- Email: [email protected]
Reply to ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group.’
412
Correspondence and communications
Reply to ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group.’
of infantile hemangiomas (IH).1 It is agreed that propranolol has a widely published range of side effects, more so when compared to that of atenolol especially in the treatment of hypertension. Propranolol has gained recent popularity in the treatment of IH due to its efficacy however the mechanism of action still remains unclear.1,2 Similarly the effect and mechanism of action of atenolol has not been widely studied in a pediatric population. Nevertheless we agree with the authors, that it could be a good alternative to propranolol if it has less side effects and similar efficacy. Early initiation of pharmacologic treatment such as propranolol within the proliferative phase of IH ensures the best outcomes regarding eventual involution, provided comorbid conditions have been appropriately managed beforehand.3 Given that 85% (23/27) of patients from the atenolol group were aged 1e6 months, it might be hard to compare success rates when only 50% of the propranolol group fell within the same age range. Although the authors refer to age adjustment, clarification is required as how this was done, as the age and efficacy are not related in a linear fashion. More crucially as the focus of the study was efficacy, propranolol was shown to be the more efficacious option due to 100% involution whereas atenolol failed to cause complete involution in 10%. Additionally, although the authors state the difference is not statistically significant, only the quantitative assessment was used for this. We would like to commend the authors on achieving their sample size, as it is the largest to date regarding the use of atenolol.1 It would be interesting to know the outcomes of the propranololeatenolol group of excluded patients, as well as that of the non-cutaneous lesions. We would also like to know whether all of the patients who did not respond to atenolol were then treated with propranolol. We do admit that propranolol has well-known side effects in the treatment of IH, but recent evidence allows for pediatric-tailored drug regimens resulting in a better safety profile.2e5 It is worth noting that one of the patients who suffered from hypoglycaemia following propranolol treatment did so as a result of steroid withdrawal, rather than propranolol itself. Presumably the patients in the atenolol group would not have this problem, as steroids would no longer be used as first line for IH. It is understandable that atenolol be used for its beta-1 specificity, but current evidence (including Graaf et al.’s study) shows that propranolol is still very efficacious.1,2 This study re-affirms the notion that atenolol can be used to treat IH, however data from this study alone is not sufficient to state that atenolol has similar efficacy to propranolol as concluded by the authors. Perhaps a larger sample size spanning similar age groups would allow for a fairer and more enlightening comparison.
Dear Sir,
Conflict of interest/funding
We read with great interest Graaf et al.’s comparative analysis between atenolol and propranolol in the treatment
None.
C.C. Breugem Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M.J. Knol Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands C.A.F.M. Bruijnzeel-Koomen Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M. Kon Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands J.M.P.J. Breur Department of Pediatric Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands S.G.M.A. Pasmans Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands *Corresponding author. Tel.: þ31 88 7557388. E-mail address: [email protected] 14 October 2013 ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bjps.2013.10.027
a
Current affiliation: Pediatric Dermatology, Erasmus Medical Center Rotterdam, The Netherlands DOI of original article: http://dx.doi.org/10.1016/ j.bjps.2013.07.035
References 1. de Graaf M, Raphael MF, Breugem CC, et al. Treatment of infantile haemangiomas with atenolol: comparison with a
Correspondence and communications
2.
3.
4.
5.
historical propranolol group. J Plast Reconstr Aesthet Surg; 2013. Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for infantile haemangioma. J Plast Reconstr Aesthet Surg 2011; 64(3). Drolet BA, Frommelt PC, Chamlin SL, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics 2012;131(1). Buckmiller LM, Munson PD, Dyamenahalli U, Dai Y, Richter GT. Propranolol for infantile hemangiomas: early experience at a tertiary vascular anomalies center. Laryngoscope 2010; 120(4). McSwiney E, Murray D, Murphy M. Propranolol therapy for cutaneous infantile haemangiomas initiated safely as a daycase procedure. Eur J Pediatr; 2013.
Ashvin Raju Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore E-mail address: [email protected] Roba Khundkar Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford, UK ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bjps.2013.10.025
Effects of perforator number and location on the total pedicle flow and perfusion of zone IV skin and fat of DIEP flaps by Douglas et al. Dear Sir, The authors, (Douglas, Wilkinson and Mackay), have tried to answer a difficult question in perforator flap surgery: what is the effect of perforator number and location on flap perfusion? Actually, no body ever has thought it is counterintuitive that including more than one perforator might negatively affect flap perfusion. Despite the fact that the study has some limitations mainly the low number of patients-, it is original and provoking and the authors should be congratulated for their efforts to deliberate such research. In their study, the authors investigated epigastric flap perfusion based on one perforator -either superior or inferior- or on both of them, both in an animal experiment and on DIEP flap patients. The results showed increased perfusion when the flap was based on a single perforator than when based on two. Moreover, this result was confirmed in DIEP flap DOI of original j.bjps.2013.10.048
article:
http://dx.doi.org/10.1016/
413 patients, where both skin and fat perfusion of zone IV was greater when single perforator was used. Concerning the location of the perforator, a superior (and hence more remote) perforator provided better flap perfusion. Therefore, the authors recommended using a single perforator rather than two when both were in the same row. They were unable to demonstrate a statistical difference between lateral and median row due to small number of patients included in the study. In our experience, dominant perforators are mainly periumbilically, on the medial row. Based on a single medial-row perforator, the DIEP flap has the highest perfusion.1 However, we still believe that surgeons should base their decisions regarding DIEA branch harvest on the clinical assessment of perforator perfusion quality, rather than relying on the theoretical superiority of a medial branch perforator.2 Obviously, harvesting a flap based on one perforator has additional advantages such as reduced dissection time and donor site morbidity due to less muscle and intercostal nerve damage. Another remarkable finding was increased zone IV perfusion when a flap was based on a single perforator. The authors assumed that the observed differences might be related to changing pressure gradients across zone IV prone to venous congestion, a conclusion that is however not adequately supported by their data. It could even tempt junior surgeons to include zone IV when a flap is harvested on a single perforator, rather than on two or more. It is obvious that adding a second perforator to a clearly dominant perforator won’t add vascular benefit to the harvested flap, however it is somehow surprising to find that the presence of an additional perforator might even reduce flap perfusion. The study data revealed that zone IV perfusion was significantly reduced. Unfortunately, the authors didn’t look at the perfusion in zone II or III. I do believe that research on the effect of correctly choosing the dominant perforator of a certain flap (in terms of rate of fat necrosis, harvested weight flap, etc.) would be more useful to surgeons, rather than whether or not zone IV can be included into the flap. Moreover, “better perfusion” doesn’t mean “adequate perfusion” of zone IV to be safely included in the flap. Losken et al. previously showed that zone IV has the lowest perfusion zone using similar measurement method with intraoperative IndoCyanine Green angiography.3 After all, it is much better to harvest a smaller but a healthy flap than a larger flap with major fat necrosis. Any remaining volume deficit can easily be corrected by secondary fat grafting when indicated. Also, correction of breast contour asymmetry is more important than volume restoration for many patients asking for secondary procedures. In conclusion, the authors presented a useful model for further research. I am looking forward to similar papers that examine the effect of including 2 perforators from a different row on flap perfusion. Historically, surgeons performing free flap reconstructions used to maximize blood perfusion to the harvested flap by including as many perforators feasible. Therefore, many of them believed that a free TRAM flap has better perfusion than a DIEP flap, as it
Correspondence and communications
Reply to ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group.’
of infantile hemangiomas (IH).1 It is agreed that propranolol has a widely published range of side effects, more so when compared to that of atenolol especially in the treatment of hypertension. Propranolol has gained recent popularity in the treatment of IH due to its efficacy however the mechanism of action still remains unclear.1,2 Similarly the effect and mechanism of action of atenolol has not been widely studied in a pediatric population. Nevertheless we agree with the authors, that it could be a good alternative to propranolol if it has less side effects and similar efficacy. Early initiation of pharmacologic treatment such as propranolol within the proliferative phase of IH ensures the best outcomes regarding eventual involution, provided comorbid conditions have been appropriately managed beforehand.3 Given that 85% (23/27) of patients from the atenolol group were aged 1e6 months, it might be hard to compare success rates when only 50% of the propranolol group fell within the same age range. Although the authors refer to age adjustment, clarification is required as how this was done, as the age and efficacy are not related in a linear fashion. More crucially as the focus of the study was efficacy, propranolol was shown to be the more efficacious option due to 100% involution whereas atenolol failed to cause complete involution in 10%. Additionally, although the authors state the difference is not statistically significant, only the quantitative assessment was used for this. We would like to commend the authors on achieving their sample size, as it is the largest to date regarding the use of atenolol.1 It would be interesting to know the outcomes of the propranololeatenolol group of excluded patients, as well as that of the non-cutaneous lesions. We would also like to know whether all of the patients who did not respond to atenolol were then treated with propranolol. We do admit that propranolol has well-known side effects in the treatment of IH, but recent evidence allows for pediatric-tailored drug regimens resulting in a better safety profile.2e5 It is worth noting that one of the patients who suffered from hypoglycaemia following propranolol treatment did so as a result of steroid withdrawal, rather than propranolol itself. Presumably the patients in the atenolol group would not have this problem, as steroids would no longer be used as first line for IH. It is understandable that atenolol be used for its beta-1 specificity, but current evidence (including Graaf et al.’s study) shows that propranolol is still very efficacious.1,2 This study re-affirms the notion that atenolol can be used to treat IH, however data from this study alone is not sufficient to state that atenolol has similar efficacy to propranolol as concluded by the authors. Perhaps a larger sample size spanning similar age groups would allow for a fairer and more enlightening comparison.
Dear Sir,
Conflict of interest/funding
We read with great interest Graaf et al.’s comparative analysis between atenolol and propranolol in the treatment
None.
C.C. Breugem Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M.J. Knol Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands C.A.F.M. Bruijnzeel-Koomen Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M. Kon Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands J.M.P.J. Breur Department of Pediatric Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands S.G.M.A. Pasmans Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands *Corresponding author. Tel.: þ31 88 7557388. E-mail address: [email protected] 14 October 2013 ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bjps.2013.10.027
a
Current affiliation: Pediatric Dermatology, Erasmus Medical Center Rotterdam, The Netherlands DOI of original article: http://dx.doi.org/10.1016/ j.bjps.2013.07.035
References 1. de Graaf M, Raphael MF, Breugem CC, et al. Treatment of infantile haemangiomas with atenolol: comparison with a
Correspondence and communications
2.
3.
4.
5.
historical propranolol group. J Plast Reconstr Aesthet Surg; 2013. Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for infantile haemangioma. J Plast Reconstr Aesthet Surg 2011; 64(3). Drolet BA, Frommelt PC, Chamlin SL, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics 2012;131(1). Buckmiller LM, Munson PD, Dyamenahalli U, Dai Y, Richter GT. Propranolol for infantile hemangiomas: early experience at a tertiary vascular anomalies center. Laryngoscope 2010; 120(4). McSwiney E, Murray D, Murphy M. Propranolol therapy for cutaneous infantile haemangiomas initiated safely as a daycase procedure. Eur J Pediatr; 2013.
Ashvin Raju Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore E-mail address: [email protected] Roba Khundkar Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford, UK ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bjps.2013.10.025
Effects of perforator number and location on the total pedicle flow and perfusion of zone IV skin and fat of DIEP flaps by Douglas et al. Dear Sir, The authors, (Douglas, Wilkinson and Mackay), have tried to answer a difficult question in perforator flap surgery: what is the effect of perforator number and location on flap perfusion? Actually, no body ever has thought it is counterintuitive that including more than one perforator might negatively affect flap perfusion. Despite the fact that the study has some limitations mainly the low number of patients-, it is original and provoking and the authors should be congratulated for their efforts to deliberate such research. In their study, the authors investigated epigastric flap perfusion based on one perforator -either superior or inferior- or on both of them, both in an animal experiment and on DIEP flap patients. The results showed increased perfusion when the flap was based on a single perforator than when based on two. Moreover, this result was confirmed in DIEP flap DOI of original j.bjps.2013.10.048
article:
http://dx.doi.org/10.1016/
413 patients, where both skin and fat perfusion of zone IV was greater when single perforator was used. Concerning the location of the perforator, a superior (and hence more remote) perforator provided better flap perfusion. Therefore, the authors recommended using a single perforator rather than two when both were in the same row. They were unable to demonstrate a statistical difference between lateral and median row due to small number of patients included in the study. In our experience, dominant perforators are mainly periumbilically, on the medial row. Based on a single medial-row perforator, the DIEP flap has the highest perfusion.1 However, we still believe that surgeons should base their decisions regarding DIEA branch harvest on the clinical assessment of perforator perfusion quality, rather than relying on the theoretical superiority of a medial branch perforator.2 Obviously, harvesting a flap based on one perforator has additional advantages such as reduced dissection time and donor site morbidity due to less muscle and intercostal nerve damage. Another remarkable finding was increased zone IV perfusion when a flap was based on a single perforator. The authors assumed that the observed differences might be related to changing pressure gradients across zone IV prone to venous congestion, a conclusion that is however not adequately supported by their data. It could even tempt junior surgeons to include zone IV when a flap is harvested on a single perforator, rather than on two or more. It is obvious that adding a second perforator to a clearly dominant perforator won’t add vascular benefit to the harvested flap, however it is somehow surprising to find that the presence of an additional perforator might even reduce flap perfusion. The study data revealed that zone IV perfusion was significantly reduced. Unfortunately, the authors didn’t look at the perfusion in zone II or III. I do believe that research on the effect of correctly choosing the dominant perforator of a certain flap (in terms of rate of fat necrosis, harvested weight flap, etc.) would be more useful to surgeons, rather than whether or not zone IV can be included into the flap. Moreover, “better perfusion” doesn’t mean “adequate perfusion” of zone IV to be safely included in the flap. Losken et al. previously showed that zone IV has the lowest perfusion zone using similar measurement method with intraoperative IndoCyanine Green angiography.3 After all, it is much better to harvest a smaller but a healthy flap than a larger flap with major fat necrosis. Any remaining volume deficit can easily be corrected by secondary fat grafting when indicated. Also, correction of breast contour asymmetry is more important than volume restoration for many patients asking for secondary procedures. In conclusion, the authors presented a useful model for further research. I am looking forward to similar papers that examine the effect of including 2 perforators from a different row on flap perfusion. Historically, surgeons performing free flap reconstructions used to maximize blood perfusion to the harvested flap by including as many perforators feasible. Therefore, many of them believed that a free TRAM flap has better perfusion than a DIEP flap, as it