Stereotactic Radiotherapy in Recurrent Glioblastoma: A Valid Salvage Treatment Option.

BACKGROUND: Glioblastoma (GBM) is a dismal disease. Recurrence is inevitable despite initial surgery and postoperative temozolomide (TMZ) and radiotherapy. Salvage surgery is the standard treatment in selected patients. Chemotherapy, biological agents, and re-irradiation are other treatment approaches available. Stereotactic radiotherapy (SRT) is nowadays a common treatment as a salvage treatment option. MATERIALS AND METHODS: We reviewed the files of 132 GBM cases treated between 2010 and 2018. All patients received TMZ and radiotherapy after surgery or biopsy. Among the patients who had recurrence, we identified 42 cases treated with salvage SRT. The CyberKnife robotic system was used to administer SRT. RESULTS: While the median follow-up time for all patients was 16 months (range 1-123), the median follow-up time for patients treated with SRT after initial diagnosis was 26.5 months (range 9-123). The median follow-up time after SRT was 10 months (range 2-107). SRT was performed in a median of 3 fractions (range 2-5). The median prescription dose was 20 Gy (range 18-30). While the median actuarial survival after initial diagnosis for patients treated with salvage SRT was 30 months (range 9-123), it was only 14 months (range 1-111) for patients who could not be treated with salvage SRT (p = 0.001). The median survival time after SRT was 12 months, and 1- and 2-year survival rates were 48 and 9%, respectively. The time to progression after SRT was 5 months (range 1-62), and 6-month and 1-year progression-free survival rates were 50 and 22%, respectively. Patients with longer time to recurrence >12 months had longer overall survival with respect to the ones having recurrence <12 months (p < 0.001). Salvage surgery had been performed in 7 out of 42 patients before SRT. These reoperated patients had significantly worse survival after SRT when compared to the patients who underwent SRT alone (p = 0.02). SRT was well tolerated and there was no grade III/IV toxicity. CONCLUSIONS: SRT is a viable salvage treatment option for recurrent GBM. SRT provides acceptable local control and survival benefit for recurrent GBM cases. SRT can be considered especially in patients with long time to recurrence.

Metabolic acidosis in an infant associated with permethrin toxicity.

Pyrethroids are broad-spectrum insecticides. Permethrin intoxication due to topical application has not been documented in humans. We report a 20-month-old infant who had used 5% permethrin lotion topically for scabies treatment. Approximately 60 mL (20 mL/day) was used and after the third application he developed agitation, nausea, vomiting, respiratory distress, tachycardia, and metabolic acidosis. His clinical symptoms and metabolic acidosis normalized within 20 hours. His follow-up was unremarkable. Toxicity of permethrin is rare, and although permethrin is a widely and safely used topical agent in the treatment of scabies and lice, inappropriate use may rarely cause toxicity. Moreover, in cases of unexplained metabolic acidosis, topically applied medications should be carefully investigated.

Tear and serum vitamin D levels in children with allergic rhinoconjunctivitis.

BACKGROUND: Although solid cohort studies confirmed a preventative role for the anti-oxidant vitamin D in allergic asthma, a limited number of studies focused on allergic rhinoconjunctivitis (ARC). Here, we aimed to determine 25-hydroxycholecalciferol levels in tear and serum in young allergic rhinoconjunctivitis patients as compared to their apparently healthy matched controls. METHODS: In total, 22 children with allergic rhinoconjunctivitis and 31 healthy control subjects underwent serum total IgE and 25-hydroxycholecalciferol measurements. Tear levels of 25-hydroxycholecalciferol were also determined in both groups. RESULTS: The mean serum total IgE level in the ARC group (143.6±132.8IU/ml) was significantly higher than that in the control group (54.8±44.1IU/ml; p=0.03). Serum 25(OH)D levels were significantly higher in the ARC group (34.1±12.7ng/ml) than in the healthy controls (21.8±11.3ng/ml; p=0.001). CONCLUSIONS: To our knowledge, this is the first reported study to show an association between serum 25-hydroxycholecalciferol and ARC in a childhood group. Higher levels of serum 25-hydroxycholecalciferol in children with allergic rhinoconjunctivitis may indicate a possible aetiopathogenic mechanism in the development of allergic rhinoconjunctivitis. This is also the first report to examine tear fluid vitamin D levels in paediatric ARC patients.

Serum hepcidin levels and iron metabolism in obese children with and without fatty liver: case-control study.

UNLABELLED: Hepcidin is a regulator of iron balance that is increased in obesity. It reduces the absorption of iron, reduces the transfer of iron from macrophages to the plasma and/or prevents mobilisation of stored iron. Obese patients with non-alcoholic fatty liver disease (NAFLD) demonstrate adipokine and cytokine release promoting inflammatory response. We aimed to analyse the hepcidin levels and iron metabolism in obese children with and without NAFLD and non-obese healthy controls. The study population consisted of 110 children aged 7-18 years in three groups: 50 obese patients without NAFLD, 30 obese patients with NAFLD, and 30 non-obese healthy controls. Serum hepcidin, ferritin, and iron levels, iron-binding capacity, lipid profile, and liver function tests were measured, and hepatic ultrasonography was performed in all participants. Obese patients' white blood cell counts, total cholesterol, triglyceride levels, and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher than those of the control group. Iron-binding capacity was significantly higher in obese patients without NAFLD compared with obese patients with NAFLD (p = 0.002). Hepcidin levels were not significantly different between obese patients and the control group. However, hepcidin levels in obese patients with NAFLD were significantly higher than those in obese patients without NAFLD (p < 0.001). CONCLUSIONS: Hepcidin levels were significantly higher in obese children with NAFLD than those without NAFLD. Obese children with NAFLD should receive attention regarding iron metabolism disorders. Serum hepcidin could be a marker of iron metabolism status and NAFLD in these groups of patients.

Vitamin D status in children with attention-deficit-hyperactivity disorder.

BACKGROUND: Attention-deficit-hyperactivity disorder (ADHD), one of the most common psychiatric disorders of childhood, has an early onset, affecting 2-18% of children worldwide. The etiopathogenesis of ADHD is obscure. In recent studies, a low level of vitamin D has been found in association with many disorders as well as in neuropsychiatric diseases. The aim of this study was therefore to investigate serum vitamin D level in pediatric ADHD patients. METHODS: A total of 60 ADHD patients and 30 healthy controls were included in the study. The age of both groups was in the 7-18-year-old range. Serum 25-OH-vitamin D, calcium, phosphorus and alkaline phosphatase were investigated. RESULTS: Serum 25-OH-vitamin D was found to be significantly lower in children and adolescents with ADHD compared to healthy controls, and no significant differences were found between the groups in terms of other variables. 25-OH-vitamin D level in the ADHD group and control group was, respectively, 20.9 ± 19.4 ng/mL and 34.9 ± 15.4 ng/mL (P = 0.001). CONCLUSION: There is an association between lower 25-OH-vitamin D concentration and ADHD in childhood and adolescence. To the authors' knowledge this is the first study to investigate the relationship between vitamin D and ADHD in children.

Clinical significance of lymph node ratio in locally advanced breast cancer molecular subtypes.

BACKGROUND: The ratio of metastatic to dissected lymph nodes (lymph node ratio; LNR) is a sensitive and superior prognostic factor for lymph node evaluation, but its relationship to cancer subtypes is unclear. PATIENTS AND METHODS: Data from 469 patients with axillary lymph node metastasis out of 640 early breast cancer cases were retrospectively analyzed. They were classified into 4 molecular subtypes; luminal A, luminal B HER2(+), HER2 overexpression, basal-like. LNRs were compared between groups and with other prognostic factors. RESULTS: The distribution of LNRs was 35.2% in luminal A, 43.2% in luminal B HER2(+), 46.9% in HER2 over-expression, and 39.1% in basal-like. A significant difference was found between luminal A and HER2 over-expression subtypes (p = 0.023). LNR was significantly correlated with tumor size and lymphovascular invasion, but not with other prognostic factors including menopausal status, laterality, grade, and perineural invasion. An LNR of 29.8% was defined as the cut-off value, and significant differences in survival rates were identified accordingly between basal-like and both luminal A (p = 0.003) and luminal B HER2(+) (p = 0.04). CONCLUSION: The LNR differs between some molecular subtypes of breast cancer, and it correlates with certain prognostic factors and survival. These data support using the LNR to assess breast cancer patients.

Assessment of atherosclerosis in obese adolescents: positive correlation of mean platelet volume and carotid intima media thickness.

AIMS: This study aims to assess the correlation of mean platelet volume (MPV) and common carotid artery (CCA) thickness in a population of obese adolescents. METHODS: Sixty-eight patients and 23 controls were enrolled. Anthropometric measurements, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, hemoglobin, white blood cell count, platelet count, MPV and insulin resistance by homeostasis model of assessment of insulin resistance were investigated. Furthermore, CCA thickness was measured by high-resolution ultrasound. RESULTS: MPV and the left CCA thickness were significantly higher in obese adolescents than the healthy controls. The association between MPV and left CCA was checked by linear regression analysis. MPV explained 19% of the variation in left CCA (P < 0.001). At multiple regression analysis, MPV maintained a positive association with the left CCA thickness (P = 0.002) independently of fatty liver grade, relative weight, total cholesterol and homeostasis model of assessment of insulin resistance. CONCLUSION: MPV is significantly correlated with CCA thickness in obese adolescents.

Optimal plan target in cases with locally advanced nasopharyngeal cancer: Comparison of VMAT, IMRT, hybrid, and tomotherapy results.

PURPOSE: In locally advanced nasopharyngeal cancer (NC), the spread of the disease, proximity to critical structures, and high dose requirement for tumor control may complicate the treatment plan. In this study, VMAT/IMRT/hybrid/tomotherapy plans were made to reach the safest and most effective dose distribution for each of the patients and the results were compared. METHODS: Double volumetric-modulated arc therapy (VMAT) and 7- and 9-field intensity-modulated radiation therapy (IMRT) plans were made to 21 locally advanced NCs with Varian Trilogy System. It was observed that appropriate dose distributions could not be achieved with IMRT or VMAT, and hybrid IMRT-VMAT plans were made. All cases were also planned with Tomotherapy Precision System, and the data of four different techniques were compared retrospectively. RESULTS: For normal tissue tolerances in 73 structures could not be obtained with VMAT and 38 structures with IMRT whereas the desired tolerance was provided with the hybrid plan. Hybrid plans were made with an average of 14 VMATs and 20 IMRTs. The maximum brainstem and spinal cord doses were found significantly lower in hybrid and tomotherapy techniques. Homogeneity index (HI) and conformity index (CI) values were the best in hybrid plans. No statistically significant difference between the hybrid plan and tomotherapy in terms of normal tissue tolerance doses and HI whereas a significant difference was found in the hybrid plan for CI. CONCLUSION: It was observed that the most ideal plans for the locally advanced NC could be obtained with tomotherapy and hybrid plan techniques that the better protection in critical structures and desired dose distribution at target volumes.

Is fractionated robotic stereotactic body radiosurgery optional salvage treatment for the re-irradiation of locally recurrent nasopharyngeal carcinoma?

Purpose: Recurrent nasopharyngeal carcinoma (NPC) after previous radiation therapy is a significant problem. This study was to determine the potential benefits from re-irradiation by fractionated stereotactic body radiotherapy (FSRT) on survival benefits and effects of severe late toxicities. Materials and Methods: Between 2009 and 2018, treatment outcomes were evaluated retrospectively in 26 patients with locally recurrent NPC treated using FSRT with CyberKnife. Five patients who had metastatic disease and one who had second recurrence were excluded from the study, and the remaining 20 patients were analyzed. The median age was 52 years (range, 28-80 years); re-treatment T stage was as follows: 6 (30%) - T2, 5 (25%) - T3, and 9 (45%) - T4. The median time from initial RT to recurrence was 22 months (range, 8-159 months). The median re-irradiation FSRT dose was 30 Gy in 5 fractions. Results: The median follow-up was 44 months; the overall survival (OS), local failure-free survival, and disease progression-free survival rates at 3 years were 89%, 73%, and 53%, respectively. All patients were evaluated for response after treatment: 9 (45%) had complete, 3 (15%) had partial, and 6 (30%) had no response. Univariate analysis demonstrated that higher cumulative total radiotherapy dose, gross tumor volume, and recurrent time interval were prognostic factors for local failure-free survival. The recurrent time interval was also an independent factor for progression-free survival and OS. The incidence of temporal lobe necrosis and trismus was 10% and 20%, respectively. One patient had Grade 5 toxicity to treatment-related bleeding. Conclusion: Tumor dose coverage is important for treating recurrent NPC, and treatment-related mortality was vascular in nature. FSRT is a promising treatment modality for recurrent NPC.

Outcomes of carotid sparing intensity-modulated radiotherapy for early stage glottic cancer in 201 patients: Multicenter study of Turkish Radiation Oncology Society/TROD-01-007.

BACKGROUND: To assess and report clinical outcomes after carotid sparing intensity-modulated radiotherapy for early stage laryngeal cancer. METHODS: We retrospectively analyzed 201 patients with early stage glottic laryngeal cancer treated with carotid sparing intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) techniques in six TROD centers. RESULTS: After a median follow-up of 31 months the actuarial 1- and 3-year local and locoregional control rates were 99.4% and 94.7%, 98.4% and 93%, respectively. T classification, anterior commissure involvement, IMRT technique, and type of fractionation were not found to be prognostic for local control. Overall, eight patients had lost their organ function due to recurrence or toxicity. Grade 3 and 4 acute laryngeal edema was seen in eight (4%) and one (0.5%) of patients, respectively. Grade 3 and 4 late laryngeal edema developed in two (1%) and one patient (0.5%), respectively. CONCLUSION: Oncologic outcomes of patients treated with carotid sparing IMRT were excellent; comparable with historical series, with acceptable side effects. Longer follow-up is needed to estimate long term effect on stroke.

Fibromuscular dysplasia as a cause of stroke in a 9-year-old girl.

Fibromuscular dysplasia is a rare, idiopathic and nonatheromatous disease. It is rarely encountered as a cause of stroke in children. We report a nine-year-old girl with stroke in whom extensive fibromuscular dysplasia of intracranial vessels was established. She also had familial combined hyperlipidemia as an additional risk factor. This case suggests that additional risk factors like hyperlipidemia in cases with fibromuscular dystrophy may facilitate the occurrence of stroke at early ages.

Effects of palliative radiotherapy and bisphosphonate usage on bone turnover marker levels in cancer patients with osteolytic bone metastases.

OBJECTIVES: In this study, we aimed to investigate the bone turnover marker levels according to bisphosphonate usage and radiotherapy (RT) in cancer patients with metastases in osteolytic pattern. PATIENTS AND METHODS: A total of 52 patients (13 males, 39 females; median age: 52 years; range, 37 to 78 years) treated with RT for osteolytic bone metastases between April 2005 and April 2006 were retrospectively analyzed. Bone-specific alkaline phosphatase (BAP), amino-terminal cross-linked telopeptide of type I collagen (NTX-I), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OC), deoxypyridinoline (DPD), pyridinoline (PYD), alkaline phosphatase (ALP), creatinine, calcium (Ca), phosphate (P), magnesium (Mg), and 24-h urine Ca levels were measured in blood and urine before the initiation of RT, six weeks and six months after RT. RESULTS: A decrease in BAP, PINP, and creatinine levels was observed after RT (Week 6 p=0.006, Month 6 p=0.008). Sixteen patients who already used bisphosphonate before RT were excluded from statistical calculation. The remaining 36 patients who were treated with bisphosphonate after the first blood test were evaluated separately. In this group of patients, BAP, PINP, NTX, creatinine, and Ca levels significantly increased at six weeks after RT. The PINP and creatinine values significantly decreased at six months after RT. The variation between two different RT arms was assessed with repeated measures variance analysis. There was a statistically significant difference for NTX, OC, and creatinine levels between the first and second measurements. CONCLUSION: Radiotherapy is an effective method in the treatment of osteolytic bone metastases. Bone turnover markers can provide an objective evaluation on RT response and parallel to imaging modalities criteria for evaluation. Bisphosphonates may alter the levels of these indicators. However, in this study, there were no statistically significant differences between the levels of markers for two different RT schedules.

Severe iron overload and hyporegenerative anemia in a case with rhesus hemolytic disease: therapeutic approach to rare complications.

A 33 weeks' gestation, a baby with rhesus hemolytic disease (RHD), who had received intrauterine transfusions twice, developed cholestatic hepatic disease and late hyporegenerative anemia. Her serum ferritin and bilirubin levels increased to 8842 ng/ml and 17.9 mg/dl, respectively. Liver biopsy showed cholestasis and severe iron overload. Treatment with recombinant erythropoietin (rHuEPO) decreased the transfusion need, and intravenous deferoxamine resulted in a marked decreased in serum ferritin levels and normalization of liver function. In patients who have undergone intrauterine transfusions due to RHD, hyperferritinemia and late hyporegenerative anemia should be kept in mind. Chelation therapy in cases with symptomatic hyperferritinemia and rHuEPO treatment in cases with severe hyporegenerative anemia should be considered.

Contribution of Magnetic Resonance Imaging in Determining Lumpectomy Cavity in Breast Radiotherapy.

BACKGROUND: Accurate localization of the lumpectomy cavity is important for breast cancer radiotherapy after breast-conserving surgery (BCS), but the LC localization based on CT is often difficult to delineate accurately. The study aimed to compare CT-defined LC planning to MRI-defined findings in the supine position for higher soft-tissue resolution of MRI. METHODS: Fifty-nine breast cancer patients underwent radiotherapy CT planning in supine position followed by MR imaging on the same day. LC was contoured by the radiologist and radiation oncologist together by CT and MRI separately. T2 weighted MR images and tomography findings were combined and the LC volume, mean diameter and the longest axis length were measured after contouring. Subsequently, patients were divided into two groups according to seroma in LC and the above-mentioned parameters were compared. RESULTS: We did not find any statistically significant difference in the LC volume, mean diameter and length at the longest axis between CT and MRI but based on the presence or absence of seroma, statistically significant differences were found in the LC volumes and the length at the longest axis of LC volumes. CONCLUSION: We believe that the supine MRI in the same position with CT will be more effective for radiotherapy planning, particularly in patients without a seroma in the surgical cavity.

Rhabdomyolysis due to Escherichia coli sepsis in three pediatric patients with acute lymphoblastic leukemia.

Rhabdomyolysis with myoglobinuria is an uncommon complication of bacterial sepsis. The authors describe three pediatric acute lymphoblastic leukemia patients who developed rhabdomyolysis during a neutropenic sepsis episode due to Escherichia coli. All of the patients needed hemodynamic supportive treatment because of septic shock. Broad-spectrum antibiotics, alkalinization, and intravenous fluid therapy was given. One patient with renal insufficiency died, despite aggressive treatment. Muscle pain and dark urine color should alert physicians to the possibility of rhabdomyolysis in immunocompromised patients with sepsis. Early and appropriate treatment is critical in these patients to prevent renal failure and shock, and for a better outcome.

Clinical features, treatment responses, and outcome of children with idiopathic thrombocytopenic purpura.

The authors investigated demographics, clinical and laboratory features, treatment responses, and outcomes of 93 children (median age 5 years) admitted for idiopathic thrombocytopenic purpura (ITP). The therapy responses of high-dose methylprednisolone (HDMP) (n = 77) and intravenous immunoglobulin (IVIG) (n = 10) treatments were similar. None of the patients with hemorrhage died. Fifteen patients (16.1%) had progressed into chronic ITP. Seven infants had a probable relationship with vaccination; none of these infants progressed into chronic ITP. In conclusion, the overall prognosis in childhood ITP is good. The therapy responses of HDMP and IVIG treatments are similar. Also, ITP cases who havw vaccination history have a benign course.

Subscapular abscess after blunt trauma.

Infection around the shoulder girdle is an infrequent and difficult diagnosis requiring a high index of suspicion and early evaluation by the physician. An infection within the area of the subscapularis muscle and the chest wall is extremely rare. To the best of our knowledge, only 4 cases of subscapular abscess have been reported. In this article, we present a 7-year-old boy with a subscapular abscess after blunt trauma.

Surgical Clips in Breast-conserving Surgery: Do they Represent the Tumour Bed Accurately?

INTRODUCTION: Radiotherapy after Breast-Conserving Surgery (BCS) is a standard treatment for breast cancer. Currently, surgical clips are used to determine the tumour bed before radiotherapy planning. This study aimed to evaluate the migration of these clips on mammograms. METHODS: The study was conducted on 121 females who were treated with radiotherapy after BCS at their first radiologic control examination 6 months after the end of treatment. MLO and CC views of all cases were evaluated regarding the clips. The distance between the surgical scar centre and the centre of the area covered by the clips was measured on both MLO and CC projections and recorded separately. This distance was determined as the clip displacement. A displacement ≤10 mm was recorded as no displacement. RESULTS: The clips were out of the images and were not evaluated in 45 cases (37.2%) on CC and in 9 cases (7.4%) on MLO projections. There were no clip displacements in 37 (30.6%) cases on CC and in 43 (35.5%) cases on MLO views. The amount of displacement ranged from 11 to 56 mm with a mean of 24.38 mm on CC views, while on MLO projections, displacement ranged from 11 to 66 mm with a mean of 24.42 mm. CONCLUSION: A clip displacement of greater than 10 mm was found in 64.5% of cases on MLO views. Therefore, we believe that the reliability of these clips for accurate delineation of the tumour bed in radiotherapy planning is controversial and other methods must be added.

Isolated myelosarcoma development in an adolescent chronic myeloid leukemia patient with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).

Additional chromosomal abnormalities are found in 5-20% of patients during chronic phase of chronic myeloid leukemia and in 60-80% preceding or accompanying blast crisis. These abnormalities are important in disease progression and, because they may occur before hematological and clinical symptoms, can be taken as a prognostic indicator. An adolescent with chronic myeloid leukemia initially presented with extreme thrombocytosis, increased megakaryopoiesis with dysmorphic features, and focal myelofibrosis in bone marrow examinations and then developed isolated myelosarcoma 1 year after onset, with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).