Effectiveness of the Tailored, Early Comprehensive Rehabilitation Program (t-ECRP) based on ERAS in improving the physical function recovery for patients following minimally invasive esophagectomy: a prospective randomized controlled trial.

BACKGROUND: Perioperative rehabilitation management is essential to enhanced recovery after surgery (ERAS). Limited reports, however, have focused on quantitative, detailed early activity plans for patients receiving minimally invasive esophagectomy (MIE). The purpose of this research was to estimate the effectiveness of the Tailored, Early Comprehensive Rehabilitation Program (t-ECRP) based on ERAS in the recovery of bowel and physical functions for patients undergoing MIE. METHODS: In this single-blind, 2-arm, parallel-group, randomized pilot clinical trial, patients admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2019 to February 2020 were selected and randomly assigned to an intervention group (IG) or a control group (CG). The participants in the IG received medical care based on the t-ECRP strategy during perioperative period, and participants in the CG received routine care. The recovery of bowel and physical functions, readiness for hospital discharge (RHD), and postoperative hospital stay were evaluated on the day of discharge. RESULTS: Two hundred and fifteen cases with esophageal cancer (EC) were enrolled and randomized to the IG (n = 107) or CG (n = 108). The mean age was 62.58 years (SD 9.07) and 71.16% were male. For EC, 53.49% were mid-location cancers and 79.07% were classified as pathological stage II and III cancers. There were no significant differences between the two groups in terms of demographic and clinical characteristics and baseline physical functions. Participants in the IG group presented significantly shorter lengths of time to first flatus (P < 0.001), first postoperative bowel movement (P = 0.024), and for up and go test (P < 0.001), and lower scores of frailty (P < 0.001). The analysis also showed that participants in the IG had higher scores of RHD and shorter lengths of postoperative stay than in the CG (P < 0.05). CONCLUSIONS: The t-ECRP appears to improve bowel and physical function recovery, ameliorate RHD, and shorten postoperative hospital stay for patients undergoing MIE. Clinicians should consider prescribing quantitative, detailed, and individualized early activity plans for these patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01998230).

Effectiveness of an early, quantified, modified oral feeding protocol on nutritional status and quality of life of patients after minimally invasive esophagectomy: A retrospective controlled study.

OBJECTIVES: Previous studies confirmed the safety and feasibility of oral feeding on the first postoperative day (POD) for patients with minimally invasive esophagectomy (MIE). Nonetheless, some clinical concern can lead to delays in early oral feeding on POD 1. To our knowledge, few reports have focused on resolving these clinical concerns. The aims of this study were to evaluate the effects of an early, quantified, modified oral feeding protocol for patients after MIE and to explore its effect on nutritional status and quality of life (QoL). METHODS: In this prospective controlled trail, 200 patients were selected as the intervention group (IG) from March 2020 to June 2021; 115 patients hospitalized from June 2019 to February 2020 were assigned to the control group (CG). For 2 wk during the postoperative period, IG participants received an early, quantified, modified oral feeding protocol. The recovery of dietary outcomes, nutritional status, and QoL were evaluated after the intervention. RESULTS: There was no significant difference between the two groups in terms of demographic and clinical characteristics and baseline physical function. After the intervention, patients in the IG showed a more rapid growth in daily total oral caloric intake and the ratio of oral calorie intake to total calorie required by the body (K/R value) from POD 1 to POD 14, and less weight loss (1.5 ± 1 versus 2.1 ± 1.7 kg; P < 0.05), better serum prealbumin (193.0 ± 26.9 versus 139.3 ± 27.2 mg/L; P < 0.05) than the CG with statistical significance. By the second week of the intervention, IG patients reported higher global QoL and function scores and lower symptom scores than patients in the CG. The IG participants presented a shorter time to first flatus and bowel movement (P < 0.001), a shorter postoperative hospital length of stay, and higher activities of daily living scores (P < 0.05) the those in the CG. CONCLUSIONS: The findings demonstrated that the early, quantified, modified oral feeding protocol can alleviate postoperative body weight loss, improve the patient's nutritional status, and have a positive effect on QoL and early recovery for patients undergoing MIE.

Hand-assisted sputum excretion can effectively reduce postoperative pulmonary complications of esophageal cancer.

BACKGROUND: This study explores whether postoperative hand-assisted expectoration can reduce postoperative pulmonary complications (PPCs) in patients with esophageal cancer. METHODS: A retrospective analysis was performed on 543 patients undergoing radical esophageal cancer (EC) surgery in our hospital from October 2018 to August 2019, 156 of whom received postoperative handassisted sputum excretion (pulmonary rehabilitation, PR) and 387 of whom who did not receive postoperative hand-assisted sputum excretion (no pulmonary rehabilitation, NPR). Because the clinical characteristics of the two groups were not balanced, we used propensity score matching (PSM) to account for the variable factors of age, gender, body mass index (BMI), chronic respiratory comorbidity, smoking index, operation time, operation method, pathological stage. The main observation index used was PPCs. RESULTS: Among these 543 patients, 365 were male (67.2%), while 178 were female (32.8%). The age ranged from 30 to 82 years, with an average of 63.6±7.5 years old. In all, 342 patients (63%) underwent video-assisted thoracic surgery (VATS) surgery, while 201 patients (37%) underwent thoracotomy. Furthermore, 72 patients in the PR group received preoperative rehabilitation training and postoperative hand-assisted sputum excretion (combination pulmonary rehabilitation, CPR), while 87 patients only received postoperative hand-assisted sputum excretion (postoperative pulmonary rehabilitation, PPR). The patients in the PR group and the NPR group were uneven in terms of clinical characteristics, and we performed PSM as a result. After matching, PPC incidence in patients in the PR group was lower than that in the NPR group (P<0.05). CONCLUSIONS: Our results show that hand-assisted sputum excretion after EC surgery can reduce PPCs.

CDK6 inhibition targeted by miR-378a-3p protects against intestinal injury induced by ionizing radiation.

Radiotherapy combined with chemotherapy is a common modality in abdominal cancer treatment. However, intestinal syndrome induced by radiation is a main factor leading to the poor prognosis of radiotherapy. In this work, we found that miR-378a-3p was markedly up-regulated in the small intestines of mice after total abdominal irradiation. Knocking-down (or overexpression) of miR-378a-3p increased (or decreased) the radiosensitivity of the small intestine cells HIEC and FHs-74-Int. Comet assay and γ-H2AX staining demonstrated that miR-378a-3p exerted its radioprotective function by reducing the accumulation of DNA damage in the cells and tissues of the small intestines. Mechanistically, miR-378a-3p could interact with the 3' UTR of CDK6 through complementary sequences and thus inhibited CDK6 expression in the small intestine cells. Rescue experiments suggested that the repression of miR-378a-3p overexpression on cell radiosensitivity and DNA damage accumulation was abrogated by the forced expression of CDK6. In summary, our results revealed for the first time that miR-378a-3p regulated the radiosensitivity and DNA damage response of small intestines by targeting CDK6. MiR-378a-3p may serve as a promising biomarker and radioprotective target in abdominal cancer.

Effects of Hypoxia and Radiation-Induced Exosomes on Migration of Lung Cancer Cells and Angiogenesis of Umbilical Vein Endothelial Cells.

Numerous studies have shown that exosomes play important roles in tumor biology development. However, the function of exosomal protein in cancer progression under different oxygen condition after irradiation is poorly understood. In this study, non-small cell lung cancer (NSCLC) A549 cells were γ-ray irradiated under normoxic or hypoxic conditions, then the exosomes released from the irradiated cells were collected and co-cultured with nonirradiated A549 cells or human umbilical vein endothelial cells (HUVECs). It was found that the exosomes significantly promoted the proliferation, migration and invasion of A549 cells as well as the proliferation and angiogenesis of HUVECs. Moreover, the exosomes released from hypoxic cells and/or irradiated cells had more powerful driving force in tumor progression compared to that generated from normoxia cells. Meanwhile, the proteins contained in the exosomes derived from A549 cells under different conditions were detected using tandem mass tag (TMT), and their expression profiles were analyzed. It was found that the exosome-derived protein of angiopoietin-like 4 (ANGPTL4) contributed to the migration of A549 cells as well as the angiogenesis of HUVECs, suggesting its potential as an effective diagnostic biomarker of metastasis and even a therapeutic target of lung cancer.

TGF-ß mediates thoracic radiation-induced abscopal effects of testis injury in rat.

To investigate the thoracic irradiation induced abscopal effect on distal testes and the underlying inflammatory factors, the rats were irradiated on right thorax with fractionated doses. It was found the testes structures were damaged including disorder of spermatogenic cell arrangement and decrease of sperm number. Moreover, the expressions of caspase-3 and caspase-8 in testis tissue were enhanced, and the concentrations of TGF-ß and TNF-α in the rat serum were increased. When TM4 cells were treated with the conditioned medium (CS) collected from irradiated rat, the cellular ROS and apoptosis was significantly increased. When the CS was neutralized with anti-TGF-ß, its toxic effects were reduced. These results suggest that the thoracic irradiation-induced TGF-ß was involved in the above abscopal damage of testes, which reinforces the necessity of new prevention strategy development of radiotherapy in avoiding any abnormal genetic consequence.

Astaxanthin attenuates total body irradiation-induced hematopoietic system injury in mice via inhibition of oxidative stress and apoptosis.

BACKGROUND: The hematopoietic system is especially sensitive to total body irradiation (TBI), and myelosuppression is one of the major effects of TBI. Astaxanthin (ATX) is a powerful natural anti-oxidant with low toxicity. In this study, the effect of ATX on hematopoietic system injury after TBI was investigated. METHODS: Flow cytometry was used to detect the proportion of hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs), the level of intracellular reactive oxygen species (ROS), expression of cytochrome C, cell apoptosis, and NRF2-related proteins. Immunofluorescence staining was used to detect Nrf2 translocation. Western blot analysis was used to evaluate the expression of apoptotic-related proteins. Enzymatic activities assay kits were used to analyze SOD2, CAT, and GPX1 activities. RESULTS: Compared with the TBI group, ATX can improve radiation-induced skewed differentiation of peripheral blood cells and accelerate hematopoietic self-renewal and regeneration. The radio-protective effect of ATX is probably attributable to the scavenging of ROS and the reduction of cell apoptosis. These changes were associated with increased activation of Nrf2 and downstream anti-oxidative proteins, and regulation of apoptotic-related proteins. CONCLUSIONS: This study suggests that ATX could be used as a potent therapeutic agent to protect the hematopoietic system against TBI-induced bone marrow suppression.

[Protective Effect of S-isopentenyl-L-cysteine against DNA Damage in Irradiated Mice].

OBJECTIVE: To evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models. METHODS: Forty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively. RESULTS: The tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (P<0.01).And it was also observed that above experimental indexes of 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (P<0.05). In addition,the micronucleus rate of 1.0Gy gamma irradiation group and 7.2Gy gamma irradiation group were both significantly higher than in the control group (P<0.01). In addition,in mice given S-isopentenyl-L-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 ± 3.3141)‰ to (28.1667±4.1345)‰ (P=0.033) and from (76.5000 ± 4.6242)‰ to (22.8333 ± 3.6553)‰(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(P<0.05). Meanwhile,after irradiating by certain dose,the value of PCE/NCE in mice given S-isopentenyl-L-cysteine before irradiation was significantly higher than the corresponding groups (P<0.05). CONCLUSION: S-isopentenyl-L-cysteine has a good protective effect against DNA damage induced by radiation.