RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial.

Background: Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. Patients and methods: In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. Results: A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis. Conclusion: This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.

The efficacy of controlled antibiotic release for prevention of polyethyleneterephthalate- (Dacron-) related infection in cardiovascular surgery.

Infection of prostheses containing polyethyleneterephthalate (Dacron) remains a dreaded complication in cardiovascular surgery despite perioperative antibiotic (AB) prophylaxis. Dacron, which is widely applied as a fabric for manufacturing vascular prostheses and also the sewing rings of artificial heart valves, remains a source for infection once implanted in the body. In order to increase the AB concentration in Dacron, an experimental study including topical application of the gentamicin derivative EMD 46/217 and fibrin sealant (F) as AB carrier was initiated. In-vitro pretreatment of Dacron with the gentamicin derivative and F was followed by constant AB release for three weeks. In a subsequent animal study, four Dacron rings with different pretreatments were implanted in the descending aorta of ten pigs after direct contamination with 10 8 Staph. aureus solution. One ring was pretreated with the AB/F compound, a second ring with the AB alone. Ring 3 (no pretreatment) and ring 4 (F alone) served as controls. After one week, the Dacron rings and their corresponding implantation sites were asserved for measurement of AB content and for culture. The AB content of AB/F rings was 24.99 +/- 7.16 mug/g wet weight, while Dacron rings pretreated with the AB alone contained no measurable drug amounts, with the exception of one specimen (0.5 mug/g)(AB/F versus AB rings: P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

[Papillary cystadenoma of the epididymis. Apropos of a rare case in a patient with grade III varicocele]. / Il cistoadenoma papillare dell'epididimo. A proposito di un raro caso in soggetto portatore di varicocele di III grado.

Primary tumours of the epididymis are rare and one of the rarest is papillary cysto-adenomas. For this reason, a case arising in a patient with Grade III varicocele seemed worth reporting. The report discusses the clinical case and describes the histological characteristics of the tumour.

A new primate model for the study of intravenous thrombotic potential and its modification.

Advances in venous reconstruction have been limited by inherent venous thrombogenicity and the absence of a suitable prosthetic material for use in the venous system. We have designed an in vivo experimental model to evaluate early blood-material interactions within the venous system and to quantitate drug efficacy in the alteration of platelet function and fibrin deposition in the baboon. An 8F catheter was placed percutaneously in the femoral vein of an adult male baboon. Indium 111-labeled autogenous platelets or iodine 125-labeled human fibrinogen was infused before the introduction, into the inferior vena cava, of a linear array of 5 x 15 mm alternating Dacron and polytetrafluoroethylene samples attached to a benzalkonium-heparin-treated guide wire. At 60 or 120 minutes the samples were removed and a 1 ml aliquot of blood was drawn. The materials and blood samples were counted in a gamma well counter, and the material counts were normalized to the circulating label present in the 1 ml blood sample. The experiment was repeated after pretreatment with heparin, aspirin, or dextran. Whole blood clotting times and bleeding times were monitored. The results showed decreased platelet and fibrin deposition on polytetrafluoroethylene when compared with Dacron in the venous system. Aspirin, heparin, and dextran were all found to decrease platelet and fibrin deposition onto intravenously placed graft material samples (p less than 0.05, Student's t test). The data confirm the ability of the model to evaluate quantitatively anticoagulants, antiplatelet agents, and prospective graft materials for use in venous reconstructions.