Search Results (28)

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

Monoclonal antibodies (mAbs) have completely changed the face of oncology over the last 50 years, and they have contributed to a major breakthrough in terms of cancer therapy. Esophageal and gastric cancers, the eighth and fifth most commonly diagnosed types of cancer worldwide, respectively, have lately, been managed more effectively, with the introduction of new therapeutic treatment strategies, especially mAbs. Combination treatments and new molecules have changed the face of the disease, while more therapies are getting approved on a daily basis. This review aims to analyse the major up-to-date clinical trials using mAbs and immunotherapy for the treatment of advanced gastro-esophageal cancers. Full article

Background/Objectives: Trefoil factor 1 (TFF1) plays a role in the mucus barrier. Methods: To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). Results: TFF1 staining was detectable in 65 of 149 tumor categories. The highest rates of TFF1 positivity were found in mucinous ovarian carcinomas (76.2%), colorectal adenomas and adenocarcinomas (47.1–75%), breast neoplasms (up to 72.9%), bilio-pancreatic adenocarcinomas (42.1–62.5%), gastro-esophageal adenocarcinomas (40.4–50.0%), neuroendocrine neoplasms (up to 45.5%), cervical adenocarcinomas (39.1%), and urothelial neoplasms (up to 24.3%). High TFF1 expression was related to a low grade of malignancy in non-invasive urothelial carcinomas of the bladder (p = 0.0225), low grade of malignancy (p = 0.0003), estrogen and progesterone receptor expression (p < 0.0001), non-triple negativity (p = 0.0005) in invasive breast cancer of no special type, and right-sided tumor location (p = 0.0021) in colorectal adenocarcinomas. Conclusions: TFF1 IHC has only limited utility for the discrimination of different tumor entities given its expression in many tumor entities. The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types. Full article

Human epidermal growth factor 2 (HER2) is a tyrosine kinase receptor that interacts with multiple signaling pathways related to cellular growth and proliferation. Overexpression or amplification of HER2 is linked to various malignancies, and there have been decades of research dedicated to targeting HER2. Despite the landmark ToGA trial, progress in HER2-positive gastrointestinal malignancies has been hampered by drug resistance. This review examines current HER2 expression patterns and therapies for gastroesophageal, colorectal, biliary tract, and small bowel cancers, while dissecting potential resistance mechanisms that limit treatment effectiveness. Full article

Breath analysis, despite being an overlooked biomatrix, has a rich history in disease diagnosis. However, volatile organic compounds (VOCs) have yet to establish themselves as clinically validated biomarkers for specific diseases. As focusing solely on late-stage or malignant disease biomarkers may have limited relevance in clinical practice, the objective of this review is to explore the potential of VOC breath tests for the diagnosis of non-cancer diseases: (1) Precancerous conditions like gastro-esophageal reflux disease (GERD) and Barrett’s esophagus (BE), where breath tests can complement endoscopic screening; (2) endoluminal diseases associated with autoinflammation and dysbiosis, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease, which currently rely on biopsy and symptom-based diagnosis; (3) chronic liver diseases like cirrhosis, hepatic encephalopathy, and non-alcoholic fatty liver disease, which lack non-invasive diagnostic tools for disease progression monitoring and prognostic assessment. A literature search was conducted through EMBASE, MEDLINE, and Cochrane databases, leading to an overview of 24 studies. The characteristics of these studies, including analytical platforms, disorder type and stage, group size, and performance evaluation parameters for diagnostic tests are discussed. Furthermore, how VOCs can be utilized as non-invasive diagnostic tools to complement existing gold standards is explored. By refining study designs, sampling procedures, and comparing VOCs in urine and blood, we can gain a deeper understanding of the metabolic pathways underlying VOCs. This will establish breath analysis as an effective non-invasive method for differential diagnosis and disease monitoring. Full article

We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline ¹⁸F-FDG-PET/CT could predict developing metastatic disease and overall survival (OS) in gastroesophageal cancer (GEC). Patients referred for primary staging who underwent ¹⁸F-FDG-PET/CT from 2008 to 2019 were evaluated retrospectively. Overall, 243 GEC patients (mean age = 64) were enrolled. Clinical, histopathology, and sarcopenia data were obtained, and primary tumor radiomics features were extracted. For classification (early-stage vs. advanced disease), the association of the studied parameters was evaluated. Various clinical and radiomics models were developed and assessed. Accuracy and area under the curve (AUC) were calculated. For OS prediction, univariable and multivariable Cox analyses were performed. The best model included PET/CT radiomics features, clinical data, and sarcopenia score (accuracy = 80%; AUC = 88%). For OS prediction, various clinical, CT, and PET features entered the multivariable analysis. Three clinical factors (advanced disease, age ≥ 70 and ECOG ≥ 2), along with one CT-derived and one PET-derived radiomics feature, retained their significance. Overall, ¹⁸F-FDG PET/CT radiomics seems to have a potential added value in identifying GEC patients with advanced disease and may enhance the performance of baseline clinical parameters. These features may also have a prognostic value for OS, improving the decision-making for GEC patients. Full article

Background: The FLOT4-AIO trial (2019) showed improved survival with perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) compared to anthracyclin triplets in gastric cancer treatment. It is unclear whether these results extend to real-world scenarios in the Netherlands. This study aimed to compare outcomes of perioperative FLOT to anthracyclin triplets in a real-world Dutch gastric cancer population. Methods: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) gastric or gastro-esophageal junction carcinoma between 2015–2021 who received neoadjuvant FLOT or anthracyclin triplets were selected from the Netherlands Cancer Registry. The primary outcome was overall survival (OS), analyzed through multivariable Cox regression. Secondary outcomes included pathological complete response (pCR), neoadjuvant chemotherapy cycle completion, surgical resection rates, and adjuvant therapy. Results: Adjusted OS showed no significant survival benefit (HR = 0.88, 95% CI 0.77–1.01, p = 0.07), even though the median OS was numerically improved by 8 months with FLOT compared to anthracyclin triplets (48.1 vs. 39.9 months, p = 0.16). FLOT patients were more likely to undergo diagnostic staging laparoscopies (74.2% vs. 44.1%, p < 0.001), had higher rates of completing neoadjuvant chemotherapy (OR = 1.35, 95% CI 1.09–1.68, p = 0.007), receiving adjuvant therapy (OR = 1.34, 95% CI 1.08–1.66, p = 0.08), and achieving pCR (OR = 1.52, 95% CI 1.05–2.20, p = 0.03). No significant differences were observed in (radical) resection rates. Conclusion(s): Real-world data showed no significant OS improvement for FLOT-treated patients compared to anthracyclin triplets, despite more staging laparoscopies. However, FLOT patients demonstrated higher rates of neoadjuvant therapy completion, proceeding to adjuvant therapy, and increased pCR rates. Therefore, we recommend the continued use of neoadjuvant FLOT therapy in the current clinical setting. Full article

Background: Cold stress suppresses antitumor response in animal models, leading to tumor growth. Recent studies have also shown a negative correlation between the average annual temperature (AAT) and cancer incidence. We hypothesized that esophageal cancer (EC) and gastric cancer (GC) patients living in warmer climates have improved survival outcomes than those living in colder climates. Methods: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database from 1996 to 2015. We retrieved the National Centers for Environmental Information data to calculate the county-level AAT. Cox multivariate regression models were performed to measure the association between temperature (measured continuously at diagnosis and in 5-degree increments) and OS/DSS, adjusting for variables. All associations were compared at a significance level of 0.05. The OS and DSS were summarized using Kaplan–Meier methods. All statistics were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Results: A total of 17,408 EC patients were analyzed. The average age of the cohort was 65 years, 79% of which were males and 21% were females. Of them, 61.6% had adenocarcinoma, and 37.6% were squamous. After adjusting for covariates, patients in regions with an AAT > 53.5 °F had an 11% improvement in OS [HR 0.89 (95% CI 0.86–0.92), p < 0.0001] and 13% in DSS [HR 0.87 (95% CI 0.84–0.90), p < 0.0001]. When the temperature was analyzed in 5 °F increments, with each increment, there was a 3% improvement in OS [HR 0.97 (95% CI 0.96–0.98), p < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95–0.97), p < 0.0001]. Subgroup analysis of squamous and adenocarcinoma showed similar results. These findings were validated in 20,553 GC patients. After adjusting for covariates, patients in regions with an AAT > 53.5 had a 13% improvement in OS [HR 0.87 (95% CI 0.85–0.90), p < 0.0001] and 14% in DSS [HR 0.86 (95% CI 0.83–0.89), p < 0.0001]. When analyzed in 5 °F increments, with each increment, there was a 4% improvement in OS [HR 0.96 (95% CI 0.952–0.971), p < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.945–0.965), p < 0.0001]. Conclusion: We showed for the first time that higher environmental temperatures are associated with significant improvements in OS and DSS in patients with gastro-esophageal cancers, notwithstanding the limitations of a retrospective database analysis. Further confirmatory and mechanistic studies are required to implement specific interventional strategies. Full article

Gastric cancer is the fifth most common malignancy worldwide and one of the main causes of cancer-related death. While surgical treatment is the only curative option for early disease, many have inoperable or advanced disease at diagnosis. Treatment in this case would be a combination of chemotherapy and immunotherapy. Gastro-esophageal (GEJ) and gastric cancer (GC) genetic profiling with current molecular diagnostic techniques has significantly changed the therapeutic landscape in advanced cancers. The identification of key players in GEJ and GC survival and proliferation, such as human epidermal growth factor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1), has allowed for the individualization of advanced cancer treatment and significant improvement in overall survival and progression-free survival of patients. This review comprehensively examines the current and emerging role of monoclonal antibody-based first-line treatments in advanced GEJ and GC. We explore the impact of monoclonal antibodies targeting HER2, VEGF, PD-1/PD-L1, and Claudin 18.2 (CLDN18.2) on the first-line treatment landscape by talking about key clinical trials. This review emphasizes the importance of biomarker testing for optimal treatment selection and provides practical recommendations based on ASCO guidelines. Full article

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 was held in Quebec City, Quebec 2–4 February 2023. The purpose of the conference was to develop consensus statements on emerging and evolving treatment paradigms. Participants included Canadian medical oncologists, radiation oncologists, pathologists and surgical oncologists from across Ontario, Quebec, and the Atlantic provinces. Consensus statements were developed following rapid review presentations and discussion of available literature. The recommendations proposed here represent the consensus opinions of physicians involved in the care of patients with gastrointestinal malignancies who participated in this meeting. Full article

This review focuses on the role of magnetic resonance imaging (MRI) in the evaluation of the gastrointestinal tract (GI MRI), analyzing the major technical advances achieved in this field, such as diffusion-weighted imaging, molecular imaging, motility studies, and artificial intelligence. Today, MRI performed with the more advanced imaging techniques allows accurate assessment of many bowel diseases, particularly inflammatory bowel disease and rectal cancer; in most of these diseases, MRI is invaluable for diagnosis, staging, and disease monitoring under treatment. Several MRI parameters are currently considered activity biomarkers for inflammation and neoplastic disease. Furthermore, in younger patients with acute or chronic GI disease, MRI can be safely used for short-term follow-up studies in many critical clinical situations because it is radiation-free. MRI assessment of functional gastro-esophageal and small bowel disorders is still in its infancy but very promising, while it is well established and widely used for dynamic assessment of anorectal and pelvic floor dysfunction; MRI motility biomarkers have also been described. There are still some limitations to GI MRI related to high cost and limited accessibility. However, technical advances are expected, such as faster sequences, more specific intestinal contrast agents, AI analysis of MRI data, and possibly increased accessibility to GI MRI studies. Clinical interest in the evaluation of bowel disease using MRI is already very high, but is expected to increase significantly in the coming years. Full article

Barrett’s esophagus is the most important complication of gastro-esophageal reflux disease and the only known precursor of esophageal adenocarcinoma. The diagnosis and treatment of Barrett’s esophagus are clinically challenging as it requires a high level of knowledge and competence in upper gastrointestinal endoscopy. For instance, endoscopists should know when and how to perform biopsies when Barrett’s esophagus is suspected. Furthermore, the correct identification and treatment of dysplastic Barrett’s esophagus is crucial to prevent progression to cancer as well as it is the endoscopic surveillance of treated patients. Herein, we report practice-oriented answers to clinical questions that clinicians should be aware of when approaching patients with Barrett’s esophagus. Full article

In the West, recent decades have demonstrated an epidemiological trend towards esophago-gastric adenocarcinomas (EGAC), with considerable associated mortality. Historically, chemotherapy has represented the sole systemic treatment option in the advanced EGAC setting, in addition to complementing the role of surgery and radiotherapy in the case of localized disease. Immune checkpoint inhibitors (ICIs) represent a novel systemic therapeutic choice and have revolutionized the management of other malignancies, including melanoma and renal cell carcinomas. This article considers the rationale for ICIs in EGAC, reviews the evidence supporting their role in the current standard of care in EGAC, and briefly considers ongoing trials and future directions for the ICI class in EGAC. Full article

Introduction: Gastric (GC) and gastro-esophageal cancer (GEC) are common neoplasms in the elderly. However, in clinical practice, the correct strategy for elderly patients who might benefit from chemotherapy (CT) is unknown. Prospective data are still poor. In this context, we performed a retrospective analysis of GC patients aged ≥75 years and treated at our institutions. Material and Methods: We retrospectively analyzed 90 patients with confirmed metastatic GC or GEC, treated with an upfront CT. Inclusion criteria were patients aged ≥75 years, PS 0–2, normal bone marrow/liver/renal function and no major comorbidities. All patients received a G8 score, and some patients with G8 ≤14 received a comprehensive geriatric assessment (CGA). The primary goal was to perform a safety evaluation based on the incidence of adverse events (AE), and the secondary goal was to determine the efficacy (PFS and OS). The chi-square test and the Kaplan–Meier method were used to estimate the outcomes. The statistical significance level was set at p < 0.05. Results: Toxicity rates were quite low: G1/G2 (51.1%) and G3/G4 (25.5%). No toxic deaths were reported. The median PFS was 6.21 months and the median OS 11 months. The G8 score and PS ECOG significantly influenced both PFS and OS. A statistically significant correlation among G8, weight loss, hypoalbuminemia and risk of G3/G4 adverse events was also found. Conclusion: Our research on selected elderly patients did not detect broad differences of efficacy and tolerability compared to a young population. Our study, although retrospective and small-sized, showed that G8 score might be an accurate tool to identify elderly GC/GEC patients who could be safely treated with CT, further recognizing patients who could receive a doublet CT and who may require a single agent chemotherapy or a baseline dose reduction. Full article

Gastric, esophageal and gastro-esophageal junction cancers are associated with inferior outcomes. For early-stage disease, perioperative chemotherapy or chemoradiation followed by surgery is the standard treatment. For most patients with advanced upper gastrointestinal tract cancers, platinum-based chemotherapy remains a standard treatment. Recently, several randomized clinical trials have demonstrated the benefit of immunotherapy involving checkpoint inhibitors alone or in combination with chemotherapy in patients with gastro-esophageal cancer and have changed the treatment landscape. The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC), involving experts from four Western Canadian provinces, convened virtually on 16 June 2021 and developed the recommendations on the role of immunotherapy in patients with gastro-esophageal cancer. Full article