Original Article Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2) Lei Gao, Jieming Lu, Peipei Zhang, Zhi-Nuan Hong, Mingqiang Kang

Right submammary thoracotomy and right vertical infra-axillary thoracotomy are performed for ventricular septal defect (VSD) to reduce the invasiveness of the conventional surgical repair through median sternotomy approach. No comparative studies have been conducted among these three procedures. From January 2016 to December 2016, 182 patients with isolated VSD who underwent surgical repair via one of these 3 approaches were reviewed to compare these three procedures. The procedure success rates were similar in these three groups. There was no statistically significant difference in operative time, aortic cross-clamping time, the duration of CPB, blood transfusion amount and medical cost. However, postoperative mechanical ventilation time, the duration of intensive care and postoperative length of hospital stay were longer in median sternotomy group than the other two groups. (P < 0.05) The median sternotomy group required the longest incision. No significant difference was noted in major adverse events. There were different advantages and disadvantages in the three kinds of operative procedures. Regarding conventional surgical repair VSD, right submammary thoracotomy and right vertical infra-axillary thoracotomy both delivered better cosmetic results for patients with isolated VSD, while all the three procedures could obtain satisfactory clinical effect.

Background: The application of neoadjuvant immune checkpoint inhibitors combined with chemotherapy (NICT) in treating locally advanced oesophageal squamous cell carcinoma (ESCC) is a subject of considerable research interest. In light of this, we undertook a comprehensive meta-analysis aiming to compare the efficacy and safety of this novel approach with conventional neoadjuvant chemotherapy (NCT) in the management of ESCC. Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to gather relevant literature on the efficacy and safety of NICT compared to conventional NCT in locally advanced ESCC published before June 2023. Effect indicators, including odds ratios (ORs) with associated 95% CIs, were employed to evaluate the safety and efficacy outcomes. The risk of bias was assessed using the Cochrane bias risk assessment tool, and subgroup analysis and sensitivity analysis were conducted to investigate the findings further. Results: A total of nine studies qualified for the meta-analysis, all of which investigated the efficacy and safety of NICT compared to conventional NCT. The pooled rates of pathologic complete response and major pathologic response in the NICT group were significantly higher compared to the NCT group, with values of 26.9% versus 8.3% (P<0.00001) and 48.1% versus 24.6% (P<0.00001), respectively. The ORs for achieving pathologic complete response and major pathologic response were 4.24 (95% CI, 2.84–6.32, I²=14%) and 3.30 (95% CI, 2.31–4.71, I²=0%), respectively, indicating a significant advantage for the NICT group. Regarding safety outcomes, the pooled incidences of treatment-related adverse events and serious adverse events in the NICT group were 64.4% and 11.5%, respectively, compared to 73.8% and 9.3% in the NCT group. However, there were no significant differences observed between the two groups in terms of treatment-related adverse events (OR=0.67, 95% CI, 0.29–1.54, P=0.35, I²=58%) or serious adverse events (OR=1.28, 95% CI, 0.69–2.36, P=0.43, I²=0%). Furthermore, no significant differences were found between the NICT and NCT groups regarding R0 resection rates, anastomotic leakage, pulmonary infection, and postoperative hoarseness. Conclusions: Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrate efficacy and safety in treating resectable oesophageal squamous cell carcinoma. Nevertheless, additional randomized trials are required to confirm the optimal treatment regimen.

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery.Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis.Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016).Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.

To investigate the safety and efficacy of perventricular device closure of perimembranous VSD (pmVSD). PubMed and Scopus were searched for studies in English focusing on perventricular device closure of pmVSD published up to the end of March 2019. We used a random-effects model to obtain pooled estimates of the success and complication rates. A total of 15 publications comprising 1368 patients with pmVSD were included. The median follow-up duration was 2 months to 5 years, with a mean patient age ranging from 2 months to 56 years. The pooled success rate was 0.95 (I2 = 86.2%, P = 0.000). The pooled rate of postoperative residual shunting was 0.02 (95% CI: 0.01–0.03, I2 = 87.3%, P < 0.001). The pooled rate of residual shunting in the follow-up period was 0.001 (95% CI:-0.001–0.002, I2 = 30.5%, P = 0.126). The pooled estimated rate of severe complications was 0.074 (95% CI: 0.046–0.102, I2 = 30.5%, P = 0.126). The pooled incidence of complete atrioventricular block (cAVB) was 0.002 (95% CI: 0.000–0.005, I2 = 0.0%, P = 0.577). Perventricular device closure may be an alternative to conventional surgical repair in selected patients with pmVSD. The success rate was stable regarding the publication year and sample size and suggested both the short learning curve of this technology and its potential for wide application. The incidence of severe arrhythmia, especially cAVB, was low. These good results may be limited by the number of enrolled patients, and a more detailed and larger sample is required for further analysis.

Purpose: Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients’ short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response. Methods: Patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (nCT)/ nICT combination with radical esophagectomy were enrolled from three medical centers in China. The authors used propensity score matching (PSM, ration:1:1, caliper=0.01) and inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Conditional logistic regression and weighted logistic regression analysis were used to further evaluate whether additional neoadjuvant immunotherapy would increase the risk of postoperative AL. Results: A total of 331 patients getting partially advanced ESCC receiving nCT or nICT were enrolled from three medical centers in China. After PSM/IPTW, the baseline characteristics reached an equilibrium between the two groups. After matching, there were no significant difference in the AL incidence between the two groups (P=0.68, after PSM; P=0.97 after IPTW), and the incidence of AL in the two groups was 15.85 versus 18.29%, and 14.79 versus 15.01%, respectively. After PSM/IPTW, both groups were similar in pleural effusion and pneumonia. After IPTW, the nICT group had a higher incidence of bleeding (3.36 vs. 0.30%, P=0.01), chylothorax (5.79 0.30%, P=0.001), and cardiac events (19.53 vs. 9.20%, P=0.04). recurrent laryngeal nerve palsy (7.85 vs. 0.54%, P=0.003). After PSM, both groups were similar in palsy of the recurrent laryngeal nerve (1.22 vs. 3.66%, P=0.31) and cardiac events (19.51 vs. 14.63%, P=0.41). Weighted logistic regression analysis showed that additional neoadjuvant immunotherapy was not responsible for AL (OR=0.56, 95% CI: [0.17, 1.71], after PSM; 0.74, 95% CI: [0.34,1.56], after IPTW). The nICT group had dramatically higher pCR in primary tumor than the nCT group (P=0.003, PSM; P=0.005, IPTW), 9.76 versus 28.05% and 7.72 versus 21.17%, respectively. Conclusions: Additional neoadjuvant immunotherapy could benefit pathological reactions without increasing the risk of AL and pulmonary complications. The authors require further randomized controlled research to validate whether additional neoadjuvant immunotherapy would make a difference in other complications, and determine whether pathologic benefits could translate into prognostic benefits, which would require longer follow-up.