Objective To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA). Methods

PurposeNeuroendocrine tumours (NET) are a heterogeneous group of neoplasms of diffuse neuroendocrine cells. Surgery is the main aim in the treatment of NETs, which becomes impossible in the case of large tumours or infiltration into other tissues and/or important blood vessels. Neoadjuvant therapy might be helpful in decreasing NET size also, leading us to the point where a tumour, previously considered inoperable, becomes operable. The aim of the study was to assess the usage of peptide receptor radionuclide therapy (PRRT) as a neoadjuvant treatment, enabling surgical intervention in primary inoperable NET.MethodsAmong 47 patients treated with PRRT, 6 patients were chosen with large, inoperable tumours, for whom enabling of complete surgical excision of the lesions might offer the prospect for a cure. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST).ResultsThe mean tumour size decreased from 6.9 (min. 3.1 cm, max. 9.6 cm) before therapy to 5.4 cm (min. 3.1 cm, max. 9.5 cm) after the treatment. According to RECIST, stabilization of the disease was observed in four and partial responses in two patients. In two patients, reduction of the tumour size enabled surgical intervention.Conclusion(1) PRRT might be considered a neoadjuvant therapy in primary inoperable NETs. (2) According to RECIST, stabilization of the disease was observed in the majority of patients. (3) We suggest that not only tumour diameter changes, but also tumour volume and contrast enhancement changes in computed tomography should be taken into consideration in assessment of the response to the therapy. (4) Somatostatin receptor scintigraphy is an important tool for qualification of the radioisotope therapy and also for the assessment of the response to PRRT.

We present a rectangle-based segmentation algorithm that sets up a graph and performs a graph cut to separate an object from the background. However, graph-based algorithms distribute the graph's nodes uniformly and equidistantly on the image. Then, a smoothness term is added to force the cut to prefer a particular shape. This strategy does not allow the cut to prefer a certain structure, especially when areas of the object are indistinguishable from the background. We solve this problem by referring to a rectangle shape of the object when sampling the graph nodes, i.e., the nodes are distributed non-uniformly and non-equidistantly on the image. This strategy can be useful, when areas of the object are indistinguishable from the background. For evaluation, we focus on vertebrae images from Magnetic Resonance Imaging (MRI) datasets to support the time consuming manual slice-by-slice segmentation performed by physicians. The ground truth of the vertebrae boundaries were manually extracted by two clinical experts (neurological surgeons) with several years of experience in spine surgery and afterwards compared with the automatic segmentation results of the proposed scheme yielding an average Dice Similarity Coefficient (DSC) of 90.97±2.2%.

Sphingosine-1-phosphate (S1P), the corresponding kinases SphK1-2, and receptors S1P1-3 and S1P5 are involved in cell survival and growth. Pathway components are overexpressed in many tumors including glioblastoma. Previous studies showed that the expression of SphK1 influenced survival of glioblastoma patients, yet the roles of SphK1-2 and receptors S1P1-3 and S1P5 have not been investigated in different forms of glioblastoma. Samples from 59 patients (37 males, 22 females, age 55.1 ± 17.1 years) suffering from primary (n = 35), recurrent (n = 18), and secondary (n = 6) glioblastomas were analyzed using quantitative real-time PCR and immunohistochemistry for expression levels of SphK1 and SphK2 and S1P1-3 and S1P5. Sixteen autopsy nontumorous brain specimens were used as controls. Expression data was correlated with clinical data and patient survival. All markers were overexpressed in the glioblastoma specimens compared to the non-neoplastic brain tissue. SphK1 and all S1P receptors were expressed in increasing order of magnitude from primary, up to recurrent and secondary glioblastomas, with values of up to 44-fold compared to normal brain tissue. In contrast, SphK2 levels were highest in primary tumors (25-fold). Expression of the sphingosine signaling pathway components was influenced by radio/radiochemotherapy in distinct ways. Immunohistochemistry for SphK1 and S1P1 confirmed the overexpression in glioblastoma. Uni- and multivariate survival analyses identified S1P5 messenger RNA levels as an independent prognostic factor of survival. The sphingosine pathway is overexpressed in glioma. Its components show distinct expression patterns in the tumor subgroups. S1P5 is identified as an independent prognostic factor in multivariate analysis, and this pathway promises to be a candidate for targeted therapies.

What are the novel findings of this work? This is the largest follow-up study to date evaluating the postnatal mortality and 30-month outcome of children who underwent fully percutaneous fetoscopic repair of myelomeningocele (MMC). What are the clinical implications of this work? Intrauterine repair of MMC by percutaneous fetoscopy, and via hysterotomy, result in a remarkably good outcome concerning mortality, prematurity, shunt-placement rates, motor and mental development and free ambulation, when compared to postnatal repair.

Introduction One of the concepts of theranostics in nuclear medicine is peptide receptor radionuclide therapy (PRRT), whereby labeled somatostatin analogs are used for imaging and treating inoperable or disseminated neuroendocrine tumors (NET). Aim The aim of the study was to determine the therapeutic efficacy and toxicity of tandem 90 Y / 177 Lu-DOTATATE in patients with disseminated NET in a multicenter trial. Materials and methods 103 patients with NET G1/G2 treated with 90 Y/ 177 Lu-DOTATATE (1:1) with amino-acid infusion for nephroprotection were included in the study. Results Overall survival from the disease diagnosis (OS-D) was 127.4 months and from the time of PRRT (OS-T) was 89.5 months. Progression-free survival (PFS) was 29.9 months. An analysis based on the proliferation index revealed a statistically significant impact on PFS and OS-T (PFS G1 vs G2, 59.3 vs 24.3 months; OS-T G1 vs G2, not reached vs 79.9 months). The effect of the primary disease site was also analyzed. For pancreatic vs small bowel vs large bowel, the PFS was 30.8 vs 30.3 vs 40.6 months, the OS-T was 94 vs 61.9 vs 131.2 months and OS-D was 130.4 vs 89.2 vs not reached months, respectively. The 2-year risk of progression was 42%. The probability of 2-year and 5-year overall survival was 89% and 62%, respectively. PRRT was well tolerated by all patients. One patient (1%) developed myelodysplastic syndrome. No other grade 3 and 4 hematological or renal toxicity was observed. Conclusions This multicenter trial showed that tandem 90 Y/ 177 Lu-DOTATATE is highly effective and safe therapy for patients with disseminated NET.

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Neuroendocrine tumors (NETs, originally termed “carcinoids”) create a relatively rare group of neoplasms with an approximate incidence rate of 2.5 to 5 cases per 100 000 persons. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome (CS), and 20% to 50% of subjects with CS are diagnosed with carcinoid heart disease (CaHD). The long-standing exposure to high serum serotonin concentration is one of the crucial factors in CaHD development. White plaque-like deposits on the endocardial surface of heart structures with valve leaflets and subvalvular apparatus thickening (fused and shortened chordae; thickened papillary muscles) are characteristic for CaHD. NT pro-BNP and 5-hydroxyindoleacetic acid are the 2 most useful screening markers. Long-acting somatostatin analogs are the standard of care in symptoms control. They are also the first-line treatment for tumor control in subjects with a metastatic somatostatin receptor avid disease. In cases refractory to somatostatin analogs, several options are available. We can increase a somatostatin analog to off-label doses, add telotristat ethyl or administer peptide receptor radionuclide therapy. Cardiac surgery, which mainly involves valve replacement, is presently the most efficient strategy in subjects with advanced CaHD and can relieve unmanageable symptoms or be partly responsible for better prognosis.