Adenocarcinoma Of Esophagogastric Junction Research Articles

The impact of different comprehensive treatment models on patients with adenocarcinoma of esophagogastric junction based on propensity score matching: a single center cohort study

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ2 test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ2 test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ2=6.971, P=0.008) and nCRT group (6.9% (2/29), χ2=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ2=10.881, P=0.001; χ2=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ2=6.740, P=0.009) and nCRT group (31.0% (9/29), χ2=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ2=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ2=4.976, P=0.083) and progression-free survival (χ2=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.

Dilemmas in definition and classification of adenocarcinoma of esophagogastric junction: from history to current status

In recent years, adenocarcinoma of esophagogastric junction (AEG) has received increased attention from the academic community. However, the esophagogastric junction (EGJ) straddles two anatomical regions: the thoracic cavity and the abdominal cavity. The histological features of the EGJ are different from those of the esophagus and stomach. There are general disagreements among the related disciplines regarding the definition and classification of AEG. By summarizing the views of different disciplines, including endoscopy, radiography, and pathology, a more comprehensive definition of the EGJ was formulated in the Japanese Classification of Gastric Carcinoma (the 15th edition), and the principle of endoscopic diagnostic priority was established. In recent years, with the development of physiological and anatomical studies, the EGJ has gradually expanded conceptually into a complex functional anatomical region covering the distal esophagus to the proximal stomach. The venous and lymphatic vessels in the EGJ are characterized by bidirectional flow, which is an important anatomical basis for the invasion and metastasis patterns of tumors in this region. The clinical practice of EGJ cancer has been promoted by the creation of Nishi and Siewert classification systems. With the support of a series of clinical studies for its scientificity and effectiveness, the Siewert classification is widely accepted by the international community, and successively introduced into major international practice guidelines. In general, the staging and management of Siewert Ⅰ and Ⅱ AEG are recommended as esophageal cancer, while Siewert Ⅲ AEG is recommended for gastric cancer. However, in the Japanese guidelines for the treatment of esophageal and gastric cancers, the Nishi classification is still used to define and classify EGJ cancer. Recent year, a Chinese consensus on the surgical treatment of AEG was formulated by multidisciplinary experts. The main controversies were summarized in the consensus, and proposals that incorporate the domestic situation were also presented. At present, only by returning to the basic anatomical and physiological perspectives, strengthening multidisciplinary communication and cooperation, and with the help of emerging bioinformatics, digital, and material technology, can it be possible to get out of the dilemma faced by traditional AEG classification and staging system.

Efficacy of the No. 10 lymphadenectomy with spleen preservation on patients with gastric cancer and/or esophagogastric junction adenocarcinoma who underwent total gastrectomy: a systematic review and meta-analysis.

BackgroundSurgery with total gastrectomy and D2 lymph node dissection (LND) has been recommended as the standard treatment for patients with advanced upper and middle gastric carcinoma and/or Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). However, whether the No. 10 lymph node (No. 10 LN, also known as splenic hilar LN) should be dissected in total gastrectomy remains controversial. We aimed to evaluate whether the No. 10 LND with spleen preservation has survival benefit for patients with gastric cancer and/or AEG who underwent the total gastrectomy.MethodsThe PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and American Society of Clinical Oncology.org (ASCO.org) were electronically searched to identify eligible studies. The primary outcome was the survival rate, and secondary outcomes included the disease-free survival (DFS) rate and side effects. The Review Manager 5.3.5 software was used for the meta-analysis. The odds ratio (OR) and mean difference with 95% confidence interval (CI) were calculated. The statistical heterogeneity was assessed using chi-square (χ2) and I2 tests.ResultsEight studies enrolling a total of 4,131 patients were eligible for our review. The meta-analysis results demonstrated that the No. 10 LND group was significantly better than the non-No. 10 LND group in terms of the 3- (OR =0.71, 95% CI: 0.62–0.81, P<0.00001) and the 5-year (OR =0.66, 95% CI: 0.58–0.75, P<0.00001) survival rates but not in the 1-year survival rate (OR =0.91, 95% CI: 0.75–1.11, P=0.36). The DFS rates in the No. 10 LND group were significantly increased after 1 (OR =0.76, 95% CI: 0.61–0.93, P=0.008), 3 (OR =0.69, 95% CI: 0.60–0.81, P<0.00001), and 5 (OR =0.66, 95% CI: 0.56–0.76, P<0.00001) years compared with those in the non-No. 10 LND group.DiscussionEvidence shows that the No. 10 LND with spleen preservation can improve the survival and the DFS rates for patients with gastric cancer and/or Siewert type II/III AEG who underwent the total gastrectomy. High-quality prospective trials are expected.

Effect of splenic hilar lymphadenectomy on locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction with a tumor diameter ≥4 cm: a five-year survival analysis

Objective: To examine the long term outcome of splenic hilar lymphadenectomy (SHL) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) with a tumor diameter ≥4 cm. Methods: A total of 489 locally advanced Siewert type Ⅱ and Ⅲ AEG patients with a tumor diameter ≥4 cm who underwent radical resection from January 2010 to April 2016 were included. There were 383 males and 106 females. There were 225 patients aged≥65 years and 264 patients aged <65 years. SHL was conducted in 270 patients(SHL group). Wilcoxon rank-sum test or χ2 test were conducted for inter-group comparison. Cox proportional hazard regression was used to analyze the long term outcome of SHL and the prognosis factors of overall survival. Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Followed-up to April 2021,the median follow-up time was 78.0 months (range: 74.0 to 85.0 months), the follow-up rate was 95.5%(467/489). The splenic hilar lymphnode metastasis rate of the SHL group was 12.6% (34/270). Younger patients (<65 years old), less complications, higher proportion of patients received adjuvant chemotherapy were demonstrated in the SHL group (χ2: 5.644 to 6.744, all P<0.05). Multivariate analysis showed that SHL was the independent prognosis factor of overall survival for patients with Siewert type Ⅱ and Ⅲ AEG and a tumor diameter≥4 cm (HR=0.68, 95%CI: 0.52 to 0.88, P=0.004) along with preoperative CA19-9, pathological T stage, pathological N stage, adjuvant chemotherapy and postoperative complication. Further subgroup analysis demonstrated that the SHL group had better 5-year overall survival than non-SHL group (62.4% vs. 39.2%, χ2=17.983, P=0.006) in Siewert type Ⅲ AEG rather than in Siewert type Ⅱ AEG(57.3% vs. 53.7%, χ2=3.031, P=0.805). Conclusion: In experienced center, splenic hilar lymphadenectomy can improve the prognosis of Siewert type Ⅲ AEG with a tumor diameter ≥4 cm.

Several issues on surgical treatment for adenocarcinoma of esophagogastric junction

There are several controversies and issues in the surgical treatment of esophagogastric junction (AEG) currently. The Siewert classification and TNM staging system are commonly used to assist clinical decision and prognosis prediction. Generally, transthoracic procedure is more suitable for Siewert Ⅰ type and longer esophageal invasion patients, while transhiatal is more suitable for Siewert Ⅲ type patients. The optimal extent of lymph node dissection for AEG should be based on tumor location and esophageal invasion range. The extent of surgical resection and the method of digestive tract reconstruction should be based on the principle of radical resection and surgical safety, and the postoperative life quality of patients should be fully considered. Roux-en-Y anastomosis is the most common and efficient anastomosis after total gastrectomy, while double tract anastomosis is recommended by many experts after proximal gastrectomy. With the continuous advancement of minimally invasive techniques, experienced centers and teams can perform digestive tract reconstruction under total laparoscopy. In the future, more high-quality studies are expected to provide evidence-based medical evidence for AEG's surgical treatment decisions.

Whether the infracardiac bursa protect right pleura during laparoscopic radical operation of Siewert type II adenocarcinoma of esophagogastric junction?

BackgroundTransthoracic single-port assisted laparoscopic five-step maneuver inferior mediastinal lymphadenectomy for Siewert type II adenocarcinoma of esophagogastric junction (AEG) has superiority in lower mediastinal lymph nodes dissection and digestive tract reconstruction. However, the right pleura was probably ruptured in this surgical technique. The aim of this study was to explore whether the infracardiac bursa (ICB) exposed could protect right pleura.MethodsWe retrospectively collected and evaluated the clinical and pathological data of patients who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymphadenectomy for Siewert II AEG at Guangdong Provincial Hospital of Chinese Medicine between May 2017 and February 2022.ResultsA total of 49 patients were eligible, including 31 patients in ICB exposed group (group A) and 18 patients in ICB unexposed group (group B). There were no statistically significant differences in baseline characteristics between the two groups. 4 patients (12.9%) had right pleura rupture in group A, while 14 patients (77.8%) in group B, and the difference was statistically significant (p < 0.001). Compared with group B, the extubation time of endotracheal intubation (10.0 (6.0 ~ 12.0) vs. 13.0 (8.0 ~ 15.0) min, p = 0.003) and thoracic drainage tube stay (6.0 (5.0 ~ 7.0) vs. 8.0 (6.0 ~ 10.5) days, p = 0.041) were significantly shorted in the group A. The drainage volume of thorax (351.61 ± 125.00 vs. 418.61 ± 207.86 mL, p = 0.146) was non-significant less and the rate of complications (3.2% vs. 11.1%, p = 0.074) was non-significant lower in group A compared with group B. The postoperative hospital stay (9.0 (8.0,13.0) vs. 9.0 (8.0,12.0) days, p = 0.983) were similar in two groups. No serious adverse event occurred in any patient.ConclusionsThe ICB exposed could protect the right pleura and may promote postoperative recovery, which may be used as an anatomical marker in inferior mediastinal lymphadenectomy.

Minimum number of necessary lymph nodes for the accurate staging of adenocarcinoma of esophagogastric junction

ObjectiveThis study aims to explore the minimum number of lymph nodes (LNs) necessary for assessing the postoperative staging of adenocarcinoma of esophagogastric junction (AEG). MethodsWe extracted the data of patients from the Surveillance Epidemiology and End Results (SEER) database, who were pathologically diagnosed with AEG between 2000 and 2017. We explored the associations between the number of LNs and overall survival (OS) by univariate and multivariate analyses and determined the proper cutoff value of the number of LNs necessary for accurate postoperative staging. ResultsOf the patients with AEG in the SEER database, 2668 met our inclusion criteria. The total number of regional LNs dissected was found to be significantly associated with survival in analyses stratified by T stage. Univariate and multivariate regression showed that age, grade, positive LNs, number of LNs examined, and T stage were independently associated with OS. For patients with T1-2 tumors, the 5-year survival rate was 58.7%, and patients with more than 11 LNs examined obtained a greater survival benefit. Among patients with T3-4 tumors, the 5-year survival rates were 28.9% and 39.7% for those with 1–16 LNs examined and for those with more than 17 LNs examined, respectively. ConclusionTo accurately determine the pathological stage of patients with AEG, no less than 11 LNs must be resected for patients with stage T1-2 disease, and no less than 16 LNs must be resected for patients with stage T3-4 disease.

Implementation of Multimodality Therapy and Minimally Invasive Surgery: Short- and Long-term Outcomes of Gastric Cancer Surgery in Medium-Volume Center

BackgroundMultimodal treatment of gastric cancer includes careful preoperative staging, perioperative oncological treatment, and selective minimally invasive approach. The aim was to evaluate whether this approach improves short- and long-term outcomes in operable gastric cancer. MethodsThis study included 181 gastric cancer patients who underwent curative intent surgery in Central Finland Central Hospital between years 2005 and 2021 for gastric or esophagogastric junction adenocarcinoma. Those 65 patients in group 1 operated between years 2005–2010 had open surgery with possible adjuvant therapy. During the second period including 58 patients (2011–2015), perioperative chemotherapy and minimally invasive surgery were implemented. The period, when these treatments were standard practise, was years 2016–2021 including 58 patients (group 3). Outcomes were lymph node yield, major complications and 1- and 3-year survival rates. ResultsMedian lymph node yield increased from 17 in group 1 and 20 in group 2 to 23 in group 3 (p < 0.001). Major complication rates in groups 1–3 were 12.3%, 32.8%, and 15.5% (group 1 vs. group 2, p = 0.007; group 2 vs. group 3, p = 0.018), respectively. Overall 1-year survival rates between study groups 1–3 were 78.5% vs. 69.0% vs. 90.2% (p = 0.018) and 3-year rates 44.6% vs. 44.8% vs. 68.1% (p = 0.016), respectively. For overall 3-year mortality, adjusted hazard ratio (HR) was 1.02 (95%CI 0.63–1.66) in group 2 and HR 0.37 (95%CI 0.20–0.68) in group 3 compared to group 1. ConclusionsIn medium-volume center, modern multimodal therapy in operable gastric cancer combined with minimally invasive surgery increased lymph node yield and improved long-term survival without increasing postoperative morbidity.

FLOT and CROSS chemotherapy regimens alter the frequency of CD27+ and CD69+ T cells in oesophagogastric adenocarcinomas: implications for combination with immunotherapy

Combining immunostimulatory chemotherapies with immunotherapy is an attractive strategy to enhance treatment responses in oesophagogastric junctional adenocarcinoma (OGJ). This study investigates the immunostimulatory properties of FLOT, CROSS and MAGIC chemotherapy regimens in the context of OGJ using in vitro and ex vivo models of the treatment-naïve and post-chemotherapy treated tumour microenvironment. FLOT and CROSS chemotherapy regimens increased surrogate markers of immunogenic cell death (HMGB1 and HLA-DR), whereas the MAGIC treatment regimen decreased HMGB1 and HLA-DR on OGJ cells (markedly for epirubicin). Tumour-infiltrating and circulating T cells had significantly lower CD27 expression and significantly higher CD69 expression post-FLOT and post-CROSS treatment. Similarly, the supernatant from FLOT- and CROSS-treated OGJ cell lines and from FLOT- and CROSS-treated OGJ biopsies cultured ex vivo also decreased CD27 and increased CD69 expression on T cells. Following 48 h treatment with post-FLOT and post-CROSS tumour conditioned media the frequency of CD69+ T cells in culture negatively correlated with the levels of soluble immunosuppressive pro-angiogenic factors in the conditioned media from ex vivo explants. Supernatant from FLOT- and CROSS-treated OGJ cell lines also increased the cytotoxic potential of healthy donor T cells ex vivo and enhanced OGJ patient-derived lymphocyte mediated-killing of OE33 cells ex vivo. Collectively, this data demonstrate that FLOT and CROSS chemotherapy regimens possess immunostimulatory properties, identifying these chemotherapy regimens as rational synergistic partners to test in combination with immunotherapy and determine if this combinatorial approach could boost anti-tumour immunity in OGJ patients and improve clinical outcomes.

SIRGs score may be a predictor of prognosis and immunotherapy response for esophagogastric junction adenocarcinoma.

BackgroundEsophagogastric junction adenocarcinoma (EGJA) is a special malignant tumor with unknown biological behavior. PD-1 checkpoint inhibitors have been recommended as first-line treatment for advanced EGJA patients. However, the biomarkers for predicting immunotherapy response remain controversial.MethodsWe identified stromal immune-related genes (SIRGs) by ESTIMATE from the TCGA-EGJA dataset and constructed a signature score. In addition, survival analysis was performed in both the TCGA cohort and GEO cohort. Subsequently, we explored the differences in tumor-infiltrating immune cells, immune subtypes, immune-related functions, tumor mutation burden (TMB), immune checkpoint gene expression, immunophenoscore (IPS) between the high SIRGs score and low SIRGs score groups. Finally, two validation cohorts of patients who had accepted immunotherapy was used to verify the value of SIRGs score in predicting immunotherapy response.ResultsEight of the SIRGs were selected by LASSO regression to construct a signature score (SIRGs score). Univariate and multivariate analyses in the TCGA and GEO cohort suggested that SIRGs score was an independent risk factor for the overall survival (OS) and it could increase the accuracy of clinical prediction models for survival. However, in the high SIRGs score group, patients had more immune cell infiltration, more active immune-related functions, higher immune checkpoint gene expression and higher IPS-PD1 and IPS-PD1-CTLA4 scores, which indicate a better response to immunotherapy. The external validation illustrated that high SIRGs score was significantly associated with immunotherapy response and immune checkpoint inhibitors (ICIs) can improve OS in patients with high SIRGs score.ConclusionThe SIRGs score may be a predictor of the prognosis and immune-therapy response for esophagogastric junction adenocarcinoma.

Total neoadjuvant therapy for locally advanced gastric cancer and esophagogastric junction adenocarcinoma: study protocol for a prospective, multicenter, single-arm, phase II clinical trial

BackgroundGastric cancer ranks high in terms of morbidity and mortality worldwide. Multimodal therapy is therefore essential for locally advanced gastric cancer. Recent studies have demonstrated that both perioperative chemotherapy and neoadjuvant chemoradiotherapy can improve the prognosis of patients. However, the completion rate of chemotherapy after surgery remains low, which may affect survival. Thus, identifying the best way to combine radiotherapy, chemotherapy and surgery is important. The aim of this study was to explore the toxicity and efficacy of the total neoadjuvant therapy modality for locally advanced gastric cancer.MethodsThis study will be a prospective, multicenter, single-arm, phase II clinical trial. Patients diagnosed with locally advanced (stage cT3-4 and cN positive, AJCC 8th) gastric cancer and gastroesophageal junction adenocarcinoma will be enrolled. Patients will initially receive radiotherapy (95% planned target volume: 45 Gy/25 f) and concurrent chemotherapy (S-1: 40–60 mg twice a day) followed by six cycles of consolidated chemotherapy (SOX, consisting of S-1 and oxaliplatin) and surgery. The primary objective will assess pathological complete response; the secondary objectives will include toxicities assessing surgical complications, the tumor downstaging rate and the R0 resection rate.DiscussionInvestigation of total neoadjuvant therapy in gastric cancer is limited. The goal of this trial is to explore the efficacy and toxicity of total neoadjuvant therapy for locally advanced gastric cancer and gastroesophageal junction adenocarcinoma.Trial registration: Clinicaltrials.gov (NCT04062058, August 20, 2019).

CROSS Versus FLOT Regimens in Esophageal and Esophagogastric Junction Adenocarcinoma

The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics. Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers. Computed tomography-measured sarcopenia, and pulmonary function (forced expiratory volume in first second/forced vital capacity/diffusion capacity for carbon monoxide) were compared pretherapy and posttherapy. Operative complications were defined as per the Esophageal Complications Consensus Group (ECCG) criteria, and severity per Clavien-Dindo. Tumor regression grade and R status were measured, and survival estimated per Kaplan-Meier. A total of 83% were male, cT3/cN+ was 92%/68% for FLOT, and 86%/60% for CROSS. The full prescribed regimen was tolerated in 40% of FLOT patients versus 92% for CROSS. Sarcopenia increased from 16% to 33% for FLOT, and 14% to 30% in CROSS ( P <0.01 between arms). Median decrease in diffusion capacity for carbon monoxide was -8.25% (-34 to 25) for FLOT, compared with -13.8%(-38 to 29), for CROSS ( P =0.01 between arms). Major pathologic response was 27% versus 44% for FLOT and CROSS, respectively ( P =0.03). In-hospital mortality, respectively, was 1% versus 2% ( P =0.9), and Clavien Dindo >III 22% versus 27% ( P =0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% ( P <0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) ( P =0.42). Both CROSS and FLOT resulted in equivalent survival. Operative outcomes were similar, however, the CROSS regimen increased postoperative respiratory failure and atrial fibrillation. Less than half of patients received the prescribed FLOT regimen, although toxicity rates were acceptable. These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk.

Survival benefits from neoadjuvant treatment in gastric cancer: a systematic review and meta-analysis

BackgroundSurgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments.Methods/designThis review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes.DiscussionThe aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice.Systematic review registrationPROSPERO CRD4202123718

Tumor size predicts worse prognosis in esophagogastric junction adenocarcinoma.

Adenocarcinoma of the esophagogastric junction (AEGJ) has an increasing incidence and is associated with limited overall survival. Several studies have tried to identify prognostic factors for AEGJ, although few have described relationships between prognosis and the tumor's size or anatomical location. Thus, this retrospective study evaluated 188 patients with resected locally advanced AEGJ. Tumor location was determined using upper endoscopy, and the following groups were created: E&E + EGJ (distal esophagus, esophagogastric junction, and distal esophagus), EGJ (esophagogastric junction), EGJ + G (esophagogastric junction and proximal stomach), G (proximal stomach), and E + EGJ + G (esophagus to the proximal stomach, including the esophagogastric junction). Other variables of interest were tumor size and differentiation, TNM stage, comorbidities, surgery type, and survival outcomes. Among 188 patients included, 163 were men (86.7%), and the mean age was 64.9years. Forty-eight (25.6%) patients underwent total gastrectomy and distal esophagectomy, while 140 (74.4%) subtotal esophagectomy with proximal gastrectomy. Presence of comorbidities, tumor size, angiolymphatic and perineural invasion, and pTNM status were different between groups according to tumor location. The mean follow-up period was 47.4months. The disease-free survival (DFS) rates were as follows: 72.7% (G), 68.0% (E&E + EGJ), 63.4% (EGJ), 57.1% (EGJ + G), and 44.4% (E + EGJ + G), while the overall survival (OS) rates were 81.0% (EGJ + G), 78.8% (G), 64.0% (E&E + EGJ), 54.9% (EGJ), and 48.1% (E + EGJ + G). Multivariate analysis revealed that tumor size of < 5cm, and tumor location G subgroups were associated with better DFS. High histological grade and advanced pT status were independent factors related to worse OS. In conclusion, the prognosis of AEGJ may be preoperatively predicted by a tumor size of ≥ 5cm and its anatomical location.

Selection of Digestive Tract Reconstruction After Partial Gastric Sparing Surgery in Patients With Adenocarcinoma of the Esophagogastric Junction of cT2-T3 Stage.

ObjectiveTo investigate the appropriate reconstruction method of the digestive tract after partial gastric sparing surgery for adenocarcinoma of the esophagogastric junction of stage cT2-T3.MethodsA retrospective analysis of the clinical data of patients with adenocarcinoma of the esophagogastric junction from January 2015 to January 2019 in the General Surgery Department of Zhengzhou University Affiliated Tumor Hospital was performed. Patients with intraoperative double tract anastomosis composed the double tract reconstruction (DTR) group, and patients with intraoperative oesophagogastrostomy with a narrow gastric conduit group composed the oesophagogastrostomy by a narrow gastric conduit (ENGC) group. We analysed and compared the short-term postoperative complications and long-term postoperative nutritional status of the two groups of patients.ResultThere were no statistically significant differences between the two groups of patients in terms of age, sex, preoperative haemoglobin level, albumin level, cT, cN, neoadjuvant therapy or not, pathological type and Siewert type. In terms of BMI and body weight, the ENGC group was higher than the DTR group, but the difference was not statistically significant (p = 0.099, p = 0.201). There was no significant difference between the two groups of patients in terms of upper resection margin, operation time, blood loss, tumor diameter, pT, pN and postoperative hospital stay. The gastric resection volume of the DTR group was much larger than that of the ENGC group, and there was a significant difference between the two (p = 0.000). The length of the lower resection margin of the DTR group was also significantly greater than that of the ENGC group (p = 0.000). In terms of surgical approach, the proportion of the DTR group with the abdominal approach was significantly higher than that of the ENGC group, and the difference between the two was statistically significant (p = 0.003). The postoperative exhaust time in the ENGC group was significantly shorter than that in the DTR group (p = 0.013). However, there was no statistically significant difference between the two groups in terms of anastomotic leakage, anastomotic bleeding, intestinal obstruction, abdominal infection, pneumonia, pancreatic leakage, lymphatic leakage,death within 30 days after surgery, or overall complications. In terms of anastomotic stenosis, the incidence in the ENGC group was higher than in the DTR group, and the difference was statistically significant (p = 0.001). There was no significant difference in oral PPI, haemoglobin or albumin levels in patients at 3 months, 6 months, or 12 months after surgery. Comparing reflux/heartburn symptoms at 3 months and 6 months after surgery, we found no statistically significant difference between the two, while in terms of reflux/heartburn symptoms at 12 months after surgery, the findings of the ENGC group were higher than those of the DTR group, and the difference was statistically significant (p = 0.045). In terms of poor swallowing, the ENGC group was always higher than the DTR group, and the difference between the two groups was statistically significant (p < 0.05). There was no statistically significant difference in body weight between the two groups at 3 months or 6 months after surgery. At 12 months after surgery, the body weight of the patients in ENGC group was significantly higher than that in the DTR group, and the difference between the two groups was statistically significant (p = 0.039).ConclusionsFor patients with cT2-T3 stage oesophagogastric junction adenocarcinoma with tumours less than 4 cm in diameter, ENGC anastomosis is recommended for patients with a high tumour upper boundary, with obesity, short mesentery, or disordered vascular arch, and for routine patients, DTR anastomosis is recommended.

Diverse contributions of the visceral fat area to the etiology of two distinct subtypes of esophago-gastric junctional adenocarcinoma

Background There are two distinct etiologies of esophago-gastric junctional adenocarcinomas (EGJACs): one associated with extensive gastric mucosal atrophy (GA), resembling non-cardiac gastric cancers; and the other related to gastro-esophageal reflux disease, resembling esophageal adenocarcinoma. In this study, we investigated the associations between the visceral fat area (VFA) and EGJACs separately in the two subtypes of EGJACs, depending on the extent of background GA. Methods Sixty-four consecutive patients with EGJACs (Siewert type 2) were enrolled from a population-based database in Akita Prefecture, Japan, between 2014 and 2019. Two age- and sex-matched healthy controls were randomly assigned to each EGJAC case. The extents of GA were evaluated endoscopically, and the VFA values were measured based on computed tomography images. Logistic regression analyses were performed to investigate the associations between EGJACs and the VFA. Results Study subjects were classified into 2 subgroups depending on the extent of endoscopic GA: 29 (45.3%) without and 35 (54.7%) with extensive GA. Multivariable regression analyses revealed that a VFA of ≥100 cm2 was significantly associated with EGJACs in subjects without extensive GA [odds ratio (95% confidence interval): 2.65 (1.08–6.54)], while there was no such association in subjects with extensive GA [odds ratio (95% confidence interval): 1.52 (0.60–3.83)]. Conclusions The contribution of the VFA to the etiology of EGJACs seems to differ depending on the extent of background GA, with the VFA more prominently associated with EGJACs in subjects without extensive GA than in those with it, providing further rationale concerning the heterogeneous nature of EGJAC etiology.

Neoadjuvant Chemoradiotherapy for Locally Advanced Gastric Cancer: Where Are We at?

Simple SummaryMore than 50% of gastric cancer are at least locally advanced at presentation. For such patients, a multimodal approach rather than mere surgical resection leads to better long-term prognosis. Neoadjuvant chemoradiotherapy is one of the common treatment strategies for local advanced gastric cancer. Based on the experience and evidence from esophago-gastric cancers, the incorporation of systemic and locoregional therapy has shown superior disease control and reduced local recurrence. However, the optimal chemotherapy regimen, patient selection, technical consideration and potential biomarkers are still under investigation. Furthermore, the comparison of neoadjuvant chemoradiotherapy with neoadjuvant/perioperative chemotherapy is also an important issue to be answered. In the review article, we addressed the current available evidence to provide a comprehensive understanding and the use of neoadjuvant chemoradiotherapy for locally advanced gastric cancer. Future studies and ongoing trials will be necessary to determine the best candidate and the role of newer systemic and radiation therapies in such patients. NCRT is a feasible treatment option for LAGC, with the ability to achieve favorable disease control and enable higher radical resection rates over those afforded by perioperative chemotherapy or surgery alone. Large clinical trials examining the comparative efficacy of NCRT and NCT are underway. The discrepancy between the satisfactory pCR rates associated with NCRT and the nonsignificant association between NCRT and survival warrants further exploration. Furthermore, newer therapies such as immunotherapy and adaptive radiotherapy may be implemented in con-junction with NCRT, and the development of useful biomarkers may ultimately lead to the de-velopment of personalized treatments for LAGC. These research directions may lead to the dis-covery of the optimal approach to administering NCRT to patients with LAGC. They may also aid in the determination of the optimal candidates for undergoing NCRT.Locally advanced gastric cancer (LAGC) has a poor prognosis with surgical resection alone, and neoadjuvant treatment has been recommended to improve surgical and oncological outcomes. Although neoadjuvant chemotherapy has been established to be effective for LAGC, the role of neoadjuvant chemoradiotherapy (NCRT) remains under investigation. Clinical experience and research evidence on esophagogastric junction adenocarcinoma (e.g., cardia gastric cancers) indicate that the likelihood of achieving sustainable local control is higher through NCRT than through resection alone. Furthermore, NCRT also has an acceptable treatment-related toxicity and adverse event profile. In particular, it increases the likelihood of achieving an R0 resection and a pathological complete response (pCR). Moreover, NCRT results in higher overall and recurrence-free survival rates than surgery alone; however, evidence on the survival benefits of NCRT versus neoadjuvant chemotherapy (NCT) remains conflicting. For noncardia gastric cancer, the efficacy of NCRT has mostly been reported in retrospective studies, and several large clinical trials are ongoing. Consequently, NCRT might play a more essential role in unresectable LAGC, for which NCT alone may not be adequate to attain disease control. The continual improvements in systemic treatments, radiotherapy techniques, and emerging biomarkers can also lead to improved personalized therapy for NCRT. To elucidate the contributions of NCRT to gastric cancer treatment in the future, the efficacy, potential toxicity, predictive biomarkers, and clinical considerations for implementing NCRT in different types of LAGC were reviewed.

P-130 Latin American population with adenocarcinoma of the esophagogastric junction: A 9-year follow up

Esophagogastric junction (EGJ) adenocarcinoma represents 27% of gastric tumors with an increasing incidence in Western countries. Additionally, up to 80% of EGJ tumors are diagnosed in advanced stages of disease, therefore the prognosis is usually poor, with a 5-year overall survival rate of less than 30%. It is known that EGJ tumors are an entity with its own epidemiological characteristics, biological behavior, and prognosis, without evidence to support optimal management. The aim of this study was to describe clinicopathological features, treatment, and outcome of Latin American patients with EGJ adenocarcinoma treated at the National Cancer Institute.

P-160 Primary gastrointestinal lymphoma in Latin American patients. A 10-year follow-up

Gastrointestinal lymphomas constitute 10-15% of non-Hodgkin´s Lymphomas and 30-40% of extra-nodal lymphomas. Primary gastric lymphoma (PGL) is the most common site (75%) and is most diagnosed in man with a mean age of 60 years. Even when prognosis is favorable at early stages of disease, most patients are diagnosed with advanced disease and treatment pattern remains under debate with not enough evidence to support optimal management. The aim of this study was to describe incidence, clinicopathological characteristics, treatment modalities and outcome of Latin American patients with PGL treated at the National Cancer Institute. Retrospective, observational study. Included patients diagnosed with EGJ adenocarcinoma, treated at the National Cancer Institute between 2011 and 2021. Statistical analysis required: X2 and t test, Kaplan Meier, Log Rank and Cox Regression. Statistical significance differences were assessed when p was bilaterally < 0.05. A total of 62 patients were included in the analysis. The 63%(n=39) of cases were male with a median age at diagnosis of 61 (26-83) years old. Comorbidities included type 2. Diabetes (14%), and systemic arterial hypertension (21%). Additionally, 42% of patients had history of smoking and alcoholism. History of disease pretreatment was a median of 3.5 (1-40). According to symptomatology, the most prevalent symptoms were weight loss (85%, n= 53), abdominal pain (80%, n= 50), bleeding (60%, n= 37) and vomiting (58%, n= 136). Regarding histology the 90%(n=56) of cases were B cell lineage. Most common immunohistochemistry markers were CD20 (95%; n=59), BCL6 (63%; n=39), and CD10 (47%; n=29), also c-MYC rearrangement was found in (21%; n=13). Respecting clinical stage, most patients were diagnosed at metastatic disease (44%; n=27), the most common extranodal site of disease was the liver (76%). Oncological treatment, the 89% (n=55) were treated with chemotherapy, being CHOP-R scheme the most common modality of treatment. Moreover, the 29% (n=18), received radiotherapy. At OS analysis, the Five-year-OS rate for total population was 54% (95%CI 54.1-85.52). Furthermore, OS analysis was conducted comparing clinical stage, clinical stage I-III patients did not reach the median-OS, compared to patients with metastatic PGL was 11 months (p=0.50). PGL is an uncommon neoplasia known for its bad prognosis and outcome, due most of PGL patients are diagnosed at metastatic disease and historically the management of PGL has been controversial. Nevertheless, the addition of Rituximab to standard chemotherapy have demonstrated to significantly increase the OS of patients. Further studies remain necessary to promote an early diagnosis and to establish the optimal management of PGL.

Preliminary experience with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after total laparoscopic proximal gastrectomy for the treatment of adenocarcinoma of esophagogastric junction

(1) adenocarcinoma of esophagogastric junction (Seiwert type II-III) was diagnosed by endoscopy and pathological examination; (2) ability to preserve at least 1/2 of the distal stomach after R0 resection of proximal stomach was evaluated preoperatively. (1) evaluation indicated distant metastasis of tumor or invasion of other organs; (2) short abdominal esophagus or existence of diaphragmatic hiatal hernia was assessed during the operation; (3) mesentery was too short or the tension was too high; (4) existence of severe comorbidities before surgery; (5) only palliative surgery was required in preoperative evaluation; (6) poor nutritional status. operation time, intraoperative blood loss, postoperative complications, time to first flatus and time to start liquid diet, postoperative hospital stay, operation cost, etc. Continuous variables that conformed to normal distribution were presented as mean ± standard deviation, and those that did not conform to normal distribution were presented as median (Q1,Q3). Results: All the patients successfully completed TLPG with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis, and postoperative pathology showed that no cancer cells were found on the upper incision margin. The operation time was (247.9±62.4) minutes, the median intraoperative blood loss was 100.0 (62.5, 100.0) ml, no intraoperative blood transfusion was required, the incision length was (4.9±1.0) cm, and the operation cost was (55.5±0.7) thousand yuan. The median time to start liquid diet was 1.0 (1.0, 2.0) days, and the mean time to flatus was (3.1±0.9) days. All the patients were discharged uneventfully. Only 1 patient developed postoperative paralytic ileus and infectious pneumonia with Clavien-Dindo classification of grade II. The patient recovered after conservative treatment. There was no surgery-related death. The postoperative hospital stay was (8.3±2.1) days. Conclusion: The double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after TLPG is safe and feasible, which can minimize surgical trauma and accelerate postoperative recovery.