Contemporary Surgical Management of Cardiac Paragangliomas ADULT CARDIAC
Basel Ramlawi, MD, Elizabeth A. David, MD, Min P. Kim, MD, Luis J. Garcia-Morales, MD, Shanda H. Blackmon, MD, David C. Rice, MD, Ara A. Vaporciyan, MD, and Michael J. Reardon, MD Methodist DeBakey Heart and Vascular Center, Cardiovascular Surgery, and Department of Thoracic and Cardiovascular Surgery, MD Anderson Cancer Center, Houston, Texas
Background. Cardiac paragangliomas are an extremely rare subset of chromaffin cell tumors that develop from neural crest cells. Methods. Between March 2004 and October 2010, 7 male patients from our two institutions who underwent surgical resection of cardiac paraganglioma were retrospectively reviewed. Results. In 5 patients, paragangliomas originated from the roof of the left atrium, and in 2 patients, they originated from the aortic root. Hospital mortality was 14%.
Conclusions. Complete surgical resection remains the mainstay of therapy and can be curative, but carries a significant risk of intraoperative bleeding and usually requires cardiopulmonary bypass and often complex resection techniques, including cardiac autotransplantation.
P
Material and Methods
aragangliomas are chromaffin tumors arising from neural crest cells that can originate from parasympathetic or sympathetic ganglia. Only 1% to 2% of paragangliomas occur in the chest [1], most in the posterior mediastinum [2]. Cardiac paragangliomas are exceedingly rare and usually arise from the roof of the left atrium but can occur in any cardiac chamber or at the base of the aortic root and pulmonary artery. Cardiac paragangliomas may cause symptoms of hypertension if hormonally active and catecholamine secreting or from mass effect of the tumor as these are usually large when found (Fig 1A and 1B). They are soft fleshy tumors that parasitize the coronary blood flow and are extremely vascular (Fig 1C and 1D). Cardiac paragangliomas do not usually have a capsule and cannot be simply shelled out in most cases but, rather, require full thickness tissue resection to obtain histologically negative margins (Fig 2). Complete surgical resection is the only effective treatment modality for these tumors. They are generally large in size, are extremely vascular, in close anatomic proximity to vital cardiac structures, and lack encapsulation. We use cardiac magnetic resonance imaging (MRI) for anatomic characterization of the tumor and cardiac catheterization to define tumor blood supply in all cases. The extreme vascularity and anatomic location of these tumors make meticulous surgical planning mandatory and may require complex surgical procedures for success. We discuss our approach to cardiac paraganglioma and follow-up results.
Accepted for publication Feb 13, 2012. Address correspondence to Dr Reardon, 6550 Fannin St, Ste 1401, Houston, TX 77030; e-mail:
[email protected].
© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2012;93:1972– 6) © 2012 by The Society of Thoracic Surgeons
Institutional Review Board approval and waiver of consent was obtained for retrospective review of all patients undergoing resection of cardiac paraganglioma at The Methodist Hospital and MD Anderson Cancer Center. Analysis of our databases identified 7 patients who underwent surgical resection of a cardiac paraganglioma between March 2004 and October 2010. Perioperative data were collected using all available medical records from diagnosis to October 2010. Follow-up included use of medical records and direct patient contact. All patients were evaluated using a combination of transthoracic echocardiography, contrast-enhanced computed tomography scanning (CT), cardiac MRI, and cardiac catheterization preoperatively. Some of the patients early in this series did not undergo cardiac MRI as it was not available; currently, our standard imaging of choice is cardiac MRI evaluation with cardiac catheterization to characterize the anatomy and vascular supply of the tumor. We have not found preoperative laboratory work to be useful in these cases, as none of our patients had elevated serum catecholamines preoperatively. When making the decision for surgical resection, our goal is always complete resection and avoidance of massive hemorrhage. We have not found preoperative embolization to be helpful in this setting as many of the tumors derive blood supply from branches of coronary arteries. We feel that en-bloc resection is the best thera-
Dr Reardon discloses that he has a financial relationship with Medtronic.
0003-4975/$36.00 doi:10.1016/j.athoracsur.2012.02.040
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Fig 1. (A, B) Cardiac magnetic resonance imaging demonstrating left atrial mass. (C, D) Coronary angiogram demonstrating tumor blood supply originating from the circumflex system.
peutic option for these patients, with reconstruction of involved structures where needed. We consider use of our previously described autotransplantation technique when there is tumor involving pulmonary veins or large portions of the left atrium [4]. En-bloc resection with reconstruction also helps to minimize the hemorrhagic
nature of these tumors, as a majority of the work is done with the aorta cross-clamped in a relatively bloodless field. There are no specific modifications made for the anesthetic management of these patients. We do not currently offer these patients neoadjuvant or adjuvant chemotherapy or radiation.
Fig 2. (A) Intraoperative photograph of cardiac paraganglioma. (B) Gross photograph of cardiac paraganglioma after resection. (C, D) Microscopic views of cardiac paraganglioma with hematoxylin and eosin stain. (original magnification: C, ⫻4; D, ⫻20). The cardiac tumor shows a well-encapsulated paraganglioma with the typical Zellballen pattern.
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Table 1. Preoperative Patient Characteristics Pt. No. ADULT CARDIAC
Sex
Age, Years
HTN
1a 2a 3 4 5b
Male Male Male Male Male
26 63 32 26 54
Yes Yes No Yes Yes
Chest pain with exertion for 2–3 years Chest pain with exertion for 5 years Incidental finding on CT scan of chest after trauma Chest pain, dyspnea on exertion for 5 years Uncontrolled HTN, paratracheal mass
Normal Normal Normal Normal Normal
6 7
Male Male
35 63
No No
Dizziness for 2 months, no chest pain or shortness of breath Incidental finding on preoperative workup for general surgical procedure
Normal Normal
Presentation
Catecholamines
Neoadjuvant or Adjuvant Therapy No No No No Embolization before first resection No No
a
b These patients were included in our series published in 2006 [4]. This patient presented to our institution for follow-up from previous resection with positive margins. The presentation described is for the initial tumor, which was embolized before the initial resection.
CT ⫽ computed tomography;
HTN ⫽ hypertension;
Pt. No. ⫽ patient number.
We follow these patients postoperatively in our clinic at 2 weeks and 4 weeks. At 3 months and 6 months we obtain repeat transthoracic echocardiography, and at 6 months we obtain cardiac MRI, which is then repeated on a yearly basis.
Results All patients were male with ages ranging from 23 to 64 years, with a mean age of 43.2 years. Four of the patients were hypertensive at the time of diagnosis (Table 1). Five patients had the tumor arising from the roof of the left atrium and 2 from the aortic root. Five patients were first-time resections, and 2 patients were repeat resections for recurrent disease after prior resections at outside institutions (Table 2). One of these tumors was incompletely resected at another institution, because resection was abandoned owing to massive hemorrhage. This tumor originally arose from the aortic root but the residual tumor had grown to a large size involving mainly the left atrium. The second redo resection occurred in a patient who underwent resection of 90% of an aortic root mass, complete resection was abandoned because of concerns over reconstruction. When this patient was referred to our institution 4 months after the original resection, the mass had
increased in size by more than six times and encompassed the aortic root and right ventricular outflow tract.
Left Atrial Tumors All the tumors originating from the left atrium were very large and required extensive resection and reconstruction. Four of the five patients required cardiac autotransplantation to allow exposure for complete tumor resection and adequate hemostasis [3– 4]. The fifth patient was one of the reoperative patients and required division of the Superior Vena Cava, Aorta and Pulmonary Artery for adequate exposure, but resection was accomplished with the heart in situ. This case was exceedingly difficult due to a severe desmoplastic reaction, the previous surgery and extreme vascularity of the tumor and surrounding area. This patient required 15 units of packed red blood cells in the operating room and severe right-side heart failure developed, requiring right ventricular assist device placement. This patient died several hours after surgery secondary to hypoxia and continued right-side heart failure. Three of these patients had microscopically negative margins, and 2 had microscopically positive margins on final pathology, including the patient who died.
Table 2. Surgical Characteristics Patient Number 1a 2a 3 4 5 6 7 a
Tumor Location Left atrium Left atrium Aorta Left atrium Left atrium Left atrium Aorta
Surgical Procedure Autotransplant Autotransplant Resection of aortic root tumor Autotransplant Resection recurrent left atrial tumor (SVC, aorta, and PA divided) Autotransplant Resection recurrent aortic root tumor (aorta, right coronary artery, RVOT, interventricular septum resected)
These patients were included in our series published in 2006 [4].
PA ⫽ pulmonary artery;
RVOT ⫽ right ventricular outflow tract;
SVC ⫽ superior vena cava.
Surgical Margins
30-Day Mortality
Negative Negative Negative Positive Positive Negative Positive
Alive Alive Alive Alive Deceased Alive Alive
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Table 3. Perioperative Data and Morbidity
a
1 2
No No
120 171
5 2
3 4 5 6
No No Yes No
84 86 76 114
0 0 15 2
7a
Yes
173
5
6 2
9 12
0.25 5 ... 7
5 11 ... 20
24
24
Morbidity None Arrhythmia, pleural effusion None None Death AF with RVR, pericardial effusion, pericarditis ASD, heart failure, respiratory failure, renal failure, persistent BPF
Intervention for Morbidity
Delayed Sternal Follow-Up, Closure Days
None Pacemaker, thoracentesis
No No
1,913 1,551
None None
No No ... Yes
495 796 ... 316
Yes
23
... Pericardial window
ASD closure, ECMO, tracheostomy, placement of HD catheter, VATS
This patient required VATS with blebectomy for pneumothorax with prolonged air leak that was an incidental finding.
AF ⫽ atrial fibrillation; ASD ⫽ atrial septal defect; BPF ⫽ bronchopleural fistula; ECMO ⫽ extracorporeal membrane oxygenation; HD ⫽ hemodialysis; ICU ⫽ intensive care unit; LOS ⫽ length of stay; OR ⫽ operating room; PRBC ⫽ packed red blood cells; Pt. No. ⫽ patient number; RVR ⫽ renal vascular resistance; VATS ⫽ video-assisted thoracoscopic surgery.
Aortic Root Tumors The 2 patients with aortic root paragangliomas required extensive resection and reconstruction. The first-time aortic root paraganglioma required aortic root replacement by standard techniques and showed negative margins on final pathology evaluation [5]. The second patient with aortic root paraganglioma was a reoperative patient with a large tumor encompassing the aortic root and right ventricular outflow tract. This patient required both aortic and pulmonary allografts, reimplantation of the left coronary artery, reconstruction of the interventricular septum, and coronary artery bypass of the right coronary artery. The margins were positive on final pathology study.
Perioperative Data All cases were technically complex, requiring aortic cross-clamp times of 76 minutes to 173 minutes, with a mean cross-clamp time of 117.7 minutes. Operating room transfusions ranged from 0 to 15 units of packed red blood cells for the patient who died. Two of the patients did not receive any packed red blood cells. Intensive care unit length of stay ranged from 6 hours to 24 days, with a mean of 6.32 days. Total hospital length of stay ranged from 5 days to 24 days, with a mean of 11.6 days. Three of the 6 surviving patients did not experience perioperative morbidity, but the other 3 had complications and required additional procedures during hospitalization for the resection (Table 3). Three of the patients were managed with delayed sternal closure after their resection at our hospital.
Follow-Up With the exception of the surgical death, all patients were discharged from the hospital. Five patients were discharged to home, and 1 patient was discharged to a
rehabilitation center. Follow-up is available on all surviving patients, ranging from 23 to 1,913 days, with a mean of 849 days, or 2.36 years. All 6 survivors are currently without disease.
Comment Chromaffin cell tumors are uncommon, occurring in between 1.5 and 9 cases per million population [6]. Approximately 90% of the body’s chromaffin cells reside in the adrenal medulla; therefore, most chromaffin cell tumors arise there, and they are termed pheochromocytoma [7, 8]. Outside of the adrenal gland, these tumors are referred to as paragangliomas. Only approximately 2% of chromaffin cell tumors occur as thoracic paragangliomas [2]. Thoracic paragangliomas may occur in the posterior mediastinum arising from the paraaortic sympathetic ganglia, where they are most common, or from the heart, where they are extremely rare. Cardiac paragangliomas can originate from the branchiomeric or visceral autonomic paraganglia resulting in aortic body and left atrial tumors, respectively. Left atrial tumors are the most common, followed by aortic body tumors, but paragangliomas have been described in all the cardiac chambers [9]. Cardiac paragangliomas may be hormonally active, secreting catecholamines, but most are not hormonally active. Approximately 10% of all paragangliomas are malignant, but that cannot be verified by histologic or biochemical status. Malignancy is defined by the presence of metastatic disease most commonly, but may also be determined by gross or microscopic local invasion found at the time of surgery [10]. The rate of malignancy can rise to as high as 50% in the setting of familial genetic defects [11]. The rate of malignancy in cardiac paragangliomas is difficult to establish owing to the lack of
ADULT CARDIAC
OR PRBC ICU Total Pt. Redo Cross-Clamp Transfused, LOS, LOS, No. Chest Time, Min Units Days Days
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reported cases, with only 30 cases reported as of 1993 [1]. In our small series, no cases have shown malignant characteristics to this point, but metastatic disease may be recognized years later and these patients warrant long-term follow-up [10]. Most paragangliomas occur in a sporadic fashion and past teaching has associated approximately 10% with genetic familial syndromes [12]. More recent publications have suggested that a familial genetic basis may exist in 25% to 50% of cases [13–16]. Recently, germ cell line mutations associated with succinate dehydrogenase has been associated with familial paraganglioma. We do not currently recommend genetic screening of these patients, but this is an area for further research consideration. The rarity of these tumors has led to a number of published case reports [5, 16 –22] and only a few small series. The largest series available is 14 patients with mediastinal paragangliomas from the Mayo Clinic [23]. Only 6 of these patients required cardiopulmonary bypass for resection. It is difficult to tell how many were primary cardiac paragangliomas versus mediastinal paragangliomas. In their series, there was 1 intraoperative death (7%) due to massive hemorrhage. Resection had positive margins (2 gross, 1 microscopic) in 3 of 14 (21%), and there were 2 recurrences in patients who had initially negative margins. A literature review by Jeevanandam and colleagues [9] includes a group of 11 patients from the University of Michigan, with 2 operative deaths (18%) due to massive hemorrhage and 2 incomplete resections (18%). In our series, we experienced a mortality of 1 of 7 (14%) due to hemorrhage and right-sided heart failure in our patient undergoing a redo left atrial resection for recurrence, and a microscopically positive margin in 3 of 7 (42%). In conclusion, cardiac paraganglioma is a rare tumor of significant surgical challenge. Complete surgical excision remains the mainstay of treatment. Surgical resection usually requires cardiopulmonary bypass and fullthickness tissue resection because of lack of tumor encapsulation and may require complex techniques such as cardiac autotransplantation. Hemorrhage during surgery remains a significant concern, and preoperative delineation of tumor blood supply is helpful with cardiac MRI. Surgical mortality is reasonable for this complex disease and long-term outcome is favorable in patients with complete resection.
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