A rare cause of intestinal obstruction in children: signet-ring cell adenocarcinoma of the colon.

BACKGROUND: Signet-ring cell adenocarcinoma of the colon is well-recognized in adult patients who are extremely rare and not well-documented in children. Our study aims to raise awareness about this rare disease and its long-term outcomes. METHODS: We retrospectively evaluated patients with signet-ring cell colon adenocarcinoma. RESULTS: Six patients, three boys and three girls, with a mean age of 14.83 (range, 13-17 years), presented with signs of intesti-nal obstruction and were diagnosed with signet-ring cell colon adenocarcinoma. All patients had air-fluid levels on abdominal X-ray. Abdominal ultrasonography of all patients revealed subileus. Abdominal computed tomography was performed in five patients, and pre-operative colonoscopy was conducted in two patients before the emergency intervention. All of the patients underwent emergent exploratory laparotomy with the preliminary diagnosis of acute abdomen. In two patients, debulking surgery followed by a stoma was performed. The remaining four patients were treated with anastomosis following intestinal resection. All girls had metastases on the ovary. One of the patients died due to the burden of multiple metastases in the early period, and three died in the sixth post-operative year. We have been following the remaining two patients since then. CONCLUSION: Although signet-ring cell carcinomas (SRCCs) are rare, they should be considered in the differential diagnosis of acute abdomen and intestinal obstruction in pediatric patients. Despite early diagnosis and treatment, SRCC has a poor prognosis in the pediatric population.

Economic and psychosocial problems experienced by pediatric with cancer patients and their families during the treatment and follow-up process.

AIM: To identify the psychosocial and economic problems of the pediatric patients with cancer who were treated at the Dr. Sami Ulus Obstetrics and Gynecology and Child Health and Diseases Training and Research Hospital's Pediatric Oncology Department and their relatives during this process. MATERIAL AND METHODS: We interviewed a total of 100 patients who were treated at Dr. Sami Ulus Obstetrics and Gynecology and Child Health and Diseases Hospital's Pediatric Oncology Department between 1996 and 2015, and were now followed up without treatment and their relatives using survey questions on the psychosocial and economic problems they experienced. RESULTS: Most of patients were from provinces outside Ankara. The average monthly income was below the level that would meet the family needs in 80% of the families and only 16% had extra income. Additional economic support had been received by 93% of the families in the patient group. Twenty-five families (25%) had been forced to sell property during the treatment. Forty-nine (49%) families had borrowed money from acquaintances and relatives or had taken out a bank loan. Serious psychological problems were experienced during and after the treatment by 46% of the mothers; 41% of the families had used religious procedures more commonly during the treatment period to cope with the psychological problems. Education was subject to a 1-2 year pause in 83% of the patients. CONCLUSION: Childhood-age patients with cancer and their families experience significant psychosocial and economic problems during and after the treatment process. Providing medical treatment and psychosocial support in harmony is an important factor that increases the success of cancer treatment. The patient and the family will require psychosocial support mechanisms throughout life, starting from the moment they face the disease. Developing national social support programs and legal regulations to form a basis for such programs are required in our country.

AMAÇ: Dr. Sami Ulus Kadin Dogum ve Çocuk Sagligi ve Hastaliklari Egitim ve Arastirma Hastanesi Çocuk Onkoloji Klinigi'nde tedavi edilmis kanserli çocuk hastalarin ve yakinlarinin bu süreçte karsilastiklari psikososyal ve ekonomik sorunlari belirlemek. GEREÇ VE YÖNTEMLER: Dr. Sami Ulus Çocuk Sagligi ve Hastaliklari Hastanesi Çocuk Onkoloji Klinigi'nde 1996­2015 yillari arasinda tedavi görmüs ve su anda hastaliksiz olarak izlemde olan toplam 100 hasta ve yakini ile görüsülerek yasadiklari psikososyal ve ekonomik sorunlara iliskin anket sorulari yönlendirildi. BULGULAR: Hastalarimizin çogu Ankara disi illerden gelmekte idi. Hasta ailelerinin %80'inin ortalama aylik gelirinin ailenin gereksinimlerini karsilama düzeyinin altinda oldugu ve sadece %16'sinin ek geliri oldugu saptandi. Hasta grubunda ailelerimizin %93'ü ek ekonomik destek almislardi. Yirmi bes aile (%25) tedavi süresince sahip olduklari bazi mal varliklarini satmak zorunda kalmisti. Kirk dokuz (%49) aile tanidik ve akrabalarindan borç almisti ya da bankadan kredi çekmisti. Annelerin %43'ünün tedavi sirasinda ve sonrasi ciddi psikolojik sorunlar yasadigi, psikolojik sorunlarla basa çikabilmek için ailelerin %40'inda tedavi döneminde dini ibadetlere egilimde artis oldugu gözlendi. Hastalarimizin %83'ünün egitimlerinde 1­2 yil gibi bir kayip yasandigi görüldü. ÇIKARIMLAR: Çocukluk çagi kanser hastalari ve aileleri tedavi sürecinde ve sonrasinda önemli oranda psikosoyal ve ekonomik sorunlar yasamaktadir. Kanserde, tibbi tedavi ile psikososyal destegin bir uyum içerisinde yürütülmesi tedavi basarisini artiran önemli bir etmendir. Hastanin ve ailesinin hastalikla tanistigi ilk andan baslayarak tüm hayat boyunca psikososyal destek mekanizmalarina gereksinim vardir. Ülkemizde ulusal olarak bu yönde gelistirilecek sosyal destek programlari ve bu programin yürütülecegi zemini olusturacak yasal düzenlemelere gereksinim vardir.

A targeted salvage therapy with Brentuximab vedotin in heavily treated refractory or relapsed pediatric Hodgkin lymphoma patients before and after stem cell transplantation.

Taçyildiz N, Tanyildiz HG, Ünal E, Dinçaslan H, Asarcikli F, Adakli Aksoy B, Vatansever G, Yavuz G. A targeted salvage therapy with Brentuximab vedotin in heavily treated refractory or relapsed pediatric Hodgkin lymphoma patients before and after stem cell transplantation. Turk J Pediatr 2019; 61: 671-676. Hodgkin`s lymphoma (HL) is highly curable disease in its early stages, but in advanced stages, it presents a dilemma when it becomes refractory or relapses after several rounds of chemotherapy. Brentuximab vedotin (BV) is an antibody-drug conjugate that targets the tumor necrosis receptor family protein member CD30 positive malignancies via an anti-CD30 monoclonal antibody linked to monomethyl auristatin-E. In adult and pediatric studies, it has been shown to be an effective salvage therapy for primary refractory HL or relapse after autologous stem cell transplant (ASCT). Between July 2012 and August 2017, we administered BV (1.8 mg/m2 every three weeks; 12 cycles totally) with doxorubucin, vinblastin, dacarbazine (AVD), rituximab + ifosfamide + carboplatin + etoposide (RICE), or bendamustine combination treatment in pediatric HL patients, who were previosuly treated for refractory or relapsed advanced stage HL before (seven patients) or after (one patient) ASCT in our center. After eight BV courses, one patient was able to undergo match unrelated donor (MUD) SCT. Another seven pediatric HL patients, who were not able to go into remission with any other classical HL chemotherapy protocols, received 4-6 courses of BV-AVD and/or RICE/bendamustine. All were able to undergo ASCT after negative positron emission tomography (PET) imaging results. After ASCT, we switched to BV as consolidation therapy until a total of 12 cycles was completed. Patients went into remission after a median 34 (range: 12-42) months from the start of BV treatment. BV is an encouraging, well- tolerated, and effective targeted therapy especially when combined with AVD or when alternated with another targeted therapy combination, including RICE, when needed.

The prognostic importance of TGF-ß, TGF-ß receptor, and fascin in childhood solid tumors.

Fascin plays a role in tumor metastasis under the influence of TGF-ß, each potentiating the effect of the other. We retrospectively investigated whether there was a prognostic relationship between TGF-ß and fascin, and disease stage, local recurrence, metastasis tendency, and response to treatment. Twelve neuroblastomas, 17 osteosarcomas, 14 Ewing's sarcomas, 15 rhabdomyosarcoma cases, and 8 rare solid tumors were included. Serum TGF-ß levels were high at the time of diagnosis in all groups (p = .015) and decreased significantly during remission (p = .008). Serum TGF-ß values in the relapse period rarely reached high levels at the time of diagnosis and even stayed under the control group values (p = .017). When TGF-ß receptor expression in tumor tissues was evaluated, the association of TGF-ß receptor positivity with metastatic disease and advanced stage was striking. We found that 88% of rhabdomyosarcoma cases with alveolar histopathology expressed the TGF-ß receptor, and the association between TGF-ß receptor positivity and alveolar histopathology seemed to be a negative prognostic marker. When fascin levels were evaluated in childhood solid tumor tissue, the risk of relapse increased when the fascin total score at diagnosis was >4. This is one of the few studies including prognostic markers such as serum TGF-ß, tissue TGF-ß, TGF-ß receptor, and fascin in pediatric solid tumors. Considering the poor prognosis of advanced stage pediatric solid tumors and the need for biomarkers to predict which patient might need more intensive therapy or warrant closer follow-up afterward, we think that TGF-ß, TGF-ß receptor, and fascin expression have an important prognostic role.

Vitamin D receptor polymorphisms in immune thrombocytopenic purpura.

BACKGROUND: Vitamin D receptor (VDR) polymorphisms have been studied in immune-mediated disorders, but not yet in immune thrombocytopenic purpura (ITP). We investigated whether VDR variants were associated with ITP in children. METHODS: The study included 44 children with a diagnosis of ITP and 100 healthy controls. Five VDR polymorphisms (Cdx-2, FokI, BsmI, ApaI and TaqI) were genotyped and used to evaluate the association of VDR variants with ITP. RESULTS: The distribution of the three Cdx-2 genotype groups (GG, GA, and AA) was significantly different between ITP patients and controls (P = 0.025); the homozygous GG genotype of Cdx-2 was overrepresented in ITP patients. The frequency of the A allele of Cdx-2 was significantly different between patients and controls (P = 0.01). The A allele of Cdx-2 was associated with a decreased risk of ITP (OR, 0.343; 95% CI: 0.150-0.782). No statistically significant difference was found between the ITP group and control group for Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P > 0.5). CONCLUSION: There appears to be an interaction between the Cdx-2 variant of VDR and childhood immune thrombocytopenia.

The Correlation Between Pre-treatment Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Parameters and Clinical Prognostic Factors in Pediatric Hodgkin Lymphoma.

OBJECTIVE: To compare standardized uptake values (SUV) derived from pre-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging and clinical prognostic factors in pediatric patients with Hodgkin lymphoma (HL). METHODS: Pre-treatment FDG PET/CT findings of 28 children with HL were evaluated in this retrospective study. Metabolic tumor volume (MTV), SUVmax normalized by weight (SUVweight), lean body mass (SUVlbm), body surface area (SUVbsa) and plasma glucose levels of tumors (SUVglucose) were calculated using pre-treatment FDG PET/CT scan images. These metabolic parameters were correlated with clinical factors [age, sex, number of lymph node groups, presence of splenic involvement, bulky mediastinal disease, Ann Arbor stage, serum white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), serum albumin and hemoglobin levels]. RESULTS: SUVbsa, SUVlbm, SUVweight, SUVglucose and MTV were higher in patients with stage III-IV disease, bulky tumor and ≥3 lymph node groups (p<0.05). SUVbsa and SUVglucose were higher in patients with splenic involvement (p<0.05). There was no significant correlation between these metabolic parameters and sex, ESR, levels of albumin and WBC (p>0.05). SUVbsa and SUVlbm were higher in patients with anemia (p<0.05). Additionally, significant increases were detected in SUVweight, MTV, and SUVglucose with increasing age (p=0.005, p=0.027, and p=0.009, respectively). SUVbsa and SUVlbm had no significant correlation with age (p>0.05). CONCLUSION: Metabolic parameters derived from pre-treatment FDG PET/CT may have an important role in predicting high-risk disease in patients with HL. Also, SUVbsa and SUVlbm may be better markers than SUVweight in the quantitative evaluation of FDG PET/CT scans in pediatric patients.

Epidemiological features and risks of hemangiomas.

Sahin G, Düzcan-Kilimci D, Tanyildiz HG. Epidemiological features and risks of hemangiomas. Turk J Pediatr 2017; 59: 664-669. Hemangiomas are the most common benign tumors of childhood. The known risk factors in developing hemangiomas are female gender, prematurity and low birth weight. Our study was designed to investigate prenatal and natal risk factors in addition to the above factors that would potentially affect development of hemangiomas. Two hundred forty hemangioma patients and 100 healthy controls were included in the study. Both groups were interviewed for age, gender, prenatal characteristics (presence of maternal pregnancy hypotension, hypertension and hyperemesis, parental smoking habits) as well as natal characteristics (delivery, birth weight, gestational age) and maternal-paternal age. Hemangiomas were mostly localized in the head and neck. Risk of developing hemangioma was higher in girls and in firstlings. History of hyperemesis during pregnancy increased incidence of hemangioma. Post-term delivery was found to be protective against developing hemangioma. We are in the opinion that there is a need for wider studies with a bigger sample size so as to detect other risk factors.

Are the methylenetetrahydrofolate reductase 1298 and 677 gene polymorphisms related to optic glioma and hamartoma risk in neurofibromatosis type 1 patients?

The methylenetetrahydrofolate reductase (MTHFR) gene plays a key role in carcinogenesis through its effects on DNA synthesis and methylation and also has a significant role in the etiology of many disorders, such as diabetes, migraine, and cardiovascular disease. Neurofibromatoses (NF) are autosomal dominant inherited diseases that can affect tissues such as bone and skin and predispose individuals to tumor development in various parts of the nervous system or body. Optic nerve glioma and brain tumors are common in children with NF, and leukemia and lymphoma incidence is also higher than normal. We therefore aimed to investigate the possible relationship between the MTHFR gene polymorphism and accompanying tumors such as neurofibroma, hamartoma, and optic glioma in children with NF1 found to have the MTHFR 677 and MTHFR 1298 gene polymorphism in this study. We included 55 pediatric patients diagnosed with NF1 between 2005 and 2014 in the study group. The control group included 44 healthy subjects without acute or chronic disease findings. A significant relationship was found between the MTHFR A1298C polymorphism and the incidence of optic glioma (p=0.014) (AA vs. AC: OR 11, 95% CI 1.27-95.17; AA vs. CC: OR 7.33, 95% CI 0.35-150.70). We also found a significant relationship between the MTHFR C1298C polymorphism and the incidence of hamartoma (p=0.019) (AA vs. AC: OR 2.12, 95% CI 0.662-6.809; p=0.203). Epilepsy incidence was high in subjects with MTHFR C677C. The MTHFR A1298C, C1298C, and C677C gene polymorphisms can be associated with a higher optic glioma, hamartoma, and epilepsy incidence, respectively, in patients diagnosed with neurofibromatosis type 1.

18F-FDG PET/CT Imaging of Hodgkin Lymphoma in a Child with Common Variable Immunodeficiency.

Common variable immunodeficiency is characterized by low levels of serum immunoglobulins and antibodies, recurrent infections, and a predisposition to malignancy. Here, we present the 18F-FDG PET/CT findings of a 7-y-old boy with common variable immunodeficiency and Hodgkin lymphoma.

Can Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Be Used As a Useful Method to Evaluate the Treatment Response to Neoadjuvant Therapy Combined With Sorafenib and Anti-VEGF in Children Diagnosed With Metastatical Bone Sarcoma?

BACKGROUND: The prognosis is still poor for patients with a metastatic bone tumor and new treatment approaches (anti-VEGF and tyrosine kinase inhibitors vs) are therefore needed. OBJECTIVES: The aim of our study was to evaluate how the primary and metastatic lesions of our patients with a bone tumor were affected by these treatments and to determine the importance of the 18F-FDG PET method. PATIENTS AND METHODS: Twenty metastatic bone tumor cases were included. Sorafenib and anti-VEGF were added to the standard treatment in cases with widespread metastatic disease at diagnosis or after neoadjuvant chemotherapy showing less than 90% tumor necrosis in the surgical sample. Positron emission tomography (PET) imaging was performed at diagnosis, the preoperative period following neoadjuvant chemotherapy, during postoperative follow-up, and when treatment was discontinued. RESULTS: The primary treatment region median SUVmax level decreased from 7.35 to 2.5 in the living patients (n = 16) while there was no significant decrease in the patients who succumbed to the disease (P < 0.001). Comparison of the pre- and post-treatment metastasis region median SUVmax levels in patients with metastatic involvement showed a decrease from 2.1 to 0 in the surviving patients but only from 4.8 to 3.2 in the deceased patients (P < 0.01). Survival results indicated that 28.6% of the patients receiving classical treatment only died while all the patients receiving additional sorafenib and anti-VEGF survived. CONCLUSIONS: 18F-PET may be a useful technique before and during the follow-up of neoadjuvant treatment in pediatric metastatic bone tumor patients. The addition of sorafenib and anti-VEGF to classical treatment has a favorable contribution to the response and therefore the survival duration.

Single-center experience with sirolimus therapy for vascular malformations.

Vascular malformations (VMs) are described as congenital malformations of the vasculature derived from capillaries, veins, lymphatic vessels, arteries, or a combination of these vessels. They can cause significant morbidity resulting from soft tissue hypertrophy-related disfiguration, bony abnormalities, and even organ compromise. They are usually treated with various interventional procedures to achieve local control; however, the chance of success decreases as the anatomical distribution of the malformation widens. Unfortunately, medical treatment options have been quite limited in these patients. Sirolimus is an antiangiogenetic and antiproliferative pharmacologic agent that has been used for the management of VM in the last decade. We report 6 pediatric patients (4 with capillary lymphaticovenous malformations, 1 with lymphaticovenous malformation, and 1 with venous malformation) seen at our clinic within the last 2 years with lesions covering wide anatomical areas. After the patients had unsuccessfully undergone various treatments at various centers, they were treated at our facility with peroral sirolimus. The mean duration of treatment was 13 months, but in 3 patients, tapered dosing continues. Five patients achieved partial responses. The response to sirolimus treatment increased as the lymphatic component of the VM increased. All patients tolerated sirolimus well; side effects were acceptable. Sirolimus is a safe and effective medical treatment for widely distributed VMs with significant lymphatic components and no further local treatment option.

How should we monitor boys with testicular microlithiasis?

Testicular microlithiasis (TM), a rare condition characterized by calcification within the seminiferous tubules, is associated with benign and malignant disorders of the testis. We review current practices of following up pediatric patients diagnosed TM incidentally on scrotal ultrasonography (US). We analyzed retrospectively patient characteristics, family history, indications for US, pathological features, US findings, outcome, and follow-up. At our institution, 2875 scrotal US examinations were performed on 2477 children with various scrotal complaints from 2008 to 2015. Testicular microlithiasis was detected in 81 patients (i.e., an incidence of 3.27%). Every 6 months, each patient underwent a clinical and ultrasonographic evaluation as well as serum tumor markers determination to detect a potential malignancy. Seventy-eight patients who had undergone scrotal US at least twice were included in this study. We evaluated the US studies for the type of TM (diffuse and focal) and change in follow-up studies. Testicular microlithiasis was typically diffuse (n = 56, 71.8%) and bilateral (n = 45, 57.7%), and it was detected the most frequently in the 9-11-year age group (27 patients, 34.6%). The most common comorbid conditions included undescended testes (31 patients, 39.7%) and hydrocele (11 patients, 14.1%). We found that serum tumor markers were within normal limits both at diagnosis and upon follow-up. No testicular tumors or new abnormal symptoms developed during the clinical follow-up. There is no convincing evidence that TM alone is premalignant in a pediatric population. In terms of follow-up, we advise regular self-examinations and annual US in the absence of risk factors.

Serum Basic Fibroblastic Growth Factor Levels in Children with Infantile Hemangioma.

OBJECTIVES: To determine serum levels of basic fibroblastic growth factor (b-FGF) in hemangioma patients under 2 y of age. METHODS: The study group consisted of 43 children with infantile hemangioma and b-FGF levels were analyzed using ELISA. RESULTS: The serum b-FGF levels were higher in hemangioma patients than in healthy control individuals (p 0.01). There were no differences between the lesion size, number of lesions, patient age and serum b-FGF levels. CONCLUSIONS: Thus, b-FGF is an important growth factor that plays a central role in hemangioma, but determining b-FGF serum levels was not helpful in distinguishing between patients who require treatment and those who do not.

Herlyn-Werner-Wunderlich Syndrome: A Rare Cause of Pelvic Pain and High CA 19-9 Levels in an Adolescent Girl.

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare developmental anomaly that includes uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. A 13-year-old girl presented with chronic abdominal pain. Magnetic resonance imaging revealed uterus didelphys, hematometrocolpos and renal agenesis on the right side with imperforate hymen. Subsequently the patient was found to have Mullerian duct anomalies. CA 19-9 level was high. At laparoscopy combined with vaginoscopy hematocolpos was drained following which she improved clinically and CA 19-9 level returned to normal.

A Rare Presentation of Paraovarian Sclerosing Stromal Tumor with High Mitotic Activity.

BACKGROUND: Sclerosing stromal tumor is an extremely rare type of benign ovarian sex cord stromal tumor. CASE: The benign characteristic of this tumor is well known but we present an uncommon case of paraovarian sclerosing stromal tumor with high mitotic activity. RESULTS AND CONCLUSION: Despite this potential malignancy, our patient was treated successfully with enucleation only.

The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma.

BACKGROUND: There are a few published studies about prognostic markers of Epstein-B virus (EBV) related to outcomes in pediatric Hodgkin Lymphoma (HL). OBJECTIVES: We aimed to investigate the prognostic value and effect of EBV on survival by using biopsy materials in children and adolescents diagnosed with HL. PATIENTS AND METHODS: EBV LMP-1 expression was examined using immunohistochemical methods in 58 tumor samples. Clinical features, overall survival (OS) and failure free survival time (FFS) were compared between EBV LMP-1 positive and negative patients. RESULTS: In 20 (35%) patients tumors were LMP-1 positive. When compared with patients above 10 years old, EBV LMP-1 was often positive in patients under 10 years old (30% vs. 70%, P = 0.02). In our most cases having B symptoms and advanced stage, EBV positiveness in Hodgkin Reed-Stenberg cells (H-RS) was not a significant determinant for survival (P = 0.78). Half of the past clinical trials in childhood HL reported longer survival rates in EBV LMP-1 positive patients. In some trials similar to our results there was no significant relationship between EBV and prognosis. CONCLUSIONS: The reason of diminished EBV positiviness may be related to technical methods such as not using immunohistochemical and in situ hybridization for EBER antigen but in laboratory conditions painting of control tissues with EBV impair this probability. In addition, cases enrolled to our study were living in Istanbul where social and economical factors are improved rather than generally.

Two Case Presentations Infected by Trichosporon asahii and Treated with Voriconazole Successfully.

Background. Trichosporon asahii is an opportunistic fungus that causes infections in immunosuppressed patients. Neutropenia developing due to malignancies is an important risk factor for fungal infection. Case Report. We present two pediatric oncology cases successfully treated with voriconazole after T. asahii infection that is known to cause fatal sepsis and invasive fungal infection. Conclusion. There is no conclusive evidence that the antifungal agent voriconazole is effective in the neutropenic patients infected with Trichosporon asahii. Liposomal amphotericin B has also been reported to be inadequate for treatment. We believe that our patients were successfully treated and survived because the antifungal agents were started early and properly, although the infection can be fatal in up to 80% of cases despite treatment.

Successful Treatment of Macroglossia Due to Lymphatic Malformation With Sirolimus.

OBJECTIVE: To evaluate the effectiveness and safety of sirolimus therapy in a child with macroglossia due to lymphatic malformation. METHODS: Sirolimus treatment was applied to the patient with an initial dosing of 0.8 mg/m2 per dose, administered orally, twice daily at approximately 12-hour intervals. RESULTS: After 9 months of sirolimus therapy, there was a nearly complete resolution of lymphatic malformation. The last evaluation was performed 6 months after withdrawal of treatment, and the lesion had almost completely resolved. CONCLUSION: This article presents a novel approach to the treatment of lymphatic malformation of the tongue using sirolimus, which appears to be safe and effective for the management of complex cases.