Heterozygous microdeletions of chromosome 2p21 encompassing only the SIX2 gene have been described in two families to date. The clinical phenotype comprised autosomal-dominant inherited frontonasal dysplasia with ptosis in one family. In the second family, conductive hearing loss was the major clinical feature described; however, the affected persons also had ptosis. Here, we present a large family combining all three predescribed features of SIX2 gene deletion. The phenotype in four affected family members in three generations consisted of bilateral congenital ptosis, epicanthus inversus, frontonasal dysplasia with broad nasal bridge and hypertelorism, frontal bossing and large anterior fontanel in childhood, narrow ear canals, and mild conductive hearing loss with onset in childhood. Thus, the phenotypic spectrum of SIX2 haploinsufficiency is widened. Moreover, 2p21 microdeletions with SIX2 haploinsufficiency appear to lead to a recognizable phenotype with facial features resembling blepharophimosis-ptosis-epicanthus inversus syndrome.
Background: Data on oncological follow-up after robotic-assisted radical cystectomy (RARC) have been reported only scarcely and individual studies have reported an increase in early recurrences and atypical recurrences. Patients and Methods: Clinical data of 89 patients with RARC were compared to 59 patients with open radical cystectomy (ORC) at a single institution. Two-year cancer-specific (2y-CSS) and 2-year overall survival (2y-OS) related to histopathological tumor stage of RARC patients calculated by Kaplan-Meier method were compared to ORC patients using log-rank test. Early clinical recurrence rate (eCR, progression ≤6 months post-cystectomy) and metastatic pattern of both groups were compared by chi-square test. Results: Median follow-up 32 months (RARC) and 47.5 months (ORC), both groups were balanced in baseline characteristics. For RARC pts, 2y-OS and CSS-free survival rates were 80 and 90%, for ORC pts 65 and 71% (all p > 0.05). Margin status was not significantly different. eCR was observed in 10 out of 89 (11%) RARC pts and in 7 out of 59 (12%) ORC pts (p = 0.9). No difference in atypical metastases was seen between groups. Conclusion: Two-year oncological outcomes of RARC patients are comparable to ORC patients without differences regarding ePR or metastatic pattern.
e16017 Background: Trials of adjuvant chemotherapy following radical cystectomy generally require chemotherapy to start approximately 90 days postoperatively. However, it is unclear, whether the interval between surgery and start of adjuvant therapy (S-AC-interval) impacts the oncological outcome. Methods: Using the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) data base, we identified patients who underwent radical cystectomy for muscle invasive bladder cancer and subsequent adjuvant chemotherapy. Uni- and multi-variate analysis of patient characteristics, surgical factors and tumor characteristics regarding their impact on S-AC-interval was performed. Uni- and multivariate analysis of progression-free and overall survival (starting from day 1 of adjuvant chemotherapy) was analysed in relation to SAC interval (both continuous and dichotomous with a cut-off at 90 days), patient characteristics, surgical factors and tumor characteristics by Kaplan-Meier and COX regression analysis. Results: Two hundred thirty-eight eligible patients were identified (83% male, median age: 64 years, 76% T3/T4, 66% pN+, 15% R+, 75% urothelial carcinoma, 71% cisplatin-based adjuvant chemotherapy). Median S-AC-interval was 57 days (range 10-321 days, ≤ 90 days: 87%, 91-120 days: 6%, > 120 days: 7%). S-AC-interval did not have association with any patient/tumor characteristics or surgery related factors (type of surgery, diversion). S-AC-interval did not impact patients´ outcomes when adjuvant chemotherapy was initiated 90 days after surgery. Median PFS and OS in patients with an S-AC-interval of 90 days was 37 and 73 months, respectively, as compared to 24 and 48 months in patients with an S-AC-interval > 90 days. Only differences in PFS reached statistical significance (37 (95% CI 26-48) months vs. 24 (95% CI 12-36) months p = .042; Log Rank test). When analyzed by different multivariate models, the impact of S-AC-interval on PFS and OS was negated by tumor related factors (pathological T-stage and N-stage). Conclusions: An S-AC-interval of below 90 days is likely to be optimal in bladder cancer patients requiring adjuvant therapy. However, regarding prognosis, tumor related pathological factors seem to be more important than the S-AC-interval.
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