Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer

Chemotherapy has produced unsatisfactory results in pancreas cancer and novel approaches, including treatment tailoring by pharmacogenetic analysis and new molecular-targeted drugs, are required. The scarcity of effective therapies may reflect the lack of knowledge about the influence of tumor-related molecular abnormalities on responsiveness to drugs. Advances in the understanding of pancreas cancer biology have been made over the past decade, including the discovery of critical mutations in oncogenes (i.e., K-Ras) as well as the loss of tumor suppressor genes, such as TP53 and p16(INK4). Other studies showed the dysregulation of the expression of proteins involved in the control of cell cycle, proliferation, apoptosis, and invasiveness, such as Bcl-2, Akt, mdm2, and epidermal growth factor receptor. These characteristics might contribute to the aggressive behavior of pancreatic cancer and influence response to treatment. Indeed, the inactivation of p53 may explain the relative resistance to 5-fluorouracil, whereas Bcl-2 overexpression is associated with reduced sensitivity to gemcitabine. However, the future challenge of pancreas cancer chemotherapy relies on the identification of molecular markers that help in the selection of drugs best suited to the individual patient. Recent pharmacogenetic studies focused on genes encoding proteins directly involved in drug activity, showing the role of thymidylate synthase and human equilibrative nucleoside transporter-1 as prognostic factor in 5-fluorouracil- and gemcitabine-treated patients, respectively. Finally, inhibitors of signal transduction and angiogenesis are under extensive investigation, and several prospective trials have been devoted to this area. Pharmacogenetics is likely to play a central role in the personalization of treatment, to stratify patients based on their likelihood of response to both standard agents (i.e., gemcitabine/nucleoside transporters) and targeted treatments (i.e., epidermal growth factor receptor gene mutations and/or amplification and tyrosine kinase inhibitors), Thus, molecular analysis should be implemented in the optimal management of the patient affected by pancreatic adenocarcinoma.     

The role of percutaneous balloon compression in the treatment of trigeminal neuralgia recurring after other surgical procedures

Trigeminal neuralgia (TN) recurring after surgery can be difficult to treat. Treatment algorithms have not been standardized or universally accepted. Here we investigated the effectiveness of percutaneous balloon compression (PBC) in the treatment of patients with TN recurrence after other surgical techniques and analyzed the role of some clinical and operative factors in determining the prognosis. The records of 22 patients (13 M and 9 F) suffering recurrent TN after one (2 gamma knife surgery, 5 percutaneous radiofrequency rhizotomy, 6 percutaneous retrogasserian glycerol rhizotomy, 3 microvascular decompression) or more (6 patients) procedures and submitted to PBC at our institution from January 2003 to February 2012 were reviewed. Seven patients had TN related to multiple sclerosis (MS). Mean follow-up was 51.81 ± 26.63 months. 81.81 % of patients reported an acute pain relief. No major complication was observed after PBC. Eight patients (36.36 %) experienced pain recurrence and underwent one (five patients) or more (three patients) PBC. At the last follow-up, we obtained an excellent outcome (BNI I–II) in 16 patients out of 22 (72.72 %) and a good outcome (BNI III) in the remaining six. No patients had an uncontrolled pain. The lack of history of MS (p = 0.0174), the pear-like shape of the balloon at the operation (p = 0.0234) and a compression time <5 min (p < 0.05) were associated to higher pain-free survival. Considering these results PBC could be considered a useful technique for patients whose pain recurs after other procedures.     

Degenerative lumbar scoliosis in elderly patients: dynamic stabilization without fusion versus posterior instrumented fusion

Background contextPosterolateral fusion with pedicle screw instrumentation is currently the most widely accepted technique for degenerative lumbar scoliosis in elderly patients. However, a high incidence of complications has been reported in most series. Dynamic stabilization without fusion in patients older than 60 years has not previously been compared with the use of posterior fusion in degenerative lumbar scoliosis.PurposeTo compare dynamic stabilization without fusion and posterior instrumented fusion in the treatment of degenerative lumbar scoliosis in elderly patients, in terms of perioperative findings, clinical outcomes, and adverse events.Study designA retrospective study.Patient sampleFifty-seven elderly patients were included. There were 45 women (78%) and 12 men (22%) with a mean age of 68.1 years (range, 61–78 years). All patients had degenerative de novo lumbar scoliosis, associated with vertebral canal stenosis in 51 cases (89.4%) and degenerative spondylolisthesis in 24 patients (42.1%).Outcome measuresClinical (Oswestry Disability Index, visual analog scale, Roland-Morris Disability Questionnaire) and radiological (scoliosis and lordosis corrections) outcomes as well as incidence of complications.MethodsPatients were divided into two groups: 32 patients (dynamic group) had dynamic stabilization without fusion and 25 patients (fusion group) underwent posterior instrumented fusion. All the patients' medical records and X-rays were reviewed. Preoperative, postoperative, and follow-up questionnaires were obtained to evaluate clinical outcomes.ResultsAt an average follow-up of 64 months (range, 42–90 months), clinical results improved similarly in both groups of patients. Statistically superior scoliosis and final lordosis corrections were achieved with posterior fusion (56.9% vs. 37.3% and ?46.8° vs. ?35.8°, respectively). However, in the dynamic group, incidence of overall complications was lower (25% vs. 44%), and fewer patients required revision surgery (6.2% vs. 16%). Furthermore, lower average values of operative duration (190 vs. 240 minutes) and blood loss (950 vs. 1,400 cc) were observed in the dynamic group than in the fusion group.ConclusionsIn elderly patients with degenerative lumbar scoliosis, pedicle screw–based dynamic stabilization was less invasive with shorter operative duration, less blood loss, and lower adverse event rates than instrumented posterior fusion. Scoliosis curve reduction and lumbar lordosis were superior after fusion; however, dynamic stabilization achieved satisfying values of both these parameters, and these results were stable after an average follow-up of more than 5 years. Furthermore, there was no difference between the two techniques in terms of functional clinical outcomes at the last follow-up.