Adenocarcinoma Of Esophagogastric Junction Research Articles

PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.

This timely study assesses the immunosuppressive effects of surgery on cytotoxic Th1-like immunity and investigates if immune checkpoint blockade (ICB) can boost Th1-like immunity in the perioperative window in upper gastrointestinal cancer (UGI) patients. PBMCs were isolated from 11 UGI patients undergoing tumour resection on post-operative days (POD) 0, 1, 7 and 42 and expanded ex vivo using anti-CD3/28 and IL-2 for 5 days in the absence/presence of nivolumab or ipilimumab. T cells were subsequently immunophenotyped via flow cytometry to determine the frequency of T helper (Th)1-like, Th1/17-like, Th17-like and regulatory T cell (Tregs) subsets and their immune checkpoint expression profile. Lymphocyte secretions were also assessed via multiplex ELISA (IFN-γ, granzyme B, IL-17 and IL-10). The 48h cytotoxic ability of vehicle-, nivolumab- and ipilimumab-expanded PBMCs isolated on POD 0, 1, 7 and 42 against radiosensitive and radioresistant oesophageal adenocarcinoma tumour cells (OE33 P and OE33 R) was also examined using a cell counting kit-8 (CCK-8) assay to determine if surgery affected the killing ability of lymphocytes and whether the use of ICB could enhance cytotoxicity. Th1-like immunity was suppressed in expanded PBMCs in the immediate post-operative setting. The frequency of expanded circulating Th1-like cells was significantly decreased post-operatively accompanied by a decrease in IFN-γ production and a concomitant increase in the frequency of expanded regulatory T cells with an increase in circulating levels of IL-10. Interestingly, PD-L1 and CTLA-4 immune checkpoint proteins were also upregulated on expanded Th1-like cells post-operatively. Additionally, the cytotoxic ability of expanded lymphocytes against oesophageal adenocarcinoma tumour cells was abrogated post-surgery. Of note, the addition of nivolumab or ipilimumab attenuated the surgery-mediated suppression of lymphocyte cytotoxicity, demonstrated by a significant increase in tumour cell killing and an increase in the frequency of Th1-like cells and Th1 cytokine production. These findings support the hypothesis of a surgery-mediated suppression in Th1-like cytotoxic immunity and highlights a rationale for the use of ICB within the perioperative setting to abrogate tumour-promoting effects of surgery and ameliorate the risk of recurrence.

Preoperative EUS vs. PET-CT Evaluation of Response to Neoadjuvant Therapy for Esophagogastric Cancer and Its Correlation with Survival.

The objective of our study was to investigate whether Endoscopic Ultrasonography (EUS) and Positron Emission Tomography-Computed Tomography (PET-CT) restaging can predict survival in upper gastrointestinal tract adenocarcinomas and to assess their accuracy when compared to pathology. We conducted a retrospective study on all patients who underwent EUS for staging of gastric or esophago-gastric junction adenocarcinoma between 2010 and 2021. EUS and PET-CT were performed, and preoperative TNM restaging was conducted using both procedures within 21 days prior to surgery. Disease-free survival (DFS) and overall survival (OS) were evaluated. A total of 185 patients (74.7% male) were included in the study. The accuracy of EUS for distinguishing between T1-T2 and T3-T4 tumors after neoadjuvant therapy was 66.7% (95% CI: 50.3-77.8%), and for N staging, the accuracy was 70.8% (95% CI: 51.8-81.8%). Regarding PET-CT, the accuracy for N positivity was 60.4% (95% CI: 46.3-73%). Kaplan-Meier analysis revealed a significant correlation between positive lymph nodes on restaging EUS and PET-CT with DFS. Multivariate COX regression analysis identified N restaging with EUS and PET-CT, as well as the Charlson comorbidity index, as correlated factors with DFS. Positive lymph nodes on EUS and PET-CT were predictors of OS. In multivariate Cox regression analysis, the independent risk factors for OS were found to be the Charlson comorbidity index, T response by EUS, and male sex. Both EUS and PET-CT are valuable tools for determining the preoperative stage of esophago-gastric cancer. Both techniques can predict survival, with preoperative N staging and response to neoadjuvant therapy assessed by EUS being the main predictors.

Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

Effects of the preoperative use and dosage of steroids on postoperative complications of gastric cancer surgery.

To investigate the effects of preoperative steroid administration, including dosage, on complications after gastrectomy for gastric cancer. We reviewed patients who underwent gastrectomy for gastric and esophagogastric junctional adenocarcinoma between 2013 and 2019 at the Department of Gastrointestinal Surgery, The University of Tokyo. Among the total 764 patients eligible for inclusion in the study, 17 were on steroid medication preoperatively (SD group) and 747 were not (ND group). The hemoglobin, serum albumin levels, and respiratory functions were significantly lower in the SD group than in the ND group. The incidence of postoperative complications classified as Clavien-Dindo (C-D) ≥ 2 was significantly greater in the SD group than in the ND group (64.7% vs. 25.6%, p < 0.001). Intra-abdominal infection (35.2% vs. 9.6%, p < 0.001) and anastomotic leakage (11.8% vs. 2.1%, p < 0.001) occurred more frequently in the SD group than in the ND group. On multiple logistic regression analysis for C-D ≥ 3 postoperative complications, the odds ratio for oral steroid use ≥ 5mg per day as prednisolone had the highest value, of 13.0 (95% confidence interval 2.46-76.2, p < 0.01). Preoperative oral steroid use was identified as an independent risk factor for postoperative complications after gastrectomy for gastric cancer. Furthermore, the complication rate appears to increase as the oral steroid dosage is increased.

Feasibility of a single-port thoracoscopy-assisted five-step laparoscopic procedure via transabdominal diaphragmatic approach for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma

Objective: We aimed to explore the feasibility of a single-port thoracoscopy- assisted five-step laparoscopic procedure via transabdominal diaphragmatic(TD) approach(abbreviated as five-step maneuver) for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma (AEG). Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) age 18-80 years; (2) diagnosis of Siewert type II AEG; (3) clinical tumor stage cT2-4aNanyM0; (4) meeting indications of the transthoracic single-port assisted laparoscopic five-step procedure incorporating lower mediastinal lymph node dissection via a TD approach; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; and (6) American Society of Anesthesiologists classification I, II, or III. The exclusion criteria included previous esophageal or gastric surgery, other cancers within the previous 5 years, pregnancy or lactation, and serious medical conditions. We retrospectively collected and analyzed the clinical data of 17 patients (age [mean ± SD], [63.6±11.9] years; and 12 men) who met the inclusion criteria in the Guangdong Provincial Hospital of Chinese Medicine from January 2022 to September 2022. No.111 lymphadenectomy was performed using five-step maneuver as follows: superior to the diaphragm, starting caudad to the pericardium, along the direction of the cardio-phrenic angle and ending at the upper part of the cardio-phrenic angle, right to the right pleura and left to the fibrous pericardium , completely exposing the cardio-phrenic angle. The primary outcome includes the numbers of harvested and of positive No.111 lymph nodes. Results: Seventeen patients (3 proximal gastrectomy and 14 total gastrectomy) had undergone the five-step maneuver including lower mediastinal lymphadenectomy without conversion to laparotomy or thoracotomy and all had achieved R0 resection with no perioperative deaths. The total operative time was (268.2±32.9) minutes, and the lower mediastinal lymph node dissection time was (34.0±6.0) minutes. The median estimated blood loss was 50 (20-350) ml. A median of 7 (2-17) mediastinal lymph nodes and 2(0-6) No. 111 lymph nodes were harvested. No. 111 lymph node metastasis was identified in 1 patient. The time to first flatus occurred 3 (2-4) days postoperatively and thoracic drainage was used for 7 (4-15) days. The median postoperative hospital stay was 9 (6-16) days. One patient had a chylous fistula that resolved with conservative treatment. No serious complications occurred in any patient. Conclusion: The single-port thoracoscopy-assisted five-step laparoscopic procedure via a TD approach can facilitate No. 111 lymphadenectomy with few complications.

Hand-sewn esophagojejunostomy in transthoracic single-port assisted laparoscopic esophagogastrectomy for Siewert type II adenocarcinoma of the esophagogastric junction with esophageal invasion &gt; 3 cm

An optimal method for digestive tract reconstruction (DTR) in laparoscopic radical resection of Siewert type II adenocarcinoma of esophagogastric junction (AEG) has not yet been standardized. The aim of this study was to evaluate the safety and feasibility of a hand-sewn esophagojejunostomy (EJ) technique during transthoracic single-port assisted laparoscopic esophagogastrectomy (TSLE) for Siewert type II AEG with esophageal invasion > 3cm. The perioperative clinical data and short-term outcomes for patients who underwent TSLE using hand-sewn EJ for Siewert type IIAEG with esophageal invasion > 3cm between March 2019 and April 2022 have been retrospectively reviewed. A total of 25 patients were eligible. All 25 patients were successfully operated. None was converted to open surgery or mortality. 84.00% of patients were male and 16.00% were female. The mean age, body mass index (BMI), and the American Society of Anesthesiologists (ASA) score were 67.88 ± 8.10years, 21.30 ± 2.80kg/m2, and 2.08, respectively. The average incorporated operative and hand-sewn EJ procedural times were 274.92 ± 57.46 and 23.36 ± 3.00min, respectively. The length of extracorporeal esophageal involvement and proximal margin was 3.31 ± 0.26cm and 3.12 ± 0.12cm, respectively. The average time for the first oral feeding and hospital stay were 6 (3-14) and 7 (3-18) days, respectively. Two patients (8.00%) developed postoperative grade IIIa complications according to the Clavien-Dindo classification, including 1 case of pleural effusion and 1 case of anastomotic leakage, both of whom were cured by puncture drainage. Hand-sewn EJ in TSLE is safe and feasible for Siewert type II AEG. This method can ensure safe proximal margins and could be a good option with an advanced endoscopic suture technique for type II tumor with esophageal invasion > 3cm.

A Case Report of Brain Metastases after Neoadjuvant Chemo and Radiotherapy for Esophagogastric Junction Adenocarcinoma in an Adult Male Patient

Background: Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy. The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain.&#x0D; Case Presentation: A male patient, 47 years old, was admitted to the hospital on July 31, 2020, mainly due to "progressive dysphagia. Two months ago, the patient had difficulty eating without obvious incentives, especially when eating hard food such as rice. The liquid diet was acceptable, accompanied by retrosternal pain and discomfort, heartburn, and obvious weight loss. The symptoms gradually aggravated without obvious relief.&#x0D; Conclusion: In summary, there are few international investigations and an absence of relevant information and literature on the environment in which tumor cells survive after radiotherapy. Clinicians can't ignore the issue of whether radiotherapy will alter the tumor cells' natural environment, leading to tumor cell escape and an increase in brain metastases.

A Nomogram Based on Nutrition-Related Indicators and Computed Tomography Imaging Features for Predicting Preoperative Lymph Node Metastasis in Curatively Resected Esophagogastric Junction Adenocarcinoma.

Preoperative noninvasive tools to predict pretreatment lymph node metastasis (PLNM) status accurately for esophagogastric junction adenocarcinoma (EJA) are few. Thus, the authors aimed to construct a nomogram for predicting PLNM in curatively resected EJA. This study enrolled 638 EJA patients who received curative surgery resection and divided them randomly (7:3) into training and validation groups. For nomogram construction, 26 candidate parameters involving 21 preoperative clinical laboratory blood nutrition-related indicators, computed tomography (CT)-reported tumor size, CT-reported PLNM, gender, age, and body mass index were screened. In the training group, Lasso regression included nine nutrition-related blood indicators in the PLNM-prediction nomogram. The PLNM prediction nomogram yielded an area under the receiver operating characteristic (ROC) curve of 0.741 (95 % confidence interval [CI], 0.697-0.781), which was better than that of the CT-reported PLNM (0.635; 95% CI 0.588-0.680; p < 0.0001). Application of the nomogram in the validation cohort still gave good discrimination (0.725 [95% CI 0.658-0.785] vs 0.634 [95% CI 0.563-0.700]; p = 0.0042). Good calibration and a net benefit were observed in both groups. This study presented a nomogram incorporating preoperative nutrition-related blood indicators and CT imaging features that might be used as a convenient tool to facilitate the preoperative individualized prediction of PLNM for patients with curatively resected EJA.

Changes in Physical Components after Gastrectomy for Adenocarcinoma of Stomach and Esophagogastric Junction

Objective: Enhanced Recovery After Surgery (ERAS) is a multidisciplinary approach that aims to optimize perioperative management, promote postoperative recovery, reduce postoperative complications, and improve long-term survival. The current study aimed to evaluate and compare the postoperative physical activity after gastrectomy between patients who underwent upper gastrointestinal surgery according to ERAS and those who underwent surgery based on the conventional care (CC) protocol. Materials and Methods: This prospective and retrospective review enrolled 60 patients (n = 31, ERAS group; n = 29, CC protocol group) diagnosed with adenocarcinoma of the stomach and esophagogastric junction who underwent curative surgical resection. Physical outcomes, including body weight, body mass index, body fat percentage, basal metabolic rate, muscle mass, gait speed, and handgrip strength at the preoperative and immediate postoperative periods and at 1, 3, and 6 months postoperatively, were comparedbetween the ERAS and CC protocol groups. Results: One month after surgery, the ERAS group had a lower percentage of body weight loss than the CC protocol group. There was no significant difference in terms of muscle mass loss between the two groups. The hand grip strength of the ERAS group increased after surgery. Further, at 1 month postoperatively, the gait speed of patients who underwent total gastrectomy in the ERAS group was significantly higher than that of patients in the CC protocol group. Conclusion: ERAS for gastrectomy was associated with a lower percentage of weight loss and a trend toward physical activity enhancement in the early postoperative period.

Facing adenocarcinoma of distal esophagus and esophagogastric junction: a CROSS versus FLOT propensity score-matched analysis of oncological outcomes in a high-volume institution.

Multimodality treatments are the gold standard for advanced resectable gastroesophageal cancer. Neoadjuvant CROSS and perioperative FLOT regimens are adopted for distal esophageal and esophagogastric junction adenocarcinoma (DE/EGJ AC). At present, none of the approaches is clearly superior in the context of a curative-intent multimodal treatment. We analyzed consecutive patients treated with CROSS or FLOT and surgery for DE/EGJ AC between August 2017 and October 2021. Propensity score matching was performed to balance baseline characteristics of patients. The primary endpoint was disease-free survival. Secondary endpoints included overall survival, 90-day morbidity/mortality rates, pathological complete response, margin-negative resection, and pattern of recurrence. Of the 111 patients included, 84 were correctly matched after PSM, 42 in each group. The 2-year DFS rate was 54.2% versus 64.1% in the CROSS and FLOT group, respectively (p = 0.182). Patients in the CROSS group showed a lower number of harvested LN when compared to the FLOT group (29.5 versus 39.0 respectively, p = 0.005). A higher rate of distal nodal recurrence was found in the CROSS group (23.8% versus 4.8%, p = 0.026). Although not significant, the CROSS group showed a trend toward higher rate of isolated distant recurrence (33.3% versus 21.4% respectively, p = 0.328), together with a higher rate of early recurrence (23.8% versus 9.5% respectively, p = 0.062). FLOT and CROSS regimens for DE/EGJ AC offer similar DFS and OS, together with comparable morbidity/mortality rates. CROSS regimen was associated with a higher distant nodal recurrence rate. Results of ongoing randomized clinical trials are awaited.

Prognostic Significance of the Proximal Margin for Esophagogastric Junction Adenocarcinoma with Type II and III Tumors after Surgery

Background: The incidence of Esophagogastric Junction Adenocarcinoma (EJA) has increased in recent years, with surgical resection the main choice of treatment. The optimal length of the proximal margin for EJA is still under debate, and the impact of EJA survival and recurrence remains unclear. The aim of the present study was to investigate the influence of the optimal length of the proximal margin on EJA. Methods: From January 2011 to December 2015, 131 patients who had EJA with type II tumors were included and retrospectively analyzed. All patients underwent radical R0 resection. The proximal margin was measured promptly after resection, and the frozen-section pathological examination was negative for the margin. Results: There were 3 cases of Siewert type I EJA (2.9%), 75 cases of Siewert type II EJA (57.9%), and 53 cases (40.1%) of Siewert type III EJA. The median number of lymph nodes examined was 19 (range: 1-41), and the median number of positive lymph nodes was 2 (range: 0–18). Sixty-three patients underwent total gastrectomy (48.1%), and 68 underwent proximal gastrectomy (51.9%). The median follow-up time was 57.3 months: (range 1.9–174.1); 34 patients (26%) relapsed and 74 (56.5%) died. The 5-year overall survival rate of type II tumor patients was 68.2%, and that of type III tumor patients was 38.5% (P=0.02). For patients with a proximal margin &lt;2cm, the median recurrence time was 41.6 months, whereas it was for 42.8 months for patients with proximal margin &gt;2cm (log–rank: 0.496). Our data analysis found that a proximal margin length of 2cm was a prognostic variable for type II and type III tumors. Conclusions: There are a number of factors associated with recurrence and overall survival at 5 years for patients who have EJA with type II and type III tumors, and a proximal margin &gt;2cm may indicate better prognosis.

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet-ring cells, and/or poorly cohesive cells.

Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet-ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well-formed glands), which is a possible confounder. We studied the pre- and post-treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well-formed glands, extracellular mucin, SRCs, and PCCs were scored in pre-treatment biopsies and post-treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3-4 (i.e. >10% residual tumour), overall survival, and disease-free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre-treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre-treatment histopathological factors were unrelated to tumour regression grade. Pre-treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19-2.53). Patients with post-treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10-2.99). In conclusion, pre-treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre-treatment and any SRCs post-treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts.

Perioperative chemotherapy versus upfront surgery with adjuvant chemotherapy in gastric and esophagogastric junction adenocarcinoma: A retrospective trial

Objective: Gastric cancer represents a common cause of cancer death worldwide. Adenocarcinoma accounts for more than 95% of all gastric malignancies. Multimodal approaches in the treatment of localized gastric cancer have changed the natural history of the disease. Compared with surgery alone, several therapeutic approaches including perioperative chemotherapy or adjuvant chemotherapy improve survival. This study aimed to compare perioperative chemotherapy and upfront surgery with adjuvant chemotherapy in gastric and esophagogastric junction adenocarcinoma, in terms of clinical features, survival outcomes and prognostic factors.

Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients with oesophageal adenocarcinoma

Objectives2-deoxy-2[18F]Fluoro-d-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival.MethodsCohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy’s and St Thomas’ NHS Foundation Trust, London (2017–2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression.ResultsOptimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03–0.34; mTR HR 0.17 95% CI 0.06–0.48; pNR HR 0.17 95% CI 0.06–0.54; mNR HR 0.13 95% CI 0.02–0.66).ConclusionsMetabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival.Key Points• FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer.• Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection.• Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.

Perioperative chemotherapy versus upfront surgery with adjuvant chemotherapy in gastric and esophagogastric junction adenocarcinoma, a retrospective trial

Perioperative chemotherapy versus upfront surgery with adjuvant chemotherapy in gastric and esophagogastric junction adenocarcinoma, a retrospective trial

Global scientific trends in laparoscopy and gastric cancer in the 21st century: A bibliometric and visual mapping analysis.

To use visual mapping and bibliometrics to analyze and summarize the valuable information on laparoscopic surgery for gastric cancer (GC) obtained in the last 20 years, so as to determine the research hotspots and trends in this field. We screened all literature on laparoscopic surgery for GC in the Web of Science published from 2000 to 2022 and analyzed the research hotspots and trends in this field using VOSviewer. A total of 2796 reports from 61 countries and regions were selected. Japanese researchers published the most papers (n=946), followed by those from China (n=747) and South Korea (n=557). Papers from Japan also had the most citations (n=21,836). Surgical Endoscopy and Other Interventional Techniques published the most reports on laparoscopic surgery for GC (n=386) and also had the highest total number of citations (n=11,076), making this journal the most authoritative in this field. Among the institutions, researchers from Seoul National University in South Korea had the highest numbers of published papers and citations. The keywords of the articles could be divided into five categories: surgical methods for GC, short-term and long-term efficacy of laparoscopic surgery, guiding role of laparoscopy in the treatment of advanced GC, diagnosis and treatment of early gastric cancer (EGC), and lymph node dissection. Keywords such as "laparoscopic proximal gastrectomy", "surgical outcomes", and "esophagogastric junction" have emerged recently, and relevant studies on laparoscopic surgery for adenocarcinoma of esophagogastric junction(AEG)have gradually become a hot topic and trend. This study adopted bibliometric analysis to identify the current research hotspots and research trends in the field of laparoscopic surgery for GC. Five main research hotspots of laparoscopic surgery for GC were also identified. Laparoscopic surgery for AEG may become an important research focus in the future.

Visceral adipose tissue secretome from early and late-stage oesophageal cancer patients differentially affects effector and regulatory T cells

AimVisceral obesity is a key risk factor in the development of oesophagogastric junctional adenocarcinoma (OGJ), predominantly via generation of systemic low grade inflammation. Obesity-induced inflammation promotes resistance to current standards of care, enhancing tumour cell growth and survival. This study investigates the effect of the visceral adipose tissue secretome from OGJ patients with early versus advanced tumours on T-cell immunity and the role of immune checkpoint blockade in enhancing anti-tumour immunity.Methods and resultsVisceral adipose conditioned media (ACM) from both early and late-stage OGJ patients significantly altered T cell activation status, upregulating co-stimulatory marker CD27 on T cells. ACM from both early and late-stage OGJ patients significantly altered immune checkpoint expression profiles downregulating immune checkpoints (ICs) on the surface of dual Th1/17-like and Th17-like cells and upregulating ICs on the surface of Th1-like cells and Treg cells. ACM derived from early-stage OGJ patients but not late-stage OGJ patients increased IFN-γ production by T cells. The addition of immune checkpoint blockers (ICBs) did not increase IFN-γ production by T cells in the presence of late-stage ACM, collectively highlighting the dichotomous immunostimulatory effect of early-stage ACM and immune-inhibitory effect of late-stage ACM. Interestingly, ACM from early-stage OGJ patients was more pro-inflammatory than ACM from late-stage patients, reflected by decreased levels of IL-17A/F, TNF-α, IL-1RA and IL-5.ConclusionThe ACM-induced upregulation of ICs on T cells highlights a therapeutic vulnerability that could be exploited by ICBs to harness anti-cancer immunity and improve clinical outcomes for OGJ patients.Graphical Schematic workflow – (A) visceral adipose tissue was taken from OAC patients at time of surgery and cultured for 72 h in media. (B) The harvested ACM was co-cultured with healthy donor PBMCs that were concurrently activated with anti-CD3/28 for 48 h and T cell immunophenotyping was carried out by flow cytometry. Key findings – (A) Early and late stage ACM enhanced a Th1-like phenotype and upregulated CTLA-4 on Th1-like cells. A Th17-like phenotype was also enhanced in addition with a Treg-like phenotype. CTLA-4 and PD-L1 were upregulated on the surface of Treg-like cells. (B) ICB-attenuated IL-17 production by T cells. However, ACM attenuated ICB-mediated reduction in IL-10 production by T cells. Higher levels of pro-inflammatory factors were found in early stage ACM compared with late stage ACM.

Integrative proteomic characterization of adenocarcinoma of esophagogastric junction

The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct proteomics and phosphoproteomics profiling of 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing of 94 tumor-NAT pairs, and RNA sequencing in 83 tumor-NAT pairs. Our analysis reveals an extensively altered proteome and 252 potential druggable proteins in AEG tumors. We identify three proteomic subtypes with significant clinical and molecular differences. The S-II subtype signature protein, FBXO44, is demonstrated to promote tumor progression and metastasis in vitro and in vivo. Our comparative analyses reveal distinct genomic features in AEG subtypes. We find a specific decrease of fibroblasts in the S-III subtype. Further phosphoproteomic comparisons reveal different kinase-phosphosubstrate regulatory networks among AEG subtypes. Our proteogenomics dataset provides valuable resources for understanding molecular mechanisms and developing precision treatment strategies of AEG.

Paraconduit hernia after minimally invasive esophagectomy – incidence and risk factors

Background Paraconduit hernia is a relatively common long-term complication after esophagectomy which has the potential to cause great morbidity and even mortality. The aim of this study is to examine the risk factors and incidence of paraconduit hernia after minimally invasive esophagectomy (MIE) in esophageal adenocarcinoma patients who have received neoadjuvant treatment. Methods Minimally invasive esophagectomies done for patients with neoadjuvant-treated esophageal or esophagogastric junction adenocarcinoma at our institution between 2008 and 2018 were included in this study. All patients with symptomatic or incidentally found paraconduit hernias on computed tomography scans were identified. Patient demographics were analyzed using logistic and Cox regression. Results The incidence of paraconduit hernia was 14 out of 171 patients (8.2%). The hernia was surgically repaired in 10 (71.4%) of patients. Laparoscopic approach was used in 90% of the repairs, with one (11.1%) conversion to laparotomy. Emergency operations accounted for three (30%) of the operations. The complication rate was 10% (n = 1) and 90-day mortality was 10% (n = 1). Neither sarcopenia nor muscle mass loss was not associated with paraconduit hernia development, whereas preoperative radiotherapy (OR = 8.57, CI = 1.98–33.8, p = .002) was a strong risk factor for paraconduit hernia. Higher BMI had a protective effect (OR = 0.83 per point, 95% CI = 0.69–0.97, p = .027). Conclusions Paraconduit hernia is a relatively common complication after MIE for neoadjuvant-treated adenocarcinoma patients. Preoperative radiotherapy was associated with a higher risk of paraconduit hernia. Minimally invasive repair of paraconduit hernia after esophagectomy is efficient and has a low complication rate both in elective and emergency cases.

Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as adjuvant therapy in ctDNA-positive gastric and esophagogastric junction adenocarcinoma: A protocol for a randomized, controlled, multicenter phase II clinical trial—EXPLORING study.

TPS486 Background: The clinical benefit of current postoperative adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. CtDNA could serve as a potential marker to identify patients (pts) who are most at risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly boost clinical benefit, albeit such evidence is rare in GA/GEJA. Here, we intend to prove the clinical benefit of the reinforcement of adjuvant chemotherapy with immunotherapy in patients who are deemed high risk of recurrence by ctDNA analysis, in hope of shedding light on further improvements in adjuvant therapy for GA/GEJA. Methods: This study is designed as a prospective, randomized, controlled, multicenter phase II study in patients histologically or cytologically diagnosed with CG/GEJC (Siewert III), 18-75 years, ECOG PS 0-1, underwent D2 gastrectomy and achieved R0 or R1 resection. Beginning from February 2022, a total of 270 stage III patients will be enrolled and subjected to ctDNA sequencing, and those with positive results will subsequently be randomized 1:1 to arm A or B. CtDNA-negative patients will be assigned to arm C and pts who had ctDNA positive but failed to be randomized will be assigned to arm D. Pts in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while pts in arm B will receive XELOX alone for 6-8 cycles. Pts in arms C&amp;D will receive the investigator’s choice of therapy. Arms A&amp;B will be monitored for ctDNA levels on a 3-month cycle for 1 year. Survival data, laboratory findings, imaging reports and nutritional status will be regularly followed-up in all arms. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the median DFS of arm B versus arm C, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules (presumably ctDNA) on the treatment response, adverse events (AEs), and the impact of nutrition status and exercise on recurrence. Clinical trial information: NCT05494060 .