Challenges and opportunities in improving left ventricular remodelling and clinical outcome following surgical and trans-catheter aortic valve replacement / 医学前沿

Over the last half century, surgical aortic valve replacement (SAVR) has evolved to offer a durable and efficient valve haemodynamically, with low procedural complications that allows favourable remodelling of left ventricular (LV) structure and function. The latter has become more challenging among elderly patients, particularly following trans-catheter aortic valve implantation (TAVI). Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss, valvular-vascular impedance to myocardial activation, force-velocity relationship, and myocardial strain. LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour. Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome. Physiological pacing via the His-Purkinje system for conduction abnormalities, further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression, LV coordinate contraction, and global vascular function. TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions. Until comparable long-term durability and the resolution of TAVI related complications become available, SAVR remains the first choice for lower risk younger patients.

Correction to: Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

Correction to: Strahlenther Onkol 2019 https://doi.org/10.1007/s00066-019-01539-1 The original version of this article unfortunately contained a mistake. The correct version of the funding information are given ….

Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

PURPOSE: The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT. METHODS: Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model. RESULTS: Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1­ and 2­year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4-40.1) and 22.0 (95% CI 16.4-27.5), while the 1­year, 3­year, and 5­year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20-0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32-0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29-0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003). CONCLUSION: Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

Comparison Of Long Term Results Between Matched Chemoradiotherapy And Surgery For Limited Stage Small Cell Lung Cancer.

PURPOSE: To compare the efficacy of chemoradiotherapy or surgery for limited-stage small cell lung cancer (SCLC). PATIENTS AND METHODS: A retrospective analysis was performed on 138 patients with limited-stage SCLC who received surgery (69 patients) or chemoradiotherapy (69 patients) between January 2000 and September 2016 in Zhejiang Cancer Hospital. Patients of the chemoradiotherapy group were selected by using "pair-matched case-control" methodology from a cohort of 503 patients who received chemoradiotherapy. RESULTS: The major prognostic factors, including T, N stage, treatment duration, age, gender, and whether or not they received prophylactic cranial irradiation were well balanced between two groups. The median overall survival (OS) time and 5-year OS rate were 37.1 months and 45.0% in the surgical group vs 45.0 months and 45.0% in the chemoradiotherapy group (P=0.846). The median progression-free survival (PFS) time and 5-year PFS rate were 27.1 months and 37.8% vs 36.2 months and 40.0%, respectively, in the two groups (P=0.610). The 5-year OS rate (62.3% vs 40.1%, P=0.038) and 5-year PFS rate (80.1% vs 40.1%, P=0.048) in the surgical group were significantly higher than those of the chemoradiotherapy group in patients with stage I disease. The 5-year OS rate (41.2% vs 50.6%, P=0.946) and 5-year PFS rate (64.7% vs 42.1%, P=0.280) of surgery for stage II SCLC were comparable to chemoradiotherapy. As for stage III SCLC, compared with the surgical group, the chemoradiotherapy group had a better 5-year OS trend (25.1% vs 47.6%, P=0.220), but the difference did not reach statistical significance. CONCLUSION: Surgery could confer survival benefits in patients with p-stage I disease, but not in patients with p-stage II and III disease.

Whole-tumor perfusion CT using texture analysis in unresectable stage IIIA/B non-small cell lung cancer treated with recombinant human endostatin.

BACKGROUND: To observe the dynamic changes of blood perfusion with whole-tumor computed tomography (CT) perfusion imaging using texture analysis in patients with unresectable stage IIIA/B non-small cell lung cancer (NSCLC) treated with recombinant human endostatin (Endostar). METHODS: This phase II clinical trial recruited 11 patients diagnosed with stage IIIA/B NSCLC. Histological examination prior to treatment revealed squamous cell carcinoma in 4 cases and adenocarcinoma in 7 cases. All patients underwent contrast-enhanced perfusion CT at baseline and a second CT scan 1 week after treatment initiation with Endostar. CT perfusion images including blood flow (BF), blood volume (BV), and permeability (PMB) were imported into OmniKinetics software to quantitatively assess the texture features. Skewness, kurtosis, and entropy were calculated at baseline and after anti-angiogenic therapy. Changes in tumor were analyzed using Wilcoxon signed-rank test. The association of parameters with survival was evaluated using Cox proportional hazards regression model. RESULTS: There were no statistical differences in the mean values of BF, BV, and PMB before and after treatment (P=0.594, 0.477 and 0.328, respectively). The skewness on BF images demonstrated significant differences at baseline and after treatment (0.6±2.7 vs. 1.0±2.6, P=0.010), while skewness of BV and PMB showed no significant variation (P=0.477 and 0.213, respectively). The kurtosis and entropy for BF, BV and PMB showed no significant differences (all P>0.05). In adenocarcinoma, the mean BF showed no significant differences at baseline and after treatment (76.5±25.7 vs. 101.2±46.4, P=0.398), while skewness for BF was significantly higher after treatment than at baseline (-0.19±3.3 vs. 0.59±3.2, P=0.028). No significant associations were found between perfusion CT imaging parameters and progression-free survival. CONCLUSIONS: These results suggested that blood perfusion showed improvement with whole-tumor perfusion CT using texture analysis in patients with stage IIIA/B NSCLC treated by Endostar.

The impact of prophylactic cranial irradiation for post-operative patients with limited stage small cell lung cancer.

To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients who received definitive surgery for surgically resected small cell lung cancer (SCLC).A retrospective analysis was performed on post-operative SCLC patients treated in Zhejiang Cancer Hospital from January 2003 to December 2015. According to the treatment modality, patients were allocated to PCI group and non-PCI group. Univariate survival analysis was performed by the Kaplan-Meier method. Multivariate survival analysis was performed by a Cox proportional hazards model.A total of 52 patients were included for analysis, among which, 19 patients were in PCI group and 33 were in non-PCI group. Multivariate analysis revealed that PCI (HR = .330; P = .041) was an independently favorable prognostic factor for the overall survival. The median overall survival (OS) time was 32.9 months in PCI group, and 20.4 months in non-PCI group. The 2-year OS rates were 78.0% and 38.0% in PCI and non-PCI group respectively (P = .023). The brain metastasis-free survival (BMFS) rate at 2-year in PCI group was significantly higher than those of non-PCI group (89.0% vs 53.0%, respectively, P = .026).In conclusion, PCI might be suggested for limited SCLC patients who received definitive surgery.

Post-treatment serum lactic dehydrogenase as a predictive indicator for distant metastasis and survival of patients with nasopharyngeal carcinoma.

PURPOSE: To examine the function of serum lactic dehydrogenase (SLDH) level after intensity-modulated radiotherapy (IMRT) as a predictive factor for and loco-regional relapse free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS), and overall survival(OS) among patients with in-situ nasopharyngeal carcinoma (NPC). RESULTS: Compared with the normal pt-SLDH group, elevated pt-SLDH demonstrated significant lower DMFS (46 versus 66 months, hazard ratio (HR) 4.07, 95% CI 2.43-6.80, p < 0.001), DFS (46 versus 63 months, HR 2.78, 95% CI 1.70-4.53, p < 0.001), and OS (54 versus 66 months, HR 2.93, 95% CI 1.65-5.23, p < 0.001). Distant metastasis were observed in 32.8% (20/61) patients with elevated pt-SLDH, and 8% (54/678) in normal SLDH (odds ratio (OR) 6.13, 95% CI 3.35-11.18, p < 0.001). COX regression showed that pt-SLDH was an independent prognostic factors for OS (HR 2.91, 95% CI 1.57-5.41, p < 0.001), DMFS (HR 4.21, 95% CI 2.51-7.07, p < 0.001), LRFS (HR 2.53, 95% CI 1.22-5.24, p < 0.001), and DFS (HR 2.81, 95% CI 1.72-4.59, p < 0.001). MATERIALS AND METHODS: The records of 739 in-situ NPC patients admitted to Zhejiang Cancer Hospital between January 2007 and May 2012 were retrospectively reviewed. The relationships between post-treatment SLDH (pt-SLDH) and LRFS, DMFS, DFS, and OS were analyzed. CONCLUSIONS: Our finding indicated that elevated pt-SLDH could be a simple available prognostic indicator for distant metastasis and survival for in-situ NPC patients.

[Screening of candidate proteins interacting with Foxp3δ2 by yeast two-hybrid system].

AIM: To screen Foxp3Delta2-interacting proteins by yeast two-hybria. METHODS: pGBKT7-Foxp3Delta2 bait plasmid was constructed. Its toxicity and transcriptional activation in yeast cell AH109 was tested by observation of phenotypes and color. RESULTS: The bait plasmid pGBKT7-Foxp3Delta2 was constructed successfully and there was no self-activation or toxicity in AH109. Forty positive clones were obtained. After sequence comparison and analysis, nine candidate proteins were finally selected for further confirmation. CONCLUSION: Yeast two hybrid system could be used for screening Foxp3Delta2-interacting proteins. These results provide essential clues for further investigation of Foxp3Delta2 function.