A 56-yr-old man was admitted to our hospital with a complaint of weight loss (6 kg/3 months), and mild shortness of breath at room air. He denied all past history of smoking, excessive alcohol drinking, or chronic diseases. On physical examination, both sclerae were grossly normal, breathing sound was clear, and no cardiac murmur was heard. Abdominal sound was normoactive, and organomegaly was not clear. Arterial blood gas analysis showed pH 7.45, PaO2 65 mmHg, PaCO2 36 mmHg, and O2 saturation 90%. There was no evidence of cardiomegaly, mass shadow, or pulmonary edema in both lung fields on chest radiograph. Laboratory findings showed alanine aminotransferase of 52 U/L, total bilirubin of 1.53 mg/dL, alkaline phosphatase of 597 U/L, and γ-GTP of 126 U/L. Hepatitis B virus surface antigen and antibody to hepatitis C virus were all negative. To evaluate biochemically abnormal findings, abdominal ultrasonography and dynamic CT scan were performed, which showed an ill-defined, poorly enhanced 6.5×7×7 cm-sized mass with several daughter nodules in the left lobe of the liver (). Tests for tumor markers revealed alfa-fetoprotein of 6.19 ng/mL, CA 19-9 of 773.2 U/mL, and CEA of 615.5 ng/mL. Ultrasonography-guided needle biopsy for the liver mass was performed, and then, the histological findings were compatible with cholangiocarcinoma (). On chest CT scan for both of unexplained mild dyspnea and tumor staging, a low density due to filling defect in the left interlobar pulmonary artery was found without any evidence of other metastatic nodules (). Pulmonary perfusion scan showed multiple perfusion defects in the left lower lung fields (). Echocardiographic examination revealed no evidence of vegetation on the cardiac valves or intracardiac thrombus. Based on the radiological and symptomatic findings of the patient, the diagnosis of pulmonary thromboembolism was made. At the time of diagnosis, coagulation tests showed elevated levels of blood clotting factors, such as D-dimer of 5,690 ng/mL, fibrinogen of 746 mg/dL, fibrinogen degradation product (FDP) of 8.02 µg/mL, and positive IgM anticardiolipin antibody (aCL Ab) of 73 PL (normal limit: <20 PL). The prothrombin time (PT) was 10.8 sec (international neutralization ratio [INR]=0.98), activated partial prothrombin time (aPTT) was 33.2 sec, and other coagulation factors including protein C and S activities, lupus anticoagulant and antithrombin III are all within the normal range. To treat the pulmonary thromboemboli, anticoagulation therapy using low-molecular-weight-heparin (LMWH) in therapeutic dose of 10 IU/kg every 12 hr was given subcutaneously. The patient's symptom was relieved with LMWH treatment over time and the follow up CT scan at 3 weeks after the diagnosis showed an almost complete resolution of the thromboemboli (). Blood oxygenation was also increased to PaO2 of 83 mmHg and O2 saturation of 97%. Follow-up coagulation tests demonstrated the normalization of FDP, D-dimer, and IgM aCL Ab titer, but only a slight decrease in fibrinogen level (). Systemic chemotherapy for the cholangiocarcinoma was performed. The patient has been followed up without further thrombosis during the next 3 months.
A 69-year-old male was admitted to a hospital in June 2016 because of right arm asthenia and dysarthria and was diagnosed as having cerebral infarction in the left middle cerebral artery area along with deep vein thrombosis. ECG demonstrated normal sinus rhythm and echocardiography revealed no intra-cardiac thrombus or vegetation. The patient was discharged from the hospital following administration of apixaban.\nIn August 2016, the patient was readmitted to the hospital because of recurrent right arm asthenia and dysarthria. MRI revealed multiple cerebral infarctions in not only the bilateral cerebral hemispheres but also the cerebellum. Trousseau’s syndrome was suspected at this time. Apixaban administration was stopped and an intravenous drip of heparin was started. Echocardiography revealed mild mitral regurgitation with vegetation on the mitral valve. Although the laboratory data suggested no evidence of infection, ceftriaxone and gentamicin were added as a precaution against infective endocarditis. The patient was then referred to our hospital for surgery.\nA CT scan revealed a left renal infarction and multiple swollen lymph nodes around both the abdominal aorta and stomach with antral hypertrophy, suggesting an advanced gastric cancer or lymphoma. As the vegetation showed no change despite the heparin and antibiotics therapy, cardiac surgery was performed on day 5 after referral. Extracorporeal circulation was instituted employing aortic and bicaval cannulation. After aortic cross-clamping, the mitral valve was exposed via a left atriotomy. Both mitral leaflets had vegetation on the surface, and major vegetation 15 mm in width was evident on the anterior leaflet (Fig. ). These were resected in their entirety and replaced with a 25-mm Epic bioprosthesis (Abbott). Continuous intravenous heparin administration was resumed on the following day, aiming for an activated partial thromboplastin time of between 40 and 50 s. Histologic analysis revealed that the vegetations were thrombi covered with vascular endothelium and that the mitral leaflet tissue was not damaged (Fig. ). On the basis of these findings, the patient was diagnosed as having NBTE.\nAn endoscopic stomach biopsy was performed on the seventh postoperative day, and histologic analysis revealed non-solid poorly differentiated adenocarcinoma with components of signet-ring cell carcinoma and moderately differentiated tubular adenocarcinoma. The patient was definitively diagnosed as having Trousseau’s syndrome and, subsequently, transferred to the department of surgery. A Billroth I distal gastrectomy was performed, and a continuous intravenous heparin drip was employed during the operation. Histologic analysis revealed poorly differentiated adenocarcinoma with a component of moderately differentiated tubular adenocarcinoma and metastatic tumor cells in the dissected lymph nodes (T4aN3bM0; stage IIIb). Further histologic analysis using alcian blue staining confirmed the presence of mucin in the tumor.\nSubcutaneous heparin injection was introduced on day 8 after the gastric surgery, and the patient was discharged from our hospital in October after acquisition of the self-injection technique. During this long hospitalization, no thromboembolic events were observed. Chemotherapy was started in November. The patient has survived for 18 months after the diagnosis of Trousseau’s syndrome without any recurrence of thromboembolism.