Malignant Pericardial Effusion Research Articles

Salvage surgery for stage IVa thymic carcinoma combined with aortic arch resection \u2013 case report

BackgroundAlthough complete surgical resection of thymic carcinoma is a prognostic factor, extended surgery combined with a major blood vessel procedure remains controversial because of the increased risk of mortality. We report a case of Stage IVa thymic carcinoma successfully resected with a pneumonectomy along with aortic arch replacement after chemotherapy.Case presentationA 45-year-old male was diagnosed with thymic carcinoma invasion to the aortic arch and left pulmonary artery. Malignant pericardial effusion was also noted, though disappeared after chemotherapy, thus surgical options were considered. A radical resection procedure including left pneumonectomy, aortic arch replacement with total rerouting of the supra-arch vessels, and right pulmonary artery plication was performed. The postoperative course was uneventful and the patient has been disease-free for 3 years.ConclusionExtended salvage surgery might be a valuable option for advanced thymic carcinoma.

ATRIAL FIBRILLATION WITH CARDIAC TAMPONADE AS A FIRST SIGN OF UNDERLYING MALIGNANCY

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: While cardiac tamponade is unusual as the initial presentation of malignancy, malignant pericardial tamponade presenting as atrial fibrillation is even rarer. We present a case of atrial fibrillation with cardiac tamponade who was subsequently diagnosed with pulmonary adenocarcinoma CASE PRESENTATION: A 65-year-old woman presented with concerns of exertional shortness of breath for 1 week with dry cough, fatigue, and chest tightness, with a sudden worsening of respiratory symptoms and palpitations. She was hypotensive, tachycardic, and afebrile. Auscultation revealed muffled heart sounds and she had jugular venous distension. Her electrocardiogram showed atrial fibrillation with rapid ventricular response and no acute ST-segment changes. Chest x-ray showed blunting of her bilateral costophrenic angles with cardiomegaly, but no acute infiltrate. Computed tomography (CT) revealed moderate bilateral pleural effusions, moderate pericardial effusion (2-cm thickness), and bilateral noncalcified pulmonary nodules, with the largest measuring 1.7 x 2.4 cm at the left upper lobe (Image 1). Transthoracic echocardiogram revealed moderate to large pericardial effusion with early tamponade physiology (Image 2). She received emergent pericardial window surgery with drainage of exudative pericardial fluid. Cytological analysis revealed tumor cells positive for Ber-EP4, CK-7, and TTF-1 and negative for CK-20, PAX-8, and calretinin, consistent with metastatic adenocarcinoma likely from the lung. The patient had marked symptomatic improvement after the procedure, and her cardiac rhythm reverted to sinus rhythm. DISCUSSION: Nearly 18%–20% of autopsies performed on cancer patients show involvement of the heart or pericardium. Malignant pericardial effusions can occur by direct invasion of cancer or by metastatic invasion via the lymphatics or hematogenous spread. Tamponade physiology in patients with malignant pericardial effusion is associated with immediate mortality in up to 85% of cases. The association of atrial arrhythmias with cardiac tamponade is rare in the literature, and the association with malignant pericardial effusion is even rarer. Two cases in the literature report cardiac tamponade with atrial fibrillation as the first manifestation of malignancy—both were lymphoid in origin. This is the first case of newly diagnosed solid pulmonary tumor manifesting as atrial fibrillation with malignant pericardial tamponade. CONCLUSIONS: Despite its rarity, malignant pericardial tamponade with atrial fibrillation and rapid ventricular rate should be recognized and managed promptly to mitigate a potentially life-threating condition. Reference #1: Krisanda TJ. Atrial fibrillation with cardiac tamponade as the initial manifestation of malignant pericarditis. Am J Emerg Med. 1990;8(6):531–533. doi:10.1016/0735-6757(90)90157-u Reference #2: Refaat MM, Katz WE: Neoplastic pericardial effusion. Clin Cardiol. 2011;34:593–598. DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by Amr Ismail, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Ximena Solis, source=Web Response No relevant relationships by Victor Test, source=Web Response

ATRIAL FLUTTERS AS AN INITIAL PRESENTATION OF LUNG CANCER CAUSING MALIGNANT PERICARDIAL EFFUSION

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pericardial effusion is a devastating cardiac condition, resulting from various etiology. Cardiac arrhythmia is an uncommon presentation of pericardial effusion, while atrial fibrillation is the most common arrhythmia found in this condition. Atrial flutter, as an initial presentation of malignant pericardial effusion, has not yet been reported. We presented a case of an elderly man with atrial flutter from malignant cardiac effusion from a newly diagnosed lung cancer. CASE PRESENTATION: An 81-year-old man, with chronic obstructive pulmonary disease and hypertension, presented with acute onset shortness of breath. He used albuterol MDI but his symptoms were not improved. On evaluation, he had heart rate 179 beats per minute (bpm), blood pressure 172/118 mmHg without pulsus paradoxus, and respiratory rate of 26. He had good mental status and did not have jugular venous distention. Lungs exam was normal. Heart exam revealed tachycardia without murmur. His blood test was unremarkable. His ECG showed atrial flutter with rapid ventricular rate and 2:1 block. He received intravenous Diltiazem 20 mg and his heart rate decreased to 90. Point of care ultrasound (POCUS) showed large pericardial effusion without tamponade physiology and no signs of pulmonary edema. Computed tomography (CT) chest illustrated large pericardial effusion with new left upper lung mass. Cytology from pericardial effusion revealed squamous cell carcinoma. He was diagnosed as malignant pericardial effusion from advance stage squamous cell lung cancer. His hospital course was complicated with septic shock and eventually death. DISCUSSION: Lung cancer is the most common metastasis cancer to the heart and pericardium because of the proximity of the tumor to the heart [1]. There are several possible explanations of malignant pericardial effusion pathogenesis. First, it can be a result of cardiac lymphatic drainage occlusion by the tumor [2]. Second, local or hematogenous spread of the tumor lead to venous blood flow obstruction and an increase in hydrostatic pressure causing pericardial effusion [3]. Third, neoplastic pericardial involvement stimulates an overproduction of pericardial fluid [3]. Pericardial effusion in cancer patients may arise from complications of treatment, including chemotherapy and radiation, and hypoalbuminemia from malignancy-related cachexia. Cytology analysis of pericardial fluid and pericardial biopsy should be performed to confirm the diagnosis. Management includes pericardiocentesis, pericardial window, pericardial sclerosis, and radiation therapy. CONCLUSIONS: We presented a rare case of atrial flutter secondary to malignant pericardial effusion from newly diagnosis of advanced-stage lung cancer. Clinicians should have pericardial effusion as a differential diagnosis of patients with atrial flutter as this is a catastrophic condition, requiring urgent management. Reference #1: DeCamp MM, et al. Malignant effusive disease of the pleura and pericardium. Chest. 1997;112(4 Suppl):2915-2955. Reference #2: Chiles C, et al. Metastatic involvement of the heart and pericardium: CT and MR imaging. Radiographics. 2011;21(2):438-449. Reference #3: Scheinin SA, Sosa-Herrera J. Cardiac tamponade resembling an acute myocardial infarction as the initial manifestation of metastatic pericardial adenocarcinoma. Methodist Debakey Cardiovasc J. 2014; 10:124–128. DISCLOSURES: No relevant relationships by Nehad Shabarek, source=Web Response No relevant relationships by Kulachanya Suwanwongse, source=Web Response

CARDIAC TAMPONADE UNMASKING AN OCCULT MALIGNANCY IN A YOUNG WOMAN

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pericardial involvement secondary to cancer is mainly the result of metastatic disease and is associated with a poor prognosis (1). The most common tumors involving the pericardium are lung and breast, hematologic malignancies and gastrointestinal cancer (1). Cardiac tamponade with hemodynamic instability occurs in 50% of patients with malignant pericardial effusions (1). We present the case of a 24-year-old woman with cardiac tamponade secondary to primary lung adenocarcinoma. CASE PRESENTATION: A 24-year-old female without medical history presented with progressive shortness of breath accompanied by orthopnea and paroxysmal nocturnal dyspnea for 3 days. She denied fever, cough, chest pain, palpitations or syncope. On admission patient was hemodynamically stable, afebrile, tachycardic, tachypneic and requiring 2L of oxygen to maintain SpO2 of 92%. Physical exam was significant for labored breathing with decreased breath sounds bilaterally. EKG showed sinus tachycardia. Chest CT with contrast was negative for pulmonary embolism but revealed a right pleural effusion, a 2.6 cm pulmonary nodule in right lower lobe and a large pericardial effusion. A few hours later, patient became hypotensive (80/62 mm Hg). Bedside echocardiogram showed tamponade physiology. Emergent pericardiocentesis was performed with drainage of 700 mL of bloody fluid and concomitant right thoracentesis with removal of 600 ml of straw-colored fluid. Pleural fluid was negative for malignancy. However, pericardial fluid was positive for metastatic adenocarcinoma consistent with lung primary. She was diagnosed with stage IV metastatic lung adenocarcinoma and started on chemotherapy with Carboplatin and Pemetrexed. Molecular studies were sent to determine targeted therapy. OBGYN was consulted for fertility preservation. DISCUSSION: A hemorrhagic effusion in a young female patient should prompt investigation for metastatic cancer, lymphoma, autoimmune disorders, tuberculosis and HIV (2). Acute pericardial disease is a sign of underlying malignancy in 4-7% of cases, usually primary lung cancer (2). The standard of care for pericardial tamponade in the setting of a neoplastic disease is pericardiocentesis (1, 2). Cytology is the gold standard of a malignant pericardial effusion with a sensitivity of 71-92% and specificity of nearly 100% (1). It is superior to pericardial biopsy (1). Systemic chemotherapy with pericardial window is more effective than the former treatment alone (2). Chemotherapy combined with molecular targeted therapy was found to have a median survival of 4.5 months (2). CONCLUSIONS: Cardiac tamponade can be the initial manifestation of an underlying cancer and should be considered in the young population. A multidisciplinary team of cardiologists, oncologists, obstetrics, and intensivists is required to provide optimal care. Reference #1: Imazio M, Colopi M, De Ferrari GM. Pericardial diseases in patients with cancer: contemporary prevalence, management and outcomes. Heart 2020; 106(8): 569-574. Reference #2: Richard I, Robinson B, Filice G et al. Primary Lung Adenocarcinoma Presenting with Pericardial Tamponade in a Young Adult: A Rare Case Presentation. Cureus 2020; 12 (1): 1-10 DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Pablo Paz, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response No relevant relationships by Ty Whisenant, source=Web Response

CARDIAC TAMPONADE AS A PRESENTATION OF AN ASYMPTOMATIC EXTRACARDIAC MALIGNANCY

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pericardial tamponade is a life-threatening event secondary to inhibition of passive diastolic filling by rapid accumulation of fluid leading to right atrioventricular diastolic collapse. Patients with pericardial metastasis showing symptoms of cardiac tamponade as the first presenting sign of extracardiac malignancy is very uncommon. CASE PRESENTATION: A 24-year-old female presented to the hospital with progressive dyspnea and lower extremity swelling that started 3 days ago. She had no significant past medical history and was taking no prescription medications. She denied illicit drug use or smoking. There was no family history of malignancy or autoimmune disorder. Her vital signs were: afebrile, blood pressure 90/60 mmHg, heart rate140bpm, respiratory rate 30/min, oxygen saturation 95% on 10 liters of a nonrebreather mask. On physical examination jugular venous distention was 2 cm.Decreased breath sounds on the right hemithorax. Heart sounds were muffled, tachycardia, with a regular rhythm. The patient had 1+ edema bilaterally in the lower extremities. Other exams were unremarkable. CT angiogram of chest found a large right pleural effusion, 2.6 cm pulmonary nodule at right lower lobe,mediastinal lymphadenopathy, and a large pericardial effusion (Fig.1). An echocardiogram showed signs of pericardial tamponade(Fig.2). Cardiology team was consulted and took the patient for an urgent pericardiocentesis with pericardial chest tube placement which drained 650 mL of hemorrhagic fluid. Pulmonology service was consulted for right-sided chest tube placement which drained 600 mL of straw-colored fluid. The patient was then returned to MICU with significantly improvement in vital signs. Pericardial cytology demonstrated malignant cells positive for BerEP4, CK-7, and TTF-1 indicating pulmonary adenocarcinoma, stage 4 given the pericardial tamponade. DISCUSSION: In a young patient without any recent cardiac procedures, history of heart disease or renal failure, other possibilities for hemorrhagic pericardial effusion should be considered such as metastatic cancers including lymphoma, autoimmune disorders, and infectious causes such as tuberculosis and HIV. The treatment of pericardial tamponade in the setting of non-small cell lung cancer is urgent pericardiocentesis, followed by pericardial window if effusion is recurrent. The overall survival in patients with malignant pericardial effusion is dictated by histological type of the underlying malignant process. CONCLUSIONS: Cardiac metastasis is mostly asymptomatic, and pericardium is most common site of metastasis. Pulmonary adenocarcinoma involves lymphatic drainage of the heart and presents with signs of cardiac tamponade even before signs of pulmonary disease. A careful physical exam, imaging, surgical intervention and critical care management were crucial as demonstrated in our case. Reference #1: Fraser, R.S., Viloria, J.B. and Wang, N.-S. (1980), Cardiac tamponade as a presentation of extracardiac malignancy. Cancer, 45: 1697-1704. doi:10.1002/1097-0142(19800401)45:7<1697::AID-CNCR2820450730>3.0.CO;2-J Reference #2: Muir, Keith & Rodger, J. (1994). Cardiac tamponade as the initial presentation of malignancy: Is it as rare as previously supposed?. Postgraduate medical journal. 70. 703-7. 10.1136/pgmj.70.828.703. Reference #3: Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol. 2007;60(1):27-34. doi:10.1136/jcp.2005.035105 DISCLOSURES: No relevant relationships by Kanak Parmar, source=Web Response No relevant relationships by Wasawat Vutthikraivit, source=Web Response

CARDIAC TAMPONADE FROM RAPID UREMIC PERICARDITIS IN PATIENT WITH WARFARIN OVER-ANTICOAGULATION

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Cardiac tamponade constitutes a medical emergency, which requires prompt recognition, diagnosis and treatment that is geared towards preventing cardiovascular collapse and cardiac arrest. CASE PRESENTATION: 81-year-old male patient with end stage renal disease on hemodialysis, paroxysmal atrial fibrillation on warfarin anticoagulation, diabetes mellitus type II, and morbid obesity, who was evaluated for history of 24-hour progression of general malaise, orthopnea, dyspnea on exertion, and dizziness after missing two sessions of hemodialysis. Physical exam was remarkable for borderline low blood pressure, +3 leg edema, distended jugular veins, bibasilar crackles, distant heart sounds, absence of cardiac murmurs or heart sounds. ECG showed pulsus alternans and low voltage criteria. Limited bedside echocardiogram was remarkable for a moderate pericardial effusion with minimal ventricular and atrial compression abnormalities. Patient was provided hemodialysis for volume overload without hemodynamic decompensation and was monitored with telemetry and bedside hemodynamics. Shortly after hemodialysis, patient developed worsening shortness of breath and became hypotensive. Patient was started on norepinephrine vasopressor therapy. A bedside limited echocardiogram showed diastolic right ventricular and right atrial collapse, non-collapsibility of the inferior vena cava and severe pericardial effusion that duplicated in size. Bedside emergent subxiphoid echocardiography-guided pericardiocentesis with instillation of agitated saline was performed with removal of about 400cc of serosanguineous fluid with resolution of hypotension and electric alternans. Labs reflected marked uremia, elevated ESR and C-reactive protein and warfarin overanticoagulation with INR of 4.5. Pericardial fluid resulted with a culture-negative exudative effusion composed of bloody material and inflammatory cells. Chest non-contrast computed tomography showed nonspecific mild mediastinal adenopathy. Positron emission tomography–computed tomography showed no significant F-18 Fluorodeoxyglucose avid lesions that were identified. Patient was provided ultrafiltration for 5 days, and started on colchicine and indomethacin with weekly follow-up of inflammatory markers and echocardiography, with marked improvement of pericardial effusion size and return of normal hemodynamics. DISCUSSION: Uremic pericarditis was identified in setting of acute pericarditis in a patient with over-anticoagulation. The hemorrhagic component resulted in rapid fluid accumulation and tamponade. The instillation of agitated saline can help assess for inadvertent chamber puncture during procedure. CONCLUSIONS: Uremic pericarditis is now an uncommon cause of pericarditis, but it can be exacerbated in the setting of inflammatory pericarditis and over-anticoagulation, leading to rapid accumulation of bloody pericardial fluid and cardiac tamponade. Reference #1: Maggiolini S, Gentile G, Farina A, et al. Safety, efficacy, and complications of pericardiocentesis by real-time echo-monitored procedure. Am J Cardiol 2016;117:1369-74. Reference #2: Sadjadi SA, Mashahdian A. Uremic pericarditis: a report of 30 cases and review of the literature. Am J Case Rep. 2015;16:169-173. Reference #3: Osuch JR, Khandekar JD, Fry WA. Emergency subxiphoid pericardial decompression for malignant pericardial effusion. Am Surg. 1985;51(6):298-300. DISCLOSURES: No relevant relationships by VICTOR MOLINA-LOPEZ, source=Web Response No relevant relationships by Hector Santiago, source=Web Response No relevant relationships by Francisco Tirado-Polo, source=Web Response

Effect of Anti-Inflammatory Drugs on Clinical Outcomes in Patients With Malignant Pericardial Effusion

BackgroundPericardiocentesis (PCC) with extended catheter drainage has become a relatively safe procedure to control pericardial effusion (PE), but little is known about long-term outcomes after PCC in malignant PE. ObjectivesThis study evaluated the effects of anti-inflammatory agents on long-term outcomes after effective drainage of PE in active cancer patients. MethodsFrom May 2007 to December 2018, 445 patients with malignant PE who underwent echocardiography-guided PCC were enrolled. Clinical, laboratory, echocardiographic and procedural findings, and clinical outcome data were collected. Use of anti-inflammatory agents including colchicine, nonsteroidal anti-inflammatory drugs, or steroids after PCC was also analyzed. Colchicine was administered in a dose of 0.6 mg orally, twice a day for 2 months. The primary outcome was defined as a composite of all-cause death and re-PCC or pericardial window operation due to recurred PE. ResultsThe procedure was successful in 97.0% of the cases, with 1 procedure-related death. During the follow-up of 2 years, 26.1% of patients developed recurrent PE, and 46.0% developed constrictive pericarditis. The colchicine treatment group showed a significantly lower risk of composite events (adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [CI]: 0.49 to 0.87; p = 0.003) as well as all-cause death (aHR: 0.60; 95% CI: 0.45 to 0.81; p = 0.001) than did the noncolchicine group. On propensity score matching, colchicine after PCC was consistently associated with a lower composite events (aHR: 0.55; 95% CI: 0.37 to 0.82; p = 0.003). ConclusionsIn cancer patients with malignant PE, PCC with extended drainage can be an appropriate therapeutic option and shows low complication rate. Patients receiving colchicine after successful PCC showed significant improvement in clinical outcome.

Laparoscopic transdiaphragmatic pericardial fenestration in palliative care: how I do it

Background The optimal therapeutic strategy for drainage of malignant pericardial effusion is not yet determined. Several techniques are described, with different benefits and disadvantages. The literature suggests that surgical drainage of pericardial effusions has less effusion recurrence; however, randomized controlled trials are not available. Due to the nature of the disease, quality of life should always be considered while making treatment decisions. Methods A retrospective analysis of all consecutive patients from November 2016 until June 2019 of our institution in the Netherlands was performed. All patients underwent laparoscopic pericardial fenestration after echocardiography and request for operative treatment by the cardiologist. The same operation technique was performed in every case. Results Four out of five of our patients needed pericardial fenestration because of oncological diseases. No hemodynamically instability was noted during this fast technique, achieving direct relief of symptoms. No treatment-related morbidity or mortality, nor the need for re-intervention was encountered. We compared the outcome of our five patients with the existing evidence in the literature. Conclusions In this article, we highlight the laparoscopic transdiaphragmatic pericardial fenestration as a treatment of preference in a non-acute palliative setting. This laparoscopic approach is safe, and can be a valuable alternative among the other well-known approaches.

Intrapericardial instillation of bleomycin prevents recurrence of malignant pericardial effusions: Series of 46 cases and comprehensive literature review

Malignant pericardial effusion is a severe complication of lung and breast cancer. The median survival is less than 4 months and recurrences occurs in about 40% of cases. Systemic chemotherapy and/or local treatments are necessary, even if there is no consensus. We collected data from patients in our center from 1997 to 2016 who received at least one intrapericardial instillation of bleomycin (60mg). At the same time, we conducted a review of the relevant literature on the subject. We included 46 patients in the analysis. Median survival was 2.6 months [95% CI: 1.7; 4.7]. Overall survival was 49% [33%; 63%] at 3 months and 28% [15%; 42%] at 6 months. In the lung cancer subgroup, overall survival was 18% [3%; 44%] at 3 months. In the breast cancer subgroup, overall survival was 73% [44%; 89%] at 3 months and 46% [21%; 69%] at 6 months. The best response rates in the literature are obtained with local instillation of bleomycin or cisplatin. Malignant pericardial effusions in breast cancer patients had a better prognosis. This is certainly related to the prognosis of the underlying disease. We have not found an increase in overall survival with intrapericardial chemotherapy injections, but preventing recurrence of malignant pericardial effusions is a benefit in itself, thus avoiding a lethal complication.

A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing, advanced solid tumors.

3552 Background: Delta-like 3 (DLL3) is highly and specifically expressed in solid tumors, such as neuroendocrine carcinomas (NECs), malignant melanoma (MM), and medullary thyroid carcinoma (MTC). Rovalpituzumab tesirine (Rova-T) is a DLL3-targeting antibody-drug conjugate. Methods: This Phase 1/2 study (NCT02709889) enrolled patients with relapsed/refractory DLL3+ (&gt;1% by IHC) advanced solid tumors and ECOG performance status of 0-1. Rova-T was given IV at 0.2, 0.3, or 0.4 mg/kg on d 1 of each 6-wk cycle (q6wk) for dose escalation (3+3 design) in disease-specific cohorts in Phase I. The recommended Phase 2 dose (RP2D) was tested in Phase II. Safety and dose-limiting toxicities (DLTs) were primary endpoints; efficacy outcomes were secondary endpoints. Results: The study enrolled 200 patients; 101 had NECs (large cell NEC [n=13], neuroendocrine prostate cancer [n=21], high-grade gastroenteropancreatic NEC [n=36], other [n=31]) and 99 had other solid tumors (MM [n=20], MTC [n=13], glioblastoma [GBM; n=23], other [n=43]). The median age was 61 y (range, 28-84); 63% were male. The RP2D was 0.3 mg/kg q6wk for 2 cycles in all cohorts. There were 7 DLTs in 5 patients: 2 with 0.2 mg/kg (Grade [Gr] 3 photosensitivity reaction, Gr 3 dyspnea), 2 with 0.3 mg/kg (1 with Gr 2 effusion, Gr 3 tumor lysis syndrome, and Gr 3 rhabdomyolysis; 1 with Gr 4 kidney injury), and 1 with 0.4 mg/kg (Gr 4 thrombocytopenia). Despite only 1 DLT identified with 0.4 mg/kg, the totality of the safety data suggested that this dose is not well tolerated. Common adverse events (AEs) in patients given 0.3 mg/kg (n=145) are shown (Table). Serious AEs occurred in 77/145 patients (53%), most commonly (≥3%) malignant neoplasm progression (n=18; 12%), pleural effusion (n=7; 5%), pericardial effusion (n=6; 4%), and dyspnea (n=5; 3%). The objective response rate (ORR) was 11% (21/200): 14 had NEC, 2 had MM, 2 had MTC, 2 had small cell carcinoma (SCC) not of lung origin (all partial responses), and 1 had GBM (complete response). In patients with NECs given 0.3 mg/kg, ORR, clinical benefit rate, and progression-free survival trended in favor of those with high DLL3-expressing tumors (≥50% by IHC) which represented 51% of NECs. Conclusions: Rova-T was tolerable in patients with advanced solid tumors at 0.3 mg/kg q6wk for 2 cycles. Antitumor activity was observed in patients with NEC, MM, MTC, SCC, and GBM. Clinical trial information: NCT02709889 . [Table: see text]

Application of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) on Reporting Pericardial Effusion Cytology

Introduction: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) has recently been announced. Pericardial effusion (PE) is a clinical manifestation of a large variety of both neoplastic and non-neoplastic conditions. Herein, we have applied the ISRSFC on reporting PE cytopathology and report our experience in a large academic institution. Method and Materials: After the Institutional Research Board approval, the electronic pathology database of a large academic institution was queried for PEs collected from January 2014 to January 2019. The diagnosis, patient demographics, and specimen volume were recorded for each case. The ISRSFC was applied and the cases were divided into 5 categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). Each category was evaluated separately. Results: A total of 299 cases were identified, 162 females and 137 males. The age of the subjects ranged from less than a year to 89 years (average 51.25 years). The volume ranged from 3 to 1,700 mL (average 298 mL). There were 252 NFM (84.3%), 13 AUS (4.3%), 4 SFM (1.3%), and 30 MAL (10%) cases. Metastatic lung cancer followed by metastatic breast cancer were the most common malignancies involving pericardial fluid (PF). No cases were diagnosed as ND. However, no mesothelial cells were seen in 97 specimens (38% of the negative cases). None of these patients developed malignant PE in at least 6 months of follow-up. Conclusion: The ISRSFC is a user-friendly reporting system which is easily applicable on serous fluid including PF. The vast majority of PEs was benign (84.3%). Our study shows that the presence of mesothelial cells is not necessary for specimen adequacy in serous effusions as no mesothelial cells were identified in 38% of the negative cases. Metastatic lung carcinoma was the most common diagnosis of malignant effusions.

Diagnosis and categorization of malignant effusions: A 6-year review from a single academic institution.

Cytologic detection of malignant cells in pleural, peritoneal, or pericardial effusion most likely indicates advanced stage of malignant disease. There are a few studies updating the categorization of malignant effusions. The electronic pathology database was searched to identify consecutive cases of malignant effusion during a 6-year period. Patient age and gender, origins of known malignancy, and cytologic diagnoses were recorded and summarized. A total of 1059 specimens included 561 (53%) pleural, 441 (41.6%) peritoneal, and 57 (5.4%) pericardial fluids. Most of the pleural (516, 92.0%), peritoneal (418, 94.8%), and pericardial (53, 93.0%) specimens were derived from patients with a single known malignancy. More common origins involving pleural fluid were lung (152, 27.1%) followed by breast (103, 18.4%) and gastrointestinal tract (76, 13.5%). The most common etiology for women and men was breast (102, 30.8%) and lung (67, 36.2%), respectively. More common origins involving peritoneal fluid were gastrointestinal (158, 35.8%) and gynecologic (156, 35.4%) tracts, and breast (46, 10.4%). The most common etiology for women and men was Mullerian (156, 55.5%) and gastrointestinal tract (94, 68.6%), respectively. Most common origins involving the pericardial fluid were breast (20, 37.7%) and lung (17, 29.8%). Breast and lung were the most common etiology for women (20, 57.1%) and men (8, 44.4%), respectively. Breast and lung remain to be the most common origin of both malignant pleural and pericardial effusion for women and men, respectively. The most common origin involving peritoneal effusion is Mullerian for women and gastrointestinal tract for men.

Characteristic molecular signature of pericardial effusion identifies malignant cancer in pericardial disorder patients

Pericardial effusion (PE) can develop in patients with virtually any condition that affects the pericardium, including acute pericarditis and a variety of systemic disorders. Thus, definite differentiation of malignant pericardial effusion and rapid diagnosis are known to have therapeutic and prognostic importance. The aim of this study was to identify novel molecular markers for the detection of cancer in patients with pericardial disorder. We performed one-way ANOVA analysis of whole transcriptome scans of 18 PEs from the patients with pericardial disorder including cancer. It resulted in 4385 outlier genes. Hierarchical clustering analysis showed two distinct clusters [cancer patient’s PEs (G1 + G2) vs. non-cancer PEs (G3)] within the dendrogram. To identify cancer-specific molecular signature, Welch’s t test of G1 and G3 was performed and 1639 gene elements were suggested as stringent classifiers between cancer PE and non-cancer PE. Gene set enrichment analysis of PE signature suggested that CD24, SDC1, and ST14 were strong molecular markers for identifying cancer patients among patients with pericardial disorder. Our results suggest that etiology-specific molecular signatures can discriminate cancer patients within pericardial disorder patients. CD24, SDC1, and ST14 are strong molecular markers for such discrimination.

Causes and prognosis of symptomatic pericardial effusions treated by pericardiocentesis in an Asian academic medical centre.

This study aimed to investigate the causes, clinical management and outcomes of clinically significant pericardial effusions, and evaluate the practice of pericardiocentesis within an academic medical centre in Singapore, a multiethnic country in Southeast Asia. Consecutive patients undergoing pericardiocentesis at a single Asian academic medical centre were identified. Patient demographics, echocardiographic findings, investigations, pericardiocentesis procedural details and clinical progress were tracked using a comprehensive electronic medical records system. Of 149 patients who underwent pericardiocentesis, malignancy (46.3%) was the most common cause of pericardial effusions, followed by iatrogenic postsurgical complications (17.4%). 77.3% of effusions were large and 69.8% demonstrated tamponade physiology. Pericardiocentesis guided by echocardiography and fluoroscopy was successful in 99.3% of patients and had a complication rate of 2.0%. Likelihood of effusion recurrence and survival to discharge was determined by the aetiology of the pericardial effusion. 24.6% of malignant effusions recurred, and the survival rate 12 months after drainage of a malignant pericardial effusion was 45.0%. Short-term mortality was highest among patients presenting with tamponade due to acute aortic syndromes and those with myocardial rupture due to ischaemic heart disease. Cancer and iatrogenic complications were the most common causes of pericardial effusion in this large cohort of Singapore patients. Pericardiocentesis has a high success rate and relatively low complication rate. Prognosis and clinical course after pericardiocentesis are determined by the underlying cause of the pericardial effusion.

Etiology of Pericardial Effusion and Outcomes Post Pericardiocentesis in the Western Region of Saudi Arabia: A Single-center Experience.

BackgroundPericardial effusion is the accumulation of blood or excess fluid in the cavity between the heart and the pericardium sac. Pericardial effusion can be caused by several etiologies, including malignant and non-malignant causes. Pericardiocentesis is the gold standard assessment method for pericardial effusion etiology. The aim of this study was to identify the long-term outcome of patients who presented with massive pericardial effusion and underwent pericardiocentesis at King Abdulaziz Medical City, Jeddah, a large tertiary hospital in the western part of Saudi Arabia.MethodsThis is a single-center retrospective cross-sectional study conducted at King Abdulaziz Medical City Jeddah, Saudi Arabia, between January 2013 to December 2018. Data were collected from patient’s charts; the clinical and echocardiographic findings, alongside with pericardial fluid analysis, were collected. Procedure and patients outcomes were obtained and reported.ResultsOf the 107 patients with pericardial effusion, 39 patients had moderate to severe pericardial effusion requiring pericardiocentesis. The mean age was 52 years, and 56.4% were females. The most common chronic disease was hypertension and the presence of metastasis. The most common cause of pericardial effusion was a malignancy. A majority of patients had severe pericardial effusion. Many patients had tamponade (69.6%). Patients with malignant pericardial effusion had a median survival of 54 days.ConclusionEtiologies of pericardial effusion requiring drainage depend on the population studied. Patients with malignant effusions have worse outcomes than non-malignant effusion. Pericardiocentesis is required to ascertain the cause and risk-stratify patients.

1101 Multimodality imaging in the assessment of pericardial malign disease

Abstract Metastases to the heart and pericardium are discovered at autopsy in 10%–12% of all patients with malignancies. The most common primary tumor involving the pericardium is lung cancer, followed by breast, melanoma, and lymphoma. Pericardial effusion may be the result of the tumor spreading to the visceral pericardium which increases production of fluid, or accumulation of the fluid due to the obstruction of venous and lymphatic outflow. A malignant pericardial effusion is associated with decreased survival rate. We present a 72 year-old woman, former smoker with dyslipidemia and psoriatic arthritis as well as previous bladder carcinoma that was healed in 1986. On august 2017 after an acute intestinal obstruction she was diagnosed with stage IV ileum adenocarcinoma treated initially with palliative chemotherapy (Capecitabine and oxaliplatin) that was suspended for poor tolerance and according to patient desire. Few months later the patient complained of rapidly progressive dyspnoea that prevented her normal life activity, arterial pressure and blood oxygen saturation was normal, but she was tachycardic. Echocardiogram was performed (see figure) which showed marked pericardial nodular thickening and severe pericardial effusion with echocardiographic signs of cardiac tamponade. Curiously, pericardial effusion was dense and markedly hyperechogenic. A computed tomography (CT) was performed to rule out pericardial carcinomatosis and find out the pericardial fluid composition and demostrated several pericardial nodular thickenings that suggested metastases. The pericardial fluid was dense (40 hounsfield units) and consistent with blood. After multidispiplinar consultation and in accordance with patients wishes a palliative pericardial window was performed and hematic pericardial fluid was obtained. Pericardial liquid citology demonstrates atipical cells compatible with carcinoma and pericardial biospy showed fibrinous pericarditis and reactive mesothelial hyperplasia. Pericardial carcinomatosis consists of macroscopic or microscopic affection of pericardial layers. Metastasis from colorectal cancer to the pericardium is uncommon, and usually indicates terminal stage with multiple metastases, only a few cases have been reported. Malignant Pericardial effusions in patients with cancer may also be triggered by other mechanism than cancer itself, including chemotherapy, radiation therapy, and, less commonly, an infectious disease. Whereas echocardiography is most frequently used to examine the heart and pericardium, multimodaliy imaging with magnetic resonance (MR) or/and CT offer advantages when dealing with metastatic disease. Abstract 1101 Figure. Echocardiogram and CT images

Immediate Postoperative Results in the Surgical Treatment of Neoplastic Pericarditis - 76 Consecutive Cases.

Introduction: Pericardial effusion, accumulation of fluid in the pericardial sac, may develop in any type of cancer. It was revealed in up to 20% of oncological patients. Method: We made a retrospective study of patients with pericardial efusion presented in our clinic between 2010 and 2015. We included 76 consecutive patients with indication for peri cardial drainage - we performed on them 80 surgical procedures: pericardocentesis, subxiphoid pericardial window, left paraxifoidian pericardial window, intercostal video-assisted thoracic surgery (VATS) pericardial fenestration, and classical thoracic surgery (fenestration or partial pericardiectomy). We had patients with ages between 28 and 83 years. 23 patients were admitted with cardiac tamponade. The immediate postoperatory survival is 97.3 % and the 30-days-postoperatory survival is 81.5 %. Results: The immediate postoperatory mortality is 2.7% and the 30-days-postoperatory mortality is 8.5%. Conclusions: The immediate prognosis of the patient with malignant pericardial effusion is influenced by the risk of postoperative Low-Cardiac-Output-Syndrome (LCOS), or pericardial decompression syndrome (PDS), which remains the main cause of mortality. The long-term prognosis is related to the type of malignant tumor. The most effective tehnique with the lowest rate of recurrence is pericardo-pleural window done thoracoscopically/ by VATS; pericardocentesis has the highest rate of recurrence - 90% and is associated with high rates of cardiac complications and mortality.

ISOLATED MASSIVE PERICARDIAL EFFUSION AS A HARBINGER OF BREAST CANCER RECURRENCE

Introduction: Malignant pericardial effusion with pleural effusion or lung involvement is not uncommon after breast cancer. It is a life-threatening disease if the patient presents with signs and symptoms of pericardial tamponade. Methodology: It’s a retrospective case report from a tertiary cancer center. Data were retrieved from the human information system of Shaukat Khanum Memorial Cancer Hospital and Research Centre. Case discussion: A twenty-one-year-old female with a right breast lump, which was found to be intraductal, grade III, triple-negative disease. The patient was offered chemotherapy first, later modified radical mastectomy was performed. Post-operative radiotherapy was given. After the completion of treatment, the patient presented in emergency with complaints of abdominal pain. Computed tomography scan was performed which showed pericardial effusion. Pericardiocentesis was performed and fluid was sent for cytology. It showed malignant effusion. She was drained twice with a gap of 20 days. The second time, she went into cardiac arrest and died. Conclusion: Isolated malignant pericardial effusion is a rare disease. Pericardiocentesis can be performed for the symptomatic relief of effusion. However, the chances of recurrence are there.

Nomogram construction for predicting survival of patients with non-small cell lung cancer with malignant pleural or pericardial effusion based on SEER analysis of 10,268 patients.

Determining the accurate outcome of patients with non-small cell lung cancer (NSCLC) and malignant pleural effusion (MPE) or malignant pleural pericardial effusion (MPCE) at the initial diagnosis remains a challenge. The aim of the present study was to develop an effective nomogram for individualized estimation of overall survival in these patients. Patients diagnosed between January 2010 and December 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Age, race, sex, grade, histology, laterality, stage and status of MPE or MPCE at initial diagnosis were included as covariates. Several survival models were created and the performance of each was evaluated. The most effective model was then validated by internal bootstrap resampling and by using an independent external cohort. A nomogram was created based on this survival model and the predictive accuracy of the nomogram was evaluated by calibration plots. Data from 10,268 patients with lung cancer with MPE or MPCE at initial diagnosis were collected. The multivariate analysis with a lognormal model suggested that age, race, sex, histology, stage and status of MPE or MPCE at initial diagnosis were significant independent factors to predict survival. A nomogram was constructed based on the lognormal survival model, which showed the best performance. The concordance index of the survival model in the SEER cohort was 0.736. Both internal and external validation showed an acceptable level of agreement between the nomogram-predicted survival probability and actual survival. The nomogram of the present study based on a large cohort from the SEER database may improve prognostic prediction of patients with NSCLC with MPE or MPCE at initial diagnosis, and allow physicians to make appropriate decisions for disease management of their patients.

P2.14-07 Efficacy of Single Bevacizumab Intrapleural or Intrapericardial Injection in the Treatment of Lung Cancer-Mediated Malignant Effusion

Malignant pleural or pericardial effusion is common in lung cancer, and drug intrapleural and intrapericardial injection plays an important role in the treatment. Local injection drugs include chemotherapy drugs and sclerosing agents. Patients with chemotherapy are vulnerable to bone marrow suppression and gastrointestinal side effects, and sclerosing agents would cause severe local side effects and be forbidden in the intrapericardial injection. The level of vascular endothelial growth factor (VEGF) in the malignant effusion increases significantly, therefore injecting bevacizumab locally may achieve a good response. So we investigated the efficacy and safety of single bevacizumab intrapleural or intrapericardial injection in the treatment of non-small cell lung cancer (NSCLC)-mediated malignant effusion. This prospective, open-labeled, single arm, phase II clinical trial was undertaken at the First Affiliated Hospital of Guangzhou Medical University, China. Eligible patients had histologically or cytologically confirmed NSCLC with malignant pleural or pericardial effusion. Patients unsuitable for or rejecting the systemic therapy were included in. Patients could receive TKI continous treatment after TKI-resistance while only emerging malignant effusion. And lung cancer related symptoms were caused mainly by malignant effusions. Patients were administrated by single bevacizumab 100mg intrapleural or intrapericardial injection after the drainage of effusions. Lung cancer symptom scale (LCSS), efficacy and safety were evaluated before and after the treatment. Twenty patients with lung adenocarcinoma and two patients with lung squamous cell carcinoma were included in the study from January 2014 through March 2019. LCSS after the treatment (score 494±78, mean±SD) were significantly improved compared with that before the treatment (score 377±77, mean±SD) (paired differences: score 117±64, mean±SD, 95% CI: score 89-145, P<0.001). Malignant effusions decreased obviously three weeks after the treatment compared with those before the treatment (P<0.001). The median duration of response was 91 days (127±40 days, mean±SD) in the 14 patients receiving intrapleural injection, and 111 days (91±11days, mean±SD) in the 8 patients with intrapericardial injection. There was no significant difference in the remission time of local injection between malignant pleural and pericardial effusions (P=0.987). Moreover, no severe side effects emerged, only one patient had mildly dizziness. Single bevacizumab intrapleural or intrapericardial injection is effective and safe in the treatment of lung cancer-mediated malignant effusion, while rapidly improving the malignant effusion-related symptoms in NSCLC patients. Certainly furthermore clinical trials were needed to confirm the results.