Advances and challenges in the treatment of esophageal cancer

Esophageal cancer (EC) is one of the most common cancers with high morbidity and mortality rates. EC includes two histological subtypes, namely esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC primarily occurs in East Asia, whereas EAC occurs in Western countries. The currently available treatment strategies for EC include surgery, chemotherapy, radiation therapy, molecular targeted therapy, and combinations thereof. However, the prognosis remains poor, and the overall five-year survival rate is very low. Therefore, achieving the goal of effective treatment remains challenging. In this review, we discuss the latest developments in chemotherapy and molecular targeted therapy for EC, and comprehensively analyze the application prospects and existing problems of immunotherapy. Collectively, this review aims to provide a better understanding of the currently available drugs through in-depth analysis, promote the development of new therapeutic agents, and eventually improve the treatment outcomes of patients with EC.

Simultaneous multiple intracerebral hemorrhages: clinical features, risk factors, and outcomes / 国际脑血管病杂志

Objective To investigate the clinical features, risk factors, and outcomes of simultaneous multiple intracerebral hemorrhage ( SMICH). Methods Consecutive patients with acute intracerebral hemorrhage (ICH) admitted to the Department of Neurosurgery, the First Affiliated Hospital of Xi'an Medical University from January 1, 2007 to December 31, 2016 were analyzed retrospectively. The demographics,medical history, clinical data, and imaging features of the patients were collected. SMICH was defined as ICH with two or more lesions at different parts of the brain at the same time on the first brain CT scan. Three months after discharge, patients were assessed by the modified Rankin Scale scores, 0-2 was defined as good outcome, and > 2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcomes and death. Results A total of 962 patients with ICH were enrolled during the study, 69 of them (7. 2％) were SMICH. Among the patients with SMICH, 25(36. 2％) had a good outcome, 44 (63. 8％) had a poor outcome, and 42 died, with a mortality rate of 60. 9％. Multivariate logistic regression analysis showed that oral anticoagulants (odds ratio [OR] 6. 312,95％ confidence interval [CI] 1. 967-9. 258 ), ICH etiology classification ( OR 9. 671, 95％ CI 2. 315- 12. 567), hematoma site (OR 1. 269, 95％ CI 1. 018-2. 112), and low baseline GCS score (OR 3. 267,95％ CI 1. 159-5. 627) were the independent risk factors for SMICH; age (OR 4. 156, 95％ CI 2. 315- 5. 669), hematoma site (OR 1. 231, 95％ CI 1. 018-1. 972), hematoma broke into the ventricle (OR 1. 125,95％ CI 1. 007- 2. 132 ), and low baseline GCS score ( OR 1. 336, 95％ CI 1. 005- 2. 079 ) were the independent risk factors for poor outcome in patients with SMICH; age (OR 5. 267, 95％ CI 1. 976-7. 228),hematoma broke into the ventricle (OR 1. 726, 95％ CI 1. 011-2. 236) and low baseline GCS score (OR 2. 111, 95％ CI 1. 236-3. 671 ) were the independent risk factors for death in patients with SMICH.Conclusions SMICH is a rare cerebrovascular disease with a poor outcome and a very high mortality. Oral anticoagulants, ICH etiology classification, hematoma sites, and low baseline GCS score were the independent risk factors for poor outcome of SMICH. Advanced age, hematoma sites, hematoma broke into the ventricle, and low baseline GCS score were the independent risk factors for poor outcomes in patients with SMICH. Advanced age, hematoma broke into the ventricle, and low baseline GCS score were the independent risk factors for death in patients with SMICH.

Muscle-invasive upper tract urothelial carcinoma predicts invasive bladder recurrence tumor / 中华泌尿外科杂志

Objective To evaluate the risk factors and prognosis of high risk bladder recurrence developing after radical nephroureterectomy(RNU) for upper tract urothelial carcinoma (UTUC).Methods The data of 148 UTUC patients who developed bladder tumor after RNU between January 2000 and December 2013 was retrospectively studied.There were 69 males and 79 females,aged from 34 to 82 years old (average 68 years old).83 patients were accompanied with hydronephrosis.80 patients were renal pelvic carcinoma.32 patients had the history of smoking.24 patients had the history of ureteroscope.68 patients had the tumor larger than 3 cm.Logistic regression model was used to analyze the risk factors of muscle invasive and high grade bladder recurrence lesions.We compared the clinocopathologic characteristics between primary UTUC and bladder cancer recurrence by using Fisher' s exact test.Cancer specific survival was analyzed using the Kaplan-Meier method,with the log-rank test used to assess significance.A Cox proportional hazard model was used for multivariate analysis.Results Of the 148 patients,non-muscle invasive (Tis、Ta and T1) tumors of primary UTUC and bladder recurrence were 51 (34.5％) and 119 (80.4％),respectively.High grade (G3) tumors of primary UTUC and bladder recurrence were 41 (27.7％) and 53(35.8％),respectively.During follow-up,94 (63.5％) experienced bladder recurrence once and 54 (36.5％) experienced multiple bladder recurrence.The median follow-up time was 59.5 (rang 8-142) months,48 (32.4％) patients died of UTUC.The grade of bladder cancer recurrence correlated with the grade (P =0.046),muscle-invasion (P =0.002) and tumor architecture (P =0.034) of the primary UTUC;muscle-invasive bladder cancer recurrence associated with that of the primary UTUC (P =0.009);bladder multiple recurrence related to gender (P =0.007).On multivariate logistic regression analysis,the muscle-invasion of primary UTUC was an independent risk factor for muscle-invasive (HR =5.512,95％ CI 1.654-18.37,P =0.004) and high grade (HR =3.948,95％ CI 1.589-9.813,P =0.004) bladder recurrence tumor.The muscle invasion of primary UTUC (HR =3.498,95％ CI 1.569-7.803,P =0.002) was a prognostic factor for cancer specific survival on multivariate Cox regression analysis.Conclusions Muscle-invasive UTUC tend to predict high risk bladder recurrence tumor,and the female could be more likely to appear multiple recurrence tumor.The muscle invasion of primary UTUC could be an independent prognostic factor for cancer specific survival.

Prognostic factors of patients with T2N0M0 upper tract urothelial carcinoma:a single-center retrospective study of 235 patients / 北京大学学报(医学版)

Objective: To evaluate the impacts of the prognostic factors of T2N0M0 upper tract urothelial carcinoma (UTUC) for Chinese patients.Methods: A retrospective study was conducted including 235 patients who were diagnosed with T2N0M0 UTUC in our hospital and received radical nephroureterectomy (RNU) or partial ureterectomy during January 2000 and December 2013.The 3 and 5-year can-cer-specific survival rates and bladder recurrence-free survival rates of all the patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between the two were compared using the Log-rank test.Variables with significant differences in the univariate analysis were subjected to the multivariate analysis by Cox regression model.Results: A total of 235 patients were included in this study, including 95 (40.4%) male patients and 140 (59.6%) female patients.The mean age was 66.73±10.49 years.The median follow-up time was 53 (rang: 3-142) months, and during the follow-up, 74 (31.5%) patients died of UTUC after a median of 35 months,and 96 (40.9%) patients developed intravesical recurrence after a median of 19.5 months.The 3 and 5-year cancer-specific survival rates of all the patients were 89.1% and 85.9%, respectively;the bladder recurrence-free survival rates were 85.5% and 80.2%, respectively.The independent prognostic factors of cancer-specific mortality were tumor age elder than 55 years (HR=3.138, 95%CI: 1.348-7.306, P=0.008) and diameter larger than 5 cm (HR=3.320, 95%CI: 1.882-5.857, P<0.001).The independent prognostic factors of bladder recurrence-free survival were ureter tumor (HR=1.757, 95%CI: 1.159-2.664, P=0.008) and lower tumor grade (HR=1.760, 95% CI: 1.151-2.692, P=0.009).Conclusion: T2N0M0 UTUC has a better cancer-specific survival.The intravesical recurrence was equivalent to non-muscle invasive UTUC but earlier.The tumor diameter larger than 5 cm and the patient age elder than 55 years were independently associated with cancer-specific mortality;the primary tumor located in ureter and lower tumor grade were more likely to develop intravesical recurrence.

Nuclear export signal of androgen receptor regulated of androgen receptor stability in prostate cancer / 北京大学学报(医学版)

Objective: To investigate the mechanisms of nuclear export signal of androgen receptor (NESAR) in the regulation of androgen receptor (AR) protein expression and stability in prostate cancer.Methods: The green fluorescent protein fusion protein expression vectors pEGFP-AR(1-918aa), pEGFP-NESAR (743-817aa), pEGFP-NAR (1-665aa) and pEGFP-NAR-NESAR, and lysine mutants of NESAR pEGFP-NESAR K776R, pEGFP-NESAR K807R and pEGFP-NESAR K776R/K807R, were transiently transfec-ted into prostate cancer cell line PC3.Fluorescence microscopy, Western blot and immunoprecipitation were used to detect NESAR regulation of androgen receptor stability.Results: Under the fluorescence microscope, NESAR-containing fusion proteins were cytoplasmic localization, and their fluorescence intensities were much weaker than those without NESAR.The expression levels of NESAR-containing fusion proteins were significantly lower than those without NESAR.The half-lives of GFP-NESAR and GFP-NAR-NESAR were less than 6 h, while the expression of GFP and GFP-NAR was relatively stable and the half-life was more than 24 h in the presence of cycloheximide.The expression levels of GFP-NESAR were significantly increased by proteasome inhibitor MG132 treatment in a dose-dependent manner;in contrast, MG132 did not show any significant effect on the protein levels of GFP.When new protein synthesis was blocked, MG132 could also prevent the degradation of GFP-NESAR in the transfected cells in the presence of cycloheximide, while it had no significant effect on GFP protein stability in the parallel experiment.GFP immunoprecipitation showed that the ubiquitination level of GFP-NESAR fusion protein was significantly higher than that of the GFP control.The mutations of lysine sites K776 and K807 in NESAR significantly reduced the level of ubiquitination, and showed increased protein stability, indicating that they were the key amino acid residues of NESAR ubiquitination.Conclusion: NESAR was unstable and decreased the stability of its fusion proteins.NESAR was the target of polyubiquitination and mediated the degradation of its fusion proteins through the ubiquitin-proteasome pathway in prostate cancer cells.Our research provides a new way to regulate the level and/or activity of AR proteins, thus helping us understand the molecular mechanisms of AR degradation and strict control of AR in the progression to castration-resistance.

Modified surgical treatment for Arnold-Chiari Ⅰ malformation complicated with syringomyelia / 中国医师进修杂志

Objective To evaluate the methods and effects of modified surgical treatment for Amold-Chiari Ⅰ malformation complicated with syringomyelia.Methods Twelve patients with ArnoldChiari Ⅰ malformation complicated with syringomyelia,underwent a modified surgical treatment,effects were observed.Results During the first follow-up,sensation and motion function were significantly improved in 10 cases,unchanged in 2 cases.During the second follow-up,2 cases previously unchanged were improved,while the other were with no change.During the first follow-up,lesion showed on MRI disappeared in 5 cases,reduced in 4 cases,no significant change in 3 cases,no case extend,3 cases with hydrocephalus ventricle was significantly reduced.The second follow-up,MRI showed that there was no change compared with the first follow-up.Conclusion The remove of the pia mater of tonsillar hernia + reconstruction the cisterna magna have good effect on surgical therapies for Arnold-Chiari I malformation complicated with syringomyelia.

Establishment of a new model of the blast injury to the dog brain / 解放军医学杂志

Objective To reproduce an experimental model of blast injury to dog brain simulating the mechanism of primary effect of the blast wave of explosive weapons.Methods A spherical explosive with explosive energy of 1gTNT was used to detonate at different distances(9mm,13mm)from the right temple to produce blast injury to the dog brain.The changes in physiological index before or after detonating and the surviving time after injury were recorded.The changes in the behavior of the wounded animals and characteristics of pathological changes in the brain were observed.Results Respiratory arrest,hypotension,and decreased heart rate were observed after wounding.All animals survived longer than 6 hours after the explosion injury.Obvious subdural hematoma and sub-arachnoid hemorrhage occurred frequently.Traumatic conditions of the brain were different in the two groups.Conclusions The animal model reproduced in this experiment simulates that produced by blast wave of explosive weapons.It is reproducible,easy to handle,and can be used in experimental study of blast injury to the brain.