Background: Liver transplantation (LT) is associated with a significant risk of intraoperative hemorrhage and massive blood transfusion. However, there are few relevant reports addressing the long-term impacts of massive transfusion (MT) on liver transplantation recipients. Aim: To assess the effects of MT on the short and long-term outcomes of adult liver transplantation recipients. Methods: We included adult patients who underwent liver transplantation at West China Hospital from January 2011 to February 2015. MT was defined as red blood cell (RBC) transfusion of ≥10 units within 48 hours since the application of LT. Preoperative, intraoperative and postoperative information were collected for data analyzing. We used one-to-one propensity-matching to create pairs. Kaplan-Meier survival analysis was used to compare long-term outcomes of LT recipients between the MT and non-MT groups. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors associated with MT in LT. Results: Finally, a total of 227 patients were included in our study. After propensity score matching, 59 patients were categorized into the MT and 59 patients in non-MT groups. Compared with the non-MT group, the MT group had a higher 30-day mortality (15.3% vs 0, p=0.006), and a higher incidence of postoperative complications, including postoperative pulmonary infection, abdominal hemorrhage, pleural effusion and severe acute kidney injury. Furthermore, MT group had prolonged postoperative ventilation support (42 vs 25 h, p=0.007) and prolonged durations of ICU (12.9 vs 9.5 d, p<0.001) stay. Multivariate COX regression indicated that massive transfusion (OR: 2.393, 95% CI: 1.164-4.923, p=0.018) and acute rejection (OR: 7.295, 95% CI: 2.108-25.246, p=0.02) were significant risk factors affecting long-term survivals of LT patients. The 1-year and 3-year survival rates patients in MT group were 82.5% and 67.3%, respectively, while those of non-MT group were 93.9% and 90.5%, respectively. The MT group exhibited a lower long-term survival rate than the non-MT group (HR: 2.393, 95% CI: 1.164-4.923, p<0.001). Finally, the multivariate logistic regression revealed that preoperative hemoglobin <118 g/L (OR: 5.062, 95% CI: 2.292-11.181, p<0.001) and intraoperative blood loss ≥1100 ml (OR: 3.212, 95% CI: 1.586-6.506, p = 0.001) were the independent risk factor of MT in patients undergoing LT. Conclusion: Patients receiving MT in perioperative periods of LT had worse short-term and long-term outcomes than the non-MT patients. Massive transfusion and acute rejection were significant risk factors affecting long-term survivals of LT patients, and intraoperative blood loss of over 1100 ml was the independent risk factor of MT in patients undergoing LT. The results may offer valuable information on perioperative management in LT recipients who experience high risk of MT.
may enable T-cell homing. Lack of preexisting tumor-infiltrating CD8+ T cells may account for the non-response to the immune checkpoint inhibitors. In addition, mouse preclinical models and clinical examples have shown that hypofractionated radiotherapy (HFRT) can trigger in situ vaccination and subsequent abscopal effects. The goal of the study was to figure out whether LDI could enhance the efficacy of checkpoint inhibitors. Furthermore, the study addressed whether combination of HFRT to primary tumor and LDI to metastasis could maximize the abscopal effect of HFRT. Materials/Methods: In experiment exploring the synergy between LDI and immunotherapy, CT26-bearing mice were randomly divided into 4 groups: control, aPD-1 mAb, LDI (2Gy/1f), aPD-1 mAb + LDI. In experiment exploring the abscopal effect, CT26 mouse colon carcinoma cells were injected s.c. into Balb/c mice at right and left hind legs. Subsequently, mice were randomized into 4 groups: control, HFRT (24Gy/8Gy/3f, right-side), LDI (2Gy/1f, left-side), HFRT (right-side) + LDI (left-side). Mice were followed for tumor growth and further analyses. Results: We found that in CT26 colon cancer mouse model, low-dose irradiation alone could recruit effector CD8+T cells and increase CXCL9, CXCL10 and CXCL11 levels, which are potent chemotactic signals for activated T cells. Mice with tumors did not benefit from aPD-1 mAb alone. Compared to single-therapy modality, a better tumor control was observed following aPD-1 mAb in combination with LDI. IFNg+CD8+ T cells were augmented in spleens obtained from mice in aPD-1 mAb + LDI group. Besides, HFRT to primary tumor (right-side) and LDI to the secondary tumor (left-side) could achieve better secondary tumor control, thus maximizing the abscopal effect. In combination group, we found an increase of CD8+ T cells in both secondary tumor and peripheral blood, indicating that CD8+ T cells played an important role in the efficacy. Conclusion: These results indicate that LDI may be very useful as a preparatory step to induce T-cell homing. Given its low risk of toxicity and excellent tolerability, LDI may be a clinically applicable response modifier of immunotherapy.
A total of 326 patients met the inclusion criteria, including 43, 40 and 243 patients with prior RT, surgery, and no prior treatment, respectively. The median follow-up was 59 (95% CI 48-68) months. There was no significant difference in patients and tumor factors between these groups. The median survival were 23 (95% CI 15-31), 50 (95% CI 35-65), and 32 (95% CI 25-40) months, and the 5-year survival rates were 26.2%, 42.4%, and 24.7%, respectively (PZ0.077). In those treated with previous RT, there were no significant differences in overall survival between conventionally fractionated radiation therapy and SBRT (median survival 25.0 vs 13.4month, PZ0.280). In those treated with prior surgery, there was no significant difference in overall survival between pneumonectomy and lobectomy (56.0 vs 50.0 months, PZ0.576). The were significant differences in rates of grade 1+ (44.2%, 30.0%, 21.5%, PZ0.007), and 2+ RP (18.6%, 12.5%, 7.0%, PZ0.039), but no statistically significant differences in grade 3+ pneumonitis among these three groups. Conclusion: Salvage SBRT after previous radiation or surgery provides a chance of cure, with 5-year survival not significantly different from that of SBRT for newly diagnosed NSCLC, with significantly increased but acceptable risk of radiation pneumonitis. Future study may need to set stringent limits for lung SBRT after previous surgery or radiation.
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