ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.

A prospective 10 year follow up study of patients with neurofibromatosis type 1.

OBJECTIVE: To establish the prevalence and incidence of symptoms and complications in children with neurofibromatosis type 1 (NF1) and to assess possible risk factors for the development of complications. DESIGN: A 10 year prospective multidisciplinary follow up study. PATIENTS: One hundred and fifty children diagnosed with NF1 according to criteria set by the National Institutes of Health. RESULTS: In 62 of 150 children (41.3%) complications were present, including 42 (28.0%) children with one complication, 18 (12.0%) with two complications, and two (1.3%) with three complications (mean (SD) duration of follow up 4.9 (3.8) years). Ninety five of the 150 children presented without complications (follow up, 340.8 person-years). The incidence of complications was 2.4/100 person-years in this group. An association was found between behavioural problems and the presence of complications. CONCLUSION: This is the largest single centre case series of NF1 affected children followed until 18 years of age. Children with NF1, including those initially presenting without complications, should have regular clinical examinations.

Arterial and venous repair with vascular clips: comparison with suture closure.

PURPOSE: Nonpenetrating, arcuate-legged titanium vascular closure staple (VCS) clips were initially developed for microvascular anastomoses with little experience of their use in larger vessels. The purpose of this study was to compare the VCS clips with standard suture closure of arteriotomies and venotomies in common iliac vessels of pigs. METHODS: In nine pigs, longitudinal 1 cm iliac arterial and venous incisions were repaired with VCS clips on one side and continuous 6-0 polypropylene suture on the other, and the macroscopic and microscopic results were assessed after 3 months. RESULTS: The time required for vessel repair was significantly shorter with clips than with sutures both in arteries (51 +/- 9 vs 414 +/- 36 seconds) and in veins (100 +/- 32 vs 439 +/- 45 seconds). There was no significant difference in the inner diameter, intimal thickness, or intima-to-media height ratios of the arteries or veins after either method of closure. CONCLUSIONS: Repair of 1 cm incisions in small-diameter arteries and veins with VCS clips results in wound healing as good as that achieved with standard suture closure, when assessed for patency, leakage, degree of narrowing, and intimal reaction. The time required for clip closure is considerably shorter than for suture closure.