Accuracy of imaging-guided biopsy in diagnosis of malignancy versus infection.

AIMS: Imaging-guided biopsies obtain samples for pathologic testing in addition to therapeutic interventions in patients with cancer. Our aim was to determine the diagnostic accuracy of percutaneous biopsies of pediatric solid tumors and infectious complications of cancer treatment. MATERIALS AND METHODS: This study was performed by gathering pediatric oncology patients between 1998 and 2008. A total of 41 percutaneous biopsies were performed in order to establish a diagnosis for a suspected malignancy or an infectious complication of cancer treatment. RESULTS AND CONCLUSIONS: An accurate diagnosis was achieved in 21 of 26 (87.6%) percutaneous biopsies for suspected malignancy cases or recurrence. The remaining 15 percutaneous biopsies were done for the diagnosis of infectious complications of cancer treatment with an accurate diagnosis of 60%. Imaging-guided percutaneous biopsy technique is highly accurate and safe, particularly in diagnosis of a suspected tumor.

Effects of malnutrition on oxidative burst functions and infection episodes in children with acute lymphoblastic leukemia.

INTRODUCTION: The aim of this study was to determine the effect of malnutrition on oxidative burst functions (OBF) of neutrophils in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Twenty-eight patients with ALL and thirty healthy controls were enrolled to the study. Thirteen patients with ALL were found to have malnutrition. While neutrophil OBF of ALL patients without malnutrition were studied both before induction chemotherapy and 3 months after, the same functions in ALL patients with malnutrition were studied both before induction chemotherapy and when the nutritional status improved. Control group were studied at admission and 3 months later. RESULTS: The OBF of ALL patients with and without malnutrition before induction chemotherapy were found to be significantly lower than the control group (P = 0.009), whereas the OBF were found to be similar in both patient groups with ALL (P = 0.27). The median infection episode rate and the duration of antibiotics therapy during the study period were similar in both patient groups with ALL. The repeated OBF of both patient groups with ALL were shown to increase to similar values with the control group in the third month of chemotherapy (P = 0.002). The median infection episode rate during the first month of chemotherapy was shown to decrease significantly during the third month of chemotherapy in both patient with ALL groups (P < 0.001). CONCLUSIONS: We have not been able to demonstrate an overt effect of malnutrition on OBF. However, our results still need to be verified via further larger scaled studies of OBF in leukemic children with and without malnutrition.

Cardiac effects of granisetron in a prospective crossover randomized dose comparison trial.

PURPOSE: Cardiac side effects of granisetron have been studied mostly in adult patients that are using cardiotoxic chemotherapeutics. There is limited evidence in pediatric age group and no information in pediatric oncology patients with non-cardiotoxic chemotherapeutics. METHODS: In this prospective, crossover randomized study, the cardiac side effects of granisetron are compared in pediatric oncology patients who had carboplatin based chemotherapy. They were randomized to receive either 10 or 40 µg kg(-1) dose(-1) of granisetron before each cycle of chemotherapy. We drew blood for creatine phosphokinase (CPK), CPK-muscle band (MB) and Troponin-T before and 24 h after administering granisetron. Electrocardiography (ECG) tracings were taken at 0, 1, 2, 3, 6 and 24 h of granisetron. Twenty-four hours Holter ECG monitorisation was performed after each granisetron infusion. RESULTS: A total of 16 patients (median 8.7 years of age) were treated with weekly consecutive courses of carboplatin. There was bradycardia (p = 0.000) in patients that had granisetron at 40 µg/kg and PR interval was shortened in patients that had granisetron at 10 µg/kg dose (p = 0.021). At both doses of granisetron, QTc interval and dispersion were found to be similar. CPK, CK-MB and Troponin-T values were found to be normal before and 24 h after granisetron infusion. CONCLUSIONS: As the first study that has studied cardiac side effects of granisetron in patients that are not using cardiotoxic chemotherapeutics, we conclude that granisetron at 40 µg kg(-1) dose(-1) causes bradycardia only. We have also demonstrated that granisetron does not cause any clinically cardiac side effects either at 10 or 40 µg kg(-1) dose(-1). However, our results should be supported by prospective randomized studies with larger samples of patient groups.

Effect of acid-etching procedure on selected physical properties of mineral trioxide aggregate.

AIM: To evaluate the effect of acid-etch procedures on the compressive strength and surface microhardness of tooth-coloured mineral trioxide aggregate (MTA). METHODOLOGY: White ProRoot MTA (Dentsply Tulsa Dental) was mixed and packed into cylindrical tubes of 4 mm in diameter and 6 mm in height. Three groups, each of 15 specimens were subjected to an acid-etch procedure either 4, 24 or 96 h after mixing. The compressive strength was measured and compared with unetched control groups. Differences between groups were analysed using the Kruskall-Wallis test. A further batch of cylindrical specimens of 6 mm in diameter and 12 mm in height were prepared for testing surface microhardness. Three groups of 15 specimens were subjected to the acid-etch procedure at either 4, 24 or 96 h following mixing. Data were subjected to one-way anova. Changes in the surface microstructure before and after the acid-etch procedures were analysed using a scanning electron microscope (SEM). RESULTS: There was a general trend for the compressive strength and surface microhardness of specimens to increase with time. In terms of compressive strength, the increase was significant between 4 h and the other time periods for both experimental and control groups (P < 0.0001); however, there was no significant difference between 24 and 96 h. The increase in surface microhardness was significant between 4, 24 and 96 h (P < 0.0001). In addition, there was a significant difference between experimental and control groups at all time periods (P < 0.0001). SEM examination revealed morphological differences between the intact and the etched MTA surfaces. CONCLUSIONS: Acid-etch procedures affected the compressive strength and surface microhardness of ProRoot MTA. This indicates that it may be better to postpone restorative procedures for at least 96 h after mixing MTA. Etching created surface changes that might have the potential to enhance bonding of resinous materials.

Shear bond strength of luting agents to fixed prosthodontic restorative core materials.

BACKGROUND: Bonding properties of luting cements are important for retention of restorative core materials. The aim of this study was to compare the bonding performance of a resin-modified glass ionomer cement and a self-adhesive resin cement to various fixed prosthodontic core materials. METHODS: Cylindrical specimens with a thickness of 2 mm and a diameter of 5 mm were fabricated from Au-Pd-Ag, Co-Cr, Ni-Cr-Mo, Ni-Cr-Fe alloys, titanium, zirconia and Empress II (n = 20). Each group was divided into two subgroups to be luted with two different luting agents. Composite resin blocks were cemented onto specimens with RelyXUnicem and FujiCem. A shear bond strength machine with 50 kg load cell and 0.50 mm/min crosshead speed was used. Kruskal Wallis test, Dunn's Multiple Range test and Mann-Whitney-U test were used for statistical analysis. The results were evaluated in a confidence interval of p < 0.05. RESULTS: The highest bond strength was obtained between Ni-Cr-Fe-RelyXUnicem (8.22 +/- 2.15 MPa) and the lowest was between Empress II-FujiCem (1.48 +/- 0.9 MPa). In FujiCem groups, Co-Cr and Ni-Cr-Fe showed significantly higher bond strength than Au-Pd-Ag and Empress II. In RelyX Unicem groups, Ni-Cr-Fe showed higher bond strength than Empress II. CONCLUSIONS: The types of luting agents and restorative core materials may have a significant influence on bond strength.

The effects of iron deficiency on neutrophil/monocyte apoptosis in children.

OBJECTIVES: Iron is essential for DNA synthesis; its deficiency may lead to impaired DNA synthesis and subsequent alterations in levels of apoptosis. Here, we have aimed to investigate effects of iron deficiency anaemia (IDA) on apoptotic response of phagocytic cells and to understand whether the effect is reversible after iron supplementation. MATERIALS AND METHODS: Forty-nine IDA patients and 26 healthy controls, aged between 6 months and 12 years with similar demographic status, were considered. Neutrophil- and monocyte-apoptotic responses of IDA patients and the control group were compared by flow cytometry. Then, IDA patients were provided with oral iron supplementation. On day 15 of iron therapy, neutrophil- and monocyte-apoptotic responses of IDA patients were rechecked and were compared to those of control group. RESULTS: Neutrophil- and monocyte-apoptotic responses in terms of early and late percentages of apoptosis, and percentages of necrotic cells, were significantly less in IDA patients compared to the control group. The significantly low apoptotic responses of IDA patients rose to levels of the control group by day 15 of iron therapy. Besides, the effect of IDA on apoptotic responses was found to be more enhanced in severe IDA patients that those of mild IDA patients. CONCLUSION: Correction of differences after iron supplementation therapy implies that IDA might be a cause for changes in neutophil- and monocyte-apoptotic responses. The impact of this diminution of apoptotic cellular function in IDA should be further investigated, with longitudinal studies, in order to document the impact of any severe and/or long-lasting IDA on autoimmunity and malignancy.

Pichia anomala fungaemia in immunocompromised children.

Pichia anomala is an emerging yeast causing serious nosocomial infections in newborn and immunocompromised children. We describe nosocomial port catheter infection due to P. anomala in three children who were receiving cancer chemotherapy, bloodstream infection in a preterm infant and in an infant with severe combined immunodeficiency. All patients were treated with amphotericin B. All isolates were susceptible to amphotericin B and fluconazole. No recurrence was observed during follow-up in four of five patients. The common clinical feature in all of our patients was the presence of prior antimicrobial therapy.

Partial intestinal obstruction due to childhood refractory hon-Hodgkin's lymphoma, successfully treated with taxol.

In this report, we present a six-year-old male patient with partial intestinal obstruction due to refractory Non-Hodgkin's lymphoma (NHL) whose partial obstruction was successfully treated with Taxol(R) without any surgical intervention. Following an unsuccessful treatment attempt to treat his high-grade (stage 3) B-cell lymphoma with standard and second-line chemotherapy regimens he was started on radiotherapy and third line chemotherapy during which he was admitted with partial obstructive ileus as a result of tumor progression. Treatment was continued with Taxol(R) and resulted in total cure of the ileus with reduction of palpable tumor mass over 24 h without necessitating any surgery. Taxol(R) (200 mg/m (2)/week) was administered without any major side effects/toxicities for six courses. A control CT of the abdomen revealed a significant reduction in tumor size. After the next course, the patient developed severe thrombocytopenia that unfortunately did not resolve before the patient died as a result of further tumor growth and dissemination. Although there are studies that report response to Taxol(R) treatment in adult patients with refractory NHL, our review of the literature failed to demonstrate any report about the effectiveness of Taxol(R) in childhood NHL. In conclusion, our case may indicate that Taxol(R) can be effective and be administered safely in an outpatient setting in children with refractory NHL with the aim of prolonging the survival without sacrificing good quality of life. Studies on larger number of patients are needed to make a definitive conclusion about the value of Taxol(R) in refractory childhood NHL.

Multilineage Immune-Mediated Cytopenias in Childhood: A Report of Five Patients.

This study was performed to determine whether there is any distinction to be made between single and multiple-lineage cytopenias particularly with regard to natural history and prognosis. From December 1989 to May 1994, five of 50 children (median age 7 years) with chronic immune cytopenias were diagnosed with multi-lineage immune- ediated cytopenias. Two patients presented with immune thrombocytopenia (ITP) and later developed autoimmune hemolytic anemia (AIHA); one had ITP and immune eutropenia who subsequently became Coombs' positive but never developed AIHA. One child presented with ITP and immune neutropenia and later developed AIHA. The fifth child presented simultaneously with thrombocytopenia and neutropenia with positive antineutrophil antibody but without antiplatelet antibody and Coombs' positivity. Four patients were given primary therapy with IVIG and one with prednisone. One patient responded to prednisone but relapsed subsequently. Further treatment with IVIG roduced initial normalization of his counts with occasional fluctuation of the absolute neutrophil count. Two responded to IVIG and are in complete remission (CR). Of the two nonresponders to IVIG, one responded subsequently to prednisone and is in CR. The other one, after being refractory to multimodality treatment, was diagnosed with a lupus erythematosis variant and is currently on alternate day prednisone. Moderate thrombocytopenia and absolute neutropenia still persist. Multi-lineage immune-mediated cytopenias may represent a pathogenic phenomenon that is distinct from autoimmune single-lineage disease. Clinical response to treatment may correlate with these differences that may be genetic in origin. Clinical course and response to therapy are less predictable when autoimmune disease is present.

Sagittal sinus thrombosis associated with thrombocytopenia: a report of two patients.

Reported are two patients presenting with both thrombocytopenia and sagittal sinus thrombosis. The first patient is a 42-month-old male with no identified thrombophilic risk factors who developed acute neurologic symptoms after an acute infection. The second patient is a 22-month-old female with no history of preceding infection but had a positive lupus anticoagulant test. She also developed deep venous thrombosis and was treated with intravenous heparin. Both patients are currently doing well without neurologic deficits. To the authors' knowledge the second patient is the youngest reported patient with cerebral vein thrombosis associated with thrombocytopenia and lupus anticoagulant. These observations call attention to the need for a thorough investigation of thrombophilic risk factors in pediatric patients with thrombotic complications.

High-dose mercaptopurine and intermediate-dose cytarabine during first remission of acute myeloid leukemia.

High-dose, continuous infusion of intravenous mercaptopurine (HD 6MP) followed by intermediate-dose continuous cytarabine (ID Ara-C) has been shown to produce remissions in children with relapsed acute myeloid leukemia (AML). The purpose of this pilot study was to explore the feasibility of using this drug regimen as a component of treatment during the first remission of AML. Of 17 children with newly diagnosed AML registered in the study, 14 developed complete remission on conventional induction therapy and subsequently received the HD 6MP and ID Ara-C combination. The dosages of HD 6MP were escalated from 500 mg/m2 to 1250 mg/m2 in 24-hr infusions. The initial dosages of ID Ara-C were escalated from 250 mg/m2 to 650 mg/m2/24 hr and from 1 day to 4 days. Conventional treatment for AML was administered simultaneously. Seven of the 14 children remain in initial complete remission for 15 to 46 months and have completed treatment. Severe pancytopenia was observed in all patients, but there were no toxic deaths and no deaths during remission. The inclusion of HD 6MP and ID Ara-C in the treatment of AML in first remission appears to be feasible. Evaluation of its efficacy will require a comparative clinical trial.

Fibromyxoid sarcoma in a four-year-old child: case report and review of the literature.

We present a child with a rare and chemotherapy-resistant form of soft-tissue cancer, low-grade fibromyxoid sarcoma, first noted when he was 4 years old. He is the youngest patient reported to date. An 11-year-old white male presented to. The University of Texas M.D. Anderson Cancer Center's Department of Pediatrics with a 7-year history of right thigh mass and pulmonary nodules, confirmed on examination. He had undergone extensive prior chemotherapy and surgery. He received chemotherapy with high-dose cyclophosphamide (7 g/m2) and later etoposide (150 mg/m2/day x 5), with only slight shrinkage of the thigh mass and none in the lungs. Subsequently the tumor in his proximal thigh and his lung metastases were resected, and radiation therapy was administered to the thigh. His disease remained stable for 12 months, but he then developed a pleural-based metastasis on the left side and new bilateral lung metastases also. The tumors on the left side were removed; residual disease is stable after treatment for 6 months with subcutaneous alpha-interferon-2b. Low-grade fibromyxoid sarcoma is very uncommon in children. It grows slowly and metastasizes to distant organs, chiefly to the lungs. It is resistant to conventional chemotherapy, and thus far only surgery seems to have a life-prolonging effect. Newer chemotherapeutic and possibly biologic agents should be tried in future patients, in order to find an effective way to control the disease.

Ganciclovir prophylaxis for cytomegalovirus infection in pediatric allogeneic bone marrow transplant recipients.

Twenty-nine pediatric allogeneic bone marrow transplant (BMT) recipients, ages 2-17 years, were followed prospectively for cytomegalovirus (CMV) infection. Patients at risk received ganciclovir (GCV) prophylactically at a dose of 5 mg/kg/day i.v., 3 to 5 days per week, until day 100. Surveillance blood and urines were obtained weekly. Twelve patients developed DMV infection: one patient died with CMV interstitial pneumonitis on day 19 post-transplant prior to initiating GCV prophylaxis; 10 patients developed CMV viremia (n = 9) or viruria (n = 1) between day 30 and day 95 (median day 50) while receiving GCV prophylaxis; and one patient developed asymptomatic CMV viruria on day 130, 1 month after completing GCV prophylaxis. Patients with breakthrough infections on prophylaxis were treated with intensified GCV and i.v. immunoglobulin. No patient developed visceral involvement, although five patients had recurrent viremia. Six of the seven long-term survivors continued to excrete CMV in the urine intermittently for 6 to 28 months post-transplant. GCV was well tolerated with transient, mild neutropenia in five patients and thrombocytopenia in four patients. No extramedullary toxicity was encountered. GCV prophylaxis at a dose of 15-25 mg/kg/week is not adequate to prevent CMV reactivation in children receiving marrow transplants from unrelated donors and/or T cell-depleted grafts.

Ifosfamide tolerance in osteosarcoma patients previously treated with cis-diamminedichloroplatinum-II: renal, hematologic, and neurologic observations.

We attempted to ascertain renal, hematologic, and neurologic tolerance to ifosfamide (IFX) in pediatric patients previously treated with large single and cumulative doses of cis-Diamminedichloroplatinum-II (CDP) for osteosarcoma (OS). Twenty OS patients were treated with CDP: initially 150 mg/m2 was administered every 2 weeks for a maximum of seven courses. Later, other agents, including additional CDP, were also administered. Twelve patients were treated with intra-arterial CDP, one with intra-arterial, and later intravenous CDP, and seven with intravenous CDP. Patients who relapsed were treated with IFX. Renal function was monitored by measuring creatinine clearance, serum electrolytes, total protein, albumin and CO2 content, and urine analysis during IFX therapy. Prior to initiation of IFX, creatinine clearance was above 60 ml/min/m2 in all except one patient who had developed a hemolytic uremic syndrome (HUS). Cumulative CDP doses ranged from 300 to 22,500 mg/m2, and cumulative IFX doses 12 to 128 gm/m2. Myelosuppression was monitored by obtaining routine hemograms midway between each course of treatment. Neurologic tolerance was assessed by reviewing the medical records for any abnormality. The interval between CDP and IFX ranged from 1 to 64 months. All patients experienced a progressive reduction in creatinine clearance with CDP. The reduction in creatinine clearance, measured from base-line after three to four courses varied from 10 to 53.7%, after four to seven courses from 19 to 78%, and after seven courses from 12 to 80.5%. In all patients except five, including the HUS patient, creatinine clearance remained above 60 ml/min/m2 during IFX therapy. Twelve patients developed hypo-magnesemia in the vicinity of 1.4 to 1.6 mg/dl during CDP treatment and required magnesium supplementation. They were asymptomatic and the abnormality did not affect IFX tolerance. Fourteen patients intermittently displayed variable degrees of glycosuria, phosphaturia, and/or proteinuria during IFX therapy. This was considered to be a forma frustre type of Fanconi's syndrome. Approximately 80% of courses of IFX were associated with reversible myelosuppression. No neurologic abnormalities were detected. The abnormalities detected during IFX treatment were not major, did not give rise to symptomatology, and did not require discontinuation of therapy. Renal abnormalities were considered a forma frustre type of Fanconi's syndrome. Provided a creatinine clearance of 60 ml/min/m2 is accepted as a prerequisite for treatment, and no major preexisting renal disease is present, IFX is well tolerated by most patients previously exposed to very high cumulative doses of CDP.

Wilms' tumor: cure of malignant pleural effusion exclusively with chemotherapy.

A malignant pleural effusion was diagnosed by thoracentesis in a 12-year-old patient with an established diagnosis of Wilms' tumor. He was treated with chemotherapy and achieved a reduction in the size of the primary tumor and resolution of the effusion. The primary tumor was then resected and chemotherapy continued for a total of 18 months. At the request of the parents, radiation therapy to the thorax was withheld. The patient has remained free of disease for the past 8 years.

Cisplatin-associated hemolytic uremic syndrome.

BACKGROUND: Hemolytic uremic syndrome (HUS) is an acquired disorder largely affecting infants and young children. It is characterized by the triad of microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. Although its etiology is unknown, viral and bacterial infections, disseminated malignancies in adults, and a variety of chemotherapeutic agents including cisplatin, have been implicated in its occurrence. The association of HUS with chemotherapeutic agents after its detection in a pediatric patient treated with cisplatin is reviewed. METHODS: A 16-year-old male with osteosarcoma was treated with cisplatin as part of a chemotherapy protocol. After the fourth course, his renal function deteriorated and necessitated cessation of cisplatin. Nine months after the initiation of cisplatin, HUS developed. There was no evidence of residual tumor or metastatic disease. He received numerous packed erythrocyte and platelet transfusions for persistent hemolysis and underwent several episodes of hemodialysis. Utilizing this patient as an example, the authors reviewed the incidence of HUS developing subsequent to the use of other chemotherapeutic agents. RESULTS: In the publishing literature, chemotherapy-associated HUS has been described to occur 54 days to 14 months after the initiation of chemotherapeutic regimens. A variety of agents was associated with the phenomenon. CONCLUSION: Hemolytic uremic syndrome may be a complication of cisplatin, as evidenced by the condition that occurred in a 16-year-old patient with osteosarcoma after cisplatin therapy.