Treatment of brain metastases from melanoma

Brain metastases from malignant melanoma have a poor prognosis, and treatment can be difficult because of rapid progression of the disease. To help define the treatment of this disease, we reviewed the published literature on brain metastases from melanoma. If a solitary metastasis is present, surgery might be beneficial, especially if systemic disease is absent. Stereotactic radiosurgery is a less invasive, attractive option for solitary or oligometastatic (up to 6) lesions. External beam whole-brain radiation therapy can produce responses and frequently palliates symptoms, but as the sole therapy, it is unlikely to eradicate brain metastases. Chemotherapy may be gaining a role with newer agents that penetrate the blood-brain barrier. Combined modality therapy appears to be the future direction of treatment of multiple metastases.     

Pharmacological examination of the neurokinin-1 receptor mediating relaxation of human intralobar pulmonary artery

The effect of selective tachykinin receptor agonists and antagonists on human isolated intralobar pulmonary arterial rings was investigated. Neither Substance P (SP) nor neurokinin A (NKA) contracted the arteries. Both of these agonists, however, were potent and efficacious at relaxing the arteries that were precontracted with phenylephrine. The negative log (M) EC(50) values for SP and NKA were 9.0 and 8.3, respectively. The neurokinin (NK)-3 selective agonist, senktide-analog, and the NK-2 receptor selective agonist, [beta-Ala(8)]NKA(4-10), caused neither contractions nor relaxations of the arteries, whereas the NK-1 receptor agonist Ac-[Arg6, Sar9, Met(O2)11]SP(6-11) (ASM-SP) relaxed the tissue with a potency similar to SP. The relaxations to SP, NKA, and ASM-SP were competitively antagonized by the selective NK-1 receptor antagonist CP 99994, with a pK(b) in the nanomolar range. Antagonism of the ASM-SP-induced relaxations was also noted with FK 888, RP 67580, and L 732,138, although these antagonists were much less potent than CP 99994 in this regard. Another NK-1 receptor selective antagonist, SR 140333, caused an insurmountable antagonism of the SP-induced relaxations. The NK-1 receptor-mediated relaxations could be blocked by removing the endothelium, or by a combination of N-nitro-L-arginine and indomethacin. Measurement of prostanoid generation revealed that in endothelial-intact but not endothelial-denuded tissue, ASM-SP caused a selective increase in the production of 6-keto-PGF1alpha, the stable metabolite of prostacyclin. The results indicate that stimulation of NK-1 receptors leads to relaxation of human intralobar pulmonary arteries, which is mediated largely by nitric oxide and prostacyclin released from the endothelium of these vessels.     

Adverse Tumor Biology Associated with Mesenterico-Portal Vein Resection Influences Survival in Patients with Pancreatic Ductal Adenocarcinoma

Background

Although pancreatoduodenectomy (PD) with mesenterico-portal vein resection (VR) can be performed safely in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the impact of this approach on long-term survival is controversial.

Patients and Methods

Analyses of a prospectively collected database revealed 122 consecutive patients with PDAC who underwent PD with (PD+VR) or without (PD?VR) VR between January 2004 and May 2012. Clinical data, operative results, and survival outcomes were analysed.

Results

Sixty-four (53 %) patients underwent PD+VR. The majority (84 %) of the venous reconstructions were performed with a primary end-to-end anastomosis. Demographic and postoperative outcomes were similar between the two groups. American Society of Anesthesiologists (ASA) score, duration of operation, intraoperative blood loss, and blood transfusion requirement were significantly greater in the PD+VR group compared with the PD?VR group. Furthermore, the tumor size was larger, and the rates of periuncinate neural invasion and positive resection margin were higher in the PD+VR group compared with the PD?VR group. Histological venous involvement occurred in 47 of 62 (76 %) patients in the PD+VR group. At a median follow-up of 29 months, the median overall survival (OS) was 18 months for the PD+VR group, and 31 months for the PD?VR group (p = 0.016). ASA score, lymph node metastasis, neurovascular invasion, and tumor differentiation were predictive of survival. The need for VR in itself was not prognostic of survival.

Conclusions

PD with VR has similar morbidity but worse OS compared with a PD?VR. Although VR is not predictive of survival, tumors requiring a PD+VR have more adverse biological features.