High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). OBJECTIVES: To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. RESULTS: Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. CONCLUSIONS: In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

Biochemical and Clinical Features of Insulinoma in a Patient with Turner Syndrome.

Turner syndrome (TS), i.e., mosaic or nonmosaic states with only one normal X chromosome in females, is characterized by a wide spectrum of somatic, hormonal, and metabolic features. Here we report an unusual case of recurrent hypoglycemia in a 53-year-old woman with TS. Biochemical work-up following a 72h fast revealed detectable, inappropriate for low glucose insulin levels and elevated proinsulin and beta-hydroxybutyrate (BOHB) levels. MR and multiphase CT showed a solid 2.5 cm pancreatic tail mass with absent uptake in the 111In-pentetreotide (Octreoscan) scan. Subsequent hepatic vein blood sampling after intra-arterial calcium stimulation showed sharp increase in insulin and modest increase in proinsulin levels. The patient underwent excision of the mass with resolution of symptoms. Histopathologic examination confirmed the neuroendocrine etiology of the tumor. This is, to our knowledge, the third report of TS and concomitant insulinoma. Impaired counterregulatory response to hypoglycemia in patients with TS may result in symptomatic hypoglycemia with only mild insulin elevation and elevated proinsulin in setting of hypoglycemia may be the only indication of insulinoma in these patients. BOHB levels should not be used for ruling out EHH in patients with TS.

SPECT/CT bone scintigraphy to evaluate low back pain in young athletes: common and uncommon etiologies.

Low back pain of various etiologies is a common clinical presentation in young athletes. In this article, we discuss the utility of SPECT/CT bone scintigraphy for the evaluation of low back pain in young athletes. The spectrum of lower spine lesions caused by sports injuries and identifiable on bone scan is presented along with strategies to avoid unnecessary irradiation of young patients. Also covered are pitfalls in diagnosis due to referred-pain phenomenon and normal skeletal variants specific to this age group.

Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: A systematic review of the literature.

BACKGROUND: Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear. This review was conducted to assess the knowledge on placental aging related biochemical changes leading to placental dysfunction in PTB and/or preterm premature rupture of membranes (pPROM). METHODS: We performed a systematic review of studies published over the last 50 years in two electronic databases (Pubmed and Embase) on placental aging and PTB or pPROM. RESULTS: The search yielded 554 citations, 30 relevant studies were selected for full-text review and three were included in the review. Only one study reported oxidative stress-related aging and degenerative changes in human placental membranes and telomere length reduction in fetal cells as part of PTB and/or pPROM mechanisms. Similarly, two animal studies reported findings of decidual senescence and referred to PTB mechanisms. CONCLUSION: Placental and fetal membrane oxidative damage and telomere reduction are linked to premature aging in PTB and pPROM but the risk factors and biomolecular pathways causing this phenomenon are not established in the literature. However, no biomarkers or clinical indicators of premature aging as a pathology of PTB and pPROM have been reported. We document major knowledge gaps and propose several areas for future research to improve our understanding of premature aging linked to placental dysfunction.

A novel blood-based biomarker for detection of autism spectrum disorders.

Autism spectrum disorders (ASD) are classified as neurological developmental disorders. Several studies have been carried out to find a candidate biomarker linked to the development of these disorders, but up to date no reliable biomarker is available. Mass spectrometry techniques have been used for protein profiling of blood plasma of children with such disorders in order to identify proteins/peptides that may be used as biomarkers for detection of the disorders. Three differentially expressed peptides with mass-charge (m/z) values of 2020 ± 1, 1864 ± 1 and 1978 ± 1 Da in the heparin plasma of children with ASD that were significantly changed as compared with the peptide pattern of the non-ASD control group are reported here. This novel set of biomarkers allows for a reliable blood-based diagnostic tool that may be used in diagnosis and potentially, in prognosis of ASD.