Adenocarcinoma Of The Esophagogastric Junction Research Articles

XRCC1 is linked to poor prognosis in adenocarcinoma of the esophagogastric junction after radiotherapy: transcriptome and alternative splicing events analysis.

This study aimed to (i) investigate the relationship between X-ray repair cross-complementing protein 1 gene (XRCC1) and prognosis in patients with adenocarcinoma of the esophagogastric junction (AEG), and (ii) analyze the roles of XRCC1 in human gastric adenocarcinoma (AGS) cells following X-ray radiation. A total of 46 AEG patients were enrolled and examined for XRCC1 protein by immunohistochemistry. XRCC1 was knocked down in AGS cells by transfection, and AGS cells were subsequently exposed to 6Gy of X-ray radiation. XRCC1 mRNA and protein expression was examined via quantitative real-time PCR (qRT-PCR) and Western blot analysis. The apoptosis of AGS cells was examined by flow cytometer. RNA-sequencing technology was used to identified differentially expressed genes and alternative splicing events following XRCC1 knockdown and radiation exposure. XRCC1 positivity was strongly associated with distant metastasis, pathological tumor-node-metastasis (pTNM) classification, and radiotherapy resistance in AEG patients. A significant difference in progression-free survival was observed between AEG patients with low and high XRCC1 protein expression. The knockdown of XRCC1 notably exacerbated the effects of X-ray radiation on apoptosis in AGS cells. Additionally, X-ray radiation modified the expression of genes related to apoptosis and immune response in XRCC1-knockdown AGS cells. Furthermore, the generation of splice variants was influenced by XRCC1 knockdown in AGS cells. XRCC1 may serve as a key oncogene that elucidates the role of alternative splicing events in the progression of AEG following X-ray treatment.

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

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

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

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

Tumor-Infiltrating Lymphocytes in Resected Esophageal and Gastric Adenocarcinomas Do Not Correlate with Tumor Regression Score After Neoadjuvant Chemotherapy: Results of a Case-Series Study.

Background/Objectives: Adenocarcinomas of the esophagogastric junction and stomach present clinical entities with significant cancer-related morbidity and mortality, often requiring multimodal treatments. Preoperative chemotherapy, mainly the FLOT regimen, is increasingly being utilized in the neoadjuvant setting for the treatment of these malignancies, with varying degrees of tumor response. Methods: We conducted a retrospective, single-institution review on 75 patients operated on for adenocarcinoma of the esophagogastric junction and stomach after neoadjuvant FLOT. We investigated whether tumor response correlates with disease response in lymph nodes examined on surgical specimens. We also investigated the role of tumor-infiltrating lymphocytes (TILs) in correlation with primary tumor response and disease response in lymph nodes on pathological specimens. Results: Our results suggest that TILs correlate in a differential manner with regards to primary tumors versus lymph nodes, thus suggesting that there are different biologic processes in place. Conclusions: Our results provide unique evidence on tumor-infiltrating lymphocytes in the adenocarcinoma histology of the esophagogastric junction and stomach and might be important for further studies.

Short-term outcomes and quality of life of esophagogastrostomy versus the double-tract reconstruction after laparoscopic proximal gastrectomy

BackgroundThere is no optimal reconstruction technique after proximal gastrectomy. The esophagogastrostomy (EG) is a rather simple procedure technically, but the incidences of reflux esophagitis and anastomotic stricture are higher. While the double-tract reconstruction (DTR) can lessen postoperative reflux esophagitis, it is technically complex with a long operation time. The purpose of this study was to evaluate the quality of life (QoL) and short-term outcomes of the two reconstruction techniques.MethodsWe retrospectively collected consecutive patients with upper-third gastric adenocarcinoma and adenocarcinoma of the esophagogastric junction (AEG) at our center between 2019 June and 2023 May. Patients who underwent laparoscopic proximal gastrectomy (LPG) with EG or DTR were included in this study. A comparison was made between the clinical and pathological characteristics of patients and their surgical parameters, postoperative complications, and its 1-year QoL in two groups. The QoL of the two groups was assessed by Visick grading, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-STO22 scales at 1 year after operation. The nutritional status of the two groups was evaluated by BMI, hemoglobin and serum albumin.ResultsAII the qualified patients were divided EG group (n = 63) and DTR group (n = 93). Compared to the DTR group, the blood loss volume of EG group was more (p = 0.001). There were no significant differences in operation duration, number of lymph nodes dissected, and postoperative length of stay between the two groups(p > 0.05). No statistical differences were observed in terms of the incidence of early complications and Clavien-Dindo classification as well(p > 0.05). After one year, the Visick grade of the DTR group was better than EG group (p = 0.040). The multivariable logistic regression analysis showed the only independent risk factor for reflux esophagitis was the reconstruction method. According to the EORTC QLQ-C30 questionnaire, patients in the DTR group had a better global health status(p = 0.001) and complained less about nausea and vomiting(p = 0.033), and appetite loss (p = 0.022). Patients in the DTR group complained less about reflux (p = 0.030) based on the EORTC QLQ-STO22 questionnaire. The multiple linear regression analysis revealed that the reconstruction method, reflux esophagitis and age had a linear relationship with the global health status score. Regarding nutritional status, BMI of the two groups both decreased 1 year after operation, and BMI decline value of the DTR group was lower than EG group (p = 0.001). There is no statistically significant difference between the two groups as for postoperative change in hemoglobin and serum albumin.ConclusionOur findings suggest that it is possible for skilled surgeons to achieve minimal blood loss volume without significantly increasing operation duration when performing DRT, which does not raise risk. In terms of anti-reflux, postoperative QoL and BMI maintenance, 1-year postoperative follow-up outcomes reveal the DTR is superior to EG, which deserve further research and promotion.

A preliminary exploration of reduced port laparoscopic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (ROSF)

Objective: This study aimed to share preliminary experiences of single-incision plus two ports laparoscopic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (ROSF). Methods: Following the 6th edition of the Japanese Gastric Cancer Treatment Guidelines, proximal gastrectomy with lymphadenectomy was performed. Using a single-port approach, the esophagus was transected at least 2 cm above the tumor's upper margin with linear staplers. The stomach was then extracted through a periumbilical incision, and the proximal stomach was subsequently transected extracorporeally, while ensuring appropriate resection margins on both the greater and lesser curvatures. A single flap was created before returning the remnant stomach to the abdominal cavity and re-establishing pneumoperitoneum. The No.2 clip was used to grasp and elevate the esophageal stump. An incision was made at the right lower edge of the esophageal stump to guarantee that the esophageal lumen was open. The linear stapler was then inserted into the openings of the stomach and esophagus to perform a side overlap anastomosis with a length of 3 cm. Another barbed suture was used to close the common opening of the esophagus and the stomach, and the same barbed suture were used to suture the gastric wall to the lower edge of the muscle flap. The first barbed suture was then used to sequentially suture the proximal brim of the flap to the esophagus and the right brim of the flap to the right brim of the mucosal window. After completion of anastomosis, a drainage tube was inserted through the right upper port. This procedure was employed from November 2023 to March 2024 on five patients diagnosed with adenocarcinoma of the esophagogastric junction and upper stomach. The cohort consisted of three males and two females, with an age range of 62 to 75 years and a body mass index (BMI) of 13.7 to 24.2 kg/m². All cases were preoperatively staged as T1-2N0M0, confirmed by endoscopic biopsy and enhanced CT scans of the chest, abdomen, and pelvis. Results: All five patients successfully underwent the surgery. The median surgery time was 180-325 minutes, with the intraoperative blood loss of 30-50 ml. The number of lymph nodes harvested ranged from 18 to 27. The time to first flatus, and restore liquid diet and was 2.0-5.0 and 1.0-3.0 days, respectively. The postoperative length of stay was 9.0-11.0 days. The pain scores on the Numeric Rating Scale (NRS). On the first day, the pain scores were 3.0 in two cases, 2.0 in two cases, and 1.0 in one case. On the second day, the pain scores were 2.0 in two cases and 1.0 in three cases. On the third day, the pain scores were 1.0 in four cases and 2.0 in one case. No short-term postoperative complications were observed, and there were no perioperative deaths. Conclusion: Single-incision plus two ports laparoscopic proximal gastrectomy with ROSF is safe and feasible.

Tumor thickness is associated with metastasis in patients with submucosal invasive adenocarcinoma of the esophagogastric junction.

In submucosal invasive adenocarcinoma of the esophagogastric junction (pT1b-SM AEG), the extent of tumor submucosal (SM) invasion is measured using the vertical depth of SM invasion with the muscularis mucosa. This study aimed to investigate whether tumor thickness and depth of invasion without accounting for muscularis mucosa were superior to the vertical depth of SM invasion as metastasis predictors. We enrolled patients with pT1b-SM AEG who underwent endoscopic resection or surgical resection (SR) at our institution between January 2011 and September 2019 and were followed up for ≥2years. The relationship between metastasis and clinicopathological factors was examined. Metastasis was defined as pathologically confirmed lymph node metastasis in the surgical specimen or recurrence during follow-up. This study included 57 patients (44 men; median age, 72years). Endoscopic resection and SR were performed in 16 and 41 patients, respectively. Nine patients were diagnosed with metastasis: five who underwent SR showed pathologically confirmed lymph node metastasis in the surgical specimens, and four experienced recurrences during a median follow-up of 48months. Univariate analyses showed that tumor thickness was significantly associated with metastasis (P = 0.021), and the vertical depth of SM invasion (P = 0.48) and depth of invasion (P = 0.38) were not. Furthermore, in multivariate analysis, tumor thickness ≥2800μm (odds ratio, 38.70; P = 0.013) was a significant predictor for metastasis. Tumor thickness may be a more convenient and useful predictor of metastasis in patients with pT1b-SM AEG than the vertical depth of SM invasion.

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

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

Adenocarcinoma of the esophagogastric junction: characteristics of female patients and young adult patients based on a 12-year retrospective and prospective multicenter clinicoepidemiological cohort study in Japan

BackgroundAdenocarcinoma of the esophagogastric junction (AEGJ) is most common in men and the elderly, but the disease is becoming more common in female and young adult persons. We have investigated the clinicoepidemiological characteristics of female and young adult patients with AEGJ and the 12-year trends in the Kurashiki area for young adult patients with AEGJ.MethodsPatients diagnosed with AEGJ in 12 hospitals between January 2008 and December 2019 were included in this study. Patients were divided into three groups by age (young adult [≤50 years], middle-aged [51 to 70 years], and elderly [>70 years]). Factors associated with AEGJ such as obesity, smoking, hiatal hernia and male, which were reported in our previous study, were identified.ResultsOne hundred and eighty-eight AEGJ patients, including 36 females and 20 young adults, were characterized. There was no significant change in the annual incidence of AEGJ among female (p=0.078) and young adult patients (p=0.89). Female patients without any associated factors, accounting for 53% (19/36) of the female patients and young adult patients, had significantly more histologically undifferentiated cancers than patients with at least one associated factor (58% [11/19] vs. 30% [50/169], p=0.025) and middle-aged and elderly patients (60% [12/20] vs. 30% [25/83] vs. 28% [24/85], p =0.026). Smoking was significantly less common in women than in men (8% [3/36] vs. 57% [87/152], p < 0.01). There were no significant differences between ages in the proportions of these associated factors.ConclusionsHistologically undifferentiated AEGJ cancers were more frequent in female patients without any associated factors and in young adult patients. Factors associated with AEGJ may differ between women and men, but they are similar in young adults and older adults. No increase in young adult patients with AEGJ was observed in the 12-year study.

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.

Modified hepatic left lateral lobe inversion in laparoscopic proximal gastrectomy: An analysis of 13 cases.

In laparoscopic proximal gastrectomy (LPG), the prolapse of the hepatic left lateral lobe near the lesser curvature and esophageal hiatus can obstruct the field of vision and operation. Therefore, it is necessary to retract or obstruct the hepatic left lateral lobe to ensure a clear field of vision. To investigate the safety and clinical efficacy of the modified hepatic left lateral lobe inversion technique for LPG. A retrospective analysis was conducted on the clinical data of 13 consecutive patients with early-stage upper gastric adenocarcinoma or adenocarcinoma of the esophagogastric junction treated with LPG from January to December 2023 at the Department of Gastrointestinal Surgery, Second Affiliated Hospital of Fujian Medical University. The modified hepatic left lateral lobe inversion technique was used to expose the surgical field in all patients, and short-term outcomes were observed. In all 13 patients, the modified hepatic left lateral lobe inversion technique was successful during surgery without the need for re-retraction or alteration of the liver traction method. There were no instances of esophageal hiatus occlusion, eliminating the need for forceps to assist in exposure. There was no occurrence of intraoperative hepatic hemorrhage, hepatic vein injury, or hepatic congestion. No postoperative digestive complications of Clavien-Dindo grade ≥ II occurred within 30 days after surgery, except for a single case of pulmonary infection. Some patients experienced increases in alanine aminotransferase and aspartate aminotransferase levels on the first day after surgery, which significantly decreased by the third day and returned to normal by the seventh day after surgery. The modified hepatic left lateral lobe inversion technique has demonstrated satisfactory results, offering advantages in terms of facilitating surgical procedures, reducing surgical trauma, and protecting the liver.

Learning curve for a five-step procedure, transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction

Objective: To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction. Methods: In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M(Q1, Q3) and the Mann-Whitney U test was used for inter group comparison. Results: The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x3-4.4757x2+164.97x-264.4 (P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor (P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups (P=0.238). Conclusion: Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

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.

Characteristics and Long-Term Outcome of Adenocarcinoma of the Esophagogastric Junction: A 23-Year Experience at a Tertiary Hospital in Thailand

Characteristics and Long-Term Outcome of Adenocarcinoma of the Esophagogastric Junction: A 23-Year Experience at a Tertiary Hospital in Thailand

563. CURRENT AND PROPOSED TREATMENT STRATEGIES FOR LOCALLY ADVANCED ESOPHAGEAL ADENOCARCINOMA OF THE ESOPHAGOGASTRIC JUNCTION

Abstract Background The optimal treatment strategy for locally advanced esophageal adenocarcinoma of the esophagogastric junction (AEG) is still unclear, and no consensus exists whether to treat it as an esophageal cancer or as a gastric cancer, which would include adjuvant therapy. The purpose of this study was to determine the optimal lymph node dissection, considering lymph node metastases and to develop a strategy for treatment that includes adjuvant therapy to improve the survival rate. Methods The patients were selected from a retrospective study by the Department of Surgery, Institute of Gastroenterological Surgery, Tokyo Women’s Medical University, that was conducted from 1990 to 2019. We studied 88 cases of advanced AEG in patients who underwent surgery with lymph node dissection. We retrospectively investigated the patient characteristics, pathological findings, surgical procedures, optimum extent of lymph node dissection, location of metastatic lymph nodes, recurrence pattern, and survival curves. Results Positivity for H. pylori was 29.8%. Barrett esophagus was found in 33%. Barrett esophagus was low. The calculated index for each nodal station was in stations 1, 2, 3, 7, 11 and 110 for 3-year survival and in stations 1, 2, 3 and 7 for 5-year survival. The proportion with undifferentiated histological type was high. The surgical approach underwent lower esophagectomy + proximal gastrectomy. Double-tract reconstruction was performed in 45%. Adjuvant (postoperative) chemotherapy was given to 51% patients. Preoperative (neoadjuvant) chemoradiotherapy was 17%. The 5-year overall survival rates were 24%. Conclusion We found that the optimal lymph node resection consists of the inferior mediastinum (No. 110), the lesser curvature (Nos. 1, 3, 7), No. 2, and No 11. When esophageal involvement was &amp;gt; 40 mm, we performed esophagectomy including upper thoracic lymph nodes. We were not satisfied with the result of surgical treatment including lymph node dissection alone in advanced AEG. We will recommend nab-paclitaxel combined with radiotherapy for advanced AEG to improve the survival rate.

Enhancing lymph node metastasis prediction in adenocarcinoma of the esophagogastric junction: A study combining radiomic with clinical features.

The incidence of adenocarcinoma of the esophagogastric junction (AEJ) is increasing, and with poor prognosis. Lymph node status (LNs) is particularly important for planning treatment and evaluating the prognosis of patients with AEJ. However, the use of radiomic based on enhanced computed tomography (CT) to predict the preoperative lymph node metastasis (PLNM) status of the AEJ has yet to be reported. We sought to investigate the value of radiomic features based on enhanced CT in the accurate prediction of PLNM in patients with AEJ. Clinical features and enhanced CT data of 235 patients with AEJ from October 2017 to May 2023 were retrospectively analyzed. The data were randomly assigned to the training cohort (n=164) or the external testing cohort (n=71) at a ratio of 7:3. A CT-report model, clinical model, radiomic model, and radiomic-clinical combined model were developed to predict PLNM in patients with AEJ. Univariate and multivariate logistic regression were used to screen for independent clinical risk factors. Least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomic features. Finally, a nomogram for the preoperative prediction of PLNM in AEJ was constructed by combining Radiomics-score and clinical risk factors. The models were evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analyses. A total of 181 patients (181/235, 77.02%) had LNM. In the testing cohort, the AUC of the radiomic-clinical model was 0.863 [95% confidence interval (CI)=0.738-0.957], and the radiomic model (0.816; 95% CI=0.681-0.929), clinical model (0.792; 95% CI=0.677-0.888), and CT-report model (0.755; 95% CI=0.647-0.840). The radiomic-clinical model is a feasible method for predicting PLNM in patients with AEJ, helping to guide clinical decision-making and personalized treatment planning.

Gender medicine in diseases of the upper gastrointestinal tract

Benign and malignant diseases of the upper gastrointestinal tract show gender-specific differences. The frequent gastroesophageal reflux disease is aprime example: men have an erosive reflux disease more often than women and are also younger at the time of onset. The rate of progression to a metaplastic Barrett's esophagus is also higher in men. In the case of achalasia, there are indications that surgical treatment by laparoscopic Heller's myotomy and semifundoplication 180° according to Dor leads to amarkedly better improvement in the symptoms in women compared to men, although they showed amore pronounced dilation of the tubular esophagus. The female hormone status influences the localization and histopathology of adenocarcinoma of the esophagogastric junction and gastric carcinoma. Premenopausal and postmenopausal carcinomas differ significantly in women. In addition, high microsatellite instability (MSI high) is more frequent in women and is associated with agenerally significantly better prognosis. The MSI high gastric carcinomas of women show better survival than MSI high carcinomas of men. The future inclusion of gender-specific aspects in studies of the upper gastrointestinal tract is desirable in order to generate adequate data and to enable differentiated treatment stratification in the future.

Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction

The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Overall and disease-free survival, postoperative morbidity, and mortality. The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

Characteristics of auto-quantified tumor-infiltrating lymphocytes and the prognostic value in adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, and esophageal squamous cell carcinoma.

Adenocarcinoma of the esophagogastric junction (AEGJ) with a specific pathological profile and poor prognosis has limited therapeutic options. Previous studies have found that TILs exhibit distinct characteristics in different tumors and are correlated with tumor prognosis. We established cellular training sets to obtain auto-quantified TILs in pathological images. And we compared the characteristics of TILs in AEGJ with those in esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GAC) to gain insight into the unique immune environments of these three tumors and investigate the prognostic value of TILs in these three tumors. Utilizing a case-control study design, we analyzed 214 AEGJ, 256 GAC, and 752 ESCC cases. The TCGA dataset was used to validate prognostic value of auto-quantified TILs. The specific cellular training sets were established by experienced pathologists to determine TILs counts. Kruskal-Wallis test and multi-variable linear regression were conducted to explore TILs characteristics. Survival analyses were performed with Kaplan-Meier method and Cox proportional hazards model. The three cellular training sets of these cancers achieved a classification accuracy of 87.55 at least. The median auto-quantified TILs of AEGJ, GAC, and ESCC cases were 4.82%, 1.92%, and 0.12%, respectively. The TILs demonstrated varied characteristics under distinctive clinicopathological traits. The higher TILs proportion was associated with better prognosis in esophagogastric cancers (all P < 0.05) and was an independent prognostic biomarker on AEGJ in both datasets (Taixing: HR = 0.965, 95% CI = 0.938-0.994; TCGA: HR = 0.811, 95% CI = 0.712-0.925). We found variations in TILs across ESCC, GAC, and AEGJ, as assessed by image processing algorithms. Additionally, TILs in these three cancers are an independent prognostic factor. This enhances our understanding of the unique immune characteristics of the three tumors, improving patient outcomes.

Impact of genomic and epigenomic alterations of multigene on a multicancer pedigree.

Germline mutations have been identified in a small number of hereditary cancers, but the genetic predisposition for many familial cancers remains to be elucidated. This study identified a Chinese pedigree that presented different cancers (breast cancer, BRCA; adenocarcinoma of the esophagogastric junction, AEG; and B-cell acute lymphoblastic leukemia, B-ALL) in each of the three generations. Whole-genome sequencing and whole-exome sequencing were performed on peripheral blood or bone marrow and cancer biopsy samples. Whole-genome bisulfite sequencing was conducted on the monozygotic twin brothers, one of whom developed B-ALL. According to the ACMG guidelines, bioinformatic analysis of the genome sequencing revealed 20 germline mutations, particularly mutations in the DNAH11 (c.9463G > A) and CFH (c.2314G > A) genes that were documented in the COSMIC database and validated by Sanger sequencing. Forty-one common somatic mutated genes were identified in the cancer samples, displaying the same type of single nucleotide substitution Signature 5. Meanwhile, hypomethylation of PLEK2, MRAS, and RXRA as well as hypermethylation of CpG island associated with WT1 was shown in the twin with B-ALL. These findings reveal genomic alterations in a pedigree with multiple cancers. Mutations found in the DNAH11, CFH genes, and other genes predispose to malignancies in this family. Dysregulated methylation of WT1, PLEK2, MRAS, and RXRA in the twin with B-ALL increases cancer susceptibility. The similarity of the somatic genetic changes among the three cancers indicates a hereditary impact on the pedigree. These familial cancers with germline and somatic mutations, as well as epigenomic alterations, represent a common molecular basis for many multiple cancer pedigrees.