Her-2 protein expression, cellular localization, and gene amplification in colorectal carcinoma.

This study was sought to evaluate the relationship between Her-2 protein expression, cellular localization, gene amplification, and other clinicopathologic parameters in colorectal carcinomas. Her-2 protein expression and gene amplification were assessed in paraffin sections from 106 primary colorectal adenocarcinoma cases using immunohistochemistry and fluorescence in situ hybridization. Both membranous and cytoplasmic immunostaining was evaluated. The results were correlated with each other and with tumor grade, stage, and overall survival. Membranous and cytoplasmic protein expression was identified in 6 (5.6%) and 13 (12.26%) cases, respectively. Gene amplification was detected in 4 (3.7%) cases. There was a high concordance between membranous protein expression and gene amplification (kappa=0.791). No apparent association with any of the clinicopathologic parameters was identified. Membranous Her-2 protein expression and gene amplification are encountered in a small subset of colorectal carcinomas and are highly concordant events. Cytoplasmic protein expression might be either artifactual or it might represent a cross-reacting protein or a precursor form of the mature protein.     

A phase II study of capecitabine plus oxaliplatin (XELOX): a new first-line option in metastatic colorectal cancer

Background: Capecitabine and oxaliplatin are both effective and well-tolerated monotherapies for the treatment of advanced colorectal cancer (CRC). Oxaliplatin has also been shown to be very effective when combined with 5-FU/LV in the first-line setting. Aim of the Study: Assess the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with previously untreated advanced CRC. Methods: Fifty-three patients with measurable disease received capecitabine 1,000 mg/m² twice daily on d 1–14 and oxaliplatin 130 mg/m² on d 1, every 3 wk. Of these, 52 were evaluable for safety and 49 for antitumor response. Results: There was a low rate of grade 1/2 adverse events; grade 3/4 events included leukopenia (10%), neutropenia (6%), thrombocytopenia (2%), nausea/vomiting (4%), and diarrhea (4%). The overall response rate was 39% (95% CI, 25–54%) and median time to disease progression was 7.8 mo. Conclusions: XELOX is an active and well-tolerated first-line treatment for advanced CRC. Randomized phase III studies are ongoing to compare XELOX with FOLFOX in view of the comparable efficacy and safety but superior convenience of XELOX therapy. Presented in part at the 39th American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 31–June 3, 2003.     

Quality of life outcome of critical care survivors eighteen months after discharge from intensive care

Aim

To assess the changes in health-related quality of life in patients discharged from the intensive care unit (ICU).

Methods

At the General University ICU, Trauma Hospital in Athens, 242 patients were enrolled prospectively over a study period of 18 months. Out of these, 116 participants (47.9%) completed all survey components at 6, 12, and 18 months. We used Quality of Life-Spanish (QOL-SP) to assess the health-related quality of life. Patients or their relatives were interviewed on ICU admission and at 6, 12, and 18 months after discharge from the ICU.

Results

Mean quality of life score of the patients increased from 2.9 ± 4.8 (out of maximum 25 points) on ICU admission to 7.0 ± 7.2 points at 6 months after discharge, and then decreased to 5.6 ± 6.9 points at 18 months (P<0.001; Friedman test). Multilinear regression analysis showed that the variables which had the strongest association with the quality of life on admission were age (P = 0.002) and male sex (P = 0.001), whereas age (P<0.001), length of ICU stay (P<0.001), and male sex (P = 0.002) had the strongest association 18 months after discharge from the ICU. Survival rate was 66.9% at discharge from ICU and 61.6% at hospital discharge. There were 33% deaths in the ICU, 5.3% in the hospital, and 6.2% after ICU discharge. There were 7.4% patients lost to follow-up.

Conclusions

After discharge from the ICU, patients’ quality of life was poor and showed an improvement at 18 months after discharge, but was still worse than on admission. Age, ICU length of stay, and male sex were the factors that had the strongest impact on the quality of life on admission and at 18 months after discharge from the ICU.The cost of intensive care and limited resources directed to patients with a poor prognosis raise questions about the utilization of such resources. Since the need for intensive care in several countries exceeds its availability (1), intensive care specialists are forced to admit those patients who will benefit most. There is an increasing pressure that the assessment of long-term survival and quality of life of survivors should be incorporated into outcome evaluation of intensive care unit (ICU) (2).Instruments for assessing quality of life in critically ill patients surviving intensive care include EuroQol-5D (EQ-5D), Nottingham Health Profile (NHP), Sickness Impact Profile (SIP), Medical Outcomes Study 36-item Short Form (SF-36), and Quality Of Life-Spanish (QOL-SP) (3). These instruments aim to evaluate the aspects of health important for all patients. Several cross-sectional studies have used generic, multidimensional quality of life instruments to compare health-related quality of life of intensive care patients with the that of the general population and found a considerable deterioration in the former group (3,4). However, such evidence may be misleading if pre-hospitalization health-related quality of life is not taken into account.Quality of life is an important endpoint in assessing long-term results of intensive care, but the ideal timing for such an assessment is still unclear. This topic has been covered in some reports dealing with pre-ICU assessment of health-related quality of life (3). QOL-SP questionnaire, developed by Fernandez et al (5), is specifically designed for critically ill patients. This is one of the few instruments that have been validated in a critical care population, but it is neither widely used nor well known in the critical care community. A few studies have used QOL-SP to assess medical (6), surgical (7), or multiple trauma patients (8), and to measure the quality of life before ICU, as well as the changes in quality of life from baseline to 6 and 24 months.Despite its limitations, we used this instrument to assess the changes in health-related quality of life in people who survived critical illness in a Greek medical-surgical ICU at 6, 12, and 18 months after ICU discharge, and to compare these data with their pre-admission status.     

Predictors of aneurysm occlusion following treatment with the WEB device: systematic review and case series

The Woven EndoBridge (WEB) device is becoming increasingly popular for treatment of wide-neck aneurysms. As experience with this device grows, it is important to identify factors associated with occlusion following WEB treatment to guide decision making and screen patients at high risk for recurrence. The aim of this study was to identify factors associated with adequate aneurysm occlusion following WEB device treatment in the neurosurgical literature and in our case series. A systematic review of the present literature was conducted to identify studies related to the prediction of WEB device occlusion. In addition, a retrospective review of our institutional data for patients treated with the WEB device was performed. Demographics, aneurysm characteristics, procedural variables, and 6-month follow-up angiographic outcomes were recorded. Seven articles totaling 450 patients with 456 aneurysms fit our criteria. Factors in the literature associated with inadequate occlusion included larger size, increased neck width, partial intrasaccular thrombosis, irregular shape, and tobacco use. Our retrospective review identified 43 patients with 45 aneurysms. A total of 91.1% of our patients achieved adequate occlusion at a mean follow-up time of 7.32 months. Increasing degree of contrast stasis after WEB placement on the post-deployment angiogram was significantly associated with adequate occlusion on follow-up angiogram (p?=?0.005) and with Raymond-Roy classification (p?=?0.048), but not with retreatment (p?=?0.617). In our systematic review and case series totaling 450 patients with 456 aneurysms, contrast stasis on post-deployment angiogram was identified as a predictor of adequate aneurysm occlusion, while morphological characteristics such as larger size and wide neck negatively impact occlusion.

     

Evaluation of Decellularization in Umbilical Cord Artery

Major achievements in creating decellularized whole tissue scaffolds have drawn considerable attention to decellularization as a promising approach for tissue engineering. Developing a tissue-engineered small-diameter (≤2 mm) vascular graft, using decellularized human umbilical arteries (hUAs), for reconstructive surgery is a challenging task. Polymers used in the past, proved unsuitable due to serious adverse effects and autologous vessels are available only in 40% of patients. In this study, histological and proteomic analysis was performed to evaluate the efficiency of two decellularization protocols. In decellularization protocol A, hUAs were incubated in 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) and sodium dodecyl sulfate (SDS) followed by incubation in alpha minimal essential medium (α-MEM) with foetal bovine serum (FBS) while in decellularization protocol B the hUAs were incubated in Hypotonic Tris and SDS followed by incubation in nuclease solution. Histological analysis of decelullarised hUA with both protocols revealed good preservation of extracellular cell matrix (ECM) proteins and immunofluorescent staining detected collagen I and fibronectin. The DNA content within the hUAs after decellularization with protocol A was 6.2% and with protocol B 17.3%. Proteomic analysis identified cytoplasmic enzymes such as, dehydrogenase X, α-enolase and peptidyl-prolyl cis-trans isomerase A only in native samples, while, cytoskeletal proteins such as a-actin, filamin and ECM proteins like collagens were found both in native and decellularised hUA. In conclusion, both decellularization protocols effectively removed the cellular material while the ECM remained intact. Future studies are warranted to elucidate the specific effects of altered structure–function relationships on the overall fate of decellularized hUAs.     

Foveomacular retinitis and associated optical coherence tomography findings.

A 45-year-old man presented with clinical manifestations of foveomacular retinitis, including visual symptoms and foveal lesions characteristic of solar retinopathy, but repeated questions failed to elicit a history of sun gazing. Cross-sectional retinal images produced by optical coherence tomography revealed localized loss of retinal pigment epithelium cells in both eyes. A different pattern of reflectivity at the level of the photoreceptor layer was observed between the right and left eye, reflecting asymmetry in tissue damage. This case is described to provide additional evidence that solar retinopathy and foveomacular retinitis are the same entity and may also have common optical coherence tomography findings.     

A phase II study of capecitabine plus oxaliplatin (XELOX)

Background: Capecitabine and oxaliplatin are both effective and well-tolerated monotherapies for the treatment of advanced colorectal cancer (CRC). Oxaliplatin has also been shown to be very effective when combined with 5-FU/LV in the first-line setting. Aim of the Study: Assess the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with previously untreated advanced CRC. Methods: Fifty-three patients with measurable disease received capecitabine 1,000 mg/m² twice daily on d 1–14 and oxaliplatin 130 mg/m² on d 1, every 3 wk. Of these, 52 were evaluable for safety and 49 for antitumor response. Results: There was a low rate of grade 1/2 adverse events; grade 3/4 events included leukopenia (10%), neutropenia (6%), thrombocytopenia (2%), nausea/vomiting (4%), and diarrhea (4%). The overall response rate was 39% (95% CI, 25–54%) and median time to disease progression was 7.8 mo. Conclusions: XELOX is an active and well-tolerated first-line treatment for advanced CRC. Randomized phase III studies are ongoing to compare XELOX with FOLFOX in view of the comparable efficacy and safety but superior convenience of XELOX therapy.