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Whenever a patient with a pre-existing disease undergoes surgery, physicians must take great care to ensure that all the relevant preoperative, intraoperative, and postoperative steps required during the surgical management of a patient with that disease are taken.

Generally speaking, one of the problems that surgeons fear most, besides something going terribly wrong during a procedure, is postoperative infection. This can be caused by a multitude of factors, including inadequate wound care and inadequate treatment with antibiotics. I once watched a surgeon perform a thyroidectomy without wearing a surgical mask because, according to the surgeon, “there is no evidence that it works.” What good is the clean removal of a mass if an infection subsequently develops and the patient is subjected to a lengthy postoperative hospital stay?

Read more about IPF diagnosis 

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When a patient has an interstitial lung disease, such as idiopathic pulmonary fibrosis (IPF), physicians have another worry—the development of acute postoperative exacerbations of interstitial pneumonia. 

Researchers from Toho University, in Tokyo, Japan, set out to uncover the risk factors for acute postoperative exacerbations and published their findings in Surgery Today. In this article, we discuss some of the reasons why physicians opt to undertake surgical intervention in IPF, the possible reasons for the development of acute postoperative exacerbations, and how they can be prevented.

Before Surgery 

Although guidelines vary from one country to another, the Japanese guidelines recommend surgery for patients with lung cancer and concurrent IPF or another form of interstitial pneumonia. A study confirmed the greater effectiveness of wedge resection or segmentectomy vs lobectomy for patients who have IPF with early-stage non-small-cell lung cancer, although this finding has been challenged by the results of other studies. In a separate study, 13 of 108 patients who had IPF with lung cancer and underwent pulmonary resection required another surgery, and although the second surgery was a limited resection, these patients had a high rate of acute exacerbations.

Before they decide to perform surgery, physicians typically want to know a patient’s risk for the development of acute postoperative exacerbations. Sato et al created a useful scoring system that predicted the risk for exacerbations within 30 days after pulmonary resection. Seven risk factors were identified:

  • Male sex 
  • History of acute exacerbations 
  • History of surgical procedures
  • Preoperative steroid administration
  • High serum level ofKrebs von den Lungen-6 (KL-6)
  • Low vital capacity 
  • Appearance of usual interstitial pneumonia (UIP) on computed tomography.

In addition, physicians want to be informed about a patient’s comorbidities before surgery. The postoperative mortality rates of patients who have both pulmonary fibrosis and emphysema are known be high.

Prophylaxis for Postoperative Exacerbations 

Currently, 2 medications can be used as prophylaxis: pirfenidone and nintedanib. Pirfenidone is known to reduce disease progression in IPF and may also be effective in diseases other than IPF, such as UIP. In one study, acute postoperative exacerbation developed in only 1 of 31 patients who were taking pirfenidone. In another study, pirfenidone also reportedly reduced acute exacerbations during follow-up.

Read more about IPF etiology 

Nintedanib has been found to mitigate decreased forced vital capacity (FVC) in patients with IPF. However, side effects such as diarrhea, weight loss, and liver toxicity have been reported. Although no current studies of the effectiveness of nintedanib for acute postoperative exacerbations are available, it is reported to be effective against lung cancer.

Treatment for Postoperative Exacerbations 

As previously stated, treatment guidelines differ from country to country, but because this research was conducted in Japan, we will spend some time discussing the Japanese guidelines. These recommend that corticosteroids, including immunosuppressants and pulse therapy, be administered to treat acute postoperative exacerbations. As is known, immunosuppression may not be the best strategy for vulnerable patients. 

Some studies have found thrombomodulin-α to be useful in treating acute postoperative exacerbations owing to its anticoagulant, antifibrotic, and anti-inflammatory properties. However, others have suggested that it not be used because it has not been shown to improve 90-day survival. 

Various combinations of treatments have also been proposed to manage acute postoperative exacerbations. Sakamoto et al reported that adding recombinant human thrombomodulin to conventional therapy can improve outcomes, and Furuya et al suggested a combination of pirfenidone, corticosteroids, and recombinant human thrombomodulin. 

The studies that have looked into postoperative survival rates are worth a brief mention. In one study, the 5-year survival rate was 54.2% in patients with IPF and lung cancer, whereas those with IPF only had a survival rate of 88.3%. In another study, the outcomes of patients who underwent wedge resection were significantly poorer than those of patients treated with lobectomy. In addition, the same study found that decreased vital lung capacity is predictive of a poor survival rate. 

Planning Ahead  

IPF remains a challenging disease to manage—from diagnosis to surgery to postoperative care. The difficulty lies in creating a comprehensive plan that improves the quality of life of patients without unintentionally creating other problems. For example, postoperative immunosuppressive therapy may help alleviate acute postoperative exacerbations, but if it is overdone, you risk opening the door for opportunistic infections.  

“Although the diagnosis of and treatments for IPF are difficult, we must maintain efforts to make accurate diagnoses for patients with IP and continue this type of study to improve the prognoses for patients with IPF and lung cancer,” concluded the authors of the study. 


Iyoda A, Azuma Y, Sakamoto S, Homma S, Sano A. Surgical treatment for patients with idiopathic pulmonary fibrosis and lung cancer: postoperative acute exacerbation of idiopathic pulmonary fibrosis and outcomes. Surg Today. Published online August 4, 2021. doi:10.1007/s00595-021-02343-0

Saito A, Horie M, Micke P, Nagase T. The role of TGF-β signaling in lung cancer associated with idiopathic pulmonary fibrosis. Int J Mol Sci. Published online November 15, 2018. doi:10.3390/ijms19113611