Cryoanalgesia of intercostal nerves following thoracotomy Clinical trial based on animal experiment

BACKGROUND： Cryoanalgesia at -50 ℃ for 90 seconds yields effective pain relief following thoracotomy. In China, -50 ℃ is a common temperature for intercostal cryoanalgesia following thoracotomy. However, experimental results vary. OBJECTIVE： To explore intercostal nerve pathological changes at -70 ℃ for various freezing times by studying canines, and to evaluate long-term clinical efficacy of intercostal nerve cryoanalgesia for postoperative pain relief based on the animal experiments. DESIGN, TIME AND SETTING： A comparative animal study was performed at the Animal Experimental Center of the General Hospital of the People＇s Liberation Army. Based on results from the animal study, a randomized, controlled, clinical trial was performed at the Department of Thoracic Surgery of the General Hospital of the People＇s Liberation Army between October 2006 and October 2008. PARTICIPANTS： A total of 120 patients undergoing posterolateral single incision Iobectomy at the Department of Thoracic Surgery of PLA General Hospital between October 2006 and October 2008 were selected. Nervous system diseases were excluded. METHODS： Animal experiment： 8 anaesthetized, mixed-breed dogs were used. The intercostal nerves （costal bone 6-10） were frozen at -70 ℃ for varying times （30, 60, 90, 120, and 180 seconds）. Clinical study： 120 patients were randomly assigned to 2 groups （n = 60）. In the cryoanalgesia group, the intercostal nerves were frozen prior to chest closure, and 4 costal nerves （1 at incision level, 2 above and below incision, and 1 at drainage tube level） were frozen for 90 seconds at-70 ℃, respectively. Intercostal nerves were not frozen in the control group patients. Dolantin was used to relieve postoperative pain in patients from both groups. MAIN OUTCOME MEASURES： Pathological changes in frozen intercostal nerves were examined at days 1, 10, 30, and 60 following freezing. Following surgery, the degree of postoperative pain in all patients was evaluated by visual analogue scale at days 1,3, 5, 9, 30, 60, 90, and 180. Dolantin doses at days 1, 3, 5, 9 post-surgery and postoperative complications were noted. RESULTS： Nerve damage progressively increased with length of freezing time at -70 ℃, and recovery time from damage was gradually increased. After freezing for 90 seconds, the nerves exhibited obvious histopathological damage, and then completely recovered. In addition, after freezing for 180 seconds, the histopathological changes in nerves were reversible. In the clinical study, visual analogue scale scores were significantly less in the cryoanalgesia group compared with the control group （P 〈 0.01）, which was maintained over 30 days. In the cryoanalgesia group, the mean dolantin dose administered and postoperative complications were significantly reduced compared with the control group （P 〈 0.01）. CONCLUSION： Freezing of the intercostal nerve at -70 ℃ for 90 seconds is a safe and long-term effective method for relieving post-thoracotomy pain.

Histological analysis and clinical observation of phrenic nerve cryotherapy following pulmonary resection

BACKGROUND： Residual postoperative pleural spaces （RPPS） are often encountered during pulmonary resection; this could adversely affect the outcome and prolong recovery. Nerve cryotherapy reduces postoperative complications and does not affect neural regeneration. However, it remains unclear whether nerve cryotherapy reduces RPPS occurrence following pulmonary resection.OBJECTIVE： To explore pathological changes in the phrenic nerve following exposure to -50℃ for various freezing times, and to explore the feasibility and efficacy of phrenic nerve cryotherapy following pulmonary resection based on animal experiment results.DESIGN, TIME AND SETTING： A comparative animal study was conducted at the Animal Experimental Center of General Hospital of Chinese PLA from January to June 2008. Based on results from the animal study, a randomized, controlled, clinical study was initiated at the Department of Thoracic Surgery of General Hospital of Chinese PLA between July 2008 and July 2009.PARTICIPANTS： A total of 160 patients undergoing lobectomy were selected at the Department of Thoracic Surgery of General Hospital of Chinese PLA from July 2008 to July 2009.METHODS： Animal experiment： 27 adult goats were randomly assigned to three groups （n = 9）.The phrenic nerves were frozen at -50 ℃ for 30, 60, and 90 seconds, respectively. Clinical study： 160 patients undergoing lobectomy were randomly assigned to two groups （n = 80）. In the cryoanalgesia group, patients received phrenic nerve cryotherapy; phrenic nerves were frozen above the capsula cordis for 60 seconds at -50 ℃ prior to chest closure. Patients in the control group did not receive cryotherapy.MAIN OUTCOME MEASURES： Pathological changes were observed at days 1, 30, and 60 following phrenic nerve cryotherapy. In the clinical study, RPPS incidence rate was regularly recorded. Respiratory function tests, including measured forced vital capacity and forced expiratory volume in 1 second, were regularly conducted post-surgically. The incidence of post-surgical infection complications and the average days of chest drainage and hospital stay were observed and recorded.RESULTS： Animal study： nerve damage progressively increased with prolonged freezing time at -50 ℃, and recovery time from damage gradually increased. Nerves, which were frozen for 30 and 60 seconds, recovered by 30 days, and all nerves completely recovered by 60 days. Clinical study： the RPPS incidence rate was significantly less in the cryoanalgesia group compared with the control group at 1, 5, 10, and 30 days following surgery （P〈0.05）. Simultaneously, phrenic nerve cryotherapy decreased the incidence rate of RPPS and shortened the average days of chest drainage and hospital stay in patients undergoing lobectomy （P〈0.05）. However, phrenic nerve cryotherapy did not affect forced vital capacity, forced expiratory volume in 1 second, and the incidence rate of post-surgical infection complications （P〉0.05）.CONCLUSION： Following phrenic nerve cryotherapy in the goat at -50℃, the phrenic nerve recovered to normal by 60 days. In the clinical study, phrenic nerve cryotherapy reduced the RPPS incidence rate, had no effect on pulmonary function, shortened hospital stay in patients undergoing lobectomy, and proved to be a safe, effective method.

Nanotechnology:A New Strategy for Lung Cancer Treatment Targeting Pro-Tumor Neutrophils

Primary and metastatic lung cancers are malignant lung tumors each with of which has a different pathogenesis,although both threaten patient lives.Tumor development and progression involve communication between tumor cells and the host microenvironment.Neutrophils are the most abundant immune cells in the tumor microenvironment(TME);they participate in the generation of an inflammatory milieu and influence patient survival through their anti-and pro-tumor abilities.Neutrophils can be classified into various categories according to different criteria;frequent categories include N1 antitumor neutrophils and N2 immunosuppressive neutrophils.The antitumor effects of neutrophils are reported to be mediated through a combination of reactive oxygen species,tumor necrosis factor-related apoptosis-inducing ligand,and receptor for advanced glycation end-products–cathepsin G association,as well as the regulation of the activities of other immune cells.There have also been reports that neutrophils can function as tumor promoters that contribute to lung cancer progression and metastasis by influencing processes including carcinogenesis,angiogenesis,cancer cell proliferation,and invasion ability,as well as having similar roles in the lung metastasis of other cancers.The rapid development of nanotechnology has provided new strategies for cancer treatment targeting neutrophils.

Surface structure change properties:Auto-soft bionic fibrous membrane in reducing postoperative adhesion

Peritoneal adhesion is the most common adverse effect following abdominal surgery or inflammation.The occurrence in clinical trials has been successfully reduced using barriers.However,the shortcomings of frequently used adhesion barriers,such as rapid degradation rate of gel barrier and inadequate operation ability of solid barrier,cannot be ignored.In this study,a fibrous membrane with an ECM-like structure was prepared.The adhesion properties were reduced significantly by changing the surface structure.The fibrous membrane caused less inflammatory response and much less peripheral adhesion and intestinal obstruction compared to the casting film and the commercial film with smooth surface,though with the same components.Because of the auto-soft bionic structure and similarity in the mechanical modulus of the tissues,the fibrous membrane was more flexible when it adhered to the tissues,showed excellent effectiveness and biocompatibility.In addition to the rat and miniature pig models,a randomized,placebo-controlled,and multicenter clinical pilot study with 150 patients confirmed that because of its flexibility,biodegradability,and similarity to mechanical modulus and structure with tissues involved,the fibrous membrane served as a favorable implant for preventing post-operation adhesion.