Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.

BACKGROUND: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients.
METHODS: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS).
RESULTS: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient\'s or investigator\'s decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study.
CONCLUSIONS: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.

暂无摘要。

BACKGROUND: Adenocarcinoma of the esophagogastric junction has a center of origin within 5 cm of the esophagogastric junction. Surgical resection remains the main treatment. A transthoracic approach is recommended for Siewert I adenocarcinoma of the esophagogastric junction and a transabdominal approach is recommended for Siewert III adenocarcinoma of the esophagogastric junction. However, there is a need to determine the optimal surgical approach for Siewert II adenocarcinoma of the esophagogastric junction to improve lung function and the prognosis of patients.
OBJECTIVE: To investigate and compare the surgical effects, postoperative changes in pulmonary function, and prognoses of two approaches to treating combined esophagogastric cancer.
METHODS: One hundred and thirty-eight patients with combined esophagogastric cancer treated by general and thoracic surgeries in our hospital were selected. They were divided into group A comprising 70 patients (transabdominal approach) and group B comprising 68 patients (transthoracic approach) based on the surgical approach. The indexes related to surgical trauma, number of removed lymph nodes, indexes of lung function before and after surgery, survival rate, and survival duration of the two groups were compared 3 years after surgery.
RESULTS: The duration of surgery, length of hospital stay, and postoperative drainage duration of the patients in group A were shorter than those of the patients in group B, and the volume of blood loss caused by surgery was lower for group A than for group B (P < 0.05). At the one-month postoperative review, the first second, maximum ventilation volume, forceful lung volume, and lung volume values were higher for group A than for group B (P < 0.05). Preoperatively, the QLQ-OES18 scale scores of the patients in group A were higher than those in group B on re-evaluation at 3 mo postoperatively (P < 0.05). The surgical complication rate of the patients in group A was 10.00%, which was lower than that of patients in group B, which was 23.53% (P < 0.05).
CONCLUSIONS: Transabdominal and transthoracic surgical approaches are comparable in treating combined esophagogastric cancer; however, the former results in lesser surgical trauma, milder changes in pulmonary function, and fewer complications.

UNASSIGNED: The lymphocyte/C-reactive protein (LCR) is a novel immunoinflammatory score and prognostic marker, but the relationship between lymphocyte/C-reactive proteins and clinical outcomes in patients with upper gastrointestinal cancers remains controversial. This study aimed to evaluate the relationship between LCR and the prognosis of upper gastrointestinal cancer by systematic evaluation and meta-analysis.
UNASSIGNED: We systematically searched PubMed, EMBASE, Cochrane, and Web of Science databases to obtain related studies on the relationship between LCR and esophageal cancer (EC), gastric cancer (GC), and esophagogastric junction cancers (EGJ), and used hazard ratio (HR), 95% confidence interval (95%CI) to evaluate the prognostic value of LCR. Outcome measures included overall survival (OS) and disease-free survival (DFS).
UNASSIGNED: Eight retrospective cohort studies with 2838 patients were included. Meta-analysis showed that patients with low LCR cancers had poor overall survival OS and disease-free survival DFS (HR=2.18, 95%CI=1.87-2.55; HR=1.88, 95%CI=1.56-2.26). Subgroup analysis based on cancer type, treatment modality, gender, T stage, TNM stage, country, and LCR threshold showed that lower LCR levels were all associated with worse OS and DFS (P<0.05).
UNASSIGNED: The LCR can be used as a prognostic marker for patients with upper gastrointestinal cancers, and patients with a lower LCR may have a poor prognosis. Due to the limited number of studies included and mostly retrospective studies, the above findings require validation by more high-quality studies.
UNASSIGNED: https://www.crd.york.ac.uk, identifier CRD42023392433.

BACKGROUND: To evaluate recurrence in patients with post-neoadjuvant pathological complete response (pCR) and in patients with complete response of primary tumor but persisting lymphatic spread of disease (non-pCR, ypT0ypN +) of esophageal cancer.
METHODS: Seventy-five patients (63 pCR, 12 non-pCR) were analyzed retrospectively. Pattern and incidence of local and distant recurrence as well as the impact on overall (OS) and disease-free survival (DFS) were evaluated. The efficacy of neoadjuvant chemotherapy according to FLOT protocol was compared to neoadjuvant chemoradiation according to CROSS protocol.
RESULTS: In the pCR group, isolated local recurrence was diagnosed in 3%, while no isolated local recurrence was observed in the non-pCR group due to the high incidence of distant recurrence. Distant recurrence was most common in both cohorts (isolated distant recurrence: pCR group 10% to non-pCR group 55%; simultaneous distant and local recurrence: pCR group 3% to non-pCR group 18%). Median time to distant recurrence was 5.5 months, and median time to local recurrence was 8.0 months. Cumulative incidence of distant recurrence (with and without simultaneous local recurrence) was 16% (± 6%) in pCR patients and 79% (± 13%) in non-pCR patients (hazard ratio (HR) 0.123) estimated by Kaplan-Meier method. OS (HR 0.231) and DFS (HR 0.226) were significantly improved in patients with pCR compared to patients with non-pCR. Advantages for FLOT protocol compared to CROSS protocol, especially with regard to distant control of disease (HR 0.278), were observed (OS (HR 0.361), DFS (HR 0.226)).
CONCLUSIONS: Distant recurrence is the predominant site of treatment failure in patients with pCR and non-pCR grade 1a regression, whereby recurrence rates are much higher in patients with non-pCR.

In recent years, important clinical trials for gastric cancer (GC) and esophagogastric junction cancer (EGJC) have been reported, changing the strategies of surgical and perioperative treatment. Although laparoscopic gastrectomy has already been shown to be effective for early-stage cancer, recent evidence from both Asia (JLSSG0901, CLASS-01 and KLASS-02) and Europe (LOGICA and STOMACH trials) has demonstrated that it is useful for advanced GC. Robotic surgery has been rapidly gaining popularity in recent years, and randomized controlled trials are ongoing to evaluate its efficacy. A prospective nationwide multicenter study mapped sites with frequent metastasis and revealed lymphatic flow specific to EGJC, thus establishing the optimal lymph node dissection area and surgical approach based on esophageal involvement. Perioperative chemotherapy, the mainstay of treatment in Europe, also has been established in Asia by the PRODIGY and RESOLVE studies. New clinical trials have been conducted to evaluate the efficacy of combining immunotherapy or molecular-targeted therapy with perioperative chemotherapy or chemoradiotherapy. In this review, we present important recent clinical trials regarding the treatment of GC and EGJC published in 2021 or 2022.

In Germany and Western Europe, gastroesophageal junction cancer (AEG) and proximal gastric cancer are currently treated with (transhiatal-extended) total gastrectomy (TG) according to the latest treatment guidelines. TG leads to a severe and long-lasting impairment of postoperative health-related quality of life (HRQoL) of the treated patients. Recent studies have suggested that HRQoL of these patients could be improved by proximal gastrectomy with double-tract reconstruction (PG-DTR) without compromising oncologic safety. Our aim is therefore to conduct a randomized controlled non-inferiority trial comparing PG-DTR with TG in AEG II/III and gastric cancer patients with overall survival as primary endpoint and HRQoL as key secondary endpoint.
This protocol is written with reference to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P 2015) statement. We will conduct searches in the electronic databases MEDLINE, Web of Science Core Collection, ScienceDirect, and Cochrane Library. We will also check references of relevant studies and perform a cited reference research. Titles and abstracts of the records identified by the searches will be screened, and full texts of all potentially relevant articles will be obtained. We will consider randomized trials and non-randomized studies. The selection of studies, data extraction, and assessment of risk of bias of the included studies will be conducted independently by two reviewers. Meta-analysis will be performed using RevMan 5.4 (Review Manager (RevMan) Version 5.4, The Cochrane Collaboration).
This systematic review will identify the current study pool concerning the comparison of TG and PG-DTR and help to finally refine the research questions and to allow an evidence-based trial design of the planned multicenter randomized-controlled trial.
Ethical approval is not required for this systematic review. Study findings will be shared by publication in a peer-reviewed journal.
PROSPERO CRD42021291500.

BACKGROUND: Recent developments in the field of companion diagnosis and molecular-targeting therapeutic agents have helped in developing treatments targeting human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC) and esophagogastric junction cancer (EGJC), and the importance of accurate diagnosis of HER2 expression is increasing. However, the HER2-positivity rate significantly differs among reports in GC and EGJC, and factors that affect HER2-positivity require elucidation.
METHODS: The present study retrospectively examined factors related to HER2-positivity in a single institution, including age, sex, body mass index, the American Society of Anesthesiologists physical status, tumor information, and surgery information, including time to specimen processing.
RESULTS: Our study included 165 patients tested for HER2 using GC and EGJC surgery specimens among the 1,320 patients who underwent gastrectomy from January 2007 to June 2022. In total, 35 (21.2%) and 130 (78.8%) patients were HER2-positive and -negative, respectively. Multivariate analysis revealed that intestinal type (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 1.44-8.09, p = 0.005), pM1 (OR: 3.99, 95% CI: 1.51-10.55, p = 0.005), and time to specimen processing of < 120 min (OR: 2.65, 95% CI: 1.01-6.98, p = 0.049) were independent factors that affected HER2-positivity.
CONCLUSIONS: The outcomes of the present study indicated that intestinal type, pM, and time to specimen processing are important factors affecting HER2-positive rates in GC and EGJC. Therefore, the risk of false-negative HER2 results may be reduced by decreasing the time required to process the resected specimen. Additionally, accurate diagnosis of HER2 expression may increase the opportunity to administer molecular-targeted drugs that can expect therapeutic effects to patients appropriately.
BACKGROUND: Retrospectively registered.

Incidence rates for esophagogastric junction cancer are rising rapidly worldwide possibly due to the economic development and demographic changes. Therefore, increased attention has been paid to the prevention, diagnosis, and the treatment of esophagogastric junction cancer. Although there are discrepancies in the treatment strategy between Asian and Western countries, surgery remains the mainstay of treatment for esophagogastric junction cancer. Recent developments of perioperative multidisciplinary treatment may lead to better therapeutic effect, higher complete resection rate, and better control of the residual diseases, thus result in prolonged prognosis. In this review, we will focus on the treatment of locally advanced resectable esophagogastric junction cancer, and discuss the current status and future perspectives of the perioperative treatment including chemotherapy, radiation therapy, and immunotherapy, as well as the surgical strategy. Better understanding of the latest treatment strategy and future overlook may enable to standardize and individualize the treatment for esophagogastric junction cancer, thus leading to better prognosis for those patients.