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Malignant pericardial effusion as initial solitary site of metastasis from transitional cell carcinoma of the bladder
MALIGNANT PERICARDIAL EFFUSION AS INITIAL SOLITARY SITE OF METASTASIS FROM TRANSITIONAL CELL CARCINOMA OF THE BLADDER SCOTT J. FABOZZI, M.D. JOSEPH R. NEWTON, JR., M.D. RICHARD P MORIARTY, M.D. PAUL E SCHELLHAMMER, M.D. From the Departments of Urology, Thoracic Surgery, and Pathology, the Center for Urological Oncology of Eastern Virginia Medical School, and the Sentara Cancer Institute, Norfolk, Virginia
ABSTRACT-A patient is presented whose first and sole evidence of metastatic transitional cell carcinoma of the bladder.was pericardial metastasis with life-threatening cardiac tamponade. Definitive diagnosis and management was achieved with fluid cytology and video-assisted thoracic surgical pericardial biopsy and pericardial window.
Metastatic patterns of bladder cancer can be unorthodox. A patient is described who developed a malignant pericardial effusion as the first and only evidence of distant metastasis 19 months after radical cystoprostatectomy and adjuvant methotrexate-vincristine, doxorubicin, cisplatin (MVAC) chemotherapy for treatment of invasive, grade 3 transitional cell carcinoma of the bladder. No similar such situation could be found in a review of the English literature. CASE REPORT A previously healthy 66-year-old former smoker presented with a chief complaint of progressive dyspnea of several days’ duration. His past history was significant for clinical Stage T3, grade 3, transitional cell carcinoma of the bladder treated by radical cystoprostatectomy, bilateral pelvic lymphadenectomy, and ileal conduit diversion 19 months previously. Histologic review revealed metastatic transitional cell carcinoma to 2 of 12 regional lymph nodes and a local pT3a tumor. He received two cycles of adjuvant MVAC chemotherapy (methotrexate, 30 mg/m2; vincristine, 3 mg/m2; doxorubicin, 30 mg/m2; cisplatin, 70 mg/m2) postoperatively. The patient and the medical oncologist decided against additional cycles of chemotherapy Submitted: 24, 1994
320
May
16, 1994, accepted
(with revisions): August
The evaluation of the dyspnea included a chest roentgenograph, which revealed an enlarged cardiac silhouette and heart failure. An echocardiogram demonstrated a normal-appearing pericardium with an associated large pericardial effusion. Approximately 700 cc of bloody fluid was drained via subxiphoid pericardiocentesis and an indwelling pericardial catheter was placed. The cytologic examination of the pericardial fluid showed reactive mesothelial cells and anaplastic cells of uncertain etiology (Fig. 1A). A pericardial window and biopsy were performed via videoassisted thoracic surgery into the right hemithorax, and he was discharged home on the second postoperative day. There was no grossly visible pericardial involvement; however, the pericardial biopsy specimen microscopically demonstrated metastatic transitional cell carcinoma (Fig. 1B). A bone scan and computed tomography (CT) scans of the head, chest, abdomen, and pelvis were negative for metastatic disease. He received two additional courses of MVAC chemotherapy and remained functionally well for 6 months, at which time a large right-sided pleural effusion and ascites developed. A thoracentesis and paracentesis each showed malignant cells similar to those found in the pericardial biopsy. Repeat CT of the chest, abdomen, and pelvis again failed to demonstrate soft tissue metastases. Soon after, right-sided neurologic deficits developed,
UROLOGY@
/FEBRUARY 1995 i
VOI-UMF45, NIUMRER 2
1. (A) Pericardial fluid. Note cells with enlarged, hyperchromatic, and varying sized nuclei with abundant cytoplasm. The cells are found singly and in aggregates. One cell [upper right) has a large cytoplasmic vacuole, probably secondary to imbibed pericardial fluid (x400). (B) Pericardial biopsy. Nest of tumor cells in pericardium within vascular spaces. The cytoplasm of the cells lining the vascular spaces stain with an immunoperoxidase stain for factor VIII (x400). FIGURE
and CT confirmed brain metastases. He began palliative whole brain irradiation, but his subsequent course was marked by rapid deterioration and death. COMMENT Dissemination of transitional cell carcinoma of the bladder generally follows predictable patterns. Regional and juxtaregional lymph node metastases are most commonly encountered with subsequent dissemination to liver, lung, and bone.1*2 Less commonly involved organs are the intestine, adrenal glands, and kidneys.l12 Peterson3 summarized the literature with respect to unusual manifestations of metastatic transitional cell carcinoma of the bladder and found such varied metastatic sites as omentum, psoas muscle, salivary gland, female reproductive organs, breast, and eye. Sev-
UROLOGY@ /FEBRUARY199.5 I VOLUME 45, NUMBER 2
eral autopsy series have documented metastases of bladder cancer to the heart,2-4 but prior to our report, there has been no published case of clinical malignant pericardial effusion or direct pericardial involvement from transitional cell carcinoma. As an initial and clinically solitary metastatic site, it represents a unique event. Among cancer patients, the development of malignant pericardial effusion often occurs. Between 8% and 21% of patients with malignancy will demonstrate metastatic disease to the pericardium at postmortem; development of clinically significant cardiac failure, however, is not common.5,6 Primary tumors of the breast and lung are most often associated with pericardial effusions and, together with leukemia, lymphoma, sarcoma, and melanoma, these tumors account for more than 80% of all malignant pericardial effusions.’ The most common urologic cancer associated with malignant pericardial effusion is renal cell carcinoma.8 Although metastasis to the pericardium is usually seen in association with metastases elsewhere in the chest, isolated pericardial metastasis has been reported for renal cell carcinoma and other tumor types, 8-10 Our case highlights the grave prognosis generally associated with pericardial metastases, but this is not necessarily universal.8,11 Symptoms of pericardial effusion include dyspnea, fatigue, orthopnea, and chest pain. Pulsus paradoxus may be present on blood pressure determination, and venous distention may be noticed in the neck. Plain chest radiography usually reveals an enlarged cardiac silhouette or “water bottle” heart.12 Electrocardiographic abnormalities usually include an electrical alternans pattern, which signifies alternating deep and superficial cardiac position relative to the chest wall.12 Echocardiography is the most useful modality to evaluate pericardial effusions. It provides a rapid, noninvasive way to diagnose and quantify not only the size of the effusion but the degree of cardiac impairment. l2 Differentiation of the etiology of an effusion is best done via pericardiocentesis, which also provides safe and rapid relief of the low-output symptoms of cardiac tamponade. A bloody effusion indicates malignancy in 80% to 90% of cases and was found in our patient.12 Treatment options for malignant pericardial effusions include pericardiocentesis, pericardial window, sclerotherapy, systemic chemotherapy, and radiotherapy 13,14The treatment choice depends on several factors, including the overall condition of the patient and, perhaps most importantly, the underlying malignancy In our case, a definitive diagnosis as well as definitive treatment were achieved
321
with a surgical creation of a pericardial window. Subsequent use of systemic chemotherapy was based on reports on the effectiveness of MVAC chemotherapy in metastatic transitional cell carcinoma t5 although recent reports also support the use of intrapericardial chemotherapy with a variety of underlying malignancies.16 Traditional approaches to surgical creation of a pericardial window have included a subxiphoid approach that allows drainage of the pericardial space into the peritoneal space and a limited left anterior thoracotomy that allows drainage of the pericardial space into the left pleural space. Recent advances in endoscopic instruments permit a video-assisted thoracoscopic surgical approach that creates either a right or left pericardial window for drainage into either pleural space.” A generous pericardial biopsy can be obtained at the time of video-assisted thoracic surgery and a single 20 F tube may be left in the pericardial space for 1 to 2 days. This technique does require general anesthesia and the placement of a double lumen endotracheal tube. However, the procedure can generally be accomplished in less than 30 minutes, postoperative recovery is generally uncomplicated, and patients may be discharged on the second postoperative day, allowing rapid return of the patient to pretreatment activity. l8 A pericardial window maintains longterm patency in 85% to 90% of procedures and permits drainage of recurring pericardial fluid to the large surface area of the pleura or peritoneum where it is reabsorbed. Problems with pleural effusions do not occur until the extreme terminal stage of illness when generalized lymphatic obstruction occurs. In summary, this report describes an unusual solitary and initial site of metastasis of transitional cell carcinoma of the bladder to the pericardium. Definitive diagnosis and management was efficiently achieved with aspiration fluid cytology, video-assisted thoracic surgical pericardial biopsy and pericardial window. An excellent functional status was achieved with this minimally invasive surgical approach for 6 months until the appearance of central nervous system metastases. Scott J.
Fabozzi, M.D.
600 Gresham Drive Suite 203
Novfofk, VA 23507
322
REFERENCES 1. Kishi K, Hirota T, Matsumoto K, Kakizoe T, Murase T, and Fujita J: Carcinoma of the bladder: a clinical and pathological analysis of 87 autopsy cases. J Ural 125: 36-39, 1981. 2. Babaian RJ, Johnson DE, Llamas L, and Ayala AG: Metastases from transitional cell carcinoma of the urinary bladder. Urology 16: 142-144, 1980. 3. Peterson NE: Atypical metastases from transitional vesical carcinoma. Urology 34: 148-151, 1989. 4. Fetter T, Bogaev JH, McCuskey B, and Seres JL: Carcinoma of the bladder: sites of metastases. J Ural 81: 746-748, 1959. 5. Olopade 01, and Ultmann J: Malignant effusions. CA Cancer J Clin 41: 166-179, 1991. 6. Malden LT, and Tattersall MH: Malignant effusions. Q J Med 58: 221-239, 1986. 7. Thurber D, Edwards JE, and Achor RW: Secondary malignant tumors of the pericardium. Circulation 26: 228-241, 1962. 8. Schellhammer PF, and El-Mahdi AM: Renal cell carcinoma with solitary metastases to the pericardium. Urology 21: 399-402, 1983. 9. Martini N, Freiman AH, Watson RC, and Hilaris BS: Malignant pericardial effusion. NY State J Med 76: 719-721, 1976. 10. Slater S, Knoop I, and Zuckerman S: Constrictive pericarditis caused by solitary metastatic carcinosis of the pericardium and complicated by radiation fibrosis of the mediastinum. Am Heart J 43: 401-412, 1952. 11. White JE, Fincher RM, and D’Cruz IA: Pericardial metastasis from testicular seminoma: appearance and disappearance by echocardiography, Am J Med Sci 301: 182-185, 1991. 12. Pass HI: Treatment of metastatic cancer: treatment of malignant pleural and pericardial effusions, in Devita VT Jr, Hellman S, and Rosenberg SA (Eds): Cancer: Principles and Practice oJOncoIogy, 3d ed. Philadelphia, JB Lippincott, 1989, pp 2317-2327. 13. Press OW, and Livingston R: Management of malignant pericardial effusion and tamponade. JAMA 257: 1088-1092, 1987. 14. Buzaid AC, Garewal HS, and Greenberg BR: Managing malignant pericardial effusion. West J Med 150: 174-179, 1989. 15. Sternberg CN, Yagoda A, Scher HI, Watson RC, Herr HW, Morse MJ, Sogani PC, Vaughan ED Jr, Bander N, Weiselberg LR, et al: M-VAC (methotrexate, vinblastine, doxorubicin and cis-platin) for advanced transitional cell carcinoma of the urothelium. J Urol 139: 461-469, 1988. 16. Imamura 7, Tamura T, Takenaga M, Nagatomo Y, Ishikawa T, and Nakagawa S: Intrapericardial OK-432 instillation for the management of malignant pericardial effusion. Cancer 68: 259-263, 1991. 17. Lewis RJ, Caccavale RJ, Sisler GE, and Mackenzie JW: One hundred consecutive patients undergoing video assisted thoracic operations. Ann Thorac Surg 54: 421-426, 1992. 18. Newton JR, and Szentpetery S: Video assisted thoracoscopic surgery to shorten postoperative recovery time. Abstract presentation, American College of Chest Physicians, Orlando, FL, October 1993.
UROLOGY@ I FEBRL~ARY 1995 I VOLUME45, NLMBER 2
ABSTRACT-A patient is presented whose first and sole evidence of metastatic transitional cell carcinoma of the bladder.was pericardial metastasis with life-threatening cardiac tamponade. Definitive diagnosis and management was achieved with fluid cytology and video-assisted thoracic surgical pericardial biopsy and pericardial window.
Metastatic patterns of bladder cancer can be unorthodox. A patient is described who developed a malignant pericardial effusion as the first and only evidence of distant metastasis 19 months after radical cystoprostatectomy and adjuvant methotrexate-vincristine, doxorubicin, cisplatin (MVAC) chemotherapy for treatment of invasive, grade 3 transitional cell carcinoma of the bladder. No similar such situation could be found in a review of the English literature. CASE REPORT A previously healthy 66-year-old former smoker presented with a chief complaint of progressive dyspnea of several days’ duration. His past history was significant for clinical Stage T3, grade 3, transitional cell carcinoma of the bladder treated by radical cystoprostatectomy, bilateral pelvic lymphadenectomy, and ileal conduit diversion 19 months previously. Histologic review revealed metastatic transitional cell carcinoma to 2 of 12 regional lymph nodes and a local pT3a tumor. He received two cycles of adjuvant MVAC chemotherapy (methotrexate, 30 mg/m2; vincristine, 3 mg/m2; doxorubicin, 30 mg/m2; cisplatin, 70 mg/m2) postoperatively. The patient and the medical oncologist decided against additional cycles of chemotherapy Submitted: 24, 1994
320
May
16, 1994, accepted
(with revisions): August
The evaluation of the dyspnea included a chest roentgenograph, which revealed an enlarged cardiac silhouette and heart failure. An echocardiogram demonstrated a normal-appearing pericardium with an associated large pericardial effusion. Approximately 700 cc of bloody fluid was drained via subxiphoid pericardiocentesis and an indwelling pericardial catheter was placed. The cytologic examination of the pericardial fluid showed reactive mesothelial cells and anaplastic cells of uncertain etiology (Fig. 1A). A pericardial window and biopsy were performed via videoassisted thoracic surgery into the right hemithorax, and he was discharged home on the second postoperative day. There was no grossly visible pericardial involvement; however, the pericardial biopsy specimen microscopically demonstrated metastatic transitional cell carcinoma (Fig. 1B). A bone scan and computed tomography (CT) scans of the head, chest, abdomen, and pelvis were negative for metastatic disease. He received two additional courses of MVAC chemotherapy and remained functionally well for 6 months, at which time a large right-sided pleural effusion and ascites developed. A thoracentesis and paracentesis each showed malignant cells similar to those found in the pericardial biopsy. Repeat CT of the chest, abdomen, and pelvis again failed to demonstrate soft tissue metastases. Soon after, right-sided neurologic deficits developed,
UROLOGY@
/FEBRUARY 1995 i
VOI-UMF45, NIUMRER 2
1. (A) Pericardial fluid. Note cells with enlarged, hyperchromatic, and varying sized nuclei with abundant cytoplasm. The cells are found singly and in aggregates. One cell [upper right) has a large cytoplasmic vacuole, probably secondary to imbibed pericardial fluid (x400). (B) Pericardial biopsy. Nest of tumor cells in pericardium within vascular spaces. The cytoplasm of the cells lining the vascular spaces stain with an immunoperoxidase stain for factor VIII (x400). FIGURE
and CT confirmed brain metastases. He began palliative whole brain irradiation, but his subsequent course was marked by rapid deterioration and death. COMMENT Dissemination of transitional cell carcinoma of the bladder generally follows predictable patterns. Regional and juxtaregional lymph node metastases are most commonly encountered with subsequent dissemination to liver, lung, and bone.1*2 Less commonly involved organs are the intestine, adrenal glands, and kidneys.l12 Peterson3 summarized the literature with respect to unusual manifestations of metastatic transitional cell carcinoma of the bladder and found such varied metastatic sites as omentum, psoas muscle, salivary gland, female reproductive organs, breast, and eye. Sev-
UROLOGY@ /FEBRUARY199.5 I VOLUME 45, NUMBER 2
eral autopsy series have documented metastases of bladder cancer to the heart,2-4 but prior to our report, there has been no published case of clinical malignant pericardial effusion or direct pericardial involvement from transitional cell carcinoma. As an initial and clinically solitary metastatic site, it represents a unique event. Among cancer patients, the development of malignant pericardial effusion often occurs. Between 8% and 21% of patients with malignancy will demonstrate metastatic disease to the pericardium at postmortem; development of clinically significant cardiac failure, however, is not common.5,6 Primary tumors of the breast and lung are most often associated with pericardial effusions and, together with leukemia, lymphoma, sarcoma, and melanoma, these tumors account for more than 80% of all malignant pericardial effusions.’ The most common urologic cancer associated with malignant pericardial effusion is renal cell carcinoma.8 Although metastasis to the pericardium is usually seen in association with metastases elsewhere in the chest, isolated pericardial metastasis has been reported for renal cell carcinoma and other tumor types, 8-10 Our case highlights the grave prognosis generally associated with pericardial metastases, but this is not necessarily universal.8,11 Symptoms of pericardial effusion include dyspnea, fatigue, orthopnea, and chest pain. Pulsus paradoxus may be present on blood pressure determination, and venous distention may be noticed in the neck. Plain chest radiography usually reveals an enlarged cardiac silhouette or “water bottle” heart.12 Electrocardiographic abnormalities usually include an electrical alternans pattern, which signifies alternating deep and superficial cardiac position relative to the chest wall.12 Echocardiography is the most useful modality to evaluate pericardial effusions. It provides a rapid, noninvasive way to diagnose and quantify not only the size of the effusion but the degree of cardiac impairment. l2 Differentiation of the etiology of an effusion is best done via pericardiocentesis, which also provides safe and rapid relief of the low-output symptoms of cardiac tamponade. A bloody effusion indicates malignancy in 80% to 90% of cases and was found in our patient.12 Treatment options for malignant pericardial effusions include pericardiocentesis, pericardial window, sclerotherapy, systemic chemotherapy, and radiotherapy 13,14The treatment choice depends on several factors, including the overall condition of the patient and, perhaps most importantly, the underlying malignancy In our case, a definitive diagnosis as well as definitive treatment were achieved
321
with a surgical creation of a pericardial window. Subsequent use of systemic chemotherapy was based on reports on the effectiveness of MVAC chemotherapy in metastatic transitional cell carcinoma t5 although recent reports also support the use of intrapericardial chemotherapy with a variety of underlying malignancies.16 Traditional approaches to surgical creation of a pericardial window have included a subxiphoid approach that allows drainage of the pericardial space into the peritoneal space and a limited left anterior thoracotomy that allows drainage of the pericardial space into the left pleural space. Recent advances in endoscopic instruments permit a video-assisted thoracoscopic surgical approach that creates either a right or left pericardial window for drainage into either pleural space.” A generous pericardial biopsy can be obtained at the time of video-assisted thoracic surgery and a single 20 F tube may be left in the pericardial space for 1 to 2 days. This technique does require general anesthesia and the placement of a double lumen endotracheal tube. However, the procedure can generally be accomplished in less than 30 minutes, postoperative recovery is generally uncomplicated, and patients may be discharged on the second postoperative day, allowing rapid return of the patient to pretreatment activity. l8 A pericardial window maintains longterm patency in 85% to 90% of procedures and permits drainage of recurring pericardial fluid to the large surface area of the pleura or peritoneum where it is reabsorbed. Problems with pleural effusions do not occur until the extreme terminal stage of illness when generalized lymphatic obstruction occurs. In summary, this report describes an unusual solitary and initial site of metastasis of transitional cell carcinoma of the bladder to the pericardium. Definitive diagnosis and management was efficiently achieved with aspiration fluid cytology, video-assisted thoracic surgical pericardial biopsy and pericardial window. An excellent functional status was achieved with this minimally invasive surgical approach for 6 months until the appearance of central nervous system metastases. Scott J.
Fabozzi, M.D.
600 Gresham Drive Suite 203
Novfofk, VA 23507
322
REFERENCES 1. Kishi K, Hirota T, Matsumoto K, Kakizoe T, Murase T, and Fujita J: Carcinoma of the bladder: a clinical and pathological analysis of 87 autopsy cases. J Ural 125: 36-39, 1981. 2. Babaian RJ, Johnson DE, Llamas L, and Ayala AG: Metastases from transitional cell carcinoma of the urinary bladder. Urology 16: 142-144, 1980. 3. Peterson NE: Atypical metastases from transitional vesical carcinoma. Urology 34: 148-151, 1989. 4. Fetter T, Bogaev JH, McCuskey B, and Seres JL: Carcinoma of the bladder: sites of metastases. J Ural 81: 746-748, 1959. 5. Olopade 01, and Ultmann J: Malignant effusions. CA Cancer J Clin 41: 166-179, 1991. 6. Malden LT, and Tattersall MH: Malignant effusions. Q J Med 58: 221-239, 1986. 7. Thurber D, Edwards JE, and Achor RW: Secondary malignant tumors of the pericardium. Circulation 26: 228-241, 1962. 8. Schellhammer PF, and El-Mahdi AM: Renal cell carcinoma with solitary metastases to the pericardium. Urology 21: 399-402, 1983. 9. Martini N, Freiman AH, Watson RC, and Hilaris BS: Malignant pericardial effusion. NY State J Med 76: 719-721, 1976. 10. Slater S, Knoop I, and Zuckerman S: Constrictive pericarditis caused by solitary metastatic carcinosis of the pericardium and complicated by radiation fibrosis of the mediastinum. Am Heart J 43: 401-412, 1952. 11. White JE, Fincher RM, and D’Cruz IA: Pericardial metastasis from testicular seminoma: appearance and disappearance by echocardiography, Am J Med Sci 301: 182-185, 1991. 12. Pass HI: Treatment of metastatic cancer: treatment of malignant pleural and pericardial effusions, in Devita VT Jr, Hellman S, and Rosenberg SA (Eds): Cancer: Principles and Practice oJOncoIogy, 3d ed. Philadelphia, JB Lippincott, 1989, pp 2317-2327. 13. Press OW, and Livingston R: Management of malignant pericardial effusion and tamponade. JAMA 257: 1088-1092, 1987. 14. Buzaid AC, Garewal HS, and Greenberg BR: Managing malignant pericardial effusion. West J Med 150: 174-179, 1989. 15. Sternberg CN, Yagoda A, Scher HI, Watson RC, Herr HW, Morse MJ, Sogani PC, Vaughan ED Jr, Bander N, Weiselberg LR, et al: M-VAC (methotrexate, vinblastine, doxorubicin and cis-platin) for advanced transitional cell carcinoma of the urothelium. J Urol 139: 461-469, 1988. 16. Imamura 7, Tamura T, Takenaga M, Nagatomo Y, Ishikawa T, and Nakagawa S: Intrapericardial OK-432 instillation for the management of malignant pericardial effusion. Cancer 68: 259-263, 1991. 17. Lewis RJ, Caccavale RJ, Sisler GE, and Mackenzie JW: One hundred consecutive patients undergoing video assisted thoracic operations. Ann Thorac Surg 54: 421-426, 1992. 18. Newton JR, and Szentpetery S: Video assisted thoracoscopic surgery to shorten postoperative recovery time. Abstract presentation, American College of Chest Physicians, Orlando, FL, October 1993.
UROLOGY@ I FEBRL~ARY 1995 I VOLUME45, NLMBER 2