Underwater EMR versus conventional EMR for superficial non-ampullary duodenal epithelial tumors in the Western setting.

BACKGROUND AND AIMS: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial non-ampullary duodenal epithelial tumors (SNADETs) but recently underwater EMR (U-EMR) emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR versus C-EMR for SNADETs in a Western setting. METHODS: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of EMR and the occurrence of AEs or RRA using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤ or >20 mm. RESULTS: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR n=201, 69.3%; U-EMR n=89, 30.7%). Overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (OR 4.95; 95%CI=2.87-8.53), post-procedural bleeding (OR=7.92; 95%CI=3.95-15.89) and RRA (OR=3.66; 95%CI=2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions. CONCLUSION: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRA, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs.

Higher frequency of gastric neoplasia in advanced chronic liver disease patients: Impact of screening endoscopy in an intermediate-high risk country.

BACKGROUND: The Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. METHODS: Retrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). RESULTS: We evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. CONCLUSION: We found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.

Fibrosis-related transcriptome unveils a distinctive remodeling matrix pattern in penetrating ileal Crohn's disease.

BACKGROUND AND AIMS: Stricturing (B2) and penetrating (B3) ileal Crohn's disease have been reported to present similar levels of histopathological transmural fibrosis. This study aimed to compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal Crohn's disease. METHODS: Using Nanostring technology and comparative bioinformatics, we analyzed the expression of 787 fibrosis-related genes in 36 ileal surgical specimens, 12 B2 and 24 B3, the latter including 12 cases with associated stricture(s) (B3s) and 12 without (B3o). Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis for the distribution analysis. For the selection of the differentially expressed genes a p-adjusted <0.05 and Fold Change ≤-1.5 or ≥ 1.5 was adopted. qPCR and immunohistochemistry analyses were used to validate selected differentially expressed genes. RESULTS: We included 34 patients with B2 and B3 phenotypes, balanced for age at diagnosis, age at surgery, gender, Crohn's disease localization, perianal disease and therapy. Inflammation and fibrosis histopathological scoring were similar in all cases. B2 and B3 groups showed a very good clustering regarding 30 significantly differentially expressed genes, all being remarkably upregulated in B3. More than half of these genes were involved in Crohn's disease fibrogenesis, while eight differentially expressed genes were so in other organs. The most significantly active biologic processes and pathways in penetrating disease were response to TGFßand matrix organization and degradation, as validated by immunohistochemistry. CONCLUSIONS: Despite the histopathological similarities in fibrosis between stricturing and penetrating ileal Crohn's disease, their fibrosis-related transcriptomic profiles are distinct. Penetrating disease exhibits a distinctive transcriptomic landscape related to enhanced matrix remodeling.

HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches.

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

Morphologic heterogeneity of carcinoma with signet ring cell features at different primary sites.

INTRODUCTION: Signet-ring-cells (SRC) may be observed in carcinomas from multiple primary sites. Elucidating unknown primaries from metastases with SRCs represents a diagnostic challenge. This study examined morphologic characteristics of adenocarcinomas with SRCs from stablished primary sites and described objective features which can aid in identifying the site of origin. METHODS: the series encompasses 257 cases of adenocarcinomas with SRCs from gastroesophageal junction (GEJ, n=38), stomach (n=48), pancreatobiliary system (n=16), colorectum (n=40), appendix (n=32), breast (n=41), and lung (n=42). H&E sections were examined and scored using architectural and cytologic criteria. Morphometric analysis was performed using QuPath software. RESULTS: extracellular mucin was more abundant in GEJ, colorectal, and appendiceal carcinomas. Poorly cohesive morphology was the most frequent pattern in gastric and breast carcinomas. The cytoplasmic mucin/vacuole was predominantly clear and targetoid in breast carcinomas. Breast and gastric carcinomas showed the highest nuclear to cytoplasmic (N/C) ratio, whereas appendiceal carcinoma the lowest. CONCLUSION: morphological evaluation (extracellular mucin, architectural patterns and the nature of cytoplasmic mucin/vacuole) represent an important step to determine the cancer site of origin in adenocarcinomas with SRCs and guide further ancillary studies. Cytological morphometry may help further refine morphological criteria and facilitate the construction of digital-pathology algorithms.

Gastric polyps in Familial Adenomatous Polyposis Portuguese patients: the first Western cohort with Asian features.

INTRODUCTION: Chronic atrophic gastritis may contribute to gastric polyps (GP) phenotype in familial adenomatous polyposis (FAP). Considering the high prevalence of Helicobacter-pylori (HP) infection in Portugal, we aim to characterise GP in a series of Portuguese patients. METHODS: In a retrospectively-selected series of 53 FAP patients, clinical data and histopathological features of GP and background gastric mucosa were studied. SPSS (27.0) was used for statistical analysis. RESULTS: Thirteen patients (24.5%) developed fundic gland polyps (FGP), seven (13.2%) gastric adenomas (GA) and ten (18.9%) both FGP and GA. Out of 100 GP, four were hyperplastic polyps, 58 FGP (24 with dysplasia), 35 intestinal-type GA (intGA) and three foveolar-type GA (fovGA). IntGA were larger (60% >7mm, p=0.03), occurred predominantly in the distal stomach (66.7%, p=0.024), in patients harbouring gastric intestinal metaplasia (IM) (86.7%, p<0.001) and duodenal adenomas (86.7%, p<0.001) Conclusion: This is the first Western series showing high prevalence of intGA in FAP patients, comparable to Asian cohorts. HP infection and chronic atrophic gastritis/intestinal metaplasia are likely responsible for this difference, with risk of neoplastic transformation and management implications. Biopsy/excision of GP >7mm, in the distal stomach, and in patients harbouring gastric intestinal metaplasia/duodenal adenomas should be considered.

Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

3D Chromatin Architecture Re-Wiring at the CDH3/CDH1 Loci Contributes to E-Cadherin to P-Cadherin Expression Switch in Gastric Cancer.

Cadherins are cell-cell adhesion molecules, fundamental for cell architecture and polarity. E-cadherin to P-cadherin switch can rescue adherens junctions in epithelial tumours. Herein, we disclose a mechanism for E-cadherin to P-cadherin switch in gastric cancers. CDH1 and CDH3 mRNA expression was obtained from 42 gastric tumours' RNA-seq data. CRISPR-Cas9 was used to knock out CDH1 and a putative regulatory element. CDH1-depleted and parental cells were submitted to proteomics and enrichment GO terms analysis; ATAC-seq/4C-seq with a CDH1 promoter viewpoint to assess chromatin accessibility and conformation; and RT-PCR/flow cytometry to assess CDH1/E-cadherin and CDH3/P-cadherin expression. In 42% of gastric tumours analysed, CDH1 to CDH3 switch was observed. CDH1 knockout triggered CDH1/E-cadherin complete loss and CDH3/P-cadherin expression increase at plasma membrane. This switch, likely rescuing adherens junctions, increased cell migration/proliferation, commonly observed in aggressive tumours. E- to P-cadherin switch accompanied increased CDH1 promoter interactions with CDH3-eQTL, absent in normal stomach and parental cells. CDH3-eQTL deletion promotes CDH3/CDH1 reduced expression. These data provide evidence that loss of CDH1/E-cadherin expression alters the CDH3 locus chromatin conformation, allowing a CDH1 promoter interaction with a CDH3-eQTL, and promoting CDH3/P-cadherin expression. These data highlight a novel mechanism triggering E- to P-cadherin switch in gastric cancer.

Role of Endoscopic Biopsies and Morphologic Features in Predicting Microsatellite Instability Status in Gastric Cancer: A Multicenter Comparative Study of Endoscopic Biopsies and Surgical Specimens.

Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components ( P =0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation ( P <0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases ( P =0.002 and 0.045).

DOES NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL AND GASTROESOPHAGEAL JUNCTION CANCER PATIENTS AFFECT POSTOPERATIVE OUTCOMES? A STUDY USING THE BECKER TUMOR REGRESSION GRADE SYSTEM AND LYMPH NODE REGRESSION.

BACKGROUND: The effect of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal cancer can be determined by assessing the Becker tumor regression grade in the primary tumor, as well as in lymph nodes. AIMS: The aim of this study was to investigate the anatomopathological changes caused by neoadjuvant chemoradiotherapy and their impact on clinical parameters. Specifically, we analyzed the Becker tumor regression grade, lymph node status, and regression changes and evaluated their association with the Clavien-Dindo classification of surgical complications and overall patient survival. METHODS: This is a retrospective and observational study including 139 patients diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus and treated with either neoadjuvant chemoradiotherapy followed by surgery or surgery alone. For the 94 patients who underwent neoadjuvant chemoradiotherapy, we evaluated tumor regression by Becker tumor regression grade in primary tumors. We also analyzed lymph node status and regression changes on lymph nodes with or without metastases. Overall survival analysis was performed using Kaplan-Meier curves. RESULTS: Becker tumor regression grade is associated with lower lymphatic permeation (p<0.01) and vascular invasion (p<0.001), but not with lymph node regression rate (p=0.10). Clavien-Dindo classification was associated neither with lymph node regression rate (odds ratio=0.784, p=0.795) nor with tumor regression grade (p=0.68). Patients who presented with lymphatic permeation and vascular invasion had statistically significantly lower median survival (17 vs. 30 months, p=0.006 for lymphatic permeation, and 14 vs. 29 months, p=0.024 for vascular invasion). CONCLUSION: In our series, we were unable to demonstrate an association between Becker tumor regression grade and lymph node regression rate with any postoperative complications. Patients with lower lymphatic permeation and vascular invasion have higher overall survival, correlating with a better response in the Becker tumor regression grade system.

Primary small bowel follicular lymphoma: the role of balloon-assisted enteroscopy in diagnosis and follow-up.

An asymptomatic 38-year-old male with no significant previous medical history performed routine laboratory studies that revealed iron-deficiency anemia. Esophagogastroduodenoscopy and colonoscopy were unremarkable and he undergone videocapsule endoscopy that revealed multiple small polyps along jejunum and ileum. Double-balloon enteroscopy confirmed the presence of scattered small whitish nodules and small polyps carpeting segments of jejunal mucosal and sometimes forming conglomerates with a nodular appearance. Histopathological examination showed lamina propria expansion by neoplastic follicles, predominantly composed by small lymphoid cells that, by immunohistochemistry, showed expression of CD20, CD10 and bcl-2. Computed tomography scan of abdomen and pelvis did not reveal systemic involvement, consistent with primary small bowel follicular lymphoma. Chemotherapy was started and, at reevaluation enteroscopy, although nodular jejunal segments persisted, biopsies did not show involvement by lymphoproliferative disease, which was interpreted as complete remission. Periodic clinical and biochemical evaluation and annual enteroscopic surveillance was maintained and, after three years, local recurrence of low-grade follicular lymphoma was detected. As previously, there was no evidence of systemic involvement and the decision was to maintain close surveillance. After one year, the patient remains asymptomatic and without evidence of disease progression. This case illustrates the essential role of balloon-assisted enteroscopy for diagnosis and surveillance of primary small bowel follicular lymphoma.

Acute gastrointestinal graft-versus-host disease with cytomegalovirus and Epstein-Barr virus superinfection in a patient with COVID-19.

A 60-year-old female was diagnosed with acute myeloid leukemia. After initial remission with chemotherapy, she relapsed and underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two months later, she presented to emergency department with watery diarrhea, abdominal pain and fever. She also tested positive for SARS-CoV2 on nasopharyngeal swab by polymerase chain reaction (PCR) and both cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were detected in peripheral blood. Flexible sigmoidoscopy showed diffuse edema, erythema and loss of vascular pattern with interspersed segments of mucosal denudation and exudate and bBiopsies revealed epithelial cell apoptosis, diffuse crypt atrophy and dropout, with ulceration and both CMV and EBV were detected in colon mucosa, consistent with acute severe gastrointestinal graft-versus-host disease complicated by CMV and EBV superinfection. Despite starting therapy with methylprednisolone, ganciclovir and rituximab,she presented unfavorable evolution and died after 5 weeks.

A practical approach for PD-L1 evaluation in gastroesophageal cancer.

PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint inhibitors. At present, PD-L1 is routinely assessed on biopsy samples of advanced gastroesophageal cancer patients before initiating first-line treatment. However, PD-L1 is still a suboptimal biomarker, due to changing cut-off values and scoring systems, interobserver and interlaboratory variability.This practical illustrated review discusses the range of staining patterns of PD-L1 and the potential pitfalls and challenges that can be encountered when evaluating PD-L1, focusing on gastric and gastroesophageal adenocarcinoma (G/GEA) and esophageal squamous cell carcinoma (ESCC).

Does neoadjuvant chemoradiotherapy for esophageal and gastroesophageal junction cancer patients affect postoperative outcomes? a study using the becker tumor regression grade system and lymph node regression / A radioterapia e quimioterapia neoadjuvantes para pacientes com câncer de esôfago e junção gastro-esofágica afetam os resultados pós-operatórios? um estudo usando o sistema de regressão tumoral de becker e regressão de linfonodos

ABSTRACT BACKGROUND: The effect of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal cancer can be determined by assessing the Becker tumor regression grade in the primary tumor, as well as in lymph nodes. AIMS: The aim of this study was to investigate the anatomopathological changes caused by neoadjuvant chemoradiotherapy and their impact on clinical parameters. Specifically, we analyzed the Becker tumor regression grade, lymph node status, and regression changes and evaluated their association with the Clavien-Dindo classification of surgical complications and overall patient survival. METHODS: This is a retrospective and observational study including 139 patients diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus and treated with either neoadjuvant chemoradiotherapy followed by surgery or surgery alone. For the 94 patients who underwent neoadjuvant chemoradiotherapy, we evaluated tumor regression by Becker tumor regression grade in primary tumors. We also analyzed lymph node status and regression changes on lymph nodes with or without metastases. Overall survival analysis was performed using Kaplan-Meier curves. RESULTS: Becker tumor regression grade is associated with lower lymphatic permeation (p<0.01) and vascular invasion (p<0.001), but not with lymph node regression rate (p=0.10). Clavien-Dindo classification was associated neither with lymph node regression rate (odds ratio=0.784, p=0.795) nor with tumor regression grade (p=0.68). Patients who presented with lymphatic permeation and vascular invasion had statistically significantly lower median survival (17 vs. 30 months, p=0.006 for lymphatic permeation, and 14 vs. 29 months, p=0.024 for vascular invasion). CONCLUSION: In our series, we were unable to demonstrate an association between Becker tumor regression grade and lymph node regression rate with any postoperative complications. Patients with lower lymphatic permeation and vascular invasion have higher overall survival, correlating with a better response in the Becker tumor regression grade system.

RESUMO RACIONAL: O efeito da quimioradioterapia neoadjuvante em pacientes com câncer de esôfago localmente avançado pode ser determinado pela avaliação do grau de regressão tumoral de Becker no tumor primário, bem como nos linfonodos. OBJETIVOS: Investigar as alterações anatomopatológicas causadas pela quimioradioterapia neoadjuvante e seu impacto nos parâmetros clínicos. Especificamente, analisamos o grau de regressão tumoral de Becker, o status linfonodal e as alterações de regressão e avaliamos sua associação com a Classificação Clavien-Dindo de complicações cirúrgicas e a sobrevida geral dos pacientes. MÉTODOS: Estudo retrospectivo e observacional incluindo 139 pacientes diagnosticados com carcinoma espinocelular de esôfago ou adenocarcinoma da junção esofagogástrica, tratados com quimioradioterapia neoadjuvante seguido de cirurgia ou cirurgia isolada. Para os 94 pacientes submetidos a quimioradioterapia neoadjuvante, avaliamos a grau de regressão tumoral de Becker em tumores primários. Também analisamos o status linfonodal e as alterações de regressão em linfonodos com ou sem metástases. A análise de sobrevida global foi realizada usando curvas de Kaplan-Meier. RESULTADOS: O grau de regressão tumoral de Becker está associado a menor permeação linfática (p<0,01) e invasão vascular (p<0,001), mas não à taxa de regressão linfonodal (p=0,10). A classificação de Clavien-Dindo não foi associada à taxa de regressão linfonodal (OR=0,784; p=0,795) nem ao grau de grau de regressão tumoral (p=0,68). Os pacientes que apresentavam permeação linfática e invasão vascular tiveram sobrevida mediana menor estatisticamente significativa (17 vs 30 meses; p=0,006 para a permeação linfátiva e 14 vs 29 meses; p=0,024, para a invasão vascular, respectivamente). CONCLUSÕES: Em nossa série não conseguimos demonstrar associação entre grau de regressão tumoral de Becker e taxa de regressão linfonodal com quaisquer complicações pós-operatórias. Pacientes com menor permeação linfática e invasão vascular apresentam maior sobrevida global, correlacionando-se com uma melhor resposta no sistema Becker.

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application.

Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical benefit in many solid cancer types, including gastrointestinal malignancies. However, it has been estimated that only 20-40% of patients respond to treatment. The pattern of expression and potential predictive value of PD-L1 as an immunohistochemical biomarker has been extensively studied in gastrointestinal neoplasms. Until now, its predictive value has been demonstrated, and is currently in use only in upper gastrointestinal malignancies (gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma).In this Review, we describe the technical aspects and challenges related to PD-L1 immunohistochemical assays, the current role of PD-L1 as a biomarker in clinical practice and we outline the main studies and clinical trials analyzing the prognostic and predictive value of PD-L1 in gastrointestinal cancers.

Activation of Laminin γ2 by Helicobacter pylori Promotes Invasion and Survival of Gastric Cancer Cells With E-Cadherin Defects.

BACKGROUND: Helicobacter pylori infection induces cellular phenotypes relevant for cancer progression, namely cell motility and invasion. We hypothesized that the extracellular matrix (ECM) could be involved in these deleterious effects. METHODS: Microarrays were used to uncover ECM interactors in cells infected with H. pylori. LAMC2, encoding laminin γ2, was selected as a candidate gene and its expression was assessed in vitro and in vivo. The role of LAMC2 was investigated by small interference RNA (siRNA) combined with a set of functional assays. Laminin γ2 and E-cadherin expression patterns were evaluated in gastric cancer cases. RESULTS: Laminin γ2 was found significantly overexpressed in gastric cancer cells infected with H. pylori. This finding was validated in vitro by infection with clinical isolates and in vivo by using gastric biopsies of infected and noninfected individuals. We showed that laminin γ2 overexpression is dependent on the bacterial type IV secretion system and on the CagA. Functionally, laminin γ2 promotes cell invasion and resistance to apoptosis, through modulation of Src, JNK, and AKT activity. These effects were abrogated in cells with functional E-cadherin. CONCLUSIONS: These data highlight laminin γ2 and its downstream effectors as potential therapeutic targets, and the value of H. pylori eradication to delay gastric cancer onset and progression.