Can diaphragmatic pleuritis occur as a complication of hepatic radiation therapy?

Can Diaphragmatic Pleuritis Occur During Hepatic Radiation Therapy?

Yes, diaphragmatic injury and pleural complications can occur during hepatic radiation therapy, though the evidence specifically documenting "pleuritis" as a direct radiation effect is limited; the more commonly described complications are radiation pneumonitis affecting adjacent lung tissue and diaphragmatic injury from thermal ablation procedures rather than external beam radiation.

Mechanism and Anatomical Considerations

The diaphragm is frequently included in radiation fields when treating hepatic malignancies, particularly tumors in the dome of the liver. When radiation therapy targets the liver, the treatment field often encompasses:

• The ipsilateral diaphragmatic attachments and crus 1
• Adjacent lung tissue in the lower thoracic region 1
• The pleural space immediately adjacent to hepatic lesions 1

The liver is considered an organ at risk (OAR) during thoracic radiation, and conversely, thoracic structures including the diaphragm become OARs during hepatic radiation 2.

Documented Radiation-Related Complications

Radiation Pneumonitis (Not Pleuritis)

The most well-characterized complication affecting structures near the liver during radiation is radiation pneumonitis, which typically manifests 2-6 months post-treatment with fever, cough, dyspnea, and alveolar infiltrates 3. This can occur when radiation fields include the lower lung zones adjacent to hepatic tumors 1, 3.

Critical distinction: Radiation pneumonitis affects lung parenchyma and presents with ground-glass opacities within the radiation portal, not true pleural inflammation 1.

Thermal Ablation vs. External Beam Radiation

The strongest evidence for diaphragmatic injury causing pleural complications comes from thermal ablation procedures (radiofrequency ablation and microwave ablation), not external beam radiation therapy:

• Diaphragmatic injury occurs in approximately 17% of patients undergoing hepatic thermal ablation adjacent to the diaphragm 4
• This can lead to bile-stained pleural fistula and bilious pleuritis 5
• Symptoms include right shoulder pain (referred pain from diaphragmatic irritation) lasting 2-14 days 4
• CT findings show focal diaphragmatic thickening 4

High-Dose Brachytherapy Data

Recent evidence from liver high-dose-rate interstitial brachytherapy shows that small volumes of diaphragm can tolerate extreme radiation doses (median Dmax 302 Gy, range 54-396 Gy) without clinically significant toxicity at median 23-month follow-up 6. This suggests the diaphragm has substantial radiation tolerance when small volumes are exposed.

Clinical Presentation If It Occurs

If radiation-induced diaphragmatic inflammation were to occur, the expected presentation would mirror thermal ablation injury:

• Right shoulder pain (referred pain via phrenic nerve) 4
• Pleuritic chest pain (pain with breathing)
• Dyspnea if associated with pleural effusion 1
• Imaging findings: Diaphragmatic thickening on CT, possible small pleural effusion 4

Differential Diagnosis: Hepatic Hydrothorax

In patients with underlying cirrhosis receiving hepatic radiation, pleural effusion may represent hepatic hydrothorax rather than radiation-induced pleuritis:

• Occurs through small diaphragmatic defects allowing ascites to enter the pleural space 1
• More common on the right side 1
• Diagnosed by thoracentesis showing transudate with serum-to-pleural fluid albumin gradient >1.1 g/dL 1
• This is a mechanical phenomenon, not inflammatory pleuritis 1

Practical Clinical Algorithm

When evaluating pleural symptoms during or after hepatic radiation:

1. Timing assessment:

   • <2 months post-radiation: Consider acute radiation effect, infection, or procedure-related injury 3
   • 2-6 months: Radiation pneumonitis is most likely if lung was in field 3

   • 6 months: Radiation fibrosis or unrelated cause 3

2. Imaging evaluation:

   • Chest X-ray first to identify pleural effusion 1
   • Contrast-enhanced CT chest/abdomen to assess diaphragmatic integrity, pleural disease, and relationship to radiation field 1, 7
   • Look for ground-glass opacity within radiation portal (pneumonitis) vs. pleural-based abnormality 1

3. If pleural effusion present:

   • Diagnostic thoracentesis to differentiate transudate (hydrothorax) from exudate (infection, malignancy) 1
   • Rule out spontaneous bacterial empyema, especially in cirrhotic patients 1

4. Management:

   • True radiation pneumonitis: Early corticosteroids may be effective 3
   • Hepatic hydrothorax: Diuretics, therapeutic thoracentesis for dyspnea 1
   • Suspected diaphragmatic injury: Conservative management with observation; surgical repair rarely needed 4

Critical Caveats

• No high-quality evidence specifically documents "radiation-induced diaphragmatic pleuritis" as a distinct clinical entity from external beam hepatic radiation 1, 3
• The diaphragm appears to have high radiation tolerance when small volumes receive high doses 6
• Most pleural complications in hepatic radiation patients are either radiation pneumonitis (lung parenchymal), hepatic hydrothorax (mechanical), or related to thermal ablation rather than external beam radiation 3, 5, 4
• Do not confuse radiation pneumonitis (common, well-documented) with true diaphragmatic pleuritis (poorly documented in radiation literature) 1, 3