Comparison of neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma: a retrospective study with 3-year survival analysis.

BACKGROUND: Neoadjuvant chemoimmunotherapy (nCIT) for locally advanced esophageal squamous cell cancer (ESCC) has shown short-term benefits, but long-term survival outcomes are unclear. This study compares nCIT and neoadjuvant chemotherapy (nCT) in resectable ESCC. PATIENTS AND METHODS: A retrospective analysis was conducted on ESCC patients who underwent nCT or nCIT followed by esophagectomy. Propensity score matching (PSM) with a caliper of 0.02 was employed to minimize bias. The primary endpoints included disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 131 comparable pairs of ESCC patients receiving nCT and nCIT were selected for the final analysis. The nCIT had higher rates of pathological complete response (pCR) and major pathological response (mPR) compared to nCT. Additionally, nCIT led to significant tumor down-staging, higher rates of R0 resection, and increased lymph node clearance during surgery. Patients who received nCIT exhibited improved disease-free survival (DFS) and overall survival (OS) at the 3-year follow-up. The incidence of distant and mixed relapses was lower in the nCIT group compared to the nCT group. However, the risk of locoregional relapse was comparable between the two groups. Subgroup analyses showed that the benefits of nCIT were generally observed across most patient subgroups. Interestingly, in patients without pCR or mPR, nCIT still demonstrated better survival benefits than nCT. CONCLUSION: nCIT demonstrated superior pathological response rates and improved 3-year DFS and OS compared to nCT alone in locally advanced ESCC, but long-term survival validation is needed.

Frequency and distribution pattern of lymph node metastasis after neoadjuvant chemoimmunotherapy for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Currently, neoadjuvant chemoimmunotherapy (NCIT) is widely used in the perioperative treatment of esophageal squamous cell carcinoma (ESCC). However, the patterns of lymph node metastasis following this novel treatment approach remain poorly understood. The aim of this study was to elucidate the distribution and frequency of postoperative lymph node metastasis (LNM) after NCIT. METHODS: We retrospectively analyzed cases from March 2020 to March 2023 in our hospital and selected patients who underwent NCIT followed by R0 resection for esophageal cancer. A total of 257 patients with clinical stage T3N0 or T1-3N + thoracic esophageal cancer were included. The distribution and frequency of metastatic lesions in each lymph node station were recorded according to the Japan Esophageal Society (JES) staging system. Additionally, we analyzed the patterns of lymph node metastasis based on the location of the thoracic tumor. RESULTS: Among the 257 patients, 110 (42.8%) had pathologically positive lymph nodes postoperatively. Common sites of lymph node metastasis included station 107 (12.8%), station 106recR (11.7%), and station 7 (12.5%). The lymph node stations with lower metastasis rates were station 105, station 106tbL, and station 111, each with a metastasis rate of 2.3%. In upper thoracic (Ut) cases, station 106recR (23.7%) was the most common site of lymph node metastasis, while in middle thoracic (Mt) cases, station 107 (16.7%) had the highest metastasis rate, and in lower thoracic (Lt) cases, station 7 (17.6%) had the highest metastasis rate. Lymph node metastasis (LNM) was more likely to occur in station 101R in Ut and Mt cases than in Lt cases (13.2% and 8.6%; p < 0.01). CONCLUSIONS: This study reveals the frequency and distribution patterns of lymph node metastasis following NCIT, highlighting the different patterns of lymph node metastasis based on tumor location. These findings can provide guidance for lymph node dissection during surgery.

The advantages of preoperative 3D reconstruction over 2D-CT in thoracoscopic segmentectomy.

Performing a pulmonary segmentectomy is a complex process, with precise localization of pulmonary nodules and recognition of intraoperative anatomical variations posing significant challenges. This study aims to assess the advantages of preoperative three-dimensional reconstruction (3D-RE) in thoracoscopic segmentectomy. The study, at Fujian Medical University Cancer Hospital, analyzed data from segmentectomy patients from January 2016 to February 2022. It compared 3D-RE and two-dimensional computed tomography (2D-CT) preoperative scans, focusing on perioperative complications within30 days to identify any differences. This investigation encompassed a total of 265 instances, with 148 belonging to the 3D-RE group and 117 aligned with the 2D-CT group. The 3D-RE group showed reduced intraoperative blood loss and shorter postoperative hospital stays (P < 0.001). They also had higher rates of lymph node sampling and combined subsegmentectomy and segmentectomy procedures (P < 0.01). Postoperative complications, particularly pneumonia and lung fistula, were lower in the 3D-RE group (P = 0.041). The rates of minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) were significantly higher in the 3D-RE group, while adenocarcinoma in situ (AIS) and benign cases were less common (P = 0.006). Surgical duration, chest tube duration, chest drainage volume, surgery complexity, and pathological diagnoses showed no significant differences between the groups. Utilization of preoperative 3D-RE holds potential to minimize both intraoperative and postoperative complications, thereby enhancing the safety and feasibility of undertaking segmentectomy procedures.

The relationship between the collagen score at the anastomotic site of esophageal squamous cell carcinoma and anastomotic leakage.

Background: Anastomotic leakage (AL) has always been one of the most serious complications of esophagectomy with gastric conduit reconstruction. There are many strong risk factors for AL in clinical practice. Notably, the tension at the esophagogastric anastomosis and the blood supply to the gastric conduit directly affect the integrity of the anastomosis. However, there has been a lack of quantitative research on the tension and blood supply of the gastric conduit. Changes in extracellular matrix collagen reflect tension and blood supply, which affect the quality of the anastomosis. This study aimed to establish a quantitative collagen score to describe changes in the collagen structure in the extracellular matrix and to identify patients at high risk of postoperative AL. Methods: A retrospective study of 213 patients was conducted. Clinical and pathological data were collected at baseline. Optical imaging of the "donut" specimen at the anastomotic gastric end and collagen feature extraction were performed. Least absolute shrinkage and selection operator (LASSO) regression models were used to select the significant collagen features, compute collagen scores, and validate the predictive efficacy of the collagen scores for ALs. Results: LASSO regression analysis revealed three collagen-related parameters in the gastric donuts: histogram mean, histogram variance, and histogram energy. Based on this analysis, we established a formula to calculate the collagen score. The results of the univariate analysis revealed significant differences in the preoperative low albumin values (P=0.002) and collagen scores between the AL and non-AL groups (P=0.001), while the results of the multivariate analysis revealed significant differences in the collagen scores between the AL and non-AL groups (P=0.002). The areas under the curve (AUCs) of the experimental and validation cohorts were 0.978 [95% confidence interval (CI): 0.931-0.996] and 0.900 (95% CI: 0.824-0.951), respectively. Conclusions: The collagen score established herein was shown to be related to AL and can be used to predict AL in patients who underwent esophagectomy.

MASMDDI: multi-layer adaptive soft-mask graph neural network for drug-drug interaction prediction.

Accurately predicting Drug-Drug Interaction (DDI) is a critical and challenging aspect of the drug discovery process, particularly in preventing adverse reactions in patients undergoing combination therapy. However, current DDI prediction methods often overlook the interaction information between chemical substructures of drugs, focusing solely on the interaction information between drugs and failing to capture sufficient chemical substructure details. To address this limitation, we introduce a novel DDI prediction method: Multi-layer Adaptive Soft Mask Graph Neural Network (MASMDDI). Specifically, we first design a multi-layer adaptive soft mask graph neural network to extract substructures from molecular graphs. Second, we employ an attention mechanism to mine substructure feature information and update latent features. In this process, to optimize the final feature representation, we decompose drug-drug interactions into pairwise interaction correlations between the core substructures of each drug. Third, we use these features to predict the interaction probabilities of DDI tuples and evaluate the model using real-world datasets. Experimental results demonstrate that the proposed model outperforms state-of-the-art methods in DDI prediction. Furthermore, MASMDDI exhibits excellent performance in predicting DDIs of unknown drugs in two tasks that are more aligned with real-world scenarios. In particular, in the transductive scenario using the DrugBank dataset, the ACC and AUROC and AUPRC scores of MASMDDI are 0.9596, 0.9903, and 0.9894, which are 2% higher than the best performing baseline.

Conditional Survival of Patients with Limited-Stage Small Cell Lung Cancer After Surgery: A National Real-World Cohort Study.

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.

The prognostic significance of right paratracheal lymph node dissection numbers in right upper lobe non-small cell lung cancer.

BACKGROUND: The number of dissected lymph nodes is closely related to the prognosis of patients with non-small cell lung cancer. This study explored the optimal number of right paratracheal lymph nodes dissected in right upper non-small cell lung cancer patients and its impact on prognosis. METHODS: Patients who underwent radical surgery for right upper lobe cancer between 2012 and 2017 were retrospectively enrolled. The optimal number of right paratracheal lymph nodes and the relationship between the number of dissected right paratracheal lymph nodes and the prognosis of right upper non-small cell lung cancer were analysed. RESULTS: A total of 241 patients were included. The optimal number of dissected right paratracheal lymph nodes was 6. The data were divided according to the number of dissected right paratracheal lymph nodes into groups RPLND + (≥ 6) and RPLND- (< 6). In the stage II and III patients, the 5-year overall survival rates were 39.0% and 48.2%, respectively (P = 0.033), and the 5-year recurrence-free survival rates were 32.8% and 41.8%, respectively (P = 0.043). Univariate and multivariate analyses revealed that among the stage II and III patients, ≥ 6 right paratracheal dissected lymph nodes was an independent prognostic factor for overall survival (HR = 0.53 95% CI 0.30-0.92 P = 0.025) and recurrence-free survival (HR = 1.94 95% CI 1.16-3.24 P = 0.011). CONCLUSIONS: Resection of 6 or more right paratracheal lymph nodes may be associated with an improved prognosis in patients with right upper non-small cell lung cancer, especially in patients with stage II or III disease.

The association between histological subtypes and lymph node metastasis and prognosis in early esophageal cancer: a population-based study.

BACKGROUND: There is still a lack of high-level clinical evidence and uniform conclusions on whether there are differences in lymph node metastasis (LNM) and prognosis between early esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). METHODS: Patients with surgically resected, histologically diagnosed, pT1 EAC or ESCC in the Surveillance, Epidemiology and End Results registries database from 2004 to 2015 were included. Multivariable logistic regression, Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the histology and LNM or prognosis. RESULTS: A total of 570 early esophageal cancer patients were included. The LNM rates were 13.8% and 15.1% for EAC and ESCC ( P  = 0.757), respectively. Multivariate logistic regression analysis showed no significant association between histological type and LNM (odds ratio [OR], 1.209; 95% CI, 0.538-2.715; P  = 0.646). Moreover, the prognosis of early EAC and ESCC was shown to be comparable in both multivariate Cox regression (hazard ratio [HR], 1.483; 95% CI, 0.699-3.150; P  = 0.305) and the multivariate competing risk model (subdistribution HR, 1.451; 95% CI, 0.628-3.354; P  = 0.383). After propensity score matching, there were no significant differences between early EAC and ESCC in terms of LNM (10.6% vs.18.2%, P  = 0.215), 5-year CSS (89.8% [95% CI, 81.0%-98.6%] vs. 79.1% [95% CI, 67.9%-90.3%], P  = 0.102) and 5-year cumulative incidence of CSS (10.2% [95% CI, 1.4%-19.0%] vs. 79.1% [95% CI, 9.7%-32.1%], P  = 0.124). CONCLUSION: The risk of LNM and prognosis of early ESCC and EAC are comparable, so the treatment choice for early esophageal cancer does not depend on the histologic type.

Construction and validation of a risk-scoring model to predict lymph node metastasis in T1b-T2 esophageal cancer.

BACKGROUND: Lymph node status is an important factor in determining preoperative treatment strategies for stage T1b-T2 esophageal cancer (EC). Thus, the aim of this study was to investigate the risk factors for lymph node metastasis (LNM) in T1b-T2 EC and to establish and validate a risk-scoring model to guide the selection of optimal treatment options. METHODS: Patients who underwent upfront surgery for pT1b-T2 EC between January 2016 and December 2022 were analyzed. On the basis of the independent risk factors determined by multivariate logistic regression analysis, a risk-scoring model for the prediction of LNM was constructed and then validated. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminant ability of the model. RESULTS: The incidence of LNM was 33.5% (214/638) in our cohort, 33.4% (169/506) in the primary cohort and 34.1% (45/132) in the validation cohort. Multivariate analysis confirmed that primary site, tumor grade, tumor size, depth, and lymphovascular invasion were independent risk factors for LNM (all P < 0.05), and patients were grouped based on these factors. A 7-point risk-scoring model based on these variables had good predictive accuracy in both the primary cohort (AUC, 0.749; 95% confidence interval 0.709-0.786) and the validation cohort (AUC, 0.738; 95% confidence interval 0.655-0.811). CONCLUSION: A novel risk-scoring model for lymph node metastasis was established to guide the optimal treatment of patients with T1b-T2 EC.

Prognostic Factors and Outcomes in Elderly Esophagectomy Patients with Esophageal Cancer.

BACKGROUND: Choosing the appropriate treatment for elderly patients with esophageal cancer remains a contentious issue. While surgery is still a valid option, we aimed to identify predictors and outcomes in elderly esophagectomy patients with esophageal cancer. PATIENTS AND METHODS: We analyzed characteristics, surgical outcomes, survival rates, cause-specific mortality, and recurrence in 120 patients with stage I-IV esophageal cancer. Univariate and multivariate analyses were used to identify risk factors for event-free survival (EFS) and overall survival (OS). RESULTS: The median follow-up period was 31 months, with 5-year overall survival (OS) and event-free survival (EFS) rates standing at 45.2% and 41.5%, respectively. Notably, lower body mass index (BMI ≤ 22 kg/m2) and reduced preoperative albumin levels (pre-ALB < 40 g/L) led to a significant decrease in OS rates. Postoperative pulmonary complications resulted in higher in-hospital and 90-day mortality rates. After about 31 months post-surgery, the rate of cancer-specific deaths stabilized. The most common sites for distant metastasis were the lungs, supraclavicular lymph nodes, liver, and bone. The study identified lower BMI, lower pre-ALB levels, and postoperative pulmonary complications as independent risk factors for poorer EFS and OS outcomes. CONCLUSIONS: Esophagectomy remains a safe and feasible treatment for elderly patients, though the prevention of postoperative pulmonary infection is crucial. Factors such as lower BMI, lower pre-ALB levels, advanced tumor stage, postoperative pulmonary complications, and certain treatment modalities significantly influence the outcomes in elderly esophagectomy patients. These findings provide critical insights into the characteristics and outcomes of this patient population.

Assessment of Laparoscopic Spleen-Preserving Hilar Lymphadenectomy for Advanced Proximal Gastric Cancer Without Invasion Into the Greater Curvature: A Randomized Clinical Trial.

Importance: The survival benefit of laparoscopic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy (LSTG) for locally advanced proximal gastric cancer (APGC) without invasion into the greater curvature remains uncertain. Objective: To compare the long-term and short-term efficacy of LSTG (D2 + No. 10 group) and conventional laparoscopic total gastrectomy (D2 group) for patients with APGC that has not invaded the greater curvature. Design, Setting, and Participants: In this open-label, prospective randomized clinical trial, a total of 536 patients with clinical stage cT2 to 4a/N0 to 3/M0 APGC without invasion into the greater curvature were enrolled from January 2015 to October 2018. The final follow-up was on October 31, 2021. Data were analyzed from December 2021 to February 2022. Interventions: Eligible patients were randomized to the D2 + No. 10 group or the D2 group. Main Outcomes and Measures: The primary outcome was 3-year disease-free survival (DFS). The secondary outcomes were 3-year overall survival (OS) and morbidity and mortality within 30 days after surgery. Results: Of 526 included patients, 392 (74.5%) were men, and the mean (SD) age was 60.6 (9.6) years. A total of 263 patients were included in the D2 + No. 10 group, and 263 were included in the D2 group. The 3-year DFS was 70.3% (95% CI, 64.8-75.8) for the D2 + No. 10 group and 64.3% (95% CI, 58.4-70.2; P = .11) for the D2 group, and the 3-year OS in the D2 + No. 10 group was better than that in the D2 group (75.7% [95% CI, 70.6-80.8] vs 66.5% [95% CI, 60.8-72.2]; P = .02). Multivariate analysis revealed that splenic hilar lymphadenectomy was not an independent protective factor for DFS (hazard ratio [HR], 0.86; 95% CI, 0.63-1.16) or OS (HR, 0.81; 95% CI, 0.59-1.12). Stratification analysis showed that patients with advanced posterior gastric cancer in the D2 + No. 10 group had better 3-year DFS (92.9% vs 39.3%; P < .001) and OS (92.9% vs 42.9%; P < .001) than those in the D2 group. Multivariate analysis confirmed that patients with advanced posterior gastric cancer could have the survival benefit from No. 10 lymph node dissection (DFS: HR, 0.10; 95% CI, 0.02-0.46; OS: HR, 0.12; 95% CI, 0.03-0.52). Conclusions and Relevance: Although LSTG could not significantly improve the 3-year DFS of patients with APGC without invasion into the greater curvature, patients with APGC located posterior gastric wall may benefit from LSTG. Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.

Nomogram to Predict Recurrence and Guide a Pragmatic Surveillance Strategy After Resection of Hepatoid Adenocarcinoma of the Stomach: A Retrospective Multicenter Study.

BACKGROUND: An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies. METHODS: The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model. RESULTS: The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.629; 95% CI, 0.573-0.685; P < 0.001). The nomogram accurately stratified patients into low-, middle-, and high-risk groups of postoperative recurrence. The postoperative recurrence risk rates for patients in the middle- and high-risk groups were respectively 3 and 10 times higher than for the low-risk group. The patients in the middle- and high-risk groups showed more recurrence and metastasis, particularly multiple site metastasis, within 36 months after the operation than those in the low-risk group (low, 2.2%; middle, 8.6%; high, 24.0%; P = 0.003). CONCLUSIONS: The nomogram achieved good prediction of postoperative recurrence for the patients with HAS after radical resection. For the middle- and high-risk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.

Radiographical Evaluation of Tumor Immunosuppressive Microenvironment and Treatment Outcomes in Gastric Cancer: A Retrospective, Multicohort Study.

BACKGROUND: The tumor immunosuppressive microenvironment can influence treatment response and outcomes. A previously validated immunosuppression scoring system (ISS) assesses multiple immune checkpoints in gastric cancer (GC) using tissue-based assays. We aimed to develop a radiological signature for non-invasive assessment of ISS and treatment outcomes. METHODS: A total of 642 patients with resectable GC from three centers were divided into four cohorts. Radiomic features were extracted from portal venous-phase CT images of GC. A radiomic signature for predicting ISS (RISS) was constructed using the least absolute shrinkage and selection operator (LASSO) regression method. Moreover, we investigated the value of the RISS in predicting survival and chemotherapy response. RESULTS: The RISS, which consisted of 10 selected features, showed good discrimination of immunosuppressive status in three independent cohorts (area under the curve = 0.840, 0.809, and 0.843, respectively). Multivariate analysis revealed that the RISS was an independent prognostic factor for both disease-free survival (DFS) and overall survival (OS) in all cohorts (all p < 0.05). Further analysis revealed that stage II and III GC patients with low RISS exhibited a favorable response to adjuvant chemotherapy (OS: hazard ratio [HR] 0.407, 95% confidence interval [CI] 0.284-0.584); DFS: HR 0.395, 95% CI 0.275-0.568). Furthermore, the RISS could predict prognosis and select stage II and III GC patients who could benefit from adjuvant chemotherapy independent of microsatellite instability status and Epstein-Barr virus status. CONCLUSION: The new, non-invasive radiomic signature could effectively predict the immunosuppressive status and prognosis of GC. Moreover, the RISS could help identify stage II and III GC patients most likely to benefit from adjuvant chemotherapy and avoid overtreatment.

Outcomes of Laparoscopic Total Gastrectomy Combined With Spleen-Preserving Hilar Lymphadenectomy for Locally Advanced Proximal Gastric Cancer: A Nonrandomized Clinical Trial.

Importance: The long-term survival of patients with laparoscopic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy (LSTG) for advanced upper-third gastric cancer (AUTGC) and the association of splenic hilar lymph node (LN-10) metastasis with survival remain controversial. Objective: To evaluate the long-term outcomes of LSTG and the value index of LN-10 metastasis for patients with AUTGC. Design, Setting, and Participants: The Chinese Laparoscopic Gastrointestinal Surgery Study 4 (CLASS-04) was a prospective, multicenter, single-arm trial that involved 19 centers in China. A total of 251 eligible patients with clinical stage T2, T3, or T4a upper-third gastric cancer without distant metastases were enrolled from September 1, 2016, to October 31, 2017. The final follow-up was on December 31, 2020. Interventions: All patients were enrolled to undergo LSTG. Main Outcomes and Measures: The main outcomes were the 3-year overall survival (OS) and disease-free survival (DFS). Multivariate analyses were used to explore the association of LN-10 metastasis with survival. Results: Among the 251 patients, 246 (98.0%; mean [SD] age, 60.1 [9.4] years; 197 [80.1%] male) underwent LSTG and completed the study. The 3-year OS was 79.1% (95% CI, 74.0%-84.2%), and the 3-year DFS was 73.1% (95% CI, 67.4%-78.8%). In addition, the 3-year therapeutic value index of LN-10 dissection was 4.5, exceeding the indexes for the partial D2 LN group (including LNs 5, 6, 11d, and 12a). Nineteen patients (7.7%) with LN-10 metastasis had significantly worse survival than the nonmetastasis group, and multivariate analysis revealed that splenic LN-10 metastasis was an independent risk factor (OS: hazard ratio [HR], 2.38; 95% CI, 1.08-5.26; P = .03; DFS: HR, 2.28; 95% CI, 1.12-4.63; P = .02). Moreover, patients with LN-10 metastasis were more likely to have recurrence (42.1% vs 20.7%, P = .03), especially when multiple site metastasis was present (21.1% vs 4.4%, P = .01). However, patients with LN-10 metastasis who received adjuvant chemotherapy had significantly better OS and DFS than those without adjuvant chemotherapy and achieved the same oncologic effect as those without LN-10 metastasis. Conclusions and Relevance: This results of this study suggest that LSTG for AUTGC has feasible long-term outcomes. In addition, patients with LN-10 metastasis may have worse survival and may be more prone to recurrence.

Reappraise role of lymph node status in patterns of recurrence following curative resection of gastric adenocarcinoma.

OBJECTIVE: To examine the association between lymph node status and recurrence patterns in completely resected gastric adenocarcinoma. METHODS: We retrospectively assessed 1,694 patients who underwent curative gastrectomy from January 2010 to August 2014. Patients stratified according to lymph node status and recurrence patterns among different subgroups were compared. RESULTS: Of all, 517 (30.5%) patients developed recurrent disease, and complete data of recurrence could be obtained in 493 (95.4%) patients. For pN0 patients, the patterns of recurrence were different according to pT stage: locoregional recurrence was most common in patients with pT1-2 disease (57.1%), distant recurrence was most common in patients with pT3 disease (57.1%), and peritoneal recurrence was most common in patients with pT4a disease (66.7%). For pN+ patients, distant metastasis was most common pattern irrespective of pT stage. The site-specific trend of recurrence showed that locoregional recurrence increased within 5 years in patients with pN0-2 disease but plateaued 3 years after surgery in patients with pN3 disease. Time to recurrence was significantly longer for the pN0 patients compared with the pN+ patients (median: 25 vs. 16 months, P=0.001). Moreover, post-recurrence survival was significantly better for the pN0 patients than for the pN+ patients (median: 12 vs. 6 months, P<0.001), especially in patients with non-peritoneal recurrence, late recurrence, single recurrence, and receipt of potential curative treatment. CONCLUSIONS: Among clinicopathologic factors, lymph node status is the most important factor associated with recurrence patterns after curative gastrectomy. Lymph node status may be used as an adjunct in clinical decision-making about postoperative therapeutic and follow-up strategies.

Comparison of Survival and Patterns of Recurrence in Gastric Neuroendocrine Carcinoma, Mixed Adenoneuroendocrine Carcinoma, and Adenocarcinoma.

Importance: Gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Objective: To compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Design, Setting, and Participants: This cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score-matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020. Exposures: Curative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Main Outcomes and Measures: The main outcomes were DFS and patterns of recurrence. Results: A total of 3689 patients were analyzed (median [interquartile range] age, 62 [55-69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P < .001) and 51.1% (95% CI, 46.0%-56.2%) for patients with gastric mixed adenoneuroendocrine carcinoma, compared with 57.8% (95% CI, 55.1%-60.5%) patients with gastric adenocarcinoma (P = .02). Multivariable analyses found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma (hazard ratio [HR], 1.64; 95% CI, 1.40-1.93) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.25; 95% CI, 1.05-1.49) were independent risk factors associated with worse DFS. Compared with matched patients with gastric adenocarcinoma, patients with gastric neuroendocrine carcinoma were more likely to have distant recurrence (268 patients [17.2%] vs 101 patients [23.7%]; P = .002), as were patients with gastric mixed adenoneuroendocrine carcinoma (232 patients [17.3%] vs 76 patients [22.8%]; P = .02). In multivariate analysis, gastric neuroendocrine carcinoma (HR, 2.22; 95% CI, 1.66-2.98) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.70; 95% CI, 1.24-2.34) were independent risk factors associated with distant recurrence. Additionally, T3 to T4 stage (odds ratio, 2.84; 95% CI, 1.57-5.14; P = .001) and lymph node metastasis (odds ratio, 2.01; 95% CI, 1.31-3.10; P = .002) were independent risk factors associated with distant recurrence of gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma. Conclusions and Relevance: This cohort study found that patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma had worse prognoses and were more prone to distant recurrence than those with gastric adenocarcinoma. Thus, different follow-up and treatment strategies should be developed to improve the long-term survival of patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma, especially patients with tumors penetrating into the subserosa or deeper layers or with lymph node metastasis.

A novel prognosis marker based on combined preoperative carcinoembryonic antigen and systemic inflammatory response for resectable gastric cancer.

Background: Carcinoembryonic antigen (CEA) is one of the important indexes for the diagnosis and prognosis of gastrointestinal cancer. Systemic inflammatory response (SIR) is closely related to the occurrence and development of gastrointestinal cancer. Methods: A total of 803 patients who underwent radical gastrectomy in Qinghai University Affiliated Hospital from January 2012 to December 2016 were included as training set. Multivariable Cox proportional hazard regression was used to identify associations with outcome of gastric cancer (GC). CNLR was established by combining CEA and the neutrophils to lymphocytes ratio (NLR, a typical parameter in SIR) to generate a novel prognostic score system and its prognostic value was externally validated. Results: Multivariate analysis showed that CEA and NLR were independent prognostic factors for GC patients (both p < 0.05). A higher CNLR was significantly associated with older age, male sex, larger tumor size, vascular invasion and advanced stages (all p < 0.05). Patients with higher CNLR had poor prognosis than those with lower CNLR (p < 0.05). Multivariate analysis showed that CNLR was an independent prognostic factor (p < 0.05). Incorporation of the CNLR into a prognostic model including age and TNM stage generated a nomogram, which predicted accurately 3- and 5-year survival for GC patients. And similar results were obtained in the external validation set. Conclusions: The CNLR prognostic scoring system established by combining CEA and NLR is an independent prognostic factor for GC, which can be incorporated into the traditional TNM staging to improve the prediction of long-term survival outcomes.