Experimental and clinical aspects of laser destruction of adenohypophysis

Focal destruction of the adenohypophysis by Nd:YAG laser does not destroy other structures of the hypothalamo-pituitary region. During reparative regeneration, the focus of coagulation necrosis after laser destruction of the adenohypophysis is replaced by cicatricial tissue. A method for surgical treatment of pituitary adenomas was developed. The efficiency, safety, and low traumatism of this method were confirmed in 87 patients. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 113–116, July, 2000     

Consortium approach to identifying genes for Barrett's esophagus and esophageal adenocarcinoma

Consortium approaches are becoming increasingly more common for a variety of chronic diseases and conditions. The Familial Barrett's Esophagus Consortium began in 1998 and was originally designed to investigate the evidence for familial aggregation of Barrett's esophagus, esophageal adenocarcinoma, or esophagogastric junctional adenocarcinoma. The authors have shown that this phenotype does in fact aggregate in families; therefore, linkage analyses are currently underway. The Consortium, whose goals and membership are growing, has been successfully established and maintained. In this article, details about the research design and membership are provided, as are the current and future goals of the Consortium. The authors believe that this time is especially exciting for research in this area, and they look forward to answering more questions relevant to these diseases with regard to both genetic and environmental risk factors to ultimately design more effective treatment and prevention strategies.     

PTEN regulates phospholipase D and phospholipase C

PTEN is an ubiquitously expressed tumor suppressor which plays a prominent role in the pathogenesis of many types of sporadic solid tumors, including breast cancer, as well as hematologic malignancies. Germline PTEN mutations cause 85% of Cowden syndrome (CS), characterized by a high risk of breast and thyroid cancers, and 65% of Bannayan-Riley-Ruvalcaba syndrome (BRRS), characterized by lipomatosis, hemangiomas and speckled penis. Historically, PTEN's role in tumor suppression has been linked to the down-regulation of the PI3K/AKT pathway by PTEN's lipid phosphatase activity. Beyond the AKT pathway, however, there has been minimal examination of PTEN's responsibility in lipid-derived cellular signaling. As phospholipids have been shown to be critical components in signal transduction and cellular proliferation and PTEN controls cellular phospholipid levels, we hypothesized that PTEN functions as a regulator of lipid signaling and homeostasis. Increased PTEN expression in unstimulated MCF-7 breast cancer cells results in a 51% increase in phosphatidic acid, with a decrease in phosphatidylcholine, suggesting that PTEN may regulate phospholipase D (PLD). PTEN overexpression results in a 30% increase in basal PLD activity. As phospholipase C (PLC) is both involved in PLD activation and is regulated by PIP2/3 levels, we investigated the role of PTEN on PLC activation. Our data suggest that PTEN modulates PLC:PLD activation pathways and indicate that the pathogenesis of CS/BRRS has a more complex biochemical basis beyond simply activating the PI3K pathway. This provides alternative routes for PTEN's tumor suppressor action that may be beneficial in the creation of novel targets for cancer therapy and prevention.     

Airway obstruction and acute respiratory failure due to Aspergillus tracheobronchitis

OBJECTIVE: To report a patient with lymphoma who developed Aspergillus tracheobronchitis resulting in airway obstruction and acute respiratory failure. DESIGN: Case report. SETTING: Intensive care unit of a tertiary care hospital. PATIENT: A 22-yr-old female with lymphoma who developed a respiratory infection 3 months after completing immunosuppressive therapy. She was treated empirically with broad spectrum antibiotics and subsequently received a supplementary chemotherapeutic course. Soon afterward she developed severe respiratory failure. Chest radiograph showed atelectasis of the right upper and lower lobes. INTERVENTIONS: Emergent mechanical ventilation; fiberoptic bronchoscopy. MEASUREMENTS AND MAIN RESULTS: Fiberoptic bronchoscopy revealed extensive obstruction of both main and subsegmental bronchi with a solid mass strongly adhered to the bronchial wall; both histologic examination and culture of that mass revealed Aspergillus. The patient died of refractory hypoxemia a few days later. CONCLUSIONS: Aspergillus tracheobronchitis should be considered in immunocompromised patients with suspected lung infection even when the main radiographic finding is atelectasis. Bronchoscopy and histologic examination of identified intraluminal material should be performed as soon as possible.     

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder

Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTEN-associated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway—controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-015-0356-8) contains supplementary material, which is available to authorized users.Key Words: PTEN hamartoma tumor syndrome, syndromic, genetics, social behavior, neuroimaging, mouse model     

Surface properties of ceria synthesised using Triton-X based reverse microemulsions

The effect of the tail length of Triton-X surfactants on the surface properties of ceria prepared by means of reversed micelles and Ce(OⁱPr)₄ has been systematically studied. Generally, solids with increased surface areas (up to 136 m² g⁻¹) were synthesised. It was shown that the tail length strongly affects the surface characteristics. Further studies were carried out using UV-Vis, ATR-FTIR, XRD and TGA/DSC studies of the precursor gels as well as N₂-isothermal adsorption BET, XRD, FT-IR, UV-Vis diffuse reflectance and SEM investigations of the final solids samples. An interaction mechanism between the ceria precursor molecules and the polar tail of the reversed Triton X micelles and the formation of ceria (CeO₂) particles in the aqueous nucleus of the reversed microemulsions is proposed.

The effect of the tail length of Triton-X surfactants on the surface properties of ceria prepared by means of reversed micelles and Ce(OⁱPr)₄ has been systematically studied.     

18F-fluorodeoxyglucose positron emission tomography in management of pancreatic cystic tumors

ObjectivesTo evaluate the effectiveness of PET in differentiating malignant from benign pancreatic cystic tumors.MethodsBetween 2009 and 2010, all patients with pancreatic cystic tumors who had PET, triple phase contrast computed tomography (CT) and endoscopic ultrasound (EUS) were reviewed. Clinicopathological characteristics and final histology were correlated with preoperative PET, CT and EUS to assess the value of each modality in detecting malignant from benign lesions for clinical decision-making.ResultsTwenty of a total of 116 patients with pancreatic cystic tumors had 18F-FDG PET because of diagnostic difficulties after evaluation with conventional modalities. Sensitivity and specificity of PET in differentiating malignant from benign pancreatic cystic tumors were 100% and 93.75%, with an accuracy of 95%. PET had the best sensitivity, specificity and accuracy for detecting malignant cystic tumors compared with CT and EUS. In 5 cases, the PET results altered the treatment options completely to follow-up instead of surgery (n = 2), limited resection instead of Whipple's resection (n = 1), and surgery instead of follow-up (n = 2).ConclusionsPET is an accurate, non-invasive method to distinguish malignant from benign pancreatic cystic tumors and can be used as an adjunct to facilitate clinical decision making.     

Tumor Infiltration in the Medial Resection Margin Predicts Survival After Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

Background

Microscopic tumor involvement (R1) in different surgical resection margins after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) has been debated.

Methods

Clinico-pathological data for 258 patients who underwent PD between 2001 and 2010 were retrieved from a prospective database. The rates of R1 resection in the circumferential resection margin (pancreatic transection, medial, posterior, and anterior surfaces) and their prognostic influence on survival were assessed.

Results

For PDAC, the R1 rate was 57.1?% (48/84) for any margin, 31.0?% (26/84) for anterior surface, 42.9?% (36/84) for posterior surface, 29.8?% (25/84) for medial margin, and 7.1?% (3/84) for pancreatic transection margin. Overall and disease-free survival for R1 resections were significantly worse than those for R0 resection (17.2 vs. 28.7?months, P?=?0.007 and 12.3 vs. 21.0?months, P?=?0.019, respectively). For individual margins, only medial positivity had a significant impact on survival (13.8 vs. 28.0?months, P?<?0.001), as opposed to involvement in the anterior (19.7 vs. 23.3?months, P?=?0.187) or posterior margin (17.5 vs. 24.2?months, P?=?0.104). Multivariate analysis demonstrated R0 medial margin was an independent prognostic factor (P?=?0.002, HR?=?0.381; 95?% CI 0.207?C0.701).

Conclusion

The medial surgical resection margin is the most important after PD for PDAC, and an R1 resection here predicts poor survival.