Diffusion‐weighted MRI monitoring of pancreatic cancer response to radiofrequency heat‐enhanced intratumor chemotherapy

The aim of this study was to evaluate the feasibility of using diffusion‐weighted MRI to monitor the early response of pancreatic cancers to radiofrequency heat (RFH)‐enhanced chemotherapy. Human pancreatic carcinoma cells (PANC‐1) in different groups and 24 mice with pancreatic cancer xenografts in four groups were treated with phosphate‐buffered saline (PBS) as a control, RFH at 42 °C, gemcitabine and gemcitabine plus RFH at 42 °C. One day before and 1, 7 and 14 days after treatment, diffusion‐weighted MRI and T₂‐weighted imaging were applied to monitor the apparent diffusion coefficients (ADCs) of tumors and tumor growth. MRI findings were correlated with the results of tumor apoptosis analysis. In the in vitro experiments, the quantitative viability assay showed lower relative cell viabilities for treatment with gemcitabine plus RFH at 42 °C relative to treatment with RFH only and gemcitabine only (37 ± 5% versus 65 ± 4% and 58 ± 8%, respectively, p < 0.05). In the in vivo experiments, the combination therapy resulted in smaller relative tumor volumes than RFH only and chemotherapy only (0.82 ± 0.17 versus 2.23 ± 0.90 and 1.64 ± 0.44, respectively, p = 0.003). In vivo, 14‐T MRI demonstrated a remarkable decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination therapy group. The apoptosis index in the combination therapy group was significantly higher than those in the chemotherapy‐only, RFH‐only and PBS treatment groups (37 ± 6% versus 20 ± 5%, 8 ± 2% and 3 ± 1%, respectively, p < 0.05). This study confirms that it is feasible to use MRI to monitor RFH‐enhanced chemotherapy in pancreatic cancers, which may present new options for the efficient treatment of pancreatic malignancies using MRI/RFH‐integrated local chemotherapy. Copyright © 2013 John Wiley & Sons, Ltd.     

Benefits of maxillectomy with internal dissection of the masticator space by transmandibular approach in the surgical management of malignant tumours of the upper gingiva and hard palate: a clinical review of 10 cases

The aim of this study was to review patients with tumours extending to the posterior portion of the upper gingiva and hard palate, and to evaluate the postoperative outcomes. Ten consecutive patients with tumours in the upper gingiva and hard palate, who underwent maxillectomy with internal dissection of the masticator space by the transmandibular approach, were reviewed retrospectively. Among the 10 patients, the pathological diagnosis was squamous cell carcinoma in seven, adenoid cystic carcinoma in one, malignant melanoma in one, and osteosarcoma in one. Loco-regional control was achieved in eight of nine patients (88.9%). Three patients had residual moderate trismus. Cosmetic issues were not noted in any patient. En bloc resection of the maxilla with the internal portion of the masticator space and neck through the parapharyngeal space by the transmandibular approach is a useful and satisfactory technique for the excision of a tumour with involvement of the posterior portion of the upper gingiva and hard palate.     

In vivo studies of effects of antidepressants on parotid salivary secretion in the rat

Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while antidepressants such as selective serotonin reuptake inhibitors (SSRI) are considered less xerogenic. The antimuscarinic effect of the TCAs has been considered to be the principal mechanism causing a dry mouth. Although the muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the salivation reflex arc may be affected at other levels as well. We currently wondered whether or not antidepressants exert an inhibition of the salivary reflex not only at the glandular level but at a central level as well. In this study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex- (0.5 M citric acid applied on the tongue) and methacholine-evoked salivary secretion. While all three compounds inhibited citric acid-evoked secretion (−40 to −60% at 5 mg/kg i.v. of the antidepressants), only clomipramine inhibited methacholine-evoked secretion (−30% at 5 mg/kg i.v.). On the contrary, both citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to 49%). This was particularly obvious for the salivary protein output (>200%). In the presence of α- and β-adrenoceptor antagonists, the citalopram- and venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of type may exert xerogenic effects by inhibiting the salivary reflex in the central nervous system. However, while TCAs may also hamper the secretory response by antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to lack this additional xerogenic mechanism indicating a better therapeutic profile and better opportunities for pharmacological treatment of drug-induced xerostomia.     

Tumour and placenta establishment: The importance of antigen processing and presentation

Classical and non-classical MHC class I (MHC I) molecules displayed at the cell surface are essential for the induction of innate and adaptive immune responses. Classical MHC I present endogenously derived peptides to CD8⁺ T cells for immunosurveillance of infected or malignant cells. By contrast, non-classical MHC I, in particular HLA-G, also display peptides, but primarily act as immunomodulatory ligands for the innate immune response and are an important component for extravillous trophoblast invasion to form the placenta in pregnancy. Endoplasmic Reticulum AminoPeptidase 1 (ERAP1), which trims peptides in the ER to generate ligands for MHC I loading, is a key regulator of the peptide repertoire and has a significant impact on the formation of stable MHC I at the cell surface. ERAP1 also plays a role in angiogenesis, cell cycle progression and migration, events that are shared between tumour cells and placenta formation. Here we discuss the similarities between tumour and extravillous trophoblast cells in their immune modulatory, invasion, migration and proliferation properties in the context of ERAP1 and its role in establishment of solid tumours and placenta formation.     

Reliability and validity of a smartphone-based assessment of gait parameters across walking speed and smartphone locations: Body,bag, belt,hand, and pocket

The assessment of spatiotemporal gait parameters is a useful clinical indicator of health status. Unfortunately, most assessment tools require controlled laboratory environments which can be expensive and time consuming. As smartphones with embedded sensors are becoming ubiquitous, this technology can provide a cost-effective, easily deployable method for assessing gait. Therefore, the purpose of this study was to assess the reliability and validity of a smartphone-based accelerometer in quantifying spatiotemporal gait parameters when attached to the body or in a bag, belt, hand, and pocket. Thirty-four healthy adults were asked to walk at self-selected comfortable, slow, and fast speeds over a 10-m walkway while carrying a smartphone. Step length, step time, gait velocity, and cadence were computed from smartphone-based accelerometers and validated with GAITRite. Across all walking speeds, smartphone data had excellent reliability (ICC_2,1 ≥ 0.90) for the body and belt locations, with bag, hand, and pocket locations having good to excellent reliability (ICC_2,1 ≥ 0.69). Correlations between the smartphone-based and GAITRite-based systems were very high for the body (r = 0.89, 0.98, 0.96, and 0.87 for step length, step time, gait velocity, and cadence, respectively). Similarly, Bland-Altman analysis demonstrated that the bias approached zero, particularly in the body, bag, and belt conditions under comfortable and fast speeds. Thus, smartphone-based assessments of gait are most valid when placed on the body, in a bag, or on a belt. The use of a smartphone to assess gait can provide relevant data to clinicians without encumbering the user and allow for data collection in the free-living environment.