Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

Talaromyoxaones A and B: Unusual Oxaphenalenone Spirolactones as Phosphatase Inhibitors from the Marine-Derived Fungus Talaromyces purpureogenus SCSIO 41517.

(+)- and (-)-talaromyoxaones A and B (1 and 2, respectively), two new oxaphenalenone derivatives with a hemiacetal frame and an unprecedented spirolactone frame of a 2'H,3H,4'H-spiro[isobenzofuran-1,3'-pyran]-3-one unit that show biosynthetic enantiodivergence, and two new oxaphenalenone analogues (±)-11-apopyrenulin (3) and (+)- or (-)-abeopyrenulin (4) were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations of ECD spectra. Compounds 1 and 2 showed selective inhibitory activity against phosphatases SHP1, SHP2, and MEG2 with IC50 values of 1.3-3.4 µM, and the potential modes of action for 1 were investigated by a preliminary molecular docking study.

Effect of SIB-IMRT-based selective dose escalation of local tumor on the prognosis of patients with esophageal cancer.

BACKGROUND: To investigate the effect of SIB-IMRT-based selective dose escalation to local tumor on the prognosis of patients with esophageal cancer (EC). METHODS: A total of 302 EC patients were enrolled. The prognostic factors of the entire group were initially analyzed, and the composition ratios of the two groups and the different doses of each fraction for PTV were compared. The propensity-score matching (PSM) was carried out (1:1 ratio), and the prognostic factors for the two groups were analyzed according to the results of COX. RESULTS: The median overall survival (OS) for all patients was 30.0 months (23.495-36.505 months), and the median disease-free survival (DFS) was 21.3 months (7.698-24.902 months). In multivariate analysis, chemotherapy, cTNM stage and dose-per-fraction for the PTV were independent prognostic factors for OS (P = 0.013, 0.000, 0.028) and DFS (P = 0.033, 0.000, 0.047). Multivariate analysis of patients after PSM revealed that cTNM staging and dose-per-fraction were the independent prognostic factors for OS (P = 0.000, 0.015). Chemotherapy, cTNM staging and dose-per-fraction for the PTV were the independent prognostic factors for DFS (P = 0.025, 0.010, 0.015). There was no significant difference in grade ≥ 2 acute toxicities between the two groups. A subgroup analysis of patients with a single dose of 2 Gy and > 2 Gy in the SIB-IMRT group showed that OS and DFS of the latter were significantly better than those of the former. CONCLUSION: The selective dose escalation to local tumors based on SIB-IMRT technique can improve the survival of patients received radical radiotherapy without increasing toxicities.

Quantitative determination and validation of octreotide acetate using 1 H-NMR spectroscopy with internal standard method.

Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated 1 H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards.

Computed tomography lymphangiography findings in 27 cases of lymphangioleiomyomatosis.

Background Lymphangioleiomyomatosis (LAM) is a rare disease involving the bronchi, lymphatic vessels, and veins. However, there are few reports about lymphatic vessel abnormalities associated with LAM. Purpose To evaluate computed tomography (CT) lymphangiography findings in cases of LAM, especially lymphatic vessel abnormalities. Material and Methods Twenty-seven patients with LAM underwent direct lymphangiography (DLG), followed by a post-procedural thoracoabdominal CT examination. Results All 27 patients were diagnosed with LAM, including 25 (93%) with chylothorax, eight (30%) with chyloperitoneum, seven (26%) with chylous fluid in the chest and abdomen, and one (4%) with lower-limb lymphedema. The CT lymphangiography showed that 27/27 (100%) patients presented iliac or retroperitoneal lymphatic vessel dilation; 20/27 (74%) presented thoracic duct outlet obstruction; 9/27 (33%) presented pleural lymph leakage; and 13/27 (48%) presented an abnormal distribution of contrast agent in the contralateral lumbar trunk, 3/27 (11%) in the pulmonary field, 1/27 (4%) in the abdominal cavity, and 4/27 (15%) in the pelvic cavity. Five of the 27 patients (19%) had retroperitoneal lymphangioleiomyomas, with contrast agent accumulation in three cases during CT lymphangiography. Two of the 27 (7%) patients had enlarged lymph nodes in the retroperitoneum. All 27 patients (100%) diagnosed with LAM displayed various lung cysts on thoracic high-resolution CT scans. Conclusion CT lymphangiography findings can be used to diagnose most LAM cases accurately. Moreover, these findings also display the various lymphatic vessel abnormalities associated with LAM.

Analysis of the causes of failure after radical surgery in patients with PT3N0M0 thoracic esophageal squamous cell carcinoma and consideration of postoperative radiotherapy.

BACKGROUND: Five-year overall survival rate of TESCC after surgery is low (approximately 30% to 60%), so it is meaningful to discuss the significance of PORT. METHODS: We retrospectively collected the data of 227 patients with PT3N0M0 esophageal cancer (EC). The failure pattern after surgery was analyzed. Difference of adjuvant PORT in patients with PT3N0M0 TESCC and the appropriate population were explored based on the relevant studies. RESULTS: There were 58 cases with intrathoracic locoregional recurrence (LRR) after radical surgery and 27 cases with distant metastasis, including 10 cases of recurrence. The recurrence rate of mediastinal lymph nodes in the thoracic cavity was 50.0%. Univariate analysis revealed that compared with patients with middle and lower thoracic EC, the 3/5-year survival rate of patients with upper thoracic EC was significantly lower, accompanied with remarkably higher thoracic LRR. Compared with those with moderately- and well-differentiated TESCC, the 3/5-year survival rate of patients with poorly differentiated TESCC was significantly lower, whereas the distant metastasis rate was notably higher. Multivariate analysis revealed that different lesion locations and different pathologic differentiation were the independent prognostic factors. The lesion location and degree of differentiation were the independent influencing factors for thoracic LRR and distant metastasis, respectively. CONCLUSION: The intrathoracic LRR is the major failure pattern for patients with PT3N0M0 TESCC after conventional two-field lymphadenectomy. In addition, recurrence rate of PT3N0M0 TESCC was significantly higher in upper thoracic EC than in middle and lower thoracic EC. PORT is recommended to patients with PT3N0M0 upper TESCC.

Seasonal Mass Changes and Crustal Vertical Deformations Constrained by GPS and GRACE in Northeastern Tibet.

Surface vertical deformation includes the Earth's elastic response to mass loading on or near the surface. Continuous Global Positioning System (CGPS) stations record such deformations to estimate seasonal and secular mass changes. We used 41 CGPS stations to construct a time series of coordinate changes, which are decomposed by empirical orthogonal functions (EOFs), in northeastern Tibet. The first common mode shows clear seasonal changes, indicating seasonal surface mass re-distribution around northeastern Tibet. The GPS-derived result is then assessed in terms of the mass changes observed in northeastern Tibet. The GPS-derived common mode vertical change and the stacked Gravity Recovery and Climate Experiment (GRACE) mass change are consistent, suggesting that the seasonal surface mass variation is caused by changes in the hydrological, atmospheric and non-tidal ocean loads. The annual peak-to-peak surface mass changes derived from GPS and GRACE results show seasonal oscillations in mass loads, and the corresponding amplitudes are between 3 and 35 mm/year. There is an apparent gradually increasing gravity between 0.1 and 0.9 µGal/year in northeast Tibet. Crustal vertical deformation is determined after eliminating the surface load effects from GRACE, without considering Glacial Isostatic Adjustment (GIA) contribution. It reveals crustal uplift around northeastern Tibet from the corrected GPS vertical velocity. The unusual uplift of the Longmen Shan fault indicates tectonically sophisticated processes in northeastern Tibet.

Quantitative analysis of sitagliptin using the (19)F-NMR method: a universal technique for fluorinated compound detection.

To expand the application scope of nuclear magnetic resonance (NMR) technology in quantitative analysis of pharmaceutical ingredients, (19)F nuclear magnetic resonance ((19)F-NMR) spectroscopy has been employed as a simple, rapid, and reproducible approach for the detection of a fluorine-containing model drug, sitagliptin phosphate monohydrate (STG). ciprofloxacin (Cipro) has been used as the internal standard (IS). Influential factors, including the relaxation delay time (d1) and pulse angle, impacting the accuracy and precision of spectral data are systematically optimized. Method validation has been carried out in terms of precision and intermediate precision, linearity, limit of detection (LOD) and limit of quantification (LOQ), robustness, and stability. To validate the reliability and feasibility of the (19)F-NMR technology in quantitative analysis of pharmaceutical analytes, the assay result has been compared with that of (1)H-NMR. The statistical F-test and student t-test at 95% confidence level indicate that there is no significant difference between these two methods. Due to the advantages of (19)F-NMR, such as higher resolution and suitability for biological samples, it can be used as a universal technology for the quantitative analysis of other fluorine-containing pharmaceuticals and analytes.

The quasi-biennial vertical oscillations at global GPS stations: identification by ensemble empirical mode decomposition.

Modeling nonlinear vertical components of a GPS time series is critical to separating sources contributing to mass displacements. Improved vertical precision in GPS positioning at stations for velocity fields is key to resolving the mechanism of certain geophysical phenomena. In this paper, we use ensemble empirical mode decomposition (EEMD) to analyze the daily GPS time series at 89 continuous GPS stations, spanning from 2002 to 2013. EEMD decomposes a GPS time series into different intrinsic mode functions (IMFs), which are used to identify different kinds of signals and secular terms. Our study suggests that the GPS records contain not only the well-known signals (such as semi-annual and annual signals) but also the seldom-noted quasi-biennial oscillations (QBS). The quasi-biennial signals are explained by modeled loadings of atmosphere, non-tidal and hydrology that deform the surface around the GPS stations. In addition, the loadings derived from GRACE gravity changes are also consistent with the quasi-biennial deformations derived from the GPS observations. By removing the modeled components, the weighted root-mean-square (WRMS) variation of the GPS time series is reduced by 7.1% to 42.3%, and especially, after removing the seasonal and QBO signals, the average improvement percentages for seasonal and QBO signals are 25.6% and 7.5%, respectively, suggesting that it is significant to consider the QBS signals in the GPS records to improve the observed vertical deformations.

Prediction of positive pulmonary nodules based on machine learning algorithm combined with central carbon metabolism data.

BACKGROUND: Lung cancer causes a huge disease burden, and early detection of positive pulmonary nodules (PPNs) as an early sign of lung cancer is extremely important for effective intervention. It is necessary to develop PPNs risk recognizer based on machine learning algorithm combined with central carbon metabolomics. METHODS: The study included 2248 participants at high risk for lung cancer from the Ma'anshan Community Lung Cancer Screening cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to screen 18 central carbon-related metabolites in plasma, recursive feature elimination (RFE) was used to select all 42 features, followed by five machine learning algorithms for model development. The performance of the model was evaluated using area under the receiver operator characteristic curve (AUC), accuracy, precision, recall, and F1 scores. In addition, SHapley Additive exPlanations (SHAP) was performed to assess the interpretability of the final selected model and to gain insight into the impact of features on the predicted results. RESULTS: Finally, the two prediction models based on the random forest (RF) algorithm performed best, with AUC values of 0.87 and 0.83, respectively, better than other models. We found that homogentisic acid, fumaric acid, maleic acid, hippuric acid, gluconic acid, and succinic acid played a significant role in both PPNs prediction model and NPNs vs PPNs model, while 2-oxadipic acid only played a role in the former model and phosphopyruvate only played a role in the NPNs vs PPNs model. This model demonstrates the potential of central carbon metabolism for PPNs risk prediction and identification. CONCLUSION: We developed a series of predictive models for PPNs, which can help in the early detection of PPNs and thus reduce the risk of lung cancer.

Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.

[Low dose volume histogram analysis of the lungs in prediction of acute radiation pneumonitis in patients with esophageal cancer treated with three-dimensional conformal radiotherapy].

OBJECTIVE: To investigate the predictive value of low dose volume of the lung on acute radiation pneumonitis (RP) in patients with esophageal cancer treated with three-dimensional conformal radiotherapy (3D-CRT) only, and to analyze the relation of comprehensive parameters of the dose-volume V5, V20 and mean lung dose (MLD) with acute RP. METHODS: Two hundred and twenty-two patients with esophageal cancer treated by 3D-CRT have been followed up. The V5-V30 and MLD were calculated from the dose-volume histogram system. The clinical factors and treatment parameters were collected and analyzed. The acute RP was evaluated according to the RTOG toxicity criteria. RESULTS: The acute RP of grade 1, 2, 3 and 4 were observed in 68 (30.6%), 40 (18.0%), 8 (3.6%) and 1 (0.5%) cases, respectively. The univariate analysis of measurement data:The primary tumor length, radiation fields, MLD and lung V5-V30 had a significant relationship with the acute RP. The magnitude of the number of radiation fields, the volume of GTV, MLD and Lung V5-V30 had a significant difference in whether the ≥ grade 1 and ≥ grade 2 acute RP developed or not. Binary logistic regression analysis showed that MLD, Lung V5, V20 and V25 were independent risk factors of ≥ grade 1 acute RP, and the radiation fields, MLD and Lung V5 were independent risk factors of ≥ grade 2 acute RP. The ≥ grade 1 and ≥ grade 2 acute RP were significantly decreased when MLD less than 14 Gy, V5 and V20 were less than 60% and 28%,respectively. When the V20 ≤ 28%, the acute RP was significantly decreased in V5 ≤ 60% group. When the MLD was ≤ 14 Gy, the ≥ 1 grade acute RP was significantly decreased in the V5 ≤ 60% group. When the MLD was >14 Gy, the ≥ grade 2 acute RP was significantly decreased in the V5 ≤ 60% group. CONCLUSIONS: The low dose volume of the lung is effective in predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-CRT only. The comprehensive parameters combined with V5, V20 and MLD may increase the effect in predicting radiation pneumonitis.

[Hennekam syndrome: a case report and review of literature].

OBJECTIVE: To study the clinical characteristics of Hennekam syndrome. METHODS: We described a case of long-term iron deficiency anemia, characteristic facial anomalies, growth retardation, and intestinal lymphangiectasia. To our knowledge, this is the first case of Hennekam syndrome reported in China. Meanwhile, relevant literature was also reviewed. RESULTS: A total of 35 cases of Hennekam syndrome were identified, consisting of 18 males and 17 females (age ranging 0 - 40 years old). Lymphangiectasia, lymphedema, facial anomalies (hypertelorism, flat nasal bridge and flat face) and developmental retardation were the major clinical manifestations of the syndrome. CCBE1 mutation may have played an important role in the pathogenesis of the syndrome. Long-term moderate-to-severe iron deficiency anemia was a distinctive feature of our case. Lymphangiography revealed lymphangiectasia of small intestine and lower limb, as well as thoracic outlet obstruction. Complete elimination of anemia and significant increase of serum albumin level were observed several months after the adhesiolysis procedure of the distal end of thoracic duct. However, anemia and severe hypoalbuminemia relapsed after taking greasy food. CONCLUSIONS: Hennekam syndrome is a rare autosomal recessive syndrome characterized by defective lymphatic development. Congenital lymphangiectasia should be considered in the patients with unexplained developmental retardation and hypoalbuminemia. Moreover, intestinal lymphangiectasia can be a rare cause of gastrointestinal bleeding.

[Application of direct lymphangiography in the diagnosis of primary chyluria].

OBJECTIVE: To discuss the role of direct lymphangiography in the diagnosis of primary chyluria. METHODS: Iodized oil was infused into lymphatic vessel of unilateral foot in 25 cases. The condition of lymphatic system imaging was dynamically observed via Innova 2100-IQ digital flat-panel angiography system. RESULTS: All of them underwent direct lymphangiography. The results revealed unilateral (n = 18) or bilateral (n = 7) renal reflux of contrast media. Among 22 stenotic cases, there were partial (n = 18) or whole (n = 4) cervical section of thoracic duct, no imaging in cervicothoracic section of thoracic duct (n = 1); thin imaging in cervical section and partial thoracic section (n = 2); retroperitoneal lymphangictasia & tortuous lymphatic vessels (n = 21); reflux of contrast medium to pelvic and/or contralateral sacroiliac part (n = 13). CONCLUSION: Capable of acquiring dynamic images of chyle (lymph) circulation, direct lymphangiography provides accurate estimation for the location, scope, extent of lesions of renal chylous reflux in primary chyluria so as to guide surgery. Stenotic cervical section of thoracic duct plays an important etiologic role in primary chyluria.

The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

Objective: To investigate the predictive value of Controlling Nutritional Status (CONUT) score and systemic inflammation (SIS) score in the prognosis, short-term efficacy, and immune-related side effects of patient with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) receiving immunotherapy as second line therapy combined with or without radiotherapy. Methods: Forty-eight patients with R/M ESCC who received second-line therapy with Camrelizumab were retrospectively studied. They were divided into the high and low score groups according to the CONUT and SIS score. Univariate and multivariate analyses were used to analyze factors that might affect patient prognosis and the effects of different CONUT score and SIS on the short-term efficacy and immune-related toxic and side effects of patients. Results: The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 42.9% and 22.5%, and 29.0% and 5.8%, respectively. The CONUT score ranged from 0 to 6 (3.31 ± 1.43), whereas the SIS score ranged from 0 to 2 (1.19 ± 0.73). Multivariate analysis showed that treatment related toxicity, number of cycles of Camrelizumab used, short-term effect and SIS score were independent prognostic factors for OS (P=0.044, 0.021, 0.021, 0.030, respectively), whereas SIS and CONUT scores were independent prognostic factors for PFS (P=0.005, 0.047, respectively). Patients with low CONUT/SIS score had a low incidence rate of immune-related adverse reactions (X2 = 9.735, 5.693; P=0.002, 0.017) and better short-term efficacy (X2 = 4.427, 7.438; P=0.035, 0.006). Conclusion: R/M ESCC patients with low CONUT/SIS score have better prognosis, higher objective response rate, lower incidence of immune-related toxic and side effects after receiving immunotherapy as second-line therapy. CONUT scores and SIS scores may be reliable prognostic indicators for patient receiving immunotherapy as second-line therapy for R/M ESCC.

Corrigendum: The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

[This corrects the article DOI: 10.3389/fonc.2023.1167625.].

Targeted metabolomics reveals the association between central carbon metabolism and pulmonary nodules.

With the widespread application of low-dose computed tomography (LDCT) technology, pulmonary nodules have aroused more attention. Significant alteration in plasma metabolite levels, mainly amino acid and lipid, have been observed in patients of PNs. However, evidence on the association between central carbon metabolism and PNs are largely unknown. The aim of this study was to investigate the underlying association of PNs and plasma central carbon metabolites. We measured the levels of 16 plasma central carbon metabolites in 1954 participants who gained LDCT screening in MALSC cohort. The inverse probability weighting (IPW) technique was used to control for bias due to self-selection for LDCT in the assessed high-risk population. The least absolute shrinkage and selection operator (LASSO) penalized regression was used to deal with the problem of multicollinearity among metabolites and the combined association of central carbon metabolites with PNs was estimated by using quantile g-computation (QgC) models. A quartile increase in 3-hydroxybutyric acid, gluconic acid, succinic acid and hippuric acid was positively associated with the PNs risk, whereas a quartile increase in 2-oxadipic acid and fumaric acid was negatively associated with the risk of PNs in multiple-metabolite models. A positive but insignificant joint associations of the mixture of 16 metabolites with PNs was observed by using QgC models analyses. Further studies are warranted to clarify the association between circulating metabolites and PNs and the biological mechanisms.

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma.

OBJECTIVE: This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). METHODS: In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed. RESULTS: The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1-45.7 months) and 15.3 months (95% CI 12.8-17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8-75.7 months) and 20.5 months (95% CI 14.1-27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0-21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1-14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. CONCLUSIONS: ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

[Prognostic analysis of clinicopathological factors in patients after radical resection of esophageal carcinoma].

OBJECTIVE: To explore factors affecting the survival in patients after radical resection of esophageal carcinoma, and to provide a valuable reference for selecting treatment protocol after surgery. METHODS: Clinicopathological data of 618 esophageal cancer patients who underwent radical resection at the Fourth Hospital of Hebei Medical University from May 2002 to June 2006 were collected and reviewed in this study. All patients had no cancer history, did not receive preoperative radiotherapy or chemotherapy, and had Karnofsky performance scores ≥ 70. Univariate analysis was performed by using log-rank test to determine predictors of survival, and multivariable analysis was performed by a Cox regression model. RESULTS: The overall 1-, 3-, 5-year survival rates were 83.32%, 53.33%, 36.02%, respectively, and the median survival time was 38.33 months. The Cox regression analysis showed that operation mode, intraoperative findings of the extent of tumor invasion, pathological T stage, and the number of metastatic lymph nodes were significant predictors of survival. For patients with lymph node metastasis, the overall 1-, 3-, and 5-year survival rates did not significantly differ between the operation alone group and the postoperative prophylactic radiotherapy group. For patients without lymph node metastasis, the 1-, 3-, and 5-year survival rates were 94.34%, 51.55%, and 34.41%, respectively, in the postoperative radiotherapy group, significantly higher than those in the operation alone group (63.08%, 23.30% and 4.36%; χ(2) = 15.99, P < 0.01). CONCLUSIONS: The independent prognostic factors of esophageal cancer patients after radical resection include the operation mode, intra-operative findings of the extent of tumor invasion, pathological T stage, the number of lymph node metastasis and the number of regions of lymph node metastasis. Postoperative prophylactic radiotherapy is beneficial for esophageal cancer patients with lymph node metastasis.