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Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Patients and Methods

We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.

Results

Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.

Conclusions

FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.  相似文献   
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HOCK LEONG EE  MBBS  MRCP    CHEE LEOK GOH  MBBS  FRCP    KHOO    ES-Y. CHAN  PHD    POR ANG  MBBS  MRCP 《Dermatologic surgery》2006,32(1):34-40
BACKGROUND: Acquired bilateral nevus of Ota-like macules (Hori's nevus) is a common dyschromatosis among Asian women. Q-switched lasers have been used successfully as a treatment modality. OBJECTIVE: The purpose of this study was to compare the efficacy of using the Q-switched 532 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser followed by the 1,064 nm laser versus the Q-switched 1,064 nm Nd:YAG laser alone in the treatment of Hori's nevus. METHODS: This is a prospective left-right comparative study. Ten women with bilateral Hori's nevus were recruited and treated with a combination of the Q-switched 532 and 1,064 nm Nd:YAG lasers on the right cheek and the Q-switched 1,064 nm Nd:YAG laser alone on the left cheek. Only one laser treatment session was performed. The degree of pigmentation was objectively recorded with a mexameter. Subjective assessment was made by both patients and two blinded, nontreating dermatologists. RESULTS: At 6 months, there was a statistically significant difference (p = .009) of 35.10 points using objective mexameter measurements between the two sides, favoring the side treated with a combination of 532 and 1,064 nm laser treatment. Subjective grading by the patients and blinded dermatologists also confirmed that combination therapy was more successful after one treatment. Although combination treatment had a higher incidence of mild postinflammatory changes, this disappeared within 2 months. CONCLUSIONS: Concurrent use of the Q-switched 532 nm Nd:YAG laser in combination with the 1,064 nm laser is more effective in pigment clearance than the Q-switched 1,064 nm Nd:YAG laser alone for Hori's nevi.  相似文献   
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BACKGROUND: Impaired neuropsychological test performance, especially on tests of executive function and attention, is often seen in children diagnosed with autism spectrum disorders (ASD). Structures involved in fronto-striatal circuitry, such as the caudate nucleus, may support these cognitive abilities. However, few studies have examined caudate volumes specifically in children with ASD, or correlated caudate volumes to cognitive ability. METHODS: Neuropsychological test scores and caudate volumes of children with ASD were compared to those of children with bipolar disorder (BD) and of typically developing (TD) children. The relationship between test performance and caudate volumes was analyzed. RESULTS: The ASD group displayed larger right and left caudate volumes, and modest executive deficits, compared to TD controls. While caudate volume inversely predicted performance on the Wisconsin Card Sorting Test in all participants, it differentially predicted performance on measures of attention across the ASD, BD and TD groups. CONCLUSIONS: Larger caudate volumes were related to impaired problem solving. On a test of attention, larger left caudate volumes predicted increased impulsivity and more omission errors in the ASD group as compared to the TD group, however smaller volume predicted poorer discriminant responding as compared to the BD group.  相似文献   
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Background  

To determine patterns of childhood lead exposure in a community living near a lead and zinc smelter in North Lake Macquarie, Australia between 1991 and 2002.  相似文献   
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