Ovarian adenocarcinoma complicated by malignant pericarditis

GYNECOLOGIC

ONCOLOGY

24, 171-176 (1986)

Ovarian Adenocarcinoma DANIEL

Complicated by Malignant Pericarditis

M. DONATO,

M.D., BERND-UWE AND HERVY E. AVERETTE,

SEWN, M.D.,

PH.D.,

M.D.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Miami School of Medicine, Miami, Florida 33101 Received February 19, 1985 Neoplastic pericarditis is a rare complication of gynecologic illustrated in the case presented, the physician involved in the should be aware of this possible life-threatening complication. by a brief review of the pertinent clinical, pathophysiologic, this condition. 0 1986 Academic Press, Inc.

malignancies. However, as care of patients with cancer The case report is followed and therapeutic aspects of

INTRODUCTION

Gynecologic tumors, as well as primary malignancies which occur below the diaphragm, are uncommon causes of malignant pericardial disease. However, when a primary tumor does involve the heart/pericardium, symptomatic pericardial disease as well as the development of cardiac tamponade may occur. As the latter is a medical emergency, physicians caring for patients with gynecologic malignancies should be aware of the therapeutic options available, and be prepared to coordinate appropriate interventions. Our recent encounter with such a case prompted this report and brief review of the relevant clinical aspects, pathophysiology, and management of this unusual complication. CASE REPORT

The patient is a 61-year-old white female with stage III poorly differentiated adenocarcinoma of the ovary diagnosed approximately 6 months prior to her referral to the University of Miami/Jackson Memorial Medical Center. The patient was initially treated by surgical cytoreduction (95%), followed by six courses of combination chemotherapy consisting of &-platinum and adriamycin. However, due to progressive disease (recurrent ascites and pleural effusions), the patient was started on a new regime of chemotherapy including fluorouracil (5-FU), cytoxan, and prednisone and referred for further therapy. A CT scan performed at this time did not reveal evidence for recurrent intraabdominal disease. On admission, the patient gave a recent history of increasing dyspnea, orthopnea, and pedal edema. She denied previous cardiorespiratory disease. Physical examination at this time revealed jugular venous distention (JVD), and bilateral 171 0090-8258186 $1.50 Copyright 0 1986 by Academic Press. Inc. All rights of reproduction in any form reserved.

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basilar rales (R > L). A pulsus paradoxus was absent, and auscultation of the precordium was normal. Abdominal-pelvic exam was unremarkable, however, bilateral pedal edema was prominent. Initial chest X ray revealed a globular, enlarged cardiac silhouette, with evidence of a loculated right pleural effusion. The remaining lung parenchyma appeared normal. With the radiographic finding of prominent cardiomegaly in the absence of pulmonary congestion, the possibility of a pericardial effusion was considered, and an echocardiogram was obtained. Findings on echocardiography included a large pericardial effusion with a hyperdynamic, small heart, a significant decrease in size of both ventricles, and right artial collapse. All the above findings in conjunction with the patient’s clinical status were consistent with the presumptive diagnosis of pericardial tamponade. The patient was then transferred to the cardiac intensive care unit (CCU), and a pericardial catheter was inserted. Under Swan-Ganz monitoring, more than 1 liter of sanguinous fluid was removed over the ensuing 24 hr. A significant clinical and hemodynamic improvement was noted after removal of the initial 200-300 ml of fluid. The fluid was exudative in composition, and the cytology was interpreted as highly suspicious for an adenocarcinoma. All cultures were negative at this time. Consultation with thoracic surgery was obtained, and it was agreed that after initial stabilization of the patient, instillation of a sclerosing agent (tetracycline) would be an appropriate modality to curtail further accumulations. If this failed or recurrent tamponade threatened, a decision for a more invasive surgical procedure could be made at that time. Tetracycline (500 mg) was mixed in 10 ml of 1% xylocaine, and instilled into the pericardium. The catheter was clamped for 6 hr, then placed to gravity drainage. The patient initially tolerated the instillation procedure well, but succumbed within 24 hr following the initiation of therapy. No autopsy was performed at the family’s request. DISCUSSION

Neoplastic involvement of the heart/pericardium has been found to occur in lo-20% of autopsies performed in patients dying of disseminated cancer [l-6]. It appears that the incidence of cardiac involvement with metastatic cancer has increased over the past 40 years, and may be a result of the increased survival in patients with the aid of chemotherapy and radiotherapy [7]. The pericardium is the most frequent site of metastatic disease involving the heart, as 85% of patients with cardiac involvement have tumor within the pericardium [8]. These metastasis are derived mainly from primary tumors of the lung (males) or breast (females) [3-5,7,9-151. The mechanism for dissemination of these tumors involves retrograde lymphatic permeation from mediastinal lymph nodes [9,15]. The literature contains fewer than 30 reported cases of gynecologic neoplasms associated with pericardial involvement to this author’s knowledge [7,11,14,1626]. The uterus (corpus + cervix) and ovary were the most common sources of metastatic foci involving the heart/pericardium. Unfortunately, as most of these case reports were from large autopsy series where retrospective data was

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utilized, precise histologic diagnoses were usually not included. The pericardium was the most common site for cardiac involvement with these primary tumors, however, three case reports have documented the occurrence of isolated intraventricular lesions. In the latter series, the cervix (squamous cell) was the primary site in two cases, while the corpus (unspecified type) was the etiology in the last [21-231. In most cases, regardless of the primary foci, the cardiac involvement remained subclinical, and diagnosis was made only at necropsy. As gynecologic tumors have only rarely been implicated in neoplastic pericarditis, the exact mechanism for pericardial involvement is not known, but probably involves initial intrathoracic spread and subsequent extension into the subepicardial lymphatics. The signs and symptoms of malignant pericardial disease can be subtle or nonspecific in nature, consequently the majority of cases will remain subclinical [7,13,14,16,27,28]. New onset dyspnea, easy fatigability, and other symptoms of right heart failure are the most common complaints for symptomatic pericardial disease. The classic signs of pulsus paradoxus, distant heart sounds, and audible friction rubs are often not present [7]. Fluid accumulation within the pericardial sac will produce an increase in the intrapericardial pressure which will be equally distributed to all cardiac chambers and great veins [ 13,291. Tamponade may therefore remain asymptomatic as compensatory mechanisms to maintain the cardiac output (CO) will be invoked (peripheral vasoconstriction, increased central venous pressure (CVP) and cardiac rate) [29]. When these mechanisms are overcome, symptomatic tamponade will occur, as the cardiac output can no longer be maintained. The hemodynamic findings of tamponade consist of elevations in CVP, pulmonary capillary wedge pressure (PCWP), and end diastolic pressures of the atria and ventricles. All will tend to equal the increased intrapericardial pressure [13,29]. This “equilization of pressures” is only found with tamponade or constrictive pericarditis [29]. On admission our patient was noted to have signs of right heart failure (JVD, pleural effusion, and pedal edema) and adriamycin-induced cardiomyopathy could have been one etiology in this case. However, the chest X ray findings (cardiomegaly, absence of pulmonary congestion) did not substantiate the diagnosis of congestive failure, but rather suggested the possibility of a pericardial effusion. Echocardiography was utilized to delineate the etiology of the cardiomegaly and the findings confirmed the presence of a large pericardial effusion with the possibility of cardiac tamponade. It is important to point out that while the echocardiogram is very accurate in making the diagnosis of a pericardial effusion, a diagnosis of cardiac tamponade cannot be made with this modality. Tamponade can only be diagnosed by assessing the clinical and hemodynamic status of the patient [30]. Despite the fact that a majority of cancer patients who have asymptomatic pericardial involvement will also have widespread metastasis, a search for the underlying etiology should be sought as approximately 40% of patients can be found to have a non-malignant cause [31]. Pericardiocentesis has been the mainstay for the diagnosis and treatment of symptomatic pericardial disease. The risk to the patient can be minimized if this procedure is performed by an experienced physician in an intensive care setting.

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Fluid analysis for cytology, microbiology, and viral studies can help to determine the etiology of the effusion. Cytologic interpretations of pericardial fluid have been found to be 85-90% accurate in the diagnosis of malignant involvement [10,31-331. Furthermore, the histologic type of malignancy can be determined in a majority of specimens studied [33]. The above facts were substantiated in our case, as a single sample of pericardial fluid sent to cytology was positive for an adenocarcinoma. It has been demonstrated that the stage and aggressiveness of the primary tumor as well as the response to previous chemotherapy or radiotherapy are the most important parameters affecting the outcome of malignant pericardial disease [17,34,35]. Therefore, the clinician must individualize patient care with these parameters in mind. If the patient presents with clinical and hemodynamic signs of cardiac tamponade, pericardiocentesis can be performed under Swan-Gantz monitoring to stabilize the patient and to attempt to establish a diagnosis. A dramatic improvement will usually be seen with removal of a relatively small amount of fluid, as the compliance of the pericardial sac is limited [29]. Posner et al. [31] suggests an initial trial of anti-inflammatory therapy in cancer patients who present with a new pericardial effusion in the absence of cardiac tamponade. In their review, a significant proportion of patients were found to have an “idiopathic” etiology (non-specific inflammation). If no response is noted, or a recurrent effusion occurs, a diagnostic pericardiocentesis should be performed to establish a diagnosis. When a malignant etiology has been determined, a variety of therapeutic options are available to combat recurrent pericardial effusions (instillation procedures, systemic chemotherapy, local radiotherapy, and/or surgery). Of all the instillation agents available, tetracycline seems to be the most efficacious. The use of this sclerosing agent circumvents major problems associated with the use of antineoplastic agents or radioisotopes such as pancytopenia or hazardous radiation exposure. In a recent study, excellent control of malignant pericardial effusions occurred in 30 of 33 patients with the use of tetracycline [17]. The only reported side effects were mild febrile episodes in 40% of patients. In contrast, systemic chemotherapy and local radiotherapy have produced rather poor control of symptomatic pericardial involvement in most cases [7,36]. Surgical drainage of the pericardium can be employed in those patients with recurrent or unresponsive effusions. Placement of a subxyphoid tube, pleuropericardial “window” formation (limited pericardiectomy), or total pericardiectomy will all serve to accomplish this goal [34,37,38]. In seriously ill patients with recurrent effusions, insertion of a subxyphoid tube under local anesthesia would be the procedure of choice [34,37,38]. The pleuropericardial window (removal of a small portion of parietal pericardium) will allow drainage of pericardial fluid into the left chest. This procedure is also used for recurrent effusions, however, it is a more extensive procedure which requires general anesthesia and entrance via a left thoracotomy [37,38]. A total pericardectomy (removal of all accessible parietal pericardium) is usually reserved for patients with recurrent effusions

PERICARDIAL

INVOLVEMENT

who have a long life expectancy,

BY

OVARIAN

17.5

CARCINOMA

or patients with a severe constrictive

component

[35,38].

As our patient had failed all previous therapeutic modalities, a decision for palliation was made once the malignant etiology of the pericardial effusion was established. The response to initial therapy with tetracycline unfortunately could not be evaluated as the patient expired within 24 hr after initiation of therapy. The etiology of her demise could well have been a fatal arrythmia, however, an acute pericardial or myocardial event could not be ruled out as an autopsy was not performed. In summary, the case report illustrates a rare metastatic complication of ovarian adenocarcinoma as well as the clinical aspects of malignant pericardial disease. Despite the poor prognosis of patients who develop this complication, some patients can be palliated for significant periods of time. Rational decisions have to be made to ensure each patient optimum care and reasonable “quality” of life. ACKNOWLEDGMENT The authors acknowledge Dr. Richard J. Thurer, Department of Cardiothoracic advice concerning patient management and critical review of this manuscript.

Surgery, for his

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