Clinical Impact of Tumour Involvement of the Anastomotic Doughnut in Oesophagogastric Cancer Surgery

INTRODUCTION

Published colorectal cancer surgery data suggest no role for the analysis of the anastomotic doughnuts following anterior resection. The usefulness of routine histological analysis of the upper gastrointestinal doughnut is not clear. Our study assessed the impact of cancer involvement of the doughnut on clinical practice. Factors associated with doughnut involvement and the effect on patients'' survival were also analysed.

PATIENTS AND METHODS

The clinicopathological details of 462 patients who underwent potentially curative oesophagogastrectomy for cancer with a stapled anastomosis between 1994 and 2006 in two specialist centres were retrospectively analysed. Univariate, multivariate and survival analyses were carried out.

RESULTS

Approximately 5% of doughnuts (22 of 462) were histologically involved with cancer. Microscopic involvement of the proximal resection margin, local lymph node metastasis and lymphatic invasion within the main resected specimen were independently associated with doughnut involvement (all P < 0.05). However, these three factors taken together failed to predict doughnut involvement. Doughnut involvement was an independent adverse prognostic factor for overall survival (P = 0.0013).

CONCLUSIONS

In contrast to findings in colorectal surgery, doughnut involvement with cancer appears to have useful prognostic information following oesophagogastrectomy. Routine histological analysis of upper gastrointestinal doughnuts is justified. Doughnut involvement could potentially strengthen the indications for adjuvant therapy in the future.     

Involvement of insula and cingulate cortices in control and suppression of natural urges

The physiology of control and suppression of natural urges isnot well understood. We used [¹⁵O]H₂O positron-emission tomographyimaging to identify neural circuits involved in suppressionof spontaneous blinking as a model of normal urges. Suppressionof blinking was associated with prominent activation of bilateralinsular-claustrum regions, right more than left; activationwas also found in bilateral anterior cingulate cortex (ACC),supplementary motor areas, and the face area of the primarymotor cortex bilaterally. These results suggest a central rolefor the insula possibly together with ACC in suppression ofblinking.     

Leukocyte Telomere Length Is Not Associated With BMD,Osteoporosis, or Fracture in Older Adults: Results From the Health,Aging and Body Composition Study

Short leukocyte telomere length (TL), low BMD, and osteoporosis have been associated with increased inflammation. Previous reports suggest an association between TL, BMD, and osteoporosis in women. We sought to verify these associations and to determine whether TL is related to fracture in a cohort of older men and women. Participants included 2750 community‐dwelling older persons from the longitudinal Health, Aging, and Body Composition Study (Health ABC) in who average leukocyte TL was measured at baseline using qPCR. We used unconditional logistic regression to determine the association of TL with prevalent fracture, Cox proportional hazards regression for the association with 7‐yr incident fracture, and mixed linear models for the association with BMD, change in BMD, and the number of incident fractures. TL was negatively correlated with age, weight, fasting insulin, and fasting glucose in men and women, and additionally, with C‐reactive protein and IL‐6 in men. TL was not associated with BMD; change in BMD over 1, 3, or 5 yr; osteoporosis; baseline fracture; or 7‐yr incident fracture, before or after adjustment for age, race, smoking, and health characteristics. TL is not associated with BMD, osteoporosis, or fracture in older men or women in this sample.     

Experience with intravenous ribavirin in the treatment of hemorrhagic fever with renal syndrome in Korea

Results of a clinical study using intravenous (IV) ribavirin for treating Department of Defense personnel with hemorrhagic fever with renal syndrome (HFRS) acquired in Korea from 1987 to 2005 were reviewed to determine the clinical course of HFRS treated with IV ribavirin. A total of 38 individuals enrolled in the study had subsequent serological confirmation of HFRS. Four of the 38 individuals received three or fewer doses of ribavirin and were excluded from treatment analysis. Of the remaining 34 individuals, oliguria was present in one individual at treatment initiation; none of the remaining 33 subjects developed oliguria or required dialysis. The mean peak serum creatinine was 3.46 mg/dl and occurred on day 2 of ribavirin therapy. Both the peak serum creatinine and the onset of polyuria occurred on mean day 6.8 of illness. Reversible hemolytic anemia was the main adverse event of ribavirin, with a >or=25% decrease in hematocrit observed in 26/34 (76.5%) individuals. While inability to adjust for all baseline variables prevents comparison to historical cohorts in Korea where oliguria has been reported in 39-69% cases and dialysis required in approximately 40% HFRS cases caused by Hantaan virus, the occurrence of 3% oliguria and 0% dialysis requirement in the treatment cohort is supportive of a previous placebo-controlled HFRS trial in China where IV ribavirin given early resulted in decreased occurrence of oliguria and decreased severity of renal insufficiency.     

Understanding physical activity intentions among French Canadians with type 2 diabetes: an extension of Ajzen's theory of planned behaviour

Background  

Regular physical activity is considered a cornerstone for managing type 2 diabetes. However, in Canada, most individuals with type 2 diabetes do not meet national physical activity recommendations. When designing a theory-based intervention, one should first determine the key determinants of physical activity for this population. Unfortunately, there is a lack of information on this aspect among adults with type 2 diabetes. The purpose of this cross-sectional study is to fill this gap using an extended version of Ajzen's Theory of Planned Behavior (TPB) as reference.     

Patient knowledge of coronary risk profile improves the effectiveness of dyslipidemia therapy: the CHECK-UP study: a randomized controlled trial

BACKGROUND: Despite increasing evidence that treating dyslipidemia reduces cardiovascular events, many patients do not achieve recommended lipid targets. METHODS: To determine whether showing physicians and patients the patient's calculated coronary risk can improve the effectiveness of treating dyslipidemia in a primary care setting, patients were randomized to receive usual care or ongoing feedback regarding their calculated coronary risk and the change in this risk after lifestyle changes, pharmacotherapy, or both to treat dyslipidemia. Outcomes, based on intention-to-treat analysis, included changes in blood lipid levels, coronary risk, and the frequency of reaching lipid targets. RESULTS: Two hundred thirty primary care physicians enrolled 3,053 patients. After 12 months of follow-up, 2,687 patients (88.0%) remained in the study. After adjustment for baseline lipid values, significantly greater mean reductions in low-density lipoprotein cholesterol levels and the total cholesterol to high-density lipoprotein cholesterol ratio were observed in patients receiving risk profiles (51.2 mg/dL [to convert to millimoles per liter, multiply by 0.0259] and 1.5, respectively) vs usual care (48.0 mg/dL and 1.3, respectively), but the differences were small (-3.3 mg/dL; 95% confidence interval [CI], -5.4 to -1.1 mg/dL; and -0.1; 95% CI, -0.2 to -0.1, respectively). Patients in the risk profile group were also more likely to reach lipid targets (odds ratio, 1.26; 95% CI, 1.07 to 1.48). A significant dose-response effect was also noted when the impact of the risk profile was stronger in those with worse profiles. CONCLUSIONS: Discussing coronary risk with the patient is associated with a small but measurable improvement in the efficacy of lipid therapy. The value of incorporating risk assessment in preventive care should be further evaluated.     

Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.     

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Subcellular distribution of mass can be analyzed by a technique that involves culturing cells on interferometers and digitizing their interference contours. Contour sampling resulted in 102 variables per cell, which were predictors of oncogenic transformation. Cell phenotypes can be deconstructed by use of latent factors, which represent the covariance of the real variables. The reversal of the cancer-type phenotype by a combination of microtubule-stabilizing and -depolymerizing agents was described previously. The implications of these results have been explored by clinicians who treated patients with the combination of docetaxel and vinorelbine (Navelbine). The current study was performed to determine the effects of different combinations on phenotype and in phases of the cell cycle other than mitosis. Combinations of paclitaxel with either colchicine, podophyllotoxin, nocodazole, or vinblastine caused phenotype reversal. Paclitaxel analogue, 7-deoxytaxol, by itself caused reversal. Factors #4, (filopodia), #5 (displacement and/or deep invaginations in the periphery), #8, and #12 took on values typical of normal cells, whereas the values of #7 (p21-activated kinase), and #13 (rounding up) shifted toward the cancer-type. All combinations altered microtubule arrangement at the cell edge. Delivery schedules and drug ratios used in clinical studies were subjected to analysis. Clinical response rates were better when the combination was not interspersed with a single agent (P=0.004). The results support the idea that efficacy depends upon simultaneous exposure to both agents, and suggest a novel mechanism for combination therapies. These therapies appear to restore in transformed cells some of the features of a contact-inhibited cell, and to impede progress through the cell cycle even when provided at nanomolar concentrations.     

Effect of a high-rolling-resistance training method on the success rate and time required to learn the wheelchair wheelie skill: a randomized controlled trial

OBJECTIVE: The primary objective of this study was to test the hypotheses that a wheelie training method that begins in a high-rolling-resistance (RR) setting (1) improves the success rate and (2) reduces the training time. Our secondary objectives were to assess the effects of other factors (e.g., age, gender) on training time and to acquire data on the perceptions of the participants that would assist us in refining our training methods. DESIGN: Randomized controlled study including 48 able-bodied participants with no significant wheelchair experience. Each participant was taught the wheelie skill, using up to five training sessions. Participants in the conventional group did all of their training on a smooth, level, tile surface. The RR group began training in a high-RR setting (rear wheels initially prevented from moving at all, progressing to being on 12-cm-thick foam that permitted some movement) before moving to the tile surface. Outcome measures were success rate (%), training time (mins) to achieve wheelie competence (defined as the ability to perform two consecutive 30-sec wheelies within a 1.5-m-diameter circle, assessed at least 2 days after training), and a questionnaire. RESULTS: The success rates for those in the conventional and RR groups were 96% and 100%, respectively (P = 1.000). The mean (+/-SD) training times for the conventional and RR groups were 55.9 mins (+/-27.1) and 51.8 mins (+/-18.7) (P = 0.549). Training time was not significantly affected by trainer or age, but it was affected by sex, with women requiring an average of 21.4 mins more than men (P = 0.002). Perceptions of participants in both groups about the training were positive. Of the participants in the RR group, 14 (74%) perceived the RR technique as "very effective," and five (26%) perceived it as "moderately effective." CONCLUSIONS: Neither success rate nor training time for wheelie skill acquisition by able-bodied learners are improved by a training method using high RR. Women require more time to learn than men. Learners using the RR technique perceive it to be effective. These results have implications for training practices.