Dimitrios Doganis

Does Early Treatment of Urinary Tract Infection Prevent Renal Damage

OBJECTIVE. Therapeutic delay has been suggested as the most important factor that is likely to have an effect on the development of scarring after acute pyelonephritis. However, this opinion has not been supported by prospective studies, so we tested it. METHODS. In a prospective clinical study, we evaluated whether the time interval between the onset of the renal infection and the start of therapy correlates with the development of acute inflammatory changes and the subsequent development of renal scars, documented by dimercaptosuccinic acid scintigraphy. A total of 278 infants (153 male and 125 female) aged 0.5 to 12.0 months with their first urinary tract infection were enrolled in the study. RESULTS. The median time between the onset of infection and the institution of therapy was 2 days (range: 1–8 days). Renal inflammatory changes were documented in 57% of the infants. Renal defects were recorded in 41% of the patients treated within the first 24 hours since the onset of fever versus 75% of those treated on day 4 and onward. Renal scarring was developed in 51% of the infants with an abnormal scan in the acute phase of infection. The frequency of scarring in infants treated early and in those whose treatment was delayed did not differ, suggesting that once acute pyelonephritis has occurred, ultimate renal scarring is independent of the timing of therapy. Acute inflammatory changes and subsequent scarring were more frequent in the presence of vesicoureteral reflux, especially that which is high grade. However, the difference was not significant, which suggests that renal damage may be independent of the presence of reflux. CONCLUSIONS. Early and appropriate treatment of urinary tract infection, especially during the first 24 hours after the onset of symptoms, diminishes the likelihood of renal involvement during the acute phase of the infection but does not prevent scar formation.

Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL

We prospectively evaluated the immunological status, immune recovery and risk of infection in pediatric ALL patients treated on the BFM 95 protocol.

Differences Between Younger and Older Patients with Childhood Hodgkin Lymphoma

From 1979 to 2006, 74 children with Hodgkins lymphoma were treated at our center. Among them, 15 (14 boys and 1 girl) and 59 (33 boys and 26 girls) patients were younger and older than 8 years, respectively. Six (40%) children among younger patients and 26 (44%) among older patients had advanced stage disease. We detected 3 (20%) relapses among younger patients and 5 (8.5%) among the older patients. All of younger patients are alive whereas three of the older patients have died. Second malignancy developed in one and three children among younger and older patients, respectively. The only difference that was detected concerning the age was a male predominance among the younger patients.

Predictive factors for blood stream infections in children with cancer.

Blood Stream Infections (BSI) are among the most serious infections in children with cancer and are potentially life threatening. A retrospective study of blood cultures obtained from all newly diagnosed patients—from January 1, 2005 to December 31, 2009—with malignancy was conducted. In this study, our aim was to identify clinical and laboratory variables associated with a BSI in a child with malignancy. Among 1004 separate infection episodes detected in 261 patients, 198 were classified as true BSI (19.7%). Univariate analysis showed that factors such as younger age, race, temperature ≥40°C, presence of chills and hypotension, time interval from the last chemotherapy, treatment for recurrent disease or a history of Stem Cell Transplantation, low hemoglobin, low-Platelets count, and Absolute Neutrophils count less than 4 × 109/L were predictive for a BSI. Patients with a catheter in place and especially if this catheter was tunneled and/or multiple lumen were more likely to have a BSI. Being on antibiotics, the history of a BSI during the previous month and having received a red cell or platelet transfusion during the prior 15 days also increased the likelihood for a BSI. According to a multivariate logistic regression analysis, the factors that remained significant were the younger age, the African American race, the presence of chills or hypotension, the use of tunneled or multiple lumen catheters, the administration of antibiotics during the previous 15 days and a low-PLT count.

Optic pathway glioma in children: 10 years of experience in a single institution

ABSTRACT Optic pathway glioma (OPG) is a rare brain tumor that occurs more commonly during early childhood and is frequently associated with neurofibromatosis type 1 (NF1). In this study, our aim was to describe the characteristics, management, and outcome of patients with OPG. We retrospectively analyzed the clinical charts of all children diagnosed with OPG at our institution from 2003 to 2013. Twenty children (11 boys and 9 girls, median age: 5 and 3/12 years; NF1: 15/20) were diagnosed with OPG. The diagnosis was based on magnetic resonance imaging (MRI) findings. A biopsy was useful in 3 patients. The main reason for seeking medical advice was decreased vision (7/20 patients), whereas in 10/20 patients, the diagnosis was established during the routine follow-up for their NF1. Fifteen patients demonstrated MRI findings of optic nerve involvement and/or chiasmal tumor, whereas in 5 children, postchiasmal structures were also involved. Sixteen patients (16/20) received carboplatin-based regimens, whereas 4/20 patients were only under close observation. Six patients showed deterioration of visual acuity and/or imaging findings at the end of treatment and/or during their follow-up. Three of them (3/6) underwent tumor resection, whereas 1 (1/6) received radiation treatment. None of our patients had total blindness from both eyes. Half of our patients were diagnosed during follow-up for their NF1, the incidence of which was high in our group. Our data suggest that chemotherapy helps in the preservation of vision in the majority of children.

Malignant Peripheral Nerve Sheath Tumors in Children with Neurofibromatosis Type 1

Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5–10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department. Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them. Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear.

A Novel Karyotype in Acute Myeloid Leukemia with Basophilia

Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, −21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity.

Successful treatment in a child with anaplastic large cell lymphoma and coexistence of pulmonary tuberculosis.

A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL), whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR) in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months), pyrazinamide (the first 2 months), and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time.

SUCCESSFUL COMBINATION OF ANTIFUNGAL AGENTS AND SURGICAL RESECTION FOR PULMONARY ASPERGILLOSIS IN A CHILD WITH HODGKIN DISEASE: Review of the Literature

The authors report on a 14-year-old adolescent boy suffering of Hodgkin disease in remission, who developed autoimmune anemia and thrombopenia. He was treated with high-dose steroids and he developed serious invasive lung aspergillosis, which was treated with antifungal agents and surgical intervention. Children suffering from cancer are prone to develop systemic fungal infections secondary to the severe immunosuppression caused by the disease itself and the antineoplastic therapy. Intravenous antifungal medications and, when feasible, surgery are used for treatment of pulmonary aspergillosis. Factors related to better outcome are early diagnosis, remission of underlying disease, aggressive antifungal therapy, and recovery from neutropenia.

Voriconazole Antifungal Prophylaxis in Children With Malignancies: A Nationwide Study

Background: Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. Materials and Methods: A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients’ demographics, outcome, and adverse event (AE) data were recorded. Results: Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. Conclusions: VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.