Effects of serratus plane block and epidural analgesia on stress hormones after thoracoscopic lung surgery: a randomized trial.

　Serratus-intercostal plane block (SPB) is performed in thoracic surgery and breast cancer surgery because it is safer and easier to perform than epidural anesthesia. However, the effect of SPB on stress hormones has not been investigated.　Patients with lung cancer who were scheduled to undergo video-assisted thoracoscopic surgery (VATS) during the period from September 2017 to April 2018 were included in this single-center randomized trial. The institutional ethics committee approved this study (approval No. 2802-1). Patients were assigned to group B (SPB) or group E (epidural anesthesia). Levobupivacaine was administered as a local anesthetic to either the epidural space or serratus plane space. Blood samples were taken to measure levels of stress hormones including adrenaline, noradrenaline, dopamine, cortisol, and glucose at the induction of anesthesia and on the day following surgery.　Sixteen patients were included in the current study. Seven of those patients were assigned to group B and the other 9 patients were assigned to group E. Plasma adrenaline level in group B was significantly higher than that in group E postoperatively (P = 0.007). However, other markers were not different between the two groups, and there was no difference in pain scores between the two groups. In conclusion, SPB is an alternative analgesic method to epidural anesthesia in patients undergoing VATS

On the thermodynamic stability of clathrate hydrates IV: Double occupancy of cages

We have extended the van der Waals and Platteeuw theory to treat multiple occupancy of a single cage of clathrate hydrates, which has not been taken into account in the original theory but has been experimentally confirmed as a real entity. We propose a simple way to calculate the free energy of multiple cage occupancy and apply it to argon clathrate structure II in which a larger cage can be occupied by two argon atoms. The chemical potential of argon is calculated treating it as an imperfect gas, which is crucial to predict accurate pressure dependence of double occupancy expected at high pressure. It is found that double occupancy dominates over single occupancy when the guest pressure in equilibrium with the clathrate hydrate exceeds 270 MPa. (C) 2004 American Institute of Physics

Novel analgesics targeting brain-derived neurotrophic factor for neuropathic pain

　Brain-derived neurotrophic factor (BDNF) is necessary for the development, growth, and maintenance of nerve cells. BDNF is expressed in the dorsal root ganglion (DRG); binds to the Tropomyosin receptor kinasa B (TrkB) receptor, which has a tyrosine kinase domain, in the spinal cord; and plays an important role as a pain modulator. BDNF expression is increased in various types of pain, including acute pain, neuropathic pain, and cancer pain. Activation of the BDNF–TrkB pathway transmits pain information. In order to inhibit the BDNF–TrkB pathway, by sequestering BDNF, we constructed a cDNA expression plasmid encoding the extracellular region of rat TrkB fused to enhanced green fluorescent protein (EGFP). When the expression plasmid vector was administered to rat models of neuropathic pain, induced by spinal nerve ligation, statistically significant relief of pain was observed in terms of a 50% paw-withdrawal threshold using the von Frey test. The expression of TrkB-EGFP mRNA was detected in L5 lumbar vertebral nerves by quantitative reverse transcriptase polymerase chain reaction. To verify the pain-suppressive effect of the expression vector, truncated TrkB protein, without EGFP, was purified, and administered to pain model rats. A statistically significant suppressive effect of the truncated TrkB protein on neuropathic pain was observed 2 days after administration. The pain-suppressive effect of the truncated TrkB protein was more effective than that of the TrkB-Fc chimera protein and lasted longer than that of the TrkB antagonist ANA-12. Our results suggested that the truncated TrkB cDNA expression vector and truncated TrkB protein could be used as molecular targeted drugs in patients with neuropathic pain

Development of a novel analgesic for cancer pain targeting brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) is necessary for nerve growth. BDNF is expressed in the dorsal root ganglion (DRG) and modulates pain transduction from peripheral nociceptors. TrkB, which is a BDNF receptor with a tyrosine kinase domain, acts as a pain modulator on the cell membrane of second neuron. If an exogenous truncated TrkB lacking a tyrosine kinase domain can competitively block the binding of BDNF to endogenous TrkB, inhibitory effects on pain are expected. We constructed two expression vectors coding truncated TrkB-GFP fusion proteins, lacking intracellular tyrosine kinase domain, with and without the transmembrane domain. By transfection of the vectors to HEK293 cells, the expression and localization of the modified receptor proteins were confirmed. The truncated TrkB with the transmembrane domain, TM (+), was localized on cell membrane surface of the transfected cells, and capable of BDNF binding on cell surface. TM (-) without the transmembrane domain was secreted from the transfected cells, and the secreted TrkB protein was confirmed the capability for binding with BDNF by pull-down assay. Furthermore, we developed a rat model of cancerous osteocopic pain for evaluating an analgesic effect of the modified TrkB vectors on cancer pain. Pain-related behavior, as assessed by von Frey tests, indicated hyperalgesia after cancer cell administration. BDNF expression was higher on the affected side of the DRG at the third lumbar vertebra L3 than on the unaffected side. When the modified TrkB vectors were administrated to the cancer pain model rats, both the TM (+) and TM (-) vector administration groups exhibited an analgesic effect. These results suggest that the modified TrkB receptors and their vectors are applicable as molecular targeted drugs for pain control in cancer patients

Genotype–phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype–phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398–1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required

Percutaneous Cryoablation of Pulmonary Metastases from Colorectal Cancer

Objective: To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer. Methods: The procedures were performed on 24 patients (36–82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3–4 months. Results: The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8 % and 59%, respectively. The 3-years local progression free intervals of tumors #15 mm in diameter was 79.8 % and that of tumors.15 mm was 28.6 % (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively. Conclusion: The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression fre

Percutaneous Cryoablation for the Treatment of Medically Inoperable Stage I Non-Small Cell Lung Cancer

BACKGROUND: To evaluate the midterm results of percutaneous cryoablation for medically inoperable stage I non-small cell lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Between January 2004 and June 2010, 160 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these patients, histologically proven stage I lung cancer patients with more than one year of follow-up, were retrospectively reviewed. All of these patients were considered to be medically inoperable with Charlson comorbidity index of 3 or greater. Follow-up was based primarily on computed tomography. There were 22 patients with 34 tumors who underwent 25 sessions of cryoablation treatment. Complications were pneumothoraces in 7 treatments (28%, chest tube required in one treatment), and pleural effusions in 8 treatments (31%). The observation period ranged from 12-68 months, average 29±19 months, median 23 months. Local tumor progression was observed in one tumor (3%). Mean local tumor progression-free interval was 69±2 months. One patient died of lung cancer progression at 68 months. Two patients died of acute exacerbations of idiopathic pulmonary fibrosis which were not considered to be directly associated with cryoablation, at 12 and 18 months, respectively. The overall 2- and 3-year survivals were 88% and 88%, respectively. Mean overall survival was 62±4 months. Median overall survival was 68 months. The disease-free 2- and 3-year survivals were 78% and 67%, respectively. Mean disease-free survival was 46±6 months. Pulmonary function tests were done in 16 patients (18 treatments) before and after cryoablation. Percentage of predicted vital capacity, and percentage of predicted forced expiratory volume in 1 second, did not differ significantly before and after cryoablation (93±23 versus 90±21, and 70±11 versus 70±12, respectively). CONCLUSIONS/SIGNIFICANCE: Although further accumulation of data is necessary regarding efficacy, cryoablation may be a feasible option in medically inoperable stage I lung cancer patients

Nonimmersive Virtual Reality Mirror Visual Feedback Therapy and Its Application for the Treatment of Complex Regional Pain Syndrome: An Open-Label Pilot Studyp me_819 622..629

Abstract Objective. Chronic pain conditions such as phantom limb pain and complex regional pain syndrome are difficult to treat, and traditional pharmacological treatment and invasive neural block are not always effective. Plasticity in the central nervous system occurs in these conditions and may be associated with pain. Mirror visual feedback therapy aims to restore normal cortical organization and is applied in the treatment of chronic pain conditions. However, not all patients benefit from this treatment. Virtual reality technology is increasingly attracting attention for medical application, including as an analgesic modality. An advanced mirror visual feedback system with virtual reality technology may have increased analgesic efficacy and benefit a wider patient population. In this preliminary work, we developed a virtual reality mirror visual feedback system and applied it to the treatment of complex regional pain syndrome. Design. A small open-label case series. Five patients with complex regional pain syndrome received virtual reality mirror visual feedback therapy once a week for five to eight sessions on an outpatient basis. Patients were monitored for continued medication use and pain intensity. Results. Four of the five patients showed >50% reduction in pain intensity. Two of these patients ended their visits to our pain clinic after five sessions. Conclusion. Our results indicate that virtual reality mirror visual feedback therapy is a promising alternative treatment for complex regional pain syndrome. Further studies are necessary before concluding that analgesia provided from virtual reality mirror visual feedback therapy is the result of reversing maladaptive changes in pain perception