Ann Thorac Surg 2014;98:1141–4
CORRESPONDENCE
Reference
Katarina Walden, MD
1. Wald en K, Jeppsson A, Nasic S, Backlund E, Karlsson M. Low preoperative fibrinogen plasma concentration is associated with excessive bleeding after cardiac operations. Ann Thorac Surg 2014;97:1199–206.
Department of Anesthesia and Intensive Care Sahlgrenska University Hospital Gothenburg, Sweden
1143
Salmir Nasic, MS
We thank Li and associates [1] for their interest in our recent publication [2]. In the article we demonstrate that there is an independent association between the preoperative fibrinogen concentration and excessive bleeding (>1,000 mL during the first 12 postoperative hours). We also investigated the association between the preoperative fibrinogen concentration and red blood cell (RBC) transfusions during the hospital stay but were unable to show any significant association. Li and associates have concerns about the absence of a significant association between the fibrinogen concentration and RBC transfusions for three reasons. First, they claim that it is unclear whether we mean transfusion of RBCs or of all blood products, even though we clearly stated at several places in the manuscript that we investigated the association between fibrinogen and RBC transfusion. Furthermore, Li and colleagues claim we should have investigated the association between fibrinogen and plasma and platelet transfusion. We agree that this would have been interesting. We have now performed a post hoc analysis that shows there were no significant differences in the preoperative fibrinogen concentration between patients who did or did not receive a plasma transfusion (3.8 1.2 vs 3.8 1.0 g/L; p ¼ 0.34), or between patients who did or did not receive a platelet transfusion (3.8 1.2 vs 3.8 1.0 g/L; p ¼ 0.69). Second, Li and colleagues claim that we should have divided the patients who received RBC transfusions in subgroups according to the number of units transfused. In the post hoc analysis, we have now compared patients that received 1 to 2, 3 to 6, and more than >6 RBC units, and there was no significant difference in the preoperative fibrinogen concentration among the three groups (3.9 1.0, 4.0 1.1, and 4.1 1.4 g/L, respectively; p ¼ 0.16 by analysis of variance). Finally, Li and colleagues state that we should have studied RBC transfusions during a limited period rather than during the entire hospital stay. Unfortunately, we are lacking data about the transfusion period for most of the patients in our database, so a post hoc analysis cannot be performed. However, in our opinion, the total RBC transfusion during the hospital stay is a more important measure than transfusions during a limited period. A more restrictive transfusion policy during one period may result in more transfusions at a later stage. Again, we thank Li and associates for their comments. Anders Jeppsson, MD, PhD Department of Cardiothoracic Surgery Sahlgrenska University Hospital SE-41345 Gothenburg, Sweden and Department of Molecular and Clinical Medicine Institute of Medicine The Sahlgrenska Academy University of Gothenburg Gothenburg, Sweden e-mail: [email protected]
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
Research and Development Centre Skaraborg Hospital Sk€ovde, Sweden Martin Karlsson, MD, PhD Department of Medicine Skaraborg Hospital Lidk€oping, Sweden
References 1. Li B, Tan B, Chen C, Zhao L, Qin L. Is preoperative fibrinogen really not associated with blood transfusion? (letter). Ann Thorac Surg 2014;98:1142–3. 2. Walden K, Jeppsson A, Nasic S, Backlund E, Karlsson M. Low preoperative fibrinogen plasma concentration is associated with excessive bleeding after cardiac operations. Ann Thorac Surg 2014;97:1199–206.
Postsurgical Follow-Up Is Always Necessary in Bronchial Carcinoid To the Editor: Lou and colleagues [1] analyzed a cohort of patients with bronchial carcinoids in an article published in this journal and concluded that surveillance imaging may not be warranted due to the low percentage of recurrences. We totally disagree with the authors’ conclusions. Several surgical groups have considered this neoplasm benign for years, and consequently, follow-up was not performed or was limited to 5 years after surgical intervention. However, the peak of recurrences in typical carcinoid neoplasms occurs generally after 5 years from the operation (often 10 years) [2–4], and lifelong follow-up is therefore necessary. On the contrary, in atypical carcinoids the recurrences are generally observed within 5 years [2–4]. Several biases do not support the conclusions of the authors: 1. The study is based only on a retrospective analysis of a database (electronic medical records) and not on a clinical assessment. 2. The patients were followed up by clinicians or nurse practitioners, and the method of follow-up was not standardized but left to the discretion of the clinician (!); it is therefore not surprising that one-third of recurrences were diagnosed only by symptoms, differently from what happens in patients followed up in referral centers where adequate follow-up is performed. 3. The most definitive bias is that median follow-up time was less than 4 years from the operation (!!). 4. The imaging was limited to chest roentgenograms or computed tomography imaging of the chest, therefore underestimating liver metastases and bone metastases that require magnetic resonance imaging and nuclear medicine techniques [5]. In bronchial carcinoid, an accurate and protracted follow-up is crucial to prolong quality of life and survival of patients. All over
0003-4975/$36.00
MISCELLANEOUS
Reply To the Editor:
1144
CORRESPONDENCE
Europe and North America, hundreds of patients, very often of a young age, might be easily cured at the first initial recurrence but, unfortunately, are frequently observed in referral tertiary centers with dramatic metastatic spread to distal organs. Efforts of dedicated scientific societies, such as the European Neuroendocrine Tumor Society, are at the moment directed to evidence, in their guidelines, the need of a uniformly protracted follow-up in accurate timing, clinical management, and radiologic workup [5]. Piero Ferolla, MD, PhD Niccolo Daddi, MD, PhD Francesco Puma, MD Lucio Crino, MD Multidisciplinary Neuroendocrine Tumors Center European Neuroendocrine Tumor Society Center of Excellence Umbria Regional Cancer Network Via E. dal Pozzo 06126 Perugia, Italy e-mail: [email protected]
References 1. Lou F, Sarkaria I, Pietanza C, et al. Recurrence of pulmonary carcinoid tumors after resection: implications for postoperative surveillance. Ann Thorac Surg 2013;96:1156–62. 2. Ferolla P, Daddi N, Urbani M, et al. Tumorlets, multicentric carcinoids, lymph-nodal metastases, and long-term behavior in bronchial carcinoids. J Thorac Oncol 2009;4:383–7. 3. Daddi N, Ferolla P, Urbani M, et al. Surgical treatment of neuroendocrine tumors of the lung. Eur J Cardiothorac Surg 2004;26:813–7. 4. Faggiano A, Ferolla P, Grimaldi F, et al. Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. J Endocrinol Invest 2012;35:817–23. € 5. Oberg K, Hellman P, Ferolla P, et al. Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23(Suppl 7): vii120–3.
MISCELLANEOUS
Reply To the Editor: In response to Ferolla and colleagues [1], we would like to clarify that our conclusion that surveillance may not be warranted pertained only to the node-negative typical carcinoids, in which the risk of recurrence was exceedingly small [2]. We agree that surveillance is important for atypical carcinoids and carcinoids with nodal involvement. The limitations noted by Ferolla and colleagues—the retrospective nature and lack of standardization—have been acknowledged and also apply to most of the relevant literature, including the references cited by Ferolla and colleagues. Heterogeneity in practice is inevitable given the lack of consensus between guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, etc), but there has been growing use of computed tomography (CT) scans for lung cancer follow-up. Currently, the standard algorithm at our institution uses CT imaging every 6 to 12 months.
Ann Thorac Surg 2014;98:1141–4
Ferolla and colleagues presume that one-third of our patients with recurrences presented with symptoms due to lack of adequate follow-up; however, there are no data to support this, and most of the recurrences were identified incidentally or through symptoms experienced between scheduled follow-up visits. Data on longer follow-up will be informative, and we will revisit this cohort in the future. Ferolla and colleagues suggest that CT is inadequate and that magnetic resonance imaging and nuclear medicine studies are needed to detect distant metastases. However, the European Society for Medical Oncology guidelines, coauthored by Ferolla, recommend CT scans every 2 to 3 years for typical carcinoids, with no mention of nuclear or magnetic resonance imaging studies. To our knowledge, there are no studies demonstrating the value of routine magnetic resonance imaging or nuclear studies for follow-up purposes. Finally, Ferolla and colleagues suggest that many patients have curable local recurrences that are missed because of inappropriate follow-up, only to present later as metastatic disease. However, in our study, in which patients did undergo routine follow-up with CT scans, the incidence of local recurrence was very low. None of the references cited by Ferolla and colleagues provide any evidence to support this hypothesis. The design of follow-up must weigh the risk of recurrences against the potential for harm arising from the follow-up itself in the form of unnecessary additional imaging and procedures on the basis of false-positive results [3]. Additional testing was performed unnecessarily in 25% of lung cancer survivors because of false-positive scans [4]. We agree that, “accurate follow-up is crucial to prolong quality of life and survival of patients.” Ideally, one should consider the “number needed to treat”—in this case, the number of patient scans needed to identify one curable local recurrence. For node-negative typical carcinoids, this number is likely to be exceedingly high. Feiran Lou, MD James Huang, MD Thoracic Service Memorial Sloan Kettering Cancer Center 1275 York Ave New York, NY 10065 e-mail: [email protected]
References 1. Ferolla P, Daddi N, Puma F, Crin o L. Postsurgical follow-up is always necessary in bronchial carcinoid (letter). Ann Thorac Surg 2014;98:1143–4. 2. Lou F, Sarkaria I, Pietanza C, et al. Recurrence of pulmonary carcinoid tumors after resection: implications for postoperative surveillance. Ann Thorac Surg 2013;96:1156–62. 3. Bach PB, Mirkin JN, Oliver TK, et al. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA 2012;307:2418–29. 4. Lou F, Huang J, Sima CS, Dycoco J, Rusch V, Bach PB. Patterns of recurrence and second primary lung cancer in earlystage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg 2013;145: 75–82.
CORRESPONDENCE
Reference
Katarina Walden, MD
1. Wald en K, Jeppsson A, Nasic S, Backlund E, Karlsson M. Low preoperative fibrinogen plasma concentration is associated with excessive bleeding after cardiac operations. Ann Thorac Surg 2014;97:1199–206.
Department of Anesthesia and Intensive Care Sahlgrenska University Hospital Gothenburg, Sweden
1143
Salmir Nasic, MS
We thank Li and associates [1] for their interest in our recent publication [2]. In the article we demonstrate that there is an independent association between the preoperative fibrinogen concentration and excessive bleeding (>1,000 mL during the first 12 postoperative hours). We also investigated the association between the preoperative fibrinogen concentration and red blood cell (RBC) transfusions during the hospital stay but were unable to show any significant association. Li and associates have concerns about the absence of a significant association between the fibrinogen concentration and RBC transfusions for three reasons. First, they claim that it is unclear whether we mean transfusion of RBCs or of all blood products, even though we clearly stated at several places in the manuscript that we investigated the association between fibrinogen and RBC transfusion. Furthermore, Li and colleagues claim we should have investigated the association between fibrinogen and plasma and platelet transfusion. We agree that this would have been interesting. We have now performed a post hoc analysis that shows there were no significant differences in the preoperative fibrinogen concentration between patients who did or did not receive a plasma transfusion (3.8 1.2 vs 3.8 1.0 g/L; p ¼ 0.34), or between patients who did or did not receive a platelet transfusion (3.8 1.2 vs 3.8 1.0 g/L; p ¼ 0.69). Second, Li and colleagues claim that we should have divided the patients who received RBC transfusions in subgroups according to the number of units transfused. In the post hoc analysis, we have now compared patients that received 1 to 2, 3 to 6, and more than >6 RBC units, and there was no significant difference in the preoperative fibrinogen concentration among the three groups (3.9 1.0, 4.0 1.1, and 4.1 1.4 g/L, respectively; p ¼ 0.16 by analysis of variance). Finally, Li and colleagues state that we should have studied RBC transfusions during a limited period rather than during the entire hospital stay. Unfortunately, we are lacking data about the transfusion period for most of the patients in our database, so a post hoc analysis cannot be performed. However, in our opinion, the total RBC transfusion during the hospital stay is a more important measure than transfusions during a limited period. A more restrictive transfusion policy during one period may result in more transfusions at a later stage. Again, we thank Li and associates for their comments. Anders Jeppsson, MD, PhD Department of Cardiothoracic Surgery Sahlgrenska University Hospital SE-41345 Gothenburg, Sweden and Department of Molecular and Clinical Medicine Institute of Medicine The Sahlgrenska Academy University of Gothenburg Gothenburg, Sweden e-mail: [email protected]
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
Research and Development Centre Skaraborg Hospital Sk€ovde, Sweden Martin Karlsson, MD, PhD Department of Medicine Skaraborg Hospital Lidk€oping, Sweden
References 1. Li B, Tan B, Chen C, Zhao L, Qin L. Is preoperative fibrinogen really not associated with blood transfusion? (letter). Ann Thorac Surg 2014;98:1142–3. 2. Walden K, Jeppsson A, Nasic S, Backlund E, Karlsson M. Low preoperative fibrinogen plasma concentration is associated with excessive bleeding after cardiac operations. Ann Thorac Surg 2014;97:1199–206.
Postsurgical Follow-Up Is Always Necessary in Bronchial Carcinoid To the Editor: Lou and colleagues [1] analyzed a cohort of patients with bronchial carcinoids in an article published in this journal and concluded that surveillance imaging may not be warranted due to the low percentage of recurrences. We totally disagree with the authors’ conclusions. Several surgical groups have considered this neoplasm benign for years, and consequently, follow-up was not performed or was limited to 5 years after surgical intervention. However, the peak of recurrences in typical carcinoid neoplasms occurs generally after 5 years from the operation (often 10 years) [2–4], and lifelong follow-up is therefore necessary. On the contrary, in atypical carcinoids the recurrences are generally observed within 5 years [2–4]. Several biases do not support the conclusions of the authors: 1. The study is based only on a retrospective analysis of a database (electronic medical records) and not on a clinical assessment. 2. The patients were followed up by clinicians or nurse practitioners, and the method of follow-up was not standardized but left to the discretion of the clinician (!); it is therefore not surprising that one-third of recurrences were diagnosed only by symptoms, differently from what happens in patients followed up in referral centers where adequate follow-up is performed. 3. The most definitive bias is that median follow-up time was less than 4 years from the operation (!!). 4. The imaging was limited to chest roentgenograms or computed tomography imaging of the chest, therefore underestimating liver metastases and bone metastases that require magnetic resonance imaging and nuclear medicine techniques [5]. In bronchial carcinoid, an accurate and protracted follow-up is crucial to prolong quality of life and survival of patients. All over
0003-4975/$36.00
MISCELLANEOUS
Reply To the Editor:
1144
CORRESPONDENCE
Europe and North America, hundreds of patients, very often of a young age, might be easily cured at the first initial recurrence but, unfortunately, are frequently observed in referral tertiary centers with dramatic metastatic spread to distal organs. Efforts of dedicated scientific societies, such as the European Neuroendocrine Tumor Society, are at the moment directed to evidence, in their guidelines, the need of a uniformly protracted follow-up in accurate timing, clinical management, and radiologic workup [5]. Piero Ferolla, MD, PhD Niccolo Daddi, MD, PhD Francesco Puma, MD Lucio Crino, MD Multidisciplinary Neuroendocrine Tumors Center European Neuroendocrine Tumor Society Center of Excellence Umbria Regional Cancer Network Via E. dal Pozzo 06126 Perugia, Italy e-mail: [email protected]
References 1. Lou F, Sarkaria I, Pietanza C, et al. Recurrence of pulmonary carcinoid tumors after resection: implications for postoperative surveillance. Ann Thorac Surg 2013;96:1156–62. 2. Ferolla P, Daddi N, Urbani M, et al. Tumorlets, multicentric carcinoids, lymph-nodal metastases, and long-term behavior in bronchial carcinoids. J Thorac Oncol 2009;4:383–7. 3. Daddi N, Ferolla P, Urbani M, et al. Surgical treatment of neuroendocrine tumors of the lung. Eur J Cardiothorac Surg 2004;26:813–7. 4. Faggiano A, Ferolla P, Grimaldi F, et al. Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. J Endocrinol Invest 2012;35:817–23. € 5. Oberg K, Hellman P, Ferolla P, et al. Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23(Suppl 7): vii120–3.
MISCELLANEOUS
Reply To the Editor: In response to Ferolla and colleagues [1], we would like to clarify that our conclusion that surveillance may not be warranted pertained only to the node-negative typical carcinoids, in which the risk of recurrence was exceedingly small [2]. We agree that surveillance is important for atypical carcinoids and carcinoids with nodal involvement. The limitations noted by Ferolla and colleagues—the retrospective nature and lack of standardization—have been acknowledged and also apply to most of the relevant literature, including the references cited by Ferolla and colleagues. Heterogeneity in practice is inevitable given the lack of consensus between guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, etc), but there has been growing use of computed tomography (CT) scans for lung cancer follow-up. Currently, the standard algorithm at our institution uses CT imaging every 6 to 12 months.
Ann Thorac Surg 2014;98:1141–4
Ferolla and colleagues presume that one-third of our patients with recurrences presented with symptoms due to lack of adequate follow-up; however, there are no data to support this, and most of the recurrences were identified incidentally or through symptoms experienced between scheduled follow-up visits. Data on longer follow-up will be informative, and we will revisit this cohort in the future. Ferolla and colleagues suggest that CT is inadequate and that magnetic resonance imaging and nuclear medicine studies are needed to detect distant metastases. However, the European Society for Medical Oncology guidelines, coauthored by Ferolla, recommend CT scans every 2 to 3 years for typical carcinoids, with no mention of nuclear or magnetic resonance imaging studies. To our knowledge, there are no studies demonstrating the value of routine magnetic resonance imaging or nuclear studies for follow-up purposes. Finally, Ferolla and colleagues suggest that many patients have curable local recurrences that are missed because of inappropriate follow-up, only to present later as metastatic disease. However, in our study, in which patients did undergo routine follow-up with CT scans, the incidence of local recurrence was very low. None of the references cited by Ferolla and colleagues provide any evidence to support this hypothesis. The design of follow-up must weigh the risk of recurrences against the potential for harm arising from the follow-up itself in the form of unnecessary additional imaging and procedures on the basis of false-positive results [3]. Additional testing was performed unnecessarily in 25% of lung cancer survivors because of false-positive scans [4]. We agree that, “accurate follow-up is crucial to prolong quality of life and survival of patients.” Ideally, one should consider the “number needed to treat”—in this case, the number of patient scans needed to identify one curable local recurrence. For node-negative typical carcinoids, this number is likely to be exceedingly high. Feiran Lou, MD James Huang, MD Thoracic Service Memorial Sloan Kettering Cancer Center 1275 York Ave New York, NY 10065 e-mail: [email protected]
References 1. Ferolla P, Daddi N, Puma F, Crin o L. Postsurgical follow-up is always necessary in bronchial carcinoid (letter). Ann Thorac Surg 2014;98:1143–4. 2. Lou F, Sarkaria I, Pietanza C, et al. Recurrence of pulmonary carcinoid tumors after resection: implications for postoperative surveillance. Ann Thorac Surg 2013;96:1156–62. 3. Bach PB, Mirkin JN, Oliver TK, et al. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA 2012;307:2418–29. 4. Lou F, Huang J, Sima CS, Dycoco J, Rusch V, Bach PB. Patterns of recurrence and second primary lung cancer in earlystage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg 2013;145: 75–82.
