A previously healthy 45-year-old woman presented with a 2-week history of tenderness in both lower legs and dizziness. She was suspected to have a cerebellar stroke, pulmonary emboli, and bilateral deep venous thrombosis on enhanced computed tomography at previous hospital. In addition, undiagnosed malignancy was suspected on the findings of abdominal computed tomography, which revealed a 4-cm enhanced irregular mass in sigmoid colon adjacent to the left ovary with poor demarcation. Then, she was transferred to our hospital for further evaluation and treatment. On presentation, her body temperature was 38.1 °C and did not have a heart murmur. Laboratory findings revealed elevated white blood cells counts, anemia, and markedly elevated CA 19-9. C-reactive protein was within normal range. There were no immunologic findings associated with lupus erythematosus, antiphospholipid syndrome, other collagen diseases, or hematologic disorders. The coagulation panel was within normal limits except for elevated D-dimer levels at 19.6 μg/ml. She was started on apixaban, which is a direct factor Xa inhibitor. Initially, general surgery team tried to perform colonoscopy; however, she had severe abdominal pain and fever soon after taking premedication for colonoscopy. Abdominal computed tomography showed occlusive ileus. Transverse colostomy was performed on the same day emergently for decompression. Then, she was referred to cardiology department to evaluate preoperative cardiac function before additional surgery for treatment and diagnosis. Preoperative transthoracic echocardiography (TTE) revealed mobile vegetations on the mitral and aortic valves. Transesophageal echocardiography (TEE) also showed that all three coronary cusps of the aortic valve had 7–8 mm vegetations. Mild aortic insufficiency was seen around the vegetations. Similarly, both anterior and posterior mitral leaflets were thickened and had vegetations. The anterior mitral leaflet also had a 15-mm mobile mass and a few string-like bodies. Mild mitral regurgitation was observed from the center of the valve orifice (Fig. ).\nGiven the echocardiographic findings, infectious endocarditis was suspected. Although three separate blood cultures were negative, meropenem were started empirically. Head magnetic resonance imaging showed no infarction, bleeding, or infected arterial aneurysm. She underwent an emergent operation to prevent recurrent thrombotic emboli 4 weeks after chief complaint was initiated.\nA median sternotomy was performed, and cardiopulmonary bypass was instituted via ascending aortic and bicaval cannulation. After aortic cross-clamping, myocardial protection was achieved by the retrograde administration of cold blood cardioplegia. Then, aortotomy was performed, and antegrade blood cardioplegia was selectively administered into the coronary ostia. Vegetations were observed on all three cusps of the aortic valve. Both left and right coronary cusps had been destroyed structurally, and valve replacement using a biological valve (Carpentier-Edwards PERIMOUNT Magna Ease, 21 mm) was required. Since we could not rule out infectious endocarditis at that time, we chose a biological valve instead of a mechanical valve to minimize the postoperative bleeding risk due to anticoagulation. Next, right-sided left atriotomy was performed. Similar to the aortic valve, vegetations were attached to the anterior and posterior leaflets of the mitral valve. We successfully performed valve repair by careful debridement and ring annuloplasty. Remaining of surface of mitral valve was ablated with electric cautery. Weaning from cardiopulmonary bypass was possible with inotropic support.\nAfter the operation, anticoagulation therapy with warfarin was initiated. Follow-up TTE revealed no residual mitral regurgitation or vegetations on either the prosthetic aortic valve or native mitral valve. The pathology report revealed a few large brown-colored vegetations on both aortic and mitral valves that histopathologically consisted of eosinophilic fibrin. No bacterial organisms were detected microscopically (Fig. ).\nBased on these results, we suspected that the valve lesions were NBTE associated with occult malignancy. Three weeks after the cardiac operation, the general surgery team performed sigmoid colectomy and left salpingo-oophorectomy to remove the underlying malignancy causing thrombotic emboli. No mesenteric or hepatic metastases were observed. Histopathological examination revealed endometrioid adenocarcinoma in pelvic cavity and direct invasion in sigmoid colon. After 1-year follow-up, she has not experienced recurrent thromboembolic events on anticoagulation of warfarin and adjuvant chemotherapy for endometrioid adenocarcinoma.\nNBTE was originally described by Ziegler in 1888 and has been reported to be associated with malignancy. Adenocarcinoma is the most common associated malignancy. Patients with adenocarcinoma reportedly have a fivefold higher risk of NBTE than patients with other histological types of malignant tumor []. Moreover, NBTE in the course of gynecological neoplasms (ovarian, cervical) is reported to have the highest risk of ischemic stroke [].\nHistological examination of the resected valve remains the gold standard for the diagnosis of NBTE. The vegetations of NBTE are friable, white or tan masses, usually situated along the lines of the valve closure, on the leaflets, which may be normal or previously damaged. They vary greatly in size from tiny lesions to large and exuberant masses. NBTE consists of degenerating platelets interwoven with strands of fibrin and forming a bland, featureless eosinophilic mass except for a few trapped leukocytes []. Differential diagnosis between NBTE and infectious blood culture-negative endocarditis can only be made histologically by identifying valvular inflammation, vegetation, and the organisms or other changes consistent with endocarditis.\nTreatment of NBTE consists of systemic anticoagulation and therapy directed at treating the underlying malignancy or associated condition. Heparin is more effective than warfarin for hypercoagulability associated with malignancy [–]. However, Borowski et al. reported a case of recurrent embolism in the course of NBTE in spite of anticoagulation therapy [], and other authors also have reported that treatment with heparin alone does not prevent further emboli []. This implies that anticoagulation therapy alone may not be sufficient to control hypercoagulability due to underlying malignancy. We cannot prevent recurrent embolization without removing the cancer in patients with NBTE associated with malignancy, because malignancy can still create a hypercoagulable state in spite of anticoagulation therapy. Eventually, this would result in recurrence of NBTE and thrombotic emboli.\nSurgical indications and appropriate timing for surgery for NBTE have not been formally studied. In general, surgical indications for NBTE are the same as for infectious endocarditis and include uncontrollable heart failure or infection and mobile vegetations. In the present case, patient was relatively stable and TEE showed mobile vegetations which could cause stroke; emergent open-heart surgery was warranted. Although open-heart surgery might be waved because of systemic condition related to the malignancy, open-heart surgery should be performed as soon as possible when they are stable enough to underwent surgery and meet one of surgical indications listed above. Preservation of the valve might be possible in more cases of NBTE in which the valve is structurally and functionally normal after the vegetation is removed than that of bacterial infectious endocarditis.\nAppropriate timing of surgery for underlying malignancy after the cardiac operation in NBTE has also not been reported. Our patient underwent surgery for underlying malignancy soon after histopathological examination confirmed a diagnosis of NBTE. We believe that surgical intervention should be performed as soon as possible once the diagnosis of NBTE is made after cardiac surgery to prevent recurrent vegetations and embolization.
A 36-year-old male football player with no significant past medical history recently diagnosed with unprovoked deep venous thrombosis of the lower limb, presented with acute right-sided hemiplegia, hemi-sensory loss, facial upper motor neuron lesion and expressive aphasia. Prior to the presentation, the patient had a history of undocumented fever, but no reported history of chest pain, shortness of breath, weight loss, night sweating, drug abuse, alcohol consumption or family history of similar presentation. With the aid of the above information, the computed tomography (CT) of the brain showed multiple bilateral occipital and frontoparietal areas of hypodensities more on the left cerebral hemisphere. The transthoracic echocardiogram revealed left ventricular ejection fraction of 60%, the presence of masses attached to mitral and aortic valves needed to be evaluated further by tranesophageal echocardiogram (TEE). The TEE showed multiple highly mobile, irregular shape masses attached to right and left coronary cusps of the aortic valve, largest mass measuring 20 × 18 mm2 with eccentric severe aortic regurgitation, no associated abscess or fistula, similar echogenicity mass attached to anterior mitral valve measures 7 × 4 mm2, and posterior mitral valve mass measures 5 × 3 mm2, and there was mild mitral regurgitation and no intracardiac shunt ( and ()). Magnetic resonance imaging (MRI) of the brain ( and ()) revealed multifocal diffusion restrictions involving bilateral high frontal and left thalamus, bilateral occipital lobes, and bilateral cerebellar hemispheres, with no significant mass effect. Forty-eight hours of follow-up CT of the brain confirmed the presence of hemorrhagic transformation. Clinically, the patient showed improvement in the expressive aphasia and the right-sided hemiplegia during the first week of admission. The patient was clinically stable throughout his hospitalization course. The follow-up investigations of all the tests performed on the patient leads to the following conclusions: (1) all blood cultures were negative; (2) Brucella titer and serology for Q fever were negative; (3) markers for tumors came back positive (CA-125 102 U/mL, CA19-9 5247 U/mL, CEA 13.6 U/mL); (4) thrombophilic evaluation, including anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), antiphospholipid antibodies (cardiolipin IgG and IgM), Factor-V Leiden mutation, homocysteine, Protein-S, Protein-C and Antithrombin-III levels, was unremarkable; and (5) CT scan of chest, abdomen and pelvis unveiled the presence of hypovascular hepatic mass having dimensions of 7.8 × 5.7 × 6.4 cm3, which invaded the right portal vein as well as the right hepatic duct with multiple porta hepatis and retroperitoneal lymphadenopathies, thereby leading to an alarming stage of cholangiocarcinoma (). On a similar note, the peripheral right lung showed lesion with central cavitation probably infarction or metastasis, in addition to the presence of bilateral hypodense renal cervical lesions. The patient underwent ultrasound-guided liver biopsy showed well-differentiated adeno-carcinoma, consistent with the diagnosis of cholangiocarcinoma ( and ()).\nThe follow-up transthoracic echocardiogram after 10 days of admission showed the presence of a small calcified aortic valve mass, which measures 6 × 4 mm2, mild aortic and mitral regurgitation and no evidence of mitral valve mass ( and ()). At this stage, upon his and his family request, the patient was transferred to an oncology center in the United States, where he was recommended for palliative treatment. Unfortunately, 6 months later, the patient died.