Intestinal-type Adenocarcinoma Research Articles

Incidence of Gastric Adenocarcinoma in Those With Gastric Atrophy: A Systematic Review.

Gastric atrophy (GA), or atrophic gastritis, is a pre-neoplastic lesion of gastric cancer (GC). It is part of the Correa cascade, which culminates in intestinal-type gastric adenocarcinoma. The cascade posits that intestinal-type gastric adenocarcinoma develops along a defined pathway of pre-neoplastic stages. The cascade begins with chronic gastritis, most commonly caused by Helicobacter pylori (H. pylori) infection, and proceeds through GA, gastric intestinal metaplasia (GIM), both complete and incomplete, dysplasia, both low and high-grade, and culminating in intestinal-type gastric adenocarcinoma. Attempts in Europe have been made to identify patients at risk of developing GC and target them with surveillance oesophagogastroduodenoscopy (OGD). However, there remains uncertainty about GA's risk of developing into GC. This poses issues in terms of guiding the need for and determining intervals for surveillance OGDs, which are a costly form of surveillance. As such, we attempted to gather all available studies assessing the risk of GC developing from GA, which is the first step in the Correa cascade.This study was a comprehensive systematic review of published papers, reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This systematic review, which included a substantial 25,455 patients across 18 studies, found that the relative risk (RR) of GC in those with GA, using standardised incidence ratios as a measure of RR, was 15.1, with a 95% confidence interval ranging from 13.5 to 16.9. We conclude thatGA does increase the risk of developing GC, and this risk may be higher than previously appreciated. Further large-scale studies are needed in Western cohorts of patients to precisely define this risk and guide the need for surveillance programs. These future studies must be standardised to account for H. pylori status, the topographical distribution of the GA, and the methods for assessing the degree of GA.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis

ObjectivePrecancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood.DesignAn integrated analysis...

Sinonasal intestinal-type adenocarcinoma in northern Portugal: a woodworker’s occupational hazard

Abstract Background Sinonasal carcinomas (SNC) constitute about 3% of all head and neck carcinomas, squamous cell carcinoma being the most common histologic subtype. Some geographical patterns in incidence are observed, as occupational exposure to wood dust is associated with intestinal-type adenocarcinoma (ITAC). Aims This study aims to describe the prevalence and characteristics of sinonasal ITAC cases in a region of northern Portugal with a robust wood industry. Methods A retrospective study of all sinonasal malignancies diagnosed over 5 years, in a tertiary hospital, primarily focused on ITAC subtypes. Data on sociodemographic and clinical variables were collected through electronic medical records and telephonic assessments. Results Of all 33 cases, 85% were ITAC. ITAC predominantly affected males (96%) with a mean age of 66.2 years. Most patients diagnosed with sinonasal ITAC had occupational wood dust exposure (96%), particularly to hardwoods. Initial symptoms included unilateral nasal obstruction (75%) and epistaxis (71%). Despite a median time of 3 months from symptoms to consultation, 50% presented at an advanced stage, with a 29% mortality rate. Conclusions Sinonasal ITAC is an occupational hazard of woodworkers and represents the vast majority of SNC in the region. This study advocates for targeted community interventions, emphasizing occupational safety measures and healthcare awareness to reduce morbimortality associated with this occupational cancer.

Clinical Pathological and Immunohistochemical Correlations in Gastric Cancer.

Due to its high aggressiveness and polyclonal tumor state, stomach cancer is considered a severe health problem. In this study, we analyzed Her2 and Ki67 in correlation with patient data for the possibility of prognostic factors. The study included 48 cases of gastric tumors that had been surgically treated in a period of five years. The percentage was statistically significant for intestinal-type adenocarcinomas located in the medio-gastric region (p = 0.05); in the diffuse subtype, there were no Her2 positive samples, and in the mixed subtype only one out of three samples was Her2 positive. Our results confirm the existing data, and we can conclude that this link can be considered a prognostic factor in the progression and treatment effectiveness.

Prognostic value analysis and survival model construction of different treatment methods for advanced intestinal type gastric adenocarcinoma

BackgroundIntestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). MethodsWe extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve. ResultsAge, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P < 0.05). The nomogram model, constructed from these indicators, demonstrated superior predictive consistency for OS and CSS compared to the AJCC-TNM staging system. ROC curve analysis confirmed the model's higher accuracy, and calibration curve analysis indicated good agreement between the nomogram's predictions and actual observed outcomes. ConclusionThe nomogram model derived from SEER database analyses accurately predicts OS and CSS for patients with intestinal-type gastric adenocarcinoma. This model promises to facilitate more tailored treatments in clinical practice.

Gender Differences in Sinonasal Cancer Incidence: Data from the Italian Registry.

Although rare, sinonasal cancers (SNCs) have a high occupational attributable fraction. We applied gender-based approaches to descriptive analyses, incidence, and patterns of exposures using the Italian National Sinonasal Cancer Registry (ReNaTuNS: Registro Nazionale Tumori Naso-Sinusali). The study included 2851 SNC patients. SNC was diagnosed more often in men (73%) than in women (27%). The most frequent morphology in men was intestinal-type adenocarcinoma (33%), whereas in women, it was squamous cell carcinoma (49%). Nasal cavities were predominant in both genders (50%), ethmoidal sinus in men (24%), and maxillary in women (24%). Incidence rates were 0.76 (per 100,000 person-years) in men and 0.24 in women and increased by age, more evidently in men, peaking over 75 years in both. Occupational exposures to wood and leather dusts were the most frequent (41% for men, 33% for women). Few exposures were extra-occupational or domestic. Unlikely exposure was relevant in women (57%). The surveillance of SNC cases through a registry that allows for the identification of and compensation for this occupational disease is important in Italy, where numerous workers are exposed to carcinogens for SNC, without even being aware. Considering the rarity of the disease, particularly among women, the ReNaTuNS can provide a method to analyze gender differences.

Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Campylobacter jejuni Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion.

Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic, epigenetic, microbiota, and environmental factors. We present the case of a 46-year-old Caucasian male patient with CVID and an immune dysregulation phenotype. The particular elements of the case consisted of an atypical clinical course, which undoubtedly demonstrates the great variability of clinical manifestations that these types of patients can suffer from, including bacterial and viral infections, autoimmune phenomena, and neoplasia. Notably, the patient suffered from recurrent gastrointestinal infection with macrolide-resistant Campylobacter jejuni and gastroduodenal disease and viraemia by cytomegalovirus (CMV). In addition, CMV was postulated as the main pro-oncogenic factor contributing to the development of early-onset intestinal-type gastric adenocarcinoma, for which the patient underwent gastrectomy. The patient's evolution was difficult, but finally, as a result of the multidisciplinary approach, clinical stabilization and improvement in his quality of life were achieved. Based on our brief literature review, this is the first reported case of this clinical complexity. Our experience could help with the management of future patients with CVID and may also update current epidemiological data on CVID.

Tumor Budding, p53, and DNA Mismatch Repair Markers in Sinonasal Intestinal-Type Adenocarcinoma: A Retrospective Study Supports the Adverse Prognostic Impact of Tumor Budding.

Sinonasal intestinal-type adenocarcinoma (ITAC) is a very rare, closely occupational-related tumor with strong histological similarities to colorectal cancer (CRC). In the latter, tumor budding (TB) is widely recognized as a negative prognostic parameter. The aim of this study was to evaluate the prognostic role of TB in ITAC and to correlate it with other established or emerging biomarkers of the disease, such as p53 and deficient DNA mismatch repair (MMR) system status/microsatellite instability (MSI). We retrospectively analyzed 32 consecutive specimens of patients with ITAC diagnosis treated in two institutions in Northern Italy. We reviewed surgical specimens for TB evaluation (low-intermediate/high); p53 expression and MMR proteins were evaluated via immunohistochemistry. Results were retrospectively stratified using clinical data and patients' outcomes. According to bud counts, patients were stratified into two groups: intermediate/high budding (>4 TB) and low budding (≤4 TB). Patients with high TB (>4) have an increased risk of recurrence and death compared to those with low TB, with a median survival of 13 and 54 months, respectively. On multivariate analysis, considering TB, therapy, and stage as covariates, TB emerged as an independent prognostic factor net of the stage of disease or type of therapy received. No impact of p53 status as a biomarker of prognosis was observed and no alterations regarding MMR proteins were identified. The results of the present work provide further significant evidence on the prognostic role of TB in ITAC and underline the need for larger multicenter studies to implement the use of TB in clinical practice.

Association of E-Cadherin Expression with Histological Type and Grade of Gastric Adenocarcinoma

Objectives: To determine the immune expression of E-Cadherin in gastric adenocarcinomas and its association with tumor histological type and grade to evaluate its prognostic significance. Methodology: This descriptive cross-sectional study was conducted at the Pakistan Institute of Medical Sciences Islamabad, from December 2017 to January 2021. Eighty-one patients from both genders, aged 21 to 83 years, undergoing gastric biopsies and Gastrectomy specimens to diagnose gastric adenocarcinoma were included in our study. Immunohistochemical processing was performed and the results were interpreted by the consultant pathologist for the expression of E-cadherin on gastric adenocarcinoma. The data were analyzed with SPSS version 17. Results: There was a significant statistical association between loss of E-Cadherin with histological type of adenocarcinoma (p = 0.000). In total 81 cases, there were 53 (65%) cases of intestinal type adenocarcinoma and 28 (35%) cases of diffuse type adenocarcinoma. Of the 28 cases with diffuse type gastric Adenocarcinoma, 10 cases showed complete loss of E-Cadherin. This complete loss of Cadherin was also seen in four out of 53 cases of intestinal adenocarcinoma, all of which were poorly differentiated intestinal type of adenocarcinomas. Total cases of well differentiated type of adenocarcinoma were nine; all of these showed high expression of E-Cadherin. Conclusion: There is a strong association of E-Cadherin expression with the histological type and grade of gastric adenocarcinoma according to Lauren’s classification. As the grade of the adenocarcinoma gets higher there is more loss of E-Cadherin expression which proves its prognostic significance. It was also established that gastric adenocarcinoma is a disease of elderly with male predominance.

Genome-wide somatic mutation analysis of sinonasal adenocarcinoma with and without wood dust exposure

BackgroundSinonasal adenocarcinoma is a rare cancer, encompassing two different entities, the intestinal-type sinonasal adenocarcinoma (ITAC) and the non-intestinal-type sinonasal adenocarcinoma (non-ITAC). Occurrence of ITAC is strongly associated with exposure to hardwood dusts. In countries with predominant exposure to softwood dust the occurrence of sinonasal adenocarcinomas is lower and the relative amount of non-ITACs to ITACs is higher. The molecular mechanisms behind the tumorigenic effects of wood dust remain largely unknown.MethodsWe carried out whole-genome sequencing of formalin-fixed paraffin-embedded (FFPE) samples of sinonasal adenocarcinomas from ten wood dust-exposed and six non-exposed individuals, with partial tobacco exposure data. Sequences were analyzed for the presence of mutational signatures matching COSMIC database signatures. Driver mutations and CN variant regions were characterized.ResultsMutation burden was higher in samples of wood dust-exposed patients (p = 0.016). Reactive oxygen species (ROS) damage-related mutational signatures were almost exclusively identified in ITAC subtype samples (p = 0.00055). Tobacco smoke mutational signatures were observed in samples of patients with tobacco exposure or missing information, but not in samples from non-exposed patients. A tetraploidy copy number (CN) signature was enriched in ITAC subtype (p = 0.042). CN variation included recurrent gains in COSMIC Cancer Gene Census genes TERT, SDHA, RAC1, ETV1, PCM1, and MYC. Pathogenic variants were observed most frequently in TP53, NF1, CHD2, BRAF, APC, and LRP1B. Driver mutations and copy number gains did not segregate by subtype.ConclusionsOur analysis identified distinct mutational characteristics in ITAC and non-ITAC. Mutational signature analysis may eventually become useful for documentation of occupation-related cancer, while the exact mechanisms behind wood dust-driven carcinogenesis remain elusive. The presence of homologous recombination deficiency signatures implies a novel opportunity for treatment, but further studies are needed.

Retrospective analysis of the incidence of appendiceal neoplasm and malignancy in patients treated for suspected acute appendicitis

BackgroundNonoperative management of uncomplicated appendicitis is currently being promoted as treatment option, albeit 0.7–2.5% of appendectomies performed due to suspected acute appendicitis show histologically malignant findings. The purpose of this study was to investigate the incidence of neoplasm and malignancy of the appendix in patients presenting with suspected acute appendicitis in real world setting.MethodsThis is a retrospective single-centre investigation of 457 patients undergoing appendectomy between the years 2017–2020. The patients’ demographics, symptoms and diagnosis, intraoperative findings, and histopathological results were analysed.ResultsIn 3.7% (n = 17) histological analysis revealed neoplasms or malignancies. Median age was 48 years (20–90 years), without sex predominance. Leukocytes (11.3 ± 3.7 G/l) and C-reactive protein (54.2 ± 69.0 mg/l) were elevated. Histological analysis revealed low-grade mucinous appendiceal neoplasia (n = 3), sessile serrated adenoma of the appendix (n = 3), neuroendocrine tumours (n = 7), appendiceal adenocarcinoma of intestinal type (n = 3), and goblet cell carcinoma (n = 1). Additional treatment varied between no treatment or follow-up due to early tumour stage (n = 4), follow-up care (n = 3), additional surgical treatment (n = 8), or best supportive care (n = 2).ConclusionsPreoperative diagnosis of appendiceal tumours is difficult. Nonoperative management of patients with acute, uncomplicated appendicitis potentially prevents the correct diagnosis of malignant appendiceal pathologies. Therefore, close follow-up or surgical removal of the appendix is mandatory.

Genomic and Pathologic Profiling of Very Well-Differentiated Gastric Adenocarcinoma of Intestinal Type: A Study With Emphasis on Diffuse-Type Transformation.

Very well-differentiated adenocarcinoma of intestinal type is a distinct subtype of gastric cancer characterized by anastomosing glands with a hand-in-hand pattern and low-grade cytologic atypia resembling intestinal metaplasia. This is a slow-growing neoplasm with an indolent clinical course; however, a subset demonstrates transformation into adenocarcinoma with higher-grade histology, typically diffuse-type carcinoma, and behaves aggressively. This study aimed to better characterize the genomic and pathologic features, with a focus on factors associated with diffuse-type transformation. A total of 58 cases with (n=31) and without (n=27) diffuse-type transformation were analyzed for molecular and pathologic features. First, comprehensive deep DNA sequencing was conducted in 18 cases (discovery cohort), followed by a digital droplet polymerase chain reaction of hot spot RHOA mutations in 40 cases (validation cohort). In total, RHOA mutations were the most common alteration (34%), followed by loss of ARID1A (12%), p53 alterations (10%), and CLDN18 :: ARHGAP26/6 fusions (3.4%). FGFR2 amplification was identified in an advanced case with a p53 alteration. Altered p53 expression was recognized only in higher-grade components and was significantly associated with advanced disease ( P =0.0015) and diffuse-type transformation ( P =0.026). A mixed mucin phenotype was also strongly correlated with advanced disease ( P <0.001) and diffuse-type transformation ( P <0.001). Decreased E-cadherin expression was frequently observed (74%) in poorly cohesive components. This study demonstrated that a subset of RHOA -mutant diffuse-type gastric cancers develops through the transformation of very well-differentiated adenocarcinoma of intestinal type. Our observations suggest a mixed mucin phenotype as a risk factor and alterations in p53 and E-cadherin as drivers of diffuse-type transformation.

Assessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models

Malignant tumors derived from the epithelium lining the nasal cavity region are termed sinonasal cancers, a highly heterogeneous group of rare tumors accounting for 3 – 5 % of all head and neck cancers. Progress with next-generation molecular profiling has improved our understanding of the complexity of sinonasal cancers and resulted in the identification of an increasing number of distinct tumor entities. Despite these significant developments, the treatment of sinonasal cancers has hardly evolved since the 1980s, and an advanced sinonasal cancer presents a poor prognosis as targeted therapies are usually not available. To gain insights into potential targeted therapeutic opportunities, we performed a multiomics profiling of patient-derived functional tumor models to identify molecular characteristics associated with pharmacological responses in the different subtypes of sinonasal cancer. MethodsPatient-derived ex vivo tumor models representing four distinct sinonasal cancer subtypes: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma and SMARCB1 deficient sinonasal carcinoma were included in the analyses. Results of functional drug screens of 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses of the tumor tissues and the ex vivo cell cultures to establish associations between drug sensitivity and molecular characteristics including driver mutations. ResultsThe different sinonasal cancer subtypes display considerable differential drug sensitivity. Underlying the drug sensitivity profiles, each subtype was associated with unique molecular features. The therapeutic vulnerabilities correlating with specific genomic background were extended and validated with in silico analyses of cancer cell lines representing different human cancers and with reported case studies of sinonasal cancers treated with targeted therapies. ConclusionThe results demonstrate the importance of understanding the differential biology and the molecular features associated with the different subtypes of sinonasal cancers. Patient-derived ex vivo tumor models can be a powerful tool for investigating these rare cancers and prioritizing targeted therapeutic strategies for future clinical development and personalized medicine.

Twelve years after: The french national network on rare head and neck tumours (REFCOR)

BackgroundRare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database. MethodsProspective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions. ResultsA total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis. ConclusionMelanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.

Sinonasal Adenocarcinoma: Clinicopathological Characterization and Prognostic Factors.

Sinonasal (SN) malignancies are rare. Within SN adenocarcinomas, the most frequent are intestinal-type adenocarcinomas (ITACs). ITAC has been associated with wood and leather dust occupational exposure and TP53 mutations. Not much information is available regarding its characterization and treatment. The aim of this study is to characterize the clinicopathologic and prognostic factors of patients with sinonasal adenocarcinomas (SNACs) treated in our tertiary-level hospital. A retrospective, consecutive study including SNAC patients diagnosed between 2004-2023 was conducted. Clinicopathological data was collected, and p53 status was assessed in the tumor specimens. The association between p53 status and clinicopathological variables, as well as their impact on survival, was evaluated. In total, 35 were included, most of them having ITAC (91.4%) with papillary subtype (37.5%); the majority were subjected to occupational risk exposure (82.9%). Overexpression of p53 was identified in 48.6% of the tumors. Papillary and colonic subtypes were associated with higher median progression-free survival (mPFS) than mucinous and solid subtypes (mPFS 37 months, 95% CI, 20.0-54.0, vs. 9 months, 95% CI, 7.15-10.85, p=0.01); the former was also associated with higher median overall survival (mOS) (mOS 64 months, 95% CI, 37.18-90.81 vs. 14 months, 95% CI, 0-41.58, p=0.02). Histologic grade 1-2 and macroscopic complete resection were associated with higher PFS (PFS of five months of 90.9% vs. 33.3%, p=0.01; mPFS of 37 months, 95% CI, 4.93-69.07 vs. 10 months, 95% CI, 6.43-13.57, p=0.04, respectively). Disease recurrence with distant metastases was associated with lower OS (11 months, 95% CI, 6.1-15.9 vs. 53 months, 95% CI, 22.70-83.30, p=0.04). This study reinforces the importance of protective occupational measures. Future studies will be important to validate the best treatment strategy in the advanced stages of this disease and also to identify new prognostic and/or therapeutic target biomarkers in SNAC.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Next-generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal-type sinonasal adenocarcinoma.

Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC. Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing. Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence. We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.

Machine learning for differentiating between pancreatobiliary-type and intestinal-type periampullary carcinomas based on CT imaging and clinical findings

PurposeTo develop a diagnostic model for distinguishing pancreatobiliary-type and intestinal-type periampullary adenocarcinomas using preoperative contrast-enhanced computed tomography (CT) findings combined with clinical characteristics.MethodsThis retrospective study included 140 patients with periampullary adenocarcinoma who underwent preoperative enhanced CT, including pancreaticobiliary (N = 100) and intestinal (N = 40) types. They were randomly assigned to the training or internal validation set in an 8:2 ratio. Additionally, an independent external cohort of 28 patients was enrolled. Various CT features of the periampullary region were evaluated and data from clinical and laboratory tests were collected. Five machine learning classifiers were developed to identify the histologic type of periampullary adenocarcinoma, including logistic regression, random forest, multi-layer perceptron, light gradient boosting, and eXtreme gradient boosting (XGBoost).ResultsAll machine learning classifiers except multi-layer perceptron used achieved good performance in distinguishing pancreatobiliary-type and intestinal-type adenocarcinomas, with the area under the curve (AUC) ranging from 0.75 to 0.98. The AUC values of the XGBoost classifier in the training set, internal validation set and external validation set are 0.98, 0.89 and 0.84 respectively. The enhancement degree of tumor, the growth pattern of tumor, and carbohydrate antigen 19–9 were the most important factors in the model.ConclusionMachine learning models combining CT with clinical features can serve as a noninvasive tool to differentiate the histological subtypes of periampullary adenocarcinoma, in particular using the XGBoost classifier.

Choice of surgery in intestinal-type adenocarcinoma of the sinonasal tract: a long-term comparative study.

Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide the post-operative and survival results from a single-center long-term follow-up. We report long-term follow-up of 92 ITAC cases treated between 1998 and 2018, treated with EEA (n = 40) or EXTS (n = 52). Survival estimates, post-operative complications and duration of hospitalization were compared between surgical modalities. Baseline characteristics were similar. A higher number of T4b tumors (16%), and subsequently more tumoral invasion (39%), was present in patients undergoing EXTS compared to EEA (3% and 18%, respectively). No difference in Barnes histology subtypes was noticed. Patients undergoing EEA had a shorter post-operative hospitalization stay versus EXTS (4 versus 7days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4years; HREEA = 0.53), especially for patients with T3-4a tumors (11.4 versus 3.0years; HREEA = 0.41). Patients with T3-4 stage, tumoral invasion, positive surgical margins, mucinous or mixed histology, and prolonged post-operative hospital stay showed poor local relapse-free, disease-free, overall, and DSS. Long-term follow-up in locally advanced ITAC demonstrates that resection by EEA is correlated with improved DSS compared to EXTS, especially for T3-4 tumors. No significant differences between both treatment modalities was observed regarding per- and post-operative complications, although hospitalization in patients undergoing EEA was shorter than for patients treated with EXTS. These results confirm that EEA should remain the preferred surgical procedure in operable cases of sinonasal ITAC.

CEACAM5 and TROP2 define metaplastic and dysplastic transitions in human antral gastric precancerous lesions and tumors.

Mucosal gastric atrophy and intestinal metaplasia (IM) increase the risk for the development of gastric cancer (GC) as they represent a field for development of dysplasia and intestinal-type gastric adenocarcinoma. We have investigated the expression of two dysplasia markers, CEACAM5 and TROP2, in human antral IM and gastric tumors to assess their potential as molecular markers. In the normal antral mucosa, weak CEACAM5 and TROP2 expression was only observed in the foveolar epithelium, while inflamed antrum exhibited increased expression of both markers. Complete IM exhibited weak CEACAM5 expression at the apical surface, but no basolateral TROP2 expression. On the other hand, incomplete IM demonstrated high levels of both CEACAM5 and TROP2 expression. Notably, incomplete IM with dysplastic morphology (dysplastic incomplete IM) exhibited higher levels of CEACAM5 and TROP2 expression compared to incomplete IM without dysplastic features (simple incomplete IM). In addition, dysplastic incomplete IM showed diminished SOX2 and elevated CDX2 expression compared to simple incomplete IM. CEACAM5 and TROP2 positivity in incomplete IM was similar to that of gastric adenomas and GC. Significant association was found between CEACAM5 and TROP2 positivity and histology of GC. These findings support the concept that incomplete IM is more likely associated with GC development. Overall, our study provides evidence of the heterogeneity of gastric IM and the distinct expression profiles of CEACAM5 and TROP2 in dysplastic incomplete IM. Our findings support the potential use of CEACAM5 and TROP2 as molecular markers for identifying individuals with a higher risk of GC development in the context of incomplete IM.