Summaryintroduction Surgery for trachomatous trichiasis prevents blindness and is advocated by the WHO as part of the SAFE strategy for the global elimination of trachoma. We conducted a randomised community trial to investigate the effect of providing surgery in villages on surgical uptake in The Gambia.

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The molecular basis of double cortex syndrome was investigated in 2 male patients. Magnetic resonance imaging of the patients' heads showed diffuse subcortical band heterotopia, as is seen in female patients. We found a heterozygous mutation for Asp50Lys or Arg39Stop in both patients. Microsatellite polymorphism analysis revealed that both patients had inherited a single X chromosome from their mothers. Restriction enzyme analysis using DNA extracted from the hair roots of each patient showed four different patterns in the combination of cells carrying wild and mutant alleles, which strongly suggest somatic mosaicism. We conclude that somatic mosaic mutations in the doublecortin gene in male patients can cause subcortical band heterotopia, and that molecular analysis using hair roots is a useful method for detecting somatic mosaicism.

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RESULTS: VH types included squamous (n¼27), glandular (n¼8), micropapillary (n¼6), sarcomatoid (n¼5), clear cell (n¼4), neuroendocrine (n¼3), nested (n¼1), spindle (n¼1), inverted papilloma (n¼1), and mixed variants (n¼15). VH was more likely to present with extravesical disease (16.9% vs 7.5%, p<0.01), be upstaged at RC (60.6% vs 30.8%, p<0.01), have lymphovascular invasion (LVI) (40.8% vs 28.8%, p<0.01), and lymph node metastasis at RC (28.2% vs 14.4%, p<0.01). The mean days to cystectomy did not differ between PUC and VH (61.1 vs 63.9, p¼0.58). Median follow-up time was 3.5 years. On univariate analysis, for patients with VH, delays greater than 8 weeks were associated with worse OS (HR¼2.20, p¼0.02), while for PUC, only delays greater than 12 weeks reached significance (HR¼1.54, p¼0.04). Multivariable analysis controlling for age, comorbidities, tumor stage, lymph node status, LVI, and surgical margins confirmed worse OS for each month in delay to RC for VH (HR¼1.35, p<0.01). The 5-year overall survival for VH with time to RC of less than 8 weeks was 63% compared to 34% for greater than 8 weeks (p¼0.02).CONCLUSIONS: Variant histology portends a poor prognosis and was more likely to have LVI, be upstaged at RC, and have lymph node metastasis when compared to PUC. Delays in RC greater than 8 weeks for patients with VH were associated with worse overall survival, thus highlighting the need for timely diagnosis and treatment.