Postoperative routine computed tomography allows detection of early-stage acute exacerbations of interstitial pneumonia

Introduction

Acute exacerbation of interstitial pneumonia (IP-AE) is one of the most serious postoperative complications of lung resection. When patients with interstitial pneumonia (IP) undergo lung resection, IP-AE frequently occurs 4–8 days after surgery. A previous review study revealed that IP-AE developed in 5.8% (range, 1.1–11.7%) of patients with IP. Once it occurred, the prognosis was poor, with a mortality rate of 56.7% (range, 0–100%), even after intensive care (1). Several studies have addressed the risk factors, prevention, and treatment after disease onset (2-19). A previous retrospective study revealed that a history of acute exacerbation (AE), anatomical lung resection, preoperative steroid use, male sex, Krebs von den Lungen-6 (KL-6) >1,000 U/mL, and % vital capacity (%VC) ≤80% were risk factors for AE (20). Another study examined whether the perioperative administration of sivelestat could prevent AE (2). In addition, a multicenter prospective study is ongoing to investigate whether limited surgery, such as wedge resection or segmentectomy, reduces the incidence of IP-AE compared with lobectomy. No evidence-based treatment is available for IP-AE; however, in clinical practice, it is treated with steroid pulse therapy (7). Therapeutic intervention for IP-AE is conducted after its diagnosis with a computed tomography (CT) scan, which is performed after the onset of clinical symptoms. This approach implies that intervention can only begin once IP-AE is fully developed, suggesting that earlier detection and intervention may improve outcomes. However, no evidence supports this hypothesis. In recent years, high-resolution CT (HRCT) has been positioned as a central tool for the diagnosis and longitudinal follow-up of interstitial lung disease (ILD), and in systemic sclerosis-associated ILD (SSc-ILD) the utility of baseline assessment and serial monitoring has been emphasized. At the same time, even when HRCT can detect abnormalities during asymptomatic phases, treatment decisions should not be based on imaging alone; rather, they are recommended to integrate clinical findings, pulmonary function, and temporal evolution (21,22). Although prior studies have identified certain high-risk groups for IP-AE to some extent, IP-AE is clinically observed even in patients who do not meet these criteria and are judged preoperatively to be at low risk. Accordingly, reliance solely on preoperative risk stratification may forfeit opportunities for preemptive intervention. Given the high lethality of IP-AE, screening with routine CT (rCT) during a limited period in the early postoperative phase represents a rational strategy that may enable the detection of abnormalities preceding symptom onset and facilitate earlier initiation of therapy.

Since December 2014, at Institute of Science Tokyo, an rCT scan has been performed after lung resection in patients with IP to detect IP-AE early, even without apparent worsening or the appearance of dyspnea. To determine whether radiological changes precede clinical findings and whether these changes are reliable for diagnosing IP-AE, we retrospectively analyzed our rCT data. We present this article in accordance with the STARD reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1798/rc).

Methods

Patient selection

A total of 1,391 consecutive pulmonary resections for lung cancer were performed between December 2014 and March 2024 at the Institute of Science Tokyo. Figure 1 illustrates the flowchart of the patients who participated in this study. Eligibility for rCT was determined by preoperative HRCT findings consistent with IP, irrespective of postoperative pathological confirmation (23). Histopathologic confirmation of IP was not available at the time rCT was scheduled or performed; eligibility for rCT reflected radiologic suspicion, whereas the final diagnosis for the analytic cohort was established histopathologically. Among 1,391 consecutive lung cancer resections (December 2014–March 2024), 120 patients with radiologically suspected IP underwent planned postoperative rCT. An additional 44 patients had IP identified only on postoperative pathology despite no preoperative radiologic suspicion and therefore did not undergo rCT; these 44 cases and one patient who developed AE before the scheduled rCT were excluded from the present analysis. Although an emergency CT was acquired for diagnostic purposes in the latter patient with symptoms, it fell outside the predefined observation window and was therefore excluded from the present analysis. Taken together, the overall study cohort comprised 165 patients, all of whom were ultimately diagnosed with IP on histopathology; 120 underwent planned rCT based on preoperative radiologic suspicion, whereas 45 were identified only on postoperative pathology and therefore had no planned rCT (this group includes the single patient who developed AE before the scheduled rCT). Lung cancer staging was performed according to the 8^th edition of the tumor-node-metastasis (TNM) classification for lung cancer (24). The surgical procedure—wedge resection, segmentectomy, or lobectomy—was determined for each patient at a thoracic surgical conference after a review of the patient’s tumor characteristics and overall clinical background. There were no missing index-test or reference-standard results in the analyzed cohort; cases without planned rCT or with AE before the scheduled rCT were excluded a priori and are shown in Figure 1. This was a single-center retrospective observational study; acquisition of postoperative rCT and initiation of corticosteroid therapy were determined by routine clinical judgment and did not constitute a prospective intervention. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics committee of the Institute of Science Tokyo (approval No. M2000-1097) and individual consent for this retrospective analysis was waived.

Figure 1 Flowchart of patients included in this study. IP, interstitial pneumonia; IP-AE, acute exacerbation of interstitial pneumonia; rCT, routine computed tomography.

Perioperative management

On the day of admission, blood tests, including blood count, C-reactive protein, lactate dehydrogenase, and arterial blood gas test, were performed. Chest radiography was also performed on the same day. Postoperative blood tests were performed on postoperative days (PODs) 1, 3, 5, and 7. Postoperative arterial blood gas tests were not performed routinely but only during oxygenation deterioration. Chest radiographs were obtained daily until the chest drainage tube was removed. Patients were discharged once the chest drainage tube had been removed and a chest radiograph obtained the following day showed no abnormalities.

To reduce the risk of IP-AE, perioperative oxygen administration was minimized, and sivelestat, a neutrophil elastase inhibitor (4.8 mg/kg/day), was administered for 48 h postoperatively. A broad-spectrum antibacterial agent such as Ampicillin-sulbactam was administered postoperatively until the chest drainage tube was removed to prevent bacterial pneumonia and empyema.

Definition of postoperative IP-AE

Postoperative IP-AE was defined by referring to the international working group flowchart (25). The criteria for IP-AE in this study were: (I) onset within 30 days after lung resection; (II) worsening or appearance of dyspnea; (III) increase in the interstitial shadow on a chest radiograph and chest CT scan; and (IV) no evidence of other causes presenting these findings. IP-AE onset was defined as the point at which the clinician diagnosed IP-AE and started treatment based on a combination of clinical and radiological findings.

According to our institutional protocol, an rCT scan is obtained between PODs 2 and 7, and then interpreted by the thoracic surgeons and radiologists. No therapeutic decision was triggered by any prespecified rCT score threshold; the five-point and summed rCT scores were developed retrospectively for research purposes and were not used in clinical care. Because the evaluation of diagnostic accuracy was predicated on the availability of rCT images, the single patient who developed IP-AE before the scheduled rCT was excluded from the analysis.

Clinical onset day (day 0) was defined as the first day on which the patient fulfilled either of the following criteria: (I) new or worsening dyspnea; or (II) objective hypoxemia.

When IP-AE was diagnosed, intravenous steroid pulse therapy was administered to all patients. Additional treatments after steroid pulse therapy, such as oral steroids, immunosuppressants, antifibrotic agents, or endotoxin adsorption therapy, were determined by respiratory medicine physicians, depending on the IP-AE status. We adopted the international working group definition as the reference standard because it is the most widely accepted framework for postoperative AE in ILD and ensures comparability across studies. Assessors of the reference standard had access to the clinical information and routine imaging as per standard care.

Definition and evaluation of rCT

rCT was defined as (I) a HRCT scan obtained between PODs 2 and 7; and (II) a scan performed while the patient exhibited neither new nor worsening dyspnea nor objective hypoxemia. rCT was, in principle, obtained on PODs 2–3; however, the acquisition date could vary due to institutional scheduling constraints such as weekends. All rCT examinations were performed irrespective of thoracic drain placement.

Previous observational studies have shown that postoperative IP-AE most frequently emerges between PODs 4 and 8. Therefore, we scheduled rCT according to the predefined definition to capture sub-clinical radiologic changes before symptom onset (26). Chest CT examinations were performed on multidetector scanners with 16–192 detector rows. Non-contrast scans were acquired at end-inspiration in the supine position. Acquisition used submillimeter collimation, and images were reconstructed with a sharp lung kernel (e.g., Bl57 or vendor-equivalent). Thin-section images with slice thickness ≤2 mm and no interslice gap were used for interpretation. Reconstructions employed filtered back projection or the vendor’s standard iterative algorithm, while slice thickness and kernel were kept consistent across the study period.

Two expert radiologists (K.K. and T.A.) independently reviewed the rCT and the corresponding preoperative HRCT images. Preoperative HRCT was also adjudicated by the same two thoracic radiologists to confirm the presence of IP according to predefined radiologic criteria. In this study, “radiologically suspected IP” was defined as preoperative HRCT findings consistent with fibrosing ILD, including (I) usual IP (UIP)-spectrum patterns (definite or probable UIP); (II) indeterminate/possible UIP; and (III) fibrotic non-UIP patterns such as fibrotic non-specific IP (NSIP). Our five-point score adopts a probability-based, five-category structure modeled on established standardized frameworks in the Reporting and Data Systems (RADS) family for grading disease likelihood on imaging tests [Coronavirus Disease 2019 RADS (CO-RADS), Prostate Imaging RADS (PI-RADS), and Liver Imaging RADS (LI-RADS)] (27-29). Accordingly, IP-AE findings were evaluated using this five-point grading scheme. Using the five-point likelihood scale summarized in Table 1, with representative HRCT slices for scores 1–5 shown in Figure 2, each radiologist rated the probability of IP-AE as follows: 1, unsuspected IP-AE (0–9%); 2, postoperative or nonspecific changes (10–39%); 3, unable to rule out IP-AE (40–59%); 4, suspicious for IP-AE (60–80%); 5, consistent with IP-AE (>80%).

Figure 2 Representative HRCT slices illustrating rCT scores 1–5. The red arrowheads indicate findings suspicious for rIP-AE, whereas the green arrowheads indicate nonspecific changes. (A) Score 1: pre-existing UIP pattern only; no new GGOs or consolidations. (B) Score 2: thin, localized GGOs or atelectasis confined to the resected lung margin or staple line, consistent with expected postoperative change. (C) Score 3: patchy GGOs extending across the interlobar fissure into an adjacent or contralateral lobe; early rIP-AE cannot be fully excluded. (D) Score 4: confluent bilateral GGOs/consolidations involving multiple lobes, suggestive of rIP-AE. (E) Score 5: diffuse, extensive GGOs accompanied by dense consolidations, radiologically compatible with rIP-AE. GGO, ground-glass opacity; HRCT, high-resolution computed tomography; rCT, routine computed tomography; rIP-AE, radiological acute exacerbation of interstitial pneumonia; UIP, usual interstitial pneumonia.

The two thoracic radiologists performed independent, blinded readings of all rCT studies, without access to outcomes or to each other’s ratings. For the primary analysis, no on-study consensus adjudication was undertaken; instead, discrepancies were handled analytically by (I) prespecifying the final rCT score as the sum of the two five-point ratings; and (II) quantifying inter-reader agreement using the quadratic-weighted κ with complementary agreement visualizations. In this study, we define postoperative AE detected solely on rCT images as radiological IP-AE (rIP-AE), whereas exacerbation diagnosed on the basis of combined clinical manifestations, laboratory findings, and imaging is termed clinical IP-AE (cIP-AE). The radiologist readers had access to the preoperative HRCT and the rCT images but were blinded to clinical outcomes and to the reference-standard determinations when assigning the five-point scores.

Statistical analysis

We calculated the sensitivity and specificity of the rCT score for detecting potential cIP-AE. To assess the performance of the rCT score, we calculated the area under the receiver operating characteristic (ROC) curve (AUC) for the cohort. A separate ROC analysis was performed for cIP-AE events that occurred within 14 days after surgery, and sensitivity and specificity at each score threshold were summarized. Statistical analyses were performed using EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan), version 1.61 (30). For analytical purposes, the treatment threshold was defined as the lowest rCT score that achieved 100% specificity. Interobserver agreement for the five-point rCT score was assessed using the quadratic-weighted κ statistic. Ninety-five percent confidence intervals (CIs) were calculated for the AUC (DeLong method) and, for interpretability, for sensitivity and specificity at two principal operating points: the threshold maximizing Youden’s J statistic and the minimal score achieving 100% specificity; estimates for other thresholds were reported as point estimates due to the limited number of events. To assess internal validity and optimism, we performed bootstrap resampling (1,000 iterations) to obtain optimism-corrected AUC estimates for the rCT summed score. To explore the incremental predictive value of the rCT score beyond established risk factors, we fitted logistic regression models for cIP-AE: a base model with % vital capacity (%VC) ≤80%, KL-6 ≥1,000 U/mL, and preoperative steroid use, and an expanded model additionally including the rCT score (primary analysis as a continuous summed score; sensitivity analysis as a binary indicator defined post-hoc by the high-specificity operating point). Model improvement was evaluated using the likelihood-ratio test and the change in AUC (ΔAUC). Beyond the quadratic-weighted κ, we also displayed a 5×5 confusion matrix of reader scores and a Bland-Altman plot as complementary visualizations. This retrospective consecutive-sample study had no a priori sample size calculation; all eligible cases within the study period were included.

Results

A summary of the clinicopathological data of the patients enrolled in this study is presented in Table 2. The median age of the cohort was 72.0 years, and the median Brinkman index was 1,016. The median %VC on spirometry was 95.3%, and the proportion of the patients with %VC ≤80% was 19.2%. The median serum KL-6 was 552 U/mL, and the ratio of patients with KL-6 ≥1,000 U/mL was 15.8%. Approximately 90% of the patients were men, and 1.7% had a history of cIP-AE. Preoperative steroid use was observed in 11.7% of the patients, and 56.7% of patients were radiologically diagnosed as having a UIP pattern on their preoperative CT. Pathologically, 30.8% of patients were diagnosed with adenocarcinoma and 48.3% with squamous cell carcinoma. The proportions of patients diagnosed with pathological stages I, II, III, or IV were 50.8%, 25.8%, 22.5%, and 0.8%, respectively. No adverse events related to the rCT were observed. rCT was obtained on POD 3 (range, 2–7).

Table 3 presents the postoperative results of patients with lung cancer and IP. Of the 120 patients, cIP-AE occurred in 14. The 30-day mortality rate was 0.8%, and the 90-day mortality rate was 3.3%. Among the 14 patients who received methylprednisolone pulse therapy, no grade ≥3 complications occurred according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. In five of the 14 cIP-AE cases, clinicians initiated steroid pulse therapy on the basis of the qualitative rCT interpretation before any deterioration in oxygenation. Retrospective scoring showed that four of these five scans corresponded to a summed rCT score ≥9 (100% specificity = all progressed to cIP-AE), whereas one scan scored 8. The remaining nine patients (scores ≤8) received steroids only after clinical worsening. All four patients who died within 3 months of the onset of cIP-AE died due to cIP-AE.

Figure 3 summarizes the ROC analysis of the five-point rCT score. In the entire cohort (Figure 3A), the AUC was 0.956; the optimal threshold was ≥6, yielding 85.7% (95% CI: 57.2–98.2%) sensitivity and 88.7% (95% CI: 81.1–94.0%) specificity, whereas a stricter cutoff of ≥9 achieved 100% (95% CI: 96.6–100%) specificity (100% specificity; all progressed to cIP-AE) and a sensitivity of 35.7% (95% CI: 12.8–64.9%). In bootstrap internal validation (1,000 resamples), the optimism was 0.002 and the optimism-corrected AUC was 0.953 (Table 4). Restricting the analysis to events within 14 days after surgery (n=11) produced a similar AUC of 0.976 with the same ≥6 threshold (Figure 3B, Table 5), with a 95% CI of 0.440–1.000. For interobserver agreement, the quadratic-weighted κ was 0.72. All scans were interpretable, and indwelling drains did not produce any metal artifacts that impeded the assessment of ground-glass opacities (GGOs) or consolidations. A 5×5 confusion matrix and a Bland-Altman plot are provided as complementary visualizations (Figures S1,S2); the mean difference was 0.133 with limits of agreement of −1.390 to 1.656.

Figure 3 ROC curves of the five-point rCT score for detecting postoperative IP-AE. (A) Analysis of the entire cohort (n=120), showing an AUC of 0.956 (95% CI: 0.902–0.988). (B) Analysis limited to IP-AE events within 14 days after surgery (n=11), yielding an AUC of 0.976 (95% CI: 0.951–1.000). AUC, area under the receiver operating characteristic curve; CI, confidence interval; IP-AE, acute exacerbation of interstitial pneumonia; rCT, routine computed tomography; ROC, receiver operating characteristic; Se, sensitivity; Sp, specificity.

In an exploratory multivariable logistic regression evaluating the incremental predictive value of rCT information beyond established risk factors (%VC ≤80%, KL-6 ≥1,000 U/mL, and preoperative steroid use), the AUC of the base model was 0.648, whereas that of the expanded model, including the summed rCT score (continuous), was 0.960, yielding ΔAUC = 0.312. Model fit also improved on the likelihood-ratio test [χ²=45.85, degrees of freedom (df) =1, P=1.3×10⁻¹¹]. In a sensitivity analysis using a binary rCT score of ≥9, the AUC was 0.797 (Table S1).

Details of the patients who developed cIP-AE are presented in Table 5. Thirteen of the 14 patients who experienced cIP-AE were men, and one was a woman. Eleven of 14 patients underwent anatomical resection for lung cancer. Of the 14 patients with cIP-AE, five had a positive rCT score (≥9). Four patients in the rCT-positive group (score ≥9) received steroid pulse therapy based solely on the rCT findings, and one patient in the rCT-negative group (score 8) was also treated pre-emptively. In total, five of 14 cIP-AE cases received early therapy. Limiting the analysis to rCT-positive cases (summed score ≥9), radiologic findings suspicious for AE were detected a mean of 3.2 days before symptom onset, and therapy was initiated a mean of 1.4 days prior to symptom onset (Table 6).

Discussion

In this study, two important clinical observations were made. First, postoperative rIP-AE can be diagnosed using rCT without the onset of worsening or the appearance of dyspnea. Second, our findings suggest that, with an appropriate radiologic cutoff, postoperative rCT can accurately identify early rIP-AE. Furthermore, the quadratic-weighted κ between the two radiologists was 0.72, indicating substantial interobserver agreement and thereby supporting the robustness of the five-point rCT scoring system. Although early postoperative CT findings can overlap with aspiration pneumonia and inflammatory changes, rCT alone can raise a high-probability suspicion of cIP-AE when interpreted against the high specificity of the result of this study.

Postoperative rIP-AE can be diagnosed on rCT before any decrease in oxygen saturation (SpO₂) or the onset of dyspnea, as all affected patients showed at least subtle radiologic changes at the time of rCT. Pathologically, in IP-AE, very early changes—namely increased alveolar wall permeability with mild inflammation and exudation—may appear on rCT as GGOs (31). In this ultra-early phase, the extent of disease is limited and respiratory physiological compensation operates; therefore, a decline in resting oxygenation may not manifest immediately. Approximately one-third of the patients who developed cIP-AE could be diagnosed as rIP-AE on rCT before any decline in SpO₂ or dyspnea occurred. A previous retrospective study revealed that the mortality rate due to cIP-AE could be reduced by performing postoperative CT three times within 2 weeks after surgery for cIP-AE detection (26). The results of our study indicated that a single rCT scan, which was performed without the onset of worsening or the appearance of dyspnea within POD 7, was sufficient to detect rIP-AE that occurred within 2 weeks after surgery. Moreover, our study provided information on the evaluation criteria for the CT scans and the sensitivity or specificity of rIP-AE detection.

In the present study, when an rCT score of nine or higher was defined as the cutoff, the specificity of postoperative cIP-AE detection by rCT and the positive predictive value were both 100%, indicating that radiologic findings alone justify early treatment. Statistically, the ideal cutoff rCT score was 6. However, the positive predictive value in this setting was 45.5%. Accordingly, we position a score ≥6 as a sensitivity-oriented screening threshold to prompt short-interval reassessment (e.g., repeat rCT, vitals/SpO₂, laboratory tests) rather than an immediate trigger for steroid pulse therapy. In clinical practice, cIP-AE is treated with steroid pulse therapy (7). If this ideal cutoff value were applied, approximately half of the patients would receive unnecessary treatment. Steroid therapy has been reported to cause adverse effects. Especially among patients who have undergone lung resection, treatment should be limited to those with cIP-AE, as steroid-induced tissue fragility and poor tissue fusion can cause postoperative prolonged air leak or bronchial fistula (32,33). Therefore, to minimize false positives when contemplating steroid pulse therapy, we adopted a high-specificity treatment-trigger threshold of ≥9. From a clinical perspective, universal rCT in ILD would carry radiation exposure and costs. Whether earlier intervention would prevent prolonged, resource-intensive critical care that would otherwise result from cIP-AE—and thereby offset these costs—remains uncertain.

This study has several limitations. First, this was a retrospective study with a small cohort. In particular, there were only 14 cases of cIP-AE, and one case might have a significant impact on the outcomes of this study. Moreover, selection bias cannot be excluded, as our analysis included only cases with planned rCT, diagnostic accuracy may therefore be overestimated. In addition, the rCT acquisition window (PODs 2–7) varied for operational reasons (e.g., weekends), introducing timing heterogeneity. Second, the optimal timing for performing rCT was not established in this study. Therefore, determining the most appropriate schedule for rCT to detect rIP-AE should be considered. Notably, rCT can detect rIP-AE before the onset of symptoms even on its own; however, early postoperative GGOs and consolidations may partially overlap with aspiration pneumonia, infection, hemorrhage, edema, or postoperative inflammatory changes. Accordingly, decisions to initiate treatment should be based on a standardized algorithm that is triggered by imaging findings and integrates vital signs, laboratory data, and temporal changes. Third, even if rIP-AE is detected early using rCT, the improvement in prognosis is uncertain. Further studies are required to elucidate the effects of early interventions on rIP-AE. Fourth, image interpretation was performed by two thoracic radiologists from the same institution, and potential institutional bias due to shared interpretive tendencies cannot be entirely excluded. Although inter-reader agreement was acceptable (κ=0.72), further evaluation is needed to establish generalizability.

Conclusions

In conclusion, a postoperative rCT can detect rIP-AE that subsequently progresses to cIP-AE before any deterioration in respiratory status becomes apparent. The novelty of this study lies in systematically showing that scheduled postoperative rCT can identify rIP-AE prior to clinical worsening. If rCT is performed for postoperative observation in patients with IP, some cIP-AE can be detected early, and prompt intervention can be provided. The impact of early intervention for cIP-AE on mortality is not established and requires verification in prospective studies. Accordingly, these findings should be regarded as hypothesis-generating rather than practice-changing. Future studies should evaluate whether earlier detection and prompt intervention translate into improved survival and more efficient healthcare resource utilization.

Acknowledgments

Parts of this work were presented at the 39^th Annual Meeting of the Japanese Association for Chest Surgery (2022, Tokyo, Japan), the 63^rd Annual Meeting of the Japan Lung Cancer Society (2022, Fukuoka, Japan), and the 45^th Annual Meeting of Japanese Society of Respiratory Care Medicine (2023, Nagoya, Japan).

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1798/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1798/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1798/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1798/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics committee of the Institute of Science Tokyo (approval No. M2000-1097) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Chida M, Kobayashi S, Karube Y, et al. Incidence of acute exacerbation of interstitial pneumonia in operated lung cancer: institutional report and review. Ann Thorac Cardiovasc Surg 2012;18:314-7. [Crossref] [PubMed]
2. Fukui M, Takamochi K, Oh S, et al. Study on Perioperative Administration of a Neutrophil Elastase Inhibitor for Interstitial Pneumonias. Ann Thorac Surg 2017;103:1781-7. [Crossref] [PubMed]
3. Ito H, Nakayama H, Yokose T, et al. A prophylaxis study of acute exacerbation of interstitial pneumonia after lung cancer surgery. Jpn J Clin Oncol 2020;50:198-205. [Crossref] [PubMed]
4. Kagimoto A, Tsutani Y, Handa Y, et al. Prediction of Acute Exacerbation of Interstitial Pneumonia Using Visual Evaluation of PET. Ann Thorac Surg 2021;112:264-70. [Crossref] [PubMed]
5. Kagimoto A, Tsutani Y, Kushitani K, et al. Serum S100 calcium-binding protein A4 as a novel predictive marker of acute exacerbation of interstitial pneumonia after surgery for lung cancer. BMC Pulm Med 2021;21:186. [Crossref] [PubMed]
6. Kanayama M, Osaki T, Nishizawa N, et al. Modified risk scoring system for acute exacerbation of interstitial lung disease. Asian Cardiovasc Thorac Ann 2019;27:18-22. [Crossref] [PubMed]
7. Kondoh Y, Taniguchi H, Kawabata Y, et al. Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases. Chest 1993;103:1808-12. [Crossref] [PubMed]
8. Maniwa T, Endo M, Isaka M, et al. Acute exacerbation of interstitial lung disease with lung cancer after surgery: evaluation with 2-18-fluoro-2-deoxy-D-glucose positron emission tomography. Surg Today 2014;44:494-8. [Crossref] [PubMed]
9. Maniwa T, Isaka M, Nakagawa K, et al. Chest-tube drainage is a sign of acute exacerbation of interstitial lung disease associated with lung cancer. Surg Today 2013;43:408-11. [Crossref] [PubMed]
10. Miyajima M, Watanabe A, Sato T, et al. What factors determine the survival of patients with an acute exacerbation of interstitial lung disease after lung cancer resection? Surg Today 2018;48:404-15. [Crossref] [PubMed]
11. Oishi H, Sakurada A, Notsuda H, et al. Correlation between preoperative (18)F-FDG PET/CT findings and postoperative short-term prognosis in lung cancer patients with idiopathic interstitial pneumonia after lung resection. Respir Investig 2021;59:106-13. [Crossref] [PubMed]
12. Ozawa Y, Shibamoto Y, Hiroshima M, et al. Preoperative CT Findings for Predicting Acute Exacerbation of Interstitial Pneumonia After Lung Cancer Surgery: A Multicenter Case-Control Study. AJR Am J Roentgenol 2021;217:859-69. [Crossref] [PubMed]
13. Sato T, Teramukai S, Kondo H, et al. Impact and predictors of acute exacerbation of interstitial lung diseases after pulmonary resection for lung cancer. J Thorac Cardiovasc Surg 2014;147:1604-1611.e3. [Crossref] [PubMed]
14. Shintani Y, Ohta M, Iwasaki T, et al. Predictive factors for postoperative acute exacerbation of interstitial pneumonia combined with lung cancer. Gen Thorac Cardiovasc Surg 2010;58:182-5. [Crossref] [PubMed]
15. Sugiura H, Takeda A, Hoshi T, et al. Acute exacerbation of usual interstitial pneumonia after resection of lung cancer. Ann Thorac Surg 2012;93:937-43. [Crossref] [PubMed]
16. Suzuki H, Sekine Y, Yoshida S, et al. Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography. Surg Today 2011;41:914-21. [Crossref] [PubMed]
17. Tang H, Ren Y, She Y, et al. Is operation safe for lung cancer patients with interstitial lung disease on computed tomography? Ther Adv Respir Dis 2020;14:1753466620971137. [Crossref] [PubMed]
18. Yamaguchi K, Nakao S, Iwamoto H, et al. Predictive role of circulatory HMGB1 in postoperative acute exacerbation of interstitial lung disease in lung cancer patients. Sci Rep 2021;11:10105. [Crossref] [PubMed]
19. Yamamichi T, Shimada Y, Masuno R, et al. Association between F-18 fluorodeoxyglucose uptake of noncancerous lung area and acute exacerbation of interstitial pneumonia in patients with lung cancer after resection. J Thorac Cardiovasc Surg 2020;159:1111-1118.e2. [Crossref] [PubMed]
20. Sato T, Kondo H, Watanabe A, et al. A simple risk scoring system for predicting acute exacerbation of interstitial pneumonia after pulmonary resection in lung cancer patients. Gen Thorac Cardiovasc Surg 2015;63:164-72. [Crossref] [PubMed]
21. Ledda RE, Campochiaro C. High resolution computed tomography in systemic sclerosis: From diagnosis to follow-up. Rheumatol Immunol Res 2024;5:166-74. [Crossref] [PubMed]
22. Ruaro B, Baratella E, Confalonieri P, et al. High-Resolution Computed Tomography: Lights and Shadows in Improving Care for SSc-ILD Patients. Diagnostics (Basel) 2021;11:1960. [Crossref] [PubMed]
23. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2018;198:e44-68. [Crossref] [PubMed]
24. Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016;11:39-51. [Crossref] [PubMed]
25. Collard HR, Ryerson CJ, Corte TJ, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med 2016;194:265-75. [Crossref] [PubMed]
26. Oyama K, Kanzaki M, Kondo M, et al. Early Detection of the Acute Exacerbation of Interstitial Pneumonia after the Surgical Resection of Lung Cancer by Planned Chest Computed Tomography. Korean J Thorac Cardiovasc Surg 2017;50:177-83. [Crossref] [PubMed]
27. Chernyak V, Fowler KJ, Kamaya A, et al. Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology 2018;289:816-30. [Crossref] [PubMed]
28. Fujioka T, Takahashi M, Mori M, et al. Evaluation of the Usefulness of CO-RADS for Chest CT in Patients Suspected of Having COVID-19. Diagnostics (Basel) 2020;10:608. [Crossref] [PubMed]
29. Turkbey B, Rosenkrantz AB, Haider MA, et al. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur Urol 2019;76:340-51. [Crossref] [PubMed]
30. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013;48:452-8. [Crossref] [PubMed]
31. Marquis KM, Hammer MM, Steinbrecher K, et al. CT Approach to Lung Injury. Radiographics 2023;43:e220176. [Crossref] [PubMed]
32. Algar FJ, Alvarez A, Aranda JL, et al. Prediction of early bronchopleural fistula after pneumonectomy: a multivariate analysis. Ann Thorac Surg 2001;72:1662-7. [Crossref] [PubMed]
33. Cerfolio RJ, Bass CS, Pask AH, et al. Predictors and treatment of persistent air leaks. Ann Thorac Surg 2002;73:1727-30; discussion 1730-1. [Crossref] [PubMed]