Wilms tumor and cardiomyopathy

Abstract

It is well known that renal tumors may be associated with hypertension due to hyperreninemia and/or raised catecholamines, which in extreme cases may lead to congestive heart failure. We, however, encountered two Wilms tumor patients with dilated cardiomyopathy, who displayed no evidence of hyperreninemia or raised catecholamines, and in one not even hypertension.We conducted a retrospective case analysis on both children with special emphasis on cardiovascular physiology and activity of the renin/catecholamine system. Heart function was assessed by clinical examination and trans-thoracic echocardiography (TTE) immediately at admission, and then at regular intervals during and after therapy. In detail, the following parameters were determined: left ventricular enddiastolic diameter (LVEDd), and left ventricular shortening fraction (SF). The functional status of the neuro-endocrine system was evaluated by measurement of serum levels of renin, and of urinary levels of vanillylmandelic acid (VMA), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), epinephrine, norepinephrine, and dopamine. Further details follow.The first patient was a 2.5-years-old Caucasian girl, who presented with a right-sided Wilms tumor stage IV; her blood pressure was 100 mmHg systolic. A routine pre-treatment TTE examination revealed a dilated cardiomyopathy with an increased LVEDd (¼ 42 mm), decreased SF (¼ 22%), and a hypokinetic septum without evidence of anomalous intracardiac anatomy; ECG was normal and showed no signs of left ventricular hypertrophy. The serum level of renin and the urinary levels of VMA, HVA, 5-HIAA, epinephrine, norepinephrine, and dopamine were not elevated. After chemotherapy, following the SIOP 93-01/GPOH protocol (modified by exclusion of doxorubicin, and by inclusion of etoposide and carboplatin), and complete tumor excision plus radiation therapy (total dose of 20 Gy), the patient is in complete remission. The histologic examination of the specimen revealed a classic triphasic Wilms tumor stage pT2b. In the early postoperative period, the LV function started to return gradually to normal with a LVEDd of 38 mm and a SF of 35% at 3 years after presentation. The second child was an 8-months-old Caucasian girl, who presented with a right-sided Wilms tumor and arterial hypertension of up to 154 mmHg systolic. Standard ECG showed abnormalities of repolarization, but no signs of hypertrophy. TTE revealed a normal intracardiac anatomy, and normal LVEDd (¼ 29.7 mm), but a significantly reduced SF of 22.41%. The urinary levels of VMA, HVA, and dopamine were not elevated. Complete resection of the abdominal mass could be performed after reduction of blood pressure by captopril. Histology of the operative specimen showed a partially differentiated cystic Wilms tumor, stage pT1. Therefore, further chemotherapy was needless. Since operation the patient is in complete remission. At 12 days after operation, the LV function started to return gradually to normal with a SF of 34.6% at 2 months after presentation.

Characterization of a WiT49 cell line derived orthotopic model of Wilms tumor

“…Although effective treatment is available for the majority of Wilms tumor patients, the failure of some patients to respond to current treatments along with emerging data regarding long term risks of those treatments such as radiation-related scoliosis, gonadal failure, adverse effects on pregnancy, cardiomyopathy, and increased long-term risk of second malignancies [2–6], call for the development of new therapeutic approaches. A prerequisite for the successful screening and development of new anti-tumor agents is the availability of an appropriate animal model.…”

S1P/S1P1 signaling stimulates cell migration and invasion in Wilms tumor

“…Children at risk for adverse outcome, such as those with nuclear anaplasia, a marker for chemoresistance, or those with loss of heterozygosity for chromosomes 1p and 16q, for example, must rely on adjuvant chemotherapy and/or radiotherapy for treatment [1]. Unfortunately, these therapies are associated with significant late sequelae, such as radiation-related scoliosis, gonadal failure, adverse effects on pregnancy, cardiomyopathy, and increased long-term risk of second malignancies [2–8]. Clearly, a better understanding of the stimuli and signaling pathways involved in Wilms tumor progression would be a substantial advancement.…”

Bilateral Nephroblastoma with Dilated Cardiomyopathy as an Indication for Off-Protocol Treatment: A Case Report

“…Hypertension and cardiomyopathy may coexist with a Wilms tumor [6]. Hypertension may be caused by the mechanical compression of the renal artery or renin production by the cancer cells.…”

“…Hypertension accompanying a Wilms tumor occurs in about 10-27% of children [4,5]. Cardiomyopathy associated with a Wilms tumor is very rarely described [6][7][8].…”