1.Expressions of microRNA-127-5p in bronchoalveolar lavage fluid of patients with severe pneumonia and its diagnostic value
Zhaojun WANG ; Qinfu LIU ; Xiaohong WANG ; Yanbo WANG ; Jun ZHANG ; Wenjie ZHOU ; Xiaojun YANG
Chinese Critical Care Medicine 2017;29(7):592-595
Objective To observe differential expressions of microRNA-127-5p (miR-127-5p) in bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and the value of miR-127-5p in the diagnosis of severe pneumonia. Methods Thirty severe pneumonia patients and 10 non-respiratory infection patients who needed mechanical ventilation after surgery admitted to Department of Critical Care Medicine of General Hospital of Ningxia Medical University from January to December in 2015 were enrolled, whose specimens of BALF were collected. The differential expressions of miRNA in BALF of patients in both groups were screened by miRNA chip technique to preliminarily establish miRNA differential expression profiles in BALF of severe pneumonia, and the miRNAs which were up-regulated and down-regulated were screened out. The expression levels of miR-127-5p were determined using a real-time fluorescent quantitative polymerase chain reaction (PCR). The value of miR-127-5p expression in the diagnosis of severe pneumonia was evaluated with receiver-operating characteristic curve (ROC). Results All of the 40 patients were enrolled in the final analysis. Differential expression spectrum of miRNA in severe pneumonia patients was initially built, in which 40 miRNAs were up-regulated and 113 miRNAs were down-regulated. Compared with non-respiratory infection patients, the expressions of miR-127-5p were significantly lowered in severe pneumonia patients (2-ΔΔCT: 0.578±0.226 vs. 1.004±0.337) with statistical difference (t = 4.552, P = 0.000). ROC curve analysis showed that the area under ROC curve (AUC) of miR-127-5p for diagnosis of severe pneumonia was 0.855 [95% confidence interval (95%CI) = 0.721-0.989, P = 0.001], with the optimal sensitivity and specificity of 86.7%and 70.0% respectively with 0.840 as the critical value, and the positive likelihood ratio was 2.89, the negative likelihood ratio was 0.19. Conclusion miR-127-5p in BALF could be used as a new biomarker for the diagnosis of severe pneumonia.
2.Clinical investigation of gut microbiota dysbiosis in septic patients
Dan LIU ; Xiaohong WANG ; Xiaobin ZHANG ; Jin YAN ; Xiaojuan YANG ; Qinfu LIU ; Ting SUN ; Xiaojun YANG
Chinese Journal of Emergency Medicine 2019;28(6):736-742
Objective To investigate the characteristics of gut microbiota dysbosis in septic and non-septic patients in ICU.Methods A prospective observational research was conducted.Ten septic patients(septic group),ten patients without sepsis(non-septic group) were admitted to Department of Critical Care Medicine of General Hospital of Ningxia Medical University from February 2017 to June 2017 were enrolled.And ten healthy persons was enrolled as control group.Stool samples were collected from septic and non-septic patients within two days following admission to the intensive care unit (ICU);healthy persons' was random.High throughput 16S rRNA gene sequencing technology was used to detect fecal bacterium of three groups.Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score,Sequential Organ Failure Assessment (SOFA) score of patients were recorded on the first day after admission to ICU.Results Compared with the control group,the α diversity of gut microbiota in non-septic and septic groups showed a downward trend,the [3 diversity showed that the structure of gut microbiota in non-septic and the septic groups was significant different,and the individual differences were more obvious.At the level of phylum,compared with the control group,the proportion of Firmicutes+Bacteroidetes in non-septic and septic groups decreased significantly(P=0.013,0.028),and the proportion of Proteobacteria increased(P=0.017,0.026),while the proportion of Fusobacteria just increased in the non-septic group(P < 0.01).At the level of genus,compared with the control group,the proportion of beneficial symbiotic genus in non-septic and septic groups can be seen decreased,such as Ruminococcus(P=0.045,0.026),Pseudobutyrivibrio(P=0.009,< 0.01),Anaerostipes(P=0.011,0.003),Coprococcus(P=0.045,0.011),Phascolarctobacterium(P=0.008,0.022),Subdoligranulum(P=0.006,0.026).The proportion of Lactobacillus,Dorea,Faecalibacterium,Roseburia and Blautia showed downward trend in non-septic and septic groups,but only the decline of Lactobacillus in non-septic group had statistical difference(P=0.005),and the decline of Dorea,Faecalibacterium,Roseburia and Blautia in septic group had statistical differences(P=0.037,0.038,0.002 and 0.017,respectively).The proportion of conditional pathogenic Fusobacterium,Actinomyces,Peptstreptococcus,Streptococcus increased in non-septic group(P=0.001,0.019,0.011 and 0.014,respectively),the proportion of pathogenic Staphylococcus(P=0.035,0.006),Enterococcus(P=0.001,0.001),Anaerococcus(P=0.006,0.006) and Bacillus(both P < 0.01) increased in non-septic and septic groups.Conclusions Gut microbiota dysbiosis occured in septic and non-septic patients in the ICU,and showed that diversity decreased,structure of intestinal flora changed,obligate anaerobic bacteria decreased,facultative anaerobic bacteria increased,benefical symbiotic bacteria decreased,pathogenic bacteria increased and can be the dominate genus.
3.Clinical characteristics and risk factors of early septic patients complicated with bloodstream infection
Pei JING ; Qinfu LIU ; Mingyue YANG ; Yuting KANG ; Zhijun ZHAO ; Xiaojun YANG
Chinese Critical Care Medicine 2022;34(6):608-613
Objective:To analyze the clinical characteristics, risk factors and prognosis of early septic patients with bloodstream infection (BSI) in department of critical care medicine of Ningxia Medical University General Hospital.Methods:Patients with sepsis admitted to department of critical care medicine of Ningxia Medical University General Hospital from November 1, 2019 to August 31, 2021 were included in a prospective observational study. Blood samples were collected for culture within 24 hours of sepsis diagnosis. General information, laboratory test indicators and blood culture results within 24 hours of sepsis diagnosis were recorded. Patients were followed up and prognostic indicators [mechanical ventilation time, length of intensive care unit (ICU) stay, and 28-day survival] were observed. According to blood culture results, patients were divided into BSI group and non-BSI group. Univariate and multivariate Logistic regression analysis were performed on the general clinical characteristics of patients in the two groups to screen the risk factors of early BSI in septic patients. Receiver operator characteristic curve (ROC) was drawn to evaluate the predictive value of risk factors for early BSI in septic patients.Results:A total of 202 septic patients were included in this study, with 62 patients in BSI group and 140 patients in non-BSI group. The majority of patients in the BSI group were associated with abdominal infection (61.3%), and the majority of patients in the non-BSI group were associated with pulmonary infection (49.3%). A total of 76 strains were isolated from septic patients in BSI group, and the most common pathogens were Escherichia coli (26 strains, 34.2%), Klebsiella pneumoniae (11 strains, 14.4%), Enterococcus (7 strains, 9.2%), Bacteroides fragilis (6 strains, 7.9%) and Staphylococcus aureus (6 strains, 7.9%). There were no significant differences in mechanical ventilation time, the length of ICU stay and 28-day mortality between the BSI group and the non-BSI group. The difference of variables was statistically significant between two group according to Univariate analysis, which included body temperature, acute physiology and chronic health score Ⅱ (APACHEⅡ), use of antibiotics before admission to ICU, abdominal infection, hypersensitivity C-reactive protein (hs-CRP), serum creatinine (SCr), total bilirubin (TBil), platelet count (PLT), blood lactic acid (Lac) and hypercalcitonin (PCT). Multivariate analysis showed that low PLT [odds ratio ( OR) = 1.004, P = 0.019], high Lac ( OR = 1.314, P = 0.002), high body temperature ( OR = 1.482, P = 0.027), concomitant abdominal infection ( OR = 2.354, P = 0.040), no use of antibiotics before admission to ICU ( OR = 2.260, P = 0.049) were independent risk factors for early BSI in septic patients. The area under ROC curve (AUC) of PLT, Lac, body temperature, abdominal infection and no use of antibiotics before admission to ICU for predicting early BSI in septic patients were 0.711, 0.686, 0.594, 0.592 and 0.590, respectively. Youden index was used to calculate the optimal cut-off values, which was PLT 122.50×10 9/L, Lac 2.95 mmol/L, body temperature 39.45 ℃, respectively. The highest level of AUC was 0.754, the sensitivity was 75.8%, and the specificity was 68.8%, which were observed when the 5 items were combined. Conclusions:Early septic patients with BSI are more serious than those without BSI. Low PLT, high Lac, high temperature, concomitant abdominal infection and no use of antibiotics before admission to ICU are independent risk factors for early BSI in septic patients, and the combination of these five factors has good predictive value.
4.Application value of lung ultrasound in the diagnosis and severity assessment of ventilator-associated pneumonia
Jie LI ; Jinyuan ZHU ; Qinfu LIU ; Jinlan MA ; Can LI ; Xiaohong WANG
Chinese Critical Care Medicine 2021;33(6):702-707
Objective:To explore the value of bedside lung ultrasound in the early diagnosis and severity assessment of ventilator-associated pneumonia (VAP).Methods:A prospective observational study was conducted in 60 patients with VAP (VAP group) and 62 patients without VAP (control group) who were admitted to department of intensive care unit of General Hospital of Ningxia Medical University from September 2018 to July 2020. The gender, age and underlying diseases of non-VAP group were matched with VAP group. The general clinical data such as gender, age, underlying diseases, department source of the patient, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score were recorded. The body temperature, white blood cell count (WBC), procalcitonin (PCT), oxygenation index (PaO 2/FiO 2), alveolar artery oxygen differential pressure (P A-aDO 2) were recorded. During mechanical ventilation, the patient's body temperature, WBC, sputum characteristics, and the change of the lung ultrasound were dynamically observed. With or without dynamic air bronchogram, lung ultrasound was considered to be positive as long as there were small subpleural consolidation or tissue-like sign. Ventilator-associated pneumonia lung ultrasound score (VPLUS) and lung ultrasound score (LUSS) were performed, and chest CT scan was completed on the same day. Use positive chest CT scan as the standard to evaluate the diagnostic efficacy of lung ultrasound, VPLUS score, and the combination of the two with PCT for VAP. LUSS was used to assess the severity of disease in patients with VAP. The correlation between LUSS and PaO 2/FiO 2, P A-aDO 2, APACHEⅡscore and SOFA score were analyzed. Results:① General information: compared with non-VAP group, VAP group had more emergency surgery patients [51.7% (31/60) vs. 33.9% (21/62), P = 0.047], APACHEⅡ score and SOFA score were significantly higher (APACHEⅡscore: 15.4±5.7 vs. 13.4±3.4, P = 0.021; SOFA score: 8.8±4.2 vs. 6.3±3.3, P < 0.001), body temperature tended to rise (℃: 38.3±0.8 vs. 38.0±0.9, P = 0.054), more patients had airway purulent secretions [65.0% (39/60) vs. 41.9% (26/62), P = 0.011], and mechanical ventilation time and length of ICU stay were longer [mechanical ventilation time (days): 10.5 (6.6, 15.0) vs. 4.3 (3.0, 6.0), P < 0.001; length of ICU stay (days): 14.8 (9.0, 18.0) vs. 6.0 (4.0, 9.1), P < 0.001], 28-day mortality rate was higher [31.7% (19/60) vs. 9.7% (6/62), P = 0.003].② Diagnostic efficacy evaluation: when lung ultrasound was positive, VPLUS≥3 and PCT > 0.5 μg/L were used separately for the diagnosis of VAP, the sensitivity was 73.3%, 75.0%, 61.7%, respectively; the specificity was 80.6%, 58.1% and 59.7%, respectively; the 95% confidence interval (95% CI) was 0.685-0.842, 0.574-0.748, 0.514-0.694, respectively, all P < 0.05, positive lung ultrasound had good sensitivity and specificity. When positive lung ultrasound or VPLUS≥3 were combined with PCT > 0.5 μg/L for tandem test, the specificity of VAP diagnosis was increased to 95.2% and 83.9%, respectively; but the specificity of VAP diagnosis of positive lung ultrasound combined with PCT > 0.5 μg/L was higher than VPLUS ≥3 combined with PCT > 0.5 μg/L (95.2% vs. 83.9%, P < 0.05).③ Correlation analysis: LUSS showed a significant positive correlation with APACHEⅡ and SOFA score ( r values were 0.407, 0.399, P values were 0.001, 0.002, respectively), LUSS had no relation with PaO 2/FiO 2 and P A-aDO 2 ( r values were 0.189, -0.064, P values were 0.629, 0.149, respectively). Conclusions:Lung ultrasound can early detect VAP , and its diagnostic specificity is significantly improved when combined with PCT > 0.5 μg/L. LUSS is closely related to the severity of disease in VAP patients, therefore, lung ultrasound may be an effective method for early diagnosis and efficacy evaluation of VAP patients.
5.Analysis on the structural changes of intestinal and pulmonary flora in mice with sepsis and acute lung injury
Ge YANG ; Rui ZHANG ; Xiaohong WANG ; Yujie MA ; Qinfu LIU ; Xiaojun YANG
Chinese Journal of Emergency Medicine 2023;32(3):353-359
Objective:To investigate the microecological structure changes and correlation in blood, lung tissue and fecal intestine of mice with sepsis and acute lung injury.Methods:A total of 12 healthy male C57BL/6J mice were divided into the cecal ligation and perforation (CLP) group and sham operation (sham) group by random number table method, with six mice in each group. In the CLP group, acute lung injury model of sepsis mice was prepared by CLP method. In the sham group, only laparotomy but no perforation of cecal ligation was performed. Eye blood, lung tissue, and feces were collected from mice in each group 24 h after surgery. Lung tissue morphological changes were observed by HE staining, and 16s ribosome RNA sequencing was used to analyze the structural changes of microecology of the bacterial flora at each site in sepsis mice and find out the correlation.Results:(1) HE staining showed that mice in the CLP group had exudation into the alveolar cavity of the lung, disordered lung tissue structure, accompanied by a large number of inflammatory cell infiltration, and the lung histopathological score was significantly higher than that in the sham group ( P < 0.01). (2)α diversity analysis showed that there was no statistical significance in blood and fecal samples between the sham group and CLP group, while Ace index, Chao index and Simpson index in lung tissue samples were statistically significant ( P < 0.05). (3) β diversity analysis showed that the differences in blood and fecal samples were greater between the sham group and CLP group than that within the group, and analysis of Bray Curtis, weighted, and unweighted indexes were statistically significant ( P < 0.05). (4) At the phylum level, compared with the sham group, the abundance of Proteobacteria gradually increased, and the abundance of Firmicutes and actinobacteria was decreased in the CLP group. At the genus level, the sham group was dominated by Acinetobacter and Duchenne, while the CLP group was dominated by Escherichia coli and unclassified Enterobacter. Blood flora was more similar to lung tissue flora composition as compared with fecal flora. Conclusions:The distribution of bacterial flora in blood, lung tissue and intestine of sepsis mice with acute lung injury is partially overlapped.
6.Macrophage polarization induced by short-chain fatty acid attenuates acute lung injury in sepsis
Jinlan MA ; Ge YANG ; Yujie MA ; Qinfu LIU ; Xiaojun YANG
Chinese Critical Care Medicine 2023;35(9):933-938
Objective:To explore the effect of short-chain fatty acid (SCFA) on acute lung injury (ALI) in sepsis via macrophage polarization.Methods:① Clinical trial: 30 sepsis patients admitted to the intensive care unit (ICU) of General Hospital of Ningxia Medical University from January to December in 2022 and 10 non-sepsis patients in the same period were enrolled, stool samples were collected on the first day of admission, and SCFA butyric acid level in the two groups were studied by targeted metabolomics. ② Animal experiment: male C57BL/6J mice were selected and randomly divided into sham operation group (Sham group), sepsis caused by cecal ligation and perforation (CLP group) and SCFA intervention group (SCFA group, sodium butyrate 25 mg/kg was given by gavage 1 hour after CLP), with 6 animals in each group. Twenty-four hours after molding, the state of mice was evaluated by mouse sepsis score (MSS), the degree of pulmonary edema was evaluated by calculating the wet/dry ratio (W/D), and the pathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining, and lung injury score was performed. The serum levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6, IL-10), nuclear factor-κB (NF-κB), and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA expressions of inflammatory factors TNF-α, IL-1β, IL-6 and antioxidant factor nuclear factor E2-related factor 2 (Nrf2) in lung tissue. The expressions of macrophage polarization markers arginin-1 (ARG-1), CD206, inducible nitric oxide synthase (iNOS) and IL-1β in lung tissue were detected by immunohistochemistry.Results:① Compared with non-sepsis patients, SCFA-butyric acid level was significantly reduced in patients with sepsis (μg/g: 34.56±6.61 vs. 1 150.67±381.90, P < 0.01). ② Compared with the Sham group, MSS, lung W/D ratio, lung injury score, the levels of serum inflammatory factors TNF-α, TGF-β, NF-κB, IL-10, IL-6, IL-1β, the mRNA expressions of lung tissue inflammatory factors and antioxidant factor Nrf2, M1 macrophage polarization markers ARG-1, CD206 and M2 macrophage polarization markers iNOS and IL-1β were significantly increased in the CLP group. Compared with the CLP group, MSS, lung W/D ratio, lung injury score, the levels of serum inflammatory factors TNF-α, TGF-β, NF-κB, IL-10, IL-6, IL-1β, the mRNA expressions of lung tissue inflammatory factors and antioxidant factors Nrf2, and M1 macrophage polarization markers ARG-1 and CD206 were significantly reduced [MSS: 14.50±3.16 vs. 20.00±1.55, lung W/D ratio: 4.60±0.18 vs. 5.51±0.59, lung injury score: 47.56±2.36 vs. 88.30±6.04, serum TNF-α (ng/L): 27.99±0.58 vs. 69.55±18.53, serum TGF-β (μg/L): 9.82±2.16 vs. 18.73±1.83, serum NF-κB (μg/L): 1.23±0.09 vs. 1.95±0.28, serum IL-10 (ng/L): 78.39±2.29 vs. 140.22±19.82, serum IL-6 (ng/L): 300.64±77.60 vs. 1 442.52±494.14, serum IL-1β (ng/L): 33.13±0.99 vs. 38.39±1.31, lung IL-1β mRNA expression (IL-1β/β-actin): 1.01±0.01 vs. 2.24±0.62, lung IL-6 mRNA expression (IL-6/β-actin): 0.63±0.09 vs. 1.46±0.31, lung TNF-α mRNA expression (TNF-α/β-actin): 0.81±0.33 vs. 2.57±0.64, lung Nrf2 mRNA expression (Nrf2/β-actin): 1.59±0.25 vs. 2.96±0.89, ARG-1 positive area: (36.27±2.89)% vs. (49.75±5.03)%, CD206 positive area: (20.02±3.26)% vs. (44.24±3.61)%, all P < 0.05]. However, there was no significant difference in M2 macrophage polarization markers iNOS and IL-1β expression [iNOS positive area: (18.32±2.23)% vs. (21.77±3.57)%, IL-1β positive area: (40.42±4.78)% vs. (42.14±4.22)%, both P > 0.05]. Conclusion:SCFA may alleviate ALI in sepsis by reducing M1 polarization of pulmonary macrophages.
7.Safty and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors
Yirui ZHAI ; Qinfu FENG ; Minghui LI ; Xinyuan CHEN ; Chengfeng WANG ; Shulian WANG ; Yongwen SONG ; Shengji YU ; Xiang WANG ; Lixue XUAN ; Xiaoguang LI ; Ping BAI ; Jidong GAO ; Jing JIN ; Weihu WANG ; Yueping LIU ; Tiecheng WU ; Yexiong LI
Chinese Journal of Radiation Oncology 2010;19(5):448-451
Objective To investigate the safety and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors.Methods From May 2008 to August 2009, 52 patients with abdominal tumors were treated with intraoperative electron radiotherapy,including 14 patients with breast cancer,19 with pancreatic cancer,3 with cervical cancer, 4 with ovarian cancer, 6 with sarcoma, and 6 with other tumors.Fifteen patients were with recurrent tumors.The intraoperative radiotherapy was performed using Mobetron mobile electron accelerator, with total dose of 9 - 18 Gy.In all, 29, 4 and 19 patients received complete resection, palliative resection and surgical exploration, respectively.The complications during the operations and within 6 months after operations were graded according to Common Terminology Criteria for Adverse Events v3.0 (CTC 3.0).Results The median duration of surgery was 190 minutes.Intraoperative complications were observed in 5 patients, including 3 with hemorrhage, 1 with hypotension,and 1 with hypoxemia, all of which were treated conservatively.The median hospitalization time and time to take out stitches was 12 and 13 days, respectively.And the in-hospital mortality was 4% (2/52).Twentyfour patients suffered post-operative adverse events, including 3 postoperative infections.With a median follow-up time of 183 days, 20% of patients sufferred from grade 3 to 5 adverse events, with hematological toxicities being the most common complication, followed by bellyache.Grade 1 and 2 toxicities which were definitely associated with intraoperative radiotherapy was 28% and 4%, respectively.None of grade 3 to 5 complications were proved to be caused by intraoperative radiotherapy.Conclusions Intraoperative electron radiotherapy is well tolerable and could be widely used for patients with abdominal tumors, with a little longer time to take out stitches but without more morbidities and toxicities compared surgery alone.
8.Clinical value of postoperative radiotherapy for node-positive middle thoracic esophageal squamous cell carcinoma and modification of target volume
Shufei YU ; Wencheng ZHANG ; Zefen XUAO ; Zongmei ZHOU ; Hongxing ZHANG ; Dongfu CHEN ; Qinfu FENG ; Jun LIANG ; Jima LYU ; Jie HE ; Shugeng GAO ; Qi XUE ; Yongsheng MAO ; Kelin SUN ; Xiangyang LIU ; Guiyu CHENG ; Dekang FANG ; Jian LI
Chinese Journal of Radiation Oncology 2016;25(4):332-338
Objective To analyze the clinical value of postoperative radiotherapy for node-positive middle thoracic esophageal squamous cell carcinoma ( TESCC ) and to modify the target volume .Methods A total of 286 patients with node-positive middle TESCC underwent radical surgery in Cancer Hospital, Chinese Academy of Medical Sciences, from 2004 to 2009.In addition, 90 of these patients received postoperative intensity-modulated radiotherapy.The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for survival difference analysis.The Cox model was used for multivariate prognostic analysis.The chi-square test was used for comparing the recurrence between patients receiving different treatment modalities.Results The 5-year overall survival ( OS) rates of the surgery alone ( S) group and surgery plus postoperative radiotherapy ( S+R) group were 22.9%and 37.8%, respectively, and the median OS times were 23.2 and 34.7 months, respectively ( P=0.003) .For patients with 1 or 2 lymph
node metastases (LNMs), the 5-year OS rates of the S group and S+R group were 27.3%and 44.8%, respectively ( P=0.017);for patients with more than 2 LNMs, the 5-year OS rates of the S group and S+R group were 16.7%and 25.0%, respectively (P=0.043).The peritoneal lymph node metastasis rates of N1 , N2 , and N3 patients in the S group were 2.9%, 10.9%, and 20.0%, respectively ( P=0.024) .The S+R group had a significantly lower mediastinal lymph node metastasis rate than the S group ( for patients with 1 or 2 LMNs:8.0%vs.35.3%, P=0.003;for patients with more than 2 LNMs, 10.0%vs.42.3%, P=0.001) , and had a prolonged recurrence time compared with the S group ( 25.1 vs.10.7 months, P=0.000) .However, for patients with more than 2 LNMs, the S+R group had a significantly higher hematogenous metastasis rate than the S group (46.7%vs.26.1%, P=0.039).Conclusions Patients with node-positive middle TESCC could benefit from postoperative radiotherapy.The target volume can be reduced for patients with 1 or 2 LNMs.Prospective studies are needed to examine whether it is more appropriate to reduce the radiotherapy dose than to reduce the target volume for patients with more than 2 LNMs.A high hematogenous metastasis rate warrants chemotherapy as an additional regimen.
9.Clinical efficacy of preoperative three-dimensional radiotherapy with or without concurrent chemotherapy for esophageal carcinoma
Wei DENG ; Qifeng WANG ; Zefen XIAO ; Zongmei ZHOU ; Hongxing ZHANG ; Dongfu CHEN ; Qinfu FENG ; Jun LIANG ; Zhouguang HUI ; Jima LYU ; Jie HE ; Shugeng GAO ; Qi XUE ; Yousheng MAO ; Kelin SUN ; Xiangyang LIU ; Dekang FANG ; Guiyu CHENG ; Dali WANG ; Jian LI
Chinese Journal of Radiation Oncology 2016;(3):220-226
[ Abstract] Objective To investigate the clinical efficacy of preoperative three-dimensional radiotherapy (3DRT) with or without concurrent chemotherapy for esophageal carcinoma.Methods We retrospectively analyzed 103 esophageal carcinoma patients who received preoperative 3DRT with or without concurrent chemotherapy from 2004 to 2014 in Cancer Hospital CAMS.The median radiation dose was 40 Gy, and the TP or PF regimen was adopted for concurrent chemotherapy if needed.The overall survival (OS) and disease-free survival ( DFS) were calculated by the Kaplan-Meier method, and the survival difference and univariate prognostic analyses were performed by the log-rank test.The Cox proportional hazards model was used for multivariate prognostic analysis.Results The number of patients followed at 3-years was 54.The 3-year OS and DFS rates were 61.1% and 54.9%, respectively, for all patients.There were no significant differences between the 3DRT and concurrent chemoradiotherapy (CCRT) groups as to OS (P=0.876) and DFS (P=0.521).The rates of complete, partial, and minimal pathologic responses of the primary tumor were 48.0%, 40.2%, and 11.8%, respectively.There were significant differences in OS and DFS between the complete, partial, and minimal pathologic response groups (P=0.037 and 0.003). No significant difference in pathologic response rate was found between the 3DRT and CCRT groups (P=0.953).The lymph node metastasis rate was 26.5%, and this rate for the complete, partial, and minimal pathologic response groups was 14%, 30%, and 67%, respectively, with a significant difference between the three groups (P=0.001).The OS and DFS were significantly higher in patients without lymph node metastasis than in those with lymph node metastasis (P=0.034 and 0.020).The surgery-related mortality was 7.8% in all patients.Compared with the 3DRT group, the CCRT group had significantly higher incidence rates of leukopenia (P=0.002), neutropenia (P=0.023), radiation esophagitis (P=0.008), and radiation esophagitis ( P=0.023).Pathologic response of the primary tumor and weight loss before treatment were independent prognostic factors for OS and DFS (P=0.030,0.024 and P=0.003,0.042). Conclusions Preoperative 3DRT alone or with concurrent chemotherapy can result in a relatively high complete pathologic response rate, hence increasing the survival rate.Further randomized clinical trials are needed to confirm whether preoperative CCRT is better than 3DRT in improving survival without increasing the incidence of adverse reactions.
10.Long-term outcomes and failure patterns of prophylactic cranial irradiation in limited-stage small cell lung cancer patients managed with modern chemoradiotherapy and diagnostic methods
Xuan LIU ; Zongmei ZHOU ; Zefen XIAO ; Qinfu FENG ; Dongfu CHEN ; Jima LYU ; Jun LIANG ; Nan BI ; Xin WANG ; Lei DENG ; Tao ZHANG ; Wenqing WANG ; Xiaozhen WANG ; Zhouguang HUI ; Lyuhua WANG
Chinese Journal of Radiation Oncology 2021;30(2):114-119
Objective:To evaluate the clinical efficacy and failure patterns of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) on the basis of modern chemoradiotherapy and diagnostic techniques.Methods:In this retrospective study, clinical data of 201 LS-SCLC patients treated with chemotherapy (EP/CE regimens, ≥4 cycles) and intensity-modulated radiotherapy (IMRT) in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were reviewed. All patients were primarily managed with concurrent or sequential chemoradiotherapy and achieved complete response (CR) or partial response (PR). Ninety percent of patients were revaluated for brain metastasis (BM) by MRI and 10% by CT scan. Long-term survival and failure patterns were compared between the PCI ( n=91) and non-PCI groups ( n=110). Results:The median follow-up time was 77.3 months (95% CI 73.0-81.5 months). The median overall survival (OS), 2-and 5-year OS rates were 58.5 months, 72.5% and 47.7% in the PCI group, and 34.5 months, 61.7% and 35.8% in the non-PCI group ( P=0.075). The median progression-free survival (PFS), 2-and 5-year PFS rate were 22.0 months, 48.0% and 43.4% in the PCI group, significantly higher than 13.9 months, 34.4% and 26.7% in the non-PCI group ( P=0.002). The 2- and 5-year cumulative incidence of BM were 6.6% and 12.2% in the PCI group, and 30.0% , 31.0% in the non-PCI group ( P=0.001). The median time and rate of BM as an isolated first site of relapse were 11.9 months and 4.4% in the PCI group, and 8.7 months and 25.5% in the non-PCI group ( P<0.001). Multivariate analysis showed that response after chemoradiotherapy ( P<0.001) and PCI ( P=0.033) were the independent prognostic factors for PFS. Stratified analysis demonstrated that PCI significantly improved the 5-year PFS in patients who achieved CR (72.7% vs. 48.0%, P=0.013), while it did not improve the 5-year PFS in patients who obtained PR (26.1% vs. 20.2%, P=0.213). Conclusion:In the new era of standard chemoradiotherapy and more accurate diagnostic methods for BM, PCI was associated with improved PFS and lower incidence of BM in LS-SCLC patients.