Early Adenocarcinoma Research Articles

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.

738. WHICH PATIENTS WITH BARRETT'S ESOPHAGUS ARE MOST LIKELY FOR MALIGNIZATION? UNI AND MULTIVARIANT STUDY. RISK GROUPS

Abstract Background Barrett's esophagus (BE) is a premalignant pathology that can sometimes progress to adenocarcinoma (ADC) of the esophagus. Although the percentage of malignancy is low, one in every 200 patients/year, in the world literature there is great variability (0,1-1 % patients/year). This important discrepancy arises because we know that not all patients with BE have the same risk of malignancy. The objective of this work is allowing us to stratify patients according to their risk of malignancy. Methods We have 147 patients with a mean (range) follow-up is 13.3 years (2-33). During this period, 16 patients progressed to early esophageal ADC (10.8%), malignancy rate of 0.8 patients/year. Two study groups were obtained: 1. Patients with non-malignant BE: 131 (median age 43 years (10-79). 96 men (73%). 2. Patients with malignant BE: 16 (median age 51 years (21-74). 15 men (94%). Statistical method A univariate and multivariate statistical study was carried out to detect which factors have a greater risk of malignancy. We analyzed epidemiological, clinical, endoscopic, histological, functional factors (motility and pH) and therapeutic. RESULTS Age: 22 patients over 65 years, 22.7% of malignancy, and only 8.8% patients under 65 (p=0.05, OR=3.048). Sex 13.5 % men progressed and only 2.8 % women (p=0.045). Familial Barrett's esophagus was positive in 6 patients, 66.6% malignant, while only 8.5% without familial BE progressed (p=0.0001). EB length: patients with metaplastic segments greater than 4 cm have a 12 times greater risk of malignancy. Low grade dysplasia: 39 % patients had a diagnosis of LGD became malignant, and only 7 % patients with not LGD (p&amp;lt;0.0001, OR 8.49). Proliferation Ki67 and p53 high expression patients were malignant in 69.2% and 91.7 % (p&amp;lt;0.0001, OR 29.25 and 242.00). Esophageal functional studies 22.6% patients with esophageal body hypomotility became malignant and only 3.2 % with preserved esophageal body motility (p=0.001, OR 8.75). Neither the mean LES pressure nor the percentage of patients with hypotensive LES were statistically significant. 20.4% patients with severe acid reflux (pH &amp;lt;4 greater than 24%) became malignant versus 6.1 % patients suffered from less reflux (p=0.009, OR 3.93). Type and effectiveness of treatment Malignancy according to treatment, no differences are observed (10 % and 11.6 % en medical and surgical groups). Only 3.9 % patients with effective treatment became malignant, while in 48.1% who failed treatment (p=0.0001, OR 22.9). Multivariate analysis Only LGD reached statistical significance (p=0.007) with an OR 7.18, and the high expression of p53 (p&amp;lt;0.0001) with an OR 89.14. Risk groups Based on statistical analysis, we have established three risk groups (figure 1). We included 5 patients with High Risk (3.5%, F-U 8.6 years), all malignant (100%, 11.6% patients/year). Intermediate Risk 33 patients (22.5%, F-U 11.97 years, with progression in 11 patients (33.3%, 2.7% patients/year). Low Risk to 109 patients (74%), none became malignant. (p&amp;lt;0.0001, OR: 1.78). Conclusion In patients with high and intermediate risk, therapeutic options and endoscopic follow-up should be different than in patients with the absence of these disease characteristics, classified as low risk.

Clinical and molecular features of early onset pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is a major health burden and may become the second cause of death by cancer in developed countries. The incidence of early-onset pancreatic cancer (EOPC, defined by an age at diagnosis <50 years old) is increasing. Here, we conducted a study of all PDAC patients followed at our institution. Patients were classified as EOPC or non-early onset (nEOPC, >50). Eight hundred and seventy eight patients were included, of which 113 EOPC, exhibiting a comparable performance status. EOPC were more often diagnosed at the metastatic stage (70.0% vs 58.3%) and liver metastases were more prevalent at diagnosis (60.2% vs. 43.9%). The median overall survival (OS) from diagnosis was 18.1 months, similar between EOPC and nEOPC. Among patients who underwent surgery, recurrence-free survival was similar between age groups. Among metastatic patients, first line progression free survival was similar but EOPC received more treatment lines (72.3% vs. 58.1% received ≥2 lines). Regarding molecular alterations, the mean tumor mutational burden (TMB) was lower in EOPC (1.42 vs. 2.95 mut/Mb). The prevalence of KRAS and BRCA1/2 mutations was similar, but EOPC displayed fewer alterations in CNKN2A/B. Fifty eight patients (18.6%) had actionable alterations (ESCAT I-III) and 31 of them received molecularly matched treatments. On the transcriptomic level, despite its clinical aggressiveness, EOPC was less likely to display a basal-like phenotype. To conclude, EOPC were diagnosed more frequently at the metastatic stage. OS and 1st line PFS were similar to nEOPC. EOPC displayed specific molecular features, such as a lower TMB and fewer alterations in CDKN2A/B.

Real-world biomarker testing patterns: clinical-pathological portrait of early and late non-small cell lung cancer in hub and spoke North Italian centers.

Lung cancer is still the main cause of cancer death. In the last decades, significant innovations were introduced in non-small cell lung cancer (NSCLC) treatment and management improving patient outcomes. The discovery of immune checkpoint inhibitors and the detection of an increasing list of actionable genetic alterations are enabling a tailored approach. Herein, we assessed in a pragmatic retrospective study the rate of biomarker tests within a large pulmonary pathology-based unit (PPU) network of the Veneto region (Northern Italy). Each PPU of 7 hubs and spoke centers implemented a biomarker database with pathologic and clinical data of patients with NSCLC diagnosis over 24 months. Out of 1,817 NSCLC cases, 51% were advanced and 49% early stage, with 72% being adenocarcinomas. Programmed death ligand 1 expression and epidermal growth factor receptor mutations were available in most samples, 91% and 78%, respectively. Only 36% of advanced stages received all 5 biomarker tests with an increased rate over time. Co-occurring molecular alterations were detected in 42 cases (2%): the prevalence was (n=17) 41% and (n=25) 59% in early and late-stage adenocarcinomas, respectively. In this real-world study, while most patients received at least one biomarker test, less than 50% had all 5 biomarkers. The screening appeared to increase over time especially with the progressive use of next generation sequencing. Our results confirm the importance of systematic biomarker testing including all NSCLCs based on the evidence of several genomic alterations also in early-stage disease whose analysis may become relevant as neo-adjuvant targeted therapies are available. Non-small cell lung cancer (NSCLC); biomarkers; actionable targets; lung cancer.

Molecular pathogenesis of microsatellite instability-high early-stage colorectal adenocarcinoma in India.

The prevalence of microsatellite instability (MSI) subtype among all colon cancers in India is about 30 %, approximately two times more than that of western population suggesting different molecular pathogeneses. A NanoString analysis-based Pan cancer differential expression (DE) profile was determined in a primary cohort of early-stage CRC (tumor=10, normal=7), and correlated against MSI status. Using RT-PCR, tumor-specific DE genes were validated in another cohort of MSI-high CRC (n=15). Among the most differentially expressed genes, AXIN2, ETV4, and RNF43 were tumor cell-specific signals, while a set of genes including COL11A1, COMP, INHBA, SPP1, MMP3, TLR2, and others were immune cell-specific signals, that had a differential expression between MSI and MSS groups. When overlapped with The Cancer Genome Atlas (TCGA) studies using the Tumor immune estimation resource tool (TIMER), and protein-protein interaction analysis by STRING.db, these genes were segregated to representative tumor cells and immune cells. On validation, the tumor-specific gene signals were inversely associated with TLR4 expression. The differential expression distribution of AXIN2, ETV4, and RNF43 among tumor and immune cells, suggests more than one pathological subset in the MSI-H subgroup of early-stage CRC in the Indian population.

Preinjection With Ligation-Assisted Endoscopic Mucosal Resection for Barrett's Dysplasia and Early Esophageal Adenocarcinoma: Characteristic Histological Features of the Depth of Resection.

Endoscopic mucosal resection (EMR) is an established technique for the diagnosis and treatment of high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) in Barrett's esophagus. Submucosal preinjection is not universally used or generally recommended when performing routine ligation-assisted EMR. Prior studies, however, have demonstrated evidence of at least superficial muscle injury on ligation-assisted EMR without submucosal injection. There are limited published data supporting any potential benefit of submucosal preinjection. Our aim was to review this technique and determine the rate of any degree of muscle injury in patients with Barrett's HGD and EAC treated with submucosal preinjection before ligation-assisted EMR. Patients undergoing submucosal preinjection before ligation-assisted EMR for Barrett's esophagus at a single institution between 2012 and 2016 were identified. Data were collected regarding patient demographics and medical history, endoscopy and histopathology findings, adverse events, and subsequent outcomes. All EMR specimens were reviewed by an expert gastrointestinal pathologist. One hundred fifty consecutive EMR procedures were performed on 70 patients. Of 70 patients, 85.7% of patients were men, with a median age of 68 years. EAC was identified in 75 specimens (50%) and HGD in 44 specimens (29.3%). Deep resection margins were clear of adenocarcinoma in all specimens. Muscularis propria was not identified in any of the 150 specimens. There were no cases of post-EMR perforation. Preinjection before ligation-assisted EMR achieved complete excision with histologically clear margins, without histological evidence of any inadvertent muscularis propria.

Endoscopic Diagnosis and Treatment of Early Mucosal Neoplasms in the Oesophagus

Endoscopy is the gold standard for diagnosis of oesophageal cancer and its precursor lesions. Besides this, endoscopy treatment of these precursor lesions and early oesophageal cancer has been well evaluated and established. This includes dysplastic lesions associated with Barrett's oesophagus and early adenocarcinoma, as well as early squamous cell cancer of the oesophagus. The role of endoscopy for diagnosis and treatment of these lesions is summarised.