Objective To determine whether lymph node-targeted chemotherapy with carbon nanoparticles absorbing 5-FU affects expressions of bcl-2, bax and caspase-3 in gastric cancer tissues, metastatic lymph nodes and normal gastric mucosa. Methods Twenty-eight patients with gastric cancer in our department were divided into lymph node-targeted chemotherapy (LNTC) group and control group from October 2005 to August 2006. The patients were treated with carbon nanoparticles absorbing 5-FU before operation in LNTC group and those were operated directly in control group. The gastric cancer tissues, metastatic lymph nodes and normal gastric mucosa were collected after operation. The expressions of bcl-2, bax and caspase-3 in those tissues were determined by immunohistochemical technique. Results In LNTC group, the positive expression rate of bcl-2 in gastric cancer tissues and metastatic lymph nodes was significantly lower than those in control group (28.6% vs . 78.6% , 25.0% vs . 70.0% , P ＜ 0.05), the positive expression rate of bax (85.7% vs . 28.6% , 80.0% vs . 30.0% ) and caspase-3 (57.1% vs . 14.3% , 55.0% vs . 15.0% ) in gastric cancer tissues and metastatic lymph nodes was significantly higher than those in control group ( P ＜ 0.05). The positive expression rate of bcl-2, bax and caspase-3 in normal gastric mucosa was not significantly different between two groups ( P ＞ 0.05). Conclusion The lymph node-targeted chemotherapy with carbon nanoparticles absorbing 5-FU can down-regulate the expression of bcl-2 and up-regulate the expression of bax and caspase-3 in gastric cancer tissues and metastatic lymph nodes, and therefore by affecting the expression levels of these apoptosis molecules may be one of the ways to induce tumor cell apoptosis.
Abstract： Surgery is an effective therapy for non-small cell lung cancer (NSCLC). The standard operation includes lobectomy and systematic dissection of lymph nodes. However, postoperative tumor recurrence is common even among incipient patients due to incomplete dissection of lymph nodes and micrometastasis of lymph nodes. Injecting a carbon nanoparticles suspension is a new technique aimed at preventing this recurrence. The carbon nanoparticles carry lymph node tracers that help surgeons locate lymph nodes in order to clean them thoroughly. The tracers also target the lymph nodes for chemotherapy, thus killing residual tumor cells intraoperatively to avoid postoperative cancer recurrence. Carbon nanoparticles suspension injection is already widely and successfully used in surgery for gastrointestinal and mammary gland tumors, and is being tested for effectiveness in NSCLC patients. Some studies have indicated that carbon nanoparticles suspension injection is effective in NSCLC patients and improves their prognoses. We reviewed the features, application methods, and clinical applications of studies of carbon nanoparticles suspension injection for NSCLC.
Objective To assess the applied significance of carbon nanoparticles in central compartment lymph node dissection in treatment of cN0 papillary thyroid carcinoma. Methods Sixty-eight patients with cN0 papillary thyroid carcinoma who were treated in Tongji Hospital of Tongji Medical College from May. to Oct. in 2012 were randomly allocated to the control group （n=32） and the carbon nanoparticles trace group （tracer group， n=36）， receiving non-carbon nanoparticles trace and carbon nanoparticles trace respectively. All patients were received total resection of thyroid plus the affected side and （or） contralateral side central compartment lymph node dissection. The lymph node-related indexes（including number of dissected lymph node at Ⅵarea and lymph node metastasis rate at Ⅵarea） and operative indexs （including operation time， blood loss， drainage time， complication， and hospital stay） were collected and compared between the 2 groups. Results There were 205 and 324 dissected lymph node at central compartment in control group and tracer group respectively. The results of postoperative pathology showed that the number of lymph node in central compartment of the tracer group was much more than those of control group （8.99±2.24 vs. 6.41±1.56， P＜0.001）. The metastasis rate of central compartment lymph node were 40.6% （13/32） in control group and 47.2% （17/36） in tracer group， but there was no significant difference between the 2 groups （P=0.762）. But in medial area of laryngeal recurrent nerve， the metastasis rate in the tracer group （38.9%， 14/36） was much higher than those of control group （12.5%， 4/32）， P=0.029. There were no significant differences in the operation time， blood loss， drainage time， hospital stay， and complication incidence such as bleeding， temporary hypocalcemia， and injury of superior laryngeal nerve between 2 groups （P＞0.05）. All the patients in 2 groups had followed-up for 6 months without death， recurrence， and metastasis.Conclusions The lymphatic tracer technique of carbon nanoparticles may improve the number of dissected lymph nodes in central region of cN0 papillary thyroid carcinoma， without increasing （or prolonging） operation time， intraoperative blood loss， and postoperative hospital stay， and can accurately represent the metastasis of lymph node， thus to make the staging of the tumor accurately and guide postoperative treatment.
Objective To determine the best matching concentration of carbon nanoparticles suspension injection adsorb epirubicin by measuring the combination ratio of carbon nanoparticles suspension injection combined with epirubicin under different matching conditions. And then, to prove the adsorbability of carbon nanoparticles suspension injection adsorb epirubicin in vitro. Methods Firstly, epirubicin-carbon suspension of different concentrations will be prepared. The second, high performance liquid chromatography mass spectrometry（LC-MS） was used to assay the concentration of free epirubicin, and calculate the content of epirubicin that was combinated with carbon nanoparticles suspension injection. The difference of the ratio of carbon nanoparticles suspension injection combined with epirubicin under different matching conditions will be compared in the end. Results The combination ratio of carbon nanoparticles suspension injection combined with epirubicin solution of 5, 10, and 15 mg/ml were 85.6%, 85.7%, and 31.8%, respectively. Conclusions The adsorbability of carbon nanoparticles suspension injection adsorb epirubicin is favourable in vitro. Best matching concentration of carbon nanoparticles suspension injection adsorb epirubicin may be epirubicin solution of 5-10 mg/ml.
ObjectiveTo investigate the lymphatic targeting of 5-fluorouracil (5-FU) carbon nanoparticles in rats. Methods5-FU concentration in lymphoid tissue of rats was determined by reversed phase high performance liquid chromatography after intraperitoneal injection of 5-FU carbon nanoparticle and 5-FU ordinary form (20 mg/kg body weight). Results5-FU concentration of lymphoid tissue in the 5-FU carbon nanoparticle group was higher than that in the 5-FU ordinary form group, and could sustain a longer time. Conclusion5-FU carbon nanoparticles injection can improve the drug concentration of target lymphatic organs, also has a good lymphatic targeting
ObjectiveTo explore the value of carbon nanoparticles on surgery for thyroid carcinoma. MethodLiteratures about application of carbon nanoparticles and lymphatic mapping in the thyroid carcinoma were reviewed. ResultsThe carbon nanoparticle was a new lymph tracer with a clear lymphatic mapping and a longer time for dying, which could accurately reflect the status of cervical lymph nodes, trace the sentinel lymph node in the thyroid carcinoma. The parathyroid gland could not be stained black, it was easy to be identified and protected. ConclusionsThe carbon nanoparticle provides an effective help in treatment for thyroid carcinoma. The more extensive and more profound application of lymphatic mapping depends on more clinical study.
Objective To explore the effect of carbon nanoparticles dyeing on axillary lymph node dissection in modified radical mastectomy for breast cancer. Methods Eighty-eight patients with breast cancer who received modified radical mastectomy in Mianyang Central Hospital between Mar. 2012 and May. 2013 were recruited in the study, and they were equally divided into areola group and peripheral tumor group. After induction of anesthesia before operation, carbon nanoparticles were injected around the areolar in the areola group, and carbon nanoparticles were injected around the tumor in the peripheral tumor group. The number of dissected lymph nodes(be dyed or not be dyed), metastatic lymph nodes, and black dyed lymph nodes, as well as value of operation related indexes were recorded and compared. Results In the areola group, lymph nodes were detected in 1 453, in which 1 396 lymph nodes were stained black(96.1%); the average number of dissected lymph nodes were 33.0±7.1 per case; and 19 patients (43.2%, in total of 220 metastatic lymph nodes) of them were suffered from lymph node metastasis with the average number of metastatic lymph nodes of 5±2 per case. in addition, in the areola group, operative time were(122.1±10.2) min, blood loss were(83.8±10.1) mL, postoperative hospital stay were(7±1) d, and postoperative complications occurred in 3 patients. In the peripheral tumor group, lymph nodes were detected in 909, in which 594 lymph nodes were stained black (65.3%); the average number of dissected lymph nodes were 20.7±3.2 per case; 20 patients (45.5%, in total of 88 metastatic lymph nodes) of them were suffered from lymph nodes metastasis, with the average number of metastatic lymph nodes of 2±1 per case. In addition, in the peripheral tumor group, operative time were (121.6±11.4) min, blood loss were (84.2±11.3) mL, postoperative hospital stay were (7±2) d, postoperative complications occurred in 3 patients. The black staining rate of lymph nodes, the number of lymph nodes retrieved, and the number of metastatic lymph nodes in areola group were significantly higher than those of peripheral tumor group(P < 0.01). Operative time, blood loss, postoperative hospital stay, and postoperative complication rate did not significantly differ between the 2 groups (P > 0.05). Conclusion The dyeing effect of carbon nanoparticles suspension, which was injected at areola area after induction of anesthesia, is better than that of injected around the tumor, without increasing the incidence of complication.
ObjectiveTo investigate effect of carbon nanoparticles on number of lymph nodes harvested in radical operation of rectal cancer after neoadjuvant chemoradiotherapy. MethodsOne hundred and five patients diagnosed with low and middle rectal cancer and received radical operation after neoadjuvant chemoradiotherapy in Cancer Hospital, Chinese Academy of Medical Sciences from March 1, 2014 to October 31, 2015 were included. Thirtysix patients were injected with carbon nanoparticles by colonoscopy before surgery and were classified as study group, and the rest patients were classified as control group. According to the same principle of surgery and procedure of pathological specimen handling, the effect of carbon nanoparticles on lymph node harvested in resected specimens was analyzed. ResultsThe total lymph nodes harvested were 764 in the study group and 1 242 in the control group. Among them, the metastatic lymph nodes were 19 in the study group, 58 in the control group. Although the average lymph nodes harvested in each patient had no significant difference between the study group and the control group (21.22±7.13 versus 18.00±9.84, t=1.739, P=0.085), the proportion of patients with 12 or more than 12 lymph nodes harvested in the study group was significantly higher than that in the control group [88.9% (32/36) versus 71.0% (49/69), χ2=4.287, P=0.038]. The ratio of patients with metastatic lymph nodes [27.8% (10/36) versus 33.3% (23/69), χ2=0.339, P=0.561] and the average metastatic lymph nodes harvested in each patient (1.90±1.29 versus 2.52±2.33, t=0.788, P=0.437) all had no significant differences between the study group and the control group. ConclusionThe injection of carbon nanoparticles by colonoscopy before surgery could increase detection rate of 12 or more than 12 lymph nodes in resected specimens of patients who were diagnosed with low and middle rectal cancer and received radical operation after neoadjuvant chemoradiotherapy.
ObjectiveTo investigate the value of carbon nanoparticle adopted in reoperation for thyroid cancer recurrence. MethodsFrom July to November of 2015, patients diagnosed with thyroid cancer recurrence in department of Thyroid & Parathyroid surgery, West China Hospital, Sichuan University were enrolled in the research. All enrollment patients underwent carbon nanoparticles location guided by ultrasonography before reoperation. Relative data about surgery and location were analyzed retrospectively. ResultsTwenty-two patients were enrolled in the research. Mean operation time was (60.45±12.91) minutes. During surgery, a total of 405 (average 18.4) lymph nodes were harvested, and the staining rate was 71.9% (291/405). The pathological examination showed that there was a significant difference in the positive rate between carbon nanoparticles stained lymph nodes (45.0%, 131/291) and non-stained lymph nodes (5.3%, 6/114), P < 0.001. In addition, the positive rate in non-targeted stained lymph nodes was 30.2% (62/205). By contrast, it was 5.3% (6/114) in non-targeted non-stained lymph nodes. The difference showed significant significance (P < 0.001). ConclusionsAdoption of carbon nanoparticles in reoperation for thyroid cancer, which improves efficiency of dissection for the non-palpable lymph nodes metastasis, is worth generalizing in clinical practice.
ObjectiveTo investigate the applicated value of carbon nanoparticle lymphatic tracer in laparoscopic assisted radical gastrectomy for advanced gastric cancer. MethodsForty-two patients with advanced gastric cancer who were admitted to the Department of General Surgery in The Affiliated Cancer Hospital of Zhengzhou University from March to September in 2014, were collected prospectively and randomly divided into two groups (carbon nanoparticle group and control group), each group enrolled in 21 cases. After improving relevant auxiliary inspection, subserosal injection of carbon nanoparticle around the tumor was performed via venous infusion needle laparoscopically at the beginning of surgery in carbon nanoparticle group, while the patients routinely underwent laparoscopic assisted radical gastrectomy in control group. Comparison of the results of harvested lymph nodes and its detection time between the two groups was performed, and the perioperative complications were also evaluated. ResultsA total of 678 lymph nodes were detected in carbon nanoparticle group and 447 lymph nodes were detected in control group. The number of harvested lymph nodes in carbon nanoparticle group (32.28±4.10) was significantly higher than that of control group (21.28±2.74), P < 0.05. The mean harvest time in carbon nanoparticle group was shorter than that of control group[(24.09± 3.58) min vs. (32.76±4.76) min, P < 0.05]. The proportion of harvested small lymph node (≤5 mm) in carbon nanoparticle group was higher than that of control group[71.68% (486/678) vs. 48.99% (219/447), P < 0.01]. The number of black-dyed harvested lymph node was 506 (74.63%) and the metastasis rate of black-dyed lymph node was 26.28% (133/506) in carbon nanoparticle group, that the metastasis rate of black-dyed lymph node group was significantly higher than those of without black-dyed lymph node group[6.40% (11/172)] and control group[19.24% (86/447)], P < 0.05. No serious side effect caused by carbon nanoparticle was observed. ConclusionsThe application of diluted carbon nanoparticle lymphatic tracer has a good effect in the dissection of lymph nodes in laparoscopic assisted radical gastrectomy for advanced gastric cancer. It improves the detection rate of lymph nodes, especially the small lymph nodes, and it is safe and feasible.