Complications after medullary thyroid carcinoma surgery: multicentre study of the SQRTPA and EUROCRINE® databases.

BACKGROUND: Surgery is the curative therapy for patients with medullary thyroid carcinoma (MTC). In determining the extent of surgery, the risk of complications should be considered. The aim of this study was to assess procedure-specific outcomes and risk factors for complications after surgery for MTC. METHODS: Patients who underwent thyroid surgery for MTC were identified in two European prospective quality databases. Hypoparathyroidism was defined by treatment with calcium/active vitamin D. Recurrent laryngeal nerve (RLN) palsy was diagnosed on laryngoscopy. Complications were considered at least transient if present at last follow-up. Risk factors for at-least transient hypoparathyroidism and RLN palsy were identified by logistic regression analysis. RESULTS: A total of 650 patients underwent surgery in 69 centres at a median age of 56 years. Hypoparathyroidism, RLN palsy and bleeding requiring reoperation occurred in 170 (26·2 per cent), 62 (13·7 per cent) and 17 (2·6 per cent) respectively. Factors associated with hypoparathyroidism were central lymph node dissection (CLND) (odds ratio (OR) 2·20, 95 per cent c.i. 1·04 to 4·67), CLND plus unilateral lateral lymph node dissection (LLND) (OR 2·78, 1·20 to 6·43), CLND plus bilateral LLND (OR 2·83, 1·13 to 7·05) and four or more parathyroid glands observed (OR 4·18, 1·46 to 12·00). RLN palsy was associated with CLND plus LLND (OR 4·04, 1·12 to 14·58) and T4 tumours (OR 12·16, 4·46 to 33·18). After compartment-oriented lymph node dissection, N0 status was achieved in 248 of 537 patients (46·2 per cent). CONCLUSION: Complications after surgery for MTC are procedure-specific and may relate to the unavoidable consequences of radical dissection needed in some patients.

Surgery for multiple endocrine neoplasia type 1-related insulinoma: long-term outcomes in a large international cohort.

BACKGROUND: Insulinomas are found in 10-15 per cent of patients with multiple endocrine neoplasia type 1 (MEN1) and lead to life-threatening hypoglycaemia. Surgical outcome and the optimal surgical strategy for MEN1-related insulinoma are unknown. METHODS: Patients with MEN1-related insulinomas were identified in 46 centres in Europe and North America between 1990 and 2016. Insulinomas were considered localized if the lesion was in the pancreatic head or body/tail. Patients with pancreatic neuroendocrine tumours throughout the pancreas were suspected of having multifocal insulinoma. The primary outcome was postoperative hypoglycaemia, defined as persistent hypoglycaemia, or recurrent hypoglycaemia caused by a new insulinoma or insulin-producing liver metastases. Hypoglycaemia-free survival was estimated by the Kaplan-Meier method. RESULTS: Ninety-six patients underwent resection for MEN1-related insulinoma. Sixty-three and 33 patients had localized and multifocal insulinomas respectively. After a median follow-up of 8 (range 1-22) years, one patient (1 per cent) had persistent disease and six (6 per cent) had developed recurrent disease, of whom four had a new insulinoma. The 10-year hypoglycaemia-free survival rate was 91 (95 per cent c.i. 80 to 96) per cent. Of those with localized disease, 46 patients underwent pancreatic resection and 17 enucleation. One of these patients had persistent disease and one developed recurrent insulinoma. Among patients with multifocal disease, three developed new insulinomas and two developed insulin-producing liver metastases. CONCLUSION: Surgery for MEN1-related insulinoma is more successful than previously thought.

ANTECEDENTES: Del 10% al 15% de los pacientes con MEN1 presentan insulinomas que pueden desencadenar una hipoglucemia potencialmente mortal. Se desconoce el resultado de la cirugía y la estrategia quirúrgica óptima para el tratamiento del insulinoma relacionado con el MEN1. MÉTODOS: Se identificaron los pacientes con insulinomas relacionados con el MEN1 en 46 centros de Europa y América del Norte entre 1990 y 2016. Los insulinomas se consideraron localizados si el tumor se localizaba en la cabeza o en el cuerpo/cola del páncreas. Se sospechó la existencia de un insulinoma multifocal en los pacientes con tumores neuroendocrinos pancreáticos (pNETs). El objetivo primario de este estudio fue evaluar la hipoglucemia postoperatoria, definida como hipoglucemia persistente, hipoglucemia recidivante causada por un nuevo insulinoma o debida a metástasis hepáticas productoras de insulina. La supervivencia libre de hipoglucemia se estimó mediante el método de Kaplan-Meier. RESULTADOS: A 96 se les realizó una resección por insulinoma en el contexto del MEN1. Un total de 63 y 33 pacientes presentaron insulinomas localizados y multifocales, respectivamente. Después de una mediana de seguimiento de 7,8 años (rango 1-22), un paciente (1%) tenía enfermedad persistente y seis pacientes (6%) presentaron enfermedad recidivante, de los cuales cuatro desarrollaron un nuevo insulinoma. La supervivencia libre de hipoglucemia fue del 91% a los 10 años (i.c. del 95%, 80%-96%). De los pacientes con enfermedad localizada, 46 fueron sometidos a resección pancreática y 17 pacientes a enucleación. Entre éstos, un paciente tenía enfermedad persistente y uno desarrolló insulinoma recidivante, respectivamente. De los pacientes con enfermedad multifocal, tres desarrollaron nuevos insulinomas y dos desarrollaron metástasis hepáticas productoras de insulina. CONCLUSIÓN: La cirugía para el insulinoma en el contexto del MEN1 es más exitosa de lo que parecía en principio.

Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients.

The tenascin-X (TNX) deficient type Ehlers-Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX-deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross-sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non-sense mRNA mediated decay. In short, patients with the TNX-deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging.

NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield.

BACKGROUND: Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. OBJECTIVE: The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4, the main gene involved in isolated EL. METHODS: A NGS gene panel was analysed in 24 patients with EL. RESULTS: A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. CONCLUSION: The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1. With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition.

Reversible switching of the sol-gel transition with ultrasound in rhodium(I) and iridium(I) coordination networks.

Reversible coordination networks were prepared by combining diphenylphosphinite telechelic polytetrahydrofuran (2) with [RhCl(COD)]2 or [IrCl(COD)]2 in chloroform. Both systems resulted in stable gels at concentrations above 50 and 30 g/L for the rhodium(I) and iridium(I) networks, respectively. The rheological properties of the two coordination networks (100 g/L) were determined with oscillatory shear experiments, which showed that the elastic moduli are constant over a wide frequency range, indicating gel-like behavior; the iridium(I) gel has an elastic modulus distinctly higher (2.8x10(3) Pa) than that of the rhodium(I) gel (1.0x10(3) Pa). Ultrasonication of the rhodium(I) gel caused liquefaction after 3 min; regelation occurred 1 min after sonication was stopped. The iridium(I) gel was also liquefied after 3 min of sonication, but regelation took 1.5 h at room temperature and more than 10 days at -20 degrees C. 31P NMR measurements on model complexes showed that the large differences in gelation times are in agreement with the ligand exchange kinetics of the rhodium(I) and iridium(I) complexes. We propose that sonication of the gels results in ligand exchange, which changes the network topology without changing the coordination chemistry. Upon sonication, the fraction of metal centers in active cross-links decreases and thereby reduces the gel fraction to zero. The system is not at equilibrium, and upon standing the gel fraction increases at a rate that is determined by the exchange kinetics of the metal complex. The observed effects offer opportunities to use ultrasound in the activation of dormant transition metal catalysts.

Dendrimer-based transient supramolecular networks.

Association of a 16-fold excess of a monodisperse telechelic oligo(THF) (Mw = 1270 g/mol) containing two end groups that selectively bind to the 32 binding sites of a fifth generation dendritic host (Mw = 18,511 g/mol and radius R(h) = 2.4 nm) results in the formation of reversible and dynamic supramolecular complexes. The structure of these complexes in solution depends strongly on the concentration. At low concentration, the two end groups of one guest are proposed to complex to the same host, and flowerlike structures are formed with a radius of R(h) = 3.7 nm. At higher concentrations, both end groups of one guest are complexed to different hosts, forming a bridge between them. This gives rise to the formation of larger associates, and eventually to a transient supramolecular network. Dynamic light scattering unequivocally showed that three distinct relaxation processes, associated with the proposed structures, are present in this system. In addition to the dynamics related to the flowerlike (fast) and the transient network structures (slow), an intermediate dynamic process is attributed to the cooperative motion of a few (approximately 6) connected flowerlike structures. Rheological data elucidate the nature of the intermittent network responsible for the slowest process. A monofunctional guest, not capable of forming a network structure, was used as a reference, and starlike supramolecular structures are formed at all concentrations, indeed.