Prognostic value of inflammatory nutritional scores in locally advanced esophageal squamous cell carcinoma patients undergoing neoadjuvant chemoimmunotherapy: a multicenter study in China.

Objective: This study investigates the prognostic significance of inflammatory nutritional scores in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) undergoing neoadjuvant chemoimmunotherapy. Methods: A total of 190 LA-ESCC patients were recruited from three medical centers across China. Pre-treatment laboratory tests were utilized to calculate inflammatory nutritional scores. LASSO regression and multivariate logistic regression analyses were conducted to pinpoint predictors of pathological response. Kaplan-Meier and Cox regression analyses were employed to assess disease-free survival (DFS) prognostic factors. Results: The cohort comprised 154 males (81.05%) and 36 females (18.95%), with a median age of 61.4 years. Pathological complete response (pCR) was achieved in 17.38% of patients, while 44.78% attained major pathological response (MPR). LASSO and multivariate logistic regression analyses identified that hemoglobin, albumin, lymphocyte, and platelet (HALP) (P=0.02) as an independent predictors of MPR in LA-ESCC patients receiving neoadjuvant chemoimmunotherapy. Kaplan-Meier and log-rank tests indicated that patients with low HALP, MPR, ypT1-2, ypN0 and, ypTNM I stages had prolonged DFS (P < 0.05). Furthermore, univariate and multivariate Cox regression analyses underscored HALP (P = 0.019) and ypT (P = 0.029) as independent predictive factors for DFS in ESCC. Conclusion: Our study suggests that LA-ESCC patients with lower pre-treatment HALP scores exhibit improved pathological response and reduced recurrence rate. As a comprehensive index of inflammatory nutritional status, pre-treatment HALP may be a reliable prognostic marker in ESCC patients undergoing neoadjuvant chemoimmunotherapy.

Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study.

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.

Comparison of efficacy and safety between neoadjuvant chemotherapy and neoadjuvant immune checkpoint inhibitors combined with chemotherapy for locally advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis.

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 s ubgroup 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, I 2 =14%) and 3.30 (95% CI, 2.31-4.71, I 2 =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, I 2 =58%) or serious adverse events (OR=1.28, 95% CI, 0.69-2.36, P =0.43, I 2 =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.

Estimating the cure proportion of stage IA lung adenocarcinoma: a population-based study.

BACKGROUND: We aimed to investigate the factors influencing the cure, recurrence, and metastasis rates of stage IA lung adenocarcinoma, using a mixed cure model. METHODS: A total of 1,064 patients who underwent video-assisted thoracoscopic pulmonectomy were included. Variable screening was performed using the random forest algorithm and least absolute shrinkage and selection operator approaches. The mixed cure model was used to identify factors affecting patient cure and survival, and a sequential analysis was performed on 5%, 10%, and 20% of the presentational subtype concurrently. A receiver operating characteristics curve was used to determine the best model and construct a nomogram to predict the cure rate. RESULTS: The median follow-up time was 58 (range: 3-115) months. Results from the cure part of the mixed model indicated that the predominant subtype, presentational subtype, and tumor diameter were the main prognostic factors affecting cure rate. Therefore, the nomogram to predict the cure rate was constructed based on these factors. The survival part indicated that the predominant subtype was the only factor that influenced recurrence and metastasis. A sequential analysis of the presentational subtype showed it had no significant effect on survival (P > 0.05). Regardless of the recording mode, no significant improvement was observed in the model's discriminative ability. Only a few postoperative pathological specimens showed lymphovascular invasion (LVI); however, the survival curve suggested a significant effect on patient survival. CONCLUSIONS: After excluding the existence of long-term survivors, the predominant tumor subtype was determined to be the only factor influencing recurrence and metastasis. Although LVI is rare in stage IA lung adenocarcinoma, its significance cannot be discounted in terms of determining patient prognosis.

Additional neoadjuvant immunotherapy does not increase the risk of anastomotic leakage after esophagectomy for esophageal squamous cell carcinoma: a multicenter retrospective cohort study.

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.

Efficacy of sternocleidomastoid muscle flap in reducing anastomotic mediastinal/pleural cavity leak.

BACKGROUND: Anastomotic mediastinal/pleural cavity leak (AMPCL) is a life-threatening postoperative complication after esophagectomy. The objective of this study was to find a safe and effective surgical method to reduce the incidence of AMPCL. METHODS: A total of 223 patients who underwent surgery in Fujian Medical University Union Hospital from May 2020 to October 2021 were enrolled in this study. Data for preoperative and postoperative test indices, postoperative complications, perioperative treatment were collected. After using 1:1 propensity score matching (PSM) to match two cohort (caliper = 0.1), the relationship between various factors and the incidence of AMPCL were analyzed. RESULTS: 209 patients were included for further analysis in the end. There were 95 patients in the sternocleidomastoid muscle flap embedding group (intervention group) and 114 in the routine operation group (control group). There was a significant difference in mean age between two groups. Gender, age, body mass index, diabetes, American society of anesthesiologists score, preoperative neoadjuvant therapy, pathological stage were included in performing 1:1 PSM, and there were no significant differences between two groups. Median operative time was significantly less in intervention group. Anastomotic leak (AL) did not present significant difference between two groups (8 [8.6] vs. 13 [14.0], p = 0.247), however, the AMPCL in intervention group was significantly lower than control group (0 [0] vs. 6 [6.5], p = 0.029). CONCLUSIONS: The sternocleidomastoid muscle flap embedding could significantly reduce the incidence of AMPCL. This additional procedure is safe, and effective without increase in the occurrence of postoperative complications and hospital expenses.

Residual tumor model in esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy: Frequently involves the mucosa and/or submucosa.

Objectives: The efficacy and safety of neoadjuvant immunochemotherapy (nICT) are widely explored in locally advanced esophageal squamous cell carcinoma (ESCC). Whether the "wait-and-see" strategy is applicable in ESCC after nICT is still lacking a theoretical basis. This study aimed to preliminarily explore the distribution of residual tumors and the regression pattern of ESCC after nICT. Methods: Patients undergoing radical esophagectomy after nICT in Fujian Medical University Union Hospital between January 2020 and March 2022 were identified. The resection specimens were re-evaluated by one experienced pathologist. The pathological response was assessed by tumor regression grade (TRG) (modified Ryan scheme). The TRG grade was divided into grades 0 (pathological complete response), 1, 2, and 3. The pathological stage was evaluated in the Eighth Edition AJCC. In the non-pCR group, the residual model was divided into four types: Type I, regression towards the lumen; type II, regression towards the invasive front; type III, concentric regression; and type IV, scattered regression. Results: A total of 95 consecutive patients were included for analysis. Seventy-six (80.0%) of 95 patients were in non-pCR (pathological complete response), and nine patients (9/76, 11.84%) had isolated residual tumors in lymph nodes. There was no significant difference in baseline characteristics between the pCR group and the non-pCR group (p > 0.05). The overall distribution of TRG for all esophageal wall layers was TRG 0 = 28 (28/95, 29.5%), TRG 1 = 17 (17/95, 17.9%), TRG 2 = 18 (18.9%, 18/95), and TRG 3 = 32 (32/95, 33.7%). In 67 patients with residual tumors in the esophageal wall (TRG ≧1), 63 (63/67, 94.0%) had residual tumor cells in the mucosa and/or submucosa, and four had isolated residual tumors in the muscle layer (4/67, 6.0%). Further analysis showed eight (8/67, 11.9%) patients with submucosal involvement but without mucosal involvement. The distribution of regression patterns was type I (n = 35, 52.2%), type II (n = 3, 4.5%), type III (n = 8, 11.9%), and type IV (n = 21, 31.3%). Conclusions: The mucosa and/or submucosa are frequently involved in residual malignancy, and the frequent regression models are regression toward the lumen and random regression. There is an opportunity to carefully test the residual tumors in a subgroup of the population with ESCC following nICT. However, some patients had residual tumors only in the muscle layer or lymph nodes. The clinical application of the wait-and-see strategy in ESCC after nICT should be explored using an appropriate evaluation protocol.

Does time to esophagectomy following neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma affect outcomes?

Objectives: Neoadjuvant immunochemotherapy (nICT) is a novel pattern for locally advanced esophageal squamous cell carcinoma (ESCC), and the time to surgery (TTS) is recommended as 4-6 weeks. However, there were some patients with prolonged TTS(> 6 weeks). This study aimed to explore whether prolonged TTS (> 6 weeks) would affect the outcomes. Methods: Patients diagnosed with locally advanced ESCC between January 2020 and March 2022 and undergoing esophagectomy following nICT were identified based on a prospectively collected database. Primary outcome measures were pathological complete response (pCR) and disease-free survival (DFS), and the secondary outcomes were 30-day postoperative mortality and morbidity, surgical time, postoperative hospital stay, and hospital expense. Results: Total of 95 patients were included for analysis, with 52 patients in the standard TTS group and 43 patients in the prolonged TTS group. The clinical and demographic characteristics of the two groups were comparable. The prolonged group had a median 18 days longer TTS(P<0.001). The pCR rate was 23.08% (12/52) in the standard group and 16.28% (7/43) in the prolonged group (P=0.41). Multivariate regression analysis further indicated that TTS wasn't an independent factor in predicting pCR (P=0.41). The median follow-up time was 10.5 months in the standard TTS group and 11.2 months in the prolonged TTS group. A total of five recurrences occurred with two events in the standard TTS group and three events in the prolonged TTS group, and no significant difference was observed in DFS(P=0.60). Both groups were comparable in postoperative hospital stays, total hospital stay, hospital expenses, and comprehensive complications index (CCI). The complications and major complications were also similar in both groups. Spearman test further indicated that there was no linear correlation among TTS with hospital expenses, postoperative hospital stays, hospital stay, CCI index, lymph nodes moved number, or surgical time, with a p-value of 0.48, 0.63, 0.80, 0.92, 0.09, 0.38 respectively. Conclusions: Based on present evidence, TTS after completion of nICT is not of major importance concerning pathological response, disease-free survival, and short-term postoperative outcomes.

Difference between "Lung Age" and Real Age as a Novel Predictor of Postoperative Complications, Long-Term Survival for Patients with Esophageal Cancer after Minimally Invasive Esophagectomy.

Background: This study aimed to investigate whether the difference between "lung age" and real age (L-R) could be useful for the prediction of postoperative complications and long-term survival in patients with esophageal cancer followed by minimally invasive esophagectomy (MIE). Methods: This retrospective cohort study included 625 consecutive patients who had undergone MIE. "Lung age" was determined by the calculation method proposed by the Japanese Respiratory Society. According to L-R, patients were classified into three groups: group A: L-R ≦ 0 (n = 104), group B: 15 > L-R > 0 (n = 199), group C: L-R ≥ 15 (n = 322). Clinicopathological factors, postoperative complications evaluated by comprehensive complications index (CCI), and overall survival were compared between the groups. A CCI value >30 indicated a severe postoperative complication. Results: Male, smoking status, smoking index, chronic obstructive pulmonary disease, American Society of Anesthesiologists status, lung age, and forced expiratory volume in 1 s were associated with group classification. CCI values, postoperative hospital stays, and hospital costs were significantly different among groups. Multivariate analysis indicated that L-R, coronary heart disease, and 3-field lymphadenectomy were significant factors for predicting CCI value >30. Regarding the prediction of CCI value >30, area under the curve value was 0.61(95%: 0.56-0.67), 0.46 (95% CI, 0.40-0.54), and 0.46 (95% CI, 0.40-0.54) for L-R, Fev1, and Fev1%, respectively. Regarding overall survival, there was a significant difference between group A and group B + C (log-rank test: p = 0.03). Conclusions: Esophageal cancer patients with impaired pulmonary function had a higher risk of severe postoperative complications and poorer prognosis than those with normal pulmonary function. The difference between "lung age" and "real age" seems to be a novel and potential predictor of severe postoperative complications and long-term survival.

Prognostic Value of Carcinoembryonic Antigen Changes Before and After Operation for Esophageal Squamous Cell Carcinoma.

BACKGROUND: To study the prognostic significance of changes in the level of carcinoembryonic antigen (CEA) before and after surgery on the long-term prognosis of patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patients with ESCC who underwent radical esophagectomy (between 2010 and 2017) were divided into three groups as follows: normal group (preoperative CEA≦1.6 ng/ml), normalized group (preoperative CEA > 1.6 ng/ml and postoperative CEA≦1.6 ng/ml) and non-normalized group (preoperative CEA > 1.6 ng/ml and postoperative CEA > 1.6 ng/ml). The Kaplan-Meier analysis was used to construct survival curves. Cox proportional hazards regression models was used to determine the independent prognostic factors for ESCC. Variables with P < 0.1 in univariable analysis were included in the multivariable model used to determine the independent risk factors. RESULTS: A total of 394 patients were included. The 5-OS rate of ESCC patients in normalized group (n = 36) and non-normalized group (n = 161) were significantly shorter than normal group (n =197) patients (57.3% vs 58.3% vs 82.0%, P < 0.001). The difference in survival time distribution between normal group and normalized/non-normalized group is statistically significant, P < 0.001. However, there was no statistically significant variation in survival time distribution between the normalized and non-normalized groups, P = 0.289. In multivariate analysis, older age (> 65 years old), advanced pT-stage, advanced pN-stage, normalized group and non-normalized group were independent prognostic risk factors of worse overall survival. CONCLUSIONS: ESCC patients with high preoperative CEA level had poorer prognosis regardless of the changes of postoperative CEA level.

Nomogram for Predicting Occult Locally Advanced Esophageal Squamous Cell Carcinoma Before Surgery.

Introduction: The limitations of preoperative examination result in locally advanced esophageal squamous cell carcinoma (ESCC) often going undetected preoperatively. This study aimed to develop a clinical tool for identifying patients at high risk for occult locally advanced ESCC; the tool can be supplemented with preoperative examination to improve the reliability of preoperative staging. Materials and Methods: Data of 598 patients who underwent radical resection of ESCC from 2010 to 2017 were analyzed. Logistic multivariate analysis was used to develop a nomogram. The training cohort included patients who underwent surgery during an earlier period (n = 426), and the validation cohort included those who underwent surgery thereafter (n = 172), to confirm the model's performance. Nomogram discrimination and calibration were evaluated using Harrell's concordance index (C-index) and calibration plots, respectively. Results: Logistic multivariate analysis suggested that higher preoperative carcinoembryonic antigen levels (>2.43, odds ratio [OR]: 2.093; 95% confidence interval [CI], 1.233-2.554; P = 0.006), presence of preoperative symptoms (OR: 2.737; 95% CI, 1.194-6.277; P = 0.017), presence of lymph node enlargement (OR: 2.100; 95% CI, 1.243-3.550; P = 0.006), and advanced gross aspect (OR: 13.103; 95% CI, 7.689-23.330; P < 0.001) were independent predictors of occult locally advanced ESCC. Based on these predictive factors, a nomogram was developed. The C-indices of the training and validation cohorts were 0.827 and 0.897, respectively, indicating that the model had a good predictive performance. To evaluate the accuracy of the model, we divided patients into high-risk and low-risk groups according to their nomogram scores, and a comparison was made with histopathological data. Conclusion: The nomogram achieved a good preoperative prediction of occult locally advanced ESCC; it can be used to make rational therapeutic choices.

Prognostic Nomogram for Predicting Long-Term Overall Survival of Esophageal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy Plus Surgery: A Population-Based Study.

Objective: Neoadjuvant chemoradiotherapy (nCRT) plays an important role in patients with locally advanced esophageal cancer (EC). We aim to determine the prognostic risk factors and establish a reliable nomogram to predict overall survival (OS) based on SEER population. Methods: Patients with EC coded by 04-15 in the SEER database were included. The data were divided into training group and verification group (7:3). The Cox proportional-risk model was evaluated by using the working characteristic curve (receiver operating characteristic curve, ROC) and the area under the curve (AUC), and a nomogram was constructed. The calibration curve was used to measure the consistency between the predicted and the actual results. Decision curve analysis (DCA) was used to evaluate its clinical value. The best cut-off value of nomogram score in OS was determined by using X-tile software, and the patients were divided into low-risk, medium-risk, and high-risk groups. Results: A total of 2,209 EC patients who underwent nCRT were included in further analysis, including 1,549 in the training cohort and 660 in the validation group. By Cox analysis, sex, marital status, T stage, N stage, M stage, and pathological grade were identified as risk factors. A nomogram survival prediction model was established to predict the 36-, 60-, and 84-month survival. The ROC curve and AUC showed that the model had good discrimination ability. The correction curve was in good agreement with the prediction results. DCA further proved the effective clinical value of the nomogram model. The results of X-tile analysis showed that the long-term prognosis of patients in the low-risk subgroup was better in the training cohort and the validation cohort (p < 0.001). Conclusion: This study established an easy-to-use nomogram risk prediction model consisting of independent prognostic factors in EC patients receiving nCRT, helping to stratify risk, identify high-risk patients, and provide personalized treatment options.

Indocyanine Green Fluorescence Using in Conduit Reconstruction for Patients With Esophageal Cancer to Improve Short-Term Clinical Outcome: A Meta-Analysis.

Objectives: This meta-analysis evaluated the short-term safety and efficacy of indocyanine green (ICG) fluorescence in gastric reconstruction to determine a suitable anastomotic position during esophagectomy. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes 2020 (PRISMA) were followed for this analysis. Results: A total of 9 publications including 1,162 patients were included. The operation time and intraoperative blood loss were comparable in the ICG and control groups. There was also no significant difference in overall postoperative mortality, reoperation, arrhythmia, vocal cord paralysis, pneumonia, and surgical wound infection. The ICG group had a 2.66-day reduction in postoperative stay. The overall anastomotic leak (AL) was 17.6% (n = 131) in the control group and 4.5% (n = 19) in the ICG group with a relative risk (RR) of 0.29 (95% CI 0.18-0.47). A subgroup analysis showed that the application of ICG in cervical anastomosis significantly reduced the incidence of AL (RR of 0.31, 95% CI 0.18-0.52), but for intrathoracic anastomosis, the RR 0.35 was not significant (95% CI 0.09-1.43). Compared to an RR of 0.35 in publications with a sample size of <50, a sample size of >50 had a lower RR of 0.24 (95% CI 0.12-0.48). Regarding intervention time of ICG, the application of ICG both before and after gastric construction had a better RR of 0.25 (95% CI 0.07-0.89). Conclusions: The application of ICG fluorescence could effectively reduce the incidence of AL and shorten the postoperative hospital stay for patients undergoing cervical anastomosis but was not effective for patients undergoing intrathoracic anastomosis. The application of ICG fluorescence before and after gastric management can better prevent AL. Systematic Review Registration: PROSPERO, CRD:42021244819.

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2).

Background: More and more evidence has confirmed the efficacy and safety of immunotherapy drugs, such as camrelizumab and pembrolizumab. There are several phase-I/II studies showing that toripalimab has an acceptable safety profile and promising clinical activity in patients with advanced solid tumors. To further confirm its efficacy and safety, the aim of the study was to evaluate toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: This study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase II trial (registration number: ChiCTR2100052784). The patients eligible for inclusion criteria at Fujian Medical University Union Hospital from October 2019 to October 2020 were included in this study. Patients who were suitable for surgery underwent minimally invasive esophagectomy (MIE) within 4-6 weeks after neoadjuvant therapy. Pathological complete response (pCR) and adverse events (AEs) were the primary end points. Secondary endpoints included R0 resection rate, major pathological response (MPR), interval to surgery, and 30-day complications. Results: A total of 20 patients were enrolled from October 2019 to October 2020. All patients successfully completed 2 cycles of neoadjuvant therapy. Treatment-related AEs were common during neoadjuvant therapy, with leucopenia the most frequently occurring AE (4/20, 25%). With respect to immune-related AEs, immune dermatitis occurred in 2 patients, including 1 patient with grade I and 1 patient with grade III. Based on radiologic evaluation, the objective response rate (ORR) was 70% (14/20). Twelve patients underwent McKeown MIE. The pCR rate of the primary tumor was 16.7% (2/12), and the MPR rate of the primary tumor was 5/12 (41.7%). The mean interval to surgery was 33.2 days, and no patients experienced delayed surgery due to treatment-related AEs. Pneumonia was the most common 30-day postoperative complication (3/12, 25%). Anastomotic leakage (AL) only occurred in 1 patient during the hospital stay. There were no treatment- or surgery-related deaths. Conclusions: Based on our results, toripalimab combined with docetaxel and cisplatin as a novel neoadjuvant therapy was safe and effective in locally advanced ESCC.

A nomogram to predict the recurrence-free survival and analyze the utility of chemotherapy in stage IB non-small cell lung cancer.

BACKGROUND: Large part of patients of stage IB non-small cell lung cancer (IB NSCLC) may suffer recurrence after surgery. This study is to determine risk factors and establish a nomogram for postoperative recurrence and to provide a reference for adjuvant chemotherapy selection in patients with stage IB NSCLC. METHODS: A total of 394 patients with postoperative stage IB NSCLC who visited Fujian Medical University Union Hospital between January 2010 and June 2016 were selected. Patients were divided into training and validation cohorts based on the time of diagnosis. Independent risk factors were identified using a Cox proportional hazards regression model. A nomogram was created to predict recurrence-free survival (RFS) and was validated with an independent cohort. The predictive ability of the nomogram was evaluated using the concordance index (C-index) and calibration curve. RFS between the high- and low-risk groups was determined using Kaplan-Meier curves, and subgroup analysis of chemotherapy was performed. RESULTS: Visceral pleura invasion, micropapillary structures, tumor size, preoperative serum carcinoembryonic antigen (CEA) level, preoperative serum cytokeratin-19 fragments (Cyfra21-1) level, and postoperative histology were identified as independent risk factors for stage IB NSCLC recurrence. Discrimination of the nomogram showed good prognostic accuracy and clinical applicability, with a C-index of 0.827 and 0.866 in the training and validation cohorts, respectively. The difference in RFS between the high- and low-risk groups in both cohorts was significant (P<0.05). Finally, a significant difference was observed on whether high-risk group should accept postoperative chemotherapy (P<0.05). CONCLUSIONS: This nomogram can predict postoperative recurrence probability in patients with stage IB NSCLC, and can select patients with risk factors who need adjuvant chemotherapy.

Safety and Feasibility of Esophagectomy Following Combined Immunotherapy and Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score Matching Analysis.

Objectives: The combination of neoadjuvant chemotherapy and immunotherapy (nICT) is a novel treatment for locally advanced esophageal cancer. There is concern that nICT may increase operation difficulty, postoperative morbidity, and mortality. This study aimed to compare short-term outcomes among esophagectomy after neoadjuvant chemoradiotherapy (nCRT) and nICT and for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis of a prospectively maintained database was performed to identify patients (from January 2017 through July 2021) who underwent surgery for ESCC following neoadjuvant therapy. A 1:1 propensity score matching (PSM) with a caliper 0.05 was conducted to balance potential bias. Results: A 1:1 PSM was conducted based on clinical stage, age, body mass index (BMI), and tumor location, and then 32 comparable pairs were matched. After PSM, age, gender, BMI, American Society of Anesthesiologists (ASA) status, smoking history, clinical stage, tumor location, lymphadenectomy field, pathological stage, anastomotic position, route of gastric conduit, procedure type, and operative approach were comparable between groups. Compared with the nICT group (median, 300 min), the operation time was significantly longer in the nCRT group (median, 376 min). However, both groups were comparable in intraoperative blood loss, thoracic drainage volume, intensive care unit (ICU) stay, postoperative hospital stays, and hospital cost. Further, 30-day mortality, 30-day readmission, ICU readmission, and major complications were similar in both groups. The nCRT group had an advantage in pathological response. The pathological complete response (pCR) was 18.8% (6/32) in the nICT group and 43.8% (14/32) in the nCRT group (p = 0.03). The major pathological response (MPR) was 71.9% (23/32) in the nCRT group and 34.4% (11/32) in the nICT group (p = 0.03). Conclusions: Based on our preliminary experience, esophagectomy appears to be safe and feasible following combined neoadjuvant immunotherapy with chemotherapy for locally advanced esophageal cancer.

Nomogram for predicting recurrence and metastasis of stage IA lung adenocarcinoma treated by videoassisted thoracoscopic lobectomy.

OBJECTIVE: This study aimed to construct a nomogram to effectively predict recurrence and metastasis in patients with stage 1A lung adenocarcinoma after video-assisted thoracoscopic surgery (VATS) lobectomy. METHODS: Our study included 337 patients. The 3-year recurrence-free survival rate and the 5-year recurrence-free survival (5-RFS) rate were analyzed. Multivariate Cox proportional hazards regression was conducted to identify independent risk factors. We established a nomogram and performed Harrell's Concordance index, calibration plots, integrated discrimination improvement, and decision curve analyses to assess its discrimination and calibration. RESULTS: The median follow-up time was 45 months. In a multivariate analysis, tumor diameter, pathological subtype, preoperative carcinoembryonic antigen level, and preoperative CYFRA21-1 level were independent prognostic factors for RFS (P < 0.05). These risk factors were used to construct a nomogram to predict postoperative recurrence and metastasis in these patients. Internal verification was performed using the bootstrap method. The C-index was 0.946 (95% confidence interval: 0.923-0.970), indicating that the model had a good predictive performance. Using the nomogram and X-tile software, the patients were divided into two groups: the high-risk (5-RFS rate, 0.10-0.90) and low-risk groups (5-RFS rate, 0.90-0.99); the difference in the RFS rate between the groups was significant (χ2 = 86.705, P < 0.001). CONCLUSIONS: Our nomogram had a better predictive ability for recurrence and metastasis in patients with stage 1A lung adenocarcinoma after VATS lobectomy resection than the Tumor-Node-Metastasis staging system and other predictive models. This nomogram can help provide individualized treatment strategies and follow-up times.

Safety and feasibility of esophagectomy following combined neoadjuvant immunotherapy and chemotherapy for locally advanced esophageal cancer: a propensity score matching.

OBJECTIVES: This study aims to investigate the efficacy and feasibility of esophagectomy following combined neoadjuvant immunotherapy and chemotherapy for locally advanced esophageal cancer. METHODS: We retrospectively identified patients who were treated with neoadjuvant immunotherapy and chemotherapy (NICT, n = 27) or chemotherapy alone (NCT, n = 95) at our institution between January, 2017 and April, 2021. The primary end point was 30-day complications. Major complications were defined as Clavien-Dindo classification grade ≥ 3. Secondary end points were interval to surgery, operation time, postoperative thoracic drainage, thoracic drainage tube stay, 30-day readmission rate, and 30-day mortality. Propensity score matching (PSM) was used to reduce bias caused by potential confounding. RESULTS: All patients included successfully completed neoadjuvant therapy and underwent McKeown minimally invasive esophagectomy negative margins. Out of 122 eligible patients, 26 patients in NICT group and 52 patients in NCT group were identified by 1:2 PSM. After PSM, the clinical stage was matched and demographic characteristics of the two groups were well balanced, including age, gender, BMI, ASA status, age-adjusted Charlson index, smoking, drinking, chemotherapy regimens, neoadjuvant cycle, tumor location, lymphadenectomy, pathological stage, histologic sub-type, anastomotic position, route of gastric conduit, procedure type, and operative approach were comparable between groups after PSM. Although NICT group had a higher incidence of pneumonia and pleural effusion, however, the CCI index, other complication and major complications were comparable between the two groups. There were no significant differences in operation time, intraoperative blood loss, thoracic drainage tube stays, thoracic drainage volume, ICU stay, postoperative hospital stay and hospital cost. Furthermore, 30-day mortality, 30-day readmission, ICU readmission were similar in both groups. CONCLUSIONS: Based on our preliminary experience, esophagectomy is safe and feasible following combined neoadjuvant immunotherapy with chemotherapy for locally advanced esophageal cancer.

Predictive value of systemic immune-inflammation index for pathological complete response in patients receiving neoadjuvant immunochemotherapy for locally advanced esophageal cancer.

Objectives: Neoadjuvant immunochemotherapy (nICT) has been confirmed with promising pathological complete response (pCR) among locally advanced esophageal squamous cell carcinoma (ESCC). However, there were still no reliable and accurate predictors to predict the treatment response. This study aimed to explore the predictive value of inflammatory and nutritional parameters. Methods: Patients with ESCC who underwent radical surgery after nICT between January 2020 and April 2022 were included in the study. First, the least absolute shrinkage and selection operator regression (LASSO) logistic regression analysis was used to screen independent inflammatory and nutritional parameters. Secondly, univariate and multivariate logistic regression were used to screen and predict independent risk factors for pCR. Thirdly, a nomogram was constructed based on the independent predictive factors, and 30% of the included population was randomly selected as the validation cohort. We used the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve to evaluate the nomogram model. Results: A total of 97 ESCC patients were screened for analysis, with 20 patients with pCR (20.32%). Only the systemic immune-inflammation index (SII) was screened after LASSO-logistic regression when λ was 0.06. The cut-off value of SII was 921.80 with an area under curve (AUC) value of 0.62. We defined SII > 921.80 as high SII and SII ≦ 921.80 as low SII. Further, the univariate and multivariate analysis further determined SII(OR = 3.94, 95%CI:1.26-12.42, P = 0.02) and clinical stage(OR = 0.35, 95%CI:0.12-0.98, P = 0.05) were independent predictive factors of pCR. One novel nomogram was established with an AUC value of 0.72 in the training cohort and 0.82 in the validation cohort. The Brier score of the calibration curve was 0.13. The calibration curve showed good agreement between the predicted results and the actual results in both the training cohort and the validation cohort. Compared with the clinical stage, the DCA confirmed a better clinical value of the nomogram model in both the training cohort and the validation cohort. Conclusions: High pretreatment SII and early clinical stage were independently associated with pCR among ESCC receiving nICT. We further established and validated one novel nomogram model to effectively predict pCR among ESCC after nICT.