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Successful management of intracardiac extension of tumor thrombus in a patient with advanced nonseminomatous germ cell testicular cancer
SUCCESSFUL MANAGEMENT OF INTRACARDIAC EXTENSION OF TUMOR THROMBUS IN A PATIENT WITH ADVANCED NONSEMINOMATOUS GERM CELL TESTICULAR CANCER DIANE M.E SAVARESE, M.D., MICHAEL J. ROHRER, M.D., A. THOMAS PEZZELLA, M.D., ASHLEY DAVIDOFF, M.D., ARMANDO E. FRAIRE, M.D., AND MAN1 MENON, M.D.
ABSTRACT-A young patient with testicular germ cell tumor presenting with inferior vena cava thrombus extending into the right heart with free-floating thrombus in the right ventricle and a simultaneous epidural spinal cord compression is presented. Due to the perceived high risk of embolization and the urgent need to begin systemic chemotherapy, he was managed with tumor thrombectomy utilizing cardiopulmonary bypass and hypothermic circulatory arrest followed shortly thereafter by systemic chemotherapy. There were no perioperative complications, and he is alive and without recurrence 24 months following four cycles of systemic chemotherapy. uROLwa 46: 883-887, 1995.
E
xtension of renal cell carcinoma (RCC) into the inferior vena cava (IVC) and proximally to the right heart has been described, but this complication has rarely been reported in germ cell tumors. In this report, we describe a patient with advanced nonseminomatous germ cell tumor, who presented with right ventricular tumor extension, and his successful management utilizing tumor thrombectomy followed by systemic chemotherapy CASE REPORT
A 25year-old previously healthy white man presented with a 2-day history of severe low back and epigastric pain, painless swelling of the left testicle, and a 20 pound weight loss. Physical examination disclosed an 11 X 11 cm firm nontender left scrotal mass, a normal neurologic examination, and no intra-abdominal masses. A chest radiograph demonstrated multiple bilateral pulmonary nodules. Plain films of the lumbosacral spine showed no evidence of other metastatic disease. Serum beta human chorionic gonadotropin (P-hCG) was 5944 IU/mL (normal, less than 3 IU/mL), and alpha-fetoprotein (AFP) was more than 3500 ng/mL (normal, less than 15 ng/mL). The patient underwent left inguinal orchiectomy and was noted to have a necrotic mass replacing the testis. Microscopically, a teratocarcinoma with From the Departments of Medicine, Surgery, Pathology, and Radiology, University of Massachusetts Medical Center, Worcester, Massachusetts Reprint requests: Diane M.F. Savarese, M.D., Department of Medicine, University of Massachusetts Medical Center, Worcester, MA 01655 Submitted: April 13, 1995, accepted (with revisions): July 5, 1995 UF?OLOGY@ 46 (61, 1995
FIGURE 1. Microscopic appearance of testicular tumor. Note predominanceof embryonal carcinoma component in the left field and a reticular pattern of endodermal sinus tumor in the right field. [Hemaloxylin-eosin, x200.)
a major component of endodermal sinus tumor (28.5%) and minor components of embryonal carcinoma (5% to 10%) and choriocarcinoma was identified (Fig. 1). The epididymis was involved by tumor, but the spermatic cord surgical margin was free of tumor. Immunocytostains for P-hCG, placental alkaline phosphatase, and AFP were focally positive. Staging computed tomography (CT) scans of the chest, abdomen, and pelvis demonstrated multiple bilateral pulmonary nodules, extensive mediastinal adenopathy, marked para-aortic and left retrocrural lymphadenopathy, and was highly suggestive of recently formed thrombus in the IVC extending proximally to the level of the right atrium (RA). A venacavogram showed occlusion of the IVC with obstruction extending from the a83
FIGURE 3. Preoperative two-dimensional echocardiograph demonstrating solid tumor thrombus (arrows) within the right atrium [RA) and right ventricle (RV). LV = left ventricle; LA = left atrium.
FIGURE 2. Preoperative venacavogram showing occlusion of the inferior vena cava extending from T10 to LZ with evidence of multiple collaterals and reconstitution of the azygos vein.
second lumbar level to T10 with evidence of multiple collaterals (Fig. 2). Echocardiogram showed a freely mobile echodense mass extending from the IVC into the RA and through the tricuspid valve into the right ventricle (RV) (Fig. 3). Magnetic resonance imaging (MRI) scan of the spine disclosed bright signal intensity at Ll, suggestive of bony metastasis with tumor extension into the spinal canal through the neural foramen and epidural spinal cord compression. In view of the epidural spinal cord compression, urgent treatment with chemotherapy was indicated. In consultation with the cardiac and vascular surgery teams, cardiopulmonary bypass with 884
hypothermic circulatory arrest was recommended. Through a median sternotomy incision, the heart was approached. Cardiopulmonary bypass was initiated, with care taken not to manipulate the RA. A large single venous cannula was utilized. Circulatory arrest at 15°C was used. A large right atriotomy incision was made. The operative findings revealed a gelatinous tumor filling the RA with extension down the IVC and across the tricuspid valve into the RV This material was meticulously removed. The atrium was irrigated copiously A large Fogarty embolectomy catheter was then placed distally into the IVC where gelatinous tumor thrombus was removed with multiple passes. An intraoperative venacavogram identified no retained thrombus. Because the preoperative venacavogram had suggested thrombus in the distal IVC and renal veins, and the fear of postoperative pulmonary embolization from tumor thrombus remaining in the renal vein or more distal, a suprarenal Greenfield filter was placed. This was performed after the patient was fully rewarmed, was in normal sinus rhythm, and off cardiopulmonary bypass. Postoperatively, the patient was anticoagulated, and his postoperative course was uncomplicated. His neurologic examination remained unchanged, and chemotherapy with cisplatin, bleomycin, and etoposide was begun on the 6th postoperative day. He was discharged from the hospital on the 10th postoperative day Pathologic evaluation revealed the thrombus removed from the IVC, RA, and RV to be a branching cordlike segment of friable soft gray-tan tissue, measuring 15.0 X 1.0 X 0.6 cm in maximum dimension (Fig. 4A). Microscopically, the sections showed a red cell thrombus with multiple embedded fragments of teratocarcinoma represented almost entirely by the embryonal carcinoma component with focal areas reacting positively for AFP UROLOGY@ 46 (6), 1995
(A) Inferior vena cava (WC) and right atrium thrombus. Note branching pale gray tumor thrombi. (B) Microscopic appearance of IVC tumor. Note papillary tufts cut at right angles and glands reminiscent of embryonal carcinoma seen in Figure 1, (Hematoxylin-eosin, x200.)
FIGURE 4.
and P-hCG, indicating minor yolk sac and choriocarcinoma components (Fig. 4B) The patient received a total of four chemotherapy courses, administered in 21-day cycles. His back pain resolved after the first 2 weeks of therapy. At the end of four cycles of chemotherapy, AFP was 4 ng/mL and P-hCG was less than 3 IU/mL. CT scans of the chest, abdomen, and pelvis at the completion of chemotherapy showed dramatic resolution of almost all pulmonary parenchymal and mediastinal abnormalities with a residual less than 1 cm para-aortic lymph node, persistent aortopulmonary window mediastinal adenopathy, persistent right paraspinous mass, and a right upper lobe lung mass. Because of the persistence of residual masses, and the inability to exclude reliably the presence of residual malignancy or teratoma by radiographic features1 or normalization of markers2 exploratory right thoracotomy was performed. The resected right upper lobe lung nodule showed only necrotic tissue without viable tumor, and a right subcarinal node and right hilar lymph node were also without evidence of viable tumor. He has now been followed for 24 months since completion of chemotherapy without evidence of recurrence as determined by physical examination, serum AFP and @hCG levels, and serial CT scanning. Systemic anticoagulation was discontinued after a 3-month course, without thrombotic or embolic complications. COMMENT The most common primary tumor involving the NC is RCC. Despite initial reports to the contrary, long-term survival can be achieved in patients with RCC and WC extension by aggressive surgical management, including tumor thrombecuROLOGYa
46 (61, 1995
tomy of intravascular extension. In patients with RCC, IVC thrombi rarely extend cephalad into the heart, occurring in only 3 of 126 consecutive autopsies in one series.3 In patients with RCC, the level of thrombus extension may have prognostic implications; the literature supports few 5year survivors after resection of tumors propagating above the diaphragm.4 In patients with testicular cancer, two possible mechanisms of IVC involvement are postulated. Paracaval sites are the primary zone for lymphatic spread of right testicular tumors, and direct invasion of tumor metastases into the IVC can lead to thrombosis. Secondly, the direct insertion of the right gonadal vein into the IVC provides a direct route for vascular spread into the IVC, most likely accounting for the preponderance of right-sided testicular tumors associated with IVC tumor thrombus. The true incidence of IVC involvement by metastatic germ cell tumors is difficult to ascertain. Husband and Bellamy5 reviewed the CT scans of 650 patients with testicular cancer and found only 4 cases of IVC invasion among 397 patients with retroperitoneal disease. Two autopsy series of patients with testicular germ cell tumors have suggested IVC involvement in 3% and 11% of patients.6,7 In most cases of suspected IVC thrombosis, venacavography represents the most definitive diagnostic study and helps plan operative management8 A venacavogram is an essential part of planning the operative management. The finding of extension of the process from the renal vein is an unusual pattern for pure thrombosis and helps to define the process as malignant with extension from gonadal vein involvement. The characteristic radiographic findings are single or multiple 885
luminal filling defects, often with displacement of the vessel. Occasionally, the venacavogram fails to define the cephalad extent of thrombus and other modalities such as MRI are recommended. Although contrast CT scanning has been reported to be 93% accurate for detection of WC thrombus in patients with RCC, it too may fail to demonstrate the proximal extent of thrombus, as in the case of our patient.8 Echocardiography may be useful to assess the presence of thrombus in the supradiaphragmatic IVC, especially if MRI is equivocal. A curious feature of intravascular vena cava tumor thrombi is that they show little tendency to infiltrate the venous wall, endocardium, or myocardium. This tendency is of great importance to a successful surgical removal of the tumor thrombus3 In a few cases, however, it has been necessary to dissect tumor thrombus within the heart because of intimal adherence at that level9 Among the most significant potential complications of IVC thrombosis is the risk of pulmonary embolization of thrombus, acute pulmonary hypertension, and death. Pulmonary tumor emboli may occur either by spontaneous fragmentation of the tumor thrombus or as a consequence of manipulation of the tumor thrombus at the time of the operation3 These pulmonary tumor emboli may lead to sudden and unexpected death if large enough or may contribute to the development of symptomatic pulmonary metastatic disease, although there is evidence that the majority of such tumor fragments are destroyed within the vessel lumen without evidence of parenchymal invasion.lO The risk of embolization of thrombotic or neoplastic material in patients with IVC thrombus from retroperitoneal malignancy is unclear. In patients with intravascular extension of RCC, postoperative and intraoperative fatality due to massive embolism of tumor has been a well-recognized complication. In his autopsy series of patients with testicular cancer, Bredael et ~1.~ showed that 9% of patients who die of testicular cancer have pulmonary emboli (PE) as a terminal event. In the previously described series of 650 patients with testicular tumors who underwent CT scanning, IVC involvement was detected in 4 patients (0.6%), 1 of whom had clinical evidence of recurrent PE.5 O’Brien and Lynchll described a case in which, 4 days following orchiectomy, recurrent PE occurred despite heparinization. Resnick et al.l’ described a patient with embryonal cell testicular cancer and tumor thrombus in the IVC in whom a perfusion lung scan was suggestive of a PE. Libertino et a1.i3 reported on 1 patient who developed a perioperative PE following thrombectomy for RCC with IVC extension. In another single case report of a patient with testicular tumor and IVC thrombus, pulmonary symptoms at pre886
sentation were attributed to, and responded to, treatment for pneumonia, but perfusion lung scanning was consistent with PE.14 Stockier and Raghaven15 reported on 3 patients with advanced germ cell tumors, documented venous involvement and pulmonary embolization, one of which occurred during chemotherapy PE may also be the presenting symptom of testicular cancer.16 The present case with massive retroperitoneal tumor extending into the epidural space called for urgent institution of systemic chemotherapy. In patients with advanced nonseminomatous germ cell testicular cancer, systemic platinum-based chemotherapy followed by surgical resection of residual masses has resulted in long-term survival rates in excess of 8O%.l* Even though the thrombus may likely have resolved with systemic chemotherapy, we considered that the loosely adherent tumor mass that was floating freely in the RV placed the patient at a higher risk for embolization. Tumor thrombectomy was judged to be the most expedient method of diminishing this risk of embolization. l7 Because laparotomy and extensive intra-abdominal dissection would delay initiation of systemic chemotherapy, we proceeded with cardiopulmonary bypass and hypothermic circulatory arrest. The surgical approach to supradiaphragmatic IVC tumor has evolved over time. Marshall et al. l8 first described the use of extracorporeal circulation in removal of RCC with high WC extension. Later, Ardekani et al.lg reported the first case of RCC obstructing the IVC and extending into the heart and which was recognized and treated successfully using cardiopulmonary bypass (CPB) without deep hypothermia. Marshall and Reitzg reported their experience with CPB and deep hypothermic circulatory arrest (DHCA) for RCC in 8 of 12 patients who had suprahepatic tumor thrombi from RCC. There was only 1 postoperative death and 1 of the 8 patients remained alive 3 years postoperatively Novick and associatesZo reported their experience in 43 patients with large IVC thrombi from retroperitoneal malignancies who underwent surgical treatment with CPB and DHCA. In this series there were no patients with testicular cancer. Major postoperative complications occurred in 13 patients or 30.2%. The operative mortality was 4.7%. There were no cases of perioperative tumor embolization. There were 17 patients in this series whose thrombi extended into the right atrium; the 3-year survival for this group of patients was 56%. CPB is essential for tumors that extend into the atrium, and helpful in the management of tumors that extend into the IVC at the level of the hepatic veins, since vascular control of the IVC above the tumor and below the hepatic veins is technically
difficult. Temporary occlusion of the retrohepatic NC can be safely achieved, but occlusion of the suprahepatic IVC often causes a profound decrease in venous return with hypotension. CPB with DHCA allows direct visual inspection of the entire vena caval lumen in a completely bloodless field. Furthermore, atriotomy can be performed easily, facilitating removal of atria1 thrombus as well as friable or adherent pieces of thrombus in the intrahepatic IVC, reducing the risk of sudden uncontrolled hemorrhage or embolization. The operation is done entirely above the diaphragm, avoiding the morbidity of abdominal dissection in a patient with a bulky retroperitoneal mass. The morbidity of total circulatory arrest and CPB should be minimal in a relatively young patient with no pre-existing cardiac disease. In summary, this patient underwent successful management of a potentially serious intracardiac tumor thrombus utilizing a median sternotomy with minimal postoperative morbidity, allowing him to begin systemic chemotherapy 6 days postoperatively The use of tumor thrombectomy followed by Greenfield filter placement and systemic anticoagulation was well tolerated in this patient without significant postoperative morbidity. Following four courses of systemic chemotherapy, he has continued to do well without evidence of tumor recurrence, 24 months after initial presentation. REFERENCES 1. Stomper PC, Kalish LA, Garnick MB, Richie JP, and Kantof PW: CT and pathologic predictive features of residual mass histologic findings after chemotherapy for nonseminomatous germ cell tumors: can residual malignancy or teratoma be excluded? Radiology 180: 711-714, 1991. 2. Einhorn LH, Williams SD, Mandelbaum I, and Donohue JP: Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction. Cancer 48(4): 904-908, 1981. 3. Svane S: Tumor thrombus of the inferior vena cava resulting from renal carcinoma. A report on 12 autopsied cases. Stand J Urol Nephro13: 245-256, 1969. 4. Sosa RE, Mueche EC, Vaughn ED Jr, and McCarron JP Jr: Renal cell carcinoma extending into inferior vena cava:
the prognostic significance of the level of vena caval involvement. J Urol 132: 1097-1100, 1984. 5. Husband JE, and Bellamy EA: Unusual thoracoabdominal sites of metastases in testicular tumors. AJR Am J Roentgen01 145: 1165-1171, 1985. 6. Bredael JJ, Vugrin D, and Whitmore WF Jr: Autopsy findings in 154 patients with germ cell tumors of the testis. Cancer 50: 548-551, 1982. 7. Johnson DE, Appelt G, Samuels ML, and Luna M: Metastases from testicular carcinoma. Study of 78 autopsied cases. Urology 8: 234-239, 1976. 8. Richie JP, Garnick MB, Seltzer S, and Bettmann MA: Computerized tomography scan for diagnosis and staging of renal cell carcinoma. J Urol 129: 1114-1116, 1983. 9. Marshall FF, and Reitz BA: Technique for removal of renal cell carcinoma with suprahepatic vena caval tumor thrombus. Urol Clin North Am 13: 551-557, 1986. 10. Winterbauer RH, Elfenbein IB, and Ball WC Jr: Incidence and clinical significance of tumor embolization to the lungs. Am J Med 45: 271-290, 1968. 11. O’Brien WM, and Lynch JH: Thrombosis of the inferior vena cava by seminoma. J Urol 137: 303-305, 1987. 12. Resnick MI, Walvoord DJ, and Bulkley GJ: Testicular tumor presenting as inferior vena caval thrombosis. J Urol 109: 656-658, 1973. 13. Libertino JA, Zinman L, and Watkins E Jr: Long-term results of resection of renal cell cancer with extension into inferior vena cava. J Urol 137: 21-24, 1987. 14. Sharifi R, Ray P, Schade SG, and Lee M: Inferior vena cava thrombosis: unusual presentation of testicular tumor. Urology 32: 146-150, 1988. 15. Stockier M, and Raghaven D: Neoplastic venous involvement and pulmonary embolism in patients with germ cell tumors. Cancer 68: 2633-2636, 1991. 16. Kwok CK, Horowitz MD, Livingstone AS, and Block NL: Mature testicular teratoma with vena caval invasion presenting as pulmonary embolism. J Urol 149: 129-131, 1993. 17. Einhorn LH, and Donohue J: Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87: 293-298, 1977. 18. Marshall VF, Middleton RG, Holswade GR, and Goldsmith EL: Surgery for renal cell carcinoma in the vena cava. J Urol 103: 414420, 1970. 19. Ardekani RG, Hunter JA, and Thompson A: Hidden hypernephroma simulating right atria1 tumor. Ann Thorac Surg 11: 371-375, 1971. 20. Novick AC, Kaye MC, Cosgrove DM, Angermeier K, Pontes JE, Montie JE, Streem SB, Klein E, Stewart R, and Goormastic M: Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena caval thrombi. Ann Surg 212: 472477, 1990.
887
ABSTRACT-A young patient with testicular germ cell tumor presenting with inferior vena cava thrombus extending into the right heart with free-floating thrombus in the right ventricle and a simultaneous epidural spinal cord compression is presented. Due to the perceived high risk of embolization and the urgent need to begin systemic chemotherapy, he was managed with tumor thrombectomy utilizing cardiopulmonary bypass and hypothermic circulatory arrest followed shortly thereafter by systemic chemotherapy. There were no perioperative complications, and he is alive and without recurrence 24 months following four cycles of systemic chemotherapy. uROLwa 46: 883-887, 1995.
E
xtension of renal cell carcinoma (RCC) into the inferior vena cava (IVC) and proximally to the right heart has been described, but this complication has rarely been reported in germ cell tumors. In this report, we describe a patient with advanced nonseminomatous germ cell tumor, who presented with right ventricular tumor extension, and his successful management utilizing tumor thrombectomy followed by systemic chemotherapy CASE REPORT
A 25year-old previously healthy white man presented with a 2-day history of severe low back and epigastric pain, painless swelling of the left testicle, and a 20 pound weight loss. Physical examination disclosed an 11 X 11 cm firm nontender left scrotal mass, a normal neurologic examination, and no intra-abdominal masses. A chest radiograph demonstrated multiple bilateral pulmonary nodules. Plain films of the lumbosacral spine showed no evidence of other metastatic disease. Serum beta human chorionic gonadotropin (P-hCG) was 5944 IU/mL (normal, less than 3 IU/mL), and alpha-fetoprotein (AFP) was more than 3500 ng/mL (normal, less than 15 ng/mL). The patient underwent left inguinal orchiectomy and was noted to have a necrotic mass replacing the testis. Microscopically, a teratocarcinoma with From the Departments of Medicine, Surgery, Pathology, and Radiology, University of Massachusetts Medical Center, Worcester, Massachusetts Reprint requests: Diane M.F. Savarese, M.D., Department of Medicine, University of Massachusetts Medical Center, Worcester, MA 01655 Submitted: April 13, 1995, accepted (with revisions): July 5, 1995 UF?OLOGY@ 46 (61, 1995
FIGURE 1. Microscopic appearance of testicular tumor. Note predominanceof embryonal carcinoma component in the left field and a reticular pattern of endodermal sinus tumor in the right field. [Hemaloxylin-eosin, x200.)
a major component of endodermal sinus tumor (28.5%) and minor components of embryonal carcinoma (5% to 10%) and choriocarcinoma was identified (Fig. 1). The epididymis was involved by tumor, but the spermatic cord surgical margin was free of tumor. Immunocytostains for P-hCG, placental alkaline phosphatase, and AFP were focally positive. Staging computed tomography (CT) scans of the chest, abdomen, and pelvis demonstrated multiple bilateral pulmonary nodules, extensive mediastinal adenopathy, marked para-aortic and left retrocrural lymphadenopathy, and was highly suggestive of recently formed thrombus in the IVC extending proximally to the level of the right atrium (RA). A venacavogram showed occlusion of the IVC with obstruction extending from the a83
FIGURE 3. Preoperative two-dimensional echocardiograph demonstrating solid tumor thrombus (arrows) within the right atrium [RA) and right ventricle (RV). LV = left ventricle; LA = left atrium.
FIGURE 2. Preoperative venacavogram showing occlusion of the inferior vena cava extending from T10 to LZ with evidence of multiple collaterals and reconstitution of the azygos vein.
second lumbar level to T10 with evidence of multiple collaterals (Fig. 2). Echocardiogram showed a freely mobile echodense mass extending from the IVC into the RA and through the tricuspid valve into the right ventricle (RV) (Fig. 3). Magnetic resonance imaging (MRI) scan of the spine disclosed bright signal intensity at Ll, suggestive of bony metastasis with tumor extension into the spinal canal through the neural foramen and epidural spinal cord compression. In view of the epidural spinal cord compression, urgent treatment with chemotherapy was indicated. In consultation with the cardiac and vascular surgery teams, cardiopulmonary bypass with 884
hypothermic circulatory arrest was recommended. Through a median sternotomy incision, the heart was approached. Cardiopulmonary bypass was initiated, with care taken not to manipulate the RA. A large single venous cannula was utilized. Circulatory arrest at 15°C was used. A large right atriotomy incision was made. The operative findings revealed a gelatinous tumor filling the RA with extension down the IVC and across the tricuspid valve into the RV This material was meticulously removed. The atrium was irrigated copiously A large Fogarty embolectomy catheter was then placed distally into the IVC where gelatinous tumor thrombus was removed with multiple passes. An intraoperative venacavogram identified no retained thrombus. Because the preoperative venacavogram had suggested thrombus in the distal IVC and renal veins, and the fear of postoperative pulmonary embolization from tumor thrombus remaining in the renal vein or more distal, a suprarenal Greenfield filter was placed. This was performed after the patient was fully rewarmed, was in normal sinus rhythm, and off cardiopulmonary bypass. Postoperatively, the patient was anticoagulated, and his postoperative course was uncomplicated. His neurologic examination remained unchanged, and chemotherapy with cisplatin, bleomycin, and etoposide was begun on the 6th postoperative day. He was discharged from the hospital on the 10th postoperative day Pathologic evaluation revealed the thrombus removed from the IVC, RA, and RV to be a branching cordlike segment of friable soft gray-tan tissue, measuring 15.0 X 1.0 X 0.6 cm in maximum dimension (Fig. 4A). Microscopically, the sections showed a red cell thrombus with multiple embedded fragments of teratocarcinoma represented almost entirely by the embryonal carcinoma component with focal areas reacting positively for AFP UROLOGY@ 46 (6), 1995
(A) Inferior vena cava (WC) and right atrium thrombus. Note branching pale gray tumor thrombi. (B) Microscopic appearance of IVC tumor. Note papillary tufts cut at right angles and glands reminiscent of embryonal carcinoma seen in Figure 1, (Hematoxylin-eosin, x200.)
FIGURE 4.
and P-hCG, indicating minor yolk sac and choriocarcinoma components (Fig. 4B) The patient received a total of four chemotherapy courses, administered in 21-day cycles. His back pain resolved after the first 2 weeks of therapy. At the end of four cycles of chemotherapy, AFP was 4 ng/mL and P-hCG was less than 3 IU/mL. CT scans of the chest, abdomen, and pelvis at the completion of chemotherapy showed dramatic resolution of almost all pulmonary parenchymal and mediastinal abnormalities with a residual less than 1 cm para-aortic lymph node, persistent aortopulmonary window mediastinal adenopathy, persistent right paraspinous mass, and a right upper lobe lung mass. Because of the persistence of residual masses, and the inability to exclude reliably the presence of residual malignancy or teratoma by radiographic features1 or normalization of markers2 exploratory right thoracotomy was performed. The resected right upper lobe lung nodule showed only necrotic tissue without viable tumor, and a right subcarinal node and right hilar lymph node were also without evidence of viable tumor. He has now been followed for 24 months since completion of chemotherapy without evidence of recurrence as determined by physical examination, serum AFP and @hCG levels, and serial CT scanning. Systemic anticoagulation was discontinued after a 3-month course, without thrombotic or embolic complications. COMMENT The most common primary tumor involving the NC is RCC. Despite initial reports to the contrary, long-term survival can be achieved in patients with RCC and WC extension by aggressive surgical management, including tumor thrombecuROLOGYa
46 (61, 1995
tomy of intravascular extension. In patients with RCC, IVC thrombi rarely extend cephalad into the heart, occurring in only 3 of 126 consecutive autopsies in one series.3 In patients with RCC, the level of thrombus extension may have prognostic implications; the literature supports few 5year survivors after resection of tumors propagating above the diaphragm.4 In patients with testicular cancer, two possible mechanisms of IVC involvement are postulated. Paracaval sites are the primary zone for lymphatic spread of right testicular tumors, and direct invasion of tumor metastases into the IVC can lead to thrombosis. Secondly, the direct insertion of the right gonadal vein into the IVC provides a direct route for vascular spread into the IVC, most likely accounting for the preponderance of right-sided testicular tumors associated with IVC tumor thrombus. The true incidence of IVC involvement by metastatic germ cell tumors is difficult to ascertain. Husband and Bellamy5 reviewed the CT scans of 650 patients with testicular cancer and found only 4 cases of IVC invasion among 397 patients with retroperitoneal disease. Two autopsy series of patients with testicular germ cell tumors have suggested IVC involvement in 3% and 11% of patients.6,7 In most cases of suspected IVC thrombosis, venacavography represents the most definitive diagnostic study and helps plan operative management8 A venacavogram is an essential part of planning the operative management. The finding of extension of the process from the renal vein is an unusual pattern for pure thrombosis and helps to define the process as malignant with extension from gonadal vein involvement. The characteristic radiographic findings are single or multiple 885
luminal filling defects, often with displacement of the vessel. Occasionally, the venacavogram fails to define the cephalad extent of thrombus and other modalities such as MRI are recommended. Although contrast CT scanning has been reported to be 93% accurate for detection of WC thrombus in patients with RCC, it too may fail to demonstrate the proximal extent of thrombus, as in the case of our patient.8 Echocardiography may be useful to assess the presence of thrombus in the supradiaphragmatic IVC, especially if MRI is equivocal. A curious feature of intravascular vena cava tumor thrombi is that they show little tendency to infiltrate the venous wall, endocardium, or myocardium. This tendency is of great importance to a successful surgical removal of the tumor thrombus3 In a few cases, however, it has been necessary to dissect tumor thrombus within the heart because of intimal adherence at that level9 Among the most significant potential complications of IVC thrombosis is the risk of pulmonary embolization of thrombus, acute pulmonary hypertension, and death. Pulmonary tumor emboli may occur either by spontaneous fragmentation of the tumor thrombus or as a consequence of manipulation of the tumor thrombus at the time of the operation3 These pulmonary tumor emboli may lead to sudden and unexpected death if large enough or may contribute to the development of symptomatic pulmonary metastatic disease, although there is evidence that the majority of such tumor fragments are destroyed within the vessel lumen without evidence of parenchymal invasion.lO The risk of embolization of thrombotic or neoplastic material in patients with IVC thrombus from retroperitoneal malignancy is unclear. In patients with intravascular extension of RCC, postoperative and intraoperative fatality due to massive embolism of tumor has been a well-recognized complication. In his autopsy series of patients with testicular cancer, Bredael et ~1.~ showed that 9% of patients who die of testicular cancer have pulmonary emboli (PE) as a terminal event. In the previously described series of 650 patients with testicular tumors who underwent CT scanning, IVC involvement was detected in 4 patients (0.6%), 1 of whom had clinical evidence of recurrent PE.5 O’Brien and Lynchll described a case in which, 4 days following orchiectomy, recurrent PE occurred despite heparinization. Resnick et al.l’ described a patient with embryonal cell testicular cancer and tumor thrombus in the IVC in whom a perfusion lung scan was suggestive of a PE. Libertino et a1.i3 reported on 1 patient who developed a perioperative PE following thrombectomy for RCC with IVC extension. In another single case report of a patient with testicular tumor and IVC thrombus, pulmonary symptoms at pre886
sentation were attributed to, and responded to, treatment for pneumonia, but perfusion lung scanning was consistent with PE.14 Stockier and Raghaven15 reported on 3 patients with advanced germ cell tumors, documented venous involvement and pulmonary embolization, one of which occurred during chemotherapy PE may also be the presenting symptom of testicular cancer.16 The present case with massive retroperitoneal tumor extending into the epidural space called for urgent institution of systemic chemotherapy. In patients with advanced nonseminomatous germ cell testicular cancer, systemic platinum-based chemotherapy followed by surgical resection of residual masses has resulted in long-term survival rates in excess of 8O%.l* Even though the thrombus may likely have resolved with systemic chemotherapy, we considered that the loosely adherent tumor mass that was floating freely in the RV placed the patient at a higher risk for embolization. Tumor thrombectomy was judged to be the most expedient method of diminishing this risk of embolization. l7 Because laparotomy and extensive intra-abdominal dissection would delay initiation of systemic chemotherapy, we proceeded with cardiopulmonary bypass and hypothermic circulatory arrest. The surgical approach to supradiaphragmatic IVC tumor has evolved over time. Marshall et al. l8 first described the use of extracorporeal circulation in removal of RCC with high WC extension. Later, Ardekani et al.lg reported the first case of RCC obstructing the IVC and extending into the heart and which was recognized and treated successfully using cardiopulmonary bypass (CPB) without deep hypothermia. Marshall and Reitzg reported their experience with CPB and deep hypothermic circulatory arrest (DHCA) for RCC in 8 of 12 patients who had suprahepatic tumor thrombi from RCC. There was only 1 postoperative death and 1 of the 8 patients remained alive 3 years postoperatively Novick and associatesZo reported their experience in 43 patients with large IVC thrombi from retroperitoneal malignancies who underwent surgical treatment with CPB and DHCA. In this series there were no patients with testicular cancer. Major postoperative complications occurred in 13 patients or 30.2%. The operative mortality was 4.7%. There were no cases of perioperative tumor embolization. There were 17 patients in this series whose thrombi extended into the right atrium; the 3-year survival for this group of patients was 56%. CPB is essential for tumors that extend into the atrium, and helpful in the management of tumors that extend into the IVC at the level of the hepatic veins, since vascular control of the IVC above the tumor and below the hepatic veins is technically
difficult. Temporary occlusion of the retrohepatic NC can be safely achieved, but occlusion of the suprahepatic IVC often causes a profound decrease in venous return with hypotension. CPB with DHCA allows direct visual inspection of the entire vena caval lumen in a completely bloodless field. Furthermore, atriotomy can be performed easily, facilitating removal of atria1 thrombus as well as friable or adherent pieces of thrombus in the intrahepatic IVC, reducing the risk of sudden uncontrolled hemorrhage or embolization. The operation is done entirely above the diaphragm, avoiding the morbidity of abdominal dissection in a patient with a bulky retroperitoneal mass. The morbidity of total circulatory arrest and CPB should be minimal in a relatively young patient with no pre-existing cardiac disease. In summary, this patient underwent successful management of a potentially serious intracardiac tumor thrombus utilizing a median sternotomy with minimal postoperative morbidity, allowing him to begin systemic chemotherapy 6 days postoperatively The use of tumor thrombectomy followed by Greenfield filter placement and systemic anticoagulation was well tolerated in this patient without significant postoperative morbidity. Following four courses of systemic chemotherapy, he has continued to do well without evidence of tumor recurrence, 24 months after initial presentation. REFERENCES 1. Stomper PC, Kalish LA, Garnick MB, Richie JP, and Kantof PW: CT and pathologic predictive features of residual mass histologic findings after chemotherapy for nonseminomatous germ cell tumors: can residual malignancy or teratoma be excluded? Radiology 180: 711-714, 1991. 2. Einhorn LH, Williams SD, Mandelbaum I, and Donohue JP: Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction. Cancer 48(4): 904-908, 1981. 3. Svane S: Tumor thrombus of the inferior vena cava resulting from renal carcinoma. A report on 12 autopsied cases. Stand J Urol Nephro13: 245-256, 1969. 4. Sosa RE, Mueche EC, Vaughn ED Jr, and McCarron JP Jr: Renal cell carcinoma extending into inferior vena cava:
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