Thirteen-year long-term follow-up in a rare case of anaplastic astroblastoma: What makes the difference?

Background: Astroblastomas are uncommon neuroepithelial tumors of the central nervous system with a distinct, yet, controversial radiological, histological, and molecular profile. Debatable differences between low- and high-grade astroblastoma have been reported in the medical literature; indeed, despite the increasing relevance of molecular genetic profiling in the realm of astroblastoma, its application is still in its early stages. As a result, the diagnostic criteria for astroblastoma remain undecided with yet no real consensus on the most ideal management. Case Description: This report describes a case of astroblastoma diagnosed 13 years ago in a young woman who despite six episodes of recurrence, transformation, and progression was able to retain a perfomace status of 0 by World Health Organization standard, throughout. Conclusion: This report discusses the clinical, radiological, histological features, and management of this rare tumor with an extraordinarily long survival, with an aim to strengthen the literature on management options. To the best of our knowledge, this is the longest surviving case of anaplastic astroblastoma reported in the available medical literature.

An unusual case of ectopic prostate tissue in an intradural lipoma of the conus medullaris.

We report the first case of ectopic prostate tissue in a lipoma of the spine. Ectopic prostate tissue is well documented at a number of sites within the human body. Ectopic prostate tissue has previously been reported in the spine but usually in the context of spinal teratomas. This case is unique in that this is the first description of the presence of benign prostatic tissue in a lipoma of the conus medullaris. This is a highly unusual finding and probably reflects divergent differentiation or a malformative process.

Cardiac stereotactic ablative radiotherapy for control of refractory ventricular tachycardia: initial UK multicentre experience.

BACKGROUND: Options for patients with ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or catheter ablation remain limited. Stereotactic radiotherapy has been described as a novel treatment option. METHODS: Seven patients with recurrent refractory VT, deemed high risk for either first time or redo invasive catheter ablation, were treated across three UK centres with non-invasive cardiac stereotactic ablative radiotherapy (SABR). Prior catheter ablation data and non-invasive mapping were combined with cross-sectional imaging to generate radiotherapy plans with aim to deliver a single 25 Gy treatment. Shared planning and treatment guidelines and prospective peer review were used. RESULTS: Acute suppression of VT was seen in all seven patients. For five patients with at least 6 months follow-up, overall reduction in VT burden was 85%. No high-grade radiotherapy treatment-related side effects were documented. Three deaths (two early, one late) occurred due to heart failure. CONCLUSIONS: Cardiac SABR showed reasonable VT suppression in a high-risk population where conventional treatment had failed.

Recurrence of fourth ventricular choroid plexus papilloma with late occurrence of a spinal drop metastasis.

Choroid plexus papillomas are rare tumours, which occasionally spread both intracranially and down the spinal canal. Spinal metastasis has been reported infrequently and only once many years since the initial diagnosis. This is the first reported case of late recurrence, metastasis and transformation of a benign to an atypical lesion.

Product-line extensions and pricing strategies of brand-name drugs facing patent expiration.

OBJECTIVE: This study proposed an alternative to brand loyalty as the explanation for the continued price rigidity of patent-expired brand-name prescription drugs despite the increase in market entry of generic drugs facilitated by the 1984 Drug Price Competition and Patent Term Restoration Act. Study hypotheses were to test (1) whether market entries of new-product extensions are associated with market success of original brand-name drugs before generic drug entry, and (2) whether original brand-name drugs exhibit price rigidity to generic entry only when they are extended. METHODS: The design is a retrospective follow-up study for the prescription drug brands that lost their patents between 1987 and 1992. The drug brands were limited to nonantibiotic, orally administered drugs containing only 1 active pharmaceutical ingredient. Information on patent expiration, entry of a product extension, and market success were determined from the U.S. Food and Drug Administration.s Orange Book, First DataBank, and American Druggist, respectively. Market success was defined as whether an original drug brand was listed in the top 100 prescriptions most frequently dispensed before facing generic entry. Product-line extension was defined as the appearance of another product that a company introduces within the same market after its existing product. Drug prices were average wholesale prices from the Drug Topics Red Book. The relationship between product-line extension and market success was examined using a logistic regression analysis. The price rigidity to entry was tested using a panel regression analysis. RESULTS: A total of 27 drug brands lost their patents between 1987 and 1992. Drug brands that achieved market success were 16 times more likely to be extended than were those that did not (OR=16, 95% confidence interval, 2.12-120.65). The price rigidity to entry existed in drug brands with extensions (beta=2.65%, P <0.033), but not in those brands without extensions (beta=-2.40%, P <0.001). CONCLUSION: This study provided some support for the alternative explanation to brand loyalty that a new product-line extension introduced for an original brand helps the original price be rigid despite the entry of generic drugs facilitated by the 1984 Drug Price Competition and Patent Term Restoration Act.

Abscess formation within a Rathke's cleft cyst.

We report and discuss the rare case of a pituitary abscess forming within a Rathke's cleft cyst (RCC). A 66-year-old gentleman presented with visual deterioration and symptoms suggestive of hypopituitarism. The patient underwent transsphenoidal debulking of the lesion whereupon purulent material was discovered. Histological examination was suggestive of RCC together with numerous neutrophils characteristic of abscess. Microbiological culture of the material grew Staphylococcus aureus. The patient was treated for a RCC abscess and received antibiotics and endocrine replacement therapy. The patient has been followed up for 2 years without recurrence. Although uncommon, we recommend the consideration of RCC abscess as a differential diagnosis of a pituitary mass lesion as clinical presentation and radiological assessment are not specific in identifying these lesions preoperatively.

Expression of the endoplasmic reticulum oxidoreductase Ero1α in gastro-intestinal cancer reveals a link between homocysteine and oxidative protein folding.

AIM: Ero proteins are central to oxidative protein folding in the endoplasmic reticulum (ER), but their expression varies in a tissue-specific manner. The aim of this work was to establish the expression of Ero1α in the digestive system and to examine the behavior of Ero1α in premalignant Barrett's esophagus, esophageal (OE) and gastric cancers and esophageal cancer cell lines. RESULTS: Ero1α is expressed in the columnar epithelium of Barrett's tissue, and in OE tumors and gastric tumors. Homocysteine, a precursor in the metabolism of cysteine and methionine, induces the active Ox1 form of Ero1α in the OE cancer cell line OE33. INNOVATION: These results demonstrate for the first time that Ero1α can sense the level of an amino acid precursor, identifying a potential link between diet, antioxidants, and oxidative protein folding in the ER. CONCLUSION: The high expression of Ero1α in cancers of the esophagus and stomach demonstrates the importance of ER redox regulation in the gastro-intestinal (GI) tract in health and disease. Proteins and metabolites involved in disulfide bond formation and redox regulation may be suitable targets for both biomarker and drug development in GI cancer.

Tissue-specific expression and dimerization of the endoplasmic reticulum oxidoreductase Ero1beta.

Endoplasmic reticulum oxidoreductases (Eros) are essential for the formation of disulfide bonds. Understanding disulfide bond catalysis in mammals is important because of the involvement of protein misfolding in conditions such as diabetes, arthritis, cancer, and aging. Mammals express two related Ero proteins, Ero1alpha and Ero1beta. Ero1beta is incompletely characterized but is of physiological interest because it is induced by the unfolded protein response. Here, we show that Ero1beta can form homodimers and mixed heterodimers with Ero1alpha, in addition to Ero-PDI dimers. Ero-Ero dimers require the Ero active site, occur in vivo, and can be modeled onto the Ero1p crystal structure. Our data indicate that the Ero1beta protein is constitutively strongly expressed in the stomach and the pancreas, but in a cell-specific fashion. In the stomach, selective expression of Ero1beta occurs in the enzyme-producing chief cells. In pancreatic islets, Ero1beta expression is high, but is inversely correlated with PDI and PDIp levels, demonstrating that cell-specific differences exist in the regulation of oxidative protein folding in vivo.