Can the preoperative prognostic nutritional index be used as a postoperative predictor of gastric or gastroesophageal junction adenocarcinoma?

Gastric cancer and adenocarcinoma of the esophagogastric junction are major challenges to global public health due to their high morbidity and mortality. Despite continuous improvements in treatment techniques, patient prognosis is still affected by multiple factors. The preoperative prognostic nutritional index (PNI), a simple clinical indicator, has received widespread attention in recent years. Fiflis et al conducted a systematic review and reported that a high PNI was associated with significantly better survival in patients with gastric cancer. They also found that the PNI had prognostic value in patients with cancer of different TNM stages and had a positive effect even in advanced gastric cancer patients. Although the study did not address the impact of treatment regimens and had limited data sources, the results support the validity of the PNI as a biomarker for predicting the survival of gastric cancer patients. Future studies should further standardize the calculation method of the PNI, explore its applicability in different populations, and integrate other clinical parameters to construct more accurate prediction models.

Characteristics of auto-quantified tumor-infiltrating lymphocytes and the prognostic value in adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, and esophageal squamous cell carcinoma.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEGJ) with a specific pathological profile and poor prognosis has limited therapeutic options. Previous studies have found that TILs exhibit distinct characteristics in different tumors and are correlated with tumor prognosis. We established cellular training sets to obtain auto-quantified TILs in pathological images. And we compared the characteristics of TILs in AEGJ with those in esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GAC) to gain insight into the unique immune environments of these three tumors and investigate the prognostic value of TILs in these three tumors. METHODS: Utilizing a case-control study design, we analyzed 214 AEGJ, 256 GAC, and 752 ESCC cases. The TCGA dataset was used to validate prognostic value of auto-quantified TILs. The specific cellular training sets were established by experienced pathologists to determine TILs counts. Kruskal-Wallis test and multi-variable linear regression were conducted to explore TILs characteristics. Survival analyses were performed with Kaplan-Meier method and Cox proportional hazards model. RESULTS: The three cellular training sets of these cancers achieved a classification accuracy of 87.55 at least. The median auto-quantified TILs of AEGJ, GAC, and ESCC cases were 4.82%, 1.92%, and 0.12%, respectively. The TILs demonstrated varied characteristics under distinctive clinicopathological traits. The higher TILs proportion was associated with better prognosis in esophagogastric cancers (all P < 0.05) and was an independent prognostic biomarker on AEGJ in both datasets (Taixing: HR = 0.965, 95% CI = 0.938-0.994; TCGA: HR = 0.811, 95% CI = 0.712-0.925). CONCLUSIONS: We found variations in TILs across ESCC, GAC, and AEGJ, as assessed by image processing algorithms. Additionally, TILs in these three cancers are an independent prognostic factor. This enhances our understanding of the unique immune characteristics of the three tumors, improving patient outcomes.

A retrospective analysis of lymph node dissection in Siewert II adenocarcinoma of the esophagogastric junction.

BACKGROUND: Analyze the pattern of lymph node metastasis in Siewert II adenocarcinoma of the esophagogastric junction (AEG) and provide a basis for the principles of surgical access. METHODS: The clinical data of 112 Siewert type II AEG patients admitted to the Fifth Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2020 to 2022 were retrospectively collected. The probability of lymph node metastasis in each site and the clearance rate of lymph nodes in each site by different surgical approaches were analyzed. RESULTS: The lymph node metastasis rates in the middle and upper mediastinum group, the lower mediastinum group, the upper perigastric + supra pancreatic group, and the lower perigastric + hepatoduodenal group were 0.0%, 5.4%, 61.6%, and 17.1%, (P < 0.001). The number of lymph nodes cleared in the middle and upper mediastinum group was 0.00, 0.00, 4.00 in the transabdominal approach (TA), left thoracic approach (LT), and Ivor-Lewis (IL) group, (P < 0.001); The number of lymph nodes cleared in the lower mediastinal group was 0.00, 2.00, 2.00, (P < 0.001); The number of lymph node dissection in the perigastric + hepatoduodenal group was 3.00, 0.00, and 8.00, (P < 0.001). The overall complication rates were 25.7%, 12.5%, and 36.4%, (P = 0.058). CONCLUSION: Siewert II AEG has the highest rate of lymph node metastasis in the upper perigastric + supra-pancreatic region, followed by the lower perigastric + hepatoduodenal, lower mediastinal, middle, and upper mediastinal regions. Ivor-Lewis can be used for both thoracic and abdominal lymph node dissection and does not increase the incidence of postoperative complications.

The impact of the length of proximal margin on the prognosis in adenocarcinoma of gastroesophageal junction: A real-world study and strategies.

BACKGROUND: The optimal proximal margin (PM) length for Siewert II/III adenocarcinoma of the esophagogastric junction (AEJ) remains unclear. This study aimed to determine the optimal PM length using an abdominal approach to guide surgical decision-making. METHODS: A prospective study analyzed 304 consecutive patients diagnosed with Siewert II/III AEJ between January 2019 and December 2021. Total gastrectomy was performed via the abdominal approach, and PM length was measured on fixed gross specimens. X-Tile software determined the optimal PM cut-point based on progression-free survival (PFS). Univariate analyses compared baseline characteristics across PM groups, while survival analyses utilized Kaplan-Meier estimation and Cox proportional hazards regression for assessing the impact of margin length on survival. Multivariable analyses were conducted to adjust for confounding variables. RESULTS: The study included 264 AEJ cases classified as Siewert II (71.97%) or III (28.03%). The median gross PM length was 1.0 cm (IQR: 0.5 cm-1.5 cm, range: 0 cm-6 cm). PM length ≥1.2 cm was associated with a lower risk of disease progression compared to PM length 0.4 cm on PFS (HR = 0.41, 95% CI 0.20-0.84, P = 0.015). Moreover, PM ≥ 1.2 cm improved prognosis in subgroups of T4 or N3, tumor size <4 cm, Siewert II, and Lauren classification. CONCLUSIONS: For Siewert type II/III AEJ, a proximal margin length ≥1.2 cm (1.65 cm in situ) is associated with improved outcomes. These findings offer valuable insights into the association between PM length and outcomes in Siewert II/III AEJ, providing guidance for surgical approaches and aiding clinical decision-making to enhance patient outcomes.

The development and validation of automated machine learning models for predicting lymph node metastasis in Siewert type II T1 adenocarcinoma of the esophagogastric junction.

Background: Lymph node metastasis (LNM) is considered an essential prognosis factor for adenocarcinoma of the esophagogastric junction (AEG), which also affects the treatment strategies of AEG. We aimed to evaluate automated machine learning (AutoML) algorithms for predicting LNM in Siewert type II T1 AEG. Methods: A total of 878 patients with Siewert type II T1 AEG were selected from the Surveillance, Epidemiology, and End Results (SEER) database to develop the LNM predictive models. The patients from two hospitals in Suzhou were collected as the test set. We applied five machine learning algorithms to develop the LNM prediction models. The performance of predictive models was assessed using various metrics including accuracy, sensitivity, specificity, the area under the curve (AUC), and receiver operating characteristic (ROC) curve. Results: Patients with LNM exhibited a higher proportion of male individuals, a poor degree of differentiation, and submucosal infiltration, with statistical differences. The deep learning (DL) model demonstrated relatively good accuracy (0.713) and sensitivity (0.868) among the five models. Moreover, the DL model achieved the highest AUC (0.781) and sensitivity (1.000) in the test set. Conclusion: The DL model showed good predictive performance among five AutoML models, indicating the advantage of AutoML in modeling LNM prediction in patients with Siewert type II T1 AEG.

Preoperative ultrasound-guided dual localization with titanium clips and carbon nanoparticles for predicting the surgical approach and guiding the resection of Siewert type II esophagogastric junction adenocarcinoma.

OBJECTIVE: To investigate the superiority of preoperative ultrasound-guided titanium clip and nanocarbon dual localization over traditional methods for determining the surgical approach and guiding resection of Siewert type II adenocarcinoma of the esophagogastric junction (AEG). METHOD: This study included 66 patients with Siewert type II AEG who were treated at the PLA Joint Logistics Support Force 900th Hospital between September 1, 2021, and September 1, 2023. They were randomly divided into an experimental group (n = 33), in which resection was guided by the dual localization technique, and the routine group (n = 33), in which the localization technique was not used. Surgical approach predictions, proximal esophageal resection lengths, pathological features, and the occurrence of complications were compared between the groups. RESULT: The use of the dual localization technique resulted in higher accuracy in predicting the surgical approach (96.8% vs. 75.9%, P = 0.02) and shorter proximal esophageal resection lengths (2.39 ± 0.28 cm vs. 2.86 ± 0.39 cm, P < 0.001) in the experimental group as compared to the routine group, while there was no significant difference in the incidence of postoperative complications (22.59% vs. 24.14%, P = 0.88). CONCLUSION: Preoperative dual localization with titanium clips and carbon nanoparticles is significantly superior to traditional methods and can reliably delineate the actual infiltration boundaries of Siewert type II AEG, guide the surgical approach, and avoid excessive esophageal resection.

Transthoracic single-port-assisted laparoscopic gastrectomy versus laparoscopic transhiatal approach for Siewert type II adenocarcinoma of the esophagogastric junction: a single-center retrospective study.

BACKGROUND: The surgical approach for patients with Siewert type II AEG remains controversial. Several studies have described a new laparoscopic radical resection approach of Siewert type II AEG through the left diaphragm. However, the technical safety and feasibility of the new surgical approach compared with the transhiatal approach have not yet been tested. STUDY DESIGN: We retrospectively reviewed patients with AEG who underwent TSLG and LTH operations in the Guangdong Provincial Hospital of Chinese Medicine between January 2017 and April 2021. Histologically confirmed AEG and D2 lymphadenectomy with curative R0 patients were included, and patients with Siewert I/III AEG or distant metastasis were excluded. Blood loss, the amount of harvested lymph node, and complications related to surgery were evaluated. RESULTS: A total of 99 patients with Siewert type II AEG were analyzed, 44 in the TSLG group and 55 in the LTH group. There was no difference in clinicopathological features between the two groups. The more harvested lymph node (23.33 ± 11.41 vs. 32.18 ± 12.85, p < 0.01), lower mediastinal lymph node (1.07 ± 2.08 vs. 3.25 ± 3.31, p < 0.01), and longer proximal margin length (3.08 ± 1.19 vs. 4.47 ± 0.95 cm, p < 0.01) were observed in the TSLG group. The rate of cure (R0 gastrectomy) in the TSLG group was higher than that in the LTH group (100% vs. 89.09%, p = 0.03). CONCLUSION: The TSLG approach is associated with improved surgical views, simplified lymphatic dissection in the inferior mediastinum, and more reliable margins. TSLG surgery may be an effective addition to LTH surgery, particularly when lower mediastinal lymph node metastases are suspected.

Clinical outcomes of the robot-assisted Ivor Lewis procedure for adenocarcinoma of the esophagogastric junction with semi-instrument overlap intrathoracic anastomosis.

Background: The main difficulty of minimally invasive Ivor Lewis (IL) procedure for adenocarcinoma of the esophagogastric junction (AEGJ) is the intrathoracic esophagogastric anastomosis (IEA). We aimed to assess the safety and feasibility of the IL procedure with the da Vinci surgical system for treatment of AEGJ with semi-mechanical intrathoracic IEA. Methods: The cohort included 72 patients with AEGJ who received treatment at the Department of Minimally Invasive Esophagus Surgery of the Tianjin Medical University Cancer Institute and Hospital from August 2020 to March 2023. Of these 72 patients, 17 received neoadjuvant chemo-immunotherapy. The robot-assisted minimally invasive IL procedure was performed using a linear stapler for overlap side-to-side intrathoracic anastomosis and the stapler defect was closed with double full-layer continuous sutures by robotic hand-sewn (semi-mechanical) IEA. Results: Of the 72 AEGJ patients, 2 were converted to exploration, 7 were converted to laparotomy and thoracotomy for circular-stapled intrathoracic anastomosis, and 6 were converted to thoracotomy for circular-stapled anastomosis, which included 2 cases of extensive pleural adhesion and 4 cases of overlap anastomosis failure, whereas 57 underwent the robot-assisted minimally invasive IL procedure with semi-mechanical IEA. Among the 9 patients converted to laparotomy, the laparotomy rate was closely related to the Siewert classification (P<0.005) and preoperative use of neoadjuvant therapy (P<0.05). Among the 57 patients who underwent the robot-assisted minimally invasive IL procedure with semi-mechanical IEA, there were 2 cases of anastomotic leakages (2/57, 3.5%), no case of anastomotic stricture, 5 cases of postoperative pneumonia (5/57, 8.77%), 2 cases of intensive care unit admission (2/57, 3.5%), and 1 case of readmission within 30 days (1/57, 1.75%). None of the patients died within 30 days after surgery. Conclusions: The robot-assisted minimally invasive IL procedure with semi-mechanical IEA is both safe and feasible for AEGJ. However, caution is advised for patients with Siewert type III AEGJ and those who have already received preoperative neoadjuvant therapy.

Total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert II AEG.

PURPOSE: The optimal procedure is still controversial about Siewert type II AEG, We are attempt to explore the efficacy and feasibility of total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert type II AEG. METHOD: Data of patients with Siewert type II AEG who received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis in the Hebei General Hospital were collected from October 2020 to October 2021, The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, the length of stay in ICU, the resume oral feeding time, the length of postoperative hospital stay, postoperative complications and other related indicators of the patients were collected to evaluate the safety and feasibility of this operation. RESULT: A total of 17 patients received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosisin the treatment of Siewert type II AEG were analyzed in our research. The mean operation time was 253 ± 24.8 min (196-347 min); The median surgical blood loss was 250 ml (20-2400 ml); The average number of dissected lymph nodes were 28 ± 4.6 (17-36); The median duration of drainage tube was 5 days (3-7days); The median length of stay in ICU was 18 h(10-34 h); The median time of resume oral feeding was 6 days (5-7days); The median postoperative hospital stay was 11 days (8-15 days). Among the all enrolled patients, one patient underwent the conversion to laparotomy due to the massive intraoperative bleeding, one patient developed anastomotic stenosis at jejunum side-to-side anastomosis on the first month after surgery, there was no case of death during the operation and postoperative anastomotic fistula. All patients achieved R0 resection with an average distance of 6 cm (4-8.5 cm) from the upper margin of the tumor to the resection margin. CONCLUSION: The operation of total laparoscopic total gastric and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis is technically feasible and sufficiently safe in the treatment of Seiwert type II AEG from our primary clinical experience. This procedure could be one of the alternatives for the radical treatment of Siewert type II AEG.

Influence of Primary Tumor Resection on Survival of Patients With Metastatic Siewert Type II Adenocarcinoma of the Esophagogastric Junction: A Population-Based, Propensity-Matched Analysis.

OBJECTIVE: It remains unclear whether primary tumor resection improves survival in patients with metastatic Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Therefore, our study attempted to investigate the prognostic value of primary tumor resection on metastatic AEG. METHODS: In total, 4200 patients diagnosed with metastatic AEG were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were categorized into two groups according to the performance of primary tumor resection. Pearson's chi-square test, Kaplan-Meier survival curve, and Cox regression analysis were conducted in this study. In addition, propensity-score matching was conducted to match 323 patients who received primary tumor resection and another 323 patients without. RESULTS: Multivariate Cox regression analysis demonstrated that primary tumor resection was a significant prognostic factor in patients with metastatic AEG before matching. Moreover, in the matched cohort, metastatic AEG patients receiving primary tumor resection had significantly longer overall survival (hazard ratio [HR]: .54, 95% confidence interval [CI]: .46-.64, P < .001) and cancer-specific survival (HR: .53, 95% CI: .45-.63, P < .001). Subgroup analysis similarly revealed that primary tumor resection was significantly associated with better survival in most subgroups. CONCLUSION: The present population-based study identified that primary tumor resection led to significantly superior survival in patients with metastatic AEG. These findings are likely to contribute to the development of individualized therapy in metastatic AEG.

Hub genes in adenocarcinoma of the esophagogastric junction based on weighted gene co-expression network analysis and immunohistochemistry.

BACKGROUND: Gastric cancer (GC) is the fifth most common malignant tumor, and it is usually fatal. Adenocarcinoma of the esophagogastric junction (AEG) accounts for about 50% of all GC cases. However, the systematic co-expression analysis of this tumor does not fully explain its pathogenesis. This study aimed to identify hub genes based on weighted gene co-expression networks and immunohistochemistry analyses. METHODS: The RNA-seq data of 22 AEG patients were processed using weighted gene co-expression network analysis. We differentiated the modules with clinical tumor markers and performed Gene Ontology and pathway enrichment analysis. We identified the hub genes related to the biological processes of tumorigenesis based on weighted gene co-expression network analysis and immunohistochemistry analysis. RESULTS: Twenty-five distinct co-expression gene modules were identified; the tumorigenic genes CD93, TRIM28, SLC3A2, CBX4, PATL1, and ZNF473 had high intramodular connectivity. Immunohistochemistry confirmed that these hub genes are upregulated in AEG. Statistical analysis indicated that the expression of CD93 was correlated with the T stage and maximum tumor diameter. CONCLUSION: Weighted gene co-expression network analysis and immunohistochemistry identified CD93 as a hub gene that might be critical for AEG biology.

Selection of two intrathoracic anastomosis methods for transabdominal radical surgery for Siewert type II adenocarcinoma of the esophagogastric junction.

Introduction: The most common intrathoracic anastomosis techniques for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) are the overlap and transorally inserted anvil (OrVil) methods. However, the criteria for choosing between these two methods require further study. Aim: This retrospective study aimed to compare the efficacy and safety of overlap versus OrVil anastomosis in transabdominal radical surgery for Siewert type II adenocarcinoma of the esophagogastric junction. Material and methods: A total of 34 patients with Siewert type II AEG who underwent transabdominal radical surgery and intrathoracic anastomosis with the overlap or OrVil methods at our center from January 2018 to June 2019 were retrospectively analyzed. The relevant surgical and postoperative complication data of the two groups were collected and analyzed. Results: Clinical characteristics: the mean tumor size was 7.5 ±2.4 cm in the OrVil group and 4.3 ±1.9 cm in the overlap group (p < 0.05). Surgery: the distance from the upper resection margin of the esophagus to the tumor was 3.2 ±0.84 cm in the OrVil group and 2.4 ±0.6 cm in the overlap group (p < 0.05). Postoperative complications: there were two cases of pleural effusion in the OrVil group and 18 cases of pleural effusion in the overlap group (p < 0.05). Conclusions: There is no significant difference between the OrVil and overlap anastomosis in terms of the feasibility and safety; however, OrVil anastomosis can provide a higher margin of resection of the esophagus and is suitable for tumors with extensive esophageal invasion.

Anastomotic stenosis following proximal gastrectomy with single flap valvulopasty successfully managed with endoscopic stricturotomy: a case report.

Background: Due to its nutritional advantages over total gastrectomy, proximal gastrectomy (PG) with anti-reflux techniques has gained significant attention in East Asian countries in recent years. The double flap technique (DFT) and modified side overlap and fundoplication by Yamashita (mSOFY) are two promising anti-reflux interventions following PG. However, anastomotic stenosis after DFT and gastroesophageal reflux after mSOFY have been reported in several patients. To address these concerns, a hybrid reconstruction procedure was designed, namely, right-sided overlap with single flap valvulopasty (ROSF), for proximal gastrectomy, with the aim of reducing anastomotic stricture and reflux. Among the 38 patients who underwent ROSF at our hospital, one developed Stooler grade II anastomotic stenosis. Herein, we present the successful management of this patient through endoscopic stricturotomy (ES). Case summary: A 72-year-old female complaining of "epigastric pain and discomfort for more than 1 month" was diagnosed with adenocarcinoma of the esophagogastric junction (Siewert type II). She underwent laparoscopic-assisted PG and ROSF procedures at our hospital and recovered well after surgery. However, she started experiencing progressive difficulty in eating and vomiting approximately 3 weeks after the intervention. Endoscopy revealed Stooler grade II esophagogastric anastomotic stenosis. ES with insulated tip (IT) Knife nano was eventually performed, and the patient was able to resume a normal diet without experiencing any discomfort during the 5-month follow-up period. Conclusion: Endoscopic stricturotomy using IT Knife nano successfully treated anastomotic stenosis following ROSF with no associated complications. Thus, ES to treat anastomotic stenosis after PG with valvulopasty can be considered a safe option and should be performed in centers with the required expertise.

The clinical outcomes of laparoscopic proximal gastrectomy with double-tract reconstruction versus tube-like stomach reconstruction in patients with adenocarcinoma of the esophagogastric junction based on propensity score-matching: a multicenter cohort study.

Purpose: Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic proximal gastrectomy with tube-like stomach reconstruction (LPG-TLR) are both function-preserving procedures performed for treating AEG. However, there is no clinical consensus on the selection of digestive tract reconstruction after proximal gastrectomy, and the best way to reconstruct the digestive tract remains controversial. This study aimed at comparing the clinical outcomes of LPG-DTR and LPG-TLR to provide some reference to the choice of AEG surgical modalities. Methods: This was a multicenter, retrospective cohort study. we collected clinicopathological and follow-up data of patients with consecutive cases diagnosed with AEG from January 2016 to June 2021 in five medical centers. According to the way of digestive tract reconstruction after tumor resection, patients who underwent LPG-DTR or LPG-TLR were included in the present study. Propensity score matching (PSM) was performed to balance baseline variables that might affect the study outcomes. The QOL of the patients was evaluated using the Visick grade. Results: A total of 124 eligible consecutive cases were finally included. Patients in both groups were matched using the PSM method, and 55 patients from each group were included in the analysis after PSM. There was no statistically significant difference between the two groups in terms of the operation time, amount of intraoperative blood loss, days of postoperative abdominal drainage tube placement, postoperative hospitalization days, total hospitalization cost, the total number of lymph nodes cleared, and the number of positive lymph nodes (P>0.05). There was a statistically significant difference between the two groups in terms of time to first flatus after surgery and postoperative soft food recovery time (P<0.05). For the nutritional status, the weight levels at 1 year after surgery was better in the LPG-DTR group than in the LPG-TLR group (P<0.05). There was no significant difference in Visick grade between the two groups (P>0.05). Conclusion: The anti-reflux effect and quality of life of LPG-DTR for AEG were comparable to those of LPG-TLR. Compared with LPG-TLR, LPG-DTR provide better nutrition status for patients with AEG. LPG-DTR is a superior reconstruction method after proximal gastrectomy.

Comparison of thoracoabdominal versus abdominal-transhiatal surgical approaches in Siewert type II adenocarcinoma at the esophagogastric junction: Protocol for a prospective multicenter randomized controlled trial.

Background: Siewert type II adenocarcinoma of the esophagogastric junction (Siewert II AEG) can be resected by the right thoracoabdominal surgical approach (RTA) or abdominal-transhiatal surgical approach (TH) under minimally invasive conditions. Although both surgical methods achieve complete tumor resection, there is a debate as to whether the former method is superior to or at least noninferior to the latter in terms of surgical safety. Currently, a small number of retrospective studies have compared the two surgical approaches, with inconclusive results. As such, a prospective multicenter randomized controlled trial is necessary to validate the value of RTA (Ivor-Lewis) compared to TH. Methods: The planned study is a prospective, multicenter, randomized clinical trial. Patients (n=212) with Siewert II AEG that could be resected by either of the above two surgical approaches will be included in this trial and randomized to the RTA group (n=106) or the TH group (n=106). The primary outcome will be 3-year disease-free survival (DFS). The secondary outcomes will include 5-year overall survival (OS), incidence of postoperative complications, postoperative mortality, local recurrence rate, number and location of removed lymph nodes, quality of life (QOL), surgical Apgar score, and duration of the operation. Follow-ups are scheduled every three months for the first 3 years after the surgery and every six months for the next 2 years. Discussion: Among Siewert II AEG patients with resectable tumors, this is the first prospective, randomized clinical trial comparing the surgical safety of minimally invasive RTA and TH. RTA is hypothesized to provide better digestive tract reconstruction and dissection of mediastinal lymph nodes while maintaining a high quality of life and good postoperative outcome. Moreover, this trial will provide a high level of evidence for the choice of surgical procedures for Siewert II AEG. Clinical trial registration: Chinese Ethics Committee of Registering Clinical Trials, identifier (ChiECRCT20210635); Clinical Trial.gov, identifier (NCT05356520).

Hand-sewn esophagojejunostomy in transthoracic single-port assisted laparoscopic esophagogastrectomy for Siewert type II adenocarcinoma of the esophagogastric junction with esophageal invasion > 3 cm.

BACKGROUND: An optimal method for digestive tract reconstruction (DTR) in laparoscopic radical resection of Siewert type II adenocarcinoma of esophagogastric junction (AEG) has not yet been standardized. The aim of this study was to evaluate the safety and feasibility of a hand-sewn esophagojejunostomy (EJ) technique during transthoracic single-port assisted laparoscopic esophagogastrectomy (TSLE) for Siewert type II AEG with esophageal invasion > 3 cm. METHODS: The perioperative clinical data and short-term outcomes for patients who underwent TSLE using hand-sewn EJ for Siewert type II AEG with esophageal invasion > 3 cm between March 2019 and April 2022 have been retrospectively reviewed. RESULTS: A total of 25 patients were eligible. All 25 patients were successfully operated. None was converted to open surgery or mortality. 84.00% of patients were male and 16.00% were female. The mean age, body mass index (BMI), and the American Society of Anesthesiologists (ASA) score were 67.88 ± 8.10 years, 21.30 ± 2.80 kg/m2, and 2.08, respectively. The average incorporated operative and hand-sewn EJ procedural times were 274.92 ± 57.46 and 23.36 ± 3.00 min, respectively. The length of extracorporeal esophageal involvement and proximal margin was 3.31 ± 0.26 cm and 3.12 ± 0.12 cm, respectively. The average time for the first oral feeding and hospital stay were 6 (3-14) and 7 (3-18) days, respectively. Two patients (8.00%) developed postoperative grade IIIa complications according to the Clavien-Dindo classification, including 1 case of pleural effusion and 1 case of anastomotic leakage, both of whom were cured by puncture drainage. CONCLUSION: Hand-sewn EJ in TSLE is safe and feasible for Siewert type II AEG. This method can ensure safe proximal margins and could be a good option with an advanced endoscopic suture technique for type II tumor with esophageal invasion > 3 cm.

Evaluating prognostic value and stage migration effects using a positive lymph node ratio in adenocarcinoma of the esophagogastric junction.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Lymph node metastasis is an important clinical issue in AEG patients. This study investigated the usefulness of a positive lymph node ratio (PLNR) to stratify prognosis and evaluate stage migration. METHODS: We retrospectively analysed 117 consecutive AEG patients (Siewert type I or II) who received a lymphadenectomy between 2000 and 2016. RESULTS: A PLNR cut-off value of 0.1 most effectively stratified patient prognosis into two groups (P < 0.001). Also, prognosis could be clearly stratified into four groups: PLNR = 0, 0 < PLNR < 0.1, 0.1 ≤ PLNR < 0.2, and 0.2 ≤ PLNR (P < 0.001, 5-year survival rates (88.6%, 61.1%, 34.3%, 10.7%)). A PLNR ≥ 0.1 significantly correlated with tumour diameter ≥ 4 cm (P < 0.001), tumour depth (P < 0.001), greater pathological N-status (P < 0.001), greater pathological Stage (P < 0.001), and oesophageal invasion length ≥ 2 cm (P = 0.002). A PLNR ≥ 0.1 was a poor independent prognostic factor (hazard ratio 6.47, P < 0.001). The PLNR could stratify prognosis if at least 11 lymph nodes were retrieved. A 0.2 PLNR cut-off value discriminated a stage migration effect in pN3 and pStage IV (P = 0.041, P = 0.015) patients; PLNR ≥ 0.2 might potentially diagnose a worse prognosis and need meticulous follow-up post-surgery. CONCLUSION: Using PLNR, we can evaluate the prognosis and detect higher malignant cases who need meticulous treatments and follow-up in the same pStage.

Prognostic impact of sarcopenia in patients with locally advanced adenocarcinoma of the esophagogastric junction treated with neoadjuvant chemoradiotherapy.

Background: Few studies have evaluated the significance of sarcopenia in predicting the outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG), especially those who received neoadjuvant chemoradiotherapy (NCRT). We aimed to identify the sarcopenic status and its impact on the outcomes of patients with locally advanced AEG who received NCRT followed by radical surgery or systemic therapy. Materials and methods: Patients with T3-4N+M0 AEG with accessible abdominal computed tomography (CT) before and after NCRT were retrospectively analyzed. Body composition parameters, particularly the skeletal muscle index (SMI), were assessed using a CT-based method, and sarcopenia was defined using a predetermined SMI cutoff value. Survival analysis was conducted using the Kaplan-Meier method. A Cox proportional hazards regression model was used to identify independent prognostic factors. Receiver operating characteristic curve analysis was carried out, and the area under the curve (AUC) was calculated to test the prognostic accuracy of different factors. Results: A total of 63 patients were enrolled, 65.1 and 79.4% of whom developed pre- and post-NCRT sarcopenia, respectively. Patients with pre-NCRT sarcopenia had lower radical surgery rates (70.7 vs. 95.5%, p = 0.047) than those without sarcopenia; however, sarcopenic status did not affect other short-term outcomes, including treatment-related toxicity and efficacy. Pre-NCRT sarcopenia was identified as an independent predictive factor for poor overall survival (OS) [adjusted hazard ratio (HR), 6.053; p = 0.002] and progression-free survival (PFS) (adjusted HR, 2.873; p = 0.031). Compared with nutritional indices such as the Nutritional Risk Screening 2002, weight loss during NCRT, and post-NCRT sarcopenia, pre-NCRT sarcopenia was regarded as the best predictive index for the 5-year OS (AUC = 0.735) and PFS rates (AUC = 0.770). Conclusion: Pre-NCRT sarcopenia may be an independent predictive factor for OS and PFS rates in patients with locally advanced AEG receiving multimodal treatment.

Surgical approach to advanced Siewert II cancer: beyond the borders? The West Side.

The surgical approach to Siewert type II cancer should be individualized as there is no "one size fits all" option. Criteria for individualization are epidemiological, functional, oncologic and surgical items. However, our preferred procedure for advanced adenocarcinoma of the esophagogastric junction type II is esophagectomy, if this or transhiatal extended gastrectomy are both possible with R0 resection. Esophagectomy has the advantages of a longer esophageal safety margin, complete mediastinal lymphadenectomy, easier anastomosis, routine minimal invasive gastrolysis with abdominal lymphadenectomy and preservation of a gastric reservoir.

Adenocarcinoma of the stomach and esophagogastric junction with low DNA methylation show poor prognoses.

BACKGROUND: Gastric cancer (GC) is characterized by unique DNA methylation epigenotypes (MEs). However, MEs including adenocarcinomas of the esophagogastric junction (AEG) and background non-neoplastic columnar mucosae (NM) remain to be clarified. METHODS: We analyzed the genome-wide DNA MEs of AEG, GC, and background NM using the Infinium 450 k beadarray, followed by quantitative pyrosequencing validation. Large-scale data from The Cancer Genome Atlas (TCGA) were also reviewed. RESULTS: Unsupervised two-way hierarchical clustering using Infinium data of 21 AEG, 30 GC, and 11 NM revealed four DNA MEs: extremely high-ME (E-HME), high-ME (HME), low-ME (LME), and extremely low-ME (E-LME). Promoter methylation levels were validated by pyrosequencing in 146 samples. Non-inflammatory normal mucosae were clustered into E-LME, whereas gastric or esophagogastric junction mucosae with chronic inflammatory changes caused by either Helicobacter pylori infection or reflux esophagitis were clustered together into LME, suggesting that inflammation status determined DNA MEs regardless of the cause. Three cases of Barrett's-related adenocarcinoma were clustered into HME. Among 94 patients whose tumors could be clustered into one of four MEs, 11 patients with E-LME cancers showed significantly shorter overall survival than that in the other MEs, even with the multivariate Cox regression estimate. TCGA data also showed enrichment of AEG in HME and a poorer prognosis in E-LME. CONCLUSIONS: E-LME cases, newly confirmed in this study, form a unique subtype with poor prognosis that is not associated with inflammation-associated elevation of DNA methylation levels. LME could be acquired via chronic inflammation, regardless of the cause, and AEG might preferentially show HME.