Search Results (77)

Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article

Background: Proximal gastrectomy (PG) with double tract reconstruction (DTR) offers organ preservation for early gastric cancers, leading to reduced vitamin B12 deficiency, less weight loss, and improved quality of life. The JCOG1401 study confirmed excellent long-term outcomes for PG in stage I gastric cancer. However, in locally advanced proximal gastric cancer (LAPGC), preserving the gastric body and lymph node station 4d may compromise margin clearance and adequate lymphadenectomy. Methods: We propose a modified PG that removes the distal esophagus, gastroesophageal junction (GEJ), cardia, fundus, and gastric body, preserving only the antrum and performing DTR. Lymphadenectomy is also adapted, removing stations 1, 2, 3a, 4sa, 4sb, 4d, 7, 8, 9, 10 (spleen preserving), 11, and lower mediastinal nodes (stations 19, 20, and 110), while preserving stations 3b, 5, and 6. Indications for this procedure include GEJ (Siewert type II and III) and proximal gastric cancers with ≤2 cm distal esophageal involvement and ≤5 cm gastric involvement. Results: In our initial experience with 14 patients, we achieved R0 resection in all patients, adequate lymph node harvest (median 24 nodes, IQR 18–38), and no locoregional recurrences at a median follow-up of 18 months. We also found favorable postoperative weight loss, reflux, and anemia in the PG cohort. Conclusion: While larger studies and long-term data are still needed, our early results suggest that modified PG—despite sparing only the antrum—retains the key benefits of PG over total gastrectomy, including better weight maintenance and improved hemoglobin levels, while maintaining oncologic outcomes for LAPGC. Full article

Background: Zolbetuximab, a monoclonal antibody targeting claudin-18.2 (CLDN18.2), which was recently approved as first-line treatment for advanced gastric cancer (AGC), presents unique safety challenges, particularly infusion-related gastrointestinal toxicity and hypoalbuminemia. This study aimed to present our experience with zolbetuximab administration in patients with AGC, focusing on the safety and management effectiveness of our adapted protocol in routine clinical practice. Methods: This study presents our single-institution real-world experience implementing a proactive management protocol (“Project VYLOY”) using zolbetuximab to mitigate these toxicities. We adopted a standardized stepwise infusion protocol and antiemetic premedication to reduce infusion-related nausea and vomiting. Patients with CLDN18.2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received zolbetuximab combined with chemotherapy were included. Results: Twenty-four patients were included. The median infusion duration was 215 min, with an interruption rate of 25.0%. In cycle 1, 62.5% experienced infusion-associated adverse events, primarily grade 1 nausea (54%) and vomiting (25%). Hypoalbuminemia (grade ≥ 2) occurred in 57% of first-line patients, potentially linked to zolbetuximab-induced gastritis and gastrointestinal protein loss. Proactive antiemetic support and infusion rate adjustments substantially reduced infusion interruptions in subsequent cycles (10.9%). Patients without prior gastrectomy had higher nausea and vomiting rates, confirming the stomach’s role in mediating toxicity. Conclusions: Our results suggest that proactive management can improve the safety and tolerability of zolbetuximab, especially by reducing infusion-related toxicity in real-world practice. Full article

Epidermal growth factor receptor 2 (ERBB2/HER2) is a critical biomarker in gastric cancer management, but the clinical implications of specific ERBB2 mutations remain poorly characterized. Methods/Results: We investigated the ERBB2 R678Q mutation, utilizing the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which involved the analysis of 3116 gastric/gastroesophageal junction adenocarcinomas. ERBB2 mutations were identified in 130 cases, with R678Q present in 40 patients. These patients exhibited significantly lower response rates to oxaliplatin-based regimens compared to ERBB2 wild-type cases (19.0% vs. 38.0%, p = 0.03), while other ERBB2 mutations demonstrated no such resistance. No significant differences in the response were observed to the ramucirumab or nivolumab regimens. Conclusions: Our findings suggest that the ERBB2 R678Q mutation may predict a poor response to oxaliplatin-based therapy. This study provides real-world evidence supporting the potential clinical relevance of this specific ERBB2 mutation in treatment decision making for gastric cancer. Full article

Background/Objectives: Survival rates for esophageal cancer patients have markedly improved. Inevitably, attention has been drawn to functional and quality-of-life problems. The aim of the current study was to investigate the prevalence of dumping syndrome in patients following esophageal resection and its correlation with postoperative quality of life. Methods: This cross-sectional study involved disease-free patients who underwent a potentially curative resection for esophageal or gastroesophageal junction carcinoma between January 2019 and January 2024 in a single academic institution. Patients were asked to fill in two questionnaires: the Dumping Syndrome Rating Scale (DSRS) and the QLQ-OG25. A Composite Dumping Syndrome Index (CDSI) was calculated by adding the summary severity and frequency scores for each patient. Results: During the study period, 42 patients underwent esophagectomy for malignant esophageal or junctional tumors. In total, 14 eligible patients responded to the questionnaires at a mean time of 19.7 (±20.8) months following their operation. Three patients (21%) reported having at least quite severe problems related to at least two dumping symptoms. Six patients (43%) reported that they avoid certain foods in order to alleviate related problems. A high CDSI score was associated with significantly increased OG25 scores for dysphagia, eating restriction, odynophagia, pain and discomfort, and reflux (p < 0.05). Conclusions: Early dumping syndrome can occur in a significant proportion of patients following esophagectomy and may adversely affect quality of life. Full article

Upper gastrointestinal (GI) malignancies, including esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinomas, remain a major global health concern, with poor overall survival and high recurrence rate despite aggressive treatment. Patients with very early tumors (cT1a) can benefit from endoscopic therapy. However, patients with locally advanced disease require multimodal therapies that may combine surgery, radiation, and systemic therapies. This review provides a comprehensive overview of recent advancements in the treatment of locally advanced upper GI adenocarcinomas. Surgical resection remains the cornerstone of curative treatment, with perioperative chemotherapy emerging as the standard of care. While preoperative chemoradiation has demonstrated some benefits in esophageal and GEJ cancers, recent data suggest a more limited role for radiation going forward. Immunotherapy has shown some promise in both the adjuvant and perioperative settings but has yet to establish definitive survival benefit. The integration of HER2-targeted therapies into treatment regimens for HER2-positive locally advanced gastroesophageal cancers has not yielded significant improvements, underscoring the need for more effective strategies. Ongoing research focuses on better predictive biomarkers, personalized treatment approaches, and potential organ preservation strategies for patients achieving a clinical complete response. Continued advancements in treatment modalities and precision medicine are critical to improving survival for patients with locally advanced upper GI adenocarcinomas. Full article

Purpose: To investigate the impact of paratracheal lymphadenectomy on survival in patients undergoing an esophagectomy for cancer. The secondary objective was to assess the effect on short-term outcomes. Methods: Between 2011–2017, patients with an esophageal or gastroesophageal junction carcinoma treated with elective transthoracic esophagectomy with two-field lymphadenectomy were included from the Dutch Upper Gastro-intestinal Cancer Audit registry. After 1:1 propensity score matching of patients with and without paratracheal lymphadenectomy within histologic subgroups, short-term outcomes and overall survival were compared between the two groups. Results: A total of 1154 patients with adenocarcinoma and 294 patients with squamous cell carcinoma were matched. Lymph node yield was significantly higher (22 versus 19 nodes, p < 0.001) in patients with paratracheal lymphadenectomy for both tumor types. Paratracheal lymphadenectomy was associated with more recurrent laryngeal nerve injury (10% versus 5%, p = 0.002) and chylothorax in patients with adenocarcinoma (10% versus 5%, p = 0.010) and with more anastomotic leakage in patients with squamous cell carcinoma (42% versus 27%, p = 0.014). The 3- and 5-year survival in patients with and without a paratracheal lymphadenectomy were for adenocarcinoma, respectively, 58% versus 56% and 48% in both groups (log rank: p = 0.578) and for patients with a squamous cell carcinoma, 62% in both groups and 57% versus 54% (log rank: p = 0.668). Conclusions: The addition of paratracheal lymphadenectomy significantly increases lymph node yield in transthoracic esophagectomy but did not result in improved survival for esophageal cancer patients in the current dataset. However, there was an increase in postoperative morbidity in patients who underwent a paratracheal lymphadenectomy. Full article

Introduction: Transhiatal esophagectomy (THE) is used for specific gastroesophageal junction adenocarcinomas. THE is a high-risk surgical procedure. We aimed to assess the impact of postoperative sepsis (sepsis or septic shock) on the 1-year mortality after THE and to determine the risk factors associated with these outcomes. Secondly, we aimed to assess the impact of postoperative sepsis and other risk factors on 1-year cancer recurrence. Method: A retrospective, observational study was undertaken at the Paoli-Calmettes Institute, Marseille, from January 2012 to March 2022. Results: Of 118 patients, 24.6% (n = 29) presented with postoperative sepsis. Their 1-year mortality was 11% (n = 13), and their 1-year cancer recurrence was 23.7% (n = 28). In the multivariate analysis, independent factors for 1-year mortality were the following: postoperative sepsis (OR: 7.22 (1.11–47); p = 0.038), number of lymph nodes removed (OR: 0. 78 (0.64–0.95); p = 0.011), recurrence at one year (OR: 9.22 (1.66–51.1); p = 0.011), mediastinitis (OR: 17.7 (1.43–220); p = 0.025) and intraoperative driving pressure (OR: 1.77 (1.17–2.68); p = 0.015). For postoperative sepsis, independent factors were low-dose vasopressors (OR: 0.26; 95% CI: 0.07–0.95; p = 0.049), a cervical abscess (OR: 5.33; 95% CI: 1.5–18.9; p = 0.01), bacterial pneumonia (OR: 11.1; 95% CI: 2.99–41.0; p < 0.001) and a high SOFA score on day 1 (OR: 2.65; 95% CI: 1.36–5.19; p = 0.04). For 1-year cancer recurrence, independent factors were the number of lymph nodes removed (sHR: 0.87; 95% CI: 0.79–0.96; p = 0.005), pTNM stages of III or IV (sHR: 8.29; 95% CI: 2.71–25.32; p < 0.001) and postoperative sepsis (sHR: 6.54; 95% CI: 1.70–25.13; p = 0.005). Conclusions: Our study indicates that after THE, postoperative sepsis influences survival and cancer recurrence. We identified the associated risk factors, suggesting an early diagnosis might decrease mortality and recurrence. Full article

Gastric cancer is common globally and has a generally poor prognosis with a low 5-year survival rate. Targeted therapies and immunotherapies have improved the treatment landscape, providing more options for efficacious treatment. The use of these therapies requires predictive biomarker testing to identify patients who can benefit from their use. New therapies on the horizon, such as CLDN18.2 monoclonal antibody therapy, require laboratories to implement new biomarker tests. A multidisciplinary pan-Canadian expert working group was convened to develop guidance for pathologists and oncologists on the implementation of CLDN18.2 IHC testing for gastric and gastroesophageal junction (G/GEJ) adenocarcinoma in Canada, as well as general recommendations to optimize predictive biomarker testing in G/GEJ adenocarcinoma. The expert working group recommendations highlight the importance of reflex testing for HER2, MMR and/or MSI, CLDN18, and PD-L1 in all patients at first diagnosis of G/GEJ adenocarcinoma. Testing for NTRK fusions may also be included in reflex testing or requested by the treating clinician when third-line therapy is being considered. The expert working group also made recommendations for pre-analytic, analytic, and post-analytic considerations for predictive biomarker testing in G/GEJ adenocarcinoma. Implementation of these recommendations will provide medical oncologists with accurate, timely biomarker results to use for treatment decision-making. Full article

Background/Objectives: Esophagectomy is the mainstay of treatment in esophageal cancer. Minimally invasive esophagectomy (MIE) remains a challenging procedure and has been associated with a high rate of complications and mortality. Routine lymphadenectomy includes two-field lymphadenectomy for distal-esophageal or gastroesophageal junction Siewert I–II tumors. Superior mediastinal lymphadenectomy (SML) refers to an extended two-field lymphadenectomy or total mediastinal lymphadenectomy during MIE for cancer. The exact benefits of SML have been the subject of prolonged debate, with no conclusive evidence indicating improved clinical and oncological results. Herein, we aim to present our surgical technique of thoracoscopic SML during MIE in the prone position, with short-term clinical and oncological outcomes. Methods: About 150 consecutive patients underwent totally MIE within 3 years period (2016–2019). SML included right-paratracheal nodes and nodes along the right-recurrent laryngeal nerve throughout its mediastinal route in cases of extended two-field lymphadenectomy, as well as left-paratracheal nodes and nodes along the left recurrent laryngeal nerve during total mediastinal lymphadenectomy. Eligible patients underwent SML during two-stage or three-stage MIE. Results: Twenty consecutive patients underwent SML during the study period. The 30- and 90-day mortality rates were 0. Pulmonary complications were observed in 16.5% of the patients. There was 1 right recurrent laryngeal nerve palsy noted. The median length of stay was 9 days. The median number of resected lymph nodes was 45, with the median SML nodes count being 8. The median follow-up was 24 months. Conclusions: SML during prone position thoracoscopy for esophageal cancer is safe and feasible, although technically demanding. Minimally invasive esophagectomy with SML may offer meaningful benefits in oncological outcomes without introducing additional significant morbidity. Further comparative studies are needed to better elucidate our results. Full article

Background: This study aimed to analyze the relationship between the levels of tumor markers—specifically, carcinoembryonic antigen (CEA) and Ca19-9 antigen—determined in both serum (sCEA and sCa19-9) and intraoperative peritoneal washings (pCEA and pCa19-9) and the advanced stage of gastric cancer (including the occurrence of cancer cells in cytology from abdominal fluid). Methods: This study included 47 patients with histopathologically confirmed gastric cancer or gastroesophageal junction cancer who underwent surgical treatment. The material for the cytological examination and assessment of CEA and Ca19-9 concentrations in peritoneal fluid was collected intraoperatively. Later, blood was drawn to assess the CEA and Ca19-9 concentrations in blood serum. Results: There was a statistical correlation between a positive cytology result or the presence of peritoneal carcinomatosis and a positive result for the tumor markers obtained from abdominal washings. This correlation was not observed with marker levels obtained from blood serum. The pCEA marker was highly sensitive (93.3%) and specific (93.8%) for detecting cancer cells. The pCa19-9 marker was less effective in detecting cancer but matched pCEA in identifying the absence of cancer. No differences were observed in sCEA and sCA19-9 levels between patients who underwent neoadjuvant chemotherapy and those who did not receive this treatment. However, statistical analysis showed that this relationship did not apply to pCEA and pCa19-9 levels. Conclusions: Intraoperative determinations of tumor marker levels in peritoneal washings may be a predictive factor for a poor prognosis in patients with gastric cancer. Full article

Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods: Fecal and tumor samples were collected from patients with stage II–III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray–Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella. Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI. Full article

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett’s esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age (p < 0.007); lower platelet levels (p < 0.02); rectal p87 elevation in SR (p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) (p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR. Full article

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Full article