Erman Atas

Cardiac troponin-I, brain natriuretic peptide and endothelin-1 levels in a rat model of doxorubicin-induced cardiac injury.

BACKGROUND Cardiotoxicity, during or after therapy, is the most serious side effect of doxorubicin (DXR). The risk of developing cardiac impairment increases concomitantly with an increase in the cumulative dose of DXR. AIM The aim was to evaluate the levels of cardiac troponin-I (cTnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) in DXR induced cardiac injury. MATERIALS AND METHODS Thirty-nine Wistar albino rats were divided into three groups; a control group and two-study groups that received low-dose DXR (LDD) and high-dose DXR (HDD) in a weekly schedule for reaching a cumulative dose. RESULTS Serum cTnI level was significantly increased in both LDD and HDD-treated groups. Although serum BNP was not significantly increased either LDD or HDD-treated groups, ET-1 levels was significantly increased in only HDD-treated groups. Histopathologic injury was more evident in HDD-treated group. CONCLUSIONS Serum cTnI was increased even in LDD and parallel to it low cardiac injury induced by DXR. In the low-dose group, BNP and ET-1 levels were not elevated significant as cTnI despite cardiac injury. Thus, cTnI may be a predictive marker in of DXR-induced cardiotoxicity.

Outcome of autologous hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory Hodgkin's lymphoma.

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty‐nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara‐C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow‐up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non‐relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.

Raynaud's phenomenon in a child with medulloblastoma as a late effect of chemotherapy

There are a lot of early or late side effects of chemotherapies. One of them is Raynauds phenomenon (RP). Vascular toxicity associated with antineoplastic agents is notified in bleomycin alone therapy or in combination with cisplatin, vinblastine, and vincristine. The mechanism of RP associated with antineoplastic agents is unknown. All children receiving vinblastine, vincristine, bleomycin and cisplatin therapy, are followed and questioned about their complaint on RP. Long-term follow-up of surviving patients is recommended. Oncologists should be aware of the potential late toxic effects of antineoplastic drugs.

Inappropriate antidiuretic syndrome hypersecretion after a single dose of cisplatin.

Severe hyponatremia with seizure owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral/renal salt wasting syndrome related with high mortality. The correct diagnosis of the hyponatremia for each case is important because of the alteration of the treatment approach. SIADH is an important clinical manifestation that does not occur after all chemotherapy courses. We cannot estimate whether the disease will occur on, which course of the chemotherapy in this case.

Clofarabine associated capillary leak syndrome in a child with lymphoma successfully treated with intravenous immunoglobulin

Clofarabine is an effective drug in relapsed leukemia and lymphoma that has some adverse effects which can be fatal like capillary leak syndrome (CLS). Identification and management of CLS is important that may result in mortality. Although prophylactic treatment with steroids may prevent CLS and improve survival, intravenous immunoglobulins are used in the treatment with great success in steroid resistant cases. However, the knowledge about the effects and the dose of intravenous immunoglobulins (IVIG) in pediatric patients is limited. Herein, we reported a patient with relapsed lymphoma who developed CLS successfully and was treated with IVIG.

Evaluation of children with lympadenopathy

AIM To examine children who present with enlargement of lymph nodes in terms of demographic, clinical, serological and radiological aspects. MATERIAL AND METHODS Ninety-eight patients who presented with a complaint of enlargement of lymph nodes were examined in terms of demographic, clinical, serological and radiological aspects by screening file data retrospectively. The character of lymph nodes (reactive, malign) was evaluated according to the distribution, number, sizes and blood supply determined in ultrasonographic measurements. Fishers Exact test and Mann-Whitney U Test were used in comparison of the groups. Kappa value was used in assessment of compatibility between the two groups. RESULTS Cervical lymphadenomegaly was found most frequently in accordance with the complaint of swelling in the neck. Erythrocyte sedimentation rate, ultrasonography, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) IgM were not found to be statistically significatly different between the normal and abnormal physical examination groups (erythrocyte sedimentation rate; p=0.623, USG; p=0.753, EBV and CMV; p=1.00). Cytomegalovirus and EBV IgM were not found to be statistically significatly different between the normal and abnormal ultrasonography groups (CMV; p=0.35, EBV; p=0.36). There was no compatibility between physical examination and ultrasonography (=0.32). CONCLUSION Lymphadenopathy is a common problem in the childhood and necessitates a careful physical examination and follow-up. Laboratory and imaging methods should be used when necessary. Although lymphadenopathy is mostly related with infections, care should be taken in terms of malignancy and malignancy should be eliminated. The important point is systemic evaluation and follow-up of the patient. It is important to note physical examination findings and clinical follow-up findings, because frequent ultrasonographic investigations may confuse physicians and families with high values of lymph node measurements despite normal physical examination. Therefore, using our fingertips with a good physical examination is still our most sensitive diagnostic tool instead of ultrasonography.

The timing of autologous stem cell transplantation and the prognostic factors affecting the prognosis in children with relapsed Hodgkin lymphoma.

Although ASCT is used as a standard treatment following second remission for adults in oncology practice, data are lacking for relapsed childhood HL. Therefore, we evaluated the exact timing of the ASCT treatment, as well as factors affecting the prognosis in children with relapsed HL who underwent ASCT. Patients were divided into two groups (Group 1: ASCT after second remission [n = 6], Group 2: ASCT after >2 remissions [n = 3]). Overall, DFS rate was 64.8% at 24 months after ASCT. In Group 1, post‐transplant DFS and OS were 83.3% and 75%, respectively, and the post‐transplant response without event rate was 5/6 (83.3%). However, in Group 2 this was 1/3 (33.3%). Nonetheless, the timing of ASCT was not a significant prognostic factor for DFS and OS in univariate analyses (p = 0.21 and p = 0.73, respectively). Median follow‐up time was 21 months after transplant, and DFS and OS were 62.5% and 75% in early relapse group (n = 6) at 24 months. DFS and OS were both 66.7% in late relapse (n = 3). In addition, response rates of ASCT without event were 66.7% for both early and late relapse groups. Relapse types (early: 3–12 months, late: >12 months) was not a significant prognostic factor for DFS and OS in univariate analyses (p = 0.96 and p = 0.92). While we found ASCT to be a useful treatment following second remission, it does not demonstrate better success in early relapse cases, when compared to late relapse cases. Therefore, after second remission for relapsed HL, ASCT is advisable regardless of the time of relapse.

Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide

After hematopoietic stem cell transplantation (HSCT), patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI) which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa) and octreotide infusion.

Small intestinal lactoferrin and calprotectin levels in different stages of necrotizing enterocolitis in a rat model

PURPOSE Necrotizing enterocolitis (NEC) is a severe disease of mostly premature infants with high morbidity and mortality rates. There is no reliable biomarker for detecting newborns at risk for NEC development. We aimed to investigate small intestinal lactoferrin (LF) and calprotectin (CAL) levels as predictors and indicators of disease severity in an experimental newborn rat model. MATERIALS AND METHODS Newborn pups were randomly divided into two groups, NEC and control. The NEC group pups were decapitated on the second, third and fourth days of the experiment for an assessment of the different stages of NEC. In the study group, hypoxia-reoxygenation model used to induce NEC. As biochemical parameters, small intestinal LF and CAL levels were measured with an enzyme-linked immunosorbent assay technique and intestinal injury scoring was evaluated as a pathologic parameter. RESULTS Small intestinal levels of both LF and CAL increased in the second and the third day groups, but began to decrease by the fourth day. The first, second and third day levels of LF and CAL were higher than controls. The intestinal injury scores of all NEC groups were significantly higher than the control group. CONCLUSION Small intestinal lactoferrin and calprotectin were good markers for demonstrating NEC. However, instead of spot testing, monitoring the levels of these markers may be more informative.

131I-Metaiodobenzylguanidine conditioning regimen in children with neuroblastoma undergoing stem cell transplantation.

Radio-labeled 131I-metaiodobenzylguanidine (MIBG) therapy is used in the treatment of highrisk neuroblastoma as a part of conditioning regimen in combination with other chemotherapy agents (1). The maximum-tolerated dose of 131IMIBG is reported as 12 mCi/kg (2, 3). However, mucositis as well as myelosuppression is the major toxicity (4). 131I-MIBG may increase the toxicity of the drug regimen. Herein, we report and discuss 131I-MIBG dose and toxicity in two children that were treated with 131I-MIBG, followed by myeloablative doses of carboplatin, etoposide, and melphalan with stem cell rescue. The first case was a nine-month-old female child who presented with right abdominal palpable mass. She was diagnosed with stage IV neuroblastoma and treated with chemotherapy including cyclophosphamide, vincristine, etoposide, cisplatin, dacarbazine, ifosfamide, and adriamycin for six courses in addition to surgical resection resulting in a 2 cm residual right adrenal mass. She underwent autologous bone marrow transplantation (ABMT), including 100 mCi (10 mCi/kg) 131 I-MIBG treatment on day 21 followed by melphalan 45 mg/m/day on days 8 to 5, etoposide 200 mg/m/day, and carboplatin 300 mg/m/day on day 5 to 2. On day +15, she presented with grade 4 mucositis, diarrhea, and massive gastrointestinal bleeding without any evidence of engraftment. After all vigorous efforts, she died on day +18. The second case was an eight-yr-old girl with stage IV neuroblastoma. She was treated with the same chemotherapy for six courses, and there was a 4-cm residual mass after surgical resection. She received radiotherapy to the residual mass. After the first recurrence from the primary site of tumor with multiple metastases in the abdomen, she was treated with ICE chemoterapy regimen, including ifosfamide, carboplatin, and etoposide and then underwent ABMT with the same conditioning regimen including 100 mCi (3.1 mci/kg) 131-I-MIBG on day 21. On day +7, she developed grade 3–4 mucositis, diarrhea and grade 1 autologous GVHD involving an erythematous skin rash on the face and trunk region. There was no platelet engraftment on day +25 when she developed acute hypertension and intracranial bleeding. She died on day +31. CD34 positive stem cell selection and granulocyte colony stimulating factor supplementation was added to the treatment of the two patients that has shown great efficiency in engraftment and prognosis of the patients with neuroblastoma (5, 6). Treatment with 131I-MIBG in combination with myeloablative chemotherapy and ABMT is reported as a feasible option (3). Indications for 131I-MIBG therapy include the following: (i) if no other treatment is possible (surgery, chemotherapy, external beam radiotherapy), (ii) when at least one-yr survival is expected, (iii) all (or most) identifiable lesions should accumulate tracer on the MIBG scan, and (iv) and a radiation dose of 0.5 cGy/MBq can be delivered to the tumor (7, 8). We used an MIBG conditioning regimen for ABMT. Myelosuppression is the most common toxicity, and non-hematologic toxicity is generally mild but there is no definite correlation between dose and response or toxicity (4). Major non-hematologic toxicities reported as grade 2–3 mucositis, diarrhea, and renal dysfunction. Erythematous skin rash, hematuria, asymptomatic hypothyroidism were the other complications (2, 9). Mucositis is the leading toxicity reported and reached to grade 4 in half of the patients (9). In our patients, major non-hematologic toxicities were mucositis and diarrhea, which was consistent with previous literature. Erythematous skin rash was found to be consistent with GVHD pathologically in our second case. Contrary to our current observation, there