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eComment. The Nuss technique: A track full of hazards

Alain J Wurtz, Emmanuel Brian

Thoracic Department, Institut Mutualiste Montsouris, Paris France

Re: "Risk of serious perioperative complications with removal of double bars following the Nuss Procecure", Bilgi, et al., doi:10.1093/icvts/ivw332

Interactive CardioVascular and Thoracic Surgery doi:10.1093/icvts/ivw364 
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved

Following a well-conducted prospective study, Bilgi and coworkers report the assessment of complication occurrence at the time of bar removal in patients having undergone a Nuss operation ([1]. We would like to congratulate the authors for this nice contribution to the highly debated field of pectus surgical repair. In fact, this work deserves some additional comments. First, the overall complication rate was 17.5%, but the authors, surprisingly, state that the initial procedure is associated with a 3-5% morbidity rate, according to their mentioned references [1]. The discrepancy between percentages could mean that the step of bar removal is found to be the riskiest procedure in the surgical course of patients undergoing the Nuss technique, which is obviously unrealistic [2]. Otherwise, we take the opportunity to mention that the authors failed to refer to additional cases of patients sustaining lethal or near-fatal haemorrhagic complications at the time of bar removal as a consequence of ventricle laceration [3-5]. All these patients were wearer of a single bar. The cause of these catastrophic outcomes is thought to be a postoperative pericardial effusion leading to a "symphysis", i.e., a complete obliteration of the space between the pericardium and heart, and dense fusion of all adjacent tissues and bar, as shown by Bouchard and coworkers [3]. Another uncommon mechanism of heart lesion is the progressive intracardiac migration of the bar, which was retrospectively noticed by Sakakibara and coworkers on chest computed tomography performed before bar removal [5]. Similar findings were shown in a 18-year-old boy, whose history were reported in The DailyMail in 2014 (http://www.dailymail.co.uk/health/article-2739727/Bullied-teenager-nearly-died-steel-bar-inserted-disguise-sunken-chest-came-1cm-heart.html). Bar removal and cardiac repair required a 14-hour procedure under CPB. Fortunately, the patient made a satisfactory recovery. Apart from that, difficulties occasionally encountered during bar removal due to neo-ossification are other causes for concern. Finally, the safety of the so-called minimally invasive Nuss procedure appears for us strongly questionable [2]. Consequently, in our Institution we have opted to routinely perform pectus excavatum repair by means of a simplified Ravicht-type procedure including the placement of a straight titanium plate secured to the base of sternum. This device is easily removed under local anaesthesia through a 1-cm long lateral incision during an outpatient procedure 6 months after the initial operation, as shown on the video available on the CTSnet website (http://www.ctsnet.org/article/simplified-open-repair-pectus-deformities).

References

[1] Bilgi Z, Ermerak NO, Cetinkaya C, Lacin T, Yüksel M. Risk of serious perioperative complications with removal of double bars following the Nussprocedure. Interact CardioVasc Thorac Surg 20 October 2016; doi:10.1093/icvts/ivw322.

[2] Wurtz A. The Nuss Procedure: Above all, do no harm. Ann Thorac Surg 2015;99:1865-70.

[3] Bouchard S, Hong AR, Gilchrist BF, Kuenzler KA. Catastrophic cardiac injuries encountered during the minimally invasive repair of pectus excavatum. Sem Pediatr Surg 2009;18:66-72.

[4] Haecker FM, Berberich T, Mayr J, Gambazzi F. Near-fatal bleeding after transmyocardial ventricle lesion during removal of the pectus bar after the Nuss procedure. J Thorac Cardiovasc Surg 2009;138:1240-1.

[5] Sakakibara K, Kinoshita H, Ando K, Yasuda Y, Mori Y, Fujiwara Y. Right?ventricular?perforation?due to a stabilizing bar installed for the'Nuss'procedure. Minerva Anestesiol 2013;79:820-1.

Conflict of interest: none declared.

Published: October 31 2016

eComment. Tissue frailty in Cardiac surgery

Isala Clinic, Zwolle, The Netherlands

Re: "Tracheal rupture after intubation and placement of an endotracheal balloon catheter (A-view®) in cardiac surgery" Timman, et al., 23 (3): 506-507 doi:10.1093/icvts/ivw127

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved body
Thanks for sharing this experience [1], a first after more than 2000 clinical cases with modified TOE. Atherosclerosis of the ascending aorta (AA) is indeed associated with serious adverse outcomes in cardiac surgery, justifying the use of a device to maximize TOE views in the AA by resolving the blindspot [2,3]. In any modified TOE case, one should be aware of the proximity of the rigid TOE probe and the intra-tracheal balloon, thus requiring gentle manipulation of both. Although in this specific case the cause of the event cannot be proven, we emphasize the careful handling including a limited filling (20-30 ml) of the balloon taking into consideration patient dimensions. Moreover we agree on the contraindication for the use of a trachea balloon device, or to perform TOE, in patients with a high risk of tissue frailty (e.g. MCTD) as stipulated in the device IFU.

[1] Timman ST, Mourisse JM, van der Heide SM, and Verhagen AF. Tracheal rupture after intubation and placement of an endotracheal balloon catheter A-view in cardiac surgery. Interact CardioVasc Thorac Surg 2016;23:506-507.

[2] Jansen Klomp WW et al. Poster Presentation Society Cardio Thoracic Anesthesia, San Diego, April 2016.

[3] van Zaane B, Nierich AP, Brandon Bravo Bruinsma GJ, Rosseel PM, Ramjankhan FZ, de Waal EE et al. Br J Anaest 2010;105:131-138.

Conflict of interest: Inventor of A-view method. Medical director of Stroke2prevent

Published: September 27, 2016

eComment. Neoadjuvant chemoradiotherapy: where is the real controversy?

Long-Qi Chen Han-Yu Deng, Zhi-Qiang Wang

Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China

Re: "Does neoadjuvant chemoradiotherapy increase survival in patients with resectable oesophageal cancer?" Buderi, et al., doi:10.1093/icvts/ivw281

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved
We read with great interest the article by Buderi et al. [1], "Does neoadjuvant chemoradiotherapy increase survival in patients with resectable oesophageal cancer?" The authors presented eleven up-to-date randomized controlled trials and concluded that neoadjuvant chemoradiotherapy followed by surgery for resectable oesophageal cancer offers similar or even improved survival results compared to surgery alone [1]. We identified other high-quality, relevant systematic reviews and meta-analyses, nearly all of which [2, 3] also concluded that neoadjuvant chemoradiotherapy followed by surgery provides significant survival benefits for patients with resectable oesophageal cancer compared with surgery alone. The National Comprehensive Cancer Network clinical practice guidelines in oncology for oesophageal and oesophagogastric junction cancers [4] also recommend neoadjuvant chemoradiotherapy as a preferred preoperative treatment strategy for patients with resectable, locally advanced oesphageal cancer. Consequently, we want to emphasize that neoadjuvant chemoradiotherapy did bring survival benefits to patients with resectable, locally advanced oesophageal cancer, not the similar survival results compared with surgery alone as concluded by Buderi et al.[1]. With regard to the concept of survival benefits of neoadjuvant chemoradiotherapy, many researchers began to question whether combining radiotherapy with neoadjuvant chemotherapy provides a survival benefit for patients with resectable oesophageal cancer who are potentially at increased risk from the adverse effects of radiation. We recently conducted an up-dated meta-analysis [5] in which we reported that patients with resectable, locally advanced oesophageal squamous cell carcinoma who had neoadjuvant chemoradiotherapy showed a significantly increased survival rate compared to those who had neoadjuvant chemotherapy. In comparison, the survival rate for patients with resectable, locally advanced oesophageal adenocarcinoma did not improve if radiotherapy was combined with neoadjuvant chemotherapy. Further research on this question is badly needed. Therefore, even though we believe that neoadjuvant chemoradiotherapy could increase the survival rate of patients with resectable oesophageal cancer, we feel a controversy still exists as to which neoadjuvant strategy (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy or even neoadjuavent radiotherapy) represents the optimum preoperative option for patients with resectable locally advanced oesophageal squamous cell carcinoma and adenocarcinoma, respectively, because these two pathological types are different entities.

References

[1] Buderi SI, Shackcloth M, Page RD. Does neoadjuvant chemoradiotherapy increase survival in patients with resectable oesophageal cancer? Interact CardioVasc Thorac Surg 2016; doi:10.1093/icvts/ivw281.

[2] Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta- analysis. Lancet Oncol 2011;12:681-92.

[3] Pasquali S, Yim G, Vohra RS, Mocellin S, Nyanhongo D, Marriott P et al. Survival After Neoadjuvant and Adjuvant Treatments Compared to Surgery Alone for Resectable Esophageal Carcinoma: A Network Meta- analysis. Annals of surgery 2016. (Published July 15 2016, available at: http://www.ncbi.nlm.nih.gov/pubmed/27429017)

[4] NCCN Guidelines for Treatment of Cancer by Site: Esophageal and Esophagogastric Junction Cancers. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#esophageal.(Accessed 13 September 2016)

[5] Deng HY, Wang WP, Wang YC, Hu WP, Ni PZ, Lin YD et al. Neoadjuvant chemoradiotherapy or chemotherapy? A comprehensive systematicreview and meta-analysis of the options for neoadjuvant therapy for treating oesophageal cancer. Eur J Cardiothorac Surg 2016;

Conflict of interest: none declared.

Published September 21, 2016

eComment. More with less: the role of minimally invasive surgery as a bridging procedure in the treatment of the aorto-oesophageal fistula

Demetrios Moris Georgios Karaolanis, and Dimitrios Schizas

1st Department of Surgery, Laikon General Hospital, School of Medicine, Athens, Greece

Re: "Surgical management without resection of the oesophagus for aorto-oesophageal fistula secondary to aortic arch aneurysm rupture" Omura, et al., doi:10.1093/icvts/ivw239

Interactive CardioVascular and Thoracic Surgery doi:10.1093/icvts/ivw330 
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved
Georgios Karaolanis1, Dimitrios Schizas1, Demetrios Moris2
1Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece 
2Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

Aortoaesophageal fistula (AEF) is a rare cause of gastrointestinal bleeding with high morbidity and mortality rates. Due to its low incidence and the urgency of symptoms at presentation, no standard of care has been described. We read with great interest the recent publication by Omura et al. [1]. The authors described the case of a 79-year-old man who presented with sudden-onset haemoptysis and who had a history of graft replacement in the descending thoracic aorta. He also had a history of chronic kidney disease.

Computerized tomography (CT) revealed an AEF secondary to the rupture of an aortic arch aneurysm near the origin of the left subclavian artery. The authors performed open heart surgery using cardiopulmonary bypass and replaced the aortic arch with a Dacron graft. They sutured the fistula and covered the graft and the repair site of the oesophagus with an omental flap. However, this approach raises some issues regarding the appropriate procedure in this critical situation.

Thoracic endovascular aortic repair (TEVAR) in the last decade has offered a minimally invasive alternative and is especially valuable as a bridging procedure under urgent situations in high-risk patients [2,3]. We wonder whether the authors considered in this case the deployment of a stent graft in the aortic arch and the insertion of a self-expandable stent in the oesophagus that could gain time to plan the next step and to stabilize the patient, as recently described in the literature [2,3]. AEF has the potential of acute exsanguination and continuous contamination of the circulation with micro-organisms that can cause a constant septic condition in the patient [4].

Moulakakis et al. [4] recently reported an interesting meta-analysis in which many studies showed excellent results after performing TEVAR as the first stage and oesophagectomy with gastric "pull-up" and omental pedicle transposition to cover the aneurysm sac as the second stage. All patients were alive during follow-up with no signs of graft infection. Similar conclusions were reached by another study [5].

Another issue of interest is whether the authors described the omental pedicle transposition procedure they performed. How did the authors harvest the omentum and how was the transposition performed? Do the authors think that these additional manoeuvers added to the overall morbidity of the patient? Moreover, no definite conclusions could be drawn about the mid- and long-term efficacy of their approach because the follow-up period was short and the potential for late complications of oesophageal origin was still high.

In summary, it seems that, in patients with AEF, a minimally invasive approach, as suggested in the cited literature [2-5], consisting of TEVAR and stenting in the oesophagus followed by oesophagus resection with gastric "pull-up" and omental pedicle transposition, when the patient has been stabilized, is a promising option in critical situations of AEF. Therefore, we look forward for the authors' comments since, according to the status of their patient, a less invasive approach is a feasible alternative.

References

[1] Omura A, Yoshida M, Koda Y, Mukohara N. Surgical management without resection of the oesophagus for aorto-oesophageal fistula secondary to aortic arch aneurysm rupture. Interact Cardiovasc Thorac Surg 19 August 2016; doi: 10.1093/icvts/ivw239.

[2] Chiesa R, Melissano G, Marone EM, Marrocco-Trischitta MM, Kahlberg A. Aorto-oesophageal and aortobronchial fistula following thoracic endovascular aortic repair: a national survey. Eur J Vasc Endovasc Surg 2010;39:273-9.

[3] Jonker FHW, Heijmen R, Trimarchi S, Verhagen HJM, Moll FL, Muhs BF. Acute management of aortobronchial and aortoesophageal fistulas using thoracic endovascular aortic repair. J Vasc Surg 2009;50:999-1005.

[4] Moulakakis KG, Mylonas SN, Antonopoulos CN, Kakisis JD, Sfyroeras GS, Mantas G et al. Comparison of treatment strategies for thoracic endograft infection. J Vasc Surg. 2014;60:1061-71.

[5] Georvasili VK, Bali C, Peroulis M, Kouvelos G, Avgos S, Godevenos D et al. Management of an aorto-esophageal fistula, complicating a descending thoracic aortic aneurysm endovascularly repaired. Gen Thorac Cardiovasc Surg 2016;64:216-9.

Conflict of interest: none declared.

Published August 31, 2016

eComment. Could the definitive chemoradiated stage III non-small-cell-lung cancer N3 patient be "saved" by salvation lung resection?

Natalia Motas, Tedor Horvat

Institute of Oncology, Bucharest, Romania

Re: "Feasibility and efficacy of salvage lung resection after definitive chemoradiation therapy for Stage III non-small-cell lung cancer" Shimada, et al., doi:10.1093/icvts/ivw245

Interactive CardioVascular and Thoracic Surgery doi:10.1093/icvts/ivw313 
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved
We studied with great interest the work of Shimada and colleagues [1].

Locally advanced non-small-cell lung cancer (NSCLC) clinical stage III, is proven to be a heterogeneous population of cases. The worst prognosis in stage III is attributed to N3 cases and the vast majority of surgeons (but not all of them) excludes N3 cases from surgery.

For locally advanced NSCLC treated with definitive chemoradiation, salvage lung resection is a surgical resection with curative intent [2-4].

In the presented paper there are two cases of former N3, both alive and free of disease at 2 and 3 years after salvage resection. It is not clear what kind of N3 they were: mediastinal contralateral or supraclavicular zone? It is also unclear if the N3 zones were resected. Even if the PET-CT after radical chemoradiation is negative in the area of the former N3, it is possible that this area is microscopically positive for tumour cells.

So the issue is: should previous positive N3 areas be histologically explored before any surgical decision? And if positive, should they be resected under the same anaesthesia with the salvation lung resection in order to accomplish a true "salvation"? And if negative, should they also be resected? Resecting the whole disease as it was first diagnosed could be one of the valid answers.

As authors concluded, the key to successful salvage surgery in stage III NSCLC after curative-intent chemoradiation therapy is careful selection of the patients.

References

[1] Shimada Y, Suzuki K, Okada M, Nakayama H, Ito H, Mitsudomi T et al. Feasibility and efficacy of salvage lung resection after definitive chemoradiation therapy for Stage III non-small-cell lung cancer. Interact CardioVasc Thorac Surg 2016; 19 August 2016; doi: 10.1093/icvts/ivw245.

[2] Bauman JE, Mulligan MS, Martins RG, Kurland BF, Eaton KD, Wood DE. Salvage lung resection after definitive radiation (>59 Gy) for non-small cell lung cancer: surgical and oncologic outcomes. Ann Thorac Surg 2008;86:1632-8; discussion 38-39.

[3] Kuzmik GA, Detterbeck FC, Decker RH, Boffa DJ, Wang Z, Oliva IB et al. Pulmonary resections following prior definitive chemoradiation therapy are associated with acceptable survival. Eur J Cardiothorac Surg 2013;44:e66-70.

[4] Yang CF, Meyerhoff RR, Stephens SJ, Singhapricha T, Toomey CB, Anderson KL et al. Long-term outcomes of lobectomy for non-small cell lung cancer after definitive radiation treatment. Ann Thorac Surg 2015;99:1914-1920.

Conflict of interest: none declared

Published August 24 2016

eComments. Phosphocreatine in cardiovascular disease: how can we relate the evidence to clinical practice?

Evgeny Fominskiy, Giovanni Landoni

IRCCS San Raffaele Scientific Institute, Milan, Italy

Re: "Cardiac protection with phosphocreatine: a meta-analysis" Landoni, et al., 23 (4): 637-646 doi:10.1093/icvts/ivw171

Interactive CardioVascular and Thoracic Surgery doi:10.1093/icvts/ivw307 
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved
Dear Editor, We would like to thank Dr. Brown for his comments [1] on our article suggesting benefits of phosphocreatine (PCr) in patients with heart disease [2]. In the meta-analysis, PCr was studied in three settings that are clinically heterogeneous but homogeneous in origin. Acute or chronic ischaemia with further altered energetics plays an important role during surgery in the mechanisms of myocardial damage in patients with coronary artery disease and chronic heart failure [3,4]. Because PCr is an essential part of the intracellular energy transfer system, it has the potential to be useful in clinical cases due to ischaemia [5]. We used the pathophysiological approach in defining the studied population. The meta-analysis and further subanalyses confirmed our hypothesis that PCr is beneficial in three of the settings we investigated. The dose of PCr varied from study to study. Nevertheless, in most cardiac surgery studies, PCr was added to the cardioplegia solution to reach a concentration of 10 mmol/l and was administered intravenously before initiation of cardiopulmonary bypass. PCr (2 g) was administered to patients with coronary artery disease by intracoronary bolus or intravenously with further continuous infusion for an average of 5 days. In patients with chronic heart failure, 1 g to 8 g PCr was administered intravenously for 1 to 56 days. In only one study, PCr was administered per os for 90 days. Thus, despite the fact that the overall dosage varied, the dose and mode of PCr administration were comparable in individual clinical settings. Despite these limitations, the meta-analysis is the first comprehensive review of the topic and emphasizes the necessity for more well-designed trials.

References

[1] Brown OI. eComment Phosphocreatine in cardiovascular disease: how can we relate the evidence to clinical practice? 27 June 2016; doi:10.1093/icvts/ivw243.

[2] Landoni G, Zangrillo A, Lomivorotov VV, Likhvantsev V, Ma J, De Simone F et al.Y Cardiac protection with phosphocreatine: a meta-analysis. Interact CardioVasc Thorac Surg. J17 Junew 2016; doi: 10.1093/icvts/ivw171.

[3] Neubauer S. The failing heart--an engine out of fuel. N Engl J Med 2007;356:1140-51.

[4] Shen W, Spindler M, Higgins MA, Jin N, Gill RM, Bloem LJ et al. The fall in creatine levels and creatine kinase isozyme changes in the ailing heart are reversible: complex post-transcriptional regulation of the components of the CK system. J Mol Cell Cardiol 2005;39:537-44.

[5] Santacruz L, Jacobs DO. Structural correlates of the creatine transporter function regulation: the undiscovered country. Amino Acids 2016;48:2049-55.

Conflict of interest: none declared.

Published August 18 2016

eReply. Diagnostic intricacies and fortuitous treatment approaches for carbapenem-resistant Klebsiella pneumoniae

Daniele R. Giacobbe, Antonio Salsano, Anna Marchese, and Francesco Santini

Infectious Disease Division, University of Genoa (DISSAL) and IRCCS San Martino-IST, Genoa, Italy

Re: "Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery" Salsano, et al., 23 (5): 762-768 doi:10.1093/icvts/ivw228

Interactive CardioVascular and Thoracic Surgery doi:10.1093/icvts/ivw289 
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved
Daniele Roberto Giacobbe1, Antonio Salsano2, Anna Marchese3, Francesco Santini2
1 Division of Infectious Diseases, University of Genoa (DISSAL) and IRCCS San Martino-IST, Genoa, Italy 
2 Division of Cardiac Surgery, IRCCS San Martino-IST, Genoa, Italy 
3 Microbiology Unit, University of Genoa (DISC) and IRCCS San Martino-IST, Genoa, Italy

Mestrovic and Bedenic provided some interesting comments on our article entitled "Risk factors for carbapenem-resistant Klebsiella pneumoniae infections after open heart surgery" [1, 2]. Their points mainly concern diagnostic intricacies and antimicrobial therapy.

With regard to the formers, they emphasize the role of a meticulous diagnostic laboratory work-up, since minimum inhibitory concentrations (MICs) for carbapenems of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) might vary markedly across strains. Consequently, some of them remain susceptible to carbapenems [3], although this is the exception rather than the rule in our centre. With regard to our study, it should be stressed that it was conceived to investigate risk factors and prognosis of frank carbapenem resistance as defined by clinical breakpoints. On the other hand, from an epidemiologic standpoint, we agree that deeper investigations such as multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) might provide important insights on KPC-Kp diffusion. In our centre, more than 80% of the strains belong to the pandemic clone sequence type 258 (ST258), although other clones - mainly ST101 and ST307 - have also been detected in recent years (personal unpublished data).

The second part of Mestrovic and Bedenic comments deals with antimicrobial therapy of KPC-Kp infections. In this regard, although combination therapies showed a possible survival benefit over monotherapy in observational studies, it should be noted that no randomized clinical trials are currently available to reliably compare the efficacy/tolerability between specific combinations. Keeping in mind this important limitation, we think two points raised by Mestrovic and Bedenic should be further discussed. The first point touches the controversial issue of including meropenem in combination regimens. From a pharmacokinetic/pharmacodynamic standpoint, we recently showed that high-dose meropenem might retain bactericidal activity against blood KPC-Kp isolates with meropenem MIC up to 32 mg/l [4]. Given that any possible benefit beyond this threshold appears unlikely, and that an unrestricted administration might lead to a self-perpetuating selection of resistance both in patients and in the environment, we think the use of meropenem for treating KPC-Kp infections should strictly rely on actual MICs of locally prevalent clones. The second point is that the evidence supporting the use of a double carbapenem combination is based on in vitro studies and limited case series. Pending more robust information, we think this regimen should only be used for pan-resistant strains, and/or when lacking dependable alternatives.

In conclusion, a deep and constantly evolving knowledge of the local microbiological epidemiology is not only essential for diagnosis and infection-control, but it is also a key aspect of the therapeutic approach to KPC-Kp infections.

References

[1] Salsano A, Giacobbe DR, Sportelli E, Olivieri GM, Brega C, Di Biase C et al. Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery. Interact CardioVasc Thorac Surg, 1 Jul 2016; doi:10.1093/icvts/ivw228.

[2] Mestrovic T, Bedenic B. Diagnostic intricacies and fortuitous treatment approaches for carbapenem-resistant Klebsiella pneumoniae. eComment, 23 July 2016; doi:10.1093/icvts/ivw266.

[3] Nordmann P, Naas T, Poirel L. Global spread of carbapenemase producing Enterobacteriaceae. Emerg Infect Dis 2011;17:1791-1798.

[4] Del Bono V, Giacobbe DR, Marchese A, Parisini A, Fucile C, Coppo E et al. Meropenem for treating KPC-producing Klebsiella pneumoniae bloodstream infections: should we get to the PK/PD root of the paradox? Virulence. 18 Jul 2016; doi:10.1080/21505594.2016.1213476.

Conflict of interest: none declared.

Published August 16, 2016

eComment. Can we really infer anything from this cohort?

Matthew D. Carr

Hull York Medical School, Hull, UK

Re: "Early outcomes of lung transplantation for bronchiolitis obliterans syndrome after allogeneic haematopoietic stem cell transplantation: a single-centre experience" Jung, et al., doi:10.1093/icvts/ivw231

Interactive CardioVascular and Thoracic Surgery doi:10.1093/icvts/ivw290 
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved
I praise Jung et al. [1] for attempting to improve the outlook for patients suffering from bronchiolitis obliterans syndrome (BOS) after allogeneic stem cell transplantation, as it would seem that the current treatment regime is lacking. I also applaud them for being aware of some of the shortcomings of their study. However, the authors fail to comment on many other limitations that directly affect their conclusion that lung transplantation could be a reasonable therapeutic option for BOS.

The authors acknowledge that the study is hindered by only including 9 patients, though one may also say that this cohort is too heterogenous to derive any meaningful conclusions from. Firstly, the large age range of patients (16-56 at transplantation) makes it difficult to draw any reasonable deductions about the consequences of lung transplantation on morbidity and mortality, given the role that age will also play intraoperatively and in postoperative recovery. Furthermore, the range of time between BOS diagnosis and transplantation was 7-59.8 months, likely meaning that patients towards the higher end of that range were in worse physical condition prior to transplantation, again impacting postoperative recovery.

Most importantly, the authors state that the follow-up time post-transplantation was between 1.2 and 59.9 months, which seems inadequate given that one patient had a recurrence of BOS 45.3 months after lung transplantation. Making interpretations about lung transplantation complications while only giving some patients a 1.2-month follow-up seems unreasonable, and fails to account for later potential complications that other patients were monitored for. In their discussion, the authors also neglect to mention that the patients were treated for different haematological malignancies with stem cells from varying sources, that the post-transplantation immunosuppression regimens were diverse, and that some of the patients had considerable smoking histories, all of which would affect the treatment outcomes on which the authors base their conclusion.

One could say that it remains unclear whether lung transplantation offers a superior treatment option for BOS than the current regime, especially considering that previous work cited by the authors focuses either on single cases or on a low cohort number [2,3]. The knowledge that lung transplantation carries a risk of graft rejection and BOS recurrence would suggest that it is premature to be advocating for lung transplantation as a means of treatment, especially in the Republic of Korea where this study was undertaken and where this procedure has only recently been introduced [1].

To further this important work, I agree with the authors that a controlled trial on BOS management is required, perhaps comparing lung transplantation to the current treatment regime, or trying to improve the current regime so that it is demonstrably superior to lung transplantation.

References

[1] Jung HS, Lee JG, Yu WS, Lee CY, Haam SJ, Paik HC. Early outcomes of lung transplantation for bronchiolitis obliterans syndrome after allogeneic haematopoietic stem cell transplantation: a single-centre experience. Interact CardioVasc Thorac Surg 1 August 2016; doi: 10.1093/icvts/ivw231.

[2] Calhoon JH, Levine S, Anzueto A, Bryan CL, Trinkle JK. Lung transplantation in a patient with a prior bone marrow transplant. Chest 1992; 102: 948.

[3] Redel-Montero J, Bujalance-Cabrera C, Vaquero-Barrios JM, Santos-Luna F, Arenas-De Larriva M, Moreno-Casado P, Espinosa-Jimenez D. Lung transplantation for bronchiolitis obliterans after allogenic bone marrow transplantation. Transplant Proc 2010;42:3023-5.

Conflict of interest: none declared.

Published August 16, 2016

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