between tape and bladder neck, generally also imply a more distal tape. Imaging parameters such as tape position and mobility were very similar between the three different tapes (Table 4). There was a trend towards greater horizontal distances between tape and bladder neck (significant on Tukey’s multiple comparisons for the comparison of SPARC vs. IVS), and for greater horizontal distances between tape and symphysis pubis on Valsalva (Tukey’s
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Figure 1 Mid-sagittal two-dimensional translabial ultrasound images of tensionless vaginal tape (TVT), intravaginal slingplasty (IVS) and suprapubic arc procedure (SPARC) (from left to right). The tapes are evident as echogenic stripes posterior (to the right) of the mid-urethra.
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd.
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Stress incontinence condition Cured/ improved (n = 116)
Not cured/ improved (n = 20)
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1.91 (1.08) 1.67 (0.49) −1.25 (0.65) 1.11 (0.57) 1.74 (0.38) −0.63 (0.59) 0.93 (0.53) −0.81 (0.58) −1.74 (0.59) 1.99 (0.64)
2.27 (1.1) 1.88 (0.38) −0.95 (0.49) 0.95 (0.36) 1.78 (0.45) −0.85 (0.47) 0.77 (0.54) −1.01 (0.61) −1.80 (0.59) 2.11 (0.73)
NS 0.04 0.025 0.11 NS 0.076 NS NS NS NS
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NS, non-significant; x and y, distances between inferior tape margin and bladder neck; x–r and y–r, distances between tape and symphysis pubis at rest; x–s and y–s, distances between tape and symphysis pubis at rest on Valsalva.
was significant for SPARC vs. both other tapes). Horizontal tape mobility was less in the SPARC group (Tukey’s significant test for IVS vs. SPARC), implying that the tape did not move as close to the symphysis pubis on Valsalva, resulting in less compression of the urethra between tape and symphysis pubis. Total tape mobility, however, did not differ between the three implants.
DISCUSSION This imaging study was conducted within a randomized controlled trial testing three suburethral slings used for
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Figure 2 Three-dimensional pelvic floor ultrasound images of tensionless vaginal tape (TVT), intravaginal slingplasty (IVS) and suprapubic arc procedure (SPARC) (from left to right) in the axial plane. The tapes are evident as ‘u’-shaped structures surrounding the urethra laterally and posteriorly.
Type of suburethral sling TVT (n = 47)
IVS (n = 45)
SPARC (n = 44)
Bladder neck descent x y x–r y–r x–s y–s Horizontal tape mobility Vertical tape mobility Total tape mobility
2.02 (1.14) 1.69 (0.56) −1.16 (0.64) 1.11 (0.59) 1.67 (0.36) −0.68 (0.44) 0.82 (0.58) −0.85 (0.50) −1.78 (0.64) 2.04 (0.65)
2.18 (1.14) 1.80 (0.47) −1.01 (0.63) 0.96 (0.55) 1.81 (0.46) −0.78 (0.64) 0.80 (0.42) −1.01 (0.63) −1.74 (0.67) 2.07 (0.79)
1.67 (0.91) 1.62 (0.37) −1.44 (0.57) 1.19 (0.47) 1.75 (0.34) −0.52 (0.63) 1.10 (0.53) −0.64 (0.58) −1.71 (0.45) 1.90 (0.50)
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Table 4 Translabial imaging of bladder neck descent and position and mobility of suburethral tapes
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the surgical treatment of urodynamic stress incontinence. Such studies are still very scarce at present, with the only fully published randomized controlled trial limited to a comparison of clinical results after TVT and IVS, with 50 patients in each arm3 . •While the full perioperative and clinical postoperative results of this study have been published elsewhere7 , the data presented here was obtained to determine whether the use of these three slings results in different anatomical outcomes, and whether such differences could explain variations in clinical outcome. Previous work using the same or similar methodology has shown that translabial ultrasound currently is the most convenient and informative method available for imaging suburethral slings11,13 – 16 . Magnetic resonance imaging has been employed to detect changes after TVT17 but has yet to be shown to be able to demonstrate the tape itself, and plain X-ray imaging requires the insertion of radio-opaque markers at time of surgery18 . The location of suburethral tapes differs from traditional slings in that the inventors of the procedure insisted on placement beneath the middle third of the urethra19 , which is effected by minimal dissection. On
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*P < 0.05 for ANOVA and comparison IVS vs. SPARC. †P < 0.05 for ANOVA and comparison TVT or IVS vs. SPARC. x and y, distances between inferior tape margin and bladder neck. x–r and y–r, distances between tape and symphysis pubis at rest. x–s and y–s, distances between tape and symphysis pubis at rest on Valsalva. IVS, intravaginal sling; NS, non-significant; SPARC, suprapubic arc sling; TVT, tensionless vaginal tape.
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd.
the whole, the assumption of mid-urethral placement has been confirmed by imaging studies13,15 – 17,20 . The importance of sling location remains an unresolved issue21 , and it appears that the compressive effect of a suburethral sling can occur over a wide range of locations along the urethra18,22 . It appears that in this study more distal tapes were over-represented among the failures (Table 3). However, some of the documented significances may well be spurious in view of the number of analyses undertaken, and the authors feel that the data is not strong enough to derive firm conclusions regarding a relationship between placement and subjective success. As there were marked differences between the three slings tested in this study, with regards to both the materials used and to the insertion mode, it seemed reasonable to assume that anatomical, if not clinical, outcomes would be found to vary between groups, but this was not the case. Most tested parameters did not differ significantly between groups, and this applied to symptoms and subjective perception of cure and satisfaction (Table 2), flowmetry indices and tape location and mobility (Table 4). With regards to the clinical data, this confirms the findings of the only other
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6. Dietz HP, Vancaillie P, Svehla M, Walsh W, Steensma AB, Vancaillie TG. Mechanical properties of urogynecologic implant materials. Int Urogynecol J Pelvic Floor Dysfunct 2003; 14: 239–243. 7. Lim YN, Muller R, Corstiaans A, Dietz HP, Barry C, Rane A. Suburethral slingplasty evaluation study in North Queensland, Australia: The SUSPEND Trial. Aust N Z J Obstet Gynaecol 2005; 45: 52–59. 8. Haylen BT, Ashby D, Sutherst JR, Frazer MI, West CR. Maximum and average urine flow rates in normal male and female populations – the Liverpool nomograms. Br J Urol 1989; 64: 30–38. 9. Dietz HP. Ultrasound imaging of the pelvic floor: Part I: twodimensional aspects. Ultrasound Obstet Gynecol 2004; 23: 80–92. 10. Dietz HP. Ultrasound imaging of the pelvic floor. Part II: threedimensional or volume imaging. Ultrasound Obstet Gynecol 2004; 23: 615–625. 11. Dietz HP, Mouritsen L, Ellis G, Wilson PD. Does the tensionfree vaginal tape stay where you put it? Am J Obstet Gynecol 2003; 188: 950–953. 12. Pritchard G, Schluter P. Standardization of 3D datasets for fetal morphology examination: comparison with real time assessment in midtrimester ultrasound exami-nation. Singapore J Obstet Gynecol 2004; 35(Suppl.1): 19–20. 13. Martan A, Masata J, Svabik K, Halaska M, Voigt P. The ultrasound imaging of the tape after TVT procedure. Neurourol Urodyn 2002; 21: 322–324. 14. Virtanen HS, Kiilholma P. Urogynecologic ultrasound is a useful aid in the assessment of female stress urinary incontinence – a prospective study with TVT procedure. Int Urogynecol J Pelvic Floor Dysfunct 2002; 13: 218–222. 15. Sarlos D, Kuronen M, Schaer G. How does tension-free vaginal tape correct stress incontinence? Investigation by perineal ultrasound. Int Urogynecol J Pelvic Floor Dysfunct 2003; 14: 395–398. 16. Dietz HP, Wilson PD, Gillies K, Vancaillie TG. How does the TVT achieve continence? Neurourol Urodyn 2000; 19: 393–394. 17. Halaska M, Otcenasek M, Martan A, Masata J, Voigt R, Seifert M. Pelvic anatomy changes after TVT procedure assessed by MRI. Int Urogynecol J Pelvic Floor Dysfunct 1999; 10(Suppl.1): 87–88. 18. Kaum H, Wolff F. TVT: On midurethral tape positioning and its influence on continence. Int Urogynecol J Pelvic Floor Dysfunct 2002; 13: 110–115. 19. Ulmsten U, Falconer C, Johnson P, Jomaa M, Lanner L, Nilsson CG, Olsson I. A multicenter study of tension-free vaginal tape (TVT) for surgical treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 1998; 9: 210–213. 20. Lo TS, Wang AC, Horng SG, Liang CC, Soong YK. Ultrasonographic and urodynamic evaluation after tension free vagina tape procedure (TVT). Acta Obstet Gynecol Scand 2001; 80: 65–70. 21. Dietz HP, Mouritsen L, Ellis G, Wilson PD. How important is TVT location? Acta Obstet Gynecol Scand 2004; 83: 904–908. 22. Dietz HP, Wilson PD. The ‘iris effect’: how two-dimensional and three-dimensional ultrasound can help us understand antiincontinence procedures. Ultrasound Obstet Gynecol 2004; 23: 267–271. 23. Nilsson CG. The tensionfree vaginal tape procedure (TVT) for treatment of female urinary incontinence. A minimal invasive surgical procedure. Acta Obstet Gynecol Scand Suppl 1998; 168: 34–37. 24. Sander P, Moller LM, Rudnicki PM, Lose G. Does the tensionfree vaginal tape procedure affect the voiding phase? Pressureflow studies before and 1 year after surgery. BJU Int 2002; 89: 694–698. 25. Dietz HP, Ellis G, Wilson PD, Herbison P. Voiding function after tension-free vaginal tape: a longitudinal study. Aust N Z J Obstet Gynaecol 2004; 44: 152–155.
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randomized comparison of TVT and IVS published to date3 . With regards to imaging data, several parameters seemed to imply that SPARC tapes were somewhat looser, confirming data obtained in a case control series of TVT vs. SPARC4 . However, significances were low and possibly spurious in view of the multiple analyses performed. In view of previous data demonstrating marked in vitro differences between these three suburethral slings6 and the even more obvious differences in insertion mode, our results at first sight may appear puzzling. As the IVS is much less elastic than the other two implants in vitro6 , one would have expected a less mobile tape and greater voiding impairment. This most definitely was not the case. However, it must be noted that the insertion technique in this trial did not make use of the cough test for adjustment. Instead, tapes were left very loose, with the operator leaving enough space between tape and urethra for the passage of Metzenbaum scissors. This resulted in placement significantly looser than if the adjustment had been made according to the original technique19,23 •. This hypothesis is supported by the fact that TVT insertion in this study resulted in less reduction of free flowmetry indices than previously reported24,25 . It appears plausible that the mobility of tape and surrounding tissues would be determined mainly by tape biomechanics in cases of tight (i.e. tensioned) tapes, and mainly by tissue biomechanics when insertion is truly ‘tension-free’. Regarding the SPARC tape, the data obtained in this study is more consistent with previously published results. The SPARC carries a central suture that prevents pretensioning of the tape on adjustment. Consequently, one would have expected the SPARC to be at the ‘loose’ end of the spectrum. In conclusion, all three tested suburethral slings could be located by 2D and 3D translabial ultrasound. Under the conditions of loose insertion without cough test adjustment, TVT, SPARC and IVS result in roughly comparable clinical and anatomical outcomes.
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REFERENCES
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1. Nilsson CG, Rezapour M, Falconer C. 7 years followup of the tension-free vaginal tape (TVT) procedure. Int Urogynecol J Pelvic Floor Dysfunct 2003; 14(Suppl.1): 35•. 2. Ward K, Hilton P; United Kingdom and Ireland Tension-free Vaginal Tape Trial Group. Prospective multicentre randomised trial of tension-free vaginal tape and colposuspension as primary treatment for stress incontinence. BMJ 2002; 325: 67. 3. Rechberger T, Rzezniczuk K, Skorupski P, Adamiak A, Tomaszewski J, Baranowski W, Jakowicki JA. A randomized comparison between monofilament and multifilament tapes for stress incontinence surgery. Int Urogynecol J Pelvic Floor Dysfunct 2003; 14: 432–436. 4. Dietz HP, Foote AJ, Mak HL, Wilson PD. TVT and Sparc suburethral slings: a case-control series. Int Urogynecol J Pelvic Floor Dysfunct 2004; 15: 129–131. 5. Glavind K, Sander P. Erosion, defective healing and extrusion after tension-free urethropexy for the treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2004; 15: 179–182.
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Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd.
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QUERIES TO BE ANSWERED BY AUTHOR & EDITOR IMPORTANT NOTE: Please mark your corrections and answers to these queries directly onto the proof at the relevant place. Do NOT mark your corrections on this query sheet.
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Queries to Author: AQ1 Please check figures as 67 + 64 + 64 = 195 minus 13 = 182, and also 51 TVT, 48 IVS, 48 SPARC total = 147. AQ2 Please check changes to Table 2 AQ3 Table 4 - Please insert units. AQ4 It seems that. . ..This sentence has been changed – is it ok? AQ5 Johnson & Johnson Ethicon Gynecare – manufacturer’s details correct? AQ6 TVT is one of three types. . . This sentence has been changed – is it ok? AQ7 ‘competitors’ ok? Would ‘types of implant’ be better? AQ8 196 women correct? AQ9 183 women and 146 correct? AQ10 136 correct? AQ11 Excel manufacturer details added – are they correct ok? Please add version. AQ12 (= 100*NORMSDIST((LN(Qmax)−(0.51136 + 0.50457*LN(voided volume)))/0.33966). Please check number of brackets. AQ13 Philips/ATL manufacturer address details added – are they correct? AQ14 Please check changes to Table 1 AQ15 Please define ICC AQ16 Please check changes to Table 3 AQ17 Table 3 - Please insert units. AQ18 ..‘in each arm’ Please clarify. AQ19 This resulted in placement. . .. This sentence has been changed – is it ok? AQ20 Please check if ref 1 is correct.
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Queries to Editor: EQ1 AS PER THE STYLE WE HAVE INSERTED THE LINK * FOR FIRST AUTHOR AND † FOR THE OTHER AUTHORS. PLEASE CHECK WHETHER IT IS OK
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