A literature review of the mechanism of osteolysis in osteosarcoma / 中华骨科杂志

Osteosarcomas are the most common primary malignant bone tumors in children and adolescents. Osteolysis is a common feature of all osteosarcomas (traditional, intramedullary, and periosteum). However, the specific mechanism of osteolysis is unknown and many researchers have studied it from different perspectives. Osteolysis is a process in which physiological bone remodeling is disrupted and excessive bone resorption occurs. Osteoclasts, the only cells with bone resorption function in the human body, play a key role in the pathological process of osteolysis in osteosarcomas. Osteoclasts play a leading role in osteolysis by secreting a high concentration of acid and collagenase, and they also mediate the occurrence and development of osteolysis in osteosarcoma through synergistic interaction with osteosarcoma cells. At the same time, osteolysis is an essential part of the pathological process of osteosarcoma, which can promote the occurrence and development of osteosarcoma and form a vicious cycle. Inhibiting osteolysis is of great significance to break this cycle and prevent the occurrence and development of osteosarcoma. However, the specific regulatory mechanism between osteosarcoma cells and osteoclasts and whether other cells in osteosarcoma are also involved in this pathological process remain unclear. Currently, bisphosphonates, small molecule inhibitors and natural compounds are the main drugs used to treat osteolysis of osteosarcoma. However, their efficacy and mechanism are still in the early stage of research. Previous studies on neoplastic osteolysis have mostly focused on metastatic bone tumors. Recently, studies on osteolysis of osteosarcoma have attracted more and more attention. The mechanism of osteoclasts and osteosarcoma cells in tumor-mediated osteolysis and the status of drug therapy of these two cell types as therapeutic targets are reviewed and analyzed. A deeper understanding of the role of osteolysis in the initiation and development of osteosarcoma will provide a theoretical basis and direction for the treatment of osteolysis in the context of osteosarcoma.

Progress of circulating tumor cells in primary bone tumor / 肿瘤研究与临床

Some primary bone tumors are prone to hematogenous metastasis and after that, the therapeutic effect is not that good and prognosis is poor. Circulating tumor cells (CTC) shed from the tumor cells of primary or metastatic focus and then enter into blood circulation. CTC may appear in the early stage of the tumor, which can implant in distant organs to form metastatic sites and self-implant in the primary sites leading to the tumor recurrence; CTC are closely related with the prognosis of patients with tumors. In most primary bone tumors, CTC are heterogeneous compared with primary tumor cells. Studying CTC from various aspects can provide a basis for the early diagnosis and treatment of primary bone tumors. This review summarizes the current researches of CTC in common primary bone tumors, and expects the future of research direction and application practice in clinic.

Progress of non-coding RNA in angiogenesis of osteosarcoma / 肿瘤研究与临床

Osteosarcoma needs to continuously induce angiogenesis to satisfy its own nutritional supply in the process of development. Therefore, the inhibition of osteosarcoma cell-induced angiogenesis as a target has become a research hot in recent years. Currently, vascular inhibitors targeting mRNA-encoded protein have been applied in clinic, but the efficacy is poor. Non-coding RNA (ncRNA) is a type of RNA molecules that do not participate in protein coding. ncRNA can regulate the angiogenesis of osteosarcoma by regulating the secretion of vascular factors such as vascular endothelial growth factor, angiogenin-2 and hypoxia-inducible factor 1 or the interaction between ncRNAs. This article reviews the role of ncRNA in the angiogenesis of osteosarcoma to provide references for clinical targeted therapy strategies for osteosarcoma.

Short-term efficacy of Billroth Ⅱ+Braun anastomosis versus Roux-en-Y anastomosis in totally three-dimensional laparoscopic distal gastrectomy / 中华消化外科杂志

Objective:To compare the short-term efficacy of Billroth Ⅱ+Braun anasto-mosis versus Roux-en-Y anastomosis in totally three-dimensional (3D) laparoscopic distal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 140 patients with gastric cancer who were admitted to the First Medical Center of Chinese PLA General Hospital from January 2016 to January 2020 were collected. There were 105 males and 35 females, aged from 23 to 84 years, with a median age of 55 years. Of the 140 patients, 54 patients undergoing totally 3D laparoscopic distal gastrectomy with Billroth Ⅱ+Braun anastomosis were allocated into Billroth Ⅱ+Braun group, and 86 patients undergoing totally 3D laparoscopic distal gastrectomy with Roux-en-Y anastomosis were allocated into Roux-en-Y group, respectively. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect remnant gastritis and its severity, bile reflux, reflux esophagitis in the postoperative 3 months up to April 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the Mann-Whitney U test. Results:(1) Surgical situations: 140 patients underwent totally 3D laparoscopic distal gastrectomy. The operation time, cases with volume of intraoperative blood loss <50 mL, 50 to 200 mL or >200 mL, the number of lymph node dissected were (233±39)minutes,15, 35, 4, 30±13 for the Billroth Ⅱ +Braun group , respectively, versus (240±52)minutes,25, 51, 10, 27±10 for the Roux-en-Y group, showing no significant difference between the two groups ( t=0.856， χ2=0.774， t=1.518， P>0.05). (2) Postoperative situations: cases with drainage tube, time to postoperative first flatus, cases with postoperative grade Ⅱ, Ⅲ, Ⅳ, Ⅴ complications, cases with postoperative complications, cases with postoperative severe complications, duration of postoperative hospital stay, surgery cost and total hospitalization cost of the Billroth Ⅱ+Braun group were 38, (3.5±0.8)days,4, 1, 0, 0, 5, 1, (9.0±5.0)days, (3.8±1.2)×10 4 yuan and (9.7±2.1)×10 4 yuan, respectively. The above indicators of the Roux-en-Y group were 59, (3.7±1.0)days, 9, 1, 0, 1, 11, 2, (9.0±4.0)days, (4.3±1.0)×10 4 yuan and (9.2±2.1)×10 4 yuan, respectively. There was a significant difference in the surgery cost between the two groups ( t=2.453, P<0.05), while there was no significant difference in cases with drainage tube, time to postoperative first flatus, cases with postoperative grade Ⅱ, Ⅲ, Ⅳ, Ⅴ complications, cases with postoperative complications, duration of postoperative hospital stay or total hospitalization cost between the two groups ( χ2=0.049, t=?1.339, Z=0.000, χ2=0.409, t=0.197, 1.383, P>0.05). There was also no significant difference in cases with postoperative severe complications between the two groups ( P>0.05).(3) Follow-up: 134 of 140 patients received the follow-up, including 52 cases in the Billroth Ⅱ+Braun group and 82 cases in the Roux-en-Y group. Results of follow-up within postoperative 3 months showed that the incidence rates of remnant gastritis, bile reflux, reflux esophagitis were 61.5%(32/52), 38.5%(20/52), 26.9%(14/52) for the Billroth Ⅱ+Braun group, respectively, versus 41.5%(34/82), 22.0%(18/82), 12.2%(10/82) for the Roux-en-Y group, showing significant differences between the two groups ( χ2=5.131, 4.270, 4.695, P<0.05). Cases with grade 0,Ⅰ,Ⅱ, Ⅲ, Ⅳ residual food were 42, 3, 5, 2,0 for the Billroth Ⅱ+Braun group, versus 67, 9, 1, 5,0 for the Roux-en-Y group, showing no significant difference between the two groups ( Z=?0.156, P>0.05). Cases with minimal lesion, grade A, grade B gastritis (severity of gastritis) were 6, 5, 3 for the Billroth Ⅱ+Braun group, versus 8, 2, 0 for the Roux-en-Y group, showing no significant difference between the two groups ( Z=?1.468, P>0.05). Conclusions:It is safe and feasible to operate Billroth Ⅱ+Braun or Roux-en-Y anastomosis in totally 3D laparoscopic distal gastrectomy. Billroth Ⅱ+Braun anastomosis can reduce the surgical cost. Roux-en-Y anastomosis has advantages in reducing the incidence of reflux esophagitis, bile reflux and reflux gastritis.

Research progress of non-coding RNA carried by exosomes in cartilage repair of osteoarthritis / 中华骨科杂志

Osteoarthritis (OA) is a common degenerative disease. Its most significant pathological change is destruction of articular cartilage and the main clinical symptoms are pain and dysfunction of joints. Recent studies have shown that the expression of non-coding RNA (ncRNA) in chondrocytes can abnormally up-regulate or down-regulate and alter the activities of chondrocytes like their proliferation, migration and apoptosis, thus leading to the occurrence and development of osteoarthritis. Exosomes are extracellular vesicles with a diameter of 40-100 nm, which are secreted in intercellular fluid, act as medium of intercellular communication. They protect ncRNA, protein, lipid and other bioactive materials from enzymatic degradation by encapsulating them and transferring to sibling chondrocytes, due to their good tissue permeability. They can also improve communication between cells and regulate the activities of chondrocytes. Thus, exosomes behave like gene carriers. The ncRNA carried by exosomes can supplement or adsorb the abnormal ncRNA in chondrocytes, so as to regulate the activity of chondrocytes, and is therefore considered as a possible candidate with capabilities to repair cartilages. In this study we reviewed existing literatures related to the roles and effects of exosome miRNA, lncRNA and circRNA on osteoarthritis. We also reviewed the pathogenesis of exosome ncRNA in osteoarthritis.

Surgical selection and metastatic warning of splenic lymph node dissection in advanced gastric cancer radical surgery: a prospective, single-center, randomized controlled trial / 中华胃肠外科杂志

Objective@#To investigate the surgical options for splenic lymph node dissection in patients with advanced gastric cancer undergoing radical total gastrectomy, and to evaluate the sentinel effect of No. 4s lymph node on splenic lymph node metastasis.@*Methods@#A prospective, single-center, randomized and controlled study was carried out (Trial registration, No.NCT02980861). Enrollment criteria: (1) >18 years old and <65 years old; (2) gastric adenocarcinoma locating in the proximal or corpus; (3) preoperative clinical staging as cT2-4aN0-3M0; (4) D2 radical total gastrectomy feasible judged before operation; (5) physical ability score 0 to 1; (6) I to III of ASA classification. Pregnant or lactating women, patients with severe mental illness or previous history of upper abdominal surgery, those suffered from other malignant tumors in the past 5 years, or heart and lung system diseases judged to affect surgery before operation, those receiving preoperative chemotherapy, radiotherapy or targeted therapies, and distant metastases being found during surgery were excluded. According to above criteria, 222 patients at The First Medical Center of Chinese PLA General Hospital from December 2016 to December 2017 were enrolled prospectively and were randomly divided into the laparoscopic splenic hilar lymph node dissection group (laparoscopic group, n=114) and the open splenic hilar lymph node dissection group (open group, n=108). The result of rapid frozen immunohistochemistry of harvested No.4s lymph nodes was used to evaluate the sensitivity and specificity of sentinel effect on splenic hilar lymph node metastasis. The surgical parameters, postoperative recovery parameters, and complication rates were compared between the two groups.@*Results@#There were 80 males and 34 females in the lapascopic group with a mean age of (56.1±10.2) years, and 69 males and 39 females in the open group with a mean age of (58.4±10.9) years. There were no significant differences in baseline data between the two groups (all P>0.05). Total blood loss was less in the laparoscopic group [(96.3±82.4) ml vs. (116.6±101.9) ml, t=1.124, P<0.001], and the amount of bleeding from the splenic hilar lymph nodes dissected was also less than that in the open group [(25.3±17.8) ml vs. (59.5±36.4) ml, t=1.172, P<0.001]. However, the operation time, the time of splenic hilar lymph node, the number of lymph node dissected and number of splenic hilar lymph node dissected were not significantly different between the two groups (all P>0.05). As compared to the open group, the laparoscopic group had shorter time to the first flatus [(1.3±1.2) days vs. (1.6±1.5) days, t=1.665, P=0.021], shorter time to fluid diet [(4.6±1.4) days vs. (4.9 ± 1.6) days, t=1.436, P=0.007], shorter time to remove nasogastric tube [(3.9±2.6) days vs. (4.3±2.4) days, t=0.687, P<0.001] and shorter hospital stay [(10.3±6.6) days vs. (12.1±7.2) days, t=0.697, P<0.001]. Complication rate was 14.0% (16/114) and 12.0% (13/108) in the laparoscopic group and the open group, respectively, without significant difference (χ2=6.723, P=0.331). The sensitivity of the No. 4s lymph node for the prediction of splenic hilar lymph node metastasis reached 89.5%, and the specificity reached 99.6%.@*Conclusions@#Laparoscopic technique is safe and feasible in the treatment of splenic hilar lymph node dissection in advanced gastric cancer. The No.4s lymph node examination has good sentinel effect on predicting the metastasis of splenic hilar lymph nodes.

Comparison of the superiority of different TNM staging systems in Siewert III adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

OBJECTIVE@#To compare the prognostic value of TNM staging systems in the 7th edition and the 8th edition AJCC in Siewert III adenocarcinoma of esophagogastric junction (AEG).@*METHODS@#Data of 160 patients with Siewert III AEG who underwent radical surgery (R0) from January 2009 to January 2013 in PLA General Hospital were collected retrospectively. Exclusion standards:(1)preoperative neoadjuvant chemoradiotherapy;(2)with distant metastasis before or during operation;(3)palliative operation or R1/R2 resection;(4)pathological type as non-adenocarcinoma;(5)number of retrieved lymph nodes less than 16;(6)diagnosed with other malignant tumors concurrently or within 5 years after operation;(7)incomplete clinical or follow-up data. According to the above criteria, 160 patients were included in this study finally. All the patients underwent radical total or proximal gastrectomy by abdominal approach. D1 or D1+ lymph node dissection was performed in early patients and D2 in advanced patients. All the patients were re-staged by the gastric cancer TNM7 (G7), the gastric cancer TNM8 (G8) and the esophageal cancer TNM7(E7). Univariate analysis and Cox regression analysis were performed. Kappa value and Akaike's information criterion (AIC, the less AIC, the better prognosis) value were compared between different staging systems in agreement and predicting prognosis.@*RESULTS@#There were 128 males and 32 females(sex ratio 4:1), and the average age was (60.2±11.6) years and 17 patients with basic disease. Of all the patients, 133 cases (83.1%) underwent radical total gastrectomy and 27 cases (16.9%) underwent proximal gastrectomy. The median number of dissected lymph nodes were 31 and the median number of positive lymph nodes were 4. Multivariate analysis showed that the G7, G8, E7 staging systems were independent prognostic factors (HR=1.374, 1.407 and 1.305 respectively,all P<0.001). Stage migration between G7 and G8 were only observed in IIIA, IIIB and IIIC, and stage migration rate was 8.1% (13/160), and the agreement was very good (weighted Kappa 0.904, P<0.001). However, the difference between G8 and E7 was quite obvious, stage migration rate was 40.6%(65/160), and the agreement between G8 and E7 was not satisfied (weighted Kappa 0.536, P<0.001). AIC value was 811.4 in G8, 812.8 in G7 and 815.9 in E7, respectively.@*CONCLUSION@#Compared with G7 and E7 staging systems, the G8 staging system is superior in predicting the prognosis of patients with Siewert III AEG.