Perianal Paget's disease (PPD) represents a skin neoplasm which can be either primary or secondary to carcinoma from an adjacent internal organ. PPD with underlying colorectal adenocarcinoma is usually looked upon as a secondary disease. We report a rare case of co-associated PPD and anorectal adenocarcinoma. The PPD was found to be located near the anorectal adenocarcinoma with normal tissues between them. Immunohistochemical stains demonstrated that the Paget's cells were CK7+/GCDFP-15-/CK20-/MUC2-/CDX2-, whereas the anorectal adenocarcinoma was shown to be CK7+/GCDFP-15-/CK20+/MUC2+/CDX2+. This immunological phenotypic profile supported the notion that PPD and anorectal adenocarcinoma were of different origins, but could not define the exact origins of PPD. In our determination, this case was a primary PPD with anorectal adenocarcinoma. PPD remains a heterogeneous and complex pathology, and additional studies are required to differentiate between the various possible origins.
Background Anlotinib, an oral small molecule tyrosine kinase inhibitor targeting VEGFR 1/2/3, FGFR 1-4, PDGFR a/β, and c-kit, had demonstrated prolonged progression-free survival (PFS) in refractory metastatic colorectal cancer (mCRC). This multicenter, single-arm, phase II, exploratory study was conducted to evaluate the efficacy and safety of anlotinib combined with capecitabine and oxaliplatin as first-line treatment for unresectable RAS/BRAF wild-type mCRC. Methods Patients aged 18–75 with RAS/BRAF wild-type unresectable mCRC, without prior systemic treatment, and ECOG performance status ≤1 were enrolled. Eligible patients received capecitabine (850 mg/m2, p.o., bid, on day 1–14 every 21 days), oxaliplatin (130 mg/m2, i.v., on day 1 every 21 days), and anlotinib (12 mg, p.o., qd, on days 1–14 every 21 days) as induction therapy. Following 6 cycles of therapy, patients who achieved response or stable disease received capecitabine and anlotinib as maintenance therapy until tumor progression. The primary endpoint was objective response rate (ORR) according to RECIST (version: 1.1), and the secondary endpoints were PFS, disease control rate (DCR), duration of response (DOR), and safety. Results Between November 2019 and February 2021, 31 patients were enrolled. One patient was excluded for refusing treatment. The primary endpoint of ORR was 76.7% (95% CI, 57.7–90.1) with 1 patient achieving a complete response and 22 patients partial response. DCR was 93.3% (95% CI, 77.9–99.2). At a median follow-up of 14.1 months (95% CI, 9.9–18.3), median PFS was 11.3 months (95% CI, 7.1–14.1), and DOR was 7.9 months (95% CI, 5.5–12.7). Twenty-five (83.3%) patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs). No grade 5 TEAE was reported. The most common grade 3 or 4 TEAEs (>10%) were hypertension (15/30; 50%), neutrophil count decreased (8/30; 26.7%), and diarrhea (4/30; 13.3%). A total of 18 (60%) patients had TEAEs that resulted in dose reduction, interruptions, or delays. Conclusions Anlotinib combined with capecitabine and oxaliplatin showed considerable ORR, DCR, PFS, and DOR in the first-line therapy of mCRC with manageable toxicity profiles. Trial registration ClinicalTrials.gov: NCT04080843
We theoretically analyzed and experimentally demonstrated an injection-locking based all-optical flip-flop memory using a simple and compact tunable V-cavity laser (VCL). A bistable region in the tuning characteristics of the VCL is employed for the flip-flop operation. The state of the VCL can be set and reset by injecting signal pulses at two different wavelengths. The pulse power for both set and reset signal is only about 1 pJ. Short response times of about 150 ps are measured for storing and erasing.
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