The Prognostic Significance of an R1 Resection in Gastric Cancer Patients Treated with Adjuvant Chemoradiotherapy

Background

A microscopically irradical (R1) resection is a well-known adverse prognostic factor after gastric cancer surgery. However, the prognostic significance of an R1 resection in gastric cancer patients who are treated with chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore, the aim of this study was to evaluate the effect of an R1 resection on (recurrence-free) survival in gastric cancer patients who were treated with CRT after surgery.

Methods

Gastric cancer patients who had undergone a resection with curative intent followed by adjuvant CRT at our institute between 2001 and 2011 were included. CRT consisted of radiotherapy (45 Gy/25 fractions) combined with concurrent capecitabine (with or without cisplatin) or 5-fluorouracil/leucovorin.

Results

A consecutive series of 110 patients was studied, including 80 (73 %) patients who had undergone an R0 resection and 30 (27 %) patients with an R1 resection. Pathologic T-classification (p = 0.26), N-classification (p = 0.77), and histologic subtype according to Laurén (p = 0.071) were not significantly different between these groups. Three-year recurrence-free survival (45 vs. 35 %, p = 0.34) and overall survival (47 vs. 48 %, p = 0.58) did not significantly differ between patients who had undergone an R0 or R1 resection. In a multivariate analysis, pathologic T-classification and N-classification were independent prognostic factors for survival.

Conclusions

A R1 resection was not an adverse prognostic factor in gastric cancer patients who had undergone CRT after the operation.     

Downregulation of Carnitine Acyl-Carnitine Translocase by miRNAs 132 and 212 Amplifies Glucose-Stimulated Insulin Secretion

We previously demonstrated that micro-RNAs (miRNAs) 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of miRNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including nonfuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT; Slc25a20) is a direct target of these miRNAs. CACT is responsible for transporting long-chain acyl-carnitines into the mitochondria for β-oxidation. Small interfering RNA–mediated knockdown of CACT in β-cells led to the accumulation of fatty acyl-carnitines and enhanced IS. The addition of long-chain fatty acyl-carnitines promoted IS from rat insulinoma β-cells (INS-1) as well as primary mouse islets. The effect on INS-1 cells was augmented in response to suppression of CACT. A nonhydrolyzable ether analog of palmitoyl-carnitine stimulated IS, showing that β-oxidation of palmitoyl-carnitine is not required for its stimulation of IS. These studies establish a link between miRNA-dependent regulation of CACT and fatty acyl-carnitine–mediated regulation of IS.     

A novel approach with “skeletonised MTR” measures tract‐specific microstructural changes in early primary‐progressive MS

We combined tract‐based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract‐specific short‐term changes in early primary‐progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty‐one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM “skeleton,” which represents the tracts that are “common” to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co‐registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a “skeletonised” MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow‐up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal‐appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract‐specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross‐subject and tract‐specific changes in MTR. Hum Brain Mapp 35:723–733, 2014. © 2013 Wiley Periodicals, Inc.     

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.     

Periodontal clinical and microbiological data in desquamative gingivitis patients

Objectives

A series of patients affected by desquamative gingivitis (DG) was investigated in order to evaluate relation patterns among clinical parameters relevant to plaque-induced periodontitis, periodontal microbiological data and the presence of DG lesions.

Patients and methods

Eight oral lichen planus (OLP) and four mucous membrane pemphigoid (MMP) patients were examined. Periodontal measurements (performed at six sites per tooth on all teeth) included probing depth (PD), gingival recession (REC), clinical attachment loss (CAL) and full-mouth plaque (FMPS) and bleeding (FMBS) scores; the presence and the exact location (site by site) of DG lesions were carefully recorded. Sub-gingival plaque samples were collected and examined by means of real-time PCR for the quantitative determination of the six most important marker organisms of periodontitis. Statistically significant differences and correlation of studied variables between DG-positive and DG-negative sites were investigated in MMP and OLP cases using Mann–Whitney test (p?<?0.05) and the Spearman rank correlation coefficient, respectively.

Results

OLP gingival lesions do not significantly affect CAL, although the presence of such lesions may reduce REC and increase PD and FMPS. MMP gingival lesions significantly worsened CAL and increased REC and FMPS. In both OLP and MMP cases, no significant difference was found between DG-positive and DG-negative sites as regards the relative percentage of the investigated species on the total bacterial load. Correlations between the presence of DG lesions and clinical parameters (CAL, PD, REC) were not significant (p?<?0.05). Significant correlations were found for the presence of gingival OLP lesions and Aggregatibacter actinomycetemcomitans (AA) and for the absence of gingival MMP lesions and AA.

Conclusions

These findings are not definitive, but highlight the need for further investigations of periodontal clinical and microbiological aspects of disorders causing DG in order to clarify their potential interference with plaque-related periodontitis.     

From the Cover: Proton transfers are key elementary steps in ethylene polymerization on isolated chromium(III) silicates

Mononuclear Cr(III) surface sites were synthesized from grafting [Cr(OSi(O^tBu)₃)₃(tetrahydrofurano)₂] on silica partially dehydroxylated at 700 °C, followed by a thermal treatment under vacuum, and characterized by infrared, ultraviolet-visible, electron paramagnetic resonance (EPR), and X-ray absorption spectroscopy (XAS). These sites are highly active in ethylene polymerization to yield polyethylene with a broad molecular weight distribution, similar to that typically obtained from the Phillips catalyst. CO binding, EPR spectroscopy, and poisoning studies indicate that two different types of Cr(III) sites are present on the surface, one of which is active in polymerization. Density functional theory (DFT) calculations using cluster models show that active sites are tricoordinated Cr(III) centers and that the presence of an additional siloxane bridge coordinated to Cr leads to inactive species. From IR spectroscopy and DFT calculations, these tricoordinated Cr(III) sites initiate and regulate the polymer chain length via unique proton transfer steps in polymerization catalysis.Almost half of the world’s high-density polyethylene is produced by the Phillips catalyst, a silica-supported chromium oxide (CrO_x/SiO₂) (1). This catalyst is prepared by incipient wetness impregnation of a chromium salt on silica, followed by high temperature calcination. Contacting this material with ethylene forms the active reduced species in situ that polymerizes ethylene. The Phillips catalyst is active in the absence of activators that are typically required for polymerization catalysts (2). Despite 50 y of research, the catalytically active site and the initiation mechanism, particularly the formation of the first Cr–C bond, remain controversial. Numerous spectroscopic techniques [infrared (IR), ultraviolet-visible (UV-Vis), electron paramagnetic resonance (EPR), X-ray absorption spectroscopy (XAS), etc.] established that the Phillips catalyst contains a complex mixture of surface Cr species, of which only ∼10% are active in polymerization (3, 4). The low number of active sites is one of the main limiting factors in using spectroscopic methods to study this material because the spectroscopic signature mainly belongs to inactive species.Previous molecular approaches to determine the Phillips catalyst ethylene polymerization mechanism focused on systems containing preformed Cr–C bonds (5–7). We recently reported the preparation of well-defined silica-supported Cr(II) and Cr(III) dinuclear sites (8), where Cr(III) species are active polymerization sites, in contrast to Cr(II), which is consistent with extensive research on homogeneous chromium complexes (9–11). We proposed that these well-defined Cr(III) silicates initiate polymerization by the heterolytic cleavage of a C–H bond of ethylene on a Cr–O bond to form a Cr–vinyl species that is capable of inserting ethylene by a Cossee–Arlman mechanism (8). However, extensive studies on Phillips catalyst invoke mononuclear polymerization sites (12–18). Furthermore, direct evidence of the active site structure and the polymerization mechanism is critically needed. Here we investigate the preparation and the detailed characterization of isolated Cr(III) sites supported on silica, prepared by grafting [Cr^III(OSi(O^tBu)₃)₃(tetrahydrofurano; THF)₂] (19) on dehydroxylated silica and a subsequent thermal treatment under vacuum. These isolated Cr(III) sites are highly active in ethylene polymerization in the absence of coactivator. Computational investigations in combination with IR spectroscopy indicate that polymerization occurs on tricoordinate Cr(III) sites and involves two key proton transfer steps: (i) formation of the first Cr–C bond through the C–H activation of ethylene across a Cr–O bond and (ii) termination by the microreverse of the initiation step while chain growth occurs by classical Cossee–Arlman insertion polymerization (20, 21).     

Trabecular Bone Score: A Noninvasive Analytical Method Based Upon the DXA Image

The trabecular bone score (TBS) is a gray‐level textural metric that can be extracted from the two‐dimensional lumbar spine dual‐energy X‐ray absorptiometry (DXA) image. TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone mineral density (BMD) measurement. Based on experimental variograms of the projected DXA image, TBS has the potential to discern differences between DXA scans that show similar BMD measurements. An elevated TBS value correlates with better skeletal microstructure; a low TBS value correlates with weaker skeletal microstructure. Lumbar spine TBS has been evaluated in cross‐sectional and longitudinal studies. The following conclusions are based upon publications reviewed in this article: 1) TBS gives lower values in postmenopausal women and in men with previous fragility fractures than their nonfractured counterparts; 2) TBS is complementary to data available by lumbar spine DXA measurements; 3) TBS results are lower in women who have sustained a fragility fracture but in whom DXA does not indicate osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar spine BMD measurements in postmenopausal women; 5) efficacious therapies for osteoporosis differ in the extent to which they influence the TBS; 6) TBS is associated with fracture risk in individuals with conditions related to reduced bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as an emerging technology that could well become a valuable clinical tool in the diagnosis of osteoporosis and in fracture risk assessment. © 2014 American Society for Bone and Mineral Research.     

Use of external fixation for perilunate dislocations and fracture dislocations

The purpose of this study was to review clinical and radiographic outcomes of perilunate dislocations and fracture dislocations treated with external fixation and K-wire fixation. Twenty patients (18 males and two females) with a mean age of 38 years (range 18–59) who had an acute dorsal perilunate dislocation or fracture dislocation were treated with the use of wrist external fixator and K-wires. The injuries included 12 perilunate dislocations, seven trans-scaphoid perilunate fracture dislocations, and one trans-styloid perilunate fracture dislocation. The median time from trauma to operation was 8 h (2–12 h). Indirect reduction via ligamentotaxis was achieved in all perilunate dislocation, and provisional K-wire fixation was added. In five of seven trans-scaphoid perilunate fracture dislocations, indirect reduction was achieved; whereas in the other two as well as in the case of trans-styloid perilunate fracture dislocation, open reduction was required. External fixator was supplemented with K-wires for stabilization of the fractures and the intercarpal intervals. The interosseous and capsular ligaments were not repaired, even after open reduction of fracture dislocations. The mean follow-up was 39 months (range 18–68 months). Range of motion and grip strength were measured. Cooney’s scoring system was used for the assessment of clinical function. Radiographic evaluation included time to scaphoid union, measurement of radiographic parameters (scapholunate gap, scapholunate angle, lunotriquetral gap, and carpal height ratio) and any development of arthritis. The flexion-extension motion arc and grip strength of the injured wrist averaged 80 and 88%, respectively, of the corresponding values for the contralateral wrists. According to Cooney’s clinical scoring system, overall functional outcomes were rated as excellent in four patients, good in eight, fair in six, and poor in two. Eighteen patients returned to their former occupations. Two patients with a trans-scaphoid perilunate injury developed nonunion of the scaphoid; one of them required scaphoid excision and midcarpal fusion. Two patients had radiographic evidence of arthritis. The use of external fixation and provisional K-wire fixation for the treatment of acute perilunate dislocations is associated with satisfactory midterm functional and radiographic outcomes. This minimally invasive treatment option is simple, reliable, and minimally invasive method that provides proper restoration and stable fixation of carpal alignment.     

Impact of a concept map teaching approach on nursing students’ critical thinking skills

Nurses confront complex problems and decisions that require critical thinking in order to identify patient needs and implement best practices. An active strategy for teaching students the skills to think critically is the concept map. This study explores the development of critical thinking among nursing students in a required pathophysiology and pharmacology course during the first year of a Bachelor of Science in Nursing in response to concept mapping as an interventional strategy, using the Health Education Systems, Incorporated critical thinking test. A two‐group experimental study with a pretest and posttest design was used. Participants were randomly divided into a control group (n = 42) taught by traditional didactic lecturing alone, and an intervention group (n = 41), taught by traditional didactic lecturing with concept mapping. Students in the concept mapping group performed much better on the Health Education Systems, Incorporated than students in the control group. It is recommended that deans, program directors, and nursing faculties evaluate their curricula to integrate concept map teaching strategies in courses in order to develop critical thinking abilities in their students.