High-density stable glasses formed on soft substrates.

Enabled by surface-mediated equilibration, physical vapour deposition can create high-density stable glasses comparable with liquid-quenched glasses aged for millions of years. Deposition is often performed at various rates and temperatures on rigid substrates to control the glass properties. Here we demonstrate that on soft, rubbery substrates, surface-mediated equilibration is enhanced up to 170 nm away from the interface, forming stable glasses with densities up to 2.5% higher than liquid-quenched glasses within 2.5 h of deposition. Gaining similar properties on rigid substrates would require 10 million times slower deposition, taking ~3,000 years. Controlling the modulus of the rubbery substrate provides control over the glass structure and density at constant deposition conditions. These results underscore the significance of substrate elasticity in manipulating the properties of the mobile surface layer and thus the glass structure and properties, allowing access to deeper states of the energy landscape without prohibitively slow deposition rates.

Polyamorphism of vapor-deposited amorphous selenium in response to light.

Enhanced surface mobility is critical in producing stable glasses during physical vapor deposition. In amorphous selenium (a-Se) both the structure and dynamics of the surface can be altered when exposed to above-bandgap light. Here we investigate the effect of light on the properties of vapor-deposited a-Se glasses at a range of substrate temperatures and deposition rates. We demonstrate that deposition both under white light illumination and in the dark results in thermally and kinetically stable glasses. Compared to glasses deposited in the dark, stable a-Se glasses formed under white light have reduced thermal stability, as measured by lower density change, but show significantly improved kinetic stability, measured as higher onset temperature for transformation. While light induces enhanced mobility that penetrates deep into the surface, resulting in lower density during vapor deposition, it also acts to form more networked structures at the surface, which results in a state that is kinetically more stable with larger optical birefringence. We demonstrate that the structure formed during deposition with light is a state that is not accessible through liquid quenching, aging, or vapor deposition in the dark, indicating the formation of a unique amorphous solid state.

Increased spontaneous apoptosis, but not survivin expression, is associated with histomorphologic response to neoadjuvant chemoradiation in rectal cancer.

PURPOSE: Survivin has been shown to be an important mediator of cellular radioresistance in vitro. This study aims to compare survivin expression and apoptosis to histomorphologic responses to neoadjuvant radiochemotherapy (RCT) in rectal cancer. MATERIALS AND METHODS: Thirty-six pre-treatment biopsies were studied. Survivin mRNA and protein expression plus TUNEL staining for apoptosis was performed. Response to treatment was assessed using a 5-point tumour regression grade. RESULTS: Survivin expression was not found to be predictive of response to RCT (p = NS). In contrast, spontaneous apoptosis was significantly (p = 0.0051) associated with subsequent response to RCT. However, no association between survivin expression and levels of apoptosis could be identified. CONCLUSIONS: This in vivo study failed to support in vitro studies showing an association between survivin and response to chemotherapy and radiation therapy. These results caution against the translation of the in vitro properties of survivin into a clinical setting.

A National Bowel Cancer Screening Programme using FIT: Achievements and Challenges.

Colorectal cancer accounts for 11% of all cancer-related deaths in Ireland. With the aim of diagnosing these cancers at an earlier stage, and detecting premalignant lesions, the National Screening Service (NSS) offered a fecal immunochemical test (FIT) to all individuals aged 60 to 69. All individuals in the age range were contacted by post and invited to participate in the programme. Those with a positive FIT result were offered a colonoscopy in an internationally accredited unit. From an eligible population of 488,628, 196,238 individuals participated giving an uptake of 40.2%. Commencing at a FIT threshold of 20 µg Hg/g feces, the positivity rate was 8.6%, which overwhelmed colonoscopy capacity and, thus, the threshold was increased to 45 µg, resulting in an overall 5% positivity rate. A total of 520 individuals had cancer detected (68.3% stage I or II), of which 104 were removed endoscopically (pT1s). Adenomas were present in 54.2% of all colonoscopies, 17.4% deemed high risk. Despite a lower uptake, males were twice as likely to have colorectal cancers as females and had a 59% increased rate of high-risk adenomas diagnosed. Challenges facing the programme include increasing participation, especially among males, and increasing colonoscopy capacity. The ability to alter the sensitivity of FIT to match colonoscopy capacity is a valuable option for such a programme as it ensures that the maximum public health benefit can be achieved within available resources.

COX-2 overexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy.

PURPOSE: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). METHODS AND MATERIALS: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. RESULTS: Good response (TRG 1+2), moderate response (TRG 3), and poor response (TRG 4+5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3+4) to treatment than were those with normal COX-2 expression (p=0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p=0.0007, chi-square test). CONCLUSIONS: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.

Spontaeneous subacute portomesenteric venous thrombosis: a case report.

Although uncommon and often asymptomatic, portal venous thrombosis can have catastrophic consequences for the individual it afflicts, particularly when the process propagates to involve the superior mesenteric vein. Familiarity with the condition's pathogenesis and presentation however permits early diagnosis and allows aggressive conservative management to achieve a successful outcome. Here we describe the successful outcome of such management for a 42-year-old male patient who developed this condition spontaneously.

Hematochezia in a patient with liver cirrhosis.

Although commonly detectable in patients with cirrhosis, rectal varices only infrequently cause significant hematochezia (0.5-3.6%). While they may be expected to resolve with treatment of the concomitant portal hypertension, there is currently no standardized approach to their management in isolation. Therefore many authorities recommend transjugular intrahepatic portosystemic shunting (TIPS) as a means of alleviating otherwise recalcitrant bleeding. Conceptually, however, rectal varices should be as amenable to local therapies as are their counterparts occurring at the esophagogastric junction. In this report, we describe the use of endoscopic banding per ano to alleviate significant rectal bleeding in a patient with poorly controlled portal hypertension. This allowed medical optimisation so that the underlying pathology could be controlled without recourse to TIPS or other means of creating a formal portosystemic shunt.

Combination of SELDI-TOF-MS and data mining provides early-stage response prediction for rectal tumors undergoing multimodal neoadjuvant therapy.

OBJECTIVE: We investigated whether proteomic analysis of the low molecular weight region of the serum proteome could predict histologic response of locally advanced rectal cancer to neoadjuvant radiochemotherapy (RCT). SUMMARY BACKGROUND DATA: Proteomic analysis of serum is emerging as a powerful new modality in cancer, in terms of both screening and monitoring response to treatment. No study has yet assessed its ability to predict and monitor the response of rectal cancer to RCT. METHODS: Sequential serum samples from 20 patients undergoing RCT were prospectively collected. Time points sampled were as follows: pretreatment, 24/48 hours, 1 week, 2 weeks, 3 weeks, 5 weeks (last day of RCT), and presurgery. Response to treatment was measured using a 5-point tumor regression grade (TRG) based on the degree of residual tumor to fibrosis. All serum samples were analyzed in duplicate using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). Support vector machine (SVM) analysis of spectra was used to generate a predictive algorithm for each time point based on proteins that were maximally differentially expressed between good and poor responders. This algorithm was then tested using leave-one-out cross validation. RESULTS: In total, 230 spectra were generated representing all available time points from 9 good responders (TRG 1+2) and 11 poor responders (TRG 3-5). SVM analysis indicated that changes within the serum proteome at the 24/48 hours time point into treatment provided optimal classification accuracy. In more detail, a cohort of 14 protein peaks were identified that collectively differentiated between good and poor responders, with 87.5% sensitivity and 80% specificity. CONCLUSIONS: Serum proteomic analysis may represent an early response predictor in multimodal treatment regimens of rectal cancer. These data suggest that this novel, minimally invasive modality may be a useful adjunct in the multimodal management of rectal cancer, and in the design of future clinical trials.