Adenocarcinoma Of Esophagogastric Junction Research Articles

Accuracy of the preoperative estimation of esophageal invasion length of adenocarcinoma of the esophagogastric junction and its discrepancy with the pathological measurement.

The incidence of esophagogastric junction (EGJ) adenocarcinoma has increased worldwide. As the EGJ is located at the boundary between the thoracic and abdominal cavities, the optimal surgical approach is a subject of debate and estimation of the esophageal invasion length (EIL) is an important factor in its selection. Data from our in-house database were extracted for consecutive patients with Siewert type I, II and III EGJ adenocarcinoma (EIL ≤ 4cm), who underwent transhiatal or transthoracic surgical resection between 2010 and 2016. The clinical records of these patients were reviewed and the accuracy of EIL estimation and its discrepancy with the pathological measurement were analyzed. A total of 82 patients were included in the final analysis. We established that EIL was underestimated in 49 of these patients (59.8%). The mean-distance discrepancy between the preoperative and pathological diagnosis of EIL in the underestimation group was 7.0mm. Multivariate analysis revealed that submucosal cancer spread was an independent risk factor for underestimation (P < 0.01). The mean length of submucosal cancer spread was longer for undifferentiated histologic type EGJ adenocarcinomas. (P < 0.01). The EIL was underestimated in approximately 60% of EGJ adenocarcinomas requiring surgical treatment. Thus, careful management is necessary, especially for EGJ adenocarcinoma of the undifferentiated histologic type.

Outcomes of Microscopic Residual Tumor after Curative-Intent Surgery in Adenocarcinoma of Esophagogastric Junction

Objective: Radical surgery is the mainstay treatment for adenocarcinoma of the esophagogastric junction. The presence of microscopic residual tumor tissue after curative-intent surgery is associated with recurrence. This study compared the outcomes of patients with microscopic residual tumor (Residual+ group) and those without microscopic residual tumor (Residual- group). Material and Methods: We retrospectively reviewed the medical records of 71 patients with adenocarcinomas of the esophagogastric junction who underwent curative-intent surgery between January 2005 and August 2018. We evaluated the clinical and pathological characteristics and compared recurrences, rates and patterns, between groups. Five-year overall survival (OS) and 3-year disease-free survival (DFS) were analyzed by Kaplan-Meier analysis. Results: Nineteen (26.8%) patients had microscopic residual tumors, consisting of 8 (11.3%) with positive resection margins, 10 (14.0%) with malignant cells from peritoneal washing fluid cytology, and 1 (1.4%) with both. The median OS in the Residual- group was significantly better than that in the Residual+ group (31.3 vs 11.9 months, P = 0.003). The Residual- group had better 5-year OS (26.2% vs 11.9%, P = 0.015) and 3-year DFS (24.4% vs 9.8%, P = 0.003) than the Residual+ group. During follow-up period, 48% of the patients in the Residual+ group experienced recurrent disease, with a median follow-up time at 7.7 months. Distant metastasis was the most common site of recurrence. Conclusion: Microscopic residual tumor after resection is associated with poorer survival outcomes and higher recurrence rates. Curative surgery should aim to achieve R0 resection in all patients with resectable adenocarcinomas of the esophagogastric junction.

FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor.

The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.

Analysis of risk factors for intraoperative bleeding in patients with Siewert type II esophagogastric junction adenocarcinoma treated by two minimally invasive surgeries and its influence on prognosis: a retrospective study.

The present study aimed to analyze the independent risk factors for intraoperative bleeding in Siewert II adenocarcinoma of the esophagogastric junction (AEG) using two minimally invasive surgical approaches, namely, the laparoscopy-assisted abdominal trans-hiatal (LTH) method and transthoracic-laparoscopic esophagectomy (TLE). The clinical data of 100 patients with SiewertII AEG admitted to our hospital from October 2017 to October 2020 were retrospectively analyzed. According to the type of surgery, the patients were divided into LTH approach group and TLE approach group. The differences between the clinical characteristics of the patients in different groups and the differences in the intraoperative bleeding and prognosis between different surgical procedures were analyzed and compared using the t-test and chi-squared test. Multiple linear regression was used to identify the independent risk factors affecting the amount of intraoperative bleeding in patients. The results of this study showed that patients in the LTH group had significantly less intraoperative bleeding and operative time and significantly better postoperative recovery than the TLE group. The results of multivariate linear regression showed that the combined trans-thoracic-abdominal approach (P=0.000), advanced age (P=0.014), larger BMI (P=0.000), and larger tumor diameter (P=0.001) were the independent risk factors influencing the increase in intraoperative bleeding. In addition to the conventional factors that affect intraoperative bleeding, such as the patient's general condition, operation time, and tumor size, LTH surgery is another way to avoid intraoperative bleeding for Siewert type II AEG patients and can significantly improve postoperative recovery.

Systemic Therapy of Gastric Cancer—State of the Art and Future Perspectives

Background: The prognosis of patients diagnosed with locally advanced and metastatic gastric and esophago-gastric junction cancer is critical. The optimal choice of systemic therapy is essential to optimize survival outcomes. Methods: A comprehensive literature review via PubMed and analysis of major oncology congresses (European Society for Medical Oncology and American Society of Clinical Oncology websites) were conducted to ascertain the current status and latest developments in the systemic treatment of patients with localized or advanced gastric and esophago-gastric junction adenocarcinoma. Results: While neoadjuvant and perioperative chemotherapy for localized tumor stages is the preferred approach in the Western Hemisphere, adjuvant chemotherapy remains the preferred course of action in East Asia. The administration of chemotherapy, typically in the form of combinations comprising platinum and fluoropyrimidine compounds in combination with docetaxel, represents a standard of care. Investigations are underway into the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most appropriate therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine biomarkers such as HER2 expression, PD-L1 combined positive score (CPS) (combined positive score), Claudin 18.2, and microsatellite instability (MSI). In the present clinical context, the standard first-line therapy is a combination of fluoropyrimidine and a platinum derivative. The selection of chemotherapy in combination with antibodies is contingent upon the specific biomarker under consideration. Conclusions: This article reviews the current state of the art based on recent clinical trial results and provides an outlook on the future of systemic therapy.

The impact of histological subtype on postoperative recurrence pattern and timing in locally advanced esophagogastric junction cancer

PurposeThe differences in tumor behavior between adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagogastric junction (EGJ) have yet to be well investigated. The purpose of this study was to gain insights that can contribute to tailored treatments and follow-up strategies by analyzing the correlation between histological subtypes and oncological outcomes.MethodsA retrospective analysis was used to determine the characteristics of the histological subtypes of EGJ cancer by comparing the appearance of postoperative recurrence. A total of 102 consecutive patients with pathological stage IIA to IVA EGJ cancer, who underwent R0 surgery in our department from 2004 to 2020, were enrolled. The recurrence pattern, timing, survival, and potential prognostic factors were compared.ResultsAfter a median follow-up time of 70.1 months, the AC group demonstrated comparable lymph node failure-free survival (P = 0.291) and significantly worse non-lymphogenous recurrence-free survival (P = 0.035) than did the SCC group. A significantly longer period from surgery to recurrence was also observed in the AC group (P = 0.029). Multivariate analysis indicated that histological subtype (P = 0.015, 95% CI 1.24–7.28) was significantly correlated with the incidence of non-lymphogenous recurrence.ConclusionsThe pattern and timing of postoperative recurrence were significantly different between the histological subtypes of EGJ cancer. Compared with EGJ SCC, EGJ AC may have a greater tendency toward non-lymphogenous progression and a greater propensity for longer surgery-to-recurrence periods.

Combination of immune checkpoint inhibitors and radiotherapy in locally advanced esophagogastric junction adenocarcinoma: A review

AbstractEsophagogastric adenocarcinoma (EGJ‐AC) poses a significant global health burden, characterized by high incidence rates and poor prognosis. Despite advancements in treatment modalities, including surgery, chemotherapy, and radiation therapy (RT), locally advanced EGJ‐AC management remains challenging. Various preclinical and clinical studies have provided insights into the synergistic effects of combining immune checkpoint inhibitors (ICIs) with RT, further supporting the combination therapy in EGJ‐AC. Immunotherapy, particularly ICIs, has emerged as a promising therapeutic approach in various malignancies, including EGJ‐AC. This narrative review aims to critically examine the rationale behind combining ICIs with standard treatment modalities, including RT or chemoradiotherapy, in the preoperative setting for locally advanced EGJ‐AC. A comprehensive literature search identified eight phase 2 randomized clinical trials evaluating the safety profile and oncologic outcomes of adding ICI agents to neoadjuvant chemoradiotherapy in this population. The results of enrolled trials show that the combination of ICIs with standard treatment modalities is a promising approach for improving survival and pathological response in patients with locally advanced EGJ‐AC. This combination treatment was associated with mostly grade 1–2 immune‐related toxicities, indicating its safety and tolerability. There were higher rates of complete or major pathologic responses compared to historical controls. Further studies, including large‐scale randomized controlled trials, are needed to address remaining questions regarding the efficacy, safety, and long‐term outcomes of combination therapy in this population.

Advanced esophagogastric junction mixed neuroendocrine–non-neuroendocrine neoplasm with long-term recurrence-free survival

BackgroundMixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) is a rare malignant gastrointestinal tumor. The prognosis of patients with MiNEN is poor because of the high frequency of recurrence and metastases. We report a case of esophagogastric junction MiNEN (EGJ-MiNEN) with a long-term recurrence-free survival of 5.5 years.Case presentationA 58-year-old male patient underwent thoracoscopic esophagectomy for esophagogastric junction adenocarcinoma. The patient’s postoperative course was uneventful. R0 resection was achieved, and the pathological diagnosis of the surgical specimen was pT3N2M0 Stage IIIA (according to the Japanese Classification of Gastric Cancer, 4th edition). Based on the pathology results, the patient was treated with postoperative adjuvant therapy with oral S-1. The patient maintained recurrence-free survival for 5.5 years postoperatively. However, 6 years postoperatively, the patient visited our department with cachexia. Computed tomography (CT) revealed a large amount of ascites and pleural effusion. He rapidly developed a poor circulatory and respiratory status and died 16 days after admission. An autopsy revealed severe bloody ascites and pleural effusion, as well as numerous nodules on the pleura and mesentery. Immunohistochemistry of the nodules revealed positivity for chromogranin A, Synaptophysin A, neural cell adhesion molecule (NCAM or CD56), and insulinoma-associated protein 1 (INSM1). The specimen showed a mixture of adenocarcinoma and neuroendocrine cell carcinoma and was diagnosed as MiNEN. Retrospective immunostaining of the surgical specimen showed similar results, and we diagnosed the patient with recurrence of EGJ-MiNEN.ConclusionMiNEN has a poor prognosis; however, in some cases, long-term recurrence-free survival is achieved with radical resection and adjuvant chemotherapy.

556. PREDICTORS OF EARLY RECURRENCE AFTER OESOPHAGECTOMY AND NEOADJUVANT FLOT

Abstract Background FLOT, a novel type of perioperative chemotherapy, has led to improved survival after surgery for oesophageal adenocarcinoma. Yet, rates of cancer recurrence remain high. There is limited research on predictors for early recurrence (ER) in patients receiving FLOT. The aim of this study was to investigate ER and survival rates and identify risk factors of ER. Methods Patients who underwent neoadjuvant FLOT and oesophagectomy for oesophageal and oesophagogastric junction adenocarcinomas at a single high-volume centre between August 2018 and January 2023 were evaluated for ER, defined as disease present within one year of surgery. Multivariable logistic regression was conducted to identify risk factors for ER. Patients who died in-hospital or within 90 days of surgery and those with positive longitudinal margin were excluded. Results 145 patients were included. 139 (95.9%) and 63 (43.4%) patients fully completed neoadjuvant and adjuvant FLOT. 44 patients (30.3%) developed recurrence and 22 patients (15.2%) had ER in the follow up period. Distant, local or mixed type of recurrence was found in 32, 6 and 6 patients respectively. The estimated recurrence free survival and overall survival at one, two and three years were 81.4%, 66.9%, 52.0% and 89.0%, 73.7%, 65.5% respectively. The estimated median survival after recurrence was 4.9 months. In multivariable analysis ypN3 status was identified to be an independent predictor of ER (OR 13.769, 95%CI 1.358-139.573, p=0.026). Conclusions This study confirms that ER after neoadjuvant FLOT is common. Patients with a high pathological nodal stage are particularly at risk. It is possible that some patients with ER might have undetected metastases prior to surgery and some do not respond well to neoadjuvant treatment. Identifying chemotherapy non-responders is an important area for future research. These results might be beneficial for prognostication and tailoring follow up care, such as regular surveillance imaging, treatment, and frequency of reviews.

566. SUPERIOR MEDISTINAL LYMPHADENECTOMY IN PRONE POSITION UTILIZING 3D-ASSISTED THORACOSCOPY. A NOVEL APPROACH

Abstract Introduction Routine lymphadenectomy during esophagectomy includes 2-field lymphadenectomy for distal-esophageal or esophago-gastric junction adenocarcinoma. Superior mediastinal lymphadenectomy (SML) refers to extended 2-field lymphadenectomy (right or left para-tracheal nodes) or total mediastinal lymphadenectomy. The exact benefits of (SML) have long been debated, but with the evolution of prone position 3D-assisted thoracoscopy favorable outcomes can be achieved in the hand of experts. Aim This study aims to describe our surgical technique of 3D-assisted thoracoscopic SML during minimally invasive esophagectomy in prone position. Material and Methods SML included right paratracheal nodes and lymph nodes (LNs) along the right recurrent laryngeal nerve throughout its mediastinal route (including the paratracheal-retrocaval compartment) in cases of extended 2-field lymphadenectomy, as well as left paratracheal nodes and LNs along the left recurrent laryngeal nerve during total mediastinal lymphadenectomy. Results Among the identified eligible cases (n=30), there was no mortality at 30- or 90-post-operative days. No anastomotic or chyle leaks were observed. Pulmonary complications occurred in 15% of patients; right recurrent laryngeal nerve palsy was noted in one patient (3.3%). The median number of resected LNs was 45, with a median count of 12 SML LNs. Conclusions Although limited by a small cohort sample, this study suggests that minimally invasive esophagectomy with SML may offer some benefits in terms of oncological outcomes without significant additional morbidity. https://wetransfer.com/downloads/6329dbd1f817d7e492f8905291f946e120240309180637/42ee79017067b59a4a73138377d9d95620240309180649/f28a32

807. A REVISED APPROACH TO THE ESOPHAGOGASTRIC JUNCTION: A MODIFIED SIEWERT CLASSIFICATION

Abstract Background Esophagogastric junction (EGJ) adenocarcinomas are challenging due to their anatomical and histopathological features and treated either as part of the esophagus or stomach cancers. Siewert (S) and Nishi classifications rely on the tumor’s epicenter to guide treatment decisions, which can lead to diagnostic and therapeutic inconsistencies. Moreover, recent studies helped define the optimal extent of lymphadenectomy for EGJ cancers. Here we present our standardized approach to EGJ cancers that integrates these insights, providing a framework to guide clinical decision-making. Methods Our modified classification relies on tumor extent rather than the epicentre, based on endoscopic measurement of the proximal and the distal limits, and the exact location of the EGJ. This approach classifies tumors based on their extent which results into six categories: SI, SI/II, SII, SII/III, SIII, and SI/II/III. Lower esophageal tumors whose distal limit lies between + 1cm and -2cm are classified as I/II. Cardia tumors whose proximal limit falls between those boundaries are II/III. Tumors that span more cephalad than + 1cm and more distally than – 2cm, are I/II/III. For Siewert I, I/II and II tumors, surgical management depends on the extent of esophageal involvement, mainly dictated by the probability of mediastinal basement nodal involvement, as defined by Kurokawa et al (2019). Additionally, a 3-field lymphadenectomy is performed when there is involvement of the cervical or recurrent laryngeal nerve lymph node stations. Results In SI, SI/II, and SI/II/III, with esophageal involvement exceeding 4 cm we favor a transthoracic esophagectomy (TTE) with total thoracic lymphadenectomy. If the involvement is between 1-4 cm, a transhiatal esophagectomy (THE) with lower mediastinal lymphadenectomy is performed. In SII, THE is done for 0-1 cm of involvement; absence of esophageal involvement permits a transhiatal extended total gastrectomy (eTG) with abdominal D2 lymphadenectomy and intra-operative margin status assessment via frozen sections. In SI/II/III and esophageal involvement of more than 4 cm, TTE is required; for esophageal involvement of 1-4 cm, we perform a THE and total gastrectomy with abdominal D2 lymphadenectomy based on distal margin findings. Conclusion This proposed modification to the classification of EGJ adenocarcinomas introduces a comprehensive framework that is tailored to the extent of tumor involvement. By addressing the limitations of existing systems and incorporating current insights, this updated classification aims to improve patient categorization and standardize treatment protocols, potentially leading to enhanced clinical outcomes.

245. ESOPHAGECTOMY AFTER NEOADJUVANT CHEMOTHERAPY WITH AN INDICATION FOR CONVERSION SURGERY FOR HIGHLY ADVANCED ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA

Abstract Background There is currently no strong evidence for preoperative chemotherapy for advanced esophagogastric junction adenocarcinoma. Furthermore, no curative treatment strategy has been established for advanced junction adenocarcinoma, including Stage IV disease, with no indication for conversion surgery. Subjects and Methods In this study, we retrospectively reviewed nine patients with highly advanced esophagogastric junctional adenocarcinoma, including Stage IV adenocarcinoma, who underwent systemic chemotherapy followed by planned resection at our hospital. Results The participants included 6 males and 3 females, with median age of 64 (range: 45–72) years. Pretreatment stages III, IVA, and IVB, categorized based on UICC TNM classification (esophageal adenocarcinoma), were observed in 1, 4, and 4 cases, respectively, with 1 case of (#104) subclavian lymph node metastases, 1 case of (#16) abdominal para-aortic lymph node metastases, and 2 cases of liver metastases, including multiple lesions. All patients received S-1 plus oxaliplatin (SOX) therapy as preoperative chemotherapy (2–40 courses). Although we observed one patient with unresectable abdomen malingnancies, the others underwent R0 resection, six underwent esophagectomy (with three total gastrectomy and one liver resection), and two open (+ continuous right thoracotomy) lower esophagectomy + total gastrectomy. Pathological stages I, II, III, and IV were observed in two, one, four, and one patients, respectively. Postoperatively, stereotactic irradiation, chemotherapy, and immune checkpoint inhibitors were administered to the patients to treat recurrent brain and liver metastases, and the 1-year survival rate was found to be 71.4% with a median observation period of 17 (range: 0–61) months. Among them, downstage and pN0 cases were relatively promising. Conclusion Even in highly advanced cases, cases with promising prognoses with multidisciplinary treatment, including surgery, were observed. We hope that large-scale clinical trials, such as JCOG2203, will help clarifying the significance of this approach, and advancements in chemotherapy regimens are expected.

504. SENTINEL LYMPH NODE NAVIGATED SURGERY IN ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA USING INDOCYANINE GREEN AND FLUORESCENCE IMAGING

Abstract Background Sentinel lymph node navigated surgery (SNNS) has been adopted for various cancers to reduce the negative impact of lymphadenectomy. Limited lymph node dissection using SNNS might be employed in the management of clinically lymph node negative early esophagogastric junction adenocarcinoma (EGJAC). However, it must be sure that sentinel lymph nodes (SLNs) reflect the patient's overall pN status. The aim of this study was to determine the feasibility and safety of SNNS using near-infrared fluorescence imaging and to obtain preliminary data about sensitivity of prediction of lymph node metastasis using SNNS. Methods Patients with cT1-2cN0 EGJAC without neoadjuvant therapy were prospectively included. One patient was enrolled after non-radical endoscopic resection of a high-risk pT1 tumor. Solution of indocyanine green (ICG) and 10% human serum albumin (ICG concentration 1,25mg/mL) was injected endoscopically into the submucosal layer at four quadrants (á 0.5mL) around the tumor or endoscopic resection scar just before the surgery. Subsequently, SLNs were identified and removed laparoscopically using fluorescence imaging. Then, esophagectomy or gastrectomy with radical lymphadenectomy were performed in all patients. Results A total of nine patients underwent SNNS followed by radical surgery. Histopathology revealed pT0pN0 in 1 patient, pT1bN0 in 3 patients, pT1bN3 in 1 patient, pT2pN1 in 2 patients, pT3pN0 in 1 patient and pT3pN2 in 1 patient. Overall, 62 SLNs were detected (median 7 SLNs per patient, range 1-16). Metastases in SLNs were found in four patients. All patients with pathologically positive lymph nodes had at least one SLN positive for metastasis. Sensitivity of prediction of pN positive status was 100%, false negative rate was 0%. There were no ICG-related adverse events or complications associated with SNNS procedure. Conclusion These results suggest that SNNS using ICG and fluorescence imaging in early EGJAC is feasible and safe. Our pilot data show promising diagnostic accuracy of predicting pathological lymph node status using SNNS. However, further studies with a larger number of patients are needed before introducing SNNS into clinical practice.

Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma.

Globally, more than 1 million new cases of gastric cancer were estimated in 2020, ranking fourth in cancer mortality. Currently although in resectable gastric cancer and esophagogastric junction (EGJ) adenocarcinoma a perioperative triplet chemotherapy regimen including a fluoropyrimidine, a platinum compound and docetaxel (FLOT) demonstrated a better overall survival, the survival rate is still very low, and a massive effort is still required to improve clinical prognosis. High microsatellite instability (MSI-H) status in gastric cancer is a favorable prognostic factor but poor data are available on its predictive role for perioperative FLOT chemotherapy in resectable gastric cancer. Here, we presented the case of two patients with advanced MSI-H gastric cancer/EGJ adenocarcinoma who had no residual tumor following neoadjuvant FLOT chemotherapy maintaining a complete response for more than 30 months, suggesting MSI-H status to be a positive prognostic marker also in patients treated with a taxane-containing triplet in this setting. We also discuss the future perspectives including the opportunity to achieve excellent clinical outcomes with immune checkpoint inhibitor (ICI)-based regimens.

Comparison of clinical efficacy between modified Kamikawa anastomosis in laparoscopic proximal gastrectomy and Roux-en-Y anastomosis in laparoscopic total gastrectomy

To investigate the short-term clinical efficacy of laparoscopic proximal gastrectomy with modified Kamikawa anastomosis and laparoscopic total gastrectomy with Roux-en-Y anastomosis. Retrospective cohort study was conducted. The clinicopathological data of 268 patients who underwent laparoscopic proximal gastrectomy for adenocarcinoma of esophagogastric junction and upper gastric adenocarcinoma from January 2016 to October 2022 were collected. Among 268 patients, 26 underwent laparoscopic proximal gastrectomy with modified Kamikawa anastomosis were assigned to Kamikawa group and 242 underwent laparoscopic total gastrectomy with Roux-en-Y anastomosis were assigned to Roux-en-Y group. The sex, age, BMI, preoperative albumin, maximum tumor diameter, histological grade, and pathological stage of patients in the Kamikawa group and the Roux-en-Y group were subjected to 1:1 propensity score matching. After matching, 16 patients in Kamikawa group and Roux-en-Y group were respectively included in this study. Outcome measures: (1) Intraoperative condition. (2) Postoperative recovery. (3) Follow-up information. The patients' nutritional status, reflux esophagitis and anastomotic stoma were investigated by outpatient and telephone follow-up. Nutritional status assessment comprising body mass index and Nutritional Risk Screening 2002 score. (1) Intraoperative condition. All patients successfully underwent laparoscopic proximal gastrectomy and total gastrectomy. Compared with Roux-en-Y group, the digestive tract reconstruction time in Kamikawa group was longer 93.0(74.0–111.0)min vs. 39.7(35.1–46.2)min, t = -2.001, P = 0.055., and the difference was statistically significant (P < 0.05). There was no statistically significant difference in total operation time and intraoperative blood loss (P > 0.05). (2) Postoperative recovery. There was no statistically significant difference between Kamikawa group and Roux-en-Y group in first anal exhaust time, first postoperative liquid intake time, postoperative hospitalization time, and postoperative complications (P > 0.05). (3) Follow-up information. All patients were followed up. BMI and NRS 2002 scores in Kamikawa group were better than those in Roux-en-Y group at 6 and 12 months after surgery 22.9 ± 3.0 kg/m2 vs. 20.8 ± 2.2 kg/m2, t = 2.165, P = 0.038; 23.1 ± 3.0 kg/m2 vs. 20.3 ± 2.2 kg/m2, t = 3.022, P = 0.005 and 2 (1–2) vs. 2 (1–3), Z = -2.585, P = 0.010; 2 (1–2) vs. 2 (1–3), Z = -2.273, P = 0.023., the difference was statistically significant (P < 0.05). There was no significant difference in GERD scale score and occurrence of ≥ Grade B reflux esophagitis at 6 and 12 months after surgery between Kamikawa group and Roux-en-Y group (P > 0.05). Anastomotic stenosis was not found in all patients by postoperative upper gastrointestinal angiography. Laparoscopic proximal gastrectomy with modified Kamikawa anastomosis is safe and feasible for the treatment of esophagogastric junction and upper gastric adenocarcinoma, and can achieve good anti-reflux effect. Besides, compared with traditional laparoscopic total gastrectomy, its postoperative nutritional status is better.

Presence of Fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers.

Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact. Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model. In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare. F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis.

Open left diaphragm method enables safe surgery with a good visual field in a laparoscopic transhiatal approach for esophagogastric junction adenocarcinoma laparoscopic transhiatal reconstruction via an open left diaphragm method.

Despite being oncologically acceptable for esophagogastric junction adenocarcinoma with an esophageal invasion length of 3-4cm, the transhiatal approach has not yet become a standard method given the difficulty of reconstruction in a narrow space and the risk of severe anastomotic leakage. This study aimed to clarify the safety and feasibility of the open left diaphragm method during the transhiatal approach for esophagogastric junction adenocarcinoma. This retrospective study compared the clinical outcomes of patients who underwent proximal or total gastrectomy with lower esophagectomy for Siewert type II/III adenocarcinomas with esophageal invasion via the laparoscopic transhiatal approach with or without the open left diaphragm method from April 2013 to December 2021. Overall, 42 and 13 patients did and did not undergo surgery with the open left diaphragm method, respectively. The median operative time was only slightly shorter in the open left diaphragm group than in the non-open left diaphragm group (369 vs. 482min; P = 0.07). Grade ≥ II postoperative respiratory complications were significantly less common in the open left diaphragm group than in the non-open left diaphragm group (17% vs. 46%, P = 0.03). Neither group had grade ≥ IV anastomotic leakage, and two cases of anastomotic leakage requiring reoperation were drained using the left diaphragmatic release technique. Transhiatal lower esophagectomy with gastrectomy using the open left diaphragm method is safe, highlighting its advantages for Siewert type II/III esophagogastric junction adenocarcinoma with an esophageal invasion length of ≤ 4cm.

Immune checkpoint inhibitor treatment in PD-L1-negative gastroesophageal cancer tumors.

e16062 Background: We aimed to investigate whether there is a subgroup of patients with gastroesophageal cancers who, despite having IHC-PD-L1 negative tumors, might still benefit from ICI treatment. Furthermore, the impact of ICI treatment on patients with tumors that are PD-L1 negative by IHC but exhibit high CD274 (PD-L1) expression remains undefined. Methods: 1,416 esophageal adenocarcinomas (EA), 486 esophageal squamous carcinomas (ES), 859 esophagogastric junction adenocarcinomas (EJA), and 1,613 gastric adenocarcinoma (GA) samples were analyzed using NGS of DNA (NextSeq, 592 genes and NovaSeq, WES) and RNA (NovaSeq, WTS) (Caris Life Sciences, Phx, AZ). PD-L1 IHC positivity was defined as &gt; 1% CPS (Agilent's 22c3). Correlation between PD-L1 CPS and CD274 expression (transcripts per million – TPM) were assessed by Spearman’s coefficient. Tumors were divided into CD274-H (high expression) and CD274-L (low expression) cohorts, representing the top 25% and bottom 25% of expression levels, respectively. Real-world overall survival (OS) data were obtained from insurance claims records and analyzed using Cox proportional hazards with hazard ratios (HR) and log-rank tests. Results: Weak correlations were observed between PD-L1 CPS and CD274 expression in adenocarcinoma histology tumors (EA: 0.374, EJA: 0.358, GA: 0.387), while a stronger correlation was found in squamous tumors (ES: 0.537). Median CD274 expression was significantly higher in PD-L1+ compared to PD-L1- ES tumors (2.65-fold) and in EA (1.68-fold), EJA (1.92-fold), and GA (1.96-fold) tumors (p &lt; 0.001). In PD-L1 IHC-negative ES, there was no association between CD274-H expression and OS (H 12.4 vs L 10.6 mo; HR 0.90, p = 0.48). However, in adenocarcinomas, CD274-H showed a slightly improved OS (12.8 vs 11.3 mo; HR 0.79, p &lt; 0.05). CD274-H trended towards worse post-Carboplatin/paclitaxel (CP) OS (ES: 13.8 vs 18.2 mo; HR 1.60; p = 0.22; Adenocarcinoma: 18.2 vs 27.4 mo; HR 1.50, p = 0.19). Interestingly, CD274-H was associated with improved post-CP/nivolumab survival in ES (96.5 vs 28 mo; HR 0.32; p = 0.047), with a similar but not statistically significant pattern in Adenocarcinoma EGC (Not Reached vs 30.2 mo; HR 0.39, p = 0.23). Furthermore, in CD274-L GEC, there was no difference in post-treatment survival with the addition of Nivolumab to CP (Squamous: 30 vs 18.2 mo; HR 0.91, p = 0.83; Adenocarcinoma: 30.2 vs 27.4 mo; HR 1.14; p = 0.76). In contrast, CD274-H showed improved survival with the addition of Nivolumab (Squamous: 96.5 mo vs 13.8 mo; HR 0.15; p = 0.01; Adenocarcinoma: NR vs 18.2 mo; HR 0.30; p = 0.08). Conclusions: High CD274 expression was associated with improved survival when Nivolumab was added to chemotherapy in patients with PD-L1-negative tumors. Further investigation is needed to confirm the potential benefits of Nivolumab treatment in gastroesophageal cancer patients with tumors that are PD-L1-negative by IHC but exhibit high mRNA expression.

Neoadjuvant serplulimab in combination with concurrent chemoradiotherapy for locally advanced, resectable esophagogastric junction adenocarcinoma.

e16103 Background: Surgery combined with perioperative therapy was recommended as standard treatment for patients with locally advanced esophagogastric junction (EGJ) adenocarcinoma, but the survival rate was still poor. Immunotherapy has shown antitumor activity and an acceptable safety profile in advanced EGJ cancer. The aim of this study was to evaluate the efficacy and safety of neoadjuvant Serplulimab combined with concurrent chemoradiotherapy in previously untreated locally advanced resectable EGJ adenocarcinoma. Methods: Eligible patients with resectable EGJ(Siewert Type II and Type III, Siewert classification 2000)adenocarcinoma stage cT3-4 or N+ were enrolled. Patients received neoadjuvant Serplulimab (300mg on day 1) plus SOX(oxaliplatin at 130mg/㎡on day 1; TS1 40-60mg two times per day on D1-D14, Q3W) in first cycle, followed by Serplulimab (300mg on day 1) combined with concurrent chemoradiotherapy (Reduced SOX regimen: oxaliplatin at 100mg/㎡on day 1, TS1 40-60mg two times per day on D1-D14, Q3W; Radiotherapy dose:45Gy in 25f) in second and third cycle. The patient finished the preoperative treatment and rested for 6-8 weeks for surgery. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints were major pathological response(MPR) rate, R0 resection rate, objective response rate(ORR), disease-free survival(DFS), overall survival(OS), and toxicity. Results: From March 8, 2023 to January 31,2024,15 patients were enrolled. Nine patients completed neoadjuvant therapy. Eight of these patients underwent radical surgical resection. One out of nine achieved a confirmed pathological complete response (pCR) after three cycles of neoadjuvant treatment. Additionally, two out of nine patients achieved major pathological response(MPR). So, the pCR rate was 11.1%, and the MPR rate was 22.2%. The Tumor and Lymph Nodes downstaging rates are 62.5% and 87.5%, respectively. The median DFS and OS were not reached. In terms of safety, fifteen patients who received at least one cycle of neoadjuvant therapy were included. The most common treatment-related adverse events(TRAE) across all grades were nausea/vomiting(6/15), anorexia(5/15), thrombocytopenia(4/15), and fatigue(4/15). Four patients (26.7%) had grade≥3 adverse events during preoperative therapy, with thrombocytopenia(3/15) and hepatic veno-occlusive disease(1/15). Immune-related adverse reactions(irAE) included myositis(1/15) and rash(1/15), both were grade 1. No grade 4 or higher TRAEs were observed. Conclusions: Initial benefits were demonstrated when using Serplulimab with concurrent chemoradiotherapy for the treatment of locally advanced, resectable EGJ adenocarcinoma patients. The efficacy and safety of Serplulimab with chemoradiotherapy will be further investigated in this trial later. Clinical trial information: NCT05918419 .

Impact of immune checkpoint inhibitors on survival outcomes in advanced gastric cancer in Japan: A real-world analysis.

Nivolumab was approved for the treatment of advanced gastric cancer in 2017 in Japan. The aim of this study was to assess the impact of nivolumab in a real-world clinical setting. This single-institutional retrospective study included patients with advanced gastric or esophagogastric junction adenocarcinoma and a history of first-line chemotherapy with platinum-based doublet or triplet regimens between 2010 and 2020. To assess the impact of nivolumab on survival, the patients were divided based on the year of nivolumab approval into a pre-2017 (2010-2016) group and a post-2017 (2017-2020) group. From a total of 1918 patients, 1093 were excluded. There were 533 patients in the pre-2017 group and 292 in the post-2017 group. Immune checkpoint inhibitors were used significantly more often in the post-2017 group than in the pre-2017 group (8.6% vs. 47.9%). Median overall survival was significantly longer in the post-2017 group (16.9 vs. 13.9 months; hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.63-0.90; p < 0.01). The proportion of patients transitioning to third-line treatment was higher in the post-2017 group than in the pre-2017 group (56.3% vs. 43.8%, p < 0.01). Median survival outcomes following progression on second-line treatment were significantly longer in the post-2017 group (4.3 vs. 3.2 months; HR 0.70, 95% CI 0.57-0.86; p < 0.01). The proportion of patients transitioning to third-line treatment and survival outcomes following progression on second-line treatment have improved since the approval of nivolumab. This drug might help to prolong overall survival in real-world practice.