Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation.

BACKGROUND: Total mesorectal excision (TME) remains commonplace for T1-2 rectal cancer owing to fear of undertreating a small proportion of patients with node-positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ-preserving surgery if specific biomarkers were validated. METHODS: Gene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsatellite instability status were also defined. Molecular parameters were correlated with histopathological indices of disease progression. Predictive models for nodal metastasis, lymphovascular invasion (LVI) and distant metastasis were constructed using a multilevel reverse logistic regression model. RESULTS: Methylation of the retinoic acid receptor ß gene, RARB, and that of the checkpoint with forkhead and ring finger gene, CHFR, was associated with tumour stage (RARB: 51·9 per cent for T1-2 versus 33·9 per cent for T3-4, P < 0·001; CHFR: 5·5 per cent for T1-2 versus 12·6 per cent for T3-4, P = 0·005). Gene methylation associated with nodal metastasis included RARB (47·1 per cent for N- versus 31·7 per cent for N+; P = 0·008), chemokine ligand 12, CXCL12 (12·3 per cent for N- versus 8·9 per cent for N+; P = 0·021), and death-associated protein kinase 1, DAPK1 (19·3 per cent for N- versus 12·3 per cent for N+; P = 0·022). RARB methylation was also associated with LVI (45·1 per cent for LVI- versus 31·7 per cent for LVI+; P = 0·038). Predictive models for nodal metastasis and LVI achieved sensitivities of 91·1 and 85·0 per cent, and specificities of 55·3 and 45·3 per cent, respectively. CONCLUSION: This methylation biomarker panel provides a step towards accurate discrimination of indolent and aggressive rectal cancer subtypes. This could offer an improvement over the current standard of care, whereby fit patients are offered radical surgery.

Methylation profiling of rectal cancer identifies novel markers of early-stage disease.

BACKGROUND: Radical surgery is the de facto treatment for early rectal cancer. Conservative surgery with transanal endoscopic microsurgery can achieve high rates of cure but the histopathological measures of outcome used to select local treatment lack precision. Biomarkers associated with disease progression, particularly mesorectal nodal metastasis, are urgently required. The aim was to compare patterns of gene-specific hypermethylation in radically excised rectal cancers with histopathological stage. METHODS: Locus-specific hypermethylation of 24 tumour suppressor genes was measured in 105 rectal specimens (51 radically excised adenocarcinomas, 35 tissues adjacent to tumour and 19 normal controls) using the methylation-specific multiplex ligation-dependent probe assay (MS-MLPA). Methylation values were correlated with histopathological indices of disease progression and validated using bisulphite pyrosequencing. RESULTS: Five sites (ESR1, CDH13, CHFR, APC and RARB) were significantly hypermethylated in cancer compared with adjacent tissue and normal controls (P < 0·050). Methylation at these sites was higher in Dukes' A than Dukes' 'D' cancers (P = 0·013). Methylation at two sites (GSTP1 and RARB) was individually associated with localized disease (N0 and M0 respectively; P = 0·006 and P = 0·008). Hypermethylation of at least two of APC, RARB, TIMP3, CASP8 and GSTP1 was associated with early (N0 M0) disease (N0, P = 0·002; M0, P = 0·044). Methylation levels detected by MS-MLPA and pyrosequencing were concordant. CONCLUSION: Locus-specific hypermethylation was more prevalent in early- than late-stage disease. Hypermethylation of two or more of a panel of five tumour suppressor genes was associated with localized disease.

Health-related quality of life improvement following surgical treatment of primary hyperparathyroidism in a United Kingdom population.

OBJECTIVE: The aim of this study was to determine if parathyroidectomy for primary hyperparathyroidism produces improvement in health-related quality of life in a United Kingdom population. METHODS: Since October 2002, patients undergoing parathyroidectomy for primary hyperparathyroidism were asked to complete the SF-36 questionnaire, a validated self assessment tool prior to surgery and at six months post surgery. The questionnaires were either mailed to the patients or given at the time of outpatient follow up. RESULTS: 24 out of 29 patients completed the questionnaire pre- and postoperatively. Compared to the national average, the median pre-operative scores were worse in all 8 domains. At 6 months post surgery, there were significant improvements in six out of eight domains (p<0.05); physical and social functioning, physical and emotional role limitations, energy and mental health. The median physical component summary score (PCS) and the mental component summary score (MCS) were also significantly improved postoperatively [Preop vs. Postop (PCS)=28.16 vs. 35.40 (P=0.03)] and Preop vs. Postop (MCS)=41.50 vs. 56.23 (P=0.005)]. The post-operative MCS was comparable with the national average. CONCLUSION: This study shows that parathyroidectomy for primary hyperparathyroidism improves health-related quality of life in a United Kingdom population.

Hurricane Katrina: prior trauma, poverty and health among Vietnamese-American survivors.

BACKGROUND: The flooding of New Orleans after Hurricane Katrina revealed the disproportionate vulnerability of ethnic minority communities for emergency preparedness, disaster relief and health. Nurses need to analyse Katrina's health consequences for the most vulnerable segments of our society. AIM: To examine factors contributing to differential health outcomes among the New Orleans Vietnamese community in response to Katrina. METHODS: A sample of 113 adult Vietnamese Katrina survivors from New Orleans was recruited. A mixed-method approach, including survey and focus groups, was used to collect data. Survey questions were modified from standardized instruments to evaluate survivors' health status and factors contributing to health outcomes. Multivariate and content analysis were used to investigate effects of prior trauma, financial strain, social support and acculturation level in predicting survivors' health outcomes. RESULTS: Findings suggested financial strain was the strongest risk factor for Vietnamese survivors' post-traumatic stress disorder (PTSD) symptoms, and physical and mental health post-disaster; while social support was a strong protective factor for health. Survivors who perceived higher impact from previous traumatic experiences had poorer physical health, but not PTSD symptoms or poor mental health after controlling for financial strain and social support, suggesting complex relationships among these measures in predicting PTSD symptoms and health. Less-acculturated individuals also reported higher levels of PTSD symptoms and poorer physical health. CONCLUSIONS: Catastrophic events like Katrina can result in disproportionate risk of negative health outcomes among vulnerable populations. Nurses should take into account prior trauma, financial strain, social support network and acculturation level, to adequately address survivors' needs.

Perioperative local anaesthetic in young paediatric patients undergoing extractions under outpatient 'short-case' general anaesthesia. A double-blind randomised controlled trial.

OBJECTIVE: To investigate if postoperative pain/discomfort and anxiety experienced by young children who had extractions under general anaesthesia (GA) were affected by perioperative injection techniques of local anaesthetic (LA). DESIGN: A single-centre, double-blind, randomised controlled trial. SETTING: Conducted in 2002/2003 at the Unit of Paediatric Dentistry, Eastman Dental Hospital, London. METHODS: Children, aged 2-6 years scheduled for extractions under GA, were randomly assigned to receive either no LA (NLA), infiltration injection (IFL) or intraligamental injection (ITR) perioperatively. All children received analgesic suppositories after induction. OUTCOME MEASURES: Anxiety was scored using the Venham Picture Scale. Postoperative pain was scored using the Simplified Toddler-Preschooler Postoperative Pain Scale and supplemented with the Modified Pain/Discomfort Scale. RESULTS: Eighteen children received NLA, 17 received IFL and 19 received ITR. Postoperative pain/discomfort and anxiety scores were not significantly different during the period of recovery. On the first night, the intraligamental group had significantly lower pain scores (p = 0.012). CONCLUSION: Postoperative pain/discomfort and anxiety during the period of recovery experienced by young children who had extractions under GA appear not to be affected by perioperative injection techniques of LA. Upon discharge, intraligamental injection appears beneficial, as it is probably well tolerated by causing less soft tissue numbness initially and thus, reduces perceived pain/discomfort.

Optical generation of coherent surface acoustics: an optically based probe of surface structure and dynamics.

Above-band-gap picosecond pulses are used to generate holographically high-frequency, coherent, surface acoustic modes on semiconductor surfaces. Optical diffraction from the surface acoustics is in superposition to a free-carrier phase grating that acts as an amplifying cross term in the diffraction process. The detection limits are of the order of 10(-4) nm for the surface displacement. Frequencies up to 2 GHz have been realized, with frequencies >20 GHz possible. A quantitative theory for the photothermal coupling has been developed. In addition, propagation of the optically generated surface modes has revealed a solid-liquid phase transition of the water layer at TiO(2)-H(2)O interfaces.