Diagnostic value of surgical lung biopsy in diffuse interstitial lung diseases: comparison with clinical and radiological diagnosis

Mohamed Khairy MD*, Ahmad Abd-Alsadek MD˚, Waheed Mohamed MD˚.

*Department of cardiothoracic surgery, Benha Faculty of Meddicine, Benha University

˚ Pneumology department, Benha Faculty of Meddicine, Benha University

Abstract

Objective: To determine accuracy of the clinical/radiological evaluation for diffuse pulmonary infiltrates compared with the pathological result of the surgical lung biopsy (SLB) and to evaluate the need for the latter in this setting.

Methods: SLB was performed in 93 consecutive patients with diffuse interstitial lung diseases during the period from November 2002 to March 2008, through VATS in 53 patients or minithoracotomy in 40 patients. The presumptive diagnosis was based on clinical, radiological and non-invasive or minimally invasive diagnostic procedures and compared with the gold standard of histological diagnosis by SLB.

Results: In 65 patients (69.9%) clinical/radiological evaluation reached a correct diagnosis, and in 28 (30.1%) a new diagnosis was obtained unexpectedly by the SLB. In usual interstitial pneumonia (UIP) sensitivity, specificity, positive and negative predictive values for the clinical/radiological diagnosis were 76.2%, 76.4%, 84.9% and 70.2% versus 58.8%, 76.2%, 58.8% and 76.2% respectively in other types. The post-test probability for the clinical/radiological evaluation was 90% in patients with UIP versus 77% in other diseases.

Conclusions Patients with typical clinical and radiologic features of UIP will usually not need to undergo biopsy. The other interstitial pneumonias usually cannot be distinguished on the basis of clinical and CT features, and thoracoscopic or open lung biopsy will usually be necessary if a precise histologic diagnosis is required.

Introduction

Interstitial lung disease (ILD) represents a spectrum of disorders including those due to known etiology (as environmental exposures, drugs or autoimmune disease) and unknown etiology. The latter includes idiopathic interstitial pneumonias (IIPs), granulomatous disorders as sarcoidosis, and other rare diffuse parenchymal diseases. The IIPs include UIP, nonspecific interstitial pneumonia (NSIP) cryptogenic organizing pneumonia (COP) and other types. Of the over 150 recognized types of ILD; UIP is the most common and one of the most deleterious (1). ILD are classified together because of several common features (2). Nonspecific findings from physical examinations, radiographs, and spirometry, and the limited utility of transbronchial biopsy (TBB) complicate noninvasive approaches to the diagnosis of ILD, so clinicians often request for SLB whether performed by open or video-assisted thoracic surgery (VATS). However, the role of SLB remains controversial and many clinicians are reluctant to allow this invasive procedure to a high-risk group of patients without assurances that results will lead to a change in therapy for a significant number (3, 4, 5). Recently several studies have described the diagnostic accuracy of high-resolution CT in diffuse infiltrative lung diseases (6, 7, 8, 9). Consequently, the value of the biopsy on the diagnosis, treatment and outcome of these patients has become even more controversial (10).

Therefore, this study was carried out to evaluate the diagnostic accuracy of high-resolution CT in patients with diffuse pulmonary infiltrates, to compare the presumptive clinical/radiological diagnosis with the histological result of SLB and to determine whether SLB is worthwhile and for which groups and when this procedure was more likely to benefit patients.

Patients and methods

During the period from November 2002 to March 2008, a total of 93 consecutive patients with diffuse pulmonary infiltrates underwent surgical lung biopsy (SLB) for diagnostic and/or treatment purpose. There were 69 men and 24 women; with a mean age of 51.5+/-8 years (range, 39 to 67 years). The medical records of these patients were reviewed. These included the following: demographic data; clinical features; chest image study including high resolution CT (HRCT); status of respiratory function; specific diagnostic test, including sputum examination and culture; bronchoscopic examination; and bronchial lavage. The duration from onset of symptoms to the date of SLB in each patient was also recorded. Patients with a solitary nodule or other focal pulmonary processes were excluded and no patients were operated on while being artificially ventilated.

SLB was performed after achievement of general anesthesia through VATS (53 patients) or a 7-10 cm minithoracotomy (40 patients), which depended on the patient’s tolerance for single-lung ventilation or the presence of pleural adhesions that precluded the use of the thoracoscope. The site and number of lung biopsy specimens were determined by the findings on the chest radiographs or the computed tomographic scans. Usually, 1 or 2 biopsy specimens 2 to 3 cm in each margin were obtained. For VATS biopsy was performed by wedge resection using endo-cavity linear staplers for securing the pulmonary margins. For minithoracotomy, the lung specimen was cut off after clamping proximally, and tissue was secured by 2 rows of running sutures. The specimens were then sent to the pathologist for permanent sectioning. Patients were extubated in the operating theatre and monitored for 2–3 h in the recovery room. A chest X-ray was performed in every patient and decision to apply suction to chest drain was individualized. Post-operative administration of analgesics was adapted to individual requirements.

The clinical diagnosis before the biopsy was compared with the pathologic diagnosis of SLB. Change in therapy indicated that the original therapy had changed/stopped or new treatments initiated as a result of the lung biopsy.

Analysis

The presumed diagnosis based on clinical and radiological findings, made preoperatively, was compared to the histological diagnosis obtained by lung biopsy. The validity and accuracy of the clinical/radiological diagnosis were investigated. Sensitivity (proportion of individuals with the disease who have a positive test) and specificity (proportion of individuals without the disease who have a negative test) were determined as measures of validity. The predictive value (positive and negative) was also determined to ascertain whether or not an individual has the disease, based on a positive test (11). The post-test probability is used to assess how good a diagnostic test is. It has advantages over sensitivity and specificity because it is less likely to change with the prevalence of the disorder (12).

Results

SLB yielded a definitive diagnosis in 100% of patients (Table 1). Overall, 84 of the 93 biopsies (90.3%) had an ILD, while 9.7% had an allergic alveolitis. UIP was most frequently noted in 59(63.4%) patients followed by NSIP in 15(16.1%) patients and COP in 7(7.5%) patients, of these patients 14(23.7%), 5(33.3%) and 3(42.8%) patients were undiagnosed before surgical biopsy respectively. One out of 3 patients (33.3%) with sarcoidosis and 5 out of 9 patients (55.5%) with allergic alveolitis were undiagnosed before SLB. So approximately 27% (23/84) of subjects in whom ILD was eventually diagnosed were thought to have had other conditions preoperatively. Two patients with pulmonary sarcoidosis had no mediastinal lymphadenopathy.

Seventy four patients were already on corticosteroid therapy prior to referral for biopsy. After lung biopsy 41(44%) patients had changes in their therapy. Ninety two (98.9%) patients survived until hospital discharge. One patient died due to acute myocardial infarction during early postoperative period.

Table1: Pathologic diagnosis of lung biopsy and effect on patient management.

Histological diagnosis / No. of patients / Clinically undiagnosed patients, no.(%) / Change in therapy, no.(%)
UIP / 59(63.4%) / 14(23.7%) / 25(42.3%)
NSIP / 15(16.1%) / 5(33.3%) / 4(26.6%)
COP / 7(7.5%) / 3(42.8%) / 3(42.8%)
Sarcoidosis / 3(3.2%) / 1(33.3%) / 2(66.6%)
Allergic alveolitis / 9(9.6%) / 5(55.5%) / 7(77.7%)
Total / 93(100%) / 28(30.1%) / 41(44%)

The correlation between the clinical/radiological and the histopathological diagnosis showed that in 65 patients (69.9%) clinical/radiological evaluation reached a correct diagnosis and in 28 (30.1%) a new diagnosis was obtained unexpectedly. In UIP sensitivity, specificity, positive and negative predictive values for the clinical/radiological diagnosis were 76.2% (95% confidence interval, 67-84), 76.4% (CI, 67-85), 84.9% (CI, 80-89) and 70.2% (CI, 65-75), respectively (Table 2). The values for other diseases collectively are also shown in (Table 2).

Table 2: correlation between the clinical/radiological and the histopathological diagnosis.

Sensitivity (%) (95% CI) / Specificity (%) (95% CI) / PPV (%) (95% CI) / NPV (%) (95% CI)
UIP / 76.2% (67–84) / 76.4% (67–85) / 84.9% (80–89) / 70.2% 65–75)
Non-UIP / 58.8% (51–68) / 76.2%(67–84) / 58.8%(51–68) / 76.2%(67–84)

The post-test probability for the clinical/radiological evaluation was 90% in patients with UIP versus 77% in other diseases, meaning that there was a good correlation between the predicted probability and the observed frequency in patients with UIP and also means that clinical/radiological evaluation is a good diagnostic tool for UIP.

There was no clinical or statistical difference in outcomes for thoracoscopic and thoracotomy approaches (Table 3).

Table 3: Outcomes for thoracoscopic and thoracotomy approaches.

VATS(n=53) / Thoracotomy(n=40) / P- Value
Duration of operation* / 60±30 / 52±22 / p <0.05
Total anesthesia time* / 90±30 / 78±40 / p <0.05
Total pethidine dose (mg) / 103±25 / 110±25 / p <0.05
FEV1 on postoperative day 1 / 45%±10% / 42%±13% / p <0.05
FEV1 on postoperative day 14 / 66%±14 / 61%±18 / p <0.05
Duration of chest tube drainage˚ / 40±17 / 46±20 / p <0.05
Duration of surgical unit stay˚ / 71±10 / 74±15 / p <0.05
Cost / 1600$ / 1100 $ / p<0.05

FEV1 = forced expiratory volume in 1 second (presented as % predicted).

* = minute ˚ =hour

Duration of operation was similar in both groups (thoracoscopy 60 ± 30 minutes, thoracotomy 52 ± 22 minutes; p <0.05). Total anesthesia time was also similar in the two groups (thoracoscopy 90 ± 30 minutes, thoracotomy 78 ± 40 minutes; p<0.05). All patients were extubated at the end of their surgical procedure. Total pethidine dose was 103 ± 25 mg in the thoracoscopy group and 110 ± 25 mg in the thoracotomy group (p <0.05). Spirometry (FEV1) values in the two groups were not significantly different on postoperative days 1 and 2 weeks (p <0.05). Also no difference was present as regards duration of chest tube drainage (thoracoscopy 40 ± 17 hours, thoracotomy 46 ± 20 hours; p <0.05) and length of stay in surgery unit (thoracoscopy 71 ± 10 hours, thoracotomy 74 ± 15 hours; p <0.05). VATS procedure was more expensive (1600$ vs 1100$) because the necessity of disposable instrumentation (p<0.05).

Discussion

When lung biopsy is necessary, the surgeon should not function merely as a technician but should play an important role in determining the timing, method, and wisdom of diagnostic efforts.

Previously the demand for lung biopsy was relatively small but since the advent of VATS techniques, there has been a steady increase in the number of referrals for lung biopsy. This change may reflect a change in attitude among the physicians toward commencing potent medical treatment without a definitive histological diagnosis or a greater acceptance of a procedure, which they feel, is less invasive than open lung biopsy.

Recently high-resolution CT (HRCT) scanning has changed the diagnostic evaluation of patients with ILD and consequently the need for SLB (13, 14, 15). The technique of high-resolution CT allows detailed evaluation of the lung parenchyma by using 1- to 2-mm-thick slices, with a reconstruction algorithm that maximizes spatial resolution. HRCT allows earlier diagnosis of UIP, helps to narrow the differential diagnosis based on the CT pattern. HRCT can also help to increase the level of diagnostic confidence for UIP, when the clinical or radiologic features are uncertain (16, 17).

Our study showed that positive predictive value of the clinical/radiological diagnosis was 84.9% in patients with UIP. This was in agreement with other studies. . Hunninghake et al (5) examined the diagnostic value of a clinical, radiologic, and pathologic diagnosis in 91 patients with suspected UIP from multiple centers. Pathologic diagnosis was used as the "gold standard." The positive predictive value of a UIP diagnosis by a core of expert radiologists was 85%. A core of expert clinicians performed similarly, at 87%. In cases in which the radiologists felt confident in the HRCT scan diagnosis, the positive predictive value of an UIP diagnosis improved to 96% (18) Koyama et al (19) also confirmed a high degree of accuracy in the HRCT scan diagnosis of UIP {100%} in 92 patients who presented with cystic lung disease. Similar data have been reported from other single-center studies (10, 20).

It is becoming increasingly accepted that a highly suggestive clinical presentation, including typical HRCT scan findings, can be used in the absence of a lung biopsy specimen to make a likely diagnosis of UIP (21). Open or video-assisted thoracoscopic surgical lung biopsy is performed in a minority of patients with chronic ILD, likely reflecting the pessimism that findings on lung biopsy will alter the proposed treatment plan (22). A review of 200 patients with UIP in the United Kingdom showed that transbronchial or open lung biopsies were performed in only 33% and 7.5% of patients, respectively; the diagnosis of UIP was made on clinical grounds in most cases (23). Clinical practice in the United States and other countries often mirrors this approach of relying largely on clinical and radiological features to make the diagnosis of UIP (24, 25).

But inspite of high predictive values in previous studies for the clinical/radiological diagnosis, still there is a percentage of patients who could not be detected clinically. In our study 14 out of 59 patients (23.7%) with UIP could not be diagnosed except by biopsy. In these patients HRCT findings was not typical. Other investigators showed also that about one-third to 40% of cases of UIP will be missed by relying on CT diagnosis alone. Less experienced observers are substantially less accurate than experienced observers (16, 17).

Our study also showed that positive predictive value of the clinical/radiological diagnosis was 58.8% in patients with non- UIP and 9out of 25 of them (36%) could not be diagnosed except by biopsy. Other investigators also showed that lung biopsy may be required when the clinical diagnosis is not UIP (26). Flaherty et al (10) showed that in about 25% of cases of UIP the CT appearances overlap with those of NSIP and since the prognosis of NSIP is substantially different from that of UIP, they recommended biopsy to distinguish these cases of "atypical UIP" from NSIP.

Assessment of the effect of lung biopsy on patient management is difficult. Various reported series show a change in patient management based on biopsy results in 27–73% of patients undergoing this procedure for diffuse infiltrates (27, 28). In our series, therapy was changed in 44% of the patients because of the biopsy results. Therapy was more likely to be changed when a specific diagnosis was made compared to when a non-specific diagnosis resulted.

Thoracotomy for open lung biopsy has been a standard surgical approach for many years (3). Recently, the use of VATS lung biopsies for diagnosis of diffuse ILD has increased. In a randomized trial, of VATS versus limited thoracotomy for diagnostic lung biopsy in ILD, no difference in post-operative pain, narcotic requirement, operation time, adequacy of biopsy, duration of chest drain, length of stay, spirometry, and complications were demonstrated (29). Also our results showed that both limited thoracotomy and VATS are acceptable choices for diagnostic lung biopsy in ILD with the consideration that VATS procedure was more expensive.

SUMMARY

The diagnosis of IIP requires integration of the morphologic patterns identified by the radiologist and pathologist with the clinical features evaluated by the clinician. A critical role for the clinician is to determine whether the interstitial abnormality is idiopathic or related to an inhalational exposure or to collagen vascular disease. The radiologist must determine whether the CT features are typical for UIP or whether the features are less specific. The decision about biopsy in the patient suspected of having an IIP should be based on consultation between the clinician and radiologist. Patients with typical clinical and radiologic features of UIP will usually not need to undergo biopsy. The other interstitial pneumonias usually cannot be distinguished on the basis of clinical and CT features, and biopsy will usually be necessary if a precise histologic diagnosis is required. When surgical biopsy is performed, the results should always be interpreted in conjunction with the CT findings, since CT shows the macroscopic morphology of the entire lung while biopsy reveals microscopic morphology in only one or two small peripheral areas. CT may also be helpful in identifying a suitable location for surgical biopsy.

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