Esophagogastric Junction Cancer Research Articles

Conversion surgery for esophageal and esophagogastric junction cancer.

As a result of the recent advances in first-line treatment including chemotherapy, radiation therapy, targeted therapy, and immune checkpoint inhibitor immunotherapy (ICI) for locally advanced/metastatic initially unresectable esophageal and esophagogastric junction cancer, surgery aiming at cure after initial treatment, so-called "conversion surgery" has become more common in this field. Several studies have indicated encouraging survival outcomes for patients after conversion surgery with R0 resection. However, various issues, such the utility and the safety of conversion surgery remain unclear. In this review, we will focus on the surgical treatment for initially unresectable esophageal and esophagogastric junction cancer after first- or later- line treatment and review recent evidence regarding the safety and the efficacy of conversion surgery. Multidisciplinary treatment including surgery may serve as a novel treatment strategy for esophageal and esophagogastric junction cancer, thus provide a curative treatment option and potentially contribute to better prognosis for initially untreatable diseases.

Efficacy of the U‐shaped flap technique in preventing reflux after minimally invasive proximal gastrectomy for proximal gastric and esophagogastric junction cancer

Efficacy of the U‐shaped flap technique in preventing reflux after minimally invasive proximal gastrectomy for proximal gastric and esophagogastric junction cancer

INTEGRATE IIa Phase III Study: Regorafenib for Refractory Advanced Gastric Cancer.

Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS). A double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment, stratified by tumor location, geographic region (Asia v rest of world), and prior vascular endothelial growth factor inhibitors. The primary end point was OS. Treatment efficacy on OS was first tested in the pooled INTEGRATE I + INTEGRATE IIa cohort and, if significant, then in the INTEGRATE IIa cohort. Secondary end points were PFS, objective response rate, safety, and quality of life (QoL). INTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo. No significant heterogeneity was observed between INTEGRATE I and INTEGRATE IIa studies on OS. Pooled OS analysis hazard ratio (HR) was 0.70 (95% CI, 0.56 to 0.87; P = .001; 361 events). INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P = .006; 238 events), the median OS was 4.5 months versus 4.0 months, and 12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively. After a preplanned adjustment for multiplicity, there were no statistically significant differences across regions or other prespecified subgroups. Regorafenib improved PFS (HR, 0.53 [95% CI, 0.40 to 0.70]; P < .0001) and delayed deterioration in global QoL (HR, 0.68 [95% CI, 0.52 to 0.89]; P = .0043). The toxicity profile was consistent with that of previous reports. Regorafenib improves survival compared with placebo in refractory AGOC.

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.

Immunotherapy as a new perspective for the therapy of esophageal cancer

Abstract The therapeutic landscape in nearly every therapeutic line in advanced/metastatic patients with squamous cell carcinoma (SCC) and esophagogastric adenocarcinoma (EGC) is enriched by recent approvals of immune checkpoint inhibitors (ICIs). In curative intended therapy, patients without pathological residual disease of SCC or GEJ (esophagogastric junction) cancer after preoperative chemoradiation and complete resection have access to adjuvant immunotherapy (independent of PD-L1 (programmed cell death protein 1) status, nivolumab, CHECKMATE 577). For metastatic SCC in the first-line, nivolumab combined with chemotherapy or with ipilimumab (TPS (tumor proportion score) ≥1 %, SCC, CHECKMATE 648) are approved, as well as second-line nivolumab alone regardless of PD-L1 status (ATTRACTION 03). For both, locally advanced or metastatic SCC and EGC, chemotherapy with pembrolizumab is available for patients with CPS (combined positive score) ≥10 (KEYNOTE 590) and for adenocarcinoma with nivolumab (CPS ≥5, CHECKMATE 649). Recent added approvals are chemotherapy with pembrolizumab in CPS ≥1 patients (KEYNOTE 859) and the addition of trastuzumab for personalized therapy in HER-2 positive/CPS ≥1 gastric and GEJ patients (KEYNOTE 811).

329. PREDICTION OF MEDIASTINAL LYMPH NODE METASTASIS IN SIEWERT TYPE I/II ESOPHAGOGASTRIC JUNCTION CANCER WITH ESOPHAGEAL INVASION

Abstract Background Mediastinal lymph node dissection (LND) is a critical factor to decide the surgical strategy for Esophagogastric junction (EGJ) cancers. As a result of a prospective multicenter study in Japan, surgical algorithm including the extent of LND for EGJ cancers has recently been proposed according to the length of esophageal invasion. However, preoperative measure predicting upper mediastinal LN metastasis is still lacking, and the oncologic efficacy of mediastinal LND remain unknown. Methods The aim of this study was to identify preoperative factors predicting mediastinal LN metastasis, and we hypothesized that preoperative CT image would be of utility. Patients who underwent surgical treatment for Siewert Type I/II EGJ cancer with esophageal invasion with curative intent between 2000 and 2022 at the Tokai University Hospital were retrospectively reviewed. Results A total of 103 patients were enrolled. Among them, 55, 74, and 74 patients underwent upper, middle, and lower mediastinal LND, respectively. Upper/middle/lower mediastinal LN metastasis was observed in 14/13/23 of those patients, respectively, with lower thoracic paraesophageal LNs (29%), middle thoracic paraesophageal LNs (18%), and right recurrent nerve LNs (16%) being the three most common metastatic sites. Estimated invasion depth of the primary lesion≧cT3 (p≦0.007), tumor size≧4cm (p≦0.002), esophageal invasion length≧4cm (p≦0.007) and minor axis of the LN≧5mm by preoperative CT image (p&amp;lt;0.001) were significant preoperative factors related to mediastinal LN metastasis. Conclusion Clinical T factor, tumor size, the size of mediastinal LN by CT image, as well as esophageal invasion length, were important preoperative factors to predict mediastinal LN metastasis, and those factors should be taken into consideration to decide the surgical strategy for EGJ cancers with esophageal invasion. Survival impact of mediastinal LND still remain unclear, and further accumulation of cases and prospective studies are awaited.

322. IMPACT OF POSTOPERATIVE NUTRITIONAL SUPPORT MODES ON CLINICAL AND PATIENT-REPORTED OUTCOMES IN ENHANCED RECOVERY AFTER ESOPHAGECTOMY FOR CANCER

Abstract Background Enhanced Recovery After Surgery (ERAS) for esophagectomy has been demonstrated to be safe and effective. However, there is significant variation in the nutritional support treatment modes during the perioperative period. We have recently developed a novel ERAS nutritional support mode. In this study, we compared this new mode with the previous ERAS nutritional support treatment mode to assess their impact on clinical and Patient-Reported Outcomes (PROs), aiming to develop an optimal approach. Methods We enrolled 357 patients who underwent esophagectomy for esophageal thoracic cancer or esophagogastric junction cancer from June 2021 to August 2023. Two different ERAS nutritional support treatment protocols were used postoperatively: the control group previously received enteral nutrition by nasojejunal tube + parenteral nutrition + early oral diet after surgery, while the study group currently received parenteral nutrition + early oral diet. We compared the two groups in terms of clinical observation indicators, hematological analysis, serum protein changes and clinical outcomes. The comparison of quality of life on PROs was assessed using the MD Anderson Symptom Inventory. Symptom changes were analyzed using a mixed-effects model. Results A total of 324 patients successfully completed the ERAS nutritional support protocols. The success rates were 91% in the control group and 90.2% in the study group, with no statistically significant difference (p&amp;gt;0.05). The incidence of complications did not significantly differ between the two groups (p&amp;gt;0.05). Compared to the control group (n=223), the study group (n=101) significantly shortened the chest drain time (6.2±2.6 days vs. 6.6±1.5 days, p&amp;lt;0.05) and elevated the levels of serum total protein and albumin on the 4th postoperative day (53±5 g/L vs. 51±4 g/L, 30±2 g/L vs. 28±2 g/L, p&amp;lt;0.05). There were no statistically significant differences in the first flatus time, first defecation time, infusion time and postoperative hospital stay between the two groups (p&amp;gt;0.05). The comparison of hematological analysis, serum protein changes, changes in body weight during the perioperative period and 30-day readmission rate showed no statistically significant differences (p&amp;gt;0.05). In the MD Anderson Symptom Inventory, the study group had significantly better scores in sadness, dry mouth, enjoyment of life, and general activity dimensions compared to the control group (p=0.013, p&amp;lt;0.001, p=0.045, p=0.008). Conclusion Based on the similar rehabilitation outcomes, the simplified ERAS nutritional support treatment mode without postoperative enteral nutrition by nasojejunal tube is more optimized because it is physiological sound and significantly improves quality of life on PROs.

350. CONTINUOUS INTRAOPERATIVE NERVE MONITORING TO REDUCE THE LEFT RECURRENT LARYNGEAL NERVE PARALYSIS IN TRANSMEDIASTINAL ESOPHAGECTOMY

Abstract Introduction Transmediastinal esophagectomy (TME) is a curative option for esophageal cancer, and can achieve total mediastinal lymph node dissection (LND) with transcervical and transhiatal procedures. With the transcervical procedure, the upper mediastinal LND is highly associated with the risk of causing recurrent laryngeal nerve paralysis (RLNP). Continuous intraoperative nerve monitoring (CIONM) can visualize the risk procedure in real time, which may result in reducing postoperative RLNP. The aim of this study was to clarify the usefulness of CIONM in reducing postoperative left RLNP with TME. Material and methods A total of 227 patients who underwent TME for esophageal cancer (EC) or esophagogastric junction cancer (EGJC) between October 2017 and July 2022 at our institution were included in this study. Patients who did not undergo the upper and middle mediastinal LND (33 patients) and could not undergo CIONM (34 patients) were excluded from these 227 patients. Finally, we analyzed data on 160 patients. The clinicopathological data were reviewed from the medical record database of our institution. Results The technical implementation rate of CIONM was 87.4%. The diagnostic performance for RLNP with amplitude&amp;lt;100μV (LOS: loss of signal) at the end of transcervical procedure was as follows (sensitivity: 83.3%, specificity: 90.7%, positive diagnostic value: 88.8%). In the univariate analysis, the frequency of left RLNP was significantly higher in male, patients with primary tumor located at the upper thoracic esophagus, and patients with LOS (p&amp;lt;0.001, respectively). Moreover, the multivariate analysis identified patients with tumor located at the upper thoracic esophagus and patients with LOS (p&amp;lt;0.001) as independent risk factors for left RLNP. Conclusion In the present study, we showed the significant association between amplitude LOS and left RLNP. CIONM could contribute to reducing left RLNP by not only paying attention to amplitude reduction during surgery, but also learning the risk procedure that may cause nerve damage after surgery.

765. PATTERNS, TIMING, AND SURVIVAL OF RECURRENCE FOLLOWING SURGERY FOR ESOPHAGEAL ADENOCARCINOMA IN THE EUROPEAN MULTICENTRE ENSURE STUDY

Abstract Background After surgery for esophageal cancer approximately half of patients will develop disease recurrence. A more accurate and detailed understanding of the pattern, timing, treatment and prognosis of initial recurrence sites can guide improvements in surveillance and therapy. Therefore, the aim of this study was to accurately describe the pattern and timing of esophageal cancer recurrence, and to assess the distinct survival patterns of these recurrence locations. Methods This study included all patients who underwent surgical resection for esophageal and junctional adenocarcinoma registered in the ENSURE study. ENSURE was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers between 2009 and 2015 across 20 centers in Europe and Canada (NCT03461341). The first recurrence site was recorded and recurrence-free survival (RFS) was estimated using Kaplan-Meier curves. Sites of first recurrence were stratified into different groups and survival outcomes post recurrence detection were estimated using Kaplan-Meier curves. Results Of 3397 eligible patients, 1310 patients had disease recurrence with comprehensive follow-up data available (median RFS of 12.1 months). First recurrence was detected at multiple distant sites (n=469; 37.3%) or at a single distant site (n=463; 33.7%), while isolated local recurrence occurred in 189 (14.4%) patients. Liver-only recurrence occurred significantly earlier (median 9.0 months), while lung-only (15.2 months) and local-only occurred later (17.8 months). Patients with multiple-sites and liver-only recurrence had significant worse median post recurrence survival (7.4 and 8.3 months, respectively) when compared with lung- or local-only recurrence (10.4 and 15.9 months, respectively). Conclusion This study demonstrates that specific recurrence locations of esophageal cancer possess distinct RFS curves. Furthermore, specific recurrence locations result in different post recurrence survival outcomes. This information can help guide improvements in surveillance after esophageal cancer surgery and decisions regarding treatment of esophageal cancer recurrence.

270. ANALYSIS OF THE RELATIONSHIP BETWEEN CARDIAC DIAMETER AND ANASTOMOTIC TROUBLE IN TRANS HIATAL ESOPHAGOGASTRIC JUNCTION CANCER SURGERY

Abstract Background The number of esophagogastric junction (EGJ) cancers has been increasing in recent years, and the trans hiatal lower esophagectomy is widely used for cases with shorter esophageal invasion. However, the mediastinal surgical view through the hiatus is sometimes poor due to cardiac compression, and resection and reconstruction are often difficult in these cases. We therefore retrospectively examined the influence of cardiac diameter on short-term postoperative outcomes. Methods From June 2004 to December 2022, 97 patients underwent radical surgery for EGJ cancer at our hospital, of those 67 patients underwent trans-hiatal approach. We retrospectively analyzed the relationship between cardiothoracic ratio (CTR) on preoperative chest radiographs and left ventricular diastolic diameter (LVDd) on echocardiography and postoperative complications in patients underwent trans hiatal approach. Results Patients with preoperative CTR &amp;gt;50% had a significantly higher rate of anastomotic leakage (33% v.s. 7%, p&amp;lt;0.05), and similarly for LVDd, when divided into two groups using 43 mm as cut-off, patients with larger heart diameter had significantly more anastomotic leakage (69% v.s. 24%, p&amp;lt;0.05). We performed a multivariate analysis using CTR, ASA-PS, blood loss, operative time, BMI, and tumor diameter, and defined CTR as an independent risk factor for anastomotic leakage (OR: 7.76, 95%CI: 1.45-41.4, p&amp;lt;0.05). Conclusion Trans-hiatal approach can be used for resection of EGJ cancer. However, special attention should be paid to the prevention of anastomotic leakage in patients with cardiac comorbidities or a large preoperative CTR or LVDd.

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.

376. COMPARISON OF POST-SURGICAL NUTRITIONAL STATUS BETWEEN IVOR-LEWIS ESOPHAGECTOMY AND PROXIMAL GASTRECTOMY

Abstract Background In our institution, the surgical approach for esophagogastric junction cancer (EG) is determined based on the tumor location and the extent of esophageal invasion, opting for either Ivor-Lewis esophagectomy (IL) or proximal gastrectomy (PG). Both procedures necessitate the mitigation of postoperative weight loss, with nutritional therapy using Elemental diet 300 kcal/day initiated postoperatively and nutritional guidance provided by dietitians before discharge, and at 1, 3, 6, and 12 pos-operative months (POM). Additionally, quality of life (QOL) assessment using the PGSAS-37 questionnaire is conducted, and feedback is provided to patients. Methods The aim of this study is to compare the weight changes up to 12 POM and the temporal changes in PGSAS-37 scores following IL and PG procedures in our institution. We analyzed 45 cases who underwent IL or PG in our institution between January 2019 and December 2022, excluding cases of early recurrence within 12 months and those without questionnaire responses. Patient demographics, postoperative complications, anastomotic strictures, duration of Elemental intake (months), percentage of body weight loss (BWL) at 1, 3, 6, and 12 POM, and PGSAS-37 scores were extracted from electronic medical records. Results There were 27 IL cases and 18 PG cases. Postoperative complications of Grade 3 or higher were observed in 3 of IL group and 1 of PG group. Anastomotic strictures were observed in 1 of IL group and 6 of PG group. Duration of Elemental intake (months) was 4.5 (0-39) in IL group and 0 (0-8) in PG group (p=0.001). Median BWL (%) at 1/3/6/12 POM was IL: 4.5/8.3/10.3/13.8 and PG: 3.8/8.5/8.7/10.6. Temporal changes in total symptom score were similar in both IL and PG groups, but esophageal reflux subscale at 12 POM was significantly better in PG group (p=0.04). Conclusion The questionnaire response rates were approximately 80% at 12 months for both groups, but below 12 months ranged from 22.2% to 50%, indicating difficulty in assessing temporal changes in QOL. At 12 months, the IL group exhibited a greater percentage of weight loss than the PG group (p=0.027), but QOL evaluations, except for reflux symptoms SS, were comparable between the two groups. Both IL and PG groups experienced rapid weight loss up to 3 POM, with continued decline up to 12 months. However, improving questionnaire response rates is deemed necessary for investigating the relationship with QOL.

803. 2-YEAR RESULTS IN ESOPHAGOGASTRIC JUNCTION CANCER TREATMENT

Abstract Background Esophagogastric junction (EGJ), also known as cardia, tumors have unique characteristics with a widespread of lymph node (LN) metastatic patterns influenced by the extent of esophageal involvement. Besides, there is no worldwide consensus about its classification and the optimal lymphadenectomy and surgical resection extend. Recently, mapping the distribution of LN metastasis in these patients could provide some insights about the extent that should be the target. Furthermore, the balance between resection extension and the procedure safety is also difficult to achieve. This work aims to review the last 2 years of EGJ tumor treatment in a single oncological center. Methods We present a retrospective, single center study that included all the patients with EGJ cancer undergone surgical resection between 2022 and 2023. These tumors were classified using our modified Siewert (mSiewert) classification based on mapping endoscopy with measures of the full extension and not only the tumor’s epicenter. Patient demographics, tumor characterization, neoadjuvant treatment, surgical procedure and postoperative results were assessed, alongside with pathological and oncological metrics as recurrence, disease-free survival (DFS) and overall survival (OS). Results We included 64 cardia cancer patients who underwent a curative treatment strategy, with a median age of 68 years, mostly men (87.5%), with a median BMI of 25 kg/m2. 68.2% were classified as ECOG-PS 0 however 62.5% were classified as ASA III-IV. Most tumors were moderately (39.2%) or poorly (31.4%) differentiated adenocarcinomas. Majority were locally advanced (cT3, 78.1%) and in stage III (85.9%). Regarding tumor location, 49.2% were classified as mSiewert I-II (49.2%), followed by I-II-III (18%) and II-III (18%). 36.1% had esophageal involvement ≥4cm, 87.5% received neoadjuvant treatment split between the CROSS and FLOT protocols. Our resection rate was 85.9%. We mostly performed Mckeown esophagectomy (49.1%) and transhiatal esophagectomy (18.2%). We had a 12.7% admission rate to the intensive care unit and a 27.3% major complication rate (Clavien-Dindo ≥ 3b). Anastomotic dehiscence occurred in 16.4% of cases, with hospital mortality rate of 3.6%. The median hospital stay was 6 days, with a 16.4% readmission rate. Pathological staging revealed that 47.3% were stage III, with a median lymph node yield of 28 and a 98.2% R0 resection rate. Most patients received adjuvant treatment, primarily FLOT protocol or Nivolumab, in 38.2% and 29.1%, respectively. The recurrence rate was 28%, with a median time to recurrence of 26 weeks, mainly occurring as distant metastasis pattern (64.3%). One-year overall survival (OS) was 88.7%, and one-year disease-free survival (DFS) was 66.4%, with a median follow-up time of 48 weeks and only a 3.6% loss to follow-up rate. Conclusion This study highlights the unit’s adaptation of EGJ tumor treatment to new insights, emphasizing the importance of comprehensive classification and multimodal and multidisciplinary approach to enhance patient outcomes.

Near-infrared fluorescence clip guided robot-assisted minimally invasive esophagectomy for esophagogastric junction cancer: a case report

BackgroundAlthough treatment strategy differs between countries, surgery remain the mainstay of treatment for localized esophagogastric junction cancer. Tumor proximal margin is one of the critical factors to achieve curative resection during esophagogastric junction cancer surgery. Thus, an accurate preoperative marking of the tumor is essential, however, accuracy of conventional methods was highly dependent upon endoscopists skills. Here, we present a case of a patient with locally advanced Siewert type II esophagogastric junction cancer treated by robot-assisted minimally invasive esophagectomy utilizing near-infrared fluorescence clip as a novel marking method.Case presentationA male patient in his 70 s was diagnosed as having cT3N1M1 esophagogastric junction cancer and was treated by immunochemotherapy followed by surgery. Near-infrared fluorescence marking clips were placed 2 cm above the tumor proximal end under endoscopy prior to surgery. Location of the clips were confirmed by fluorescence imaging during robotic surgery, and the esophagus was dissected by a surgical stapler without intraoperative endoscopy. Histopathologically, the tumor was diagnosed as ypT2N0M0, with negative margins.ConclusionsNear-infrared fluorescence clip may enable easy, safe, and an accurate preoperative marking, and may be considered during endoscopic surgeries.

Final results of a randomized controlled trial: comparison of the efficacy and safety between totally laparoscopic and laparoscopic-assisted total gastrectomy for advanced siewert III esophagogastric junction cancer and upper and middle third gastric cancer.

This study aimed to compare the efficacy and safety of TLTG with the overlap technique to LATG in patients with advanced Siewert III Esophagogastric Junction Cancer and upper and middle third gastric cancer. This single-center RCT enrolled 292 patients with the mentioned cancers, randomly assigned to TLTG overlap (n=146) or LATG (n=146) groups. Data on demographics, pathology, intraoperative variables, postoperative complications, recovery parameters, and 3-year survival were collected. Main outcome: postoperative complications within 30 days. Secondary outcomes: 3-year disease-free and overall survival. TLTG versus LATG: TLTG had shorter incision, faster flatus/defecation, reduced analgesia, less opioid use, and shorter hospital stay. Similar operation time, anastomosis time, blood loss, and lymph node harvest. TLTG had lower overall post-op complication rate (P=0.047), no significant difference in serious complications (P=0.310). Variances in anastomotic stenosis occurrence at 3 months. No rehospitalization or mortality at 30 days. No significant differences in 3-month disease-free survival (P=0.058) or overall survival (P=0.236). Overlap method for anastomosis in TLTG is safe and feasible for advanced middle-upper-third gastric cancer, with positive short-term outcomes. This technique has potential as the preferred esophagojejunostomy approach in TLTG. This trial has been registered at Chinese Clinical Trial Registry: XXXXXXXX (registration date: September 4, 2019).

Safety of robotic double-flap technique following proximal gastrectomy in the introductory phase compared with laparoscopic procedure: a propensity score-matched analysis.

Proximal gastrectomy (PG) is recommended for upper-third gastric cancer and esophagogastric junction (EGJ) cancer, preserving organ function while reducing postoperative symptoms. The double-flap technique (DFT) is one approach to minimize reflux after PG. However, laparoscopic PG with DFT (LPG-DFT) has drawbacks of increased complexity, such as hand sutures for anastomosis. Robotic surgery offers potential advantages for DFT reconstruction, but the safety of robotic DFT following PG (RPG-DFT) in the introductory phase is unknown. This retrospective study compared the outcomes of RPG-DFT with LPG-DFT. Data from 402 patients (321 LPG-DFT, 81 RPG-DFT) between 2009 and 2023 were analyzed. Propensity score matching balanced patient demographics and tumor characteristics. Surgical parameters, complications, and long-term outcomes were assessed. The surgery time of LPG-DFT has stabilized in patients since 2016. Thus, LPG-DFT from 2016 was defined as a stable procedure. RPG-DFT was started in 2019, after minimally invasive DFT reconstruction had been mastered at our center. Therefore, we compared the surgical outcomes of introductory RPG-DFT with stable LPG-DFT. Matched analysis revealed that RPG-DFT in the introductory phase had significantly longer surgery times but less bleeding and shorter reconstruction times and hospital stays than stable LPG-DFT. Frequencies of short-term complications and reflux esophagitis were comparable in both groups. Although RPG-DFT in the introductory phase exhibited higher incidence of anastomotic stenosis than stable LPG-DFT, the incidence of anastomotic stenosis decreased over time. This study demonstrated the safety of RPG-DFT in the introductory phase for EGJ and upper-third stomach tumors, with outcomes comparable to stable LPG-DFT. RPG-DFT offers shorter reconstruction time and less blood loss compared with LPG-DFT. However, anastomotic stenosis is a complication to monitor in early robotic surgery.

Radiomics in Oesogastric Cancer: Staging and Prediction of Preoperative Treatment Response: A Narrative Review and the Results of Personal Experience.

Oesophageal, gastroesophageal, and gastric malignancies are often diagnosed at locally advanced stage and multimodal therapy is recommended to increase the chances of survival. However, given the significant variation in treatment response, there is a clear imperative to refine patient stratification. The aim of this narrative review was to explore the existing evidence and the potential of radiomics to improve staging and prediction of treatment response of oesogastric cancers. The references for this review article were identified via MEDLINE (PubMed) and Scopus searches with the terms "radiomics", "texture analysis", "oesophageal cancer", "gastroesophageal junction cancer", "oesophagogastric junction cancer", "gastric cancer", "stomach cancer", "staging", and "treatment response" until May 2024. Radiomics proved to be effective in improving disease staging and prediction of treatment response for both oesophageal and gastric cancer with all imaging modalities (TC, MRI, and 18F-FDG PET/CT). The literature data on the application of radiomics to gastroesophageal junction cancer are very scarce. Radiomics models perform better when integrating different imaging modalities compared to a single radiology method and when combining clinical to radiomics features compared to only a radiomics signature. Radiomics shows potential in noninvasive staging and predicting response to preoperative therapy among patients with locally advanced oesogastric cancer. As a future perspective, the incorporation of molecular subgroup analysis to clinical and radiomic features may even increase the effectiveness of these predictive and prognostic models.

DNA methylation-mediated suppression of TUSC1 expression regulates the malignant progression of esophagogastric junction cancer

BackgroundEsophagogastric junction cancer (EJC) refers to malignant tumors that develop at the junction between the stomach and the esophagus. TUSC1 is a recently identified tumor suppressor gene known for its involvement in various types of cancer. The objective of this investigation was to elucidate the regulatory influence of DNA methylation on TUSC1 expression and its role in the progression of EJC.MethodsBioinformatics software was utilized to analyze the expression of TUSC1, enriched pathways, and highly methylated sites in the promoter region. TUSC1 expression in EJC was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB), and immunohistochemistry. Methylation-specific PCR was employed to detect the methylation level of TUSC1. To analyze the effects of TUSC1 and 5-AZA-2 on tumor cell proliferation, migration, invasion, cell cycle, and apoptosis, several assays including CCK-8, colony formation, transwell, and flow cytometry were conducted. The expression of MDM2 was assessed using qRT-PCR and WB. WB detected the expression of p53, and p-p53, markers for EJC cell proliferation, epithelial-mesenchymal transition, and apoptosis. The role of TUSC1 in tumor occurrence in vivo was examined using a xenograft mouse model.ResultsTUSC1 expression was significantly downregulated in EJC. Overexpression of TUSC1 and treatment with 5-AZA-2 inhibited the malignant progression of EJC cells. In EJC, low methylation levels promoted the expression of TUSC1. Upregulation of TUSC1 suppressed the expression of MDM2 and activated the p53 signaling pathway. Inactivation of this pathway attenuated the inhibitory effect of TUSC1 overexpression on EJC cell proliferation, migration, invasion, and other behaviors. Animal experiments demonstrated that TUSC1 overexpression inhibited EJC tumor growth and metastasis in vivo.ConclusionTUSC1 was commonly downregulated in EJC and regulated by methylation. It repressed the malignant progression of EJC tumors by mediating the p53 pathway, suggesting its potential as a diagnostic and therapeutic target for EJC.

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.