Loss of heterozygosity at 18q21 is indicative of recurrence and therefore poor prognosis in a subset of colorectal cancers

Adjuvant therapies are increasingly used in colorectal cancers for the prevention of recurrence. These therapies have side-effects and should, thus, be used only if really beneficial. However, the development of recurrence cannot be predicted reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus based only on the primary stage of the cancer. Loss of heterozygosity (LOH) in the long arm of chromosome 18 is suggested to be related to poor survival and possibly to the development of metastases. We studied the value of LOH at 18q21 as a marker of colorectal cancer prognosis, association with clinicopathological variables, tumour recurrence and survival of the patients. Of the 255 patients studied, 195 were informative as regards LOH status when analysed in primary colorectal cancer specimens using the polymerase chain reaction (PCR) and fragment analysis. LOH at 18q21 was significantly associated with the development of recurrence (P= 0.01) and indicated poor survival in patients of Dukes' classes B and C, in which most recurrences (82%) occurred. An increased rate of tumour recurrence is the reason for poor survival among patients with LOH at 18q21 in primary cancer. These patients are a possible target group for recurrence-preventing adjuvant therapies. © 1999 Cancer Research Campaig

Abdominal Wound Dehiscence in Adults: Development and Validation of a Risk Model

Background: Several studies have been performed to identify risk factors for abdominal wound dehiscence. No risk model had yet been developed for the general surgical population. The objective of the present study was to identify independent risk factors for abdominal wound dehiscence and to develop a risk model to recognize high-risk patients. Identification of high-risk patients offers opportunities for intervention strategies. Methods: Medical registers from January 1985 to December 2005 were searched. Patients who had primarily undergone appendectomies or nonsurgical (e.g., urological) operations were excluded. Each patient with abdominal wound dehiscence was matched with three controls by systematic random sampling. Putative relevant patient-related, operation-related, and postoperative variables were evaluated in univariate analysis and subsequently entered in multivariate stepwise logistic regression models to delineate major independent predictors of abdominal wound dehiscence. A risk model was developed, which was validated in a population of patients who had undergone operation between January and December 2006. Results: A total of 363 cases and 1,089 controls were analyzed. Major independent risk factors were age, gender, chronic pulmonary disease, ascites, jaundice, anemia, emergency surgery, type of surgery, postoperative coughing, and wound infection. In the validation population, risk scores were significantly higher (P < 0.001) for patients with abdominal wound dehiscence (n = 19) compared to those without (n = 677). Resulting scores ranged from 0 to 8.5, and the risk for abdominal wound dehiscence over this range increased exponentially from 0.02% to 70.1%. Conclusions: The validated risk model shows high predictive value for abdominal wound dehiscence and may help to identify patients at increased risk

Effect of vitamin K1 supplementation on left colon healing in rats with extrahepatic biliary obstruction

PURPOSE: To evaluate the effects of vitamin K1 on wound healing in the left colon of rats with experimental biliary obstruction.METHODS: Sixteen male rats, divided into four groups of four animals each (L, M, LK, and MK), underwent colostomy followed by bowel suture in the left colon. Seven days before, animals in the L and LK groups had undergone common bile duct ligation. The animals in groups MK and LK received vitamin K1 supplementation. On day 7 after bowel suture, repeat laparotomy was performed for evaluation of colonic healing by burst pressure measurement and collection of samples for histopathological analysis. Changes in body weight were evaluated in the four groups.RESULTS:Weight loss was lower in animals supplemented with vitamin K. No significant differences were observed in burst pressure among the four groups (p>0.05). Histological analysis showed more hemorrhage and congestion in the biliary obstruction groups. Supplemented animals exhibited increased collagen formation and less edema and abscess formation.CONCLUSION:Vitamin K supplementation attenuated weight loss and improved colonic wound healing in rats

Hughes Abdominal Repair Trial (HART) – Abdominal wall closure techniques to reduce the incidence of incisional hernias: study protocol for a randomised controlled trial

Background Incisional hernias are common complications of midline closure following abdominal surgery and cause significant morbidity, impaired quality of life and increased health care costs. The ‘Hughes Repair’ combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. This theoretically distributes the load along the incision length as well as across it. There is evidence to suggest that this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared the Hughes Repair with standard mass closure for the prevention of incisional hernia formation following a midline incision. Methods/design This is a 1:1 randomised controlled trial comparing two suture techniques for the closure of the midline abdominal wound following surgery for colorectal cancer. Full ethical approval has been gained (Wales REC 3, MREC 12/WA/0374). Eight hundred patients will be randomised from approximately 20 general surgical units within the United Kingdom. Patients undergoing open or laparoscopic (more than a 5-cm midline incision) surgery for colorectal cancer, elective or emergency, are eligible. Patients under the age of 18 years, those having mesh inserted or undergoing musculofascial flap closure of the perineal defect in abdominoperineal wound closure, and those unable to give informed consent will be excluded. Patients will be randomised intraoperatively to either the Hughes Repair or standard mass closure. The primary outcome measure is the incidence of incisional hernias at 1 year as assessed by standardised clinical examination. The secondary outcomes include quality of life patient-reported outcome measures, cost-utility analysis, incidence of complete abdominal wound dehiscence and C-POSSUM scores. The incidence of incisional hernia at 1 year, assessed by computerised tomography, will form a tertiary outcome. Discussion A feasibility phase has been completed. The results of the study will be used to inform current and future practice and potentially reduce the risk of incisional hernia formation following midline incisions

Non-hexagonal neural dynamics in vowel space

Are the grid cells discovered in rodents relevant to human cognition? Following up on two seminal studies by others, we aimed to check whether an approximate 6-fold, grid-like symmetry shows up in the cortical activity of humans who "navigate" between vowels, given that vowel space can be approximated with a continuous trapezoidal 2D manifold, spanned by the first and second formant frequencies. We created 30 vowel trajectories in the assumedly flat central portion of the trapezoid. Each of these trajectories had a duration of 240 milliseconds, with a steady start and end point on the perimeter of a "wheel". We hypothesized that if the neural representation of this "box" is similar to that of rodent grid units, there should be an at least partial hexagonal (6-fold) symmetry in the EEG response of participants who navigate it. We have not found any dominant n-fold symmetry, however, but instead, using PCAs, we find indications that the vowel representation may reflect phonetic features, as positioned on the vowel manifold. The suggestion, therefore, is that vowels are encoded in relation to their salient sensory-perceptual variables, and are not assigned to arbitrary gridlike abstract maps. Finally, we explored the relationship between the first PCA eigenvector and putative vowel attractors for native Italian speakers, who served as the subjects in our study

Cost-effectiveness analysis of guidelines for antihypertensive care in Finland

<p>Abstract</p> <p>Background</p> <p>Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario).</p> <p>Methods</p> <p>A decision analytic model compares the ACCG and PCP scenarios using information synthesised from a set of national registers covering prescription drug reimbursements, morbidity, and mortality with data from two national surveys concerning health and functional capacity. Statistical methods are used to estimate model parameters from Finnish data. We model the potential impact of the different treatment strategies under the ACCG and PCP scenarios, such as lifestyle counselling and drug therapy, for subgroups stratified by age, gender, and blood pressure. The model provides estimates of the differences in major health-related outcomes in the form of life-years and costs as calculated from a 'public health care system' perspective. Cost-effectiveness analysis results are presented for subgroups and for the target population as a whole.</p> <p>Results</p> <p>The impact of the use of the ACCG scenario in subgroups (aged 40–80) without concomitant cardiovascular and related diseases is mainly positive. Generally, costs and life-years decrease in unison in the lowest blood pressure group, while in the highest blood pressure group costs and life-years increase together and in the other groups the ACCG scenario is less expensive and produces more life-years. When the costs and effects for subgroups are combined using standard decision analytic aggregation methods, the ACCG scenario is cost-saving and more effective.</p> <p>Conclusion</p> <p>The ACCG scenario is likely to reduce costs and increase life-years compared to the PCP scenario in many subgroups. If the estimated trade-offs between the subgroups in terms of outcomes and costs are acceptable to decision-makers, then widespread implementation of the ACCG scenario is expected to reduce overall costs and be accompanied by positive outcomes overall.</p