Further aspects concering peripheral lung carcinoma in CEUS

Dear Madam and Sir,

We kindly thank you for writing us concerning our published article entitled: “Vascularization of Primary, Peripheral Lung Carcinoma in CEUS” [1].

Of course the researcher and the examiner should bear in mind that the blood supply and the hemodynamics of the pulmonary circulation could depend on several possible, variable parameters.

The Euler-Liljestrand reflex (hypoxic vasoconstriction), comorbidities (e. g. pulmonary hypertension and heart failure), cancer location [2], neoangiogenesis [3], vessel obstruction by tumor infiltration [4] and thrombosis by e. g. micrometastasis have to mentioned. This is even more important in quantitative measurements. The extent to which these parameters practically affect vascularization often remains unclear.

Thus, the time to enhancement is not useful to discriminate between a BA and a PA pattern.

The dual blood supply of the lung nevertheless offers two different vascularization patterns when examining with CEUS. On the one hand, we can depict enhancement before systemic vascularization emerges (chest wall enhancement), defined as PA here. On the other hand, enhancement is seen simultaneously or after systemic vascularization, called BA here. In the case of an occluded pulmonary artery (branch), we would expect BA vascularization, whereas a PA pattern might include tumor vascularization by pulmonary artery and the pulmonary capillaries as well as the “Sperrarterien” and bronchial arteries.

We totally agree with the letter writer that hepatic and lung vasculatures differ on the microscopic level. Hayek described “Sperrarterien” of the lungs – thick wall vessel connections between the pulmonary artery and the bronchial artery, which are normally closed. In the case of hypoxic events like a pulmonary embolism, these “Sperrarterien” are opened and blood from the bronchial arteries flows into the distal parts of the pulmonary artery [5]. However, it is unclear whether and how these anastomoses contribute to lung cancer vascularization. Selective angiography studies showed no anastomoses [6] or broncho-pulmonary anastomoses in just a couple of patients [7]. A postmortem angiography study on lung resectates visualized several bronchopulmonary anastomoses and the pulmonary and bronchial vascularization pattern [2].

We examined patients with dorsal lung consolidations in a sitting position (n = 58, 65 %) and those with ventral lung consolidation in a half-sitting position (n = 31, 35 %). Whether a sitting or supine examination position influences CEUS vascularization in lung carcinoma has not yet been investigated to our knowledge.

In terms of air bronchograms, we hypothesized that lepidic adenocarcinomas are associated with distributed/branched air bronchograms and that tumor necrosis, independently of the tumor histology, shows local “spotted” air bronchograms. It’s just a descriptive attempt to differentiate air bronchograms by ultrasound parameters. A pathological correlation is of course desirable.

Of course, it would be nice and necessary to further investigate lung carcinoma vascularization by comparative studies using angiography, CT/MRI angiography, ultrasound (CEUS), V/P-scan, PET and pathologic samples.

• References

• 1 Findeisen H, Trenker C, Görg C. et al. Vascularization of Primary, Peripheral Lung Carcinoma in CEUS – A Retrospective Study (n = 89 Patients). Ultraschall in Med 2019; 40: 603-608 . doi:10.1055/a-0725-7865
• 2 Milne EN. Circulation of primary and metastatic pulmonary neoplasms. A postmortem microarteriographic study. Am J Roentgenol Radium Ther Nucl Med 1967; 100: 603-619 . doi:10.2214/ajr.100.3.603
• 3 Eldridge L, Moldobaeva A, Zhong Q. et al. Bronchial Artery Angiogenesis Drives Lung Tumor Growth. Cancer Res 2016; 76: 5962-5969 . doi:10.1158/0008-5472.CAN-16-1131
• 4 Galie M, D’Onofrio M, Montani M. et al. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents. Neoplasia 2005; 7: 528-536
• 5 Pump K. The Bronchial Arteries and Their Anastomoses in the Human Lung. Diseases of the Chest 1963; 43: 245-255 . doi:10.1378/chest.43.3.245
• 6 Botenga AS. The significance of broncho-pulmonary anastomoses in pulmonary anomalies: a selective angiographic study. Radiol Clin Biol 1969; 38: 309-328
• 7 Hellekant C, Svanberg L. Bronchial Angiography in the Staging of Bronchogenic Carcinoma. Acta Radiologica: Oncology, Radiation, Physics, Biology 1979; 18: 81-96 . doi:10.3109/02841867909128194