Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
– Diffuse Lung Disease chapter 48 – ROLE OF LUNG BIOPSY IN INTERSTITIAL LUNG DISEASE Vitaliy Poylin, Malcolm M. DeCamp Jr. Key Points ▪ Thoracic surgeons evaluate two distinct patient populations with interstitial lung disease: those with acute respiratory illness, often with impaired immunity, and those with progressive dyspnea and an insidious decline in lung function. ▪ The goal of a surgical lung biopsy is to define pathology leading to revised therapy that in turn leads to improved outcome. The goal is not to merely make a diagnosis. ▪ Surgical lung biopsy has greater utility in classifying the disorder and leading to effective therapy if it is performed early in the acute or chronic illness. ▪ Thoracoscopic and open lung biopsy techniques provide equivalent diagnostic information. ▪ Thoracoscopy facilitates sampling of divergent areas of the same lung and results in less trauma and faster recovery compared with a limited thoracotomy. Interstitial lung disease (ILD) is a heterogeneous group of lung conditions of both known and unknown etiology. There are more than 200 different diseases in the group, which broadly can be divided into infectious, occupational, iatrogenic, granulomatous, malignant, autoimmune/connective tissue disorder–related, and idiopathic categories (Table 48-1) (Kim et al, 2006).[1] Despite disparate etiologies, they often have similar clinical features, including dyspnea and hypoxemia, restrictive spirometry, depressed diffusion capacity, and a diffusely abnormal interstitium on lung imaging. Patients with ILD present a therapeutic conundrum for clinicians because these varied disorders with similar clinical presentations often require radically different therapies (e.g., antimicrobial therapy versus augmented immunosuppression). TABLE 48-1 -- Classification of Interstitial Lung Disease Infectious Idiopathic Occupational Iatrogenic Granulomatous Malignant Autoimmune/CTD Bacterial UIP Asbestos Radiation Sarcoidosis Lymphoma Scleroderma Fungal DIP Silica Bleomycin Histiocytosis Lymphangitic Polymyositis carcinomatosis Viral NSIP Coal Amiodarone Hypersensitivity Dermatomyositis Infectious Idiopathic Occupational Iatrogenic Mycobacterial COP Organic Protozoan Heavy metal RB-ILD Methotrexate Granulomatous Malignant Autoimmune/CTD Rheumatoid arthritis SLE Adapted from Kim DS, Collard HR, King TE Jr: Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc 3:285-292, 2006. COP, cryptogenic organizing pneumonia; CTD, connective tissue disorder; DIP, desquamative interstitial pneumonitis; NSIP, nonspecific interstitial pneumonitis; RB-ILD, respiratory bronchiolitis– associated interstitial lung disease; SLE, systemic lupus erythematosus; UIP, usual interstitial pneumonitis. CLINICAL PRESENTATION When patients with ILD are encountered by a surgeon, they are usually symptomatic with progressive dyspnea, nonproductive cough, occasional weight loss, and fever. Known environmental exposure, a prior malignancy, or a detailed drug history may suggest a cause in a fraction of these cases. Insidious onset is the most common presentation, although fulminant onset is more common in patients who are immunocompromised. Physical examination often reveals nonspecific findings consistent with hypoxemia (clubbing, tachypnea, and tachycardia), wheezing, and/or fine or coarse crackles. Extrapulmonary manifestations of collagen-vascular disease, as are seen in scleroderma or systemic lupus erythematosus (SLE), may help narrow the differential diagnosis. Pulmonary hypertension with a fixed split second heart sound, peripheral edema, and/or ascites speaks to the chronicity of the underlying process. Spirometry usually shows a nonspecific restrictive pattern with symmetrical reduction in both forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) as ILD progresses. Worsening diffusing capacity of the lung for carbon monoxide (D LCO) is perhaps the most sensitive measure to detect disease progression. From a surgical standpoint, the issue with such a nonspecific presentation is that too few patients get referred for biopsy early in the disease, when a specific diagnosis can potentially make a difference. By the time a surgeon encounters these patients, many have progressed significantly toward endstage fibrotic disease, with mature collagen replacing and expanding the air-blood barrier. At such a time, the utility of an invasive, diagnostic surgical intervention and even the subsequent institution of potentially toxic pharmacologic therapy is questionable. IMAGING Routine chest radiographs contribute little to the timely diagnosis of ILD. Radiographic changes are not obvious early in the process. As disease progresses, diffuse linear and reticular infiltrates are seen and are commonly more pronounced in the lower lobes. High-resolution computed tomography (HRCT) provides a detailed image of lung parenchyma and differentiates areas of active disease with ground-glass opacification (Fig. 48-1) from areas of the common end-stage so-called honeycomb changes of fibrosis and scarring (Fig. 48-2). These distinctions become critical when choosing a biopsy site if one is needed. FIGURE 48-1 Axial image with lung windowing from an HRCT. Slice taken at the level of the inferior pulmonary veins. Note the diffuse areas of ground-glass opacification suggestive of active inflammation affecting both lungs. FIGURE 48-2 Axial image with lung windowing from an HRCT of a patient with advanced interstitial lung disease. Slice taken below the level of the inferior pulmonary veins depicts extensive peripheral fibrosis with honeycomb changes affecting the left lower lobe more than the right. AMBULATORY DIAGNOSTIC MODALITIES Routine sputum cultures are usually obtained but are likely to be relevant only in patients with predisposing comorbidities or historical factors such as active immunosuppression, unique occupational or environmental exposures, or exotic travel. The low diagnostic yield from sputum cultures can be marginally improved by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) for microbiology and cytology studies. These two modalities are useful in identifying certain infectious sources, such as Pneumocystis jiroveci (Pneumocystis carinii) pneumonia (PCP) and fungal infections. Transbronchial biopsy has been reported to have a success rate of 25% to 59% in establishing a specific histologic diagnosis.[2] The low complication rate of about 3% makes this a useful addition to bronchoscopy and BAL. This technique is very successful in accurately diagnosing such conditions as sarcoidosis and lymphangitic carcinomatosis. Yet, small sample size and the limited number of accessible sites limits its use in most cases of ILD. Despite its ambulatory application and less invasive profile, flexible fiberoptic bronchoscopy with BAL and transbronchial biopsy remains inferior to surgical lung biopsy if the end point is a discrete histologic diagnosis. [3] SURGICAL LUNG BIOPSY The debate regarding the role of surgical lung biopsy for the patient with ILD centers on three questions: 1. Is a biopsy necessary to establish a diagnosis? 2. Will establishing a histologic diagnosis change therapy? 3. Will biopsy-driven therapy change outcome? Historical reports failed to delineate changes in therapy and overall outcome. These studies were largely retrospectiveand included patients with diverse presentations, including those who were severely ill and already confined to an intensive care unit alongside other patients who remained ambulatory and otherwise functional.[4] A more timely and relevant debate asks whether the diagnosis can be established by noninvasive means alone. The ubiquitous availability of HRCT has made this a feasible concept. Two recent prospective studies have validated a noninvasive diagnostic strategy for selected patients, but both emphasized the importance of surgical biopsy for establishing diagnosis in clinically unclear cases. Hunninghake and colleagues[5] reported that, when evaluating clinical and radiologic data, an experienced pulmonologist and radiologist were accurate in diagnosing usual interstitial pneumonitis (UIP) in 90% and 77% of cases, respectively. However, when asked for a definitive diagnosis, the accuracy dropped to 75% to 77%. Raghu and colleagues[6–8] similarly found that the accuracy of radiologic, clinical, and transbronchial diagnosis was 90% to 97% specific for interstitial pulmonary fibrosis (IPF), but sensitivity remained low at 50% to 78%. For non-IPF ILD, sensitivity and specificity were both low at 62% to 70%. Both studies concluded that, although surgical biopsy may not be necessary for some cases of IPF (especially UIP), it remains essential in more than one third of patients. It is also important to point out that these studies surveyed only experienced pulmonologists and radiologists from centers of recognized authority in ILD. Overall, it is clear that lung biopsy increases the chance of definitive tissue diagnosis in almost all patient populations. The next question is whether establishing the diagnosis will make a difference in patient management or outcome. Historical reports noted that surgical lung biopsy achieves a discrete diagnosis in 37% to 93% of cases.[2–4] Although it is difficult to derive useful information from these retrospective analyses, if we try to tease out the effects on the specific patient groups, a few distinct patterns emerge. For immunocompetent patients, two recent reports found that a discrete diagnosis caused a change in therapy in 57% to 63% of cases (Kramer et al, 1998).[9,10] In the few studies that reported overall benefit and survival, change in therapy for immunocompetent patients resulted in moderate likelihood of patient benefit (18%–26%).[9,10] At the same time, the overall operative morbidity and mortality relative to the actual procedure for these patients remained sufficiently low to make lung biopsy a rational and safe addition to management. Overall, in immunocompetent patients without respiratory distress whose HRCT shows minimal end-stage fibrotic change, biopsy is likely to change or guide therapy, and there is some evidence of improvement in survival (Tables 48-2 and 48-3). TABLE 48-2 -- Characteristics of Idiopathic Forms of Interstitial Lung Disease Characteristic UIP NSIP COP RB-ILD Mean age at presentation (yr) 57 49 42 Onset Insidious Subacute Subacute Insidious Smoking-related Increased risk No No Required Steroid-responsive No Yes Yes Slightly Complete recovery No Possible Yes Yes Mortality (%) 90 30 0 5 36 Adapted from Kim DS, Collard HR, King TE Jr: Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc 3:285-292, 2006. COP, cryptogenic organizing pneumonia; NSIP, nonspecific interstitial pneumonitis; RB-ILD, respiratory bronchiolitis–associated interstitial lung disease; UIP, usual interstitial pneumonitis. TABLE 48-3 -- Effect of Lung Biopsy (VATS and Open) on Change in Therapy and Outcome Author (Year) No. Patient Status % Change of % Change in Patients Therapy Outcome Lee et al[21] (2005) 196 Immunocompromised and immunocompetent 84 63 Kramer et al[9] 103 Immunocompromised 59 46[*] Author (Year) No. Patients Patient Status % Change of Therapy % Change in Outcome Immunocompetent 18 18 (1998) White et al[16] (2000) 63 Immunocompromised 57 26 Temes et al[10] (1999) 75 Immunocompetent 77 39 VATS, video-assisted thoracic surgery. * The mortality rate of this group was 39%. This pattern does not hold true for elderly or immunocompromised patients or those with end-stage disease. Patients with end-stage fibrosis on top of poor overall status have a higher rate of complications from anesthesia and the procedure itself, resulting in higher mortality and important morbidity, such as extra days of mechanical ventilation and prolonged air leak. [11,12] For ventilated immunocompetent patients, the rates of diagnosis and changes in therapy seem to be compatible with studies of ambulatory patients (approximately 46%). This ventilated group did experience significantly higher mortality (approaching 60%), calling into question the therapeutic index for lung biopsies once a patient is intubated. Timing of biopsy has also been debated. Delaying the biopsy may be related to some degree of therapeutic nihilism, given the absence of effective remedies for UIP (see Table 48-2)[1,11] or the pattern of diffuse alveolar damage seen frequently on specimens from critically ill patients. Performing biopsy late in the course of the disease decreases the chance of diagnosis due to coalescence of heavy indiscriminant fibrosis (honeycombing). These patients also are more likely to be in respiratory distress, which, as described earlier, reduces the likelihood that a tissue diagnosis will change the overall outcome and is certainly accompanied by much higher morbidity and mortality. In patients with fulminant forms of the disease, choosing the appropriate time may not be possible. This group of patients needs urgent or emergent lung biopsy if there is any clinical likelihood of a reversible process. IMMUNOCOMPROMISED PATIENTS Immunocompromised hosts comprise a large patient cohort affected by diffuse lung disease. Unlike patients with fibrotic lung disease, these hosts have a much higher risk of developing infectious complications. They are usually acutely ill with fever, cough, dyspnea, and progressive hypoxemia. They have often been exposed to other potential lung-damaging therapies, such as immunosuppressive drugs, chemotherapy, and irradiation. The prognosis for immunocompromised patients with pulmonary infiltrates is grim, especially if mechanical ventilation is required. In these circumstances, prompt diagnosis may be critical for survival. Because opportunistic infections can be a common cause of ILD, the workup for these patients begins with expeditious sputum culture, bronchoscopy, and BAL. Microbiologic examination of expectorated sputum and/or lavaged airway secretions has successfully identified a discrete diagnosis in 40% of immunocompromised patients.[13,14] For the balance of the patients in whom the diagnosis remains unclear, a more invasive approach is controversial. Many reports suggest that patients in whom lung biopsy is pursued do not fare better than those treated empirically.[12,15,16] Rano and colleagues[17] examined patients with hematologic malignancies and solid organ transplantation who presented with fever, dyspnea, and pulmonary infiltrates. Their overall mortality rate after surgical lung biopsy was 39% (see Table 48-2). Although prolonged time to diagnosis (>5 days) was predictive of the need for mechanical ventilation and of higher mortality, patients who underwent lung biopsy experienced outcomes similar to those diagnosed by less invasive methods. Despite a higher rate of finding a specific diagno-sis with biopsy than in immunocompetent patients, the extra information did not translate into salutary clinical outcomes. VIDEO-ASSISTED THORACIC SURGERY VERSUS OPEN BIOPSY For decades, open biopsy via a limited thoracotomy has been a gold standard for the surgical diagnosis of ILD. However, this approach is associated with increased pain, some limitation in accessible biopsy sites, and, in some uncontrolled studies, increased mortality. The emergence of video-assisted thoracic surgery (VATS) has proved to be an attractive alternative to the open technique. In largely retrospective studies, VATS has been shown to decrease the length of hospital stay and postoperative analgesic requirements, with better preservation of shoulder strength and range of motion and faster return to baseline pulmonary function.[18] There are also intriguing reports of a decrease in surgery-associated immunosuppression when patients undergoing VATS procedures were compared with those having open thoracotomy.[19] Direct comparisons between open and minimally invasive approaches suggest equivalency in diagnostic efficacy. Miller and coworkers (Miller et al, 2000),[20] in a prospective randomized study of 42 patients, found no clinical or statistical differences between the two techniques with regard to diagnostic yield, operating time, duration of chest tube drainage, postoperative length of stay, pain scores, complications, or spirometry measured both preoperatively and postoperatively. Ultimately, the choice between an open or VATS approach to lung biopsy is a clinical one based on patient anatomy, physiology, and the surgeon's facility with minimally invasive techniques. For ambulatory patients referred for biopsy to define ILD, VATS has largely supplanted thoracotomy as the procedure of choice, both for patients and for their referring physicians. These patients almost uniformly tolerate single-lung ventilation, which is a practical requirement for VATS lung biopsy. The need to convert VATS to a thoracotomy is rare and in most series is limited to 0% to 5.3%. This is usually related to the patient's inability to tolerate single-lung ventilation, pleural adhesions, or iatrogenic lung injury (Lee et al, 2005; Miller et al, 2000).[20–25] In contrast, the critically ill, severely dyspneic, oxygen-dependent or mechanically ventilated patient with a clear indication for surgical lung biopsy cannot tolerate single-lung ventilation. This necessitates the use of a thoracotomy (albeit limited) and brief intermittent periods of apnea to successfully biopsy the affected lung. LOCATION OF THE BIOPSY AND NUMBER OF SITES Contemporary imaging modalities such as HRCT guide the surgeon and represent an invaluable resource in performing high-yield biopsy. HRCT allows the surgeon to avoid areas of high fibrosis (see Fig. 48-2), the common end stage for multiple lung disorders, and guide biopsy to areas of active disease, which often appear as ground-glass opacifications (see Fig. 48-1). The site for biopsy in generalized disease remains controversial. Traditionally, the lingula was considered a poor site for the biopsy because the location was believed to be akin to the basilar aspects of the lower lobes, where fibrosis is usually more advanced.[26] More recent studies by Ayed, Miller, and Blewett and their colleagues have found that lingular (and right middle lobe) biopsies provide a diagnostic yield similar to that obtained from tissue sampled from the other areas of either lung. [24,26,28] The optimal number of samples is also debated. In a study of 100 patients with ILD, Qureshi and Soorae[25] demonstrated that a single biopsy from an active disease area is adequate for diagnosis. In their study, the site, size, number, or laterality of the biopsy specimen had no statistical influence on diagnostic yield, although there was a trend favoring two or more biopsies on the right lung. They and others have also confirmed that obtaining multiple biopsies does not increase postoperative morbidity. Given these data and the lack of evidence that multiple biopsies engender increased risk, we recommend two wedge biopsy samples from separate lobes when investigating idiopathic ILD in an ambulatory patient. The anatomic separation of such samples may assist the pathologist in classification of the underlying process and its severity. For the acutely ill, hospitalized, immunocompromised, or febrile patient, the underlying process is more likely to be diffuse. Multiple biopsies in this clinical scenario are not necessary as long as lesional tissue is obtained and confirmed by either gross examination or frozen section. Moreover, multiple biopsies in these more fragile patients are associated with important morbidity, including bleeding and prolonged air leaks. The more critical technical issue for these patients is to obtain sufficient tissue in a single wedge resection to allow for both histology and microbiologic analysis for bacteria, mycobacteria, fungi, viruses, and parasites. TECHNIQUE Surgical lung biopsy, whether performed via VATS or thoracotomy, is done with the patient under general anesthesia in the lateral decubitus position. Selective bronchial intubation and single-lung ventilation are mandatory for VATS. For left-sided biopsies, a bronchial blocker can be used, but it limits anesthetic maneuvers such as continuous positive airway pressure (CPAP) if intraoperative hypoxemia becomes problematic. Many ambulatory patients who present with hypoxemia requiring supplemental oxygen actually tolerate single-lung ventilation well. Similarly, the acutely ill patient with a focal lung process may tolerate selective ventilation for a brief procedure if the more diseased lung is the target for biopsy. If intraoperative hypoxia creates instability, brief periods of ventilation of the deflated lung or low levels of CPAP (5 cm H2 O) may allow the procedure to be completed without progressing to thoracotomy. The ipsilateral arm is abducted and strapped to an ether screen or arm holder to open the axilla and provide port access to the upper thorax (Fig. 48-3). This also facilitates a minithoracotomy low in the axilla if the patient cannot tolerate single-lung ventilation or extensive pleural adhesions are encountered. It is helpful to extend the operating table or flex the patient's hip to widen the lower intercostal spaces and deflect the hips down and away from the field. FIGURE 48-3 Proper positioning for surgical lung biopsy. The operative-side arm is abducted and secured with appropriate padding to an ether screen or arm holder to provide access to the axilla for either a utility thoracotomy or more apical port sites. If a video-assisted thoracic surgery (VATS) approach is planned, suggested camera positioning and port site options are indicated. (REPRINTED WITH THE PERMISSION OF THE CLEVELAND CLINIC FOUNDATION.) Three access ports are used (see Fig. 48-3). The camera port is usually placed in the seventh intercostal space in themidaxillary line. A 5- or 10-mm telescope with a 30-degree lens allows the camera to visualize the entire thorax. The lung is inspected, and the proposed site for biopsy (based on HRCT) is identified. The other two ports are usually placed under thoracoscopic guidance in the sixth or seventh intercostal spaces, posteriorly below the scapular tip and anteriorly below or immediately lateral to the breast. Attractive targets for biopsy include the upper lobe apices, the superior segment of the lower lobes, the basilar edges of the lower lobes, and any of the lobes along the fissures. The broad surfaces of the lung must be approached with care if there is underlying fibrosis or induration because the lung may not be compressible, resulting in malformed staples and air leak. The lung adjacent to the biopsy target is gently grasped with a ringed forceps, and an endomechanical stapler with a thick tissue cartridge is introduced and fired via the opposing port site. The instruments are reversed and a second staple firing is made, completing the wedge resection with intersecting staple lines. Remove all specimens from the chest in an impenetrable bag to prevent dissemination of disease within the pleura or seeding/contamination of the chest wall. Staple lines and each port site are inspected for hemostasis. This may necessitate relocating the camera to any or all port sites used. All staple lines should intersect to ensure pneumostasis. A single, small chest tube is placed via the original camera port and positioned in the posterior gutter with its tip in the apex. The lung is reinflated in a controlled fashion under thoracoscopic visualization to ensure re-expansion of all lobes and segments. The remaining port sites are reapproximated in layers with absorbable suture, including a subcuticular skin closure. Surgical lung biopsy for the intubated patient who requires high levels of inspired oxygen (Fio 2 ≥0.6) or positive end-expiratory pressure (PEEP ≥10) is best accomplished via a limited lateral or axillary thoracotomy. These patients are unlikely to tolerate single-lung ventilation, and manipulation of the airway to place a bronchial blocker or double-lumen endotracheal tube may precipitate a crisis. Again, the patient is positioned laterally with the arm abducted (see Fig. 48-3). A muscle-sparing approach lateral to the pectoralis major and anterior to the latissimus dorsi in front of the scapular tip exposes either lung along the fissure. The serratus anterior fibers can be split, with care taken not to divide the long thoracic nerve. Either the upper or the lower lobe can be biopsied through this exposure. We prefer to use the thick tissue cartridges and the endomechanical stapler even during open biopsies. Use of a more inferiorly placed chest tube incision to pass the stapler for one or several firings may facilitate the geometry of the biopsy. Very brief episodes of apnea during application of the stapler may help decrease pleural injury and subsequent air leak. A hemostatic survey, chest tube placement, and wound closure are standard as for any thoracotomy. Specimen handling depends on the immune status of the patient. Although a frozen section is rarely definitive, it often confirms the adequacy of the biopsy as representative of lesional tissue. Examination of fresh tissue by the pathologist may also guide further investigation, such as immunohistochemistry, fungal stains, flow cytometry, or electron microscopy. Granulomas are readily identified by frozen section. Although these lesions can be infective or noninfective, such tissues must always be cultured for fungal and mycobacterial organisms. In the immunocompromised patient, in addition to histology, tissue is routinely assayed for bacterial, fungal, acid-fast, viral, and protozoan organisms (especially PCP). Procedure-related morbidity and mortality are uncommon for VATS lung biopsy. The risk of death after an elective biopsy for ILD is reported at 0% to 2%, whereas the need to convert to open thoracotomy ranges from 0% to 5.3%. Other complications include hemothorax (0%–5%), persistent leak requiring prolonged chest tube drainage (1%–8%), and bleeding requiring re-exploration (1%– 2%). As described earlier, in immunocompromised patients or in clinical crises where intubation has occurred or is eminent, complication rates (especially respiratory failure, need for mechanical ventilation, and air leak) tend to be higher and are less likely to be caused by errors in technique. Operative mortality in this population may approach 40% to 60%, similar to that experienced by any critically ill patient in whom respiratory distress deteriorates into multisystem organ failure. [9, 11, 12, 16, 20– 25, 28] COMMENTS AND CONTROVERSIES Current CT imaging techniques and relatively noninvasive bronchoscopic biopsy strategies have lessened the need for surgical biopsy in patients with ILD. Opportunistic infections and sarcoidosis can usually be diagnosed by BAL and transbronchial biopsy, respectively. The CT imaging pattern of UIP is typical in its early stages. In many cases, surgical biopsy can be avoided. As the authors correctly point out, the goal of surgical biopsy is not only to establish a diagnosis but, more importantly, to effect a change in management to the patient's benefit. If this latter goal is unlikely to be achieved, the biopsy is of questionable utility, especially in a critically ill patient. VATS has proved to be an effective strategy for lung biopsy, but only in the elective situation of a stable patient. Adequate multifocal biopsies can be obtained by VATS, but use of a double-lumen tube and an arterial line and a more expensive operative setup are required. This commentator does not believe that VATS offers benefit over minimal anterolateral thoracotomy in terms of pain, postoperative morbidity, and operative time. This anterolateral approach is definitely superior in the critically ill patient. KEY REFERENCES Kim DS, Collard HR, King Jr TE: Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc 2006; 3:285-292. ▪ This paper led off a contemporary international symposium on ILD. The authors clearly define the distinct differences in clinical, radiologic, and histologic features; treatment; and prognosis for the noninfectious types of ILD. Kramer MR, Berkman N, Mintz B, et al: The role of open biopsy in the management and outcome of patients with diffuse lung disease. Ann Thorac Surg 1998; 65:198-202. ▪ In one of the first papers to emphasize the clinical utility of the biopsy for more than a diagnosis, these authors remind us to exercise judgment when considering risks and benefits of surgical lung biopsy. They documented an alarming operative mortality in the immunocompromised group, especially if the decision to proceed to biopsy was made late. Lee YC, Wu CT, Hsu HH, et al: Surgical lung biopsy for diffuse pulmonary disease: Experience of 196 patients. J Thorac Cardiovasc Surg 2005; 129:984-990. ▪ In this large recent series, the investigators report a high rate of change in both therapy and outcome based on the surgical biopsy. Unfortunately, it is difficult to tease apart the results between immunocompetent and immunosuppressed hosts. Miller JD, Urschel JD, Cox G, et al: A randomized, controlled trial comparing thoracoscopy and limited thoracotomy for lung biopsy in interstitial lung disease. Ann Thorac Surg 2000; 70:1647-1650. ▪ One of two small, prospective, randomized trials comparing open to thoracoscopic lung biopsy for ILD. The patients selected were largely ambulatory; critically ill, severely hypoxic, and ventilated patients were excluded. Given these restrictions, there were no differences in any of the measured surgical, pathologic, or clinical outcomes of the two groups. It is doubtful that the study was adequately powered to detect meaningful differences based on choice of incision. That the procedures yielded comparable results underscores the need for surgeons contemplating lung biopsy to select an approach that best meets the patient's needs. White DA, Wong PW, Downey R: The utility of open lung biopsy in patients with hematologic malignancies. Am J Respir Crit Care Med 2000; 161:723-729. ▪ Thoracic surgeons are often asked to evaluate patients whose bone marrow is failing because of disease or therapy. The authors, from Memorial Sloan Kettering Cancer Center, report that, although therapy changed in more than half of patients biopsied, the outcome changed only one quarter of the time.