Journal of Pediatric Surgery 51 (2016) 519–520
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Correspondence Letter to the editor To the Editor, The commentary “Back to the future: Does in-hospital delay to appendectomy for pediatric uncomplicated appendicitis increase risk for perforation?” [1] argues that when children with simple (nonperforated) appendicitis as diagnosed by CAT scan (CT) are managed with intravenous (IV) antibiotics, a significant percentage perforate their appendices in the hospital prior to their operations, and that in-hospital delay correlates with increased risk for “developing” perforation. The author, William Bonadio, advocates urgent appendectomy when simple appendicitis is diagnosed. His position explicitly contradicts the current standard of care and could provide fuel for plaintiffs' attorneys for whom delayed diagnosis of appendicitis is the most common basis for lawsuits against pediatric healthcare professionals. Two recent studies are cited as the support for the author's claim. One is in abstract form. The other, available for review, is by the author of the commentary [2]. In that retrospective, single-institution study, the premise that children in the emergency department (ED) had simple appendicitis at diagnosis is based solely on findings of CT scan. Many (22%) with CT scans interpreted as simple appendicitis were in fact perforated in the view of the surgeon or by the pathologists' interpretation. Perforations were only seen in cases where appendectomy occurred more than 9 h after ED triage. Furthermore, the rate of “developing” perforation increased by the hour in a linear fashion thereafter. While we cannot question the data from Bonadio's study, we feel as though this provocative study has significant flaws in both its methodology as well as its conclusions. In an era when ultrasound is replacing CT as the gold standard for diagnosing appendicitis in the pediatric population, the author holds the CT scan to be a highly sensitive way to determine if an appendix is perforated. We agree with the author that both retrospective reviews and clinical experience have shown that when a CT scan shows an inflamed appendix with an abscess in the abdomen or pelvis, extra luminal gas, a visible defect in the enhancing wall of the appendix, an extra luminal fecalith and/ or a “phlegmon” the patient nearly always has perforated appendicitis (in other words, these findings on CT scan are specific for perforation). However, and critical to the contention of the commentary and the study on which it is based, it is not the case that the CT is highly sensitive for perforation of the appendix. In other words, when a child has perforated appendicitis, it is not nearly 100% likely that a CT will demonstrate that. We would argue that Bonadio's data shows that the CT scan was inaccurate in diagnosing perforated appendicitis in up to 22% of the cases. The evidence for the exquisite sensitivity of CT in distinguishing perforated from nonperforated appendicitis that he offers in his study includes 5 references. One does not address this issue [3]. Another takes exactly the opposite position [4]. Sarah Bixby et al. reviewed CT scans of patients with appendicitis, of whom 62 were perforated. She summarizes her findings: “In conclusion, although certain multidetector CT findings are highly specific for the diagnosis of perforated appendicitis, poor sensitivity limits their clinical usefulness.” 0022-3468/© 2016 Elsevier Inc. All rights reserved.
If a child with appendicitis has diffuse tenderness, peritonitis, marked leukocytosis, high fever, and prolonged duration of symptoms and a CT shows appendicitis but finds no evidence of perforation, this should not be interpreted to mean this patient has simple appendicitis. Bonadio shows data that patients with perforated appendicitis were more likely to have fevers, and although it did not reach statistical significance, were more likely to have symptoms for more than 2 days (46% vs 32%). Bonadio does not provide the data for duration from ED triage to CT scan (when the patient was not receiving antibiotics) and from time of CT diagnosis to operation (after antibiotic treatment started). These data would perhaps shed more light on the process of “developing” a perforation while in hospital. The critical claim in this commentary is further debunked by the recent reports of treating simple appendicitis with antibiotics alone. Five of the 257 adults from the Finnish study (1.9%) [5] and none of the 30 children from Nationwide Children's Hospital [6] who were treated for simple appendicitis without immediate appendectomy progressed to perforation. In the commentary the author analogizes appendicitis to other “ischemic abdominal disorders” like midgut volvulus and incarcerated hernia for which delay in operation after the diagnosis is unacceptable. Appendicitis is caused by obstruction with resulting inflammation and infection. While the disease process includes ischemia, which may lead to perforation, the histopathology of nonperforated appendicitis does not resemble ischemic injury. Appendicitis is better compared to other conditions of the GI tract in which obstruction leads to inflammation and infection and can ultimately result in perforation because of ischemia such as cholecystitis and sigmoid diverticulitis, conditions for which urgent operations are rarely appropriate in the initial phases. The study on which this commentary was based can be commended for examining clinical practice with hope of improving outcomes. Bonadio's conclusions, if clinically accurate, have significant repercussions, but we believe that the evidence is too weak to support the conclusions. It would only serve to disappoint and confuse families and mislead others if a child is thought to have “developed” a perforation while awaiting an operation on antibiotics after a CT scan diagnosed case of simple appendicitis. Sincerely yours,
Stephen E. Dolgin⁎ Aaron M. Lipskar Division of Pediatric General, Thoracic and Endoscopic Surgery, Cohen Children's Medical Center of New York, Hofstra Northwell School of Medicine, USA ⁎Corresponding author. E-mail address: [email protected] Morris C. Edelman Division of Pediatric Pathology and Laboratory Medicine Cohen Children's Medical Center of New York Hofstra Northwell School of Medicine, USA
http://dx.doi.org/10.1016/j.jpedsurg.2015.12.008
520
Correspondence / Journal of Pediatric Surgery 51 (2016) 519–520
References [1] Bonadio W. Back to the future: does in-hospital delay to appendectomy for pediatric uncomplicated appendicitis increase risk for perforation? J Pediatr Surg 2015;50: 2005–6. [2] Bonadio W, Brazg J, Telt N, et al. Impact of in-hospital timing to appendectomy on perforation rates in children with appendicitis. J Emerg Med 2015;49: 597–604. [3] Pickhardt PJ, Lawrence EM, Pooler D, et al. Diagnostic performance of multidetector computed tomography for suspected acute appendicitis. Ann Intern Med 2011;154:789–96. [4] Bixby SD, Lucey BC, Soto JA. Perforated versus nonperforated acute appendicitis: accuracy of multidetector CT detection. Radiology 2006;241:780–6. [5] Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis. JAMA 2015;313:2340–8. [6] Minneci PC, Sulkowski JP, Nacion KM, et al. Feasibility of a nonoperative management strategy for uncomplicated acute appendicitis in children. JACS 2014;219:272–9.
Letter to the editor To the Editor, Shi and colleagues are to be congratulated for the report and analysis of the impact of pulmonary metastasectomy (often repeated) for relapsed hepatoblastoma [1]. Surgical therapy is the treatment of choice when the metastases are resectable, as in the primary tumor, and if not, should be used when they become resectable after chemotherapy The “go home” message is surely that continued multimodal therapy with curative intent is the basis of success. The authors note ‘As therapies for HB evolve, our understanding of HB biology improves, and novel therapies become available.’ In the spirit of this sentiment I would like to add a number of comments based on our experience [2]. The clinical significance of alpha fetoprotein (AFP) secretion by these tumors has not been fully utilized by many centers. Since this protein has a
half life of between 4 and 9 days the response to therapy can be followed by the simple readily available blood test that can be repeated every few days rather than relying on imaging every 3 months. Such an approach is used in leukemia in which the CBC permits a daily evaluation of response to therapy. Relapses can be prevented if ineffective or suboptimal therapy is discontinued within days when the drop in AFP is slower than expected. Certainly the best therapy for relapse is prevention. Although the most effective drugs used in this disease are doxorubicin and cisplatin both can cause significant toxicities. Twice weekly AFP levels can determine, in vivo, if other less toxic options such as carboplatin are effective. The diagnosis of relapse can be suspected when the AFP increases but, especially in the subgroup with very high initial levels, imaging may be initially negative and CT may only show disease when AFP levels reach more than 1000 ng/ml. Not all relapses will be diagnosed by AFP increases since many are mixed tumors, the fetal element that secretes AFP may be eliminated by therapy and the relapse can be embryonal or mesenchymal. These observations, it is hoped, could help to further improve the outlook in this condition. Ian Joseph Cohen The Rina Zaizov Department of Pediatric Hematology Oncology Schneider Children's Medical Center of Israel 14 Kaplan Street, Petah Tikva 49202, Israel E-mail address: [email protected]
http://dx.doi.org/10.1016/j.jpedsurg.2015.12.017 References [1] Yan Shi, Geller James I, Ma Irene T, et al. Relapsed hepatoblastoma confined to the lung is effectively treated with pulmonary metastasectomy. J Pediatr Surg 2015. http://dx.doi.org/10.1016/j.jpedsurg.2015.10.053. [2] Sayar Dror, Yaniv Isaac, Goshen Yacov, et al. Treatment of alpha-fetoprotein secreting hepatoblastoma by response of alpha-fetoprotein levels: A new concept. Pediatr Hematol Oncol 2001;18:509–18.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Correspondence Letter to the editor To the Editor, The commentary “Back to the future: Does in-hospital delay to appendectomy for pediatric uncomplicated appendicitis increase risk for perforation?” [1] argues that when children with simple (nonperforated) appendicitis as diagnosed by CAT scan (CT) are managed with intravenous (IV) antibiotics, a significant percentage perforate their appendices in the hospital prior to their operations, and that in-hospital delay correlates with increased risk for “developing” perforation. The author, William Bonadio, advocates urgent appendectomy when simple appendicitis is diagnosed. His position explicitly contradicts the current standard of care and could provide fuel for plaintiffs' attorneys for whom delayed diagnosis of appendicitis is the most common basis for lawsuits against pediatric healthcare professionals. Two recent studies are cited as the support for the author's claim. One is in abstract form. The other, available for review, is by the author of the commentary [2]. In that retrospective, single-institution study, the premise that children in the emergency department (ED) had simple appendicitis at diagnosis is based solely on findings of CT scan. Many (22%) with CT scans interpreted as simple appendicitis were in fact perforated in the view of the surgeon or by the pathologists' interpretation. Perforations were only seen in cases where appendectomy occurred more than 9 h after ED triage. Furthermore, the rate of “developing” perforation increased by the hour in a linear fashion thereafter. While we cannot question the data from Bonadio's study, we feel as though this provocative study has significant flaws in both its methodology as well as its conclusions. In an era when ultrasound is replacing CT as the gold standard for diagnosing appendicitis in the pediatric population, the author holds the CT scan to be a highly sensitive way to determine if an appendix is perforated. We agree with the author that both retrospective reviews and clinical experience have shown that when a CT scan shows an inflamed appendix with an abscess in the abdomen or pelvis, extra luminal gas, a visible defect in the enhancing wall of the appendix, an extra luminal fecalith and/ or a “phlegmon” the patient nearly always has perforated appendicitis (in other words, these findings on CT scan are specific for perforation). However, and critical to the contention of the commentary and the study on which it is based, it is not the case that the CT is highly sensitive for perforation of the appendix. In other words, when a child has perforated appendicitis, it is not nearly 100% likely that a CT will demonstrate that. We would argue that Bonadio's data shows that the CT scan was inaccurate in diagnosing perforated appendicitis in up to 22% of the cases. The evidence for the exquisite sensitivity of CT in distinguishing perforated from nonperforated appendicitis that he offers in his study includes 5 references. One does not address this issue [3]. Another takes exactly the opposite position [4]. Sarah Bixby et al. reviewed CT scans of patients with appendicitis, of whom 62 were perforated. She summarizes her findings: “In conclusion, although certain multidetector CT findings are highly specific for the diagnosis of perforated appendicitis, poor sensitivity limits their clinical usefulness.” 0022-3468/© 2016 Elsevier Inc. All rights reserved.
If a child with appendicitis has diffuse tenderness, peritonitis, marked leukocytosis, high fever, and prolonged duration of symptoms and a CT shows appendicitis but finds no evidence of perforation, this should not be interpreted to mean this patient has simple appendicitis. Bonadio shows data that patients with perforated appendicitis were more likely to have fevers, and although it did not reach statistical significance, were more likely to have symptoms for more than 2 days (46% vs 32%). Bonadio does not provide the data for duration from ED triage to CT scan (when the patient was not receiving antibiotics) and from time of CT diagnosis to operation (after antibiotic treatment started). These data would perhaps shed more light on the process of “developing” a perforation while in hospital. The critical claim in this commentary is further debunked by the recent reports of treating simple appendicitis with antibiotics alone. Five of the 257 adults from the Finnish study (1.9%) [5] and none of the 30 children from Nationwide Children's Hospital [6] who were treated for simple appendicitis without immediate appendectomy progressed to perforation. In the commentary the author analogizes appendicitis to other “ischemic abdominal disorders” like midgut volvulus and incarcerated hernia for which delay in operation after the diagnosis is unacceptable. Appendicitis is caused by obstruction with resulting inflammation and infection. While the disease process includes ischemia, which may lead to perforation, the histopathology of nonperforated appendicitis does not resemble ischemic injury. Appendicitis is better compared to other conditions of the GI tract in which obstruction leads to inflammation and infection and can ultimately result in perforation because of ischemia such as cholecystitis and sigmoid diverticulitis, conditions for which urgent operations are rarely appropriate in the initial phases. The study on which this commentary was based can be commended for examining clinical practice with hope of improving outcomes. Bonadio's conclusions, if clinically accurate, have significant repercussions, but we believe that the evidence is too weak to support the conclusions. It would only serve to disappoint and confuse families and mislead others if a child is thought to have “developed” a perforation while awaiting an operation on antibiotics after a CT scan diagnosed case of simple appendicitis. Sincerely yours,
Stephen E. Dolgin⁎ Aaron M. Lipskar Division of Pediatric General, Thoracic and Endoscopic Surgery, Cohen Children's Medical Center of New York, Hofstra Northwell School of Medicine, USA ⁎Corresponding author. E-mail address: [email protected] Morris C. Edelman Division of Pediatric Pathology and Laboratory Medicine Cohen Children's Medical Center of New York Hofstra Northwell School of Medicine, USA
http://dx.doi.org/10.1016/j.jpedsurg.2015.12.008
520
Correspondence / Journal of Pediatric Surgery 51 (2016) 519–520
References [1] Bonadio W. Back to the future: does in-hospital delay to appendectomy for pediatric uncomplicated appendicitis increase risk for perforation? J Pediatr Surg 2015;50: 2005–6. [2] Bonadio W, Brazg J, Telt N, et al. Impact of in-hospital timing to appendectomy on perforation rates in children with appendicitis. J Emerg Med 2015;49: 597–604. [3] Pickhardt PJ, Lawrence EM, Pooler D, et al. Diagnostic performance of multidetector computed tomography for suspected acute appendicitis. Ann Intern Med 2011;154:789–96. [4] Bixby SD, Lucey BC, Soto JA. Perforated versus nonperforated acute appendicitis: accuracy of multidetector CT detection. Radiology 2006;241:780–6. [5] Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis. JAMA 2015;313:2340–8. [6] Minneci PC, Sulkowski JP, Nacion KM, et al. Feasibility of a nonoperative management strategy for uncomplicated acute appendicitis in children. JACS 2014;219:272–9.
Letter to the editor To the Editor, Shi and colleagues are to be congratulated for the report and analysis of the impact of pulmonary metastasectomy (often repeated) for relapsed hepatoblastoma [1]. Surgical therapy is the treatment of choice when the metastases are resectable, as in the primary tumor, and if not, should be used when they become resectable after chemotherapy The “go home” message is surely that continued multimodal therapy with curative intent is the basis of success. The authors note ‘As therapies for HB evolve, our understanding of HB biology improves, and novel therapies become available.’ In the spirit of this sentiment I would like to add a number of comments based on our experience [2]. The clinical significance of alpha fetoprotein (AFP) secretion by these tumors has not been fully utilized by many centers. Since this protein has a
half life of between 4 and 9 days the response to therapy can be followed by the simple readily available blood test that can be repeated every few days rather than relying on imaging every 3 months. Such an approach is used in leukemia in which the CBC permits a daily evaluation of response to therapy. Relapses can be prevented if ineffective or suboptimal therapy is discontinued within days when the drop in AFP is slower than expected. Certainly the best therapy for relapse is prevention. Although the most effective drugs used in this disease are doxorubicin and cisplatin both can cause significant toxicities. Twice weekly AFP levels can determine, in vivo, if other less toxic options such as carboplatin are effective. The diagnosis of relapse can be suspected when the AFP increases but, especially in the subgroup with very high initial levels, imaging may be initially negative and CT may only show disease when AFP levels reach more than 1000 ng/ml. Not all relapses will be diagnosed by AFP increases since many are mixed tumors, the fetal element that secretes AFP may be eliminated by therapy and the relapse can be embryonal or mesenchymal. These observations, it is hoped, could help to further improve the outlook in this condition. Ian Joseph Cohen The Rina Zaizov Department of Pediatric Hematology Oncology Schneider Children's Medical Center of Israel 14 Kaplan Street, Petah Tikva 49202, Israel E-mail address: [email protected]
http://dx.doi.org/10.1016/j.jpedsurg.2015.12.017 References [1] Yan Shi, Geller James I, Ma Irene T, et al. Relapsed hepatoblastoma confined to the lung is effectively treated with pulmonary metastasectomy. J Pediatr Surg 2015. http://dx.doi.org/10.1016/j.jpedsurg.2015.10.053. [2] Sayar Dror, Yaniv Isaac, Goshen Yacov, et al. Treatment of alpha-fetoprotein secreting hepatoblastoma by response of alpha-fetoprotein levels: A new concept. Pediatr Hematol Oncol 2001;18:509–18.
