Local excision for ypT2 rectal cancer--much ado about something.

BACKGROUND: The role of local excision for pT2 distal rectal cancer has been challenged because of the observation of high rates of lymph node metastases and local failure. However, neoadjuvant chemoradiation therapy (CRT) has led to increased local disease control and significant tumor downstaging, possibly decreasing rates of lymph node metastases. In this setting, a possible role for local excision of ypT2 has been suggested. METHODS: A total of 401 patients with distal rectal cancer underwent neoadjuvant CRT. Tumor response assessment was performed after at least 8 weeks from CRT completion. One hundred and twelve patients with complete clinical response were not immediately operated on and were excluded from the study, and 289 patients with incomplete clinical response were managed by radical surgery. Patients with final pathological stage ypT2 were analyzed to determine the risk of unfavorable pathological features that could represent unacceptable risk for local failure after local excision. RESULTS: Eighty-eight (30%) patients had ypT2 rectal cancer. Final ypT status was not associated with pretreatment radiological staging (p = 0.62). ypT status was significantly associated with the risk of lymph node metastases, risk of perineural and vascular invasion, and recurrence (p = 0.001). Lymph node metastases were present in 19% of patients with ypT2 rectal cancer. The risk of lymph node metastases in ypT2 was associated with the presence of perineural invasion (47% vs 4%; p = <0.001), vascular invasion (59% vs 6%; p < 0.001), and decreased mean interval CRT surgery (12 vs 18 weeks; p < 0.001), but not with mean tumor size (3.2 vs 3.1 cm; p = 0.8). Disease-free and overall survival rates were significantly better for patients with ypT2N0 (p = 0.02 and 0.006, respectively). Fifty-five (63%) patients with ypT2 had at least one unfavorable pathological feature for local excision (lymph node metastases, vascular or perineural invasion, mucinous type or tumor size >3 cm). CONCLUSION: Lymph node metastases were present in 19% of patients with ypT2 and were significantly associated with poor overall and disease-free survival rates. The risk of lymph node metastases could not be predicted by radiological staging or tumor size. Radical surgery should be considered the standard treatment option for ypT2 rectal cancer after CRT.     

Incidence of Type 2 diabetes in England and its association with baseline impaired fasting glucose: the Ely study 1990-2000.

AIM: To determine the incidence of Type 2 diabetes and to examine the effect of different cut-points for impaired fasting glucose (IFG) on diabetes incidence. METHODS: Population-based longitudinal study (1990-2000) with clinical, anthropometric and biochemical measurements, including an oral glucose tolerance test (OGTT), in 1040 non-diabetic adults aged 40-69 years at baseline. Baseline glucose status was defined as normoglycaemia < 5.6, IFG-lower 5.6-6.0 and IFG-original 6.1-6.9 mmol/l. The all-IFG group included fasting glucose values of 5.6-6.9 mmol/l. RESULTS: The 10-year cumulative incidence of diabetes was 7.3 per 1000 person-years. Diabetes incidence was 2.4 [95% confidence interval (CI) 1.2, 4.8], 6.2 (4.0, 9.8) and 17.5 (12.5, 24.5) per 1000 person-years in those with normoglycaemia, IFG-lower and IFG-original, respectively. Compared with normoglycaemia, the age/sex-adjusted risk [hazard ratio (HR) and 95% CI] for incident diabetes was greatest in the IFG-original category (HR 6.9; 3.1, 15.2) and increased to a lesser degree in the IFG-lower (HR 2.5; 1.1, 5.7) and all-IFG categories (HR 4.1; 1.9, 8.7). When adjusted for confounding factors, the magnitude and direction of associations persisted, with HR 1.9, 4.4 and 2.9, for the categories IFG-lower, IFG-original and all-IFG, respectively. CONCLUSIONS: Diabetes incidence is more strongly related to IFG defined as fasting glucose between 6.1 and 6.9 mmol/l than to the lower category of 5.6-6.0 mmol/l, or entire range of 5.6-6.9 mmol/l. Future studies should examine the association of IFG with cardiovascular outcomes, but for diabetes risk our study supports the use of the IFG cut-point at 6.1 mmol/l.     

Risperidone and cognitive function in children with disruptive behavior disorders.

BACKGROUND: Effects of risperidone on cognitive function in children with disruptive behavior disorders (DBDs) and subaverage intelligence quotient (IQ) were assessed. METHODS: Data from two 6-week, double-blind, placebo-controlled studies (n = 228) were combined, as were three 1-year, open-label studies (n = 688). Patients with DBDs and subaverage IQ, 5 to14 years, received placebo or risperidone .02 to .06 mg/kg/day. Cognitive measures included the Continuous Performance Task (CPT) and Verbal Learning Test for Children (VLT-C). Efficacy was assessed using the Nisonger Child Behavior Rating Form (NCBRF). Adverse events were collected via spontaneous report; sedation was assessed using visual analog scale. RESULTS: Improvements on the NCBRF Conduct Problem subscale were significantly greater for risperidone- versus placebo-treated patients (-15.8 vs. -6.4, p < .0001) in short-term studies; significant reductions were observed in long-term studies (-16.3, p < .0001). No overall decline and some significant improvement in attention (CPT) and memory (VLT-C) were noted regardless of treatment in short-term studies. VLT-C improved significantly (p < .0001) for both groups, with no difference between treatment groups. Improvements in memory (VLT-C) and attention (CPT) were noted in long-term studies. Somnolence/sedation did not affect cognitive function. CONCLUSIONS: Cognitive function was not altered by risperidone in short-term studies and was maintained or improved with one year of treatment in children with DBDs and subaverage IQ, potentially representing age-appropriate gains.