Background: The use of capecitabine has risen exponentially in the Netherlands since 2001. Clinical trials describe a mild toxicity profile. Because circumstances in daily clinical practice can differ a lot from clinical trial setting, we performed this retrospective analysis in a large community hospital to verify toxicity in a clinical situation. Methods: A retrospective cohort study was conducted in patients with malignancies of the gastrointestinal tract or breast treated with capecitabine in the period of January 2007 to January 2009. Primary study endpoint was the incidence and severity of capecitabine-induced toxicity in daily clinical practice. Secondary endpoint concerned determination of risk factors for toxicity due to capecitabine. Results: Of 281 patients 92% experienced some degree of toxicity. Grade 3-4 toxicity occurred in 30% of patients receiving monotherapy and in 47% with combination therapy. This was in accordance with the literature. Type of toxicity varied, but gastro intestinal symptoms and hand foot syndrome were most commonly found. Risk of toxicity increased with increasing age, independently of creatinine clearance. Conclusions: Therapy with capecitabine monotherapy or capecitabine containing regiments in daily clinical practice is accompanied by considerable toxicity, but frequency and severity are consistent with published clinical trials. More toxicity can be expected with increasing age.

IntroductionGrowth hormone is secreted by the pituitary gland, which forms part of the craniofacial midline. IRF6 encodes a transcription factor involved in the development of the craniofacial midline and mutations in IRF6 are known to disturb craniofacial development. Craniofacial and pituitary development are closely related. After whole exome sequencing revealed a new mutation in IRF6 in a family with Idiopathic Growth Hormone Deficiency (IGHD), we screened the remainder of our IGHD cohort for mutations in this gene and related their genotypes to pituitary and craniofacial morphology.Materials and methodsWe sequenced all coding exons and exon–intron boundaries of IRF6 in 81 patients with IGHD. We performed a multiplex ligation-dependent probe amplification (MLPA) in order to exclude copy number variations in IRF6. We analyzed facial measurements taken from standardized digital pictures of 48 patients.ResultsWe found two new variants and eleven polymorphisms. Apart from the new mutation found in the index family (p.Arg233Cys), we found one other new heterozygous missense mutation in IRF6 (Pro456Ser). p.Arg233Cys was reported as extremely rare in exome databases (1 allele out of 120.852 alleles sequenced), strictly conserved among species and was predicted deleterious by all variant predictor programs. Pro456Ser was predicted to be benign. MLPA did not reveal any exon deletions or duplications in any of the patients.ConclusionThis is the first report of IRF6 analysis in an IGHD cohort. We found one new mutation which, based on in silico analysis, could be of functional relevance. However, we did not find any mutations in the other patients. Therefore, we conclude that IRF6 defects are rare in IGHD patients and further research should focus on new candidate genes.Electronic supplementary materialThe online version of this article (doi:10.1007/s11102-017-0808-8) contains supplementary material, which is available to authorized users.

CI, measured on digital pictures, is associated with ectopia of the posterior pituitary and this might be caused by an altered midline development, affecting both the pituitary and the facial structures of GHD patients.

Introduction: Transition from paediatric to adult endocrinology can be challenging for adolescents, their families and healthcare professionals. Previous studies have shown that up to 25% of young adults with endocrine disorders are lost to follow-up after moving out of paediatric care. This poses a health risk for young adults, which can lead to serious and expensive medical acute and long-term complications. Methods: In order to understand and prevent dropout, we studied electronic medical records (EMRs) of patients with endocrine disorders. These patients were over 15 years old when they attended the paediatric endocrine outpatient clinic (OPC) of our hospital in 2013-2014 and should have made the transfer to adult care (AC) at the time of the study. Results: Of 387 adolescents, 131 had an indication for adult follow up within our university hospital. Thirty-three (25%) were lost to follow up. In 24 of them (73%), the invitation for the adult OPC had never been sent. We describe the failures in logistic processes that eventually led to dropout in these patients. Conclusion: We found a 25% dropout during transfer from paediatric to adult tertiary endocrine care. Of all dropouts, 73% could be attributed to failure of logistic steps. In order to prevent these dropouts, we provide practical recommendations for patients, paediatric and adult endocrinologists.

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