Neutropenic patients are at high risk of developing

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1 Surgical Management of Invasive Pulmonary Fungal Infection in Hematology Patients Sanjay Theodore, MCh, Matthew Liava a, MBChB, Phillip Antippa, FRACS, Rochelle Wynne, PhD, Andrew Grigg, FRACP, Monica Slavin, FRACP, and James Tatoulis, MD, FRACS Departments of Cardiothoracic Surgery and Haematology, and Victorian Infectious Diseases Service, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia Background. The purpose of this study was to analyze our institutional results with pulmonary resection in neutropenic patients with hematologic malignancies and suspected invasive pulmonary fungal infections. Methods. We performed a retrospective medical record review of 25 immunocompromised patients with hematologic malignancies who underwent pulmonary resection between 2000 and We analyzed preoperative diagnostic technique, degree of pulmonary resection, and postoperative morbidity and mortality to determine whether surgery is a viable treatment option in this subset of patients. Results. Twenty-three of 25 patients had a minithoracotomy compared with 2 who had video-assisted thorascopic surgery resection only. Thirteen had wedge resections, 9 had lobectomies, and 3 had segmentectomies. Early surgical morbidity was 2 of 25, involving 1 pneumothorax and 1 empyema. In-hospital mortality was 2, with 1 death primarily related to surgery. Median survival was 342 days, and survival was significantly better in patients with only one lesion. No patient experienced late recurrence of invasive pulmonary fungal infection. Resected pulmonary tissue also provided the best chance for a proven diagnosis in 19 of 25 (76%). Conclusions. This study confirms that pulmonary resection in high-risk immunocompromised patients with suspected invasive fungal infection can be carried out with excellent operative morbidity and mortality. (Ann Thorac Surg 2009;87:1532 8) 2009 by The Society of Thoracic Surgeons Accepted for publication Feb 24, Address correspondence to Dr Antippa, Department of Cardiothoracic Surgery, Royal Melbourne Hospital, Victoria, 3052, Australia; phillip.antippa@mh.org.au. Neutropenic patients are at high risk of developing invasive fungal infections (IFI), particularly those patients undergoing chemotherapy for hematologic malignancies and allogeneic stem cell transplantation (SCT) [1, 2]. The annual incidence of IFI is now 3.7% to 8.8% in at risk patients following treatment with high dose chemotherapy for acute leukemia or allogeneic bone marrow transplantation [1, 3]. The epidemiology of fungal infections has changed in the last two decades with the use of fluconazole, and now molds have replaced Candida species as the most common cause of IFI [3]. Invasive aspergillosis is the most common mold infection, and the lungs are the site of infection in more than 90% of patients [4]. However, the increasing use of broad-spectrum antifungal prophylaxis to prevent invasive aspergillosis may allow fungi other than Aspergillus species to become more frequent causes of infection [5, 6]. Furthermore, infections occurring despite antifungal prophylaxis mandate aggressive diagnostic procedures to determine the cause of infection and appropriate antifungal therapy. The risk of IFI is directly related to the duration of neutropenia as well as corticosteroid use and the presence of graft-versus-host disease after SCT [1, 2]. Neutropenic patients with IFI still have high morbidity and mortality despite improved medical therapy, the availability of newer antifungal agents, and the tendency to treat patients earlier before waiting for a confirmed diagnosis of invasive aspergillosis [3, 7]. Recent multicenter reviews of patient survival from invasive aspergillosis show a 4-month mortality of 62% in all hematology patients [8] and a 77% attributable mortality at day 150 after infection in allogeneic SCT recipients [3]. The report by Jantunen and colleagues [9] on a series of allogeneic SCT recipients with invasive aspergillosis managed medically also had only a 37% response to treatment and 10.5% with a complete response; median survival after diagnosis was 37 days. Despite these limited results, medical management has been the cornerstone of treatment. The role of surgery, however, is controversial, as the risk of lung resection in the context of neutropenia and thrombocytopenia is unclear. American and European guidelines for surgical intervention in the treatment of invasive aspergillosis include a pulmonary lesion contiguous with a large vessel or pericardium, a single lesion as the source of hemoptysis, erosion into the pleural space and ribs, and on a case by case basis in localized extrapulmonary lesions [5, 10]. Other authors recommend resection of devitalized tissue particularly when Zygomycetes or Scedosporium species are involved as well as resection of a localized Aspergillus lesion before allogeneic transplanta by The Society of Thoracic Surgeons /09/$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg THEODORE ET AL 2009;87: SURGERY FOR IFI 1533 tion [6, 11]. Few centers undertake surgical intervention outside of these guidelines [12]. However, contemporary evidence shows surgery can be both diagnostic and therapeutic, leading to better outcomes when compared with medical management alone [7, 13]. To further inform this debate we describe a series of neutropenic patients with hematologic malignancies undergoing resection for fungal infection in an Australian tertiary-care referral teaching hospital. Material and Methods Samples and Setting Institutional ethics committee approval was obtained, and the requirement for patient consent was waived. Included in the analysis were all neutropenic patients with hematologic malignancies being treated with highdose chemotherapy for acute leukemia or allogeneic SCT, who underwent lung resection for proven, probable, or possible IFI between 2000 and This represented one third of hematology patients admitted for presumed IFI during the same period. Twenty-three patients in this series had received antifungal prophylaxis before surgery with at least one of the following (patients were entered into a separate study to determine the best prophylactic agent): oral itraconazole, voriconazole, or posaconazole, although 1 patient received only fluconazole and 1 patient did not receive antifungal prophylaxis. All neutropenic patients with fever persisting beyond 96 hours or recurring after response to broad-spectrum antibacterial agents underwent highresolution computed tomography (CT) of the chest. Bronchoalveolar lavage was performed routinely on those who had radiologic abnormalities suggestive of IFI (halo Fig 1. Computed tomographic scan of the chest with peripheral aircrescent sign. Fig 2. Computed tomographic scan chest with halo sign. sign, nodules, air crescent, or localized pathologic disease in the absence of a microbiologic diagnosis; Figs 1 and 2). Computed tomography-guided core biopsy was performed when feasible, and panfungal polymerase chain reaction was performed on resected lung tissue in some patients after 2002 as part of an evaluation of this test [14]. Serum and bronchoalveolar lavage galactomannan testing was not performed. Patients were operated on if radiologic findings suggested complete resection was possible, or in diffuse disease when histologic confirmation was requested to aid antifungal treatment. Definitions Neutropenia was defined as an absolute neutrophil count of less than cells/l. Invasive fungal infection was classified according to the internationally accepted definitions as proven (when there was sterile site tissue evidence of hyphae or a positive culture), probable (when host, clinical, and microbiologic criteria were met), and possible (when host and clinical factors but no microbiologic criteria were present but there was no microbiologic confirmation of infection) [15]. Early mortality was defined as death occurring within 30 days of surgery. In-hospital mortality was defined as mortality during current hospital admission owing to any cause and late mortality was death at greater than 30 postoperative days. PERIOPERATIVE AND POSTOPERATIVE SUPPORTIVE CARE. Platelet and granulocyte infusions were given to maintain platelet counts greater than /L and granulocyte counts greater than /L. Recombinant human granulocyte colony-stimulating factor was used in severely neutropenic patients. Antibiotic and antifungal medications were continued in the perioperative and postoperative

3 1534 THEODORE ET AL Ann Thorac Surg SURGERY FOR IFI 2009;87: periods. Patients were extubated in the operating room, and pain relief was administered by means of an epidural when patients had adequate platelets. All patients had patient-controlled analgesia. Initial postoperative management was in the high-dependency unit of the cardiothoracic ward, and patients were transferred to the hematology ward after removal of chest drains. Length of postoperative antifungal therapy was at the discretion of the treating hematologist. Most patients had a prolonged hospital stay in the hematology unit. Surviving patients were followed up in the hematology outpatient department. Statistical Analysis Data were analyzed using the Statistical Package for the Social Sciences (SPSS), version 15 (SPPS Inc, Chicago, IL). The distribution of continuous variables, with the exception of age, was skewed, and logarithmic transformations did not increase normality. As such, medians are reported instead of means and the measures of dispersion are 25th (quartile 1 [Q1]) and 75th (quartile 3 [Q3]) percentile ranks of the distribution. Group comparisons used 2 or Mann-Whitney U tests. Actuarial survival curves were graphed using the Kaplan Meier method to illustrate overall sample survival and to show survival differences for patients who had diagnostic versus therapeutic resections. Results Disease Characteristics Between September 2000 and May 2007, 25 patients were identified as undergoing pulmonary resection for IFI. All Table 1. Disease Characteristics a Characteristic N 25 Diagnosis Acute myelocytic leukemia Acute lymphocytic leukemia 3 12 Non-Hodgkin s lymphoma 2 8 Chronic lymphocytic leukemia 1 4 Myelodysplasia 1 4 Symptoms Lung related 7 28 Nonspecific CT scan findings Single location Multiple locations 5 20 Diffuse infiltration 3 12 Day of surgery Leukocyte count ( 10 9 /L) , 6.78 Neutrophil count ( 10 9 /L) , 4.85 Platelet count ( 10 9 /L) , Neutropenic patients Thrombocytopenic patients a Data are presented as number and % or median, quartile 1, and quartile 3. CT computed tomographic. Table 2. Diagnosis of Suspected Invasive Fungal Infection Investigation had hematologic disorders and a recent history of prolonged febrile neutropenia with documented periods of neutrophil counts less than /L after high-dose chemotherapy (Table 1). There were 10 (40%) men and 15 (60%) women in the cohort. The mean age was years (range, 20 to 72 years) at the time of surgery. The most frequent underlying hematologic diagnosis was acute myeloid leukemia. Diagnosis Eight (32.0%) patients had multiple infiltration sites on CT scan; however, the majority of infiltrates were localized lesions or halo signs (Table 1). Five (20.0%) patients underwent CT-guided core biopsy that failed to achieve histologic or microbiologic confirmation of the diagnosis. Bronchoscopy with bronchoalveolar lavage was positive in only 10% (2 of 21) of patients tested. Nineteen patients had proven IFI on the basis of hyphae visualized on histologic specimens (n 12), a cultured organism from lung tissue (n 6), or detected by polymerase chain reaction (n 1; Table 2). Culture-diagnosed species identified included two cases of Scedosporium apiospermum and one each of Aspergillus niger and Scedosporium prolificans. All other organisms identified were Aspergillus fumigatus. Table 3. Surgical Management Characteristic N 25 % Approach Minithoracotomy VATS Procedure Wedge Single lesion Multiple lesion Lobectomy Segmentectomy Complications Minor: pneumothorax Major: empyema Early mortality VATS video-assisted thoracoscopic surgery. Positive Results CT-guided biopsy 0/5 (0%) BAL 2/21 (9.5%) Surgical resection 19/25 (76.0%) Hyphae 12/19 (63.2%) Culture 6/19 (31.6%) PCR 1/19 (5.3%) BAL bronchoalveolar lavage; CT computed tomographic; PCR polymerase chain reaction.

4 Ann Thorac Surg THEODORE ET AL 2009;87: SURGERY FOR IFI 1535 Surgical Management Patients had surgery under general anesthesia, using double-lumen intubation and a limited lateral musclesparing thoracotomy. Twenty-three (92.0%) had a minithoracotomy, and 2 (8.0%) had video-assisted thoracoscopic surgery (Table 3). Two patients had primary video-assisted thoracoscopic surgery that was converted to a small, lateral muscle-sparing thoracotomy. Patients undergoing video-assisted thoracoscopic surgery resection were more likely to have diffuse bilateral disease, and resection was primarily diagnostic. Three (12.0%) patients with diffuse bilateral fungal lesions had resection performed on the lung that was most affected. Early Outcomes There were no deaths directly attributable to operative intervention within the first 30 days and no reoperations for bleeding. However, hospital mortality was 8% as 2 patients died before discharge, 1 at day 32 of cerebral aspergillosis and brain stem herniation and 1 at day 80 of bacterial sepsis. One patient experienced a pneumothorax after tube removal, and 1 patient had an empyema that required decortication. Two minor complications included a pleural effusion and a pneumothorax, both of which required intercostal drainage. Late Outcomes In December 2007, 18 (72.0%) patients were deceased. Median survival after surgery was 342 days (Q1, 124; Q3, Fig 4. Survival comparison after diagnostic versus therapeutic resection. Therapeutic resection is plotted as the dashed line, versus diagnostic procedure as the solid line. Censored patients in the therapeutic group are represented by crosses ) for the total sample as illustrated in Figure 3. There was insufficient evidence to suggest a difference in survival time between young (less than 60 years of age, 732 days; Q1, 123.7; Q3, ) versus older patients (60 years or older, 259 days; Q1, 109; Q3, 670.5; z 1.36; p 0.174). Deceased patients (n 18, 72.0%) median survival was 239 days (Q1, 102.5; Q3, 666.2). For patients alive at last follow-up in December 2007 (n 7, 28.0%), median survival was 33.2 months (Q1, 12.6; Q3, 65.8). Not surprisingly there was a significant relationship between early or late mortality and whether patients had single or multiple lesions and because 3 patients had a primarily diagnostic, not therapeutic, procedure for diffuse disease. Comparison of survival for single or multiple lesions is shown in Figure 4. Essentially patients with single lesions (n 12, 70.6%) were more likely to survive more than 90 days after surgery than patients with multiple lesions (n 2, 25.0%; 2 (1) 4.59; p 0.032; 95% confidence interval, 1.07 to 48.6). Fig 3. Total survival after lung resection for invasive fungal infection. Survival function is plotted as the solid line, with censored patients represented by crosses. Comment Patients undergoing chemotherapy for acute leukemia and allogeneic SCT are at the highest risk for IFI [16]. Mortality remains high even in patients treated at the earliest suspicion of IFI without microbiologically proven infection [17]. Although the role of surgery is not well defined in these patients, it has several potential benefits. This report highlights the diagnostic and therapeutic role

5 1536 THEODORE ET AL Ann Thorac Surg SURGERY FOR IFI 2009;87: of surgery for pulmonary IFI (predominantly invasive aspergillosis) in this subset of patients. Diagnosis of IFI in these patients is difficult as the majority of patients present with pyrexia of unknown origin unresponsive to antibiotics. Unlike other series, most of our patients presented with nonspecific symptoms and few had symptoms related to the respiratory tract. Most patients were taken to surgery with a presumptive diagnosis of invasive pulmonary aspergillosis from suspicious CT scans in the setting of febrile neutropenia [16]. High-resolution CT scans play a crucial role in arriving at a clinical diagnosis in this difficult set of patients. The halo sign has emerged as a highly suggestive sign for early invasive aspergillosis during neutropenia [18]. Other frequent signs seen in these patients are ground-glass appearance and cavitation. Surgical biopsies and resected specimens give a confirmed diagnosis with extremely good accuracy, often on the same day, which expedites the choice of appropriate antifungal treatment. Importantly, the biopsy findings in our patients detected organisms other than Aspergillus species in 3 of the 25 cases. Thus, even when a microbiologic diagnosis was not made, surgical resection and appearance of hyphae seen in tissue was still helpful in determining whether the infection was likely to be aspergillosis or another diagnosis such as infarction or fibrosis, which occurred in 4 patients. Nonsurgical investigative modalities are plagued with low yield, and have low specificity and sensitivity, particularly in the presence of empiric antifungal therapy. In our series, bronchoalveolar lavage cultured fungus in only 10% (2 of 21) of patients who had the procedure; previous series quote figures up to 40% [19]. Other new tests such as enzyme-linked immunosorbent assay for detection of galactomannan antigen are plagued by low specificity and sensitivity, especially in those receiving antifungal therapy, and an inability to diagnose IFIs caused by molds other than Aspergillus [16, 19], whereas molecular diagnostic tests such as polymerase chain reaction appear promising but have not been extensively validated as diagnostic tools [20]. Recently one group described the success of CTguided biopsy in diagnosing invasive pulmonary fungal infection with the specimen minced, homogenized, and centrifuged and then submitted to calcofluor white stain, galactomannan, and Aspergillus polymerase chain reaction testing, but this method requires further evaluation [21]. Computed tomography-guided biopsy did not yield a diagnosis in the 5 patients in our series who underwent this procedure, although sections from biopsies were examined by standard histologic stains only (Grocott methenamine silver stain, hematoxylin and eosin, and periodic acid Schiff). This may reflect only the prior use of antifungal medication and is not reflective of CTguided biopsies on patients in whom surgery was not subsequently performed. However, given the poor diagnostic yield with current standard histologic preparations, the benefits of surgical resection to provide diagnosis may be superior to CT-guided biopsy in patients with suitable lesions. Therapeutic surgery was the most common indication for intervention in our series (22 of 25 patients). Complete freedom from residual and recurrent fungal infection was obtained in all patients who underwent a therapeutic resection. Three patients had a purely diagnostic procedure because of diffuse bilateral lung lesions considered too widespread to attempt complete resection. Patients with diagnosed or suspected fungal masses had surgery for eradication of infection before transplantation. Efficacious treatment is particularly important when patients are waiting for SCT transplantation. Patients diagnosed with IFI who are undergoing repeated cycles of chemotherapy or progressing to SCT are at risk of reactivation of the IFI [22]. Patients with fibrosis and obliterative bronchiolitis only can progress to early transplantation, and those in whom a diagnosis of IFI is made can be managed with appropriate antifungal therapy before further immunosuppression. Four patients during the study period had a diagnosis of infarction or fibrosis; these patients were able to quickly progress to further chemotherapy and SCT required for their underlying malignancy. Two other patients who were diagnosed to have IFI on histologic examination had their antifungal regimen changed to a more appropriate agent. One of the factors influencing recurrence of IFI after allogeneic SCT is duration of antifungal therapy before transplantation, and a definitive diagnosis of IFI may aid in planning transplant strategies [23]. The rate of relapse and recurrence of IFI after resection has also remained extremely low in most series, making a strong case for early surgical intervention in this group of patients and consideration of combined surgical and medical therapy [16]. In a minority of patients with multiple areas of fungal disease involving both lungs, medical management was the first line of treatment and, with time, serial CT scans revealed either the regression, stasis, or progression of lesions. Those lesions that have progressed can then be targeted for surgical resection. Other, more aggressive groups achieve the same result with bilateral staged resections or video-assisted thoracoscopic surgery on one side and open resection on the other. Some groups have performed video-assisted thoracoscopic surgery resections with excellent results; however, there was a high rate of conversion to thoracotomy and several limitations of the technique: inadequate opening of staplers, difficulty with pleural invasion, and resection for deeply located lesions [24]. Mortality and morbidity were major concerns in neutropenic patients who often had concurrent thrombocytopenia. Our mortality rates and morbidity rates have been comparable if not better than previous reports. In our series, there was no surgery-related mortality within 30 days. One later death, at 32 postoperative days, was the result of progression of systemic fungal infection. Another at 80 postoperative days was owing to empyema and bacterial sepsis; total mortality was 8% (n 2). Major morbidity included one case of postoperative empyema, and there were no reexploration for bleeding. This confirms the findings of several series published recently that have shown that lung resections, both open and

6 Ann Thorac Surg THEODORE ET AL 2009;87: SURGERY FOR IFI 1537 minimally invasive, can be performed with extremely low morbidity and mortality [7, 12, 24]. Bleeding and infection rates have been low despite the fact that many of the patients were neutropenic and thrombocytopenic at the time of surgery, and other complications in published series including prolonged air leaks, pleural aspergillosis, prolonged ventilation, and recurrent pleural effusions were not encountered [12, 16, 25]. Although medical management with voriconazole and amphotericin B remain the mainstay of therapy [5, 6, 10], further evaluation of surgical therapy should be undertaken as the benefit of timely definitive diagnosis and instigation of early alterations of treatment strategies can improve outcomes in these patients. We also speculate that if the lesion is large, penetration of antifungal medication may not be adequate. The extent of resection is also a major consideration. We believe that if there is only one definitive focus of infection it is reasonable to do a wide wedge resection of the lesion. Tissue preservation is vital, and multiple wedge resections are preferable to lobectomy or segmentectomies if adequate clearance of disease can be achieved. We have performed three wedge resections from the same lobe on one occasion and have been able to preserve a significant amount of functioning lung tissue. Open thoracotomy and palpation of the lungs remains an important part of the operation to minimize tissue loss and at the same time obtain an adequate margin around the invasive mass. In conclusion, the benefits of surgery in cohorts such as this are twofold. In the first instance it appears surgery is the optimal modality for definitive diagnostic purposes. In addition, it seems there are therapeutic benefits for these difficult to treat patients, especially when surgery is performed in conjunction with maximal medical treatment and optimization of preoperative fitness. Mortality and morbidity were rarely surgical, and generally occurred secondary to the underlying hematologic disease with much less frequency than the reported mortality of patients having medical therapy in isolation. The evidence in this paper is, however, limited by the nature of case series design, and thus it is difficult to draw conclusions as to whether medical therapy alone is superior to the combination of medical and surgical intervention. Given the relatively small patient numbers and variability in the primary hematologic disorder, the location of invasive pulmonary aspergillosis disease, and the type of resection undertaken, it is also difficult to determine in which patients surgical intervention will benefit the most. What one can surmise though, is that performing pulmonary resections in this extremely unwell subgroup is feasible, with low operative morbidity and mortality. No grants or financial support were received in the preparation of this manuscript. We wish to thank Dr Suvitesh Luthra, MCh (CTVS), for his help with data collection. References 1. Thursky K, Byrnes G, Grigg A, Szer J, Slavin M. Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell transplantation. Bone Marrow Transplant 2004;34: Rex JH, Anaissie E, Boutati E, Estey E, Kantarjian H. Systemic antifungal prophylaxis reduces invasive fungal in acute myelogenous leukemia: a retrospective review of 833 episodes of neutropenia in 322 adults. Leukemia 2002;16: Pagano L, Caira M, Nosari A, et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study. Clin Infect Dis 2007;45: Patterson T, Kirkpatrick W, White M, et al. Invasive Aspergillosis. Disease spectrum, treatment practices, and outcome. Medicine 2000;79: Walsh TJ, Anaissie E, Denning D, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008;46: Thursky KA, Playford E, Seymour J, et al. Recommendations for the treatment of established fungal infections. Intern Med J 2008;38: Reichenberger F, Habicht J, Kaim A, et al. Lung resection for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases. Am J Respir Care Med 1998;158: Cordonnier C, Ribaud P, Herbrecht R, et al. Prognostic factors for death due to invasive aspergillosis after hematopoietic stem cell transplantation: a 1-year retrospective study of consecutive patients at French transplantation centres. Clin Infect Dis 2006;42: Jantunen E, Ruutu P, Piilonen A, Volin L, Parkkali T, Ruutu T. Treatment and outcome of invasive Aspergillus infections in allogenic BMT recipients. Bone Marrow Transplant 2000; 26: Herbrecht R, Fluckiger U, Gachot B, Ribaud P, Thiebaut A, Cordonnier C. Treatment of invasive candida and invasive aspergillus infections in adult haematological patients. Eur J Cancer 2007;5(Suppl 5): Sipsas NV, Kontoyiannis DP. Clinical issues regarding relapsing aspergillosis and the efficacy of secondary antifungal prophylaxis in patients with hematological malignancies. Clin Infect Dis 2006;42: Matt P, Bernet F, Habicht J, et al. Predicting outcome after lung resection for invasive pulmonary aspergillosis in patients with neutropenia. Chest 2004;126: Salerno C, Ouyang D, Pederson T, et al. Surgical therapy for pulmonary aspergillosis in immunocompromised patients. Ann Thorac Surg 1998;65: Zeng X, Kong F, Halliday C, et al. Reverse line blot hybridization assay for identification of medically important fungi from culture and clinical specimens. J Clin Microbiol 2007; 45: De Pauw B, Walsh T, Donnelly P, et al. 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7 1538 THEODORE ET AL Ann Thorac Surg SURGERY FOR IFI 2009;87: The Society of Thoracic Surgeons: Forty-Sixth Annual Meeting 18. Bruno C, Minniti S, Vassanelli A, Pozzi-Mucelli R. Comparison of CT features of aspergillus and bacterial pneumonia in severely neutropenic patients. J Thorac Imaging 2007;22: Marr AK, Laverdiere M, Gugel A, Leisenring W. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis 2005;40: Donnelly JP. Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer but still a ways to go. Clin Infect Dis 2006;42: Lass-Florl C, Resch G, Nauchbaur D, et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis 2007;45: Grigg AP, Slavin MA. Minimizing the risk of recurrent or progressive invasive mold infections during stem cell transplantation or further intensive chemotherapy. Transpl Infect Dis 2008;10: Martino R, Parody R, Fukuda T, et al. Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: a retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood 2006; 108: Gossot D, Validire P, Vaillancourt R, et al. Full thoracoscopic approach for surgical management of invasive pulmonary aspergillosis. Ann Thorac Surg 2002;73: Habicht J, Matt P, Passweg J, et al. Invasive pulmonary fungal infection in hematologic patients: is resection effective? Hematol J 2001;2: Mark your calendars for the Forty-Sixth Annual Meeting of The Society of Thoracic Surgeons (STS) to be held at the Greater Fort Lauderdale-Broward County Convention Center, Fort Lauderdale, Florida, from January 25 27, The meeting is open to all physicians, residents, fellows, engineers, perfusionists, physician assistants, nurses, or other interested individuals. Meeting attendees will be provided with the latest scientific information for practicing cardiothoracic surgeons. Attendees will benefit from traditional Abstract Presentations, as well as Surgical Forums, Breakfast Sessions, Surgical Motion Pictures, and Wet Lab sessions. Parallel sessions on Monday and Tuesday will focus on specific subspecialty interests. An advance program with a registration form, hotel reservation information, and details regarding spouse/ guest activities will be mailed to STS members this fall. Nonmembers may contact the Society s secretary, Douglas E. Wood, MD, to receive a copy of the advanced program; however, detailed meeting information will be available on the STS website at Douglas E. Wood, MD Secretary The Society of Thoracic Surgeons 633 N. Saint Clair St, Suite 2320 Chicago, IL Telephone: (312) Fax: (312) sts@sts.org website: by The Society of Thoracic Surgeons Ann Thorac Surg 2009;87: /09/$36.00 Published by Elsevier Inc