ObjectivesTo investigate contrast-enhanced ultrasound (CEUS) with VEGFR2-targeted microbubbles for monitoring therapy effects of regorafenib on experimental colon carcinomas in rats with correlation to dynamic contrast-enhanced MRI (DCE-MRI) and immunohistochemistry.Materials and MethodsHuman colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 21 (n = 11 therapy group; n = 10 control group) female athymic nude rats (Hsd: RH-Foxn1rnu). Animals were imaged at baseline and after a one-week daily treatment with regorafenib or a placebo (10 mg/kg bodyweight), using CEUS with VEGFR2-targeted microbubbles and DCE-MRI. In CEUS tumor perfusion was assessed during an early vascular phase (wash-in area under the curve = WiAUC) and VEGFR2-specific binding during a late molecular phase (signal intensity after 8 (SI8min) and 10 minutes (SI10min)), using a conventional 15L8 linear transducer (transmit frequency 7 MHz, dynamic range 80 dB, depth 25 mm). In DCE-MRI functional parameters plasma flow (PF) and plasma volume (PV) were quantified. For validation purposes, CEUS parameters were correlated with DCE-MRI parameters and immunohistochemical VEGFR2, CD31, Ki-67 and TUNEL stainings.ResultsCEUS perfusion parameter WiAUC decreased significantly (116,989 ± 77,048 a.u. to 30,076 ± 27,095a.u.; p = 0.005) under therapy with no significant changes (133,932 ± 65,960 a.u. to 84,316 ± 74,144 a.u.; p = 0.093) in the control group. In the therapy group, the amount of bound microbubbles in the late phase was significantly lower in the therapy than in the control group on day 7 (SI8min: 283 ± 191 vs. 802 ± 460 a.u.; p = 0.006); SI10min: 226 ± 149 vs. 645 ± 461 a.u.; p = 0.009). PF and PV decreased significantly (PF: 147 ± 58 mL/100 mL/min to 71 ± 15 mL/100 mL/min; p = 0.003; PV: 13 ± 3% to 9 ± 4%; p = 0.040) in the therapy group. Immunohistochemistry revealed significantly fewer VEGFR2 (7.2 ± 1.8 vs. 17.8 ± 4.6; p < 0.001), CD31 (8.1 ± 3.0 vs. 20.8 ± 5.7; p < 0.001) and Ki-67 (318.7 ± 94.0 vs. 468.0 ± 133.8; p = 0.004) and significantly more TUNEL (672.7 ± 194.0 vs. 357.6 ± 192.0; p = 0.003) positive cells in the therapy group. CEUS parameters showed significant (p < 0.05) correlations to DCE-MRI parameters and immunohistochemistry.ConclusionsCEUS with VEGFR2-targeted microbubbles allowed for monitoring regorafenib functional and molecular therapy effects on experimental colorectal adenocarcinomas with a significant decline of CEUS and DCE-MRI perfusion parameters as well as a significant reduction of specifically bound microbubbles under therapy, consistent with a reduced expression of VEGFR2.
Purpose The purpose of this study was to determine the long-term complications and outcomes of secondary intraocular lens (IOL) implantation in patients with congenital cataracts. Patients and MethodsThe medical records of children operated for secondary IOL implantation surgery between 2000 and 2014 were retrospectively reviewed. Those who had undergone their initial congenital cataract surgery before 7 months of age were included and were analyzed for intra-and postoperative factors and postoperative refractive outcomes. We focused on three complications: visual axis opacification (VAO), glaucoma, and IOL exchange after at least 1 year of follow-up. Results A total of 49 eyes of 49 patients were analyzed for intraoperative indications. Of those, 37 eyes of 37 patients had at least 1 year of follow-up and were analyzed for postoperative outcomes. The mean age at secondary implantation was 55.2 ± 21.6 months. At secondary implantation, 69.4% of eyes were implanted in the capsular bag, 28.6% in the sulcus, and 2.0% that were angle-supported. There was no significant correlation between the site of secondary IOL implantation and age at implantation (P = 0.216). The mean follow-up after implantation was 57.6 ± 33.6 months. The rate of VAO was 5.4%, the rate of glaucoma occurring after secondary implantation was 16.2%, and the rate of IOL exchange was 2.7%. The median visual acuity at final follow-up was 20/40. For patients with unilateral cataracts it was 20/60 and for bilateral patients it was 20/30. ConclusionsThe secondary IOL implantation in children is a relatively safe procedure associated with low rates of postoperative complications. Visual outcomes are acceptable and are better for bilateral patients than for unilateral patients.
Purpose To evaluate using the resected medial rectus muscle for elongation of the lateral rectus tendon in monocular surgery for large-angle sensory exotropia. Patients and Methods A prospective case series was carried out in Tanta University hospital from January 2017 to June 2018 including 16 patients with large-angle sensory exotropia ≥50PD. The near and distance angles of exotropia were measured; any restrictions in adduction or abduction were recorded and scaled from −4 to 0. Resection of the medial rectus muscle was done first; the resected segment was attached to the lateral rectus muscle after dissection by mattress sutures, and the muscle was recessed after elongation according to the preoperative distance angles. Successful motor alignment was considered if the angle measurement was within 10 PD of orthotropia at distance after 6 months. The stability of the alignment, any motility restrictions, and patient satisfaction were recorded at each follow-up visit until the 6th month. Results The mean age of the study patients was 30.68±13.30 years. The best-corrected visual acuity of the exotropic eyes by logMAR was 1.2±0.3; the mean of the preoperative distance angle of deviation was −72.19 ±14.26 PD. The mean preoperative adduction and abduction restrictions were −1.19 ±1.52 and −1.13 ±1.09, respectively. There was significant improvement in the distance angle of deviation at the last follow-up after 6 months (p=0.001*). Also, there was improvement in both adduction and abduction restriction from the first to last follow-up. Thirteen patients (81.2%) were satisfied at the 6-month follow-up. Conclusion Elongation of the lateral rectus muscle by an autograft from the resected medial rectus muscle is an easy, effective procedure for large-angle sensory exotropia. Patients achieve good postoperative alignment with minimal restriction of ocular motility.
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