Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND: Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE: In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS: Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION: Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.

Pediatric oncologists' perspectives on the use of complementary medicine in pediatric cancer patients in Switzerland: A national survey-based cross-sectional study.

BACKGROUND: There is a widespread use of complementary therapies among pediatric cancer patients. Previous studies provided evidence that communication between pediatric oncologists (POs) and patients/families about the use of these therapies is often incomplete. Furthermore, nationwide studies on this topic are rare. AIMS: We assessed POs' perspectives on the use of complementary medicine (CM) in Switzerland, on the basis of an edited survey previously used in a nationwide study. METHODS AND RESULTS: A link to an online survey was sent by e-mail to each of the fifty-two eligible pediatric oncologists in all nine Swiss Pediatric Oncology Group (SPOG) centers. Eligible respondents were board-certified (Switzerland or abroad) POs currently working at a SPOG center. The survey was available for a total period of 2 months. We received 29 filled questionnaires (overall response rate: 56%). Most POs (59%) indicated that they ask more than 50% of their patients about CM use. Frequent reasons for not asking about the use of CM were i) forgetting to ask (55%), ii) lack of knowledge on the subject (31%), and iii) lack of time (24%). More than every second PO (55%) reported having a lack of knowledge on the subject. A majority of POs (66% to 76%) indicated interest in learning more about specific CM topics (cannabinoids, hypnosis and relaxation, music therapy, herbal medicine, acupuncture, meditation, and yoga). More information and specific training opportunities on the use of CM was deemed important by 76% to 97% of POs. CONCLUSION: POs working in Switzerland identify complementary therapies as an important subject. Swiss POs are willing to acquire more knowledge on CM. More training seems to be necessary in order to increase awareness about the topic, to enhance communication about complementary therapies and thus to improve patient care.

Myoepithelial Carcinoma of Soft Tissue With an EWSR1-KLF15 Gene Fusion in an Infant.

Overall, neonatal cancer is uncommon. Because of its rarity and heterogeneity, diagnosis can be challenging. We report a unique case of a myoepithelial carcinoma in a 7 week old girl. Molecular diagnostic workup revealed a EWSR1-KLF15 gene fusion which was previously described in only six cases of myoepithelial tumors so far. All cases occurred in children and adolescents. To our knowledge, this is the first report of a congenital EWSR1-KLF15 fusion positive myoepithelial tumor in an infant.

Local Stage Dependent Necessity of Radiation Therapy in Rhabdoid Tumors of the Kidney (RTK).

PURPOSE: Rhabdoid tumor of the kidney (RTK) is one of the most aggressive childhood renal tumors. Overall survival ranges from 22% to 47%. The indication for radiation therapy (RT) in usually very young patients is an ongoing discussion. Recent protocols recommend RT independent of local stage, the latter being a good discriminator in other childhood kidney tumors. In this study, we analyze the evidence for RT in regard to risk factors, including tumor stage. METHODS AND MATERIALS: This study analyzed 58 patients with RTK from Austria, Switzerland, and Germany treated in the framework of 4 consecutive, prospective renal/rhabdoid tumor studies from 1991 to 2014. All treatment protocols included multimodality treatment, including high-intensity chemotherapy, surgery, and RT. RESULTS: Local stage distribution was not applicable, I, II, and III in 1, 6, 11, and 40, respectively. Twenty-nine (50%) patients had stage IV disease at diagnosis. Thirty-seven patients (64%) achieved complete remission, and 49% (18/37) relapsed. Thirty-four patients (60%) patients had progressive disease and died, 17 had local disease, 10 had combined disease, and 7 had distant disease; 2 treatment-related deaths were reported (3%). Twenty-one patients received RT during first-line treatment, 18 of them to all involved sites. Eight of the 34 cases of progressive disease occurred in irradiated patients. The local failure rate of treated patients with local stage II or III disease was 29% (6/18) in patients irradiated to all sites compared with 68% (15/22) in nonirradiated patients. One of 6 stage I patients received RT, and 1 patient experienced distant relapse (2-year progression-free and overall survival both 83% ± 15%). Progression-free survival for local stage II and III disease treated with RT, adjusted for early relapse or treatment abandonment, was 67% ± 11%, compared with 15% ± 7% without RT (P < .0001). CONCLUSION: The 68% local failure rate in nonirradiated patients underlines the importance of local treatment. Our experience supports the use of RT for local control in higher stage disease. In contrast, no local relapse in 6 local stage I patients, including 5 nonirradiated patients, suggests omission of RT in this favorable subset of usually infant patients with RTK.

Denosumab as a Treatment Alternative for Central Giant Cell Granuloma: A Long-Term Retrospective Cohort Study.

PURPOSE: Giant cell granuloma (GCG) of the jaw is a rare disease with high morbidity. Various treatment options have been discussed in the past. Since 2010, a pharmaceutical therapy with denosumab seems to have been successful for giant cell tumors of the femur. The authors hypothesized the equally successful use of denosumab for GCGs of the jaws. MATERIALS AND METHODS: In the present retrospective cohort study, 5 patients with large GCGs of the jaws were treated with denosumab with a follow-up of 25 to 49 months. Frequent clinical follow-ups and a radiologic follow-up were performed and systematically analyzed. RESULTS: All patients showed a curative treatment response and complete metabolic resolution of the GCGs under treatment with denosumab. CONCLUSION: A brief review of the relevant literature and a detailed evaluation of current cases led to the conclusion that denosumab therapy should be considered a therapeutic option for large central GCGs of the jaws. The results of this study suggest denosumab is a successful treatment option. A treatment length no shorter than 12 months is recommended and monitoring of treatment response can be well managed by positron-emission tomographic computed tomography or magnetic resonance imaging.

Port-a-cath-related thrombosis and postthrombotic syndrome in pediatric oncology patients.

OBJECTIVE: To investigate Port-A-Cath (PAC)-related thrombosis and postthrombotic syndrome (PTS) in children with cancer. STUDY DESIGN: The study population was a consecutive cohort of children diagnosed with cancer and a PAC implanted at diagnosis. Children were evaluated for the presence of PAC-related thrombosis by magnetic resonance venography and the presence of congenital prothrombotic risk factors and PTS. RESULTS: A total of 114 children (median age, 6.04 years) were included. Of these children, 48 (42%) were treated for solid tumors and 66 (58%) were treated for hematopoietic tumors, including 38 for acute lymphoblastic leukemia. At the time of magnetic resonance venography, 42 children (37%) had the PAC still in place, and 72 (63%) had the PAC removed. Overall, PACs were in place for a total of 324.92 PAC-years. PAC-related thrombosis was detected in 45 children (39.5%) with a current or previous PAC. Of these, 21 (47%) had a solid tumor, 14 (31%) had acute lymphoblastic leukemia, and 10 (22%) had another hematopoietic tumor. Younger age at diagnosis, female sex, duration of PAC use, and left-side PAC placement were independently associated with an increased risk of thrombosis, whereas asparaginase therapy and the presence of inherited prothrombotic risk factors were not. Mild PTS (ie, presence of prominent collateral vessels in the skin) was present in 5.6% of the children. CONCLUSION: PAC-related thrombosis is common in pediatric oncology patients. In some children, thrombotic complications can lead to the development of PTS.

Refinement of the critical region for MCKD1 by detection of transcontinental haplotype sharing.

BACKGROUND: Autosomal-dominant medullary cystic kidney disease type 1 (MCKD1) [OMIM 174000] is a hereditary nephropathy that leads to renal salt wasting and end-stage renal failure at a median age of 62 years. In a Welsh MCKD1 kindred we have recently demonstrated linkage to the MCKD1 locus on chromosome 1q23.1 and refined the critical MCKD1 region to <3.3 Mb. METHODS: In order to refine the candidate gene region for MCKD1, high-resolution haplotype analysis in three large kindreds with MCKD1 was performed. RESULTS: We report here on high-resolution haplotype analysis in this Welsh kindred, as well as in the Arizona kindred, which was used for the first definition of MCKD as a disease entity, and in a kindred from the Dutch/German border. We detected extensive haplotype sharing among all affected individuals of all three kindreds. Scrutinization of the genealogy of the Arizona kindred revealed an origin from Germany in the 17th century, thereby providing historical data for haplotype sharing by descent at the MCKD1 locus. CONCLUSION: Under the hypothesis of haplotype sharing by descent, we refined the critical genetic interval to <650 kb, thus enabling candidate gene analysis.

Familial juvenile hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease type 2: two facets of the same disease?

Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder heralded by hyperuricemia during childhood; it is characterized by chronic interstitial nephritis, with marked thickening of tubular basement membranes, and leads to progressive renal failure during adulthood. A gene for FJHN in two Czech families was recently mapped to chromosome 16p11.2, close to the MCKD2 locus, which is responsible for a variant of autosomal dominant medullary cystic kidney disease observed in an Italian family. In a large Belgian family with FJHN, a tight linkage between the disorder and the marker D16S3060, located within the MCKD2 locus on chromosome 16p12 (maximal two-point logarithmic odds score of 3.74 at a recombination fraction of theta = 0), was observed in this study. The candidate region was further narrowed to a 1.3-Mb interval between D16S501 and D16S3036. Together with the striking clinical and pathologic resemblance between previously reported medullary cystic kidney disease type 2 and FJHN occurring in the Belgian family (including the presence of medullary cysts), this study suggests that these two disorders are facets of the same disease.