Epidemiology and Characteristics of Gastric Carcinoma in Childhood-An Analysis of Data from Population-Based and Clinical Cancer Registries.

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz−Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments.

Immune-mediated thrombotic thrombocytopenic purpura in a Jehovah's Witness - Effectiveness of incorporating extracorporeal immunoadsorption to caplacizumab, steroids and rituximab.

We report the case of a Jehovah's Witness adolescent patient with immune-mediated thrombotic thrombocytopenic purpura after SARS-Cov2 infection successfully treated without therapeutic plasma exchange (TPE) using caplacizumab, corticosteroids, rituximab, and extracorporeal immunoadsorption (EIA). Further patients for whom TPE is not an option might benefit from this approach.

Daratumumab therapy for post-HSCT immune-mediated cytopenia: experiences from two pediatric cases and review of literature.

BACKGROUND: Immune-mediated cytopenias (AIC) are challenging complications following allogeneic hematopoietic stem cell transplantation (HSCT). While broad-acting immunosuppressive agents like corticosteroids are often standard of care, several novel therapies which target specific immunological pathways have recently been developed and provide hope for patients with steroid-refractory courses and may limit long-term toxicity. The successful off-label use of the plasma cell depleting anti-CD38 antibody daratumumab was published in several case reports, suggesting efficacy, i.e., in patients with antibody-mediated AIC refractory to previous B cell depletion. We want to share our experience with two children, whom we treated with daratumumab, including one fatal course with uncontrolled disease. Given the absence of substantial data from HSCT registries or prospective trials, we furthermore provide a critical review of the literature on daratumumab treatment of AIC. CASE PRESENTATIONS: Patient 1 (P1), an 11-year-old girl with lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency who developed immune-mediated thrombocytopenia (AIT) from day +58 after HSCT, showed a complete response to daratumumab after the fourth of six total daratumumab doses. She remains transfusion independent for over a year of follow-up. Previously, her thrombocytopenia was refractory to corticosteroids, rituximab, intravenous immunoglobulins (IVIG), eltrombopag, cyclosporine A, and sirolimus. Patient 2 (P2), a 6-year-old boy with CD40 ligand (CD40L) deficiency, developed both AIT and hemolytic anemia (AIHA) after HSCT on days +58 and +83, respectively, and was also treated with daratumumab after being previously refractory to prednisolone, rituximab, and IVIG. Yet, he did neither respond to daratumumab nor the concomitantly administered methyprednisolone pulse, plasmapheresis, and eculizumab and succumbed due to refractory disease. CONCLUSION: Reviewing the literature on the use of daratumumab for refractory AIC post-HSCT, we consider daratumumab a promising agent for this life-threatening disorder: ten of the twelve patients reached transfusion independency in the literature. However, treatment failures are likely to be underreported. Thus, controlled trials are needed to explore the safety and efficacy of daratumumab in this rare post-HSCT complication.

Practical Guidance of the GTH Haemophilia Board on the Use of Emicizumab in Patients with Haemophilia A.

Emicizumab has been approved for bleeding prophylaxis in patients with haemophilia A (PWHAs) with or without inhibitors. Because of substantial differences between factor VIII (FVIII) and Emicizumab, the 'Ständige Kommission Hämophilie' of the German, Austrian, Swiss Society for Thrombosis and Haemostasis Research (GTH) established a practical guidance for the use of Emicizumab in PWHAs. A systematic literature research was conducted in PubMed. Based on this and on personal experience, this practical guidance has been developed. Each single statement has been discussed among members of the 'Ständige Kommission Hämophilie' and revised accordingly. The final set of recommendations has been approved by all authors analogous to the Delphi method. This practical guidance is provided for physicians treating PWHAs with regard to general aspects, patient education, bleeding treatment, surgery, use of Emicizumab in previously untreated patients (PUPs), patients with newly diagnosed inhibitors and elderly patients. Patients should be treated in expert centres and adequate laboratory tests to monitor Emicizumab levels, FVIII replacement and inhibitors should be available. Early experience of immune tolerance induction protocols integrating Emicizumab is reviewed, and the limited experience in PUPs and very young children is described. So far, no thromboembolic complications have been reported with the concomitant use of FVIII or recombinant activated FVII for bleeding treatment or surgery. Activated prothrombin complex concentrate doses of >100 U/kg for >24 hours should be avoided whenever possible because of the high risk of thrombosis and/or thrombotic microangiopathy. In conclusion, this study is designed to support haemophilia physicians using Emicizumab in physicians treating hemophilia and using (PWHAs). With further post-marketing experience and trials, regular updates are necessary.

Health-Related Quality of Life, Treatment Satisfaction and Adherence Outcomes of Haemophilia Patients Living in a German Rural Region.

In the context of the 'Mobile Haemophilia Outpatient Care (MHOC)' project we aimed to gather insights into the health-related quality of life (HRQoL), treatment satisfaction (TS) and adherence of persons with haemophilia (PWHs) who get treated at the Saarland University Hospital Haemophilia Treatment Centre (HTC). PWHs were visited at home at least twice (baseline, follow-up) by trained medical staff. Individual interviews were performed to measure patients' HRQoL and TS with validated questionnaires (Haem-A-QoL/Haemo-QoL and Hemo-SatA/Hemo-SatP). Socio-demographic and clinical data were collected. In total, 79 PWHs were enrolled; 56 adults with a mean age of 37.4 ± 16.4 years (17-78) and 23 children [mean age of 9.8 ± 4.2 years (3-16)]. In total, 62% were severely affected; 48.1% received prophylaxis. Patients reported good HRQoL (adults: 23.1 ± 17.1; kids: 24.3 ± 11.1). Patients (M = 11.2 ± 9.5) and parents (M = 14.3 ± 7.4) were very satisfied with their provided treatment. The majority of study participants were evaluated to have a good treatment adherence. After 1-year follow-up of the MHOC, a significant improvement in HRQoL was seen in adults (p < 0.033) and in proxy ratings of parents (p < 0.0001); TS remained high with no change by MHOC intervention. Patients reported good HRQoL and TS. Most of them were evaluated as having a good treatment adherence. After implementation of the MHOC, adult patients reported a better HRQoL. Such a mobile medical care service is considered beneficial for patients, especially with limited access to a HTC.

Sickle cell disease in Germany: Results from a national registry.

BACKGROUND: Limited data on the prevalence and medical care of sickle cell disease (SCD) in Germany are available. Here, we make use of a patient registry to characterize the burden of disease and the treatment modalities for patients with SCD in Germany. PROCEDURE: A nationwide German registry for patients with SCD documents basic data on diagnosis and patient history retrospectively at the time of registration. A prospective annual documentation provides more details on complications and treatment of SCD. For the current analyses, data of 439 patients were available. RESULTS: Most patients had homozygous SCD (HbSS 75.1%, HbS/ß-thalassemia 13.2%, and HbSC 11.3%). The median age at diagnosis was 1.9 years (interquartile range, 0.6-4.4 years), most patients were diagnosed when characteristic symptoms occurred. Sepsis and stroke had affected 3.2% and 4.2% of patients, respectively. During the first year of observation, 48.3% of patients were admitted to a hospital and 10.1% required intensive care. Prophylactic penicillin was prescribed to 95.6% of patients with homozygous SCD or HbS/ß thalassemia below the age of six and hydroxycarbamide to 90.4% of patients above the age of two years. At least one annual transcranial Doppler ultrasound was documented for 74.8% of patients between 2 and 18 years. CONCLUSION: With an estimated number of at least 2000, the prevalence of SCD in Germany remains low. Prospectively, we expect that the quality of care for children with SCD will be further improved by an earlier diagnosis after the anticipated introduction of a newborn screening program for SCD.

Feasibility and Results of a Mobile Haemophilia Outpatient Care Pilot Project.

INTRODUCTION: Regular visits at haemophilia treatment centres (HTCs) in rural regions are often dependent on the access to a private car due to lack of or limited availability of public means. Therefore, a mobile haemophilia outpatient care (MHOC) concept providing home visits to haemophilia patients has been developed by the Saarland HTC, which is located in a rural German region. METHODS: Haemophilia patients and their parents were home visited at least twice (baseline, follow-up) by trained medical staff. Socio-demographic and clinical data were collected and interviews were performed asking the patients and parents about their needs and expectations towards such a MHOC. RESULTS: Seventy-nine patients were enrolled (56 adults, 23 children), 62.0% severely affected, 48.1% on prophylaxis, with a mean age of 37.4 ± 16.4 years (17-78) and 9.8 ± 4.2 years (3-16), respectively. Median travel distance to the HTC was 43.5 km (3-200). Note that 92.4% considered an intense binding to the HTC and a MHOC concept as 'rather/very important' (88.6%). They expected from a MHOC to provide consulting and educating activities, support in elderhood issues and treatment. For 35.4%, a MHOC could currently provide additional support, mainly due to patient's immobility and need of consultancy. They mainly used services in terms of consultancy in social-legal affairs and support in contacting authorities. CONCLUSION: The results of this study support the hypothesis that a MHOC concept is a needful supplement in haemophilia comprehensive care and will improve the challenging haemophilia treatment, especially for those with limited access to HTCs or with disabilities.

Gastrectomy with isoperistaltic jejunal parallel pouch in a 15-year-old adolescent boy with gastric adenocarcinoma and autosomal recessive agammaglobulinemia.

A 15-year-old adolescent boy with autosomal recessive agammaglobulinemia underwent endoscopy because of unexplained growth failure and malnutrition. Esophagogastroduodenoscopy revealed antropyloric stenosis, and a biopsy showed an invasive gastric adenocarcinoma. Chronic atrophic corpus gastritis type A and Helicobacter pylori were also identified. Abdominal magnetic resonance imaging confirmed the stenosis resulting from a semicircular intramural tumor without obvious local or distant metastatic spread. Gastrectomy with an extended lymphadenectomy was performed. Esophagoduodenal continuity was restored by an interposed jejunal parallel pouch developed from the first jejunal loop. Oral feeding was supplemented by parenteral nutrition via a Broviac catheter, and the patient is well 4 months later. Several cases of gastric cancer have been reported in children with hereditary agammaglobulinemia. Thus, endoscopy is mandatory in such patients with gastrointestinal symptoms to identify and treat tumors before metastasis occurs. Total gastrectomy, extended lymphadenectomy, and reconstruction using a jejunal reservoir with maintenance of duodenal continuity should be considered.

Chronic granulomatous disease (CGD) mimicking neoplasms: a suspected mediastinal teratoma unmasking as thymic granulomas due to X-linked CGD, and 2 related cases.

Patients with chronic granulomatous disease (CGD) suffer from severe bacterial and fungal infections and deregulated inflammation, which are often associated with granuloma formation. We describe a 2-year-old boy who was seemingly healthy at the age of 1 year when a conventional chest radiograph was taken to exclude pulmonary aspiration of a piece of apple. Incidentally, a space-occupying mediastinal mass was revealed that was further evaluated by magnetic resonance imaging. Varying solid and also cystic, septated parts of the mass could be discerned and it was considered to be a teratoma. Removal of the mass by surgery was arduous because of adhesiveness to surrounding areas and led to severe complications. Unexpectedly, histopathologic examination revealed massive acute granulomatous inflammation with liquefied thymic cysts. X-linked CGD was subsequently diagnosed by a dihydrorhodamine 123 assay and sequencing of the CYBB gene (hotspot mutation c.742-743insA). This is the third example that we are aware of, where CGD granulomas were mistaken for neoplasms. The other 2 patients were initially believed to have tumors of the stomach and the urinary bladder, respectively. All patients initially received inadequate treatment. We discuss possible strategies to avoid such tragic confusions.