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Unusual course of an abdominal aortic aneurysm in a patient treated with chemotherapy for gastric cancer
Unusual course of an abdominal aortic aneurysm in a patient treated with chemotherapy for gastric cancer Juergen Zanow, MD, Yvonne Leistner, MD, Stephan Ludewig, MD, Falk Rauchfuss, MD, and Utz Settmacher, MD, Jena, Germany Most aortic aneurysms have a degenerative genesis and show a slow expansion over years. Only a few patients with a rapid progression of mycotic or inflammatory aneurysm during some weeks or months have been reported. We report a patient with a rapidly growing symptomatic infrarenal aneurysm with a maximal diameter of 53 mm, which developed over a 5-month period from a normal aorta and did not feature typical signs of degenerative, inflammatory, or mycotic aneurysm. The aneurysm was successfully treated by endovascular repair. A complete shrinking of the aneurysm sac was demonstrated during a few weeks postoperatively. Because the patient received chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for metastatic gastric carcinoma 1 year before the aneurysm occurred, we postulate that chemotherapy induced a rapid expansion of the aorta in this patient. ( J Vasc Surg 2012;55:841-3.)
Most aortic aneurysms have a degenerative genesis and show a slow expansion over years. Only a few patients with a rapid progression of mycotic or inflammatory aneurysm during some weeks or months have been reported. We report a patient with a rapidly growing symptomatic infrarenal aneurysm with a maximal diameter of 53 mm that developed from a normal aorta during a 5-month period and did not feature typical signs of a degenerative, inflammatory, or mycotic aneurysm. CASE REPORT A 60-year-old man in good physical and mental status was referred for abdominal and back pain that had lasted for 2 weeks and was increasing in intensity. At admission, the patient had an acute pain at a palpable abdominal aortic aneurysm (AAA). He was a nonsmoker, had no history of cardiovascular disease, and had not had a fever during the previous months. Laboratory tests revealed no abnormal findings other than a highly elevated C-reactive protein (CRP) level (200 mg/L). In particular, the white blood cell count, procalcitonin, and creatinine values were normal. The patient was diagnosed 1 year before the admission with an adenocarcinoma of the stomach (uT2, intestinal type) with multiple hepatic metastases. The patient was treated by 10 cycles of chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, according to the established regimen for these agents.1 The patient From the Department of General, Visceral and Vascular Surgery, University Hospital Jena. Competition of interest: none. Reprint requests: Juergen Zanow, MD, University Hospital Jena, Department of General, Visceral and Vascular Surgery, Erlanger Allee 101, 07743 Jena, Germany (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest. 0741-5214/$36.00 Copyright © 2012 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2011.09.005
tolerated chemotherapy well, without leukopenia or other treatment-related adverse events other than moderate nausea. A computed tomography (CT) scan 5 months before the admission demonstrated a normal aorta with an axial diameter of 17 mm (Fig 1). A staging CT scan 1 week before admission showed a significant regression of tumor and metastases, but also a newly developed AAA with a maximal axial diameter of 53 mm (Fig 2). The aneurysm of the noncalcified infrarenal aorta had no intraluminal thrombus. This CT scan revealed minimal periaortic fluid collection and moderate swelling of the left iliopsoas muscle, and the infrarenal aorta did not feature the typical signs of an inflammatory or mycotic AAA (thickened and often calcified aortic wall, a mass of periaortic inflammatory tissue with relative sparing of the posterior wall). Despite the very short proximal aneurysm neck length of 10 mm, the symptomatic AAA was reconstructed by endovascular aortic repair (EVAR). The postoperative CT scan revealed the correct position of the Endurant endograft (Medtronic, Santa Rosa, Calif; main body diameter, 28 mm) and a completely excluded AAA (Fig 3). The patient was discharged on postoperative day 5 with minimal back pain and a CRP value of 60 mg/L. As soon as 6 weeks after the procedure, ultrasound imaging demonstrated a shrunken AAA with a maximal diameter of 33 mm. At this time, a gastrectomy, left hepatectomy, and segmentectomy were performed, with an uneventful postoperative course. The preoperative CRP value of 13 mg/L was within the nearly normal reference range. Histologic examination detected vital tumor cells in the liver metastases. A CT scan 6 months after EVAR showed a complete shrinkage of the aneurysm to the diameter of the endograft (Fig 3). The combined positron emission tomography scan detected no increased metabolic activity in the aortic wall or in any other location. Contrast-enhanced ultrasound imaging 1 year postoperatively demonstrated the AAA was unchanged and completely shrunk. The CT scan confirmed complete shrinkage of the AAA and did not show a recurrent or metastatic status of the gastric carcinoma.
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842 Zanow et al
Fig 1. A computed tomography scan 5 months before admission shows a normal aorta.
JOURNAL OF VASCULAR SURGERY March 2012
Fig 2. A symptomatic infrarenal abdominal aortic aneurysm with a diameter of 53 mm is seen at the time of admission. The arrows mark a minimal periaortic fluid collection and swelling of left iliopsoas muscle.
The patient is doing well and remains in post-EVAR and oncologic surveillance.
DISCUSSION Such a rapid development of an AAA of a recently normal aorta with a diameter expansion by 36 mm, or triplication of the diameter within a maximum of 5 months, is extremely unusual. For a small AAA of 3.0- to 3.4-cm diameter, a yearly expansion rate of 0.11 to 0.33 cm has been reported.2,3 Also, a rapid complete aneurysm sac retraction over the course of only a few weeks is very uncommon.4,5 Rapid aneurysm expansion was described in single case reports for mycotic6,7 or inflammatory AAAs,8 and for a patient who received chemotherapy with gemcitabine, cisplatinum, and corticosteroids.9 The etiology of the AAA in this patient remains unclear. This is partly because no material was available
for a histologic examination. A degenerative AAA can be excluded definitively. An inflammatory aneurysm, idiopathic aortitis with aneurysmal dilatation, or a mycotic AAA appear to be a possibility, due to the markedly elevated preoperative CRP value and discrete signs of periaortal inflammation. A possible leukopenic effect of previous chemotherapy to otherwise normal laboratory tests of inflammation may be discussed. However, CT scanning did not demonstrate the typical thickened aortic wall of aortitis or inflammatory AAA.10 The uneventful postoperative course, quick decrease of CRP values after one dose of antibiotics, the rapid shrinkage of the AAA, and positron emission tomography findings after EVAR argue against an inflammatory or infectious genesis of AAA.7,10,11
JOURNAL OF VASCULAR SURGERY Volume 55, Number 3
Zanow et al 843
CONCLUSIONS Owing to the rarity of such rapid growth of the AAA, this case report highlights the biologic variability of AAAs. For the patient reported here, the performed treatment appears correct at this time. REFERENCES
Fig 3. A computed tomography scan at the 6-month follow-up after endovascular repair reveals complete shrinkage of the abdominal aortic aneurysm.
Thus, we can only speculate that the rapid growth of the AAA might have been induced by the toxic effects of chemotherapy, even though there is only an anecdotal report to support this assumption.9 Acute cardiac toxicity of 5-fluorouracil is a well-known adverse event,12 but thrombus formation in a normal aorta13,14 and aortic dissection15 represent other and very rare cardiovascular adverse events of chemotherapy. The disturbed synthesis of DNA, collagen, and elastin, release of cytokines, inhibition of smooth muscle cell proliferation, and induction of metalloproteinases are so far predominately hypothetically formulated effects of chemotherapeutics that might induce AAA development.9,16,17 A higher incidence of aneurysms in long-term survivors of cancer treated with chemotherapy is not known. In contrast, neoplasm concomitant with an AAA is not uncommon, and EVAR may be a promising approach for these patients.17,18
1. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006;24:4991-7. 2. Santilli SM, Littooy FN, Cambria RA, Rapp JH, Tretinyak AS, d’Audiffret AC, et al. Expansion rates and outcomes for the 3.0-cm to the 3.9-cm infrarenal abdominal aortic aneurysm. J Vasc Surg 2002;35:666-71. 3. Brown PM, Pattenden R, Vernooy C, Zelt DT, Gutelius JR. Selective management of abdominal aortic aneurysms in a prospective measurement program. J Vasc Surg 1996;23:213-20. 4. Houbballah R, Majewski M, Becquemin JP. Significant sac retraction after endovascular aneurysm repair is a robust indicator of durable treatment success. J Vasc Surg 2010;52:878-83. 5. Wever JJ, Blankensteijn JD, Th M Mali WP, Eikelboom BC. Maximal aneurysm diameter follow-up is inadequate after endovascular abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2000;20:177-82. 6. Borris LC, Nøhr M, Petersen K. Rapid growth and early rupture of a primary mycotic aneurysm of the abdominal aorta. Eur J Vasc Surg 1989;3:461-3. 7. Iimori A, Kanzaki Y, Ito S, Kotani T, Hirano-Kuwata S, Daimon M, et al. Rapidly progressing aneurysm of infected thoracic aorta with pseudoaneurysm formation. Intern Med 2010;49:2461-5. 8. Mory M, Hansmann J, Allenberg JR, Böckler D, Boeckler D. Images in vascular medicine. Rapid expansion of an inflammatory abdominal aortic aneurysm. Vasc Med 2007;12:381-2. 9. Palm SJ, Russwurm GP, Chang D, Rozenblit AM, Ohki T, Veith FJ. Acute enlargement and subsequent rupture of an abdominal aortic aneurysm in a patient receiving chemotherapy for pancreatic carcinoma. J Vasc Surg 2000;32:197-200. 10. Thakor AS, Hiemstra TF, Cousins C, See TC. Multiple inflammatory aneurysms: a rare complication of idiopathic inflammatory aortitis. Eur J Radiol Extra 2009;70:e141-4. 11. Coppi G, Rametta F, Aiello S, Saitta G, Gennai S, Silingardi R. Inflammatory abdominal aortic aneurysm endovascular repair into the longterm follow-up. Ann Vasc Surg 2010;24:1053-9. 12. de Bruijne E, Bonapart IE, Kerker JP, Baggen R. Cardiotoxicity as an adverse effect of 5-fluorouracil. Eur J Intern Med 1999;10:49-52. 13. Apiyasawat S, Wongpraparut N, Jacobson L, Berkowitz H, Jacobs LE, Kotler MN. Cisplatin induced localized aortic thrombus. Echocardiography 2003;20:199-200. 14. Yoon S, Schmassmann-Suhijar D, Zuber M, Konietzny P, Schmassmann A. Chemotherapy with bevacizumab, irinotecan, 5-fluorouracil and leucovorin (IFL) associated with a large, embolizing thrombus in the thoracic aorta. Ann Oncol 2006;17:1851-2. 15. Sclafani F, Carnaghi C, Colombo P, Bozzarelli S, De Vincenzo F, Rimassa L, et al. Case report of acute aortic dissection during treatment with capecitabine for a late recurrence of breast cancer. Chemotherapy 2010;56:203-7. 16. Cwikiel M, Albertsson M, Eskilsson J, Stavenow L. The influence of 5-fluorouracil and methotrexate on vascular endothelium. An experimental study using endothelial cells in the culture. Ann Oncol 1996;7:731-7. 17. Shalhoub J, Naughton P, Lau N, Tsang JS, Kelly CJ, Leahy AL, et al. Concurrent colorectal malignancy and abdominal aortic aneurysm: a multicentre experience and review of the literature. Eur J Vasc Endovasc Surg 2009;37:544-56. 18. Habets J, Buth J, Cuypers PW, Nienhuijs SW, de Hingh IH. Infrarenal abdominal aortic aneurysm with concomitant urologic malignancy: treatment results in the era of endovascular aneurysm repair. Vascular 2010;18:14-9. Submitted Jun 24, 2011; accepted Sep 3, 2011.
Most aortic aneurysms have a degenerative genesis and show a slow expansion over years. Only a few patients with a rapid progression of mycotic or inflammatory aneurysm during some weeks or months have been reported. We report a patient with a rapidly growing symptomatic infrarenal aneurysm with a maximal diameter of 53 mm that developed from a normal aorta during a 5-month period and did not feature typical signs of a degenerative, inflammatory, or mycotic aneurysm. CASE REPORT A 60-year-old man in good physical and mental status was referred for abdominal and back pain that had lasted for 2 weeks and was increasing in intensity. At admission, the patient had an acute pain at a palpable abdominal aortic aneurysm (AAA). He was a nonsmoker, had no history of cardiovascular disease, and had not had a fever during the previous months. Laboratory tests revealed no abnormal findings other than a highly elevated C-reactive protein (CRP) level (200 mg/L). In particular, the white blood cell count, procalcitonin, and creatinine values were normal. The patient was diagnosed 1 year before the admission with an adenocarcinoma of the stomach (uT2, intestinal type) with multiple hepatic metastases. The patient was treated by 10 cycles of chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, according to the established regimen for these agents.1 The patient From the Department of General, Visceral and Vascular Surgery, University Hospital Jena. Competition of interest: none. Reprint requests: Juergen Zanow, MD, University Hospital Jena, Department of General, Visceral and Vascular Surgery, Erlanger Allee 101, 07743 Jena, Germany (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest. 0741-5214/$36.00 Copyright © 2012 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2011.09.005
tolerated chemotherapy well, without leukopenia or other treatment-related adverse events other than moderate nausea. A computed tomography (CT) scan 5 months before the admission demonstrated a normal aorta with an axial diameter of 17 mm (Fig 1). A staging CT scan 1 week before admission showed a significant regression of tumor and metastases, but also a newly developed AAA with a maximal axial diameter of 53 mm (Fig 2). The aneurysm of the noncalcified infrarenal aorta had no intraluminal thrombus. This CT scan revealed minimal periaortic fluid collection and moderate swelling of the left iliopsoas muscle, and the infrarenal aorta did not feature the typical signs of an inflammatory or mycotic AAA (thickened and often calcified aortic wall, a mass of periaortic inflammatory tissue with relative sparing of the posterior wall). Despite the very short proximal aneurysm neck length of 10 mm, the symptomatic AAA was reconstructed by endovascular aortic repair (EVAR). The postoperative CT scan revealed the correct position of the Endurant endograft (Medtronic, Santa Rosa, Calif; main body diameter, 28 mm) and a completely excluded AAA (Fig 3). The patient was discharged on postoperative day 5 with minimal back pain and a CRP value of 60 mg/L. As soon as 6 weeks after the procedure, ultrasound imaging demonstrated a shrunken AAA with a maximal diameter of 33 mm. At this time, a gastrectomy, left hepatectomy, and segmentectomy were performed, with an uneventful postoperative course. The preoperative CRP value of 13 mg/L was within the nearly normal reference range. Histologic examination detected vital tumor cells in the liver metastases. A CT scan 6 months after EVAR showed a complete shrinkage of the aneurysm to the diameter of the endograft (Fig 3). The combined positron emission tomography scan detected no increased metabolic activity in the aortic wall or in any other location. Contrast-enhanced ultrasound imaging 1 year postoperatively demonstrated the AAA was unchanged and completely shrunk. The CT scan confirmed complete shrinkage of the AAA and did not show a recurrent or metastatic status of the gastric carcinoma.
841
842 Zanow et al
Fig 1. A computed tomography scan 5 months before admission shows a normal aorta.
JOURNAL OF VASCULAR SURGERY March 2012
Fig 2. A symptomatic infrarenal abdominal aortic aneurysm with a diameter of 53 mm is seen at the time of admission. The arrows mark a minimal periaortic fluid collection and swelling of left iliopsoas muscle.
The patient is doing well and remains in post-EVAR and oncologic surveillance.
DISCUSSION Such a rapid development of an AAA of a recently normal aorta with a diameter expansion by 36 mm, or triplication of the diameter within a maximum of 5 months, is extremely unusual. For a small AAA of 3.0- to 3.4-cm diameter, a yearly expansion rate of 0.11 to 0.33 cm has been reported.2,3 Also, a rapid complete aneurysm sac retraction over the course of only a few weeks is very uncommon.4,5 Rapid aneurysm expansion was described in single case reports for mycotic6,7 or inflammatory AAAs,8 and for a patient who received chemotherapy with gemcitabine, cisplatinum, and corticosteroids.9 The etiology of the AAA in this patient remains unclear. This is partly because no material was available
for a histologic examination. A degenerative AAA can be excluded definitively. An inflammatory aneurysm, idiopathic aortitis with aneurysmal dilatation, or a mycotic AAA appear to be a possibility, due to the markedly elevated preoperative CRP value and discrete signs of periaortal inflammation. A possible leukopenic effect of previous chemotherapy to otherwise normal laboratory tests of inflammation may be discussed. However, CT scanning did not demonstrate the typical thickened aortic wall of aortitis or inflammatory AAA.10 The uneventful postoperative course, quick decrease of CRP values after one dose of antibiotics, the rapid shrinkage of the AAA, and positron emission tomography findings after EVAR argue against an inflammatory or infectious genesis of AAA.7,10,11
JOURNAL OF VASCULAR SURGERY Volume 55, Number 3
Zanow et al 843
CONCLUSIONS Owing to the rarity of such rapid growth of the AAA, this case report highlights the biologic variability of AAAs. For the patient reported here, the performed treatment appears correct at this time. REFERENCES
Fig 3. A computed tomography scan at the 6-month follow-up after endovascular repair reveals complete shrinkage of the abdominal aortic aneurysm.
Thus, we can only speculate that the rapid growth of the AAA might have been induced by the toxic effects of chemotherapy, even though there is only an anecdotal report to support this assumption.9 Acute cardiac toxicity of 5-fluorouracil is a well-known adverse event,12 but thrombus formation in a normal aorta13,14 and aortic dissection15 represent other and very rare cardiovascular adverse events of chemotherapy. The disturbed synthesis of DNA, collagen, and elastin, release of cytokines, inhibition of smooth muscle cell proliferation, and induction of metalloproteinases are so far predominately hypothetically formulated effects of chemotherapeutics that might induce AAA development.9,16,17 A higher incidence of aneurysms in long-term survivors of cancer treated with chemotherapy is not known. In contrast, neoplasm concomitant with an AAA is not uncommon, and EVAR may be a promising approach for these patients.17,18
1. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006;24:4991-7. 2. Santilli SM, Littooy FN, Cambria RA, Rapp JH, Tretinyak AS, d’Audiffret AC, et al. Expansion rates and outcomes for the 3.0-cm to the 3.9-cm infrarenal abdominal aortic aneurysm. J Vasc Surg 2002;35:666-71. 3. Brown PM, Pattenden R, Vernooy C, Zelt DT, Gutelius JR. Selective management of abdominal aortic aneurysms in a prospective measurement program. J Vasc Surg 1996;23:213-20. 4. Houbballah R, Majewski M, Becquemin JP. Significant sac retraction after endovascular aneurysm repair is a robust indicator of durable treatment success. J Vasc Surg 2010;52:878-83. 5. Wever JJ, Blankensteijn JD, Th M Mali WP, Eikelboom BC. Maximal aneurysm diameter follow-up is inadequate after endovascular abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2000;20:177-82. 6. Borris LC, Nøhr M, Petersen K. Rapid growth and early rupture of a primary mycotic aneurysm of the abdominal aorta. Eur J Vasc Surg 1989;3:461-3. 7. Iimori A, Kanzaki Y, Ito S, Kotani T, Hirano-Kuwata S, Daimon M, et al. Rapidly progressing aneurysm of infected thoracic aorta with pseudoaneurysm formation. Intern Med 2010;49:2461-5. 8. Mory M, Hansmann J, Allenberg JR, Böckler D, Boeckler D. Images in vascular medicine. Rapid expansion of an inflammatory abdominal aortic aneurysm. Vasc Med 2007;12:381-2. 9. Palm SJ, Russwurm GP, Chang D, Rozenblit AM, Ohki T, Veith FJ. Acute enlargement and subsequent rupture of an abdominal aortic aneurysm in a patient receiving chemotherapy for pancreatic carcinoma. J Vasc Surg 2000;32:197-200. 10. Thakor AS, Hiemstra TF, Cousins C, See TC. Multiple inflammatory aneurysms: a rare complication of idiopathic inflammatory aortitis. Eur J Radiol Extra 2009;70:e141-4. 11. Coppi G, Rametta F, Aiello S, Saitta G, Gennai S, Silingardi R. Inflammatory abdominal aortic aneurysm endovascular repair into the longterm follow-up. Ann Vasc Surg 2010;24:1053-9. 12. de Bruijne E, Bonapart IE, Kerker JP, Baggen R. Cardiotoxicity as an adverse effect of 5-fluorouracil. Eur J Intern Med 1999;10:49-52. 13. Apiyasawat S, Wongpraparut N, Jacobson L, Berkowitz H, Jacobs LE, Kotler MN. Cisplatin induced localized aortic thrombus. Echocardiography 2003;20:199-200. 14. Yoon S, Schmassmann-Suhijar D, Zuber M, Konietzny P, Schmassmann A. Chemotherapy with bevacizumab, irinotecan, 5-fluorouracil and leucovorin (IFL) associated with a large, embolizing thrombus in the thoracic aorta. Ann Oncol 2006;17:1851-2. 15. Sclafani F, Carnaghi C, Colombo P, Bozzarelli S, De Vincenzo F, Rimassa L, et al. Case report of acute aortic dissection during treatment with capecitabine for a late recurrence of breast cancer. Chemotherapy 2010;56:203-7. 16. Cwikiel M, Albertsson M, Eskilsson J, Stavenow L. The influence of 5-fluorouracil and methotrexate on vascular endothelium. An experimental study using endothelial cells in the culture. Ann Oncol 1996;7:731-7. 17. Shalhoub J, Naughton P, Lau N, Tsang JS, Kelly CJ, Leahy AL, et al. Concurrent colorectal malignancy and abdominal aortic aneurysm: a multicentre experience and review of the literature. Eur J Vasc Endovasc Surg 2009;37:544-56. 18. Habets J, Buth J, Cuypers PW, Nienhuijs SW, de Hingh IH. Infrarenal abdominal aortic aneurysm with concomitant urologic malignancy: treatment results in the era of endovascular aneurysm repair. Vascular 2010;18:14-9. Submitted Jun 24, 2011; accepted Sep 3, 2011.