Bilateral Optic Neuritis Secondary to Nivolumab Therapy: A Case Report.

Pediatric glioblastoma multiforme is an uncommon and highly mortal brain cancer. New therapeutic treatments are being intensively investigated by researchers in order to extend the survival of patients. The immune checkpoint inhibitor nivolumab in the treatment of pediatric glioblastoma multiforme is currently under review; it is a human immunoglobulin G4 monoclonal antibody that works against the programmed cell death protein 1 receptor, designed to enhance an immunologic reaction against cancer cells. Herein, we describe the first report of a bilateral optic neuritis induced by nivolumab in a grade 4 glioblastoma multiforme patient.

Adrenomedullin predicts high risk and culture positivity in children with solid tumors suffering from neutropenic fever.

AIM OF STUDY: Neutropenic fever is a source of morbidity and mortality in children with cancer. It is not possible to detect the causative agent in cultures in most cases; the research for a marker that can show the severity of the disease is ongoing. We evaluated the role of adrenomedullin (ADM) at predicting prognosis on patients with febrile neutropenia, which has been proven to be a good prognostic marker for diseases with high morbidity and mortality, such as heart failure, ischemic ventricular dysfunction, sepsis, and systemic inflammatory response syndrome. MATERIALS AND METHODS: We recorded the 36 febrile episodes of 14 children receiving chemotherapy due to solid tumors. There were 10 events with unknown origin in the low-risk group, while in the high-risk group, there were 17 events with unknown origin, 8 events with microbiological origin and 1 event with clinically proven infection. Cultures were positive only in the high-risk group. However, the changes of ADM levels through time periods (first, second, third, and seventh days) were not significant. RESULTS: The first-day plasma ADM levels significantly predicted the presence of culture positivity (AUC 0.628, 95% CI 0.40-0.85, p = 0.303) and high-risk patients with neutropenic fever (AUC 0.76, 95% CI 0.56-0.97, p = 0.016). CONCLUSION: Our study showed that increased plasma ADM was correlated with high-risk neutropenic fever and culture positivity. The ADM levels in the high-risk group were clearly high at the diagnosis and continued to the end of the treatment.

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.

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.

Treatment of a tongue lymphangioma with sirolimus after failure of surgical resection and propranolol.

Lymphangiomas of the tongue are rare, and their treatment is problematic. A 10 year-old patient with tongue lymphangioma who was previously treated with surgery and propranolol with no response was treated with sirolimus in our department. We used sirolimus with a dose of 1.6 mg/m(2)/day. After 3 months of treatment, the mass had decreased by more than 60%. We continued the treatment for 1 year with a maximum response of 70% decrease in mass. Disease remained stable 6 months after stopping therapy, the latest time of follow-up. Sirolimus appears to be effective in lymphangioma but requires further study.

Salivary gland tumors in children: a retrospective clinical review.

Seven patients with salivary gland tumors who underwent between 1972 and 2012 were retrospectively evaluated. The age of the patients ranged from 6.3 to 13 years old; five were females and two were males. Five patients had stage IVa, one patient had stage I, and one patient had stage II disease. The surgical margin was found to be positive in five cases. There were three adenoid cystic carcinoma, two adenocarcinoma, one anaplastic carcinoma, and one mucoepidermoid carcinoma. There were five parotid, one lacrimal gland, and one palatal involvement. Three patients who had low stage tumors were treated with surgery alone. Four of the cases received adjuvant radiation and chemotherapy. One patient with parotid tumor died with progressive disease. One case with lacrimal gland neoplasm was alive 48 months after discontinuation of treatment. The other palate case was lost to follow-up 1 month after the beginning of the treatment. Surgery is the primary treatment, with radiotherapy and chemotherapy used as adjuvant treatments. The treatment options need to be selected and planned for each individual patient.

Clinical features and treatment results of children with diffuse large B-cell lymphoma.

The demographic, clinical characteristics, and treatment groups of 33 children with diffuse large B-cell lymphoma (DLBCL) were recorded and analyzed among 1486 non-Hodgkin lymphoma (NHL) cases since 1972. The median age was 9.7 years (range 1.4-16.9) and male/female ratio was 24/9 = 2.6. Kaplan-Meier methods and logrank tests were used in treatment analysis. The frequency of DLBCL among 1486 NHL cases was 2.2%, however, the percentage was 9.3% in cases diagnosed after 2000. The event-free survival (EFS) and overall survival (OS) rates for 33 children were 61% and 65.1% at 5 years, respectively. The EFS and OS rates of low stage (stages I and II) disease decreased to lower level in advanced stage (stages III and IV) disease. Associated conditions and ages older than 14 years were found as poor prognostic factors in multivariate analysis. The survival rates in children with DLBCL need further improvement. This is mainly related with late referral of those children with advanced disease. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with associated conditions and older children must be handled with care since these are found as poor prognostic factors.

Comparison between daily supplementation doses of 200 versus 400 IU of vitamin D in infants.

The daily supplementation of vitamin D is mandatory for infants. However, there are still conflicting opinions about the exact daily dose. Thus, we aimed to evaluate a daily supplementation dose of 200 IU is sufficient and compared the supplementation doses of 200 and 400 IU per day. One hundred and sixty-nine infants were randomly assigned to two groups (group 1, 200 IU/day; group 2, 400 IU/day) and there were 75 infants in group 1 and 64 were in group 2 with a total number of 139. The median levels of 25-hydroxyvitamin D3 were significantly increased in group 2 at the age of 4 months (group 1, 39.60 mcg/L; group 2, 56.55 mcg/L; p < 0.0001). We clearly demonstrated that at the age of 4 months, none of the infants on the group 2 had a serum level of 25-hydroxyvitamin D3 less than 30 mcg/L. However, 21.3% of the infants in group 1 had a level below 30 mcg/L. Thus, in order to avoid vitamin D deficiency and rickets, we recommend supplementation dose of vitamin D at 400 IU/day as a safe and effective dose.

Evaluation of patients with intracranial tumors and central diabetes insipidus.

The aim of the study is to evaluate the etiologic and clinical characteristics, treatment regimens, and outcome of the patients with intracranial tumors presenting with central diabetes insipidus (DI). Sixty-nine patients with intracranial tumors presenting with central DI between 1972 and 2012 were retrospectively evaluated. Fifty-three out of 69 patients were included in the analysis. Male/female ratio was 1.52, median age was 7.6 years. Of 53 patients, 37 patients (69.8%) were diagnosed with Langerhans cell histiocytosis, 14 patients (26.4%) with germinoma, 1 (1.9%) with astrocytoma, and 1 (1.9%) with optic glioma. 10-year overall survival (OS) rate and disease-free survival rate for all patients were 91.7% and 52%. 10-year OS rate according to diagnostic criteria was 91% for Langerhans cell histiocytosis (LCH) cases, 79% for intracranial germinoma, which was statistically significant (P = .0001). Central DI may be very important clinical presentation of serious underlying disease in children. Intracranial tumors are the most frequent cause of DI. Most frequent diagnosis were LCH and germ cell tumors in our series.

Indirect hyperbilirubinemia because of eltrombopag in two cases after autologous hematopoetic stem cell transplantation.

ABSTRACT: The oral thrombopoietin receptor agonist eltrombopag has some side effects. One of them is related to bilirubin metabolism. Two patients with neuroblastoma in remission underwent stem cell transplantation with the Busulfan-melphalan regimen. Eltrombopag was started because of platelet engraftment failure. Indirect hyperbilirubinemia was detected after eltrombopag treatment. Laboratory and radiological investigations were all normal. The drugs and their side effects they used were examined. After eltombopag cutting, bilirubin levels of them returned to normal. These cases are presented to emphasize that eltrombopag can cause liver toxicity with hypertransaminesemia and hyperbilirubinemia. Drug side effects should be considered in the differential diagnosis of the patients. The significance of this case is that testing for serum aminotransferase and bilirubin levels should be monitored before and after eltrombopag use.

Pulmonary tuberculosis mimicking metastasis in a patient with osteosarcoma.

Pulmonary metastasis even at diagnosis or during treatment is an important problem in osteosarcoma treatment and treatment modality varies in patients with metastasis. Metastasectomy and aggressive induction chemotherapy are the 2 most well-known treatment options. However, reactivation of pulmonary tuberculosis can be a problem in developing countries, where the prevalence of tuberculosis is high. Here, we described a patient with osteosarcoma with pulmonary tuberculosis reactivation mimicking metastasis.

Two Subsequent Metachroneus Solid Tumors: Oncocytic Variant Adrenocortical Carcinoma and Rhabdomyosarcoma of Childhood: Case Report and Literature Review

Most cases of malignancies appear to be sporadic, but some syndromes are associated with malignancies with germline variants. Herein, a child with an unusual association of oncocytic variant adrenocortical carcinoma (ACC) and rhabdomyosarcoma (RMS) was presented. An 18-month-old-boy was admitted with virilization of the genital area, penis enlargement and erection, which had begun six months earlier. Serum total testosterone (457 ng/dL; NR <10), androstenedione (3.35 ng/mL; NR <0.5) and dehydroepiandrosterone-SO4 (206 mcg/dL; NR<35) were above the normal ranges. Right adrenal mass was detected. After adrenalectomy, histopathological examination revealed an oncocytic variant ACC. Three-month after surgery, he then presented with 6x8 cm sized swelling of the left leg. Histopathological examination revealed embryonal RMS. Testing for tumor protein (TP53) variant by DNA sequence analysis was positive; however; fluorescence in situ hybridization analysis was negative. After chemotherapy and local radiotherapy, the patient is in good condition without tumor recurrence. Only about one-third of these tumors have a variant of TP53. This status also applies to other genetic variants related to cancer. However, a significant association of malignancies strongly suggests a problem in tumor suppressor genes or new variants. Another as yet unidentified suppressor gene may also be present and effective in this locus. The occurrence of ACC as a part of a syndrome and positive family history of malignancies in patients are clinically important. These patients and their families should be scanned for genetic abnormalities. The patient with ACC should be followed-up carefully for other tumors to detect malignancy early.

Cardiac complications in patients who underwent to hematopoietic stem cell transplantation.

AIM OF STUDY: Cardiac complications may be observed after hematopoietic stem cell transplantation (HSCT). Despite significant improvement in supportive care, HSCT may be associated with significant morbidity and mortality. In this study, the aim was to evaluate the frequency of clinically serious cardiac complications after HSCT in our patients. MATERIALS AND METHODS: This is a retrospective study. Cardiac complications were analyzed in 75 patients undergone to HSCT with physical examination, electrocardiography, echocardiography, and cardiac monitorization. RESULTS: The median age was 12 years (range 11-16) and M/F ratio was 2/3 = 0.66. There are five patients with six complications among the retrospective cohort of 75. These were pericardial effusion in three patients, and sinus bradycardia in two patients and ventricular tachycardia in one patient. The incidence of cardiac complications among 75 patients with HSCT was 6.7%. The mortality rates of patients with and without cardiac complication were 40% and 34%, and both of them with cardiac complication had pericardial effusion. However, the cardiac complication was not found statistically significant factor on survival ( P = 0.82). CONCLUSION: Poor risk factors of patients, myocarditis, pericarditis, and heart failure owing to cumulative doses of anthracycline, cyclophosphamide, cytomegalovirus infection or other infections, mediastinal irradiation, and cryopreserved stem cell product with dimethyl sulfoxide may be effective on the development of cardiac complications individually. Early intervention can prevent death related to this complication.

Differentiation of benign from malignant cervical lymphadenopathy by ultrasonography in children. / Diferenciación entre linfadenopatía cervical benigna y maligna mediante ecografía en niños.

INTRODUCTION: The most common causes of cervical lymphadenopathy (LAP) are inflammatory and reactive conditions; only a small proportion have serious pathology, such as malignancy. The objective of this study was to evaluate the relationship between USG findings and histopathological diagnosis of the cervical LAP. POPULATION AND METHODS: This retrospective study comprised the cases of cervical LAP in patients aged under 20 years old followed in our center between January 2007 to December 2016. Based on pathology reports, we divided the patients into two groups: benign and malignant. Pathology results and USG findings were compared. RESULTS: After the analyze of the histopathological results and USG findings, 107 patients with persistent cervical LAP (44 malignant; 63 benign) were included in the study. Mean age of malignant and benign group were 14 ± 6.1; 11.9 ± 4.8 years, respectively. Hilar vascularity for benign LAP was highly statistically significant (P < 0.0001) and peripheral flow and mixed vascularity for malignant LAP were also statistically significant (p < 0.05). There was not a significant difference in the maximum diameter (27.3 ± 11.1 mm and 29.8 ± 12.3 mm, respectively), however, there was a significant difference in the minimum diameter between benign and malignant groups (13.7 ± 7.3 mm and 18.7 ± 8.8 mm, respectively). CONCLUSIONS: The present study suggests that there is a relationship between US and biopsy findings for the differentiation of benign from malignant LAP, especially in terms of nodal hilus and intranodal vascular pattern.

Introducción: Las causas más frecuentes de la linfadenopatía cervical son las afecciones inflamatorias y reactivas; solo unos pocos casos representan una patología seria.El objetivo fue evaluar la relación entre los hallazgos ecográficos y el diagnóstico histopatológico. Población y métodos: Este estudio retrospectivo abarcó la linfadenopatía cervical en los menores de 20 años seguidos en nuestro centro, entre enero de 2007 y diciembre de 2016. Según los informes anatomopatológicos, se dividió a los pacientes en dos grupos: benigno y maligno. Se compararon los resultados anatomopatológicos y los hallazgos ecográficos. Resultados: Después del análisis de los resultados histopatológicos y los hallazgos ecográficos, se incluyó a 107 pacientes con linfadenopatía cervical persistente (44 casos malignos; 63, benignos). La media de edad de los grupos maligno y benigno fue de 14 ± 6,1 años y de 11,9 ± 4,8 años, respectivamente. La presencia de vascularidad hiliar fue estadísticamente significativa (p < 0,0001) en la linfadenopatía benigna, mientras que el flujo periférico y la vascularidad mixta lo fueron (p < 0,05) en la linfadenopatía maligna. No se observó una diferencia significativa en el diámetro máximo (27,3 ± 11,1 mm y 29,8 ± 12,3 mm, respectivamente), pero sí en el diámetro mínimo entre los grupos benigno y maligno (13,7 ± 7,3 mm y 18,7 ± 8,8 mm, respectivamente). Conclusiones: Este estudio sugiere que existe una relación entre los hallazgos ecográficos y de la biopsia para la diferenciación entre la linfadenopatía benigna y maligna, en especial, en el patrón vascular intraganglionar y el hilio ganglionar.

Outcomes of bladder preservation therapy on survival in patients with muscle-invasive bladder cancer. / Resultados de preservación vesical en pacientes con tumor vesical musculoinfiltrante.

INTRODUCTION: The standard of care in muscle invasive bladder cancer is radical cystectomy; however; transurethral resection (TUR) followed by external radiotherapy and systemic chemotherapy demonstrates comparable results with radical cystectomy in terms of local control and survival rates. OBJECTIVES: To evaluate our results of multimodality bladder preservation therapy (BPT) in patients who had muscle-invasive bladder cancer and were reluctant to radical cystectomy. METHODS: The retrospective analysis of twenty-three patients with stage T2 transitional cell bladder cancer that were consecutively treated with BPT was performed. Treatment strategy included radical TUR followed by 3 cycles of cisplatin, gemcitabine combination, and radiotherapy of 64 Gy as adjuvant treatment. The Kaplan-Meier survival estimates and log rank were calculated. RESULTS: Median follow-up time was 58 (15-158) months. Disease-free survival (DFS) and five year overall survival (OS) rates for 23 patients were 55.9% and 63.9%, respectively. Cancer-specific OS was 67%. There were no grade 3 or higher complications. CONCLUSIONS: Our small patient group suggests that BPT can be safely applied in selected cases with bladder cancer or in patients that refused radical cystectomy.

INTRODUCCIÓN: El estándar de tratamiento en el CVMI es la cistectomía radical, aunque la RTUv + RTP+ quimioterapia sistémica demuestra resultados comparables a la cistectomía radical en términos de control local y supervivencia global. OBJETIVOS: Evaluar nuestros resultados en terapia trimodal en cáncer de vejiga músculo-invasivo que rechazan la cistectomía radical. MÉTODOS: Análisis retrospectivo de 23 pacientes con estadio T3 TVMI tratados con preservación vesical (RTUv +3 ciclos de gemcitabina, cisplatino+ 64Gy RTP adyuvante). KM estimados y log Rank fueron calculados. RESULTADOS: La mediana de seguimiento fue de 58 meses (15-158). El intervalo libre de enfermedad y la supervivencia global a los 5 anos fue de 56% y 64%, respectivamente. La Supervivencia cáncer especifica fue de 67%. No se objetivaron complicaciones grado 3 o más. CONCLUSIONES: Nuestra serie de tratamiento preservación vesical demuestra que el uso de este tratamiento en pacientes debidamente seleccionados que no quieren cistectomía radical es apropiado.

Type 4 hypersensitivity development in a case due to mifamurtide.

BACKGROUND: This report aims to discuss the mechanism of pleural and pericardial effusion related to mifamurtide which is an immunological agent used as adjuvant chemotherapy in osteosarcoma. CASE: Mifamurtide (2 mg/m < sup > 2 < /sup > ) and European and American Osteosarcoma Studies (EURAMOS) protocol were used together intravenously after complete surgical resection. No side effects occurred except for fever after the first dose. However, pleural, pericardial effusion, and splenic nodule formation began 11 months after discontinuation of mifamurtide treatment. Pleural biopsy revealed a type 4 hypersensitivity reaction. We treated the patient with 1,5 mg per day colchicine. Pericardial effusion attacks and nodules in the spleen disappeared. The patient had a mild pleural effusion attack which has not yet repeated. CONCLUSION: Mifamurtide, which activates macrophages, can also activate immunity with a stand by effect and cause a hypersensitivity reaction.

Posterior Reversible Encephalopathy Syndrome in a Normotensive Child after Allogeneic Hematopoietic Stem Cell Transplantation.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon clinicoradiological syndrome that is characterized by acute neurological symptoms such as headache, convulsion, visual disturbance, and altered consciousness. The characteristic magnetic resonance (MR) finding is vasogenic edema, predominantly in the subcortical areas of the posterior parietal and occipital lobes on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences. Herein, we described a rare case of PRES induced by cyclosporine (CsA) after an allogeneic hematopoietic stem cell transplantation (HSCT) from a sibling donor.

Utility of FDG PET/CT in the Management of Primary Testicular Lymphoma.

OBJECTIVE: Primary testicular lymphoma (PTL) is a form of extra-nodal lymphoma originating from the testicles. Currently, positron emission tomography (PET) with glucose analogue 18F-fluorodeoxyglucose (18F-FDG) is the most popular and widely used modality for evaluating tumor metabolism, and PTL usually displays increased 18F-FDG uptake. Despite the rapid increase in clinical applications of FDG PET/ computed tomography (CT), its role in PTL has neither been clearly defined nor reviewed systematically. This study reviews the usefulness and limitation of FDG PET/CT in the diagnosis and treatment of PTL. METHODS: This study included 12 patients with PTL between 2004 and 2015. We retrospectively examined PET/CT results along with patient outcome. The maximum standardized uptake value (SUVmax) was calculated. RESULTS: The mean overall survival (OS) and disease-free survival (DFS) was 44.5 months and 35.5 months, respectively. The mean SUVmax was identified as 18.5 in recurrent/metastatic group. The 1-year and 3-year OS was 94% and 69%, while the 1-year and 2-year DFS was 93.5% and 56%, respectively. CONCLUSION: FDG PET/CT is very helpful in both staging and evaluating treatment response. Although it is not a perfect tool in the initial diagnosis, it might aid in the differential diagnosis of challenging testicular tumors. Pre-treatment and post-treatment FDG uptake values may also have a prognostic value in patients with PTL.