Fibroblast Growth Factor Receptor (FGFR) Signaling in GIST and Soft Tissue Sarcomas.

Sarcomas are a heterogeneous group of rare malignancies originating from mesenchymal tissues with limited therapeutic options. Recently, alterations in components of the fibroblast growth factor receptor (FGFR) signaling pathway have been identified in a range of different sarcoma subtypes, most notably gastrointestinal stromal tumors, rhabdomyosarcomas, and liposarcomas. These alterations include genetic events such as translocations, mutations, and amplifications as well as transcriptional overexpression. Targeting FGFR has therefore been proposed as a novel potential therapeutic approach, also in light of the clinical activity shown by multi-target tyrosine kinase inhibitors in specific subtypes of sarcomas. Despite promising preclinical evidence, thus far, clinical trials have enrolled very few sarcoma patients and the efficacy of selective FGFR inhibitors appears relatively low. Here, we review the known alterations of the FGFR pathway in sarcoma patients as well as the preclinical and clinical evidence for the use of FGFR inhibitors in these diseases. Finally, we discuss the possible reasons behind the current clinical data and highlight the need for biomarker stratification to select patients more likely to benefit from FGFR targeted therapies.

The effects of environmental and compositional manipulations on the longevity of Tessari-made foam for sclerotherapy.

BACKGROUND: Tessari-made foam sclerotherapy is performed around the world in a variety of clinics differing in methods, equipment, temperatures, and altitudes. We investigated how the following factors affected the foam's longevity: silicone vs nonsilicone syringes, volume of foam made, ratio of gas to sclerosant, use of air vs 50:50 mixture of carbon dioxide and oxygen, temperature, altitude, and 10 consecutive reuses of the syringes. METHODS: Sclerosant foam was made by the Tessari double-syringe technique. To calculate the longevity, the time was taken for half of the original volume of sclerosant to settle. Half-lives were compared with use of silicone and silicone-free syringes to make the foam. We investigated how the volume (5 mL vs 2 mL) and different ratios affected the foam by observing the half-life of 4:1, 3.5:1, and 3:1 ratios of gas to sclerosant. Air and a 50:50 mixture of carbon dioxide and oxygen were both used as the gas in changing the ratio and volume to see which produced better foam. These experiments were conducted at room (23.9°C) and refrigerator (3°C) temperatures with a constant pressure. The different ratio, volume, and silicone vs nonsilicone syringe experiments were all repeated at 9314, 7460, 4575, and 2326 feet above sea level in addition to the baseline experiment, which took place at 236 feet above sea level. To test how consecutive uses of syringes affected the foam, we made consecutive batches of foam reusing each pair of syringes 10 times; this was repeated five times with silicone syringes and twice with nonsilicone syringes. RESULTS: Switching to nonsilicone syringes can increase longevity by 70%. A larger volume of foam and a 3:1 ratio produced longer half-lives at all temperatures and altitudes. The lower (3°C) temperature increased the longevity of foam in all instances, as did the use of air. A high altitude (low pressure) had a detrimental effect on the foam's longevity. Ten consecutive syringe uses had no significant impact on the foam's half-life (silicone syringe mean between first five and last five uses, P = .95). CONCLUSIONS: The optimum conditions for making foam are nonsilicone syringes, larger volumes, a 3:1 air to sclerosant ratio, and low temperatures. Silicone syringes can be reused until friction becomes a burden. Temperature has a bigger effect than altitude on longevity of the foam. Making foam in larger volumes would allow the foam to last longer. To compensate for high altitudes (low pressures), decreasing the temperature will increase the foam's longevity.

Strip-tract revascularization as a source of recurrent venous reflux following high saphenous tie and stripping: results at 5-8 years after surgery.

OBJECTIVE: We have previously reported strip-tract revascularization 1 year following high saphenous ligation and inversion stripping. This study reports the 5-8 year results in the same cohort. METHODS: Between 2000 and 2003, 72 patients presented with primary varicose veins and had undergone high saphenous ligation and inversion stripping plus phlebectomies with or without subfascial endoscopic perforator surgery. Of the 64 patients who had attended for follow-up at 1 year, 35 patients (male:female, 16:19; 39 legs) underwent duplex ultrasonography 5-8 years after surgery (response rate 55%). Duplex ultrasonography was performed and all strip-tract revascularization and reflux and groin neovascularization was documented. RESULTS: Eighty-two percent of legs of patients showed some evidence of strip-tract revascularization and reflux. Full and partial strip-tract revascularization and reflux was seen in 12.8% and 59% of limbs of patients, respectively, and 10.2% limbs of patients had neovascularization only at the saphenofemoral junction only. Seven limbs of patients showed no revascularization. CONCLUSION: Five to eight years after high saphenous tie and stripping, 82% of legs of patients showed some strip-tract revascularization and reflux and 12% showed total revascularization and reflux of the stripped great saphenous vein.

Arterial false aneurysm in the groin following endovenous laser ablation.

Endovenous laser ablation is a minimally invasive catheter-based procedure for the treatment of varicose veins. The procedure involves injecting tumescent anaesthesia around the catheterised truncal vein, before thermal ablation by the laser. We report a case of a false aneurysm arising from a branch of the inferior epigastric artery, following endovenous laser ablation. The false aneurysm was thought to be caused by injury to the artery by the needle used to inject the tumescent anaesthesia. Although a rare complication, newer tumescentless techniques such as mechanicochemical ablation and cyanoacrylate glue would prevent such a complication.

Primary avalvular varicose anomalies are a naturally occurring phenomenon that might be misdiagnosed as neovascular tissue in recurrent varicose veins.

OBJECTIVE: The objective of this study was to report a phenomenon in patients with primary varicose veins that resembles neovascular tissue in postsurgical recurrences-primary avalvular varicose anomalies (PAVA). METHODS: Between March 2012 and July 2013, 756 patients (122 men, 634 women) with primary varicose veins (mean age, 53 years; range, 18-89 years) underwent duplex ultrasonography with retrospective analysis of their reflux patterns. We diagnose PAVA as small, refluxing vessels in legs with primary varicose veins and no history of surgery, trauma, or infection in the area that show one or more of three patterns of distribution: lymph node pattern-PAVA arising directly from groin lymph nodes; peritruncal pattern-PAVA wrapping around the great, small, or anterior accessory saphenous veins; and atypical pattern. PAVA are predominantly found within the saphenous fascia, but components have been found to emerge into the superficial and deep venous compartments. RESULTS: We analyzed results from 1398 legs (756 patients). Sixty-four legs (4.6%) in 58 patients exhibited PAVA, bilateral in six patients and unilateral in 52 patients. Lymph node involvement and peritruncal PAVA were seen in 23.4% and 70.3% of legs, respectively. The small saphenous vein was the most common truncal vein to be involved (48.9% of peritruncal cases). More than one pattern of PAVA could be observed in seven legs. Of the 48 women with PAVA, 42% had concurrent pelvic vein reflux. CONCLUSIONS: Neovascularization has been identified as a major cause of clinically recurrent varicose veins. Neovascular tissue has been described after endovenous thermoablation. We suggest that this might represent PAVA undetected preoperatively in some cases. PAVA are thin-walled, serpiginous, incompetent vessels that resemble neovascular tissue. We conclude that neovascularization should be diagnosed as a source of recurrence after endovenous surgery only if PAVA had been actively looked for, and excluded, in the preoperative diagnostic duplex ultrasound examination.