Risk factors for pancreatic fistula after stapled gland transection

The objective of this study was to identify risk factors for pancreatic fistula (PF) after stapled transection in distal pancreatectomy (DP). Patients undergoing DP using a stapler for transection between 2005 and 2009 were identified from a pancreatic resection database. Variables examined included patient and tumor characteristics, staple size, and the use of mesh reinforcement. Univariate and multivariate regression analyses were performed to identify risk factors for postoperative PF. One hundred forty-nine had stapled transection, and of these, 25 (17%) had mesh reinforcement. The overall morbidity and mortality rates were 28 per cent and less than 1 per cent; 34 (23%) were diabetic. The rate of clinically significant PF was 14 per cent. On univariate analysis, diabetes (P = 0.04), a firm pancreas (P = 0.03), use of mesh staple line reinforcement (P = 0.02), use of a 4.1-mm staple cartridge (P = 0.01), and blood loss greater than 100 mL (P = 0.01) were associated with higher pancreatic fistula rates. On multivariate analysis, only the presence of diabetes (OR, 4.17; 95% CI, 1.1-15.3; P = 0.03) and the use of a 4.1-mm cartridge (OR, 8.57; 95% CI, 1.2-60.2; P = 0.03) were independently associated with pancreatic fistula formation. Stapled pancreatic transection provides an acceptable PF rate after DP. Diabetes and staple size influence PF rates. In our experience, use of mesh staple line reinforcement did not reduce the incidence of PF after stapled transection.     

Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1–positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.     

Partial response to cyclosporine in a patient with Schnitzler's syndrome

Schnitzler's syndrome is an unusual clinical association of chronic urticaria, intermittent fever and monoclonal immunoglobulin M (IgM) gammopathy. The pathogenesis of the urticaria is unclear and treatment is problematic. We describe the case of a 61-year-old woman with a long history of chronic urticaria with severe pruritus, spiking fever and malaise. The IgM-kappa monoclonal component was detected in the patient's serum 4 years after symptom onset. After ineffective treatment with antihistamines and systemic corticosteroids, oral cyclosporine resulted in complete remission of the fever and malaise, which has persisted after an 18-month follow-up. Partial but maintained remission of the urticaria was also observed, allowing corticosteroid doses to be decreased.