Clinical Characteristics and Outcomes of Cancer Cases Among Syrian Refugees From Southern Turkey.

Importance: Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are needed. Objective: To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees. Design, Setting, and Participants: This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022. Main Outcomes and Measures: Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment. Results: A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 [13.8%]), leukemia and multiple myeloma (147 [13.2%]), and lymphoma (141 [12.7%]) were common among adults, and leukemias (180 [42.8%]), lymphomas (66 [15.7%]), and central nervous system neoplasms (40 [9.5%]) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children. Conclusions and Relevance: Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.

The Mutation of CD27 Deficiency Presented With Familial Hodgkin Lymphoma and a Review of the Literature.

This study aimed to report 4 siblings with CD27 deficiency presented with Hodgkin lymphoma. The father of the family, his 2 wives, and 17 children born from these wives were included into the study. CD27 mutation of all the family members with, and without Hodgkin lymphoma were studied. The variants detected by the exome sequencing analysis were verified by Sanger sequencing and analyzed using SeqScape Software 3. It was determined that both the father of the family and his 2 wives carried the same variant heterozygously. Of the children born to the first mother, 2 children were normal, 3 were heterozygous and 5 were homozygous. Four of these 5 homozygous children were diagnosed with Hodgkin lymphoma. Of the children born to the second mother, 1 child was normal, 3 children were heterozygous and 2 children were homozygous, and none of them had developed a malignant event. We also showed that CD27 deficiency may enhance Treg differentiation. According to our information, this study augmented the relationship of Hodgkin lymphoma and CD27 deficiency. The detection of homozygous CD27 variant in all siblings who developed lymphoma strengthened the place of this mutation in the etiology of Hodgkin lymphoma. In contrast, the presence of homozygous siblings with no malignant event suggested the possible contributions of environmental factors on the etiology.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Growth-differentiation Factor-15 and Tissue Doppler Imaging in Detection of Anthracycline-induced Cardiomyopathy During Therapy of Childhood Cancers.

OBJECTIVES: The aim of this study was to evaluate the importance of growth-differentiation factor-15 (GDF-15) levels and tissue Doppler imaging (TDI) in the early detection of anthracycline-induced cardiomyopathy during the treatment of childhood cancers. PATIENTS AND METHODS: Twenty patients (13 males and 7 females) newly diagnosed with childhood cancer whose treatment protocol included anthracycline were included in the study. Echocardiography, including M-mode, pulse Doppler, and TDI, was performed after the first anthracycline treatment at cumulative doses of 100, 200, and 300 mg/m and at least 6 months after the last treatment. GDF-15 and troponin-I were also measured at these time points. RESULTS: The median age of the patients was 14 years (range, 3 to 18 y). The median cumulative anthracycline dose was 220 mg/m (range, 60 to 400 mg/m). Conventional pulse wave and pulse wave tissue Doppler methods revealed significant differences in the right ventricular myocardial performance indices of the patients who received cumulative anthracycline doses of 300 mg/m compared with their indices at least 6 months after the last treatment. The serum GDF-15 levels after the cumulative anthracycline dose of 200 mg/m were also higher than the patients' pretreatment levels. CONCLUSIONS: Doppler/TDI and GDF-15 levels may be used in the early determination of anthracycline-induced cardiomyopathy during the treatment of childhood cancers.

Effects of Prednisolone, L-Asparaginase, Gemfibrozil, and Combinations of These Elements on Mice Lipid Profile, Liver, and Pancreas.

The aim of this study is to determine the effects of L-asparaginase (L-ASP), corticosteroids (CSs), and antilipidemics, separately and in combination, on the lipid profiles and the liver and pancreas histology in mice. This study included 8 groups of 7 mice each. Before any drug administration, serum samples were taken from all of the mice. Then, normal saline was applied to the control group, and a medication or combination of medications was applied to the other groups. Levels of triglycerides, cholesterol (COL), and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were determined, and the livers and pancreases were evaluated histologically at the end of the study. Triglycerides increased significantly in the CS-only and the L-ASP-only groups, COL increased significantly in the CS-only group, and HDL increased significantly in the CS-only and the antilipidemic-only groups. LDL was significantly lower in the CS-only and the L-ASP-only groups. CSs and L-ASP were significantly effective in liver necrosis, L-ASP was significantly effective in liver balloon degeneration, and CS were significantly effective in pancreas vacuolization. Triglyceride measurement is recommended before/during CS and/or L-ASP treatment. Starting with an antilipidemic agent can be considered to avoid possible complications in patients with significantly high rates. Indicators of a possible liver or pancreas injury should also be considered.

High-risk febrile neutropenia and its management in children with solid tumors and lymphoma.

BACKGROUND/AIM: The clinical characteristics and treatment results of febrile neutropenia attacks that occurred in patients with lymphoma and solid tumors were analyzed. MATERIALS AND METHODS: A total of 50 patients with 94 high-risk attacks were evaluated for malignant diseases in this study. RESULTS: The fever etiology was determined as clinical (50%), microbiological (5.31%), clinical-microbiological (5.31%), or unknown (39.3%). A few of the attacks (21.3%) were observed in lymphoma cases and 77.7% were observed in patients with solid tumors. Patients who were in remission had 59.6% of the attacks, and 39.4% occurred in patients not in remission. Among the groups tested, 73% (the imipenem/amikacin group) and 47.9% (the piperacillin-tazobactam/amikacin group) of patients were in remission. Glycopeptide addition rates in these groups were 22.2% and 40.8% and antifungal addition rates were 8.8% and 18.3%, respectively. CONCLUSION: Clinical progress was more problematic in patients who were not in remission during the attacks. This was due to the fact that some patients had other factors that placed them in the high-risk group, as well as increased C reactive protein and procalcitonin values on the first day. Therefore, it may not be accurate to associate the success achieved in the different treatment regimens with antibiotics alone.

Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis.

BACKGROUND: Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. METHODS: We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. RESULTS: We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these "ultramutated" tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. CONCLUSIONS: We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments.

Pilomatrixoma in childhood.

CONTEXT: Pilomatrixoma is a benign tumor of the skin. Malignant transformation can be seen rarely in the small percentage. AIM: The aim of the following study is to attract attention to this tumor in the differential diagnosis because if it is not kept in mind it leads to both unnecessary interventions and treatments for the patient. PATIENTS AND METHODS: From January 2006 to December 2012, 8 patients with pilomatrixoma were evaluated retrospectively. RESULTS: A total of 8 pediatric pilomatrixoma patients' charts were reviewed retrospectively. None of the patients had familial feature. Of 8 patients 4 (50%) were male and 4 (50%) were female. The patients' age ranged from 2-18 years with a median age 11.5 years. All of the patients were admitted with the complaint of swelling at the lesion site. Two patients have multiple lesions, one of them has two and other has three lesions. A total of 11 lesion were detected in our 8 patients that 5 of them were located upper extremities (46%), 3 of them cervical region (27%), 2 of them on occipital region (18%) and 1 of them in the sacral region (9%). All lesions were excised completely. Until now, no patient had evidence of recurrence or malignant disease. CONCLUSION: As a result pilomatrixoma is a benign tumor, with atypical forms and unfortunately, no tumor-specific diagnostic feature except of a careful histopathological examination is available.

Coexistence of glomangioma and yolk sac tumour in a child: a case report.

Glomus tumours (GTs) primarily arise from glomus bodies that are located in the dermis layer of skin. However, they can be encountered ectopically in most parts of the body. As a result of researches done in a 17-month-old male patient who prssented to us with complaint of an increasingly growing swelling, he was diagnosed with a yolk sac tumour. Chemotherapy was started and then, he was operated. GT was found inside the tumoural mass. Our patient, who is the first case according to our knowledge, where the concurrence of yolk sac and glomus tumours was reported, has been discussed in the light of literature.

Synovial sarcoma in a premature newborn.

Synovial sarcoma is rarely detected in infants, with an annual incidence of 0.5 per million. Synovial sarcoma occurs more frequently in adolescents and young adults, with the majority of patients presenting between 15 and 40 years of age. It is extremely rare, however, in pediatric patients under 2 years of age. In the present study we examined a 3-day-old male infant born at 32 weeks who had a mass on his left arm. Synovial sarcoma was identified on histopathological and immunohistochemical analysis of biopsy material acquired from the mass. On whole body magnetic resonance imaging, diffuse metastases were detected in the bilateral lungs in the retroperitoneal zone, in bilateral suprarenal glands, the right liver lobe, the right kidney, and the brain. To our knowledge this is the youngest patient to be diagnosed with synovial sarcoma in the literature.

Neurothekeoma in childhood: a benign tumor mimicking malignant disease.

Neurothekeoma (NT) sometimes extends to subcutaneous adipose tissue, skeletal muscle or epidermis, and thus may imitate some malignant situations. A 17-year-old female patient was admitted to another medical center with a swelling at her waistline. Plexiform fibrous histiocytoma was diagnosed, and she was referred to our clinic. Total re-excision was performed. The new pathology report indicated features of atypical NT. A case of atypical NT, which can be misdiagnosed as a malignant mesenchymal tumor, is discussed in this paper.

Neurological complication of non Hodgkin lymphoma in childhood: experience from a single center in Turkey.

PURPOSE: Lymphomas are the third most common childhood malignant disease after leukemia and central nervous system (CNS) tumors. Early diagnosis of these complications will reduce mortality and morbidity. In this study we aimed to review the neurological complications of childhood non Hodgkin Lymphoma (NHL). PATIENTS AND METHODS: Forty four children with NHL between 2006 and 2012 were investigated retrospectively and 14 cases with neurological complications were identified. RESULTS: The most common symptom was alteration of the consciousness (10 patients, 71.4 %) followed by convulsion (5 patients, 35.7 %), and hallucination (4 patients, 28.5 %); headache, eye pain, neurogenic bladder, speech disability and facial paralysis, and hemiplegia, were less common and each of them was seen in 1 (7.1 %) of the patients. The neurological complications were mostly seen in children with precursor T lymphoblastic lymphoma followed by anaplastic large cell lymphoma. The complications were secondary to medications (Eight patients) infection (two patients); CNS relapse (two patients); or CNS involvement of the primary disease (two patients). Chemotherapy-related neurologic complications were secondary to intrathecal methotrexate, L-asparaginase, vincristine, and ifosfamide CONCLUSION: Advanced disease and PTLL subtype can be suggested as predictors of neurological complication. The survival rates of neurological complications are fairly good unless it is secondary to involvement of the primary disease. In patients with drug-induced neurological complications, the treatment can be safely re-administered after controlling the neurological complications. Therefore, clinicians managing children with NHL must be informative about neurological complications.

Development of fatty liver in children with non-Hodgkin lymphoma.

The aim of this study is to investigate the development of hepatosteatosis in children with non-Hodgkin lymphoma. Twenty-eight patients were evaluated retrospectively for hepatosteatosis by computed tomography. Mild, moderate and severe hepatosteatosis were defined as the difference between the average liver attenuation and the average spleen attenuation, equaling (-10)-(-19); (-20)-(-29); and ≥30 HU, respectively. "Vaguely" and "obvious" hepatosteatosis were defined as none or mild hepatosteatosis, and moderate and severe hepatosteatosis, respectively. In T-cell lymphoma, obvious hepatosteatosis was determined in 1 of 12 patients (8.3%) at the first evaluation, 8 of 12 patients (66.7%) at the second evaluation and 4 of 12 patients (33.3%) at the third evaluation. In B-cell lymphoma, obvious hepatosteatosis was determined in none of 16 patients at the first evaluation, 2 of 16 patients (12%) at the second evaluation and none of the patients at the third evaluation. In the second evaluation, severe high serum total cholesterol and triglyceride levels were determined in 4 of 5 patients. We observed higher fatty liver ratios, and high triglyceride and cholesterol levels, although the data were obtained from a small number of patients.

Growth-differentiation factor-15 and tissue doppler imaging in detection of asymptomatic anthracycline cardiomyopathy in childhood cancer survivors.

OBJECTIVES: Anthracyclines have led to an increased risk of cardiac morbidity and mortality. Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Tissue Doppler imaging (TDI) also has potential as a clinically useful technique for the assessment of myocardial function. Biochemical markers may be used to detect cardiac damage growth-differentiation factor-15 (GDF-15) and are emerging as a biomarker of cardiac dysfunction. The aim of this study is to assess the value of the plasma levels of GDF-15 and TDI in detecting late myocardial dysfunction in childhood cancer survivors (CCS) who were treated with anthracyclines. DESIGN AND METHODS: Thirty-eight CCS who had completed chemotherapy treatment with anthracyclines were included in this study. Control group consisted of 32 age- and gender-matched healthy volunteers. All children underwent a detailed echocardiography, which contained an M-mode, pulse Doppler and tissue Doppler imaging. However, GDF-15 and cardiac troponin-I (cTnI) were measured. RESULTS: Although, systolic function of the left ventricular was similar in all groups, there were significant differences between parameters of diastolic function of the heart. The mitral valve E wave, E/A ratio, left ventricular E'm wave, and E'm/A'm ratio were different in the patients than in the controls (p = 0.049, p = 0.037, p < 0.0001, p = 0.001, respectively). The tricuspid valve E/A ratio, right ventricular E't wave, and E't/A't ratio in the patients were also different from those of the controls (p = 0.031, p < 0.0001, p < 0.0001, respectively). Mean plasma GDF-15 was significantly higher in patients than healthy controls (p = 0.027). There were no significant differences in cTnI between both groups. CONCLUSIONS: Growth-differentiation factor-15 level may be used as a biomarker of anthracycline-induced cardiovascular disease severity in the CCS.

Intracranial metastasis of neuroblastoma: in two different areas at the same time.

INTRODUCTION: Neuroblastoma (NB) is the most common extracranial solid malignancy in children. The major cause of death from this cancer is metastasis of tumors, and metastasis can be seen in different areas of the body. Metastasis of NB occurs by hematogenous and lymphatic routes. Generally, brain metastases have been reported in only one area of the brain parenchyma. CASE REPORT: A 4-year-old male patient was treated in our clinic due to the NB that settled in the intra-abdominal region, but the patient presented with headache and nausea approximately 5 months after completion of the treatment. Whereupon, cranial imaging was performed and two masses were detected in the bilateral frontal lobe, and then the patient underwent surgery. Metastatic NB diagnosis was confirmed histopathologically. The patient's chemotherapy treatment is still ongoing. CONCLUSION: We report the case of a male patient with two separate metastatic masses in the brain parenchyma, which occurred in two different areas at the same time.

The activity of valproic Acid in the treatment of refractory hyperleukocytosis in a child with acute lymphoblastic leukemia.

Hyperleukocytosis may be associated with an early morbidity and mortality due to leukostasis. Cytoreductive therapies-such as steroids, hydroxiurea, exchange transfusion, and leukapheresis-have been used for the prevention of leukostasis. Herein, the valproic acid used for the treatment of the hyperleukocytosis did not respond to known therapies in a child; lymphoblastic lymphoma developed bone marrow relapse under the treatment is discussed.