- Email: [email protected]
Use of Fluoroscopy During Endobronchial Ultrasonography for Transbronchial Lung Biopsies of Peripheral Lung Lesions
Journal of Thoracic Oncology • Volume 3, Number 6, June 2008
carcinomas both in vivo and in vitro.2 Lung cancer cells express both ␣ and  ER; the former, which seems to occur more often in the lung of women than men is localized in the cytoplasm, the latter in the nucleus. Interesting data, regarding the intense crosstalk between ERs and growth factor such as EGF, are emerging.3–5 Direct binding of the ligand-ER complex with steroid receptor coactivators and estrogen receptor elements in DNA leads to change in gene transcription that regulate growth, differentiation, apoptosis, and angiogenesis. Alternative pathways may be activated by estrogen without direct ER binding to DNA or by kinases associated to epidermal growth factor receptor in the absence of estrogens. Many rapid effects of estrogens may be also due to activation of extranuclear signaling pathways that are mediated by cell-surface forms of ERs. The interaction between ER and EGFR/HER2 is demonstrated in NSCLC cell lines as the treatment with estradiol resulted in down-regulation of EGFR, whereas treatment with the antiestrogen fulvestrant increased the EGFR expression. In fact the combination of fulvestrant and gefitinib in NSCLC may inhibit cell proliferation, induce apoptosis and affect downstream signaling pathways. Moreover, ER  expression is decreased in response to EGF and increased in response to gefitinib.5 The recent evidence of crosstalk between the EGFR and ER pathways, along with the striking efficacy of tyrosine kinase inhibitors in women with lung cancer and the emerging role of estrogens in lung tumorigenesis, provides rationale to examine drugs that target these two pathways for lung cancer treatment in selected patients. Monica Giovannini, MD Carmen Belli, MD Eugenio Villa, MD and Vanesa Gregorc, MD Department of Medical Oncology San Raffaele Institute Milan, Italy
REFERENCES 1. Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst (Bethesda) 1996;88:183–192. 2. Stabile L, Siegfried J. Estrogen receptor pathways in lung cancer. Curr Oncol Rep 2004;6: 259 –267.
Letters to the Editor
FIGURE 1. CT chest demonstrating right middle lobe mass with dual “bronchus sign” (arrow). 3. Levin ER. Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol Endocrinol 2003;17:309 –317. 4. Pietras RJ, Marquez DC, Chen H-W, Tsai E, Weinberg O, Fishbein M. Estrogen and growth factor receptor interacations in human breast and non-small cell lung cancer cells. Steroids 2005;70:372–381. 5. Stabile LP, Lyker JS, Gubish CT, Zhang W, Grandis JR, Siegfried JM. Combined targeting of the estrogen receptor and the epidermal growth factor receptor in non-small cell lung cancer shows enhanced antiproliferative effects. Cancer Res 2005;65:1459 –1470.
Use of Fluoroscopy During Endobronchial Ultrasonography for Transbronchial Lung Biopsies of Peripheral Lung Lesions To the Editor: Fluoroscopic guidance in the performance of transbronchial biopsies is known to increase diagnostic yield by allowing biopsies to accurately target Disclosure: The authors declare no conflict of interest. Address for correspondence: Daniel Steinfort, MBBS, Department of Respiratory Medicine, Royal Melbourne Hospital. Victoria 3050, Australia. E-mail: [email protected] Copyright © 2008 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/08/0306-0685
Copyright © 2008 by the International Association for the Study of Lung Cancer
the area of interest.1 Diagnostic yields have increased further with the introduction of Endobronchial Ultrasound using Guide Sheath (EBUS-GS), with initial reports utilizing fluoroscopic guidance during the procedure.2 Recent reports have suggested Endobronchial Ultrasound (EBUS) may be performed without fluoroscopy.3 However, the authors of this study noted a lower yield in lesions in the right lower lobe, and attributed this to movement of the probe as a result of deep respiration. Dooms et al.4 recently described the use of EBUS bronchoscopy in bronchoscopically occult pulmonary lesions and noted that for potentially fluoroscopically visible lesions (⬎2 cm) no size difference was noted between successfully diagnosed lesions and undiagnosed ones, suggesting that further increasing accurate localization of lesions using fluoroscopy may have resulted in a further improved yield. Our experience is that fluoroscopy is a valuable tool in the performance of EBUS-GS bronchoscopy as it is able to confirm immediately before each biopsy that specimens are taken from the area of interest. In support of this, we report a 60-year-old man, current smoker who presented for bronchoscopy for investigation of an incidental 2.6 cm right middle lobe nodule on computed tomography chest (see Figure 1). Normal endobronchial examination was followed by EBUS-GS examination that
685
FIGURE 2. Endobronchial ultrasound image initially demonstrated in right middle lobe. Arrows mark the border of the lesion, with the ultrasound probe positioned in the middle of the lesion.
positioned in a different bronchus, the solid mass could still be visualized. Further biopsies were performed. Histologic examination confirmed bronchoalveolar carcinoma. Our case demonstrates the value of fluoroscopy in performance of EBUS-GS bronchoscopy. The two EBUS images obtained are consistent with the probe being in different bronchial segments. This is not surprising as on computed tomography chest there is clearly a dual “bronchus sign” seen. Had fluoroscopy not been used, we would have been unaware of the inadvertent repositioning of the guide sheath. This clearly has the potential to compromise diagnostic yield of the procedure. Even movement to a bronchus adjacent to a mass may compromise diagnostic yield.5 There is potential for movement of the probe after deployment in any lobe due to deep respiration or vigorous coughing. Given performance of EBUS-GS is not a real-time procedure, we feel its optimal performance in the investigation of peripheral pulmonary lesions is aided by fluoroscopic guidance, as illustrated by this case. Daniel Steinfort, MBBS Louis Irving, MBBS Department of Respiratory Medicine Royal Melbourne Hospital Victoria 3050, Australia
REFERENCES
FIGURE 3. Endobronchial ultrasound image seen subsequent to fluoroscopic demonstration of relocation of guide sheath. Ultrasound probe is now situated at periphery of lesion (arrow), as opposed to centrally (as seen in Figure 2).
demonstrated a right middle lobe solid lesion (Figure 2). As previously described,2 the probe was removed after localization of the procedure, leaving the guide sheath in place. Three transbronchial lung biopsies under fluoroscopic guidance were performed via the guide sheath. Fluoroscopic screening is performed during each biopsy to con-
686
firm, firstly, that the sheath remains in its original position and, secondly, that the biopsy forceps have passed the correct distance into the lung periphery. Screening for performance of a fourth biopsy suggested the guide sheath had moved into an adjacent bronchus (Figure 3). Repeat EBUS examination demonstrated that although the probe was
1. Cox ID, Bagg LR, Russell NJ, et al. Relationship of radiologic position to the diagnostic yield of fiberoptic bronchoscopy in bronchial carcinoma. Chest 1984;85:519 –522. 2. Kurimoto N, Miyazawa T, Okimasa S, et al. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. Chest 2004;126:959 –965. 3. Yoshikawa M, Sukoh N, Yamazaki K, et al. Diagnostic value of endobronchial ultrasonography with a guide sheath for peripheral pulmonary lesions without X-ray fluoroscopy. Chest 2007;131:1788 –1793. 4. Dooms CA, Verbeken EK, Becker HD, et al. Endobronchial ultrasonography in bronchoscopic occult pulmonary lesions. J Thorac Oncol 2007;2:121–124. 5. Yamada N, Yamazaki K, Kurimoto N, et al. Factors related to diagnostic yield of transbronchial biopsy using endobronchial ultrasonography with a guide sheath in small peripheral pulmonary lesions. Chest 2007;132: 603– 608.
Journal of Thoracic Oncology • Volume 3, Number 6, June 2008
carcinomas both in vivo and in vitro.2 Lung cancer cells express both ␣ and  ER; the former, which seems to occur more often in the lung of women than men is localized in the cytoplasm, the latter in the nucleus. Interesting data, regarding the intense crosstalk between ERs and growth factor such as EGF, are emerging.3–5 Direct binding of the ligand-ER complex with steroid receptor coactivators and estrogen receptor elements in DNA leads to change in gene transcription that regulate growth, differentiation, apoptosis, and angiogenesis. Alternative pathways may be activated by estrogen without direct ER binding to DNA or by kinases associated to epidermal growth factor receptor in the absence of estrogens. Many rapid effects of estrogens may be also due to activation of extranuclear signaling pathways that are mediated by cell-surface forms of ERs. The interaction between ER and EGFR/HER2 is demonstrated in NSCLC cell lines as the treatment with estradiol resulted in down-regulation of EGFR, whereas treatment with the antiestrogen fulvestrant increased the EGFR expression. In fact the combination of fulvestrant and gefitinib in NSCLC may inhibit cell proliferation, induce apoptosis and affect downstream signaling pathways. Moreover, ER  expression is decreased in response to EGF and increased in response to gefitinib.5 The recent evidence of crosstalk between the EGFR and ER pathways, along with the striking efficacy of tyrosine kinase inhibitors in women with lung cancer and the emerging role of estrogens in lung tumorigenesis, provides rationale to examine drugs that target these two pathways for lung cancer treatment in selected patients. Monica Giovannini, MD Carmen Belli, MD Eugenio Villa, MD and Vanesa Gregorc, MD Department of Medical Oncology San Raffaele Institute Milan, Italy
REFERENCES 1. Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst (Bethesda) 1996;88:183–192. 2. Stabile L, Siegfried J. Estrogen receptor pathways in lung cancer. Curr Oncol Rep 2004;6: 259 –267.
Letters to the Editor
FIGURE 1. CT chest demonstrating right middle lobe mass with dual “bronchus sign” (arrow). 3. Levin ER. Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol Endocrinol 2003;17:309 –317. 4. Pietras RJ, Marquez DC, Chen H-W, Tsai E, Weinberg O, Fishbein M. Estrogen and growth factor receptor interacations in human breast and non-small cell lung cancer cells. Steroids 2005;70:372–381. 5. Stabile LP, Lyker JS, Gubish CT, Zhang W, Grandis JR, Siegfried JM. Combined targeting of the estrogen receptor and the epidermal growth factor receptor in non-small cell lung cancer shows enhanced antiproliferative effects. Cancer Res 2005;65:1459 –1470.
Use of Fluoroscopy During Endobronchial Ultrasonography for Transbronchial Lung Biopsies of Peripheral Lung Lesions To the Editor: Fluoroscopic guidance in the performance of transbronchial biopsies is known to increase diagnostic yield by allowing biopsies to accurately target Disclosure: The authors declare no conflict of interest. Address for correspondence: Daniel Steinfort, MBBS, Department of Respiratory Medicine, Royal Melbourne Hospital. Victoria 3050, Australia. E-mail: [email protected] Copyright © 2008 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/08/0306-0685
Copyright © 2008 by the International Association for the Study of Lung Cancer
the area of interest.1 Diagnostic yields have increased further with the introduction of Endobronchial Ultrasound using Guide Sheath (EBUS-GS), with initial reports utilizing fluoroscopic guidance during the procedure.2 Recent reports have suggested Endobronchial Ultrasound (EBUS) may be performed without fluoroscopy.3 However, the authors of this study noted a lower yield in lesions in the right lower lobe, and attributed this to movement of the probe as a result of deep respiration. Dooms et al.4 recently described the use of EBUS bronchoscopy in bronchoscopically occult pulmonary lesions and noted that for potentially fluoroscopically visible lesions (⬎2 cm) no size difference was noted between successfully diagnosed lesions and undiagnosed ones, suggesting that further increasing accurate localization of lesions using fluoroscopy may have resulted in a further improved yield. Our experience is that fluoroscopy is a valuable tool in the performance of EBUS-GS bronchoscopy as it is able to confirm immediately before each biopsy that specimens are taken from the area of interest. In support of this, we report a 60-year-old man, current smoker who presented for bronchoscopy for investigation of an incidental 2.6 cm right middle lobe nodule on computed tomography chest (see Figure 1). Normal endobronchial examination was followed by EBUS-GS examination that
685
FIGURE 2. Endobronchial ultrasound image initially demonstrated in right middle lobe. Arrows mark the border of the lesion, with the ultrasound probe positioned in the middle of the lesion.
positioned in a different bronchus, the solid mass could still be visualized. Further biopsies were performed. Histologic examination confirmed bronchoalveolar carcinoma. Our case demonstrates the value of fluoroscopy in performance of EBUS-GS bronchoscopy. The two EBUS images obtained are consistent with the probe being in different bronchial segments. This is not surprising as on computed tomography chest there is clearly a dual “bronchus sign” seen. Had fluoroscopy not been used, we would have been unaware of the inadvertent repositioning of the guide sheath. This clearly has the potential to compromise diagnostic yield of the procedure. Even movement to a bronchus adjacent to a mass may compromise diagnostic yield.5 There is potential for movement of the probe after deployment in any lobe due to deep respiration or vigorous coughing. Given performance of EBUS-GS is not a real-time procedure, we feel its optimal performance in the investigation of peripheral pulmonary lesions is aided by fluoroscopic guidance, as illustrated by this case. Daniel Steinfort, MBBS Louis Irving, MBBS Department of Respiratory Medicine Royal Melbourne Hospital Victoria 3050, Australia
REFERENCES
FIGURE 3. Endobronchial ultrasound image seen subsequent to fluoroscopic demonstration of relocation of guide sheath. Ultrasound probe is now situated at periphery of lesion (arrow), as opposed to centrally (as seen in Figure 2).
demonstrated a right middle lobe solid lesion (Figure 2). As previously described,2 the probe was removed after localization of the procedure, leaving the guide sheath in place. Three transbronchial lung biopsies under fluoroscopic guidance were performed via the guide sheath. Fluoroscopic screening is performed during each biopsy to con-
686
firm, firstly, that the sheath remains in its original position and, secondly, that the biopsy forceps have passed the correct distance into the lung periphery. Screening for performance of a fourth biopsy suggested the guide sheath had moved into an adjacent bronchus (Figure 3). Repeat EBUS examination demonstrated that although the probe was
1. Cox ID, Bagg LR, Russell NJ, et al. Relationship of radiologic position to the diagnostic yield of fiberoptic bronchoscopy in bronchial carcinoma. Chest 1984;85:519 –522. 2. Kurimoto N, Miyazawa T, Okimasa S, et al. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. Chest 2004;126:959 –965. 3. Yoshikawa M, Sukoh N, Yamazaki K, et al. Diagnostic value of endobronchial ultrasonography with a guide sheath for peripheral pulmonary lesions without X-ray fluoroscopy. Chest 2007;131:1788 –1793. 4. Dooms CA, Verbeken EK, Becker HD, et al. Endobronchial ultrasonography in bronchoscopic occult pulmonary lesions. J Thorac Oncol 2007;2:121–124. 5. Yamada N, Yamazaki K, Kurimoto N, et al. Factors related to diagnostic yield of transbronchial biopsy using endobronchial ultrasonography with a guide sheath in small peripheral pulmonary lesions. Chest 2007;132: 603– 608.
Journal of Thoracic Oncology • Volume 3, Number 6, June 2008