Summary of the updated German national guidelines for gastric cancer and esophagogastric junction cancer v3.0 and narrative review of current developments in treatment

Esophagogastric junction cancer is defined as adenocarcinoma with the epicenter within 5cm of the esophagogastric junction in the West according to the Siewert classification. In contrast, it is defined as cancer of any histological type with the epicenter located within 2cm proximal or distal to the esophagogastric junction in Japan according to the Nishi classification. Recently, the incidence of esophagogastric junction cancer has been rapidly rising all over the world, leading to much attention. Esophagogastric junction cancer was previously treated like gastric cancer or esophageal cancer because it is a less frequently occurring tumor. Esophagogastric junction cancer is considered to have worse prognosis than gastric cancer. Therefore, in recent years, esophagogastric junction cancer has been recognized as an independent malignant disease with poor prognosis, and thus development of treatment strategies focused on esophagogastric junction cancer is needed. The mapping of frequent metastasis in the mediastinal and abdominal lymph nodes has revealed the lymphatic flow from esophagogastric junction cancer specifically, establishing the optimal lymph node dissection area and surgical approach. The development of multimodal treatment that includes chemotherapy, radiotherapy and immunotherapy has been applied to improve the survival of esophagogastric junction cancer. In this review, we summarize clinical trials with important evidence on surgical and multimodal perioperative treatments for esophagogastric junction cancer.

Objective: To investigate the associations between various blood test parameters including MLR (monocyte-lymphocyte ratio) and prognosis in post-operative esophagogastric junction cancer patients. Methods: We retrospectively studied the preoperative and postoperative data of 309 patients who underwent radical surgery for esophagogastric junction cancer. The relationship between MLR, neutrophil lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and overall survival (OS) was analyzed. Results: The cutoff values of MLR、NLR and PLR were 0.201, 1.697 and 96.960, respectively. The median OS was 51.4 months for all the patients in the study group (n=309). MLR in patients with esophagogastric junction carcinoma was associated with gender, depth of invasion, histological grade, TNM stage, NLR and PLR (P<0.05). PLR was associated with tumor size, TNM stage, NLR and MLR (P<0.05). NLR was associated with gender, tumor size, TNM stage, PLR and MLR (both P<0.05). Univariate analysis showed that tumor size, depth of tumor invasion, metastasis of lymph nodes, pathological grading, nerve infiltration, lymphovascular invasion, TNM staging, PLR and MLR were associated with the median overall survival time (P<0.05). Multivariate analysis showed that TNM stage, nerve infiltration and MLR were independent prognostic predictors for patients with esophagogastric junction cancer (P<0.05), but not PLR or NLR. Setting the optimal cut-off value of the MLR in 0.201, the area under the curve was 0.603, significantly larger than that of PLR and NLR (P<0.05). Conclusions: Preoperative MLR is a very useful predictor of patients with esophagogastric junction cancer who underwent radical rescetion. Preoperative MLR> 0.201 is an independent risk factor for postoperative survival in patients with esophagogastric cancer, and PLR> 96.960 may predict a poor prognosis risk.

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have been reported to be effective in the treatment of esophageal and esophagogastric junction cancers. The aim of this study was to detect the frequency of EGFR mutation and expression in Chinese patients with esophageal, esophagogastric junction and gastric cancers, and to clarify the value of EGFR mutation and expression in predicting the efficacy of TKI in the treatment of these tumors. In this study, 180 tumor samples with histologically confirmed esophageal cancer (39 cases), cancer of the esophagogastric junction (92 cases) and gastric cancer (49 cases) were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by real-time PCR-optimized oligonucleotide probe method. EGFR protein expression was evaluated by immunohistochemistry (IHC) in 89 tumor samples. The mutation analysis for EGFR (exons 18-21) showed no mutations in any of the hotspots of the gene in the 180 tumor samples analyzed. EGFR expression was negative in 12 tumor samples, 1+ in 31 tumor samples, 2+ in 24 tumor samples, and 3+ in 22 tumor samples. EGFR expression was 2+ or 3+ in 12 (92.3%) of the 13 esophageal squamous cell carcinomas, 29 (47.5%) of the 61 esophagogastric junction cancers, and 5 (33.3%) of the 15 gastric adenocarcinomas. Our results indicate that EGFR mutation in exons 18-21 is absent in the examined samples of esophageal, esophagogastric junction and gastric cancers. More studies are warranted to explore the predictive biological markers for the therapeutic response to EGFR TKI.

e16129 Background: Gastric cancer is the third most common malignancy in Kazakhstan and the second leading cause of cancer-related mortality. Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) perioperative chemotherapy is widely accepted treatment strategy of locally advanced gastric adenocarcinoma in Western countries. However, radical surgery is a preferable approach in Kazakhstan. The objective of this study was to assess the effectiveness and feasibility of FLOT perioperative chemotherapy in curable locally advanced gastric or esophago-gastric junction cancer. Methods: In this study, we reviewed the retrospective data of patients with locally advanced gastric or esophago-gastric junction cancer, who received FLOT perioperative chemotherapy between January 2020 and December 2022 in single center. To evaluate the effectiveness of treatment, histopathological regression, disease free survival (DFS) and 1- and 3-year overall survival outcomes were analyzed. Results: Total 136 patients with stage II and III with gastric or esophago-gastric junction cancer were treated. Fifty-six patients (41%) received FLOT preoperative chemotherapy. 9% (5) patients couldn’t complete all cycles of chemotherapy due to serious adverse events. Disease progression was observed in 10 (19%) patients after FLOT preoperative chemotherapy. Of the 46 radically operated patients, 5 (11%) had complete or near complete pathology response, 33 (72%) patients had partial response, and 8 (17%) patients had no response for preoperative chemotherapy (p = 0,405). 7 patients had not get adjuvant chemotherapy. Overall, 1- and 3-year survival were 78,6% and 34,9% respectively, disease free survival was 76,8% and 39% respectively. Conclusions: The FLOT perioperative chemotherapy was effective and feasible to administer and might be a standard treatment option among patients with locally advanced gastric or esophago-gastric junction cancer.

Background and Objectives:The European Society for Medical Oncology suggests performing EUS staging for esophagogastric junction and gastric cancers to further assess the T and N stages. The use of EUS after neoadjuvant therapy (NT) is still under debate. We aimed to evaluate the contribution of EUS after NT to staging, therapeutic choices, and prognosis prediction.Subjects and Methods:In 97 patients with esophagogastric junction and gastric cancers who received NT (chemotherapy or radiochemotherapy) followed by carcinologic surgery, EUS was performed before (uT, uN) and after (yuT, yuN) NT. We compared the results of EUS staging after NT (yuT and yuN) and final histology (ypT and ypN). We analyzed the correlation between overall survival (OS), disease-free survival (DFS), and the objective and subjective responses to NT evaluated by EUS (comparison of uT and yuT and uN and yuN with OS and DFS).Results:EUS staging detected metastasis that went undetected by computed tomography in 16% of metastatic patients. The accuracy between EUS after NT and postoperative pathological findings was 44.4% (34.2%; 54.7%) for T stage and 49.3% (37.5%; 61.1%) for N stage. On multivariate analysis, OS had significantly correlated with the objective response to NT. In the case of a response to NT, the median OS was 64.77 months, and in the case of stable disease, the median OS was 22.9 months (P = 0.01).Conclusion:EUS after NT can be used for staging. Despite its moderate accuracy, the evaluation of the response to NT by EUS seems to be correlated with patient prognosis.

In the past decades, epidemiological trends of the gastric cancer and esophagogastric junction (EGJ) cancer have changed all over the world. The morbidity and mortality of gastric cancer is on the decline, while the incidence and mortality of EGJ cancer is on the rise. This article summarizes the pathological types and the descriptive epidemiology, including the incidence, mortality, survival rate and its tendency in different gastric cancers and EGJ cancer. It also discusses the influencing factors of gastric cancer and EGJ cancer including environmental and genetic factors, which provides new ideas for the further study of the two kinds of cancers. Key words: Gastric neoplasms; Epidemiology; Esophagogastric junction; Morbidity; Mortality

Recent data support incorporation of immune checkpoint inhibitors into the treatment armamentarium for esophageal, gastroesophageal junction, and gastric (esophagogastric) cancer. This practical review focuses on clinical trials that influenced US Food and Drug Administration approvals and treatment guidelines in esophagogastric cancer, including the impact of location, stage, histology, human epidermal growth factor receptor 2 status, and PD-(L)1 expression on these guidelines. The role of immunotherapy in the locally advanced and metastatic setting is constantly expanding. Over the next few years, the many ongoing trials exploring immunotherapy are anticipated to bring new treatment regimens into the frontline setting with the potential to improve survival in patients with advanced disease.

This is a report on a case of CA19-9-producing cancer of esophagogastric junction with rectal cancer and a suspicion of Krukenberg tumor, a metastasized ovarian tumor that would mean an inoperable condition of cancer progression if that were true. This was a case of a woman in her 60s who was diagnosed with double cancers at the esophagogastric junction and rectum with a swollen left ovary. She had a laparoscopic bilateral salpingo-oophorectomy to get a histologic diagnosis, which should affect the subsequent therapeutic strategy because metastasis to the ovary meant an inoperable cancer progression. The resected ovary was diagnosed as juvenile granulosa cell tumor, but not Krukenberg tumor. Thus, subsequent curative surgeries, such as thoracolaparotomy for esophagogastric junction cancer and robot-assisted surgery for rectal cancer, were performed. Immunohistochemical examination revealed that the expression of CA19-9 was strongly observed in the tumor of esophagogastric junction, but not in the tumors of rectum or ovary. Furthermore, serum CA19-9 was drastically decreased after the resection of esophagogastric junction cancer. In aggregate, this esophagogastric junction cancer met the criteria of CA19-9-producing gastric cancer defined by Okinaga et al. So far, 46 cases of CA19-9-producing gastric cancer including this case have been reported in Japanese literature. Interestingly, this case had another characteristic of juvenile granulosa cell tumor, one of borderline malignant sex cord-stromal tumors rarely found in adults.

Esophagogastric junction carcinoma is a prominent cause of cancer fatalities and is lethal for patients with metastases and a future occurrence. About 10–20% of gastric and esophagogastric junction cancers overexpress HER-2. For individuals who might benefit from targeted therapy with anti-HER-2 medications, HER-2 targeting is essential in various cancer types. The main objective of this work is to assess the anti-cancer potential of 4-(2-amino-2-carboxyethyl) imidazole (4-2A2CI) by using density functional theory and molecular docking modeling to ascertain its structural stability and biological activity against proteins linked to esophagogastric cancer. The molecular arrangement was examined and structural optimization was carried out using the basis set CC-pVDZ. The reactive surface of 4-2A2CI was further examined using a computed molecular electrostatic potential field and the UV–Visible spectroscopy investigation was theoretically accomplished. The HOMO-LUMO energies and the predicted energy gap of 5.36 eV were used to assess the molecule structural stability and bioreactivity of 4-2A2CI. The binding ability was determined to be −6.7 kcal/mol after the docking study was conducted against the protein HER-2 implicated in esophagogastric cancer. Using in vitro methods, the cell viability, morphological examination and apoptosis of AGS cells treated with 4-2A2CI were investigated. 4-2A2CI showed an IC[Formula: see text] dosage of 60.9 [Formula: see text]M in AGS cells following the 24-hour treatment. Further, expression level of HER-2 in AGS after treatment was validated and showed reduced HER-2 expression levels. Overall outcomes showed 4-2A2CI reduced HER-2 expression and led to apoptosis-related cell death in AGS cells for treatment of esophagogastric junction cancer.

Preventing gastroesophageal reflux after proximal gastrectomy for proximal gastric and esophagogastric junction cancer remains challenging due to the lack of standardized reconstructive techniques. The double flap technique (DFT) in valvuloplastic esophagogastrostomy prevents reflux esophagitis but is less effective in esophagogastric junction cancer because of negative pressure on the inferior mediastinum. We developed the U-shaped flap technique (UFT) to enhance the anti-reflux efficacy. This study analyzed data from patients who underwent minimally invasive proximal gastrectomy for proximal gastric and esophagogastric junction cancer between August 2014 and May 2022, using a prospectively maintained database. We compared DFT and UFT for short- and long-term outcomes, focusing on gastroesophageal reflux, using one-to-one propensity score matching to control for patient-related variables. Among 217 eligible patients, 205 (100 in DFT, 105 in UFT) completed a 1-year follow-up. After propensity score matching, we selected 42 pairs of patients who underwent DFT and UFT. UFT had significantly shorter operative time (p = 0.044), similar blood loss, and similar morbidity. The UFT group had significantly fewer reflux symptoms (0% vs. 14.3%, p = 0.0011) and endoscopic Los Angeles grade B or higher reflux esophagitis (0% vs. 14.3%, p = 0.0011) than the DFT group. In lower mediastinal reconstructions for esophagogastric junction cancer, UFT showed a reduced incidence of reflux esophagitis. Our study indicates that the U-shaped flap technique (UFT) offered significant advantages in reducing postoperative reflux symptoms and endoscopic esophagitis, in a cohort of patients with proximal gastric and esophagogastric junction cancer.

The incidence of esophagogastric junction (EGJ) cancer is increasing worldwide. Siewert type II EGJ cancer encompasses intestinal and gastric phenotypes; however, the molecular profiles and clinicopathological features remain unclear. Overall, 922 patients who underwent surgical resection for EGJ or gastric cancer from 2014 to 2023 were analyzed. The tumors were classified into intestinal and gastric phenotypes using immunohistochemistry. Molecular profiling was conducted using whole-exome sequencing, and clinicopathological features, mutational patterns, immune responses, and survival outcomes were investigated. The intestinal phenotype exhibited frequent TP53 mutations and high NOX1 expression. High NOX1 expression was correlated with increased CD4 + and CD20 + lymphocyte infiltration. The intestinal phenotype was associated with better relapse-free survival (RFS) than the gastric phenotype. Metastatic patterns varied, with peritoneal and lymph node metastases being more common in the gastric and intestinal phenotypes, respectively. High NOX1 expression was an independent prognostic factor for RFS. EGJ cancers with intestinal and gastric phenotypes demonstrate distinct molecular and immune profiles that influence prognosis. The intestinal phenotype, characterized by TP53 mutations, high NOX1 expression, increased immune cell infiltration, and better survival outcomes, may impact EGJ cancer prognosis and could guide future diagnostic and therapeutic approaches.

The incidence of the esophagogastric junction (EGJ) cancer tends to increasing in recent years. Comprehensive treatment based on surgical treatment is currently a general strategy for the treatment of EGJ cancer. Because of the particularity of the anatomy and pathology of EGJ cancer, there were difficulties and controversies existing in the surgical treatment of EGJ cancer. Medical researchers have attached great importance to the treatment of EGJ cancer and made remarkable progress in it. Therefore, the authors summarize the progress of surgical treatment of EGJ cancer, and present it in four aspects of surgical approach lymph, node dissection, esophagogastric resection and digestive tract reconstruction. Key words: Esophagogastric junction cancer; Surgical treatment; Surgical approach; Lymph node dissection; Esophagogastric resection; Digestive tract reconstruction; Progress

Aim of the studyTo assess influencing factors and main health-related quality of life (HRQoL) issues in patients with cancers of the oesophago-gastric region using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire Core 30 (QLQ-C30) and its oesophago-gastric module (QLQ-OG25).Material and methodsPatients were qualified for this study based on the histological confirmation of oesophageal, oesophago-gastric or gastric cancers. Each patient filled out the Polish version of the EORTC QLQ-C30, the QLQ-OG25 module and a personal questionnaire. Patients were divided into groups based on gender, age, treatment intention, tumour localization, working status and level of education.ResultsOur study included 112 patients – 39 women (35%) and 73 men (mean age ± SD; 60.2 ±10.9). Thirty-five patients (31.3%) completed the questionnaires twice. Eighty-four (75%) patients had gastric cancer (GC), twenty-six (23.2%) oesophageal cancer (OC) and two (1.8%) cancer of the oesophago-gastric junction (OGJC). Eighty (71.4%) patients underwent surgical treatment prior to either chemo-, radio- or chemoradiotherapy. The Global Health Status scale of the QLQ-C30 inversely correlated with all the other QLQ-C30 and QLQ-OG25 symptom scales (r = –0.26 to –0.61; p < 0.05).ConclusionsThe main HRQoL problems of Polish OC, OGJC and GC patients are fatigue, insomnia, anxiety, and appetite and weight loss. Older age, receiving palliative treatment, having gastric cancer, being on retirement and having lower education are factors associated with higher symptom scores (worse symptoms) and thus poorer HRQoL.

To obtain a pathologically negative proximal margin (PM) for gastric cancer with gross esophageal invasion (EI) or esophagogastric junction (EGJ) cancer, we should transect the esophagus beyond the proximal boundary of gross EI with a safety margin because of a discrepancy between the gross and pathological boundaries of cancer. However, recommendations regarding the esophageal resection length for these cancers have not been established. Patients who underwent proximal or total gastrectomy for gastric cancer with gross EI or EGJ cancer were enrolled. A parameter ΔPM, which corresponded to the length of a discrepancy between the gross and pathological proximal boundary of the tumor, was evaluated. The maximum ΔPM, which corresponded to the minimum length ensuring a pathologically negative PM, was first determined in all patients. Then subgroup analyses according to factors associated with ΔPM ≥ 10mm were performed to identify alternative maximum ΔPMs. A total of 289 patients with gastric cancer with gross EI or EGJ cancer were eligible and analyzed in this study. The maximum ΔPM was 25mm. Clinical tumor (cTumor) size and growth and pathological types were independently associated with ΔPM ≥ 10mm. In subgroup analyses, the maximum ΔPM was 15mm for cTumor size ≤ 40mm and superficial growth type. Furthermore, the maximum ΔPM was 20mm in the expansive growth type. Required esophageal resection lengths to ensure a pathologically negative PM for gastric cancer with gross EI or EGJ cancer are proposed.

Background. In recent years, evidence supporting multimodality treatment for oesophageal, oesophagogastric junction (OGJ), and gastric cancer has accumulated. This population-based cohort-study investigates trends and predictors of utilisation of multimodality treatment for oesophagogastric cancer in the Netherlands.Patients and methods. Data were obtained from the Netherlands Cancer Registry regarding patients with oesophageal (n = 5450), OGJ (n = 2168) and gastric cancer (n = 6683) without distant metastases who had undergone R0 or R1 surgery diagnosed between 2000 and 2012. Follow-up was completed until February 2014. Preoperative/postoperative chemotherapy and/or radiotherapy combined with surgery were considered multimodality treatment. Logistic regression analysis was performed to analyse the association of age, gender, socioeconomic status, clinical T and N classification, hospital type, comprehensive cancer centre network region, and year of diagnosis, with multimodality treatment receipt. Additional analyses were performed to explore differences in trends of utilisation of multimodality treatment between academic and non-academic hospitals.Results. Multimodality treatment utilisation for oesophageal, OGJ and gastric cancer increased significantly to 90%, 85% and 56% in 2012, respectively. In oesophageal and OGJ cancer patients, preoperative chemoradiotherapy was most frequently administered (85% and 47% in 2012, respectively), and in gastric cancer patients preoperative chemotherapy (47% in 2012). Lower age, higher clinical T and N classification, and diagnosis in more recent years were significantly associated with more frequent multimodality treatment receipt. The adoption of most types of multimodality treatment in academic hospitals preceded non-academic hospitals by a year.Conclusion. In the Netherlands, the utilisation of multimodality treatment for oesophagogastric cancer has significantly increased during the past decade, especially in oesophageal and OGJ cancer. Multimodality treatment utilisation was especially dependent on patient and tumour characteristics and year of diagnosis, but multimodality treatment trends seem to be related to the publication of landmark studies, participation in nationally running clinical trials, and hospital type, preceding national guidelines.