A broad spectrum of chemotherapy is being used in the therapy of childhood cancers, which may induce liver injury, impairing quality of life and efficacy of the treatment. History of, especially viral, liver diseases may increase toxicity. The aim of the paper is to assess the incidence, type and grade, predisposing factors and treatment options of drug-induced liver injury in children with malignant diseases under cytostatic therapy at the Hemato-Oncology Department of the Pediatric Clinic 2 from Targu-Mures, over a time period spanning from 2012 to 2017. The results of the study may serve as a foundation for such treatment strategies which would enable optimal outcomes with fewer cases of liver toxicity.
During this period, we treated 26 patients with acute lymphoblastic leukemia (ALL), two patients with acute myeloblastic leukemia (AML), one patient with lymphoma and seven with solid tumors. We found liver toxicity in 77% of the patients treated for ALL, mainly during the maintenance therapy (65%) with oral 6-mercaptopurine and methotrexate. The most common clinical signs were anorexia, nausea, vomiting, abdominal pain and faltering weight gain. Cholestasis developed in two patients, while hepatocytolysis was the most common observed event (n = 24). Liver fibrosis, hypersplenism, portal hypertension and esophageal varices were found in two patients. One patient required endoscopic ligation of esophageal varices. Elevation of serum bilirubin appeared in two patients, while hypoproteinemia was observed in nine patients. None of the patients developed acute liver failure. We treated liver toxicity with hydration, alkalinization, i.v. Aspatofort, Aminosteril-N Hepa 8%, oral acetylcysteine, silymarin, ursodeoxycholic acid, Liv-52, Sargenor, and Essentiale forte.
We found hepatotoxicity in 77% of the ALL patients undergoing chemotherapy, similar results have been published by other authors.
Hepatotoxicity may develop through direct hepatic effects of cytostatics, or a preexisting liver disease impairs the metabolism and excretion of the drug, increasing its toxic effects. In our patients hepatotoxicity can be explained mainly by direct liver-injury, previous infections with hepatotropic viruses, such as cytomegalovirus, were detected only in three patients.
Liver injury appeared in 77% of our ALL patients; 65% occurred during maintenance therapy with oral 6-mercaptopurine and methotrexate. Close followup of liver function during chemotherapy is mandatory for optimal results.
Zsuzsanna Erzsébet Papp and Mária-Adrienne Horváth
Childhood cancer is a major psycho-social and health problem. International study groups establish complex, efficient, and concrete Cytostatic Protocols for every cancer type. During chemotherapy patients become extremely vulnerable to infections, so it is necessary to complete the treatment with blood substitution, anti-infection medication, growth factors and other complementary products.
Materials and Methods: We studied the importance of the wide palette of adjuvant therapy near the intensive cytostatic treatment in the period of March 2014-November 2015 at the hemato-oncology department in Pediatric Clinic of Mures County Hospital.
Results: In this period we treated 20 children (9 female, 11 male) aged between 9 months-18 years. We had 15 cases of haemopathies (13 acute leukemia and two lymphomas), and five solid tumors. Packed red blood cells, platelets, and fresh frozen plasma were given in the aplastic period. A patient benefited, on average, a total of 70ml/kg packed red blood cells and 50 U platelets. For infection prophylaxis and treatment every child benefited associated infective medication.
Discussions: Packed red blood cells, platelets, and fresh frozen plasma were given to patients with a deficiency in the ability to produce normal blood cells which are temporarily worsened by chemotherapy. Antibiotic and antifungal medications are given to all febrile and neutropenic patients. We use wide spectrum antibiotics in association for preventing sepsis. Growth factors are stimulating the bone marrow to increase leukocyte number. Since introducing additional immunostimulant medication, we observed a significant decrease of infection in the aplastic period.
Conclusions: Oncology protocols use only 3-5 cytostatic drugs. Maintaining the patient’s life during the treatment, it is necessary to use a large spectrum of supportive medications.
Desmoplastic small round cell tumor (DSRCT) is a rare malignant tumor, which affects mostly young males and has a poor prognosis. Since 1991, when it was first described as a distinct clinical entity by Gerald WL and Rosai J, some 200 cases were reported. DSRCT arises mainly from the abdominal and pelvic cavity, causes abdominal pain or discomfort, weight loss, urinary, bowel or bile obstruction due to compression. Metastases appear most frequently in the liver and lungs. Multimodal therapy is usually indicated with chemotherapy, surgery, radiotherapy and autologous stem cell transplantation. DSRCT should be differentiated from other small, blue round cell tumors, especially hematopoietic malignancies (leukemia, lymphoma), neuroblastoma, Ewing sarcoma, PNET, rhabdomyosarcoma, malignant mesothelioma, small cell carcinoma and Wilms tumors. We report the case of a patient with an extensive abdominopelvic desmoplastic small round cell tumor, with liver metastases, in an adolescent male patient, highlighting the alert deterioration of the clinical status of the patient after the biopsy, the need for a second review of the histopathological material in order to obtain a correct diagnosis, the chemoresistance of the tumor despite an apparently good clinical status, and the severe prognosis of this type of tumor.
Zsuzsanna Erzsébet Papp, Mária-Adrienne Horváth, Izabella Kelemen, Adina Hutanu and Minodora Dobreanu
Background: Pediatric onco-hematology is not a frequently encountered medical specialty, and it influences everyday life, basic activities, and the immune system, mostly through psychosocial changes, which may affect every individual and their families differently. Anxiety is the most frequently encountered mental health disorder occurring during childhood and adolescence. The effect of stress and anxiety on the immune system is suggested by the fact that stress hormones elevate proinflammatory cytokines and subsequently lower the anti-inflammatory response.
Objective: Our main objective was to analyze the relationship between anxiety disturbance and cytokine levels in oncologic pediatric patients from Târgu Mureș in order to answer the following question: does anxiety influence immunity?
Material and methods: After testing pediatric oncology patients from the Pediatrics Clinic no. 2 of Târgu Mureș, Romania with the SCARED child test, we took blood samples from each participant. IL-6, IL-10, IL-1β, IL-12p40 and TNF-α levels were evaluated with a Human Cytokine Magnetic Panel using the xMAP technique on Flexmap 3D platform (Luminex Corporation, Austin, USA). C-reactive protein levels were determined with the BN Pro Spec nephelometer with CardioPhase hsCRP (Siemens Healthcare Diagnostics, GmbH, Marburg, Germany) reagent.
Results: The 46 pediatric oncology patients had 6 main diagnostic groups, the most frequent pathology was acute leukemia (58.7%) followed by malignant solid tumors (21.74%) and lymphomas (6.52%). In the anxious group (45.65%) we observed 4 of the 5 studied anxiety types: panic disorder, separation, social, and generalized anxiety. We measured the cytokine levels of all the participants from the two main groups: anxious/non-anxious. Statistical analysis (linear regression) showed statistically significant positive correlations in the anxious group related to the IL-1β and IL-6, a moderate/weak correlation related to IL-12p40, as well as a negative moderate correlation between IL-10 values in the anxious group and a positive trend in the non-anxious group.
Conclusions: Psycho-oncology is a relatively young specialty with few studies in the last two decades. IL-1β, IL-6, and TNF-α present high levels in anxious patients, while IL-10 and IL-12p40 have low serum levels in mental disorders. C-reactive protein levels are not influenced by anxiety.
Zsuzsanna Erzsébet Papp, Mária-Adrienne Horváth, Nora Rat and Lucian Băilă
Introduction: Childhood cancer, with its major psycho-social and health impact, needs long-term chemotherapy. Increasing the intensity of treatment results in improved outcomes of hematological malignancies and solid tumors. As cytostatics have a vascular irritating effect and multiple peripheric venous punctures cause pain, insertion of a long-term central venous catheter (CVC) during chemotherapy is often necessary.
Materials and methods: All pediatric patients (aged below 18 years) with hematologic and malignant pathologies who underwent CVC insertion at the Pediatric Hemato-oncology Department of the County Emergency Clinical Hospital of Tîrgu Mureș in the February 2014 – May 2016 period were enrolled in the study.
Results: We recorded 24 cases who received central venous catheters, out of which 14 patients received tunneled CVC, 7 patients port CVC, and 3 patients received initially tunneled CVC which was changed with port CVC. Tunneled catheters were preserved in average for 186.06 days and portacaths for 256.6 days. For infection prophylaxis and treatment every child received adequate antibiotic medication.
Conclusions: The use of central lines in pediatric hemato-oncology is accessible and benefic not only for increasing patient comfort, but also to ease the nurses' work, who are often overburdened.