Adenocarcinoma Of Esophagogastric Junction Research Articles

Neoadjuvant toripalimab plus CapeOX in patients with localized dMMR/MSI-H gastric or esophagogastric junction adenocarcinoma (GC/EGJC): Results from the cohort C of phase II NICE trial.

349 Background: Surgery is the cornerstone of curative therapy for localized GC or EGJC and perioperative chemotherapy seems ineffective for those with dMMR/MSI-H tumors. Chemotherapy may booster antitumor immunity. There is a compelling need to investigate the efficacy of perioperative immunochemotherapy for those with dMMR/MSI-H tumors. Methods: NICE trial is a multicenter, multi-cohort phase II trial (NCT04744649) investigating the safety and efficacy of toripalimab combined with CapeOX regimen as perioperative treatment for localized GC or EGJC of PD-L1 CPS≥5 (IHC 22C3) (cohort A), EBV-positive (cohort B), and dMMR/MSI-H (cohort C). Among those cohorts, the cohort A was compared with the control group of perioperative CapeOX regimen in a randomized controlled trial manner, while the cohort B and C were single arm. In present study, we report the findings of Cohort C, and the patients (pts) received toripalimab 240 mg combined with standard dose CapeOX regimen q3 weeks for 4 cycles before and after surgery. The eligible tumor stages were cT3-4aNxM0 or cT2N+M0 diagnosed by chest and abdominal CT combined with staging laparoscopy as well as negative peritoneal cytology. The primary endpoint was major pathologic response (MPR, <10% viable cells) rate. Multiplex fluorescence immunohistochemistry (mIHC) was utilized to explore changes of immune microenvironment. Results: Between March 2021 and April 2023, 15 pts with dMMR/MSI-H localized GC/GEJC were recruited in Cohort C. Tumor stages were cT3N0(n=2), cT3N1-3 (n=2), cT4aN0 (n=1) and cT4aN1-3 (n=10). 14 pts completed all 4 cycles therapy preoperatively and one patient completed 2 cycles therapy because of AEs. None had disease progression, while one achieved a complete clinical response at radiology and endoscopy and refused surgery and the other 14 pts underwent resection. The R0 resection rate was 100% (14/14). The MPR rate was 92.9% (13/14) and the residual tumor percentage was 33.8% in the other one patient (cT4aN2). pCR rate was 78.6% (11/14). Therapy-related grade 3/4 AEs occurred in 5 pts of safety population (n=15). One patient occurred grade 3 immune-related liver toxicity after 2 cycles treatment and recovered after steroids therapy. No pts died during the perioperative treatment, and one patient died of COVID-19 238 days after surgery without relapse. No disease relapse was observed in all pts. The mIHC revealed a significant reduction in CD20+ B cells, CD3+ T cells, NK dim cells, and M1 macrophages within tumor area after treatment for patients who reached pCR. Conclusions: Neoadjuvant toripalimab and CapeOX regimen for the localized dMMR/MSI-H GC/GEJC is safety with high MPR rate. These data indicate that neoadjuvant immunochemotherapy may potentially become one of the treatment options for these patients. Clinical trial information: NCT04744649 .

Ten-year overall survival of localized lower thoracic and esophagogastric junction carcinoma receiving trimodality therapy: A National Cancer Database analysis.

278 Background: Trimodality therapy, consisting of chemotherapy and radiation followed by esophagectomy, represents the prevailing standard of care for most patients with localized lower thoracic and esophagogastric junction (EGJ) carcinoma. However, robust data reporting the survival of this patient group treated in the real-world setting is lacking. The primary objective of the current study was to comprehensively analyze the long-term survival of this patient population receiving treatment in a real-world setting and the variables that significantly influence the survival. Methods: We identified adult patients in the National Cancer Database with localized (cT1N+M0 or cT2-T4N+/-M0) lower thoracic or EGJ adenocarcinoma (AC) or squamous cell carcinoma (SCC) receiving trimodality therapy between 2004 and 2020 with multi-agent chemotherapy and ≥ 4139 cGy of radiation followed by esophagectomy. The primary endpoint of the analysis was overall survival (OS), estimated using the Kaplan-Meier method. The impact of clinical and demographic features on OS was determined using the log-rank test. We performed a multivariable (MV) Cox analysis to evaluate the independent association of clinical and demographic variables on OS (data presented as hazard ratio [HR] and 95% Confidence Interval [CI]). Results: The analysis included 21,965 patients, characterized by a median age of 63 years, predominance of males (85.9%), non-Hispanic white patients (89.4%), and AC histology (93.6%). Most patients had T2/T3 tumors (87.3%) and regional lymph node (LN) involvement (62.1%). The 10-year OS for the entire cohort was 27.6% (95% CI, 26.8%-28.5%), with a median OS of 40.7 months (95% CI, 39.7-41.6). For patients aged ≤ 65, the 10-year OS was 31.2% (95% CI, 30.2%-32.3%), with a median OS of 44.1 months (95% CI, 42.8-45.5). On MV analysis, the following factors were associated with inferior OS with CI in the parenthesis: age ≥ 66 years (1.17, 1.11-1.22); male gender (1.13, 1.08-1.19); histology, AC vs. SCC (1.19, 1.10-1.28); T4 vs. T1-T3 tumor stage (1.20, 1.07-1.34); lymph node involvement (1.22, 1.18-1.27); Charlson-Deyo score ≥ 2 (1.23, 1.15-1.32); uninsured vs private insurance (1.20, 1.05-1.36); and low-volume facility (1.08, 1.01-1.16). Furthermore, patients treated after 2012 (2013-2019) had modestly improved OS (0.87, 0.84-0.90), perhaps reflecting the impact of the CROSS trial result published in 2012. Conclusions: This study illustrates the grim long-term survival of patients with localized lower thoracic and EGJ cancer undergoing standard trimodality therapy, underscoring the urgent necessity for innovative therapeutic approaches for this patient group. The improvement in OS following the publication of the CROSS trial was modest.

Organ preservation with durvalumab-based immunotherapy in combination with chemoradiation as definitive therapy for early stage, cT1, and cT2N0 esophageal adenocarcinoma with indication for radical surgery: A prospective, multicenter study of the FLOT-AIO Gastric Cancer Group (IKF-t057/PRESTO trial).

TPS431 Background: The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival rates of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on the patient’s quality of life. Recent investigations showed that in locally advanced stage EGA surgery with neoadjuvant chemoradiotherapy (CROSS trial) is beneficial over surgery alone. Further benefit was achieved for locally advanced EGA by perioperative treatment with FLOT acc. to FLOT4- trial data. Immuno-oncology (IO) therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with a combination of the anti PD-L1 antibody durvalumab- FLOT - and chemoradio-therapy. Methods: This is a multicenter, single arm, open-label, phase II trial including a total of 32 pts with T1-T2N0 EGA (including GEJ) with indication for radical surgery. Enrolled pts will receive immunotherapy with durvalumab (1500 mg Q4W) in parallel to 2 cycles FLOT (50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate and 2600 mg/m2 5FU, Q2W) induction followed by 3 cycles of mFOLFOX (85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate, 400 mg/m2 5FU bolus and 1600 mg/m2 5FU over 48h, Q2W) plus concomitant radiation (25 daily fractions with 2.0 Gy = Σ50Gy). 8 weeks after last treatment, pts will undergo tumor assessment by esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography, and CT- or MRI-scans. Surgical resection would be offered only to pts in whom a locoregional persistence is confirmed. Pts with complete remission will enter the maintenance phase and will receive durvalumab monotherapy (1500 mg, Q4W) for a maximum of 12 cycles accompanied by regular tumor re-evaluation. Primary endpoint is the rate of cCR/pCR at time of re-evaluation. Secondary endpoints include rate of cCR/pCR at 1, 2 and 3 years, rate of salvage surgery, 90 day and 1 year mortality after start of treatment, safety and quality of life. In this exploratory trial a cCR/pCR rate of ≥75% would indicate that the study treatment should be further investigated, whereas a rate < 55% indicates no further investigation. First patient was enrolled on 2023-08-28. Currently one patient is recruited. Clinical trial information: NCT05713838 .

A phase II trial of CapeOX plus nivolumab for early relapsed HER2-negative gastric cancer (JACCRO GC-11: FirSTAR trial).

TPS423 Background: Fluoropyrimidine-based post-operative chemotherapy is one of the standard adjuvant therapies for curatively resected gastric cancer (GC).1,2 The current standard first-line chemotherapy consists of fluoropyrimidine and oxaliplatin combined with nivolumab in advanced HER2-negative GC patients including cases with a recurrence > 6 months after completion of post-operative chemotherapy, based on the CheckMate 649 and ATTRACTION-4 trials. However, in GC patients with early recurrence during or ≤ 6 months after completion of post-operative 5-FU based chemotherapy, optimal treatments remain to be established. A previous phase II study showed that capecitabine plus cisplatin is an active regimen for early relapsed GC after post-operative S-1 monotherapy.3 This trial aims to investigate the efficacy of capecitabine plus oxaliplatin (CapeOX) plus nivolumab for patients with early relapsed HER2-negative GC. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria include: histologically confirmed HER2-negative adenocarcinoma of stomach or esophagogastric junction; radiologically diagnosed recurrence during or ≤ 6 months after post-operative chemotherapy with S-1 or S-1 plus docetaxel conducted for stage II/III GC after curative resection; age ≥ 18 years; ECOG performance status 0-1; having measurable lesions according to RECIST ver. 1.1; and adequate oral intake and organ functions. Enrolled patients will receive 21-day cycles of nivolumab with CapeOX at the following dose until disease progression or unacceptable toxicities: capecitabine, 1000 mg/m2 twice per day on day 1-14; oxaliplatin, 130 mg/m2 on day 1; and nivolumab, 360 mg on day 1. The primary endpoint is objective response rate (ORR), and the secondary endpoints include overall survival, progression-free survival, disease control rate, duration of response, and safety. PD-L1 combined positive score will be tested for the association with efficacy. We assume null ORR of 20% and alternative ORR of 32%. With two-sided alpha level of 10% and 80% power, sample size would be calculated as 85. Thus, a total of 92 patients are planned for enrollment within a 2.5-year accrual period. Enrollment opened in March 2023. Clinical trial information: jRCTs031220572. 1. N Engl J Med. 2007;357:1810-20. 2. J Clin Oncol. 2019;37:1296-1304. 3. Gastric Cancer. 2018;21:811-8. Clinical trial information: jRCTs031220572 .

Prospective assessment of adenocarcinoma of esophagogastric junction (AEG) following radical resection: Real-world insights from the CLAEG study.

TPS415 Background: The CLAEG study (ChiCTR1900026131) is a prospective, real-world data evaluation of the clinical outcomes of patients with AEG following radical resection to investigate lymph node (LN) metastasis patterns and refine treatment strategies. Methods: Data from 44 hospitals in China were collected using a designed CRF, comprising baseline, surgical details, pathology results and recovery progress from January 1,2020. Data cut-off was August 31, 2023. The study is ongoing. Results: A total of 1322 patients were enrolled, and only 946 patients with complete data were included in the analysis. The median age was 65 years (range, 24-90). Among them, 28 patients were classified as Siewert type I, 601 as type II, and 317 as type III. Laparoscopic surgery was performed in 845 patients, while 101 underwent open surgery, with no significant difference in postoperative complication rate between them. However, the laparoscopic group demonstrated superior favorable outcomes in terms of postoperative recovery times, with shorter postoperative exhaust time (3.0 days vs 3.6 days, p<0.001), feeding time (5.0 days vs 5.8 days, p=0.013), discharge time (11.6 days vs 14.6 days, p=0.002), as well as lower intraoperative blood loss (103.9 ml vs 163.4 ml, p=0.001). Among the patients, 891 underwent transhiatal approach, while 55 underwent thoracoabdominal approach, and no significant differences in postoperative complication rates, intraoperative blood loss and hospital stay were observed between these approaches. However, the transhiatal approach was associated with a shorter operative time (244.2 min vs 309.3 min, p<0.001). LN dissection was performed in all patients within the abdominal region, with additional mediastinal LN dissection in 293 patients. The LN metastasis rates were 7.04%, 0% and 5.71% for No. 110, 111 and 112, respectively. Within the abdominal LNs, category-1 nodes included No. 1, 2, 3, 4, 5, 7, 8a, 9, 11, 19, while category-2 included No. 6, 12a, 20. Total gastrectomy was performed in 657 patients, while proximal gastrectomy was performed in 289 patients, and there were no significant differences in the rates of postoperative complications, postoperative recovery times and hospital stay between them. However, total gastrectomy took less operation time (243.7 min vs 258.0 min, p=0.019), and more LNs (36.6 vs 23.3, p<0.001) were detected in abdomen. Conclusion: The CLAEG study confirms the safety and feasibility of laparoscopy in AEG surgery, although its long-term oncology effectiveness requires further investigation. Transhiatal surgery is advantageous due to its shorter operation time. Both proximal and total gastrectomy can be considered as viable surgical options. AEG patients have a higher rate of abdominal LN metastasis but a lower rate of mediastinal node involvement, emphasizing the importance of precise abdominal LN retrieval. Clinical trial information: ChiCTR1900026131 .

Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma

Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.

Imaging of Barium Esophagogram and Abdominal Computed Tomography of Adenocarcinoma of Esophagogastric Junction: Case Report

Adenocarcinoma of the esophagogastric junction is one of the most common cancers in the world, with an estimated mortality rate 1 million deaths each year. In this case we report a patient with symptom of dysphagia for the last 3 months. Esophagogram and Abdominal Computed Tomography were performed to diagnosis and determine the staging of the disease. Pathological examination and endoscopy are also needed to support diagnosis. This case highlights the utility of radiological findings, supported by other examinations to determine the diagnosis of Adenocarcinoma of Esophagogastric Junction.

M6A modification enhances the stability of CDC25A promotes tumorigenicity of esophagogastric junction adenocarcinoma via cell cycle.

N6-Methyladenosine (m6A) modification and its regulators play critical roles in human cancers, but their functions and regulatory mechanisms in adenocarcinoma of the esophagogastric junction (AEG) remain unclear. Here, we identified that IGF2BP3 is the most significantly up-regulated m6A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m6A regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression in vitro and in vivo. By profiling transcriptome-wide targets of IGF2BP3 and the m6A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m6A-modified targets, including targets of the cell cycle pathway, such as CDC25A, CDK4, and E2F1, are critical for AEG progression. Mechanistically, the increased m6A modification of CDC25A accelerates the G1-S transition. Clinically, up-regulated IGF2BP3, METTL3, and CDC25A show a strong positive correlation in TCGA pan-cancer, including AEG. In conclusion, our study highlights the role of post-transcriptional regulation in modulating AEG tumor progression and elucidates the functional importance of the m6A/IGF2BP3/CDC25A axis in AEG cells.

Effect of different surgical approaches on the survival and safety of Siewert type II esophagogastric junction adenocarcinoma: a systematic review and meta-analysis

BackgroundWhether a transthoracic (TT) procedure by a thoracic surgeon or a transabdominal (TA) by a gastrointestinal surgeon is best for Siewert type II esophagogastric junction adenocarcinoma (EGJA) remains unknown. Survival and perioperative outcomes were compared between the two groups in this meta-analysis to clarify this argument.MethodsWe searched 7 databases for eligible studies comparing TT and TA procedures for Siewert type II EGJA. The final analyzed endpoints included intraoperative and hospitalization outcomes, recurrence, complication, and survival.ResultsSeventeen studies involving 10,756 patients met the inclusion criteria. The TA group had higher rates of overall survival (OS) (HR: 1.31 [1.20 ~ 1.44], p < 0.00001) and disease-free survival (DFS) (HR: 1.49 [1.24 ~ 1.79], p < 0.0001). The survival advantage of OSR and DFSR increased with time. Subgroup analysis of OS and DFS suggested that TA remained the preferred approach among all subgroups. More total/positive lymph nodes were retrieved, and fewer lymph node recurrences were found in the TA group. The analysis of perioperative outcomes revealed that the TA procedure was longer, had more intraoperative blood loss, and prolonged hospital stay. Similar R0 resection rates, as well as total recurrence, local recurrence, liver recurrence, peritoneal recurrence, lung recurrence, anastomosis recurrence and multiple recurrence rates, were found between the two groups. The safety analysis showed that the TT procedure led to more total complications, anastomotic leakages, cases of pneumonia, and cases of pleural effusion.ConclusionsThe TA procedure appeared to be a suitable choice for patients with Siewert type II EGJA because of its association with longer survival, fewer recurrences, and better safety.

OGC P01 Evaluating the use of FDG PET-CT for restaging patients with oesophageal adenocarcinoma treated with neoadjuvant chemotherapy

Abstract Background 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging oesophageal cancer and has an emerging role in evaluating response to neoadjuvant chemotherapy (NACT). This study aimed to evaluate the clinical utility of FDG-PET-CT and contrast-enhanced CT (CECT) in restaging patients with oesophageal adenocarcinoma treated with NACT. The accuracy for evaluating depth of tumour invasion (ypT stage), pathological nodal disease (ypN stage) and identifying distant metastases compared with CECT was assessed. The ability of FDG-PET-CT to predict pathological response in the primary tumour (pTR) and LNs (pNR) was also evaluated. Methods Cohort study of 104 patients with locally advanced oesophageal or oesophago-gastric junctional adenocarcinoma who underwent FDG-PET-CT and CECT before and after NACT at Guy’s and St Thomas’ NHS Foundation Trust, London, UK, between 2017–2020. SUV metrics related to the primary tumour and loco-regional LNs were derived on pre- and post- treatment FDG-PET-CT. pTR and pNR were evaluated using the Mandard classification. Receiver operator characteristic analysis was performed and area under the curve (AUC) calculated to evaluate the discriminatory ability of FDG-PET-CT and CECT to predict ypT3-4 or pN positive disease. Clinicopathological characteristics were compared using the Chi-squared test. Results 91/104 patients underwent surgical resection following NACT. Four patients (3.8%) had metastatic disease identified on FDG-PET-CT only. None had metastatic disease identified on CECT only. The ability of FDG-PET-CT and CECT to predict ypT stage was comparable. However, FDG-PET-CT demonstrated better discriminatory ability (FDG-PET-CT; AUC 0.71, CECT; AUC 0.62, p=0.210). FDG-PET-CT was more accurate for ypT0-2 tumours (p=0.022), whilst CECT was superior for ypT3-4 tumours (p=0.002). The ability of both modalities to predict ypN1-3 disease was poor (FDG-PET-CT; AUC 0.55, CECT; AUC 0.53, p=1.00). Metabolic response on FDG-PET-CT was predictive of pTR (AUC 0.71, p&amp;lt;0.001) and pNR (AUC 0.75, p=0.010). Conclusions FDG-PET-CT after NACT identified occult metastatic disease undetected by CECT in a number of patients in this cohort, preventing futile surgery. The accuracy of FDG-PET-CT and CECT to predict ypT and ypN stage were comparable. However, CECT was more accurate for advanced tumours and FDG-PET-CT was superior for early tumours. Metabolic response on FDG-PET-CT after NACT was predictive of pathological response in both the primary tumour and LNs which may support pre-operative prognostication. These results suggest that concurrent CECT and FDG-PET-CT may be complementary for restaging and response assessment following completion of NACT prior to surgical resection.

Most Siewert type II esophagogastric junction adenocarcinomas in Chinese patients lack a Barrett esophagus background

The histological origins and classification of Siewert II esophageal gastric junction (EGJ) adenocarcinomas are controversial. While the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system suggests that they be classified as esophageal cancer, some scholars insist that these cancers include a Barrett esophageal (BE) adenocarcinoma form and a gastric adenocarcinoma form. To obtain data relevant to this debate, in this study, a multi-center sample of 25 cases of Siewert II EGJ adenocarcinoma spanning a 6-year period were analyzed. The endoscopic characteristics of the tumor lesions and pathology characteristics of peritumoral mucosal background in biopsies were determined. Cases were classified as esophageal adenocarcinoma if the tumor center was located on the oral side of the EGJ and accompanied by BE. They were classified as gastric adenocarcinoma if the tumor center was located on the anal side of the EGJ and accompanied by atrophic gastritis. Of the 25 cases examined, 20 had evaluable background mucosal data, including 14 (56 %) classified as gastric adenocarcinoma and 3 (12 %) classified as BE adenocarcinoma. The remaining 3 cases (12 %) did not have signs of BE or atrophic gastritis, and thus were not classified. Siewert type II EGJ adenocarcinoma cases in China were found to be heterogeneous, with most cases being consistent with gastric adenocarcinoma. Thus, it would not be reasonable to classify all Siewert type II EGJ adenocarcinomas as esophageal cancer.

Prognostic Implications of Various Surgical Procedures and Postoperative Margin Status in Gastroesophageal Junction Tumors.

Esophagogastric junction (EGJ) carcinomas often require access to two compartments of the body for good margin and lymphadenectomy. Whether it is required to do so in all patients is debatable. We analyzed outcomes of patients who underwent surgeries for EGJ carcinomas in terms of margin status and survival. This is a retrospective analysis of a prospectively maintained database of patients with EGJ adenocarcinomas operated between January 2014 and December 2016. Type of surgery performed and its impact on margin status and survival were assessed. Follow-up was for a minimum of 5 years. Ninety-four patients with EGJ carcinomas were operated on during the study period. Eight (8.51%) had involved proximal margin, and 2 of these had positive distal margin also. None had distal margin alone involved. Seventeen (18.09%) and 5 (5.32%) had a close proximal and distal margin, respectively. Radial margin was close/involved in 6 (6.38%) patients. Five-year overall survival and disease-free survival for the cohort was 38% and 30.8%, respectively. Proximal gastrectomy had a higher proximal margin positivity. Positive proximal or distal margin and a close/involved radial margin were detrimental to disease free survival and overall survival. Proximal gastrectomy is associated with a higher likelihood of proximal margin positivity. Positive margin leads to lower survival. Whether involvement of margins is just a surrogate marker of aggressive tumor or is an error in assessing extent tumor needs to be studied. Large-scale prospective studies in this regard are desirable.

ApoA-I and ApoB levels, and ApoB-to-ApoA-I ratio as candidate pre-treatment biomarkers of pathomorphological response to neoadjuvant therapy in gastric and esophago-gastric junction adenocarcinoma.

&lt;b&gt;&lt;br&gt;Introduction:&lt;/b&gt; Neoadjuvant chemotherapy (NAC) is a part of the current standard of care in a locally advanced gastric adenocarcinoma (GA) and esophagogastric junction adenocarcinoma (EGJA), but only patients with good pathomorphological response (pR) to NAC benefit from prolonged overall survival.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Aim:&lt;/b&gt; The study aims to evaluate ApoA-I and ApoB as candidate pre-treatment biomarkers of pR to NAC in patients with GA and EGJA.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Materials and methods:&lt;/b&gt; Serum samples were collected from 18 patients with GA and 9 with EGJA before the initiation of NAC to determine the ApoA-I and ApoB levels. After NAC tumor regression grade (TRG) was evaluated in resected specimens according to the Mandard's tumor regression grading system and correlated with pre-treatment ApoA-I and ApoB serum concentration, and ApoB-to-ApoA-I serum concentration ratio.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Results:&lt;/b&gt; We found a positive correlation of ApoA-I level and pR (95% CI: -0.863 to -0.467; P &lt; 0.0001), a negative correlation of ApoB level and pR (95% CI: 0.445 to 0.857; P &lt; 0.0001), a negative correlation of ApoB-to-ApoA-I ratio and pR (95% CI: 0.835 to 0.964; P &lt; 0.0001).&lt;/br&gt; &lt;b&gt;&lt;br&gt;Conclusions:&lt;/b&gt; ApoA-I and ApoB levels, and ApoB-to-ApoA-I ratio are candidate pre-treatment predictors of pR to NAC in GA and may help to guide personalized therapy.&lt;/br&gt;Our work fits into the dynamically developing trend of personalized treatment. It describes a potentially important rationale for further evaluation of apolipoprotein A-I and apolipoprotein B as predictors of cancer response to neoadjuvant therapy.

278. MEDIASTINOSCOPIC ESOPHAGECTOMY WITH INTRAOPERATIVE NERVE MONITORING FOR ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA; A SINGLE-CENTER INITIAL EXPERIENCE

Abstract Background In recent years, adenocarcinoma of esophagogastric junction (EGJ) has been on the increase in Japan. Although laparoscopic resection by the transhiatal approach is commonly used, patients often have difficulty with mediastinal lymph node dissection and reconstruction after resection. Since 2020, we have been performing mediastinoscopic esophagectomy for EGJ adenocarcinoma patients with esophageal invasion exceeding 3 cm in length or with a large tumor diameter. We report on the short-term results of the surgery performed. Methods Of 15 patients with adenocarcinoma of the esophagogastric junction who underwent radical esophagectomy at our hospital during a 36-month period from January 2020 to December 2022, 5 patients underwent mediastinoscopic esophagectomy without thoracic incisions. Surgery consisted of mediastinoscopic and laparoscopic subtotal esophagectomy, mediastinal lymph node dissection, and posterior mediastinal gastric tube reconstruction with cervical anastomosis. In all cases, continuous left recurrent nerve monitoring was performed intraoperatively. Short-term surgical outcomes were evaluated in terms of age, gender, TNM classification, stage, preoperative complications, operation time, blood loss, tumor diameter, length of esophageal invasion, postoperative complications, and postoperative hospital stay. Results All five patients were male, with a mean age of 67.8 years. 4 of the 5 patients had preoperative complications. Tumor localization was Siewert classification type I in 4 patients and type II in 1. The average tumor length and esophageal invasion length was 44 ± 26 mm and 38 ± 11 mm respectively. The average operation time was 395 ± 29 minutes and blood loss was 38 ± 39 mL. Lymph node metastases was revealed in three patients. No postoperative anastomotic leakage or recurrent nerve palsy was observed. One patient developed postoperative aspiration pneumonia but was cured without reintubation. Conclusion Mediastinoscopic esophagectomy for EGJ adenocarcinoma was performed safely. RCTs conducted in Western countries reported that esophagectomy with cervical anastmosis is associated with higher rates of recurrent nerve palsy than esophagectomy by the transhiatal approach. The use of a mediastinoscope to visualize the recurrent nerve and the use of intraoperative nerve monitoring devices might reduce the frequency of recurrent nerve palsy.

Surveys on diagnosis and treatment of esophagogastric junction adenocarcinoma by the Chinese Laparoscopic Gastrointestinal Surgery Study Group-10 Research Team

Objective: To investigate the diagnosis and treatment of esophagogastric junction (AEG) adenocarcinoma by members of the Chinese Laparoscopic Gastrointestinal Surgery Study Group (CLASS)-10 research team. Methods: A questionnaire was distributed to the CLASS-10 study group, which consists of investigators and research assistants from 32 centers in China, all of whom are gastric surgeons. The questionnaire was administered before the start of the study (2020) and mid-study (2022). The survey was developed to address the participants'perceptions of surgical consultation and management of AEG and included three main areas: diagnosis, surgical treatment, and perioperative management. In the second survey, the first two sections of the initial questionnaire were supplemented: the diagnosis section with a survey on the respondent's title, type of hospital, and definition of AEG, and the surgical treatment section with a survey on the perception of inferior mediastinal lymph node dissection as addressed in the CLASS-10 study. Respondents' clinical perceptions of AEG were recorded and the differences in perceptions between the two surveys analyzed. Results: Thirty-two and 34 questionnaires were returned in the first and second surveys, respectively. Regarding the definition of AEG adenocarcinoma, the highest acceptance rate was for the Chinese expert consensus (18/34, 52.9%), in which they are defined as lesions whose epicenter is located within 5 cm proximal or distal to the esophagogastric junction (EGJ) and crossing or touching the EGJ. Regarding the anatomic landmark for the EGJ, the percentage of respondents choosing the dentate line increased from 68.8% (22/32) to 88.2% (30/34) (P=0.143) between the two surveys. As to assessment of the longitudinal diameter and epicenter, the percentage of respondents choosing gastroscopy increased from 53.1% (17/32) to 73.5% (25/34) (P=0.040). Regarding the landmark for EGJ in surgical specimens, the percentage of respondents choosing the dentate line increased from 59.4% (19/32) to 85.3% (29/34) (P=0.027). In 2022, 82.4% (28/34) respondents reported that they were "skilled" in inferior mediastinal lymph node dissection for AEG. As to a safe proximal margin, the percentage of respondents choosing "≥1 cm, <2 cm" increased from 6.3% (2/32) to 26.5% (9/34) (P=0.158). Regarding the means of determining a safe proximal margin when the tumor is not infiltrating the serosa, the percentage of respondents choosing "intraoperative palpation" increased from 3.1% (1/32) to 23.5% (8/34), whereas those choosing "intraoperative gastroscopy" decreased from 62.5% (20/32) to 35.3% (12/32) (P=0.018). Conclusions: In the CLASS10 research team, the most commonly adopted definition of AEG was the Chinese expert consensus definition. We identified an increasing trend for choosing "endoscopy" and the "dentate line" when diagnosing AEG. Further, the definition of a safe proximal margin had decreased.

Clinical characteristics and prognostic outcomes for adenocarcinoma of esophagogastric junction in early-onset patients: a population-based appraisal.

Malignancies of the upper gastrointestinal tract are rare in early-onset patients outside the hereditary genetic disorders. There are few reports describing adenocarcinoma of the esophagogastric junction (AEG) in extremely early-onset patients aged under 50years old. The aim of this study was to describe the clinicopathological features and prognosis of adenocarcinoma of esophagogastric junction (AEG) in early-onset patients among three successive periods: 1975-1989 (period 1), 1990-2004 (period 2), and 2005-2017 (period 3). Between 1975 and 2017, data were extracted from the Surveillance, Epidemiology, and End Results database, and 18,278 patients with AEG were enrolled. Three age groups of patients were identified: < 50, 50-69, and ≥ 70years of age. Clinicopathological characteristics and prognostic outcomes were reviewed and compared among three groups over three periods (1975-89, 1990-04, and 2005-2017). Multivariate Cox regression analysis was performed to adjust for covariate effects related to both overall survival (OS) and cancer-specific survival (CSS). Among three age groups, early-onset patients were more likely to present with higher tumor grade, advanced nodal, and distant metastatic disease at diagnosis than other groups (p < 0.01 for both). In comparison to the older group, a higher proportion of patients in the early-onset group received chemotherapy and radiation treatment. After adjusting for covariates, early-onset patients had a better CSS and OS than elderly patients. Early-onset AEG patients were more likely than other age groups to present with advanced disease upon diagnosis. However, the prognosis of early-onset patients was better than their older counterparts after adjustment for covariates. The dissimilarities in tolerance to treatment among early-onset, middle-aged, and elderly patients could be the reason for this difference.

Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G)

BackgroundTrifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab (RAM) as third- or later-line treatments for advanced GC or EGJ cancer, there have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy. Therefore, we have started a randomised phase II trial to evaluate the efficacy and safety of FTD/TPI plus RAM compared with FTD/TPI monotherapy as third- or later-line treatments in patients with advanced GC and EGJ adenocarcinoma.MethodsThis RETREVE trial (WJOG15822G) is a prospective, open-label, randomised, multicentre phase II trial comparing FTD/TPI plus RAM versus FTD/TPI monotherapy in a third- or later-line setting. Eligibility criteria include age of > 20 years; performance status of 0 or 1; unresectable or recurrent gastric or EGJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. FTD/TPI (35 mg/m2 twice daily, evening of day 1 to morning of day 6 and evening of day 8 to morning of day 13) was administered orally every 4 weeks, and RAM (8 mg/kg) was administered intravenously every 2 weeks. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, objective response rate, disease control rate, and safety. The expected hazard ratio of PFS is set as 0.7, assuming 4-month PFS rate of 27% in FTD/TPI monotherapy and 40% in FTD/TPI plus RAM. The number of subjects was 110, with a one-sided alpha error of 0.10 and power of 0.70.DiscussionThis study will clarify the additional effect of RAM continuation beyond disease progression on FTD/TPI in the third- or later-line setting for patients with advanced GC or EGJ cancer.Trial registrationjRCTs041220120.

Histological study of the structural layers around the esophagus in the lower mediastinum.

In Japan, the transhiatal approach, including lower mediastinal lymph node dissection, is widely performed for Siewert type II esophagogastric junction adenocarcinoma. This procedure is generally performed in a magnified view using laparoscopy or a robotic system, therefore, the microanatomy of the lower mediastinum is important. However, mediastinal microanatomy is still unclear and classification of lower mediastinal lymph nodes is not currently based on fascia or other microanatomical structures. To clarify the fascia and layer structures of the lower mediastinum and classify the lower mediastinal tissue. We dissected the esophagus and surrounding organs en-bloc from seven cadavers fixed in 10% formalin. Organs and tissues were then cut at the level of the lower thoracic esophagus, embedded in paraffin, and serially sectioned. Tissue sections were stained with Hematoxylin-Eosin (all cadavers) and immunostained for the lymphatic endothelial marker D2-40 (three cadavers). We observed the periesophageal fasciae and layers, and defined lymph node boundaries based on the fasciae. Lymphatic vessels around the esophagus were observed on immunostained tissue sections. We identified two fasciae, A and B. We then classified lower mediastinal tissue into three areas, paraesophageal, paraaortic, and intermediate, using these fasciae as boundaries. Lymph nodes were found to be present and were counted in each area. The dorsal part of the intermediate area was thicker on the caudal side than on the cranial side in all cadavers. On the dorsal side, no blood vessels penetrated the fasciae in six of the seven cadavers, whereas the proper esophageal artery penetrated fascia B in one cadaver. D2-40 immunostaining showed lymphatic vessel connections between the paraesophageal and intermediate areas on the lateral and ventral sides of the esophagus, but no lymphatic connection between areas on the dorsal side of the esophagus. Histological studies identified two fasciae surrounding the esophagus in the lower mediastinum and the layers separated by these fasciae were used to classify the lower mediastinal tissues.

Efficacy of machine learning models versus Cox regression model for predicting prognosis of esophagogastric junction adenocarcinoma

To compare the performance of machine learning models and traditional Cox regression model in predicting postoperative outcomes of patients with esophagogastric junction adenocarcinoma (AEG). This study was conducted among 203 AEG patients with complete clinical and follow-up data, who were treated in our hospital between September, 2015 and October, 2020. The clinicopathological data of the patients were processed for analysis using R language package and divided into training and validation datasets at the ratio of 3:1. The Cox proportional hazards regression model and 4 machine learning models were constructed for analyzing the datasets. ROC curves, calibration curves and clinical decision curves (DCA) were plotted. Internal validation of the machine learning models was performed to assess their predictive efficacy. The predictive performance of each model was evaluated by calculating the area under the curve (AUC), and the model fitting was assessed using the calibration curve. For predicting 3-year survival based on the validation dataset, the AUC was 0.870 for Cox proportional hazard regression model, 0.901 for eXtreme Gradient Boosting (XGBoost), 0.791 for random forest, 0.832 for support vector machine, and 0.725 for multilayer perceptron; For predicting 5-year survival, the AUCs of these models were 0.915, 0.916, 0.758, 0.905, and 0.737, respectively. For internal validation, the AUCs of the 4 machine learning models decreased in the order of XGBoost (0.818), random forest (0.758), support vector machine (0.0.804), and multilayer perceptron (0.745). The machine learning models show better predictive efficacy for survival outcomes of patients with AEG than Cox proportional hazard regression model, especially when proportional odds assumption or linear regression models are not applicable. XGBoost models have better performance than the other machine learning models, and the multi-layer perception model may have poor fitting results for a limited data volume.

Accurate Preoperative Evaluation of the Location of Esophagogastric Junction Adenocarcinoma Using Positron Emission Tomography-Computed Tomography.

The surgical procedure for esophagogastric junction (EGJ) adenocarcinoma usually depends on the location of its epicenter or proximal margin, but accurate evaluation of these positions is often difficult. The usefulness of positron emission tomography-computed tomography (PET-CT) for this purpose is unknown. Between June 2005 and February 2015, we enrolled 30 patients with cT2-4 EGJ adenocarcinoma (Siewert type I/II) who underwent surgical resection. We ascertained the sensitivity and specificity of preoperative PET-CT for identifying the primary tumor and regional lymph node metastasis, and compared PET-CT and pathological findings in terms of the distance from the EGJ to the tumor epicenter or proximal tumor margin. PET-CT detected the primary tumor with a sensitivity of 97% (29/30), and detected lymph node metastasis with a sensitivity and specificity of 22% (4/18) and 100% (8/8), respectively. No significant association was observed between the maximal standardized uptake value and histological type, tumor size, or pT status. Regarding the accuracy of evaluating tumor location, the median differences between PET-CT and pathological measurements were .6cm for the tumor epicenter and .5cm for the proximal margin from the EGJ. PET-CT and pathological findings showed agreement regarding Siewert classification type (I or II) and lengths of esophageal involvement exceeding 4cm or 2cm in 77% (10/13), 85% (11/13), and 85% (11/13) of cases, respectively. PET-CT had high sensitivity for primary EGJ adenocarcinoma. It may effectively locate the tumor epicenter and proximal margin and thus help clinicians determine the optimal surgical procedure.