ABSTRACT
The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver's cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.
Subject(s)
Humans , Liver/surgery , Hepatocytes/transplantation , Stem Cells/metabolism , Liver Diseases/surgeryABSTRACT
The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.
ABSTRACT
Neoadjuvant therapy, especially neoadjuvant chemoradiotherapy, has become the standard preoperative treatment for locally advanced resectable esophageal cancer, whereas the recurrence and distant metastasis rates after surgery remain high. In recent years, programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors have been widely adopted in immunotherapy for cancer. Whether PD-1/PD-L1 immune checkpoint inhibitors combined with neoadjuvant chemotherapy / neoadjuvant chemoradiotherapy could further improve clinical efficacy, increase the complete surgical resection rate and safety are current research hotspots. In this article, neoadjuvant immunotherapy combined with chemotherapy / radiochemotherapy for esophageal cancer was reviewed.
ABSTRACT
Objective:To evaluate the effect of definitive radiotherapy with different doses on overall survival (OS) and identify the prognostic factors of patients with non-metastatic esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of 2 344 ESCC patients treated with definitive radiotherapy (RT) alone or chemoradiotherapy from 2002 to 2016 in 10 hospitals were collected and analyzed retrospectively. After the propensity score matching (PSM)(1 to 2 ratio), all patients were divided into the low-dose group (equivalent dose in 2 Gy fractions, EQD 2Gy<60 Gy; n=303) and high-dose group (EQD 2Gy≥60 Gy; n=606) based on the dose of radiation. Survival analysis was conducted by Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox′s regression model. Results:The median follow-up time was 59.6 months. After the PSM, the 1-, 3- and 5-year overall survival (OS) rate was 66.5%, 34.7%, 27.2% in the low-dose group, 72.9%, 41.7% and 34.7% in the high-dose group, respectively ( P=0.018). The 1-, 3-and 5-year progression-free survival rate was 52.2%, 27.2%, 23.1% in the low-dose group, 58.3%, 38.1% and 33.9% in the high-dose group, respectively ( P=0.001). The outcomes of univariate analysis indicated that cervical/upper esophagus location, early (stage Ⅱ) AJCC clinical stage, node negative status, tumor length ≤5 cm, receiving intensity-modulated radiation therapy (IMRT), receiving concurrent chemotherapy and EQD 2Gy≥60 Gy were closely associated with better OS (all P<0.05). Multivariable analysis demonstrated that tumor location, regional lymph node metastasis, concurrent chemotherapy and EQD 2Gy were the independent prognostic factors for OS (all P<0.05). Conclusion:Three-dimensional conformal or IMRT with EQD 2Gy≥60 Gy yields favorable survival outcomes for patients with locally advanced ESCC.
ABSTRACT
Objective:To observe the effects of oxymatrine(OM) on the expression and release of high mobility group box 1(HMGB1) in rat pancreatic acinar cell line AR42J stimulated by hydrogen peroxide.Methods:MTT method was used to detect the effects of H 2O 2 in different concentrations on the survival of AR42J cells. AR42J cells cultured in vitro were divided into control group, H 2O 2 group and H 2O 2+ OM group. An equal volume of H 2O 2(final concentration 0.16 mmol/L) was added in H 2O 2 group and H 2O 2+ OM group, respectively, while an equal volume of triple distilled water was added in control group. In H 2O 2+ OM group, OM(final concentration 0.5 g/L)was added 0.5 h before the addition of H 2O 2, and cell samples and supernatant were collected after 24 h culture. The expression of HMGB1 protein was detected by Western blotting, the level of HMGB1 protein in cell supernatant was detected by enzyme-linked immunosorbent assay, and the intracellular distribution of HMGB1 protein was detected by immunofluorescence. Results:In the H 2O 2 group, the expression of HMGB1, the secretion of HMGB1 in the supernatant and the proportion of cytoplasmic HMGB1 in the total HMGB1 were significantly higher than those in the control group[1.04±0.04 vs 0.69±0.02, (4.84±0.13)μg/L vs (2.68±0.07)μg/L, (35.7±2.5)% vs (10.7±1.9)%], and all the differences were statistically significant (all P<0.05). After OM intervention, HMGB1 protein expression, secretion and cytoplasmic proportion were [0.82±0.02, (3.97±0.10)μg/L and (27.3±1.7)%], respectively, which were obviously lower than those in the H 2O 2 group, and all the differences were statistically significant (all P<0.05). Conclusions:H 2O 2 can induce the expression and release of HMGB1 in rat pancreatic acinar cells; OM treatment could alleviate the severity of oxidative stress injuries induced by H 2O 2 in AR42J cells.
ABSTRACT
There are various bacterial colonies in the human intestine, which play an important role in the maintenance of human intestinal function and the maintenance of the systemic immune system. After years of research, researchers have found that intestinal flora are closely related to a variety of inflammatory and immune diseases. In recent years, immunotherapy has attracted more and more attention in the treatment of malignant tumors. In these immunotherapy researches, researchers have found that the composition and changes of intestinal flora can affect the efficacy of tumor immunotherapy to a certain extent. In this paper, the literatures related to intestinal flora and tumor immunotherapy were reviewed from four aspects including the relationship between intestinal flora and body's immune mechanism, current status of tumor immunotherapy, correlation research between intestinal flora and tumor immunotherapy, and related factors that affect changes in intestinal flora composition. The researches on intestinal flora and tumor immunotherapy in the past ten years were mainly summarized. The analysis results showed that the intestinal flora plays an important role in the body's immune mechanism and is closely related to the efficacy of tumor immunotherapy.
ABSTRACT
Objective@#To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy.@*Methods@#The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively.@*Results@#The percentage of normal lung receiving at least 20 Gy (V20) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V30) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients′age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS.@*Conclusions@#Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients′ age, tumor diameter and tumor volume may impact patients′ prognosis.
ABSTRACT
Objective@#To observe the effects of oxymatrine(OM) on the expression and release of high mobility group box 1(HMGB1) in rat pancreatic acinar cell line AR42J stimulated by hydrogen peroxide.@*Methods@#MTT method was used to detect the effects of H2O2 in different concentrations on the survival of AR42J cells. AR42J cells cultured in vitro were divided into control group, H2O2 group and H2O2+ OM group. An equal volume of H2O2(final concentration 0.16 mmol/L) was added in H2O2 group and H2O2+ OM group, respectively, while an equal volume of triple distilled water was added in control group. In H2O2+ OM group, OM(final concentration 0.5 g/L)was added 0.5 h before the addition of H2O2, and cell samples and supernatant were collected after 24 h culture. The expression of HMGB1 protein was detected by Western blotting, the level of HMGB1 protein in cell supernatant was detected by enzyme-linked immunosorbent assay, and the intracellular distribution of HMGB1 protein was detected by immunofluorescence.@*Results@#In the H2O2 group, the expression of HMGB1, the secretion of HMGB1 in the supernatant and the proportion of cytoplasmic HMGB1 in the total HMGB1 were significantly higher than those in the control group[1.04±0.04 vs 0.69±0.02, (4.84±0.13)μg/L vs (2.68±0.07)μg/L, (35.7±2.5)% vs (10.7±1.9)%], and all the differences were statistically significant (all P<0.05). After OM intervention, HMGB1 protein expression, secretion and cytoplasmic proportion were [0.82±0.02, (3.97±0.10)μg/L and (27.3±1.7)%], respectively, which were obviously lower than those in the H2O2 group, and all the differences were statistically significant (all P<0.05).@*Conclusions@#H2O2 can induce the expression and release of HMGB1 in rat pancreatic acinar cells; OM treatment could alleviate the severity of oxidative stress injuries induced by H2O2 in AR42J cells.
ABSTRACT
Objective@#To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection.@*Methods@#We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model.@*Results@#122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor (P=0.010).@*Conclusions@#Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB-ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.
ABSTRACT
Objective Investigate the relationship between gross tumor volume (GTV)-related factors including GTV-T volume,the maximum thickness of the esophageal lesion plane and GTV-T volume/length(GTV-T volume divided by the length of the lesion calculated by the number of GTV-T layers) and the locoregional failure of radical intensity-modulated radiation therapy (IMRT) for esophageal carcinoma.Methods A total of 133 patients with esophageal cancer undergoing radical IMRT were enrolled.The factors related to GTV-T including GTV-T volume,the maximum thickness of the esophageal lesions,GTV-T volume/length were calculated.The relationship between GTV-T related factors and local recurrence of tumors was retrospectively analyzed.Results There was positively linear association between the locoregional failure rate of GTV-T and the volume of GTV-T.The volume of GTV-T tumor was 36 cm3,the maximum wall thickness was 2.5 cm,and the GTV-T volume/length was calculated as 5.3 cm2.These critical values could be utilized to predict the risk of locoregional failure of IMRT for esophageal carcinoma.Conclusions The GTV-T factors can be adopted to predict the local control and the risk of locoregional failure of radical IMRT for esophageal carcinoma to certain extent.
ABSTRACT
Objective To investigate the optimal dosage of thoracic radiotherapy in patients diagnosed with extensive stage small cell lung cancer (ES-SCLC).Methods Clinical data of ES-SCLC patients admitted to Tianjian Medical University Cancer Institute& Hospital between February 2010 and October 2015 were retrospectively analyzed.All patients received the first-line induction chemotherapy.Subsequently,216 patients without progression after the first-line induction chemotherapy were apportioned to the thoracic radiotherapy (n=180) group and chemotherapy alone group (n=36).According to the distribution characteristics of the biological equivalent dose,all patients were assigned into the A (31.3-40.2 Gy,n=23),B (46.0-46.8 Gy,n=38),C (49.5-53.7 Gy,n=43) and D groups (55.1-60.6 Gy,n=76).For the subgroup analysis,the low (31.3-46.8 Gy,n=61) and high dose groups (49.5-60.6 Gy,n=119) were divided.Kaplan-Meier survival analysis was used for prognostic analysis.Cox's regression model was conducted for multivariate prognostic analysis.Propensity score matching was utilized to control the confounding variables.Results The median overall survival of all patients was 13.2 months,and 8.3,11.0,15.8,17.8 and 8.1 months for patients in the A,B,C,D and chemotherapy alone groups,respectively (all P=0.000).The median overall survival did not significantly differ between A and B/ chemotherapy groups (P=0.172,P=0.495),and similar results were obtained between the C and D groups (P=0.624).The median overall survival in the B group was significantly longer than that in the chemotherapy alone group (P=0.020).Statistical significance was noted between C and D groups,and A and B groups (all P＜0.05).The median progression-free survival for all patients was 8.7 months,and 6.5,7.6,11.8,12.4 and 6.1 months in the A,B,C,D and chemotherapy alone groups,respectively (all P=0.000).The median progression-free survival did not significantly differ between A and B chemotherapy groups (P=0.588,P=0.668).The progression-free survival in the B group was slightly longer than that in the chemotherapy group without statistical significance (P=0.070).No statistical significance was observed between the C and D groups (P=0.627).Statistical significance was noted between C and D groups,and A and B groups (all P＜0.02).Uni-and multi-variate analyses prompted that the number of metastatic lesions and dose of thoracic radiotherapy were the independent predictors of the overall survival and progression-free survival (both P＜0.05).Concurrent chemoradiotherapy was the independent predictor of the overall survival (P=0.018).After the propensity score matching,the median overall survival and progression-free survival significantly differed between the low (n=50) and high dose groups (n=50) (10.9 vs.17.5 months,P=0.045;7.4 vs.10.7 months,P=0.014).Conclusions A relatively high dose ranging from 49.5 to 53.7 Gy is recommended during thoracic radiotherapy for ES-SCLC patients.An excessively low dose (≤ 40.2 Gy) probably fails to prolong the survival time,and an extremely high dose (≥55.1 Gy) cannot enable the patients to obtain survival benefits.
ABSTRACT
Objective To retrospectively analyze the effect of tumor length on the prognosis in stage Ⅱ/Ⅲ esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy and to evaluate the role of tumor length in clinical stage for non-operative ESCC patients.Methods The data of 2 086 ESCC patients who were treated with definitive radiotherapy from 2002 to 2016 in 10 hospitals (3JECROG) were analyzed.The effect of tumor length on overall survival (OS) was analyzed and stratified analysis of tumor length was done in different stages of ESCC.Results The median OS and median progression-free survival (PFS) time of the whole group were 25.6 months and 18.2 months respectively.The Cox multivariate analysis showed that treatment moda,aga,alinical stage and tumor length were independent prognostic factors.The median,1-,3-,and 5-year OS were 28.9 months,77.3％,45.0％,and 36.3％ versus 21.9 months,69.9％,37.9％,and 28.1％ for patients with ≤ 5 cm and patients ＞ 5 cm respectively (P＜0.05).For stage Ⅱ patienta,abe median OS were 42.1 and 38.9 months respectively in ≤ 5 cm group and＞5 cm group (P=0.303).And for stage Ⅲ patienta,abe median OS were 23.9 and 19.3 months respectively in ≤5 cm group and＞5 cm group (P＜0.001).The median OS with N1was 24.1 and 18.4 montha,aespectively in ≤5 cm group and＞5 cm group (P＜0.001).Conclusions The tumor length was an independent prognostic factor for stage Ⅱ/Ⅲ patients treated definitive radiotherapy.The tumor length may be helpful in clinical staging of ESCa,aspecially for stage Ⅲ and N1.
ABSTRACT
Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.
ABSTRACT
Objective@#To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells.@*Methods@#A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry.@*Results@#Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference (P=0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P=0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results (P=0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients(P<0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc expression, increased cell proliferation and repressed apoptosis.@*Conclusions@#NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP may be a new therapeutic strategy for ESCC patients.
ABSTRACT
Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.
ABSTRACT
Tumor immune escape is one of the important reasons for tumor development.Immunological checkpoint molecules play a key role in tumor immune escape,and have attracted much attention in basic and clinical studies recently.Immune checkpoint molecules transmit inhibitory signal to anti-tumor immune cells and inhibit their activity through receptor/ligand interactions,thereby exerting anti-tumor function.Molecular expression of the immunological checkpoints of esophageal cancer is closely related to prognosis.At present,clinical trials of treating esophageal cancer using specific antibodies to block the immune checkpoint related signaling pathways are being widely carried out and show some initial effects.However,there are still some patients who are resistant to this treatment.As a result,it is urgent to find novel biomarkers that can accurately predict the therapeutic effects of antitumor immunotherapy for esophageal cancer.In this paper,the researches on esophageal cancer immunological checkpoints and its clinical application were reviewed from four aspects,including the immune checkpoint molecules and their antibodies,the relationship between the expression of esophageal cancer immunological checkpoints and the prognosis,the clinical trials of esophageal cancer immunotherapy and novel biomarkers for predicting the efficacy.It is expected to provide new ideas for further researches on the molecular mechanism of immune escape of esophageal cancer,immunotherapy of esophageal cancer and the combination of various treatments.
ABSTRACT
The incidence of esophageal cancer in elderly patients has been increasing each year because of the aging society. Esopha-geal cancer in elderly patients has become a common clinical disease. Because physiological hypofunction and consequent aging-or treatment-related complications are always observed in elderly patients, it is necessary to consider the applicable treatment strategy and intensity after these patients have undergone a complete evaluation. Radiotherapy is currently one of the most important treat-ment strategies for elderly patients. Here, we review the progress in the use of surgery and radiotherapy combined chemotherapy and other treatments for esophageal cancer in elderly patients.
ABSTRACT
Objective Waist-to-height ratio (WHtR), a measurement of the distribution of body fat, correlated with abdominal obesity indicating that it might be a better predictor of cardiovascular risk and metabolic disease.We, therefore, evaluated optimal WHtR cutoff points according to the risk of framingham risk score ( FRS ) and metabolic syndrome ( MS ) in Chinese .Methods The subjects were from China National Diabetes and Metabolic Disorders Survey during 2007 -2008.Receiver operating characteristic analysis was used to examine the optimal cutoff values of WHtR according to the risk of FRS and MS . Results A total of 27820 women and 18419 men were included in the evaluation .The average age was (45.0 ±13.7 ) years.The proportions of FRS ≥10% and MS increased with WHtR both in men and women.The cutoff points of WHtR for the risk of FRS ≥10%and MS were 0.51, 0.52 in men, and 0.52, 0.53 in women, respectively.When FRS ≥10% and MS were taken into consideration with a certain weights, the pooled cutoffs of WHtR were 0.51 in men, and 0.53 in women, respectively.By using the similar method, the optimized cutoff points were 0.52, 0.51, 0.50 for men and 0.51, 0.53, 0.54 for women in age group 20-39, 40-59 and ≥60 years, respectively.Conclusions The optimal cutoffs of WHtR are 0.51 in men, and 0.53 in women for FRS≥10% in combination with MS indicating that this WHtR cutoff points might be used as indexes to evaluate obesity and risk of obesity -related diseases .
ABSTRACT
Objective To analyze the effects of gross tumor volume(GTV-T)and positive lymph node volume(GTV-LN)on the prognosis of radical concurrent chemoradiotherapy for esophageal squamous cell carcinoma(ESCC). Methods A total of 79 patients with stage N1ESCC undergoing radical radiotherapy in our hospital from 2012 to 2015 were enrolled as subjects. GTV-T and GTV-LN were calculated by the Pinnacle39.0 treatment planning system. The receiver operating characteristic(ROC)curves were used to evaluate the value of the GTV-LN/GTV-T ratio in the prediction of local recurrence(LR)and distant metastasis(DM)of ESCC. Results The median follow-up time was 17.2 months in all patients. The ROC curves were made using the GTV-LN/GTV-T ratio. The optimal cut-off values of GTV-LN/GTV-T ratio for predicting the risk of LR and DM were 0.34 and 0.59, respectively. The statistical analysis revealed that the LR rates were 50% and 8% in patients with GTV-LN/GTV-T ratios of<0.34 and ≥0.34, respectively(P<0.01), while the DM rates were 11% and 43% in patients with GTV-LN/GTV-T ratios of<0.59 and ≥0.59, respectively(P= 0.003). Conclusions The GTV-LN/GTV-T ratio may be a predictor of LR and DM in patients with ESCC. Further studies on the GTV-LN/GTV-T ratio may help to make personalized chemoradiotherapy strategies for patients with ESCC.
ABSTRACT
Objective To evaluate the efficacy of rescue treatment for recurrent esophageal cancer after radical esophagectomy, and to provide insights into the development of comprehensive treatment for esophageal cancer.Methods The clinical data of 218 patients who were confirmed with recurrent metastatic esophageal cancer after R0 resection and received rescue treatment in our hospital from 2004 to 2014 were retrospectively reviewed.The survival rate was determined by the Kaplan-Meier method.Univariate and multivariate prognostic analyses were performed using the log-rank test and Cox proportional hazards model, respectively.Results The median post-recurrence follow-up time was 53 months.The 1-and 3-year overall survival (OS) rates after recurrence were 57.2% and 24.4%, respectively.Among the 163 patients with local recurrence, the 1-and 3-year OS rates were 70% and 42% for patients treated with chemoradiotherapy (n=40), 55% and 24% for those with radiotherapy alone (n=106), and 23% and 8% for those with supportive therapy (n=13)(chemoradiotherapy vs.radiotherapy alone P=0.045, radiotherapy alone vs.supportive therapy P=0.004;none of the patients who were treated with chemotherapy alone survived for one year or more).Univariate analysis showed that N staging, TNM staging, and post-recurrence rescue treatment regimen were independent prognostic factors for esophageal cancer (all P=0.001).On the other hand, multivariate analysis indicated that only rescue treatment regimen was the independent prognostic factor for esophageal cancer (P=0.013).Conclusions Rescue chemoradiotherapy or radiotherapy alone can bring significant survival benefits for patients with recurrent and metastatic, especially locally recurrent, esophageal cancer following radical esophagectomy.