Early Adenocarcinoma Research Articles

Abstract B013: Hallmarks of progression in early neoantigen-expressing lung adenocarcinoma

Abstract Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality, largely due to its high prevalence rate and limited therapeutic options. Immunotherapy remains one of the most promising therapeutic avenues, yet further research is necessary to enhance therapy effectiveness for a broader range of patients. Central to the mechanism of immunotherapy is the detection of tumor neoantigens by cytotoxic T cells, which trigger the elimination of tumor cells. However, it is largely unknown how the early interaction between T cells and neoantigen-expressing tumor cells affects the acquisition of cancer hallmarks and tumor progression. To study this, our lab has developed the iNversion-INduced Joined neoAntigen (NINJA) genetically engineered mouse model in which we can initiate expression of a neoantigen in Kras-mutant, Trp53-null, tdTomato-expressing lung adenocarcinoma cells (KPT-NINJA). This system enables us to analyze tumor initiation, progression, and advanced LUAD development over 20 weeks in both neoantigen-expressing and non-expressing tumors. We defined cancer hallmark acquisition and tumor progression in our model by using a combination of multiplex immunofluorescence and computational algorithms to quantify tumor size, immune infiltration, metastasis, and expression of cancer molecular markers p-ERK and Ki67. We isolated tumor cell and immune cell subsets using neural networks to segment cells and tumor structures and used the colocalization of molecular markers to confirm the identity of various cell types. Our initial data validated that within immunogenic tumors there is an increase of T cell infiltration in tumors and have found immunogenic tumors are associated with overall smaller tumors at early time points. Interestingly, these tumors are associated with a decrease in p-ERK expression, suggesting immune infiltration is negatively correlated with p-ERK expression and tumor size. Together, these data indicate that increased immunogenic pressure may be disrupting early tumor proliferation and hallmark progression, shaping the trajectory of development at a very early stage. We are also correlating other molecular markers of tumor progression with immune infiltration, such as Ki67 expression, which we will colocalize with the other findings to construct a model of how tumors acquire hallmark capabilities from an immunogenic perspective. By isolating the mechanism of early tumor progression in immunogenic contexts, we can begin to predict disease trajectory. This will contribute to a better understanding of the mechanisms behind immune evasion and may uncover crucial insights to broaden immune therapy efficacy. Citation Format: Ishan Bansal, Jennifer Loza, Brian G. Hunt, Kelli Connolly, Srividhya Venkatesan, Nikhil Joshi. Hallmarks of progression in early neoantigen-expressing lung adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B013.

Trends and Outcomes of Neoadjuvant Chemotherapy for Clinical Stage T1 Pancreatic Cancer.

Neoadjuvant chemotherapy (NC) for early pancreatic ductal adenocarcinoma (PDAC) remains controversial. We investigate the adoption of NC and its impact on survival in clinical T1 (cT1) PDAC. National Cancer Database (2006-2017) was reviewed for cT1 PDAC. Patients receiving NC and surgery were compared with patients undergoing upfront surgery (US). A total of 5886 patients were included. NC use increased from 4.8% in 2006 to 18.8% in 2017. The NC group (n = 618) versus the US group (n = 5268) had: younger age (66 years vs. 68 years), smaller tumor size (2 cm vs. 2.2 cm), more pancreas head tumors (77% vs. 70.6%), lower lymph-vascular invasion (25.9% vs. 40.6%), and less lymph node positivity (43.6% vs. 54.5%), p < 0.001. Factors associated with receipt of NC were: younger age, recent year of diagnosis, and treatment at an academic program. In the NC group versus the US group, median OS was 35.2 months versus 28.3 months, p < 0.001. Factors associated with improved survival included: well differentiated pathology, R0 surgical margins, and receipt of chemotherapy. In cT1 PDAC, chemotherapy is associated with improved survival. In a surgery-first approach, only 59% of patients receive adjuvant chemotherapy. These data suggest consideration of neoadjuvant therapy for early pancreatic cancer.

Early gastric adenocarcinoma with enteroblastic differentiation diagnosed synchronously with a conventional gastric adenocarcinoma.

Early gastric adenocarcinoma with enteroblastic differentiation diagnosed synchronously with a conventional gastric adenocarcinoma.

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

A phase III randomized trial on the addition of a contact x-ray brachytherapy boost to standard neoadjuvant chemo-radiotherapy for organ preservation in early rectal adenocarcinoma: 5 year results of the OPERA trial

The OPERA trial has shown that a contact X Ray Brachytherapy 50kV (CXB) boost with neoadjuvant chemoradiotherapy (NCRT) can increase organ preservation (OP) rate for early rectal adenocarcinoma (ADK) of low-mid rectum. We report the results after 5 years of follow-up. OPERA was a multicenter, phase III trial that included operable patients (pts), with cT2-cT3b low-mid rectal ADK, tumors <5 cm, cN0 or cN1 <8 mm. All pts received external beam radiotherapy (EBRT): 45Gy in 25 fractions with concurrent capecitabine. Pts were randomly assigned (1:1) to receive a boost of EBRT in group A (9Gy/5 fractions) or a boost with CXB (90Gy/3 fractions) in group B. The primary end point was OP rate. Out of 148 patients randomized, 141 were eligible. Between week 14-24, a clinical complete (or near) response was observed in 44 pts in group A (64%) vs 66 in group B (92%); p<0.001. The 3-year OP rate was 59% in group A vs 81% in group B (p=0.003). After update the median follow-up was 61.1 months [56.8-64.5]. The 5-year local regrowth was 39% in group A and 17% in group B (p=0.1). The difference in OP was still highly significant between both groups: A 56% vs B 79% (p=0.004). The difference was more significant if tumors < 3cm, with an OP rate of 93% in group B compared to 54% in group A. Of the 28 local regrowths, 3 occurred after 3 years of follow-up. Rectal bleeding (grade 1-2), which was the most prevalent toxicity during follow-up, disapeared most of the time after three years. Bowel function was not worsened by the CXB boost. The OPERA trial was the first trial to demonstrate that CXB dose escalation was increasing the OP rate with good bowel function at 3 years. At 5 years, these results are sustained, specially in small early-stage tumors. The occurrence of some local regrowth after 3 years necessitates close surveillance of these pts during the 5-year period.

Endoscopic and clinicopathological features of early gastric papillary adenocarcinoma.

Gastric papillary adenocarcinoma (GPA), a well-differentiated gastric adenocarcinoma, is associated with a worse prognosis compared to other differentiated gastric adenocarcinomas. Therefore, there is an urgent need to characterize its endoscopic manifestations for guiding biopsy site selection and achieving accurate diagnosis. From January 1, 2016, to December 31, 2022, the data of 46 cases of early gastric papillary adenocarcinoma (EGPA) and 183 cases of early gastric differentiated tubular adenocarcinoma (EGDTA) diagnosed via pathological examination following endoscopic submucosal dissection (ESD) at the Second Hospital of Shandong University were collected. Propensity score matching (PSM) was employed to match 92 EGDTA patients at a ratio of 1:2, serving as the control group. Differences between the two groups were analyzed using multivariable logistic regression. Lastly, the relationship between vessels within epithelial circle (VEC) structures in EGPA and the degree of malignancy was assessed. Compared with EGDTA, EGPA was more likely to infiltrate the submucosa, more frequently associated with poorly differentiated cancer components, and more prone to invading lymphatic and blood vessels. EGPA was primarily located in the lower stomach and manifested as a uniformly elevated pattern under endoscopy, while VEC structural positivity could be visualized under ME-NBI. Moreover, EGPA lesions had larger diameters and were characterized by high expression of gastric mucins, namely MUC5AC and MUC6. When EGPA infiltrated the submucosa or contained poorly differentiated cancer components, the VEC structures were smaller. The present study demonstrated that EGPA exhibits a higher degree of malignancy. Endoscopic findings of a raised lesion with a uniform color under endoscopy and the presence of VEC structures under ME-NBI suggest a high possibility of EGPA. Moreover, smaller VEC structures were associated with a higher degree of malignancy, which may assist in guiding the selection of biopsy sites under endoscopy.

Early Onset Pancreatic Adenocarcinoma (EOPAC): presentation, clinical course and treatment outcomes in comparison to Average Onset Pancreatic Adenocarcinoma (AOPAC): a retrospective cohort study

BackgroundPancreatic adenocarcinoma (PAC) is a disease of decimal prognosis, with around 50% of patients presenting with metastatic disease. Previous trials reported a high incidence of early onset pancreatic cancer (EOPAC) in Egypt, presenting about 25% of patients with PAC. The clinic-pathological features and prognosis of EOPAC needs more study.Patients and methodsA retrospective analysis of patients’ records at Shefa Al-Orman comprehensive cancer center database. Patients with histo-pathologically confirmed diagnosis of PAC. We categorized patients according to the age at diagnosis into EOPAC (≤ 50 years) and average onset PAC (AOPAC). Data on risk factors, family history, presenting symptoms, clinic-pathological features, treatment, and prognosis were extracted. Patients with histopathologically confirmed diagnosis of pancreatic cancer diagnosed between December 2016-December 2022 were included.ResultsThe study cohort consisted of 412 patients. EOPAC represented 20.3% of patients, with no significant differences in risk factors and family history compared to AOPAC. Duration of symptoms before diagnosis is longer in EOPAC, with the majority of EOPAC presenting with localized disease (23.8%) and locally advanced tumors (28.5%) compared to AOPAC. AOPAC presented more with metastatic disease (64% vs. 45.2%, p = 0.003). EOPAC are usually submitted to more aggressive treatment including radical surgery, neoadjuvant therapy, and aggressive chemotherapy regimens in metastatic disease. Disease free survival (DFS) of EOPAC was shorter than AOPAC (11 months vs. 17 months, p = 0.889), but overall survival OS was significantly longer in EOPAC (10 months vs. 6 months, p = 0.013).ConclusionPatients with EOPAC in Egypt represent around 25% of cases. EOPAC tend to have a shorter disease free survival (DFS) in patients presenting with localized disease. The overall survival (OS) is longer in EOPAC compared to AOPAC. Further studies are mandatory to identify the epidemiological and risk factors of EOPAC in Egypt.

9334 Pancreatic Adenocarcinoma Presenting As Diabetic Ketoacidosis

Abstract Disclosure: J. Alvarez: None. M.H. Horani: None. Background: Pancreatic adenocarcinoma is often diagnosed at an advanced stage due to late onset of clinical features including poor appetite, weight loss, weakness, epigastric pain, and rarely impaired glucose tolerance. In patients who present with impaired glucose tolerance or diabetic ketoacidosis without prior history of diabetes, pancreatic adenocarcinoma should be considered. Clinical Case: Patient is a 45-year woman with depression, HTN, irritable bowel syndrome who was found unresponsive by family and presented to the ED for acute encephalopathy. On exam, she was obtunded, tachypneic, with fruity-smelling breath and dry mucous membranes. Initial labs showed glucose of 950 mg/dL (70-99 mg/dL), lipase 539 U/L (8-78 U/L), lactic acid 4 mmol/L 0.5-2 mmol/L), ketone-BHB 170.75 mg/dL (0-2.81 mg/dL), A1c 16.5%. She had no prior history or family history of diabetes. She was admitted to hospital for DKA management.CXR to evaluate dyspnea showed bilateral opacities so CT chest/abdomen/pelvis without contrast was ordered. This showed bilateral multilobar pneumonia, trace pleural effusions, 6.7 x 3.8 cm lobulated fluid collection along pancreatic tail, 12.1 x 6.6 x 4.4 cm RLQ cystic lesion and 4.4 cm lesion vs loculation along the right pelvic sidewall.Initially, GI recommended repeat imaging of the pancreas in 4-6 weeks. OBGYN was consulted for pelvic masses and recommended IR-guided biopsy of right pelvic mass which showed rare mildly atypical mucinous epithelium present, cystic mucinous neoplasm cannot be excluded.CEA and CA125 tumor markers returned elevated. These biopsies showed adenocarcinoma (solid component) and rare atypical mucinous epithelium consistent with cystic mucinous neoplasm (cystic fluid). Patient was deemed medically stable for discharge with recommended follow-up to appropriate specialists. Following discharge, she was officially diagnosed with Stage III (cT4, cN0, cM0) pancreatic adenocarcinoma and started on appropriate chemotherapeutic regimen. Discussion: The current understanding is long-standing type 2 diabetes mellitus as a risk factor for pancreatic cancer based on previous studies.The inverse relationship of pancreatic cancer causing new onset diabetes is more rare, but if cancer is suspected in these patients it could potentially help in the diagnosis of early stage adenocarcinoma. Other case reports have suggested implementation of the enriching new-onset diabetes for pancreatic cancer (ENDPAC) score in addition to CT and EUS as screening for pancreatic cancer may help with earlier diagnosis.

P4.04C.06 DNA Methylation Analysis in Plasma for Early Diagnosis Inlung Adenocarcinoma

P4.04C.06 DNA Methylation Analysis in Plasma for Early Diagnosis Inlung Adenocarcinoma

Novel prediction model of early screening lung adenocarcinoma with pulmonary fibrosis based on haematological index

BackgroundLung cancer (LC), a paramount global life-threatening condition causing significant mortality, is most commonly characterized by its subtype, lung adenocarcinoma (LUAD). Concomitant with LC, pulmonary fibrosis (PF) and interstitial lung disease (ILD) contribute to an intricate landscape of respiratory diseases. Idiopathic pulmonary fibrosis (IPF) in association with LC has been explored. However, other fibrotic interrelations remain underrepresented, especially for LUAD-PF and LUAD-ILD.MethodsWe analysed data with statistical analysis from 7,137 healthy individuals, 7,762 LUAD patients, 7,955 ILD patients, and 2,124 complex PF patients collected over ten years. Furthermore, to identify blood indicators related to lung disease and its complications and compare the relationships between different indicators and lung diseases, we successfully applied the naive Bayes model for a biomarker-based prediction of diagnosis and development into complex PF.ResultsMales predominantly marked their presence in all categories, save for complex PF where females took precedence. Biomarkers, specifically AGR, MLR, NLR, and PLR emerged as pivotal in discerning lung diseases. A machine-learning-driven predictive model underscored the efficacy of these markers in early detection and diagnosis, with NLR exhibiting unparalleled accuracy.ConclusionsOur study elucidates the gender disparities in lung diseases and illuminates the profound potential of serum biomarkers, including AGR, MLR, NLR, and PLR in early lung cancer detection. With NLR as a standout, therefore, this study advances the exploration of indicator changes and predictions in patients with pulmonary disease and fibrosis, thereby improving early diagnosis, treatment, survival rate, and patient prognosis.

Knowledge mapping analysis of ground glass nodules: a bibliometric analysis from 2013 to 2023.

In recent years, the widespread use of computed tomography (CT) in early lung cancer screening has led to an increase in the detection rate of lung ground glass nodules (GGNs). The persistence of GGNs, which may indicate early lung adenocarcinoma, has been a focus of attention for scholars in the field of lung cancer prevention and treatment in recent years. Despite the rapid development of research into GGNs, there is a lack of intuitive content and trend analyses in this field, as well as a lack of detailed elaboration on possible research hotspots. The objective of this study was to conduct a comprehensive analysis of the knowledge structure and research hotspots of lung ground glass nodules over the past decade, employing bibliometric methods. The Web of Science Core Collection (WoSCC) database was searched for relevant ground-glass lung nodule literature published from 2013-2023. Bibliometric analyses were performed using VOSviewer, CiteSpace, and the R package "bibliometrix". A total of 2,218 articles from 75 countries and 2,274 institutions were included in this study. The number of publications related to GGNs has been high in recent years. The United States has led in GGNs-related research. Radiology has one of the highest visibilities as a selected journal and co-cited journal. Jin Mo Goo has published the most articles. Travis WD has been cited the most frequently. The main topics of research in this field are Lung Cancer, CT, and Deep Learning, which have been identified as long-term research hotspots. The GGNs-related marker is a major research trend in this field. This study represents the inaugural bibliometric analysis of applied research on ground-glass lung nodules utilizing three established bibliometric software. The bibliometric analysis of this study elucidates the prevailing research themes and trends in the field of GGNs over the past decade. It also furnishes pertinent recommendations for researchers to provide objective descriptions and comprehensive guidance for future related research.

Impact of sex on premature mortality for elderly patients with early adenocarcinoma of the esophagus or stomach

Impact of sex on premature mortality for elderly patients with early adenocarcinoma of the esophagus or stomach

Association of pancreatic atrophy patterns with intraductal extension of early pancreatic ductal adenocarcinoma: a multicenter retrospective study.

Focal pancreatic parenchymal atrophy (FPPA) and upstream pancreatic atrophy (UPA) may indicate the presence of early pancreatic cancer. In early pancreatic cancer, the tumor occasionally spreads laterally along the main pancreatic duct, presenting challenges in determining the extent of surgical resection. This study aimed to investigate the association of pancreatic atrophy pattern and intraductal cancer extension. Thirty-two patients with early-stage pancreatic cancer who underwent surgery at five participating centers were enrolled. Pancreatic atrophy was defined as the narrowing of parenchyma compared to the surrounding parenchyma and was classified as either FPPA (partial atrophy surrounding the pancreatic duct stenosis) or UPA (global atrophy caudal to the site of duct stenosis). Intraductal cancer extension was defined as an extension exceeding 10mm. Preoperative computed tomography revealed FPPA, UPA, and no parenchymal atrophy in 13, 13, and 6 patients. Cases with FPPA or UPA showed significantly longer cancer extensions than those without atrophy (P = 0.005 and P = 0.03, respectively). Intraductal cancer extension was present in all but one case of FPPA. 69% (9/13) of the cases with UPA showed intraductal cancer extension, whereas cases without atrophy showed no intraductal cancer extension. Importantly, two patients with FPPA or UPA showed positive resection margins during surgery and three patients with FPPA or UPA showed recurrence in the remnant pancreas. The presence of FPPA and UPA indicates lateral cancer extension in early-stage pancreatic cancer. Preoperative assessment of the pancreatic parenchyma may provide valuable insights for determining the extent of surgical resection.

The value analysis of high-resolution thin-layer CT in the identification of early lung adenocarcinoma: An observation study.

The aim of this study was to explore the clinical value of high-resolution thin-layer computed tomography (CT) for the identification of early lung adenocarcinoma. Ninety patients with early lung adenocarcinoma who were diagnosed and treated in our hospital were selected as study subjects and divided into noninvasive (NIG, n = 51) and invasive (IG, n = 39) groups according to their pathological findings. Both groups underwent high-resolution target scanning. Differences in lesion size, density, and distribution between the 2 groups were compared. Intergroup differences in the CT signs were examined. A receiver-operating characteristic curve was established to calculate the diagnostic efficacy of high-resolution, thin-layer CT for early lung adenocarcinoma infiltration. The maximum diameter and density of the tumors were significantly higher in the IG than in the NIG (P < .05). The proportions of CT signs of lobulation, spicule, and vessel convergence were higher in the IG patients compared to the NIG (P < .05). High-resolution thin-layer CT for the diagnosis of lung adenocarcinoma infiltration had an AUC of 0.6702 (P < .05), a diagnostic sensitivity of 64.10%, and a diagnostic specificity of 60.78%. High-resolution thin-layer CT had certain differential diagnostic efficacy for early lung adenocarcinoma, which clearly presents various CT signs of early lung adenocarcinoma lesions.

Expression and significance of cystine transporter SLC7A11/xCT in early colorectal cancer specimens from endoscopic submucosal dissection.

The SLC7A11/xCT cystine transporter is intricately linked with ferroptosis. By mediating intracellular cystine flux, it regulates oxidative stress within neoplastic cells, thereby curtailing ferroptosis and influencing the emergence of colorectal cancer. This study aimed to gauge the SLC7A11/xCT expression across various tumorigenic stages in early colorectal adenocarcinoma tissues, shedding light on its specific role in the genesis of these early malignancies. Sixty specimens that underwent endoscopic submucosal dissection (ESD) resection with pathologic diagnosis of colorectal adenocarcinoma were collected. SLC7A11/xCT expression was pinpointed using immunohistochemistry, and correlations with the patients' clinical-pathological features were drawn. Additionally, a comprehensive bioinformatics assessment was undertaken to discern differential SLC7A11/xCT expressions across a spectrum of cancers. Immunohistochemical assessments unveiled a pronounced cytoplasmic SLC7A11/xCT expression, manifesting as a brownish-yellow hue, particularly in nascent colorectal cancer samples. Its expression was discernibly correlated with both patient gender and adenocarcinoma differentiation grade (P<0.05). Nevertheless, factors such as patient age, tumor localization, infiltration depth, diameter, adjacent adenoma histology, its major axis, and dysplasia degree bore no statistical significance with SLC7A11/xCT levels (P>0.05). Bioinformatics insights pointed to an upregulated SLC7A11/xCT expression across diverse malignancies, inclusive of colon adenocarcinoma, esophageal cancer, acute myeloid leukemia, lung squamous cell carcinoma, colorectal cancer, and endometrial cancer (P<0.05). Elevated SLC7A11/xCT expression marks early colorectal adenocarcinoma, with the intensity of this expression being intertwined with the patient's gender and the tumor's differentiation grade. It is postulated that colorectal cancer cells might amplify SLC7A11/xCT to stymie ferroptosis, thus fostering neoplastic proliferation, metastasis, and cellular stemness.

Prevalence and Risk Factors for Malignant Nodal Involvement in Early esophago-gastric Adenocarcinoma: Results from the Multicenter Retrospective Congress Study (endosCopic resectiON, esophaGectomy or Gastrectomy For Early Esophagogastric Cancers).

The aim of this study was to quantify LNM risk and outcomes following treatment of early esophago-gastric (EG) adenocarcinoma. The standard of care for early T1N0 EG cancer is endoscopic resection (ER). Radical surgical resection is recommended for patients perceived to be at risk of lymph node metastasis (LNM). Current models to select organ-preserving vs. surgical treatment are inconsistent. CONGRESS is a UK-based multicentre retrospective cohort study. Patients diagnosed with clinical or pathological T1N0 EG adenocarcinoma from 2015-2022 were included. Outcomes and rates of LNM were assessed. Cox regression was performed to assess the impact of prognostic and treatment factors on overall survival. 1,601 patients from 26 centres were included, with median follow-up 32 months(IQR 14-53). 1285/1612(80.3%) underwent ER, 497/1601(31.0%) underwent surgery. Overall rate of LNM was 13.5%. On ER staging, tumour depth (T1bsm2-3 17.6% vs. T1a 7.1%), lymphovascular invasion (17.2% vs. 12.6%), or signet cells (28.6% vs. 13.0%) were associated with LNM. In multivariable regression analysis, these were not significantly associated with LNM rates or survival. Adjusting for demographic and tumour variables, surgery after ER was associated with significant survival benefit, HR 0.33(0.15-0.77),P=0.010. This large multicentre dataset suggests that early EG adenocarcinoma is associated with significant risk of LNM. This data is representative of current real clinical practice with ER-based staging, and suggests previously held beliefs regarding reliability of predictive factors for LNM may need to be reconsidered. Further research to identify patients who may benefit from organ-preserving vs. surgical treatment is urgently required.

202. MULTI-ARRAY MIRNA APPROACH AND ASSOCIATED PROTEIN EXPRESSION PROFILING FOR THE DEVELOPMENT OF PREDICTIVE AND PROGNOSTIC BIOMARKERS IN ESOPHAGEAL ADENOCARCINOMA

Abstract Background Esophageal adenocarcinoma (EA) may develop metastases even in early stage (pT1) disease, but molecular bi-omarkers are lacking to guide therapeutic decisions regarding the type of treatment. Endoscopic submucosal dis-section (ESD) is an effective treatment of early esophageal adenocarcinomas. However, ESD only an option for patients without lymph node metastases. The aim of this study is to detect possible biomarkers with which one could estimate lymphatic metastasis. Methods A multi-array miRNA study with consecutive in silico analysis of dependent genes and in situ analysis of selected proteins was chosen to detect possible biomarkers. A retrospective analysis including twenty cases of EA of the distal esophagus/esophagogastric junction after ESD without or after esophagectomy with lymph node metastasis (each n=10) was performed. The DNA of the Formalin-Fixed Paraffin-Embedded (FFPE) material of these patients was analysed using an advanced miRNA Human Card (spotted with 754 unique microRNAs) with consecutive in silico gene regulation and immunohistochemical analysis of the associated proteins. Result The multi-array miRNA of the tumour sample with EA showed an upregulation of 25 and a downregulation of 20 microRNAs, with the highest differences for the miRNAs miR-100-5p, miR-501-3p and miR-576-5p (upregulation) and miR-150-3p, miR-190a-5p and miR-545-3p (downregulation). The in silico analysis of these mirRNAs revealed the downstream paired partners RDX-Rock2, DICER1-AGO2, YAF2-EZF6 and TET2-5HMC, which were significantly differentially expressed by in-situ immunohistochemical staining. Biologically relevant downstream gene and pro-tein targets, which were also significantly differentially expressed in-situ in relation to the tumour stage of EA could be found. Conclusion This molecular study provides evidence for a specific miRNA marker profile when comparing cases with localized and advanced EA. These preclinical experimental biomarker analyses may help to guide therapeutic decisions in cases with EA, although validation in a larger cohort of EA is necessary to draw firm conclusions.

508MO Organ preservation in early rectal adenocarcinoma: 5-year results of the randomized opera trial

508MO Organ preservation in early rectal adenocarcinoma: 5-year results of the randomized opera trial

Long-term outcomes of endoscopic submucosal dissection for early esophageal adenocarcinoma in the Eastern population: a comprehensive analysis

BackgroundEndoscopic submucosal dissection (ESD) is a preferred method for early esophageal cancer, yet its application to esophageal adenocarcinoma (EAC), especially in the Eastern population with its relative rarity, lacks sufficient literature. This study evaluated ESD’s long-term outcomes for EAC, focusing on noncurative resections and diagnostic accuracy. MethodsBetween 2012 and 2022, a retrospective study included 68 patients undergoing ESD for early EAC at Jiangsu Province Hospital. Primary outcomes encompassed ESD efficacy, en bloc resection, R0 resection, curative resection rates, and follow-up. Secondary outcomes involved noncurative ESD, T1a/T1b stage comparison, and diagnostic consistency. ResultsPostoperative staging revealed T1a (n = 53) and T1b tumors (n = 15). En bloc resection rate was 97.1%, R0 resection rate was 79.4%, and noncurative rate was 30.9%. T1a had significantly higher R0 rate and curative resection rate. Among noncurative ESDs, 33.3% underwent esophagectomy, 42.9% had surveillance endoscopies, 19.1% repeated curative ESD, and 4.7% were lost to follow-up. Average follow-up was 63.76 ± 28.47 months. Furthermore, 6 patients had recurrence, 3 had residual lesions, and 6 deaths occurred, unrelated to ESD. No significant difference in survival or recurrence rates between curative and noncurative ESD groups was observed. ESD led to a histologic diagnosis change in 70.6% of cases, all upstaged. ConclusionESD is effective for EAC, with higher curative rates for T1a than T1b. Noncurative ESD cases may benefit from conservative approaches. Long-term follow-up underscores poor consistency between residual lesions and positive margins. ESD serves as a valuable diagnostic staging tool, particularly for T1b cases, considering the low accuracy of endoscopic ultrasound and preoperative biopsy.

504. SENTINEL LYMPH NODE NAVIGATED SURGERY IN ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA USING INDOCYANINE GREEN AND FLUORESCENCE IMAGING

Abstract Background Sentinel lymph node navigated surgery (SNNS) has been adopted for various cancers to reduce the negative impact of lymphadenectomy. Limited lymph node dissection using SNNS might be employed in the management of clinically lymph node negative early esophagogastric junction adenocarcinoma (EGJAC). However, it must be sure that sentinel lymph nodes (SLNs) reflect the patient's overall pN status. The aim of this study was to determine the feasibility and safety of SNNS using near-infrared fluorescence imaging and to obtain preliminary data about sensitivity of prediction of lymph node metastasis using SNNS. Methods Patients with cT1-2cN0 EGJAC without neoadjuvant therapy were prospectively included. One patient was enrolled after non-radical endoscopic resection of a high-risk pT1 tumor. Solution of indocyanine green (ICG) and 10% human serum albumin (ICG concentration 1,25mg/mL) was injected endoscopically into the submucosal layer at four quadrants (á 0.5mL) around the tumor or endoscopic resection scar just before the surgery. Subsequently, SLNs were identified and removed laparoscopically using fluorescence imaging. Then, esophagectomy or gastrectomy with radical lymphadenectomy were performed in all patients. Results A total of nine patients underwent SNNS followed by radical surgery. Histopathology revealed pT0pN0 in 1 patient, pT1bN0 in 3 patients, pT1bN3 in 1 patient, pT2pN1 in 2 patients, pT3pN0 in 1 patient and pT3pN2 in 1 patient. Overall, 62 SLNs were detected (median 7 SLNs per patient, range 1-16). Metastases in SLNs were found in four patients. All patients with pathologically positive lymph nodes had at least one SLN positive for metastasis. Sensitivity of prediction of pN positive status was 100%, false negative rate was 0%. There were no ICG-related adverse events or complications associated with SNNS procedure. Conclusion These results suggest that SNNS using ICG and fluorescence imaging in early EGJAC is feasible and safe. Our pilot data show promising diagnostic accuracy of predicting pathological lymph node status using SNNS. However, further studies with a larger number of patients are needed before introducing SNNS into clinical practice.