Physical activity enhances the effect of immune checkpoint blockade by inhibiting the intratumoral HIF1-α/CEACM1 axis.

Immune checkpoint blockade therapy has demonstrated significant therapeutic effects in certain types of cancers. However, there is limited reporting on the influence of physical activity on its efficacy. This study aimed to investigate the impact of physical activity on anti-PDL-1-mediated immune checkpoint therapy and the interplay of immune cells therein. HePa1-6 tumor-bearing mice were treated with anti-PDL-1 in conjunction with physical activity to assess tumor progression. Flow cytometry was utilized to analyze immune cell infiltration and differentiation levels within the tumor. The expression of HIF-a/CEACAM1 within the tumor due to physical activity was evaluated. HePa1-6 cells with high CEACAM1 expression were validated in mice to determine their inhibitory effects on immune cell proliferation and differentiation. A CD3/CEACAM1 chimeric antibody was developed for treating CEACAM1-overexpressing tumors, and flow cytometry was employed to assess T-cell response. Physical activity enhanced the efficacy of anti-PDL1 by suppressing the HIF-a/CEACAM1 axis within the tumor. In vivo experiments revealed that tumors with high CEACAM1 expression decreased infiltration and activation of CD8 + T cells within the tumor, suppressing T cell cytotoxicity without affecting Treg infiltration. In vitro, high CEACAM1 expression impacted the proliferation and activation of CD8 + T cells in a co-culture system. The constructed CD3/CEACAM1 chimeric antibody significantly activated the TCR within CEACAM1-overexpressing tumors and inhibited tumor progression. The findings suggest that physical activity augments the effectiveness of immune checkpoint blockade by inhibiting the intratumoral HIF1-α/CEACM1 axis.

Internal Ring Defect Closure Technique in Laparoscopic Mesh Hernioplasty for Indirect Inguinal Hernia.

PURPOSE: The best way to reduce seroma formation after laparoscopic indirect hernia repair is debated. We noticed that internal ring defect closure in laparoscopic mesh hernioplasty could provide promising outcomes with an effect on diminishing seroma formation. We introduce our closure technique and report our experience. METHODS: This prospective study was conducted from May 2019 to May 2021. Patients with European Hernia Society classification L3 indirect or scrotal hernia were recruited and underwent laparoscopic transabdominal patch plasty (TAPP). Hernia defect closure was performed before mesh deployment. The primary outcomes were seroma formation, postoperative pain, and hernia recurrence. Perioperative data and postoperative complications were also recorded. RESULTS: Consecutive 77 patients with 89 indirect hernias (including 51 scrotal hernias) were recruited in two regional tertiary hospitals. All operations were successful without open conversion. The mean size of the hernia defect was 3.7 ± 0.5 cm (range, 2.5-5.0 cm). The mean operative time for each hernia repair (peritoneum to peritoneum) was 48.3 ± 10.8 min (range, 33-72 min), and the mean time required for internal ring closure was 6.7 ± 2.2 min (range, 4-10 min). Intraoperative bleeding was minimal. The mean visual analog scale pain score at rest on the first postoperative day was 2.2 (range, 1-4). The average postoperative length of hospital stay was 18 h (range, 14-46 h). During a mean follow-up period of 9.4 months (range, 3-23 months), no hernia recurrence or chronic pain were noted. Seroma formation was detected on six sides of unilateral hernias (6.7%) on postoperative day 7, with a mean volume of 45.8 ml (range, 24-80 ml). All seromas were mild and resolved spontaneously within 3 months, with no need for evacuation or other treatment and without major impact on the final outcome. CONCLUSIONS: Defect closure in laparoscopic mesh hernioplasty for large indirect hernias is safe and feasible and can significantly reduce postoperative seroma formation and relative complications. This approach is recommended in large indirect or scrotal hernia repair.

Modified single-port laparoscopic herniorrhaphy for pediatric inguinal hernias: based on 1,107 cases in China.

BACKGROUND: Laparoscopic surgery is an alternative procedure for pediatric inguinal hernia (PIH), with a major trend toward increasing use of extracorporeal knotting and decreasing use of working ports. We report our experience with the modified single-port laparoscopic herniorrhaphy for repair of PIH and retrospectively evaluate a consecutive series of 1,107 cases in our institution. METHODS: Between February 2006 and July 2011, 1,107 children with indirect inguinal hernia were treated by laparoscopic surgery. All patients underwent high ligation surgery with a modified single-port laparoscopic technique, mainly performed by extracorporeal suturing with an ordinary taper needle (1/2 Arc 11 × 34). The clinical data were retrospectively analyzed. RESULTS: All surgery was successful without any serious complications. During the operations, contralateral patent processus vaginalis was found and subsequently repaired in 221 cases (20.0%). The mean operative time was 11 (range 5-14) min in 815 cases of unilateral repair and 20 (range 14-27) min in 292 cases of bilateral repair. The mean of postoperative hospital stay was 48 (range 26-52) h. Complications occurred in seven cases (0.63%) and were properly managed, with no major impact on outcome of the operations. There were six recurrent cases (0.54%) in the patients who had been followed-up for 9-74 months. There was no obvious scaring visible in any patients after treatment. CONCLUSIONS: The modified single-port laparoscopic technique for the repair of PIH is a safe and reliable procedure with minimal invasion and satisfactory outcome. It is easy to perfect and to perform and therefore is a worthy choice for PIH.

[The standardized practice of laparoscopic-assisted radical right hemicolectomy in order to achieve complete mesocolic excision].

OBJECTIVE: To explore the feasibility of laparoscopic-assisted radical right hemicolectomy with the outcome being a complete mesocolic excision (CME). METHODS: Between February 2010 and June 2011, we performed the standardized surgery of laparoscopic-assisted radical right hemicolectomy with an aim of CME on 14 patients. There were 10 males and 4 females, with an average age of 57 years (range 36 to 74 years). All the pathologic results in 14 cases were primary colonic adenocarcinoma. The TNM stages were distributed as follows: 2 in II A, 3 in II B, 3 in III A, 5 in III B and 1 in III C. RESULTS: Surgery was successfully performed for all patients without open conversion. The average operation time was (178 ± 37) minutes (range 127 to 221 minutes), average intraoperative blood loss was (67 ± 23) ml (range 30 to 110 ml), while the average number of lymph node harvest was 21 ± 7 (range 14 to 31), and the postoperative hospital stay was (10.0 ± 2.2) days (range 7 to 15 days). Minor complications occured in 2 patients. Major complications and post-operative mortality were not observed. All the patients were followed up for 3 to 19 months, no tumor recurrence or metastasis was identified. CONCLUSION: The standardized surgery of laparoscopic-assisted radical right hemicolectomy with the final outcome of CME is safe and feasible.

[Infusion of autologous mesenchymal stem cells prolongs the survival of dogs receiving living donor liver transplantation].

OBJECTIVE: To investigate the mechanism of autologous mesenchymal stem cells (MSCs) in prolonging the survival of dogs receiving living donor liver transplantation. METHODS: Canine models of allogenic living donor liver transplantation was established in 14 beagle dogs by non-venous by-pass method, and in 7 of the recipients, autologous MSCs labeled by BrdU was infused into the portal vein, with the other 7 dogs as the control. The survival time of the two groups of the dogs was observed after the operation. The liver function (AST and ALT levels), liver pathologies and the differentiation of the transplanted cells were also evaluated postoperatively. RESULTS: Compared with the control group, the dogs receiving MSC transplantation showed significantly increased median survival time (P<0.001) with lowered levels of AST and ALT (P<0.01). The two groups exhibited similar graft rejection after the operation. In dogs with MSC transplantation, the BrdU-labeled MSCs differentiated into liver-like cells in the liver and secreted albumin. CONCLUSION: Autologous MSCs infusion through the portal vein during allogenic living donor liver transplantation can prolong the survival of the recipient dogs. The stem cells transplanted can differentiate into mature liver-like cells and secrete albumin in the hepatic tissue.