The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Application of a pattern-based approach to histological diagnosis in very early onset IBD (VEO-IBD) in a multicentric cohort of children with emphasis on monogenic disease with IBD-like morphology.

AIMS: Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before the age of 6 years, encompassing both 'pure' IBD, such as ulcerative colitis (UC) and Crohn's disease (CD) and monogenic diseases (MDs), the latter often involving genes associated with primary immunodeficiencies. Moreover, histological features in gastrointestinal (GI) biopsies in MD can also have IBD-like morphology, making differential diagnosis difficult. Correct diagnosis is fundamental, as MDs show a more severe clinical course and their inadequate/untimely recognition leads to inappropriate therapy. METHODS AND RESULTS: Biopsy samples from the lower and upper GI tract of 93 clinically diagnosed VEO-IBD children were retrospectively selected in a multicentre cohort and histologically re-evaluated by 10 pathologists blinded to clinical information. Each case was classified according to morphological patterns, including UC-like; CD-like; enterocolitis-like; apoptotic; eosinophil-rich; and IBD-unclassified (IBD-U). Nine (69%) MD children showed IBD-like morphology; only the IBD-U pattern correlated with MD diagnosis (P = 0.02) (available in 64 cases: 51 non-MD, true early-onset IBD/other; 13 MD cases). MD patients showed earlier GI symptom onset (18.7 versus 26.9 months) and were sent to endoscopy earlier (22 versus 37 months), these differences were statistically significant (P < 0.05). Upper GI histology was informative in 37 biopsies. CONCLUSIONS: The diagnosis of the underlying cause of VEO-IBD requires a multidisciplinary setting, and pathology, while being one of the fundamental puzzle pieces, is often difficult to interpret. A pattern-based histological approach is therefore suggested, thus aiding the pathologist in VEO-IBD reporting and multidisciplinary discussion.

Diagnostic yield of endoscopic and EUS-guided biopsy techniques in subepithelial lesions of the upper GI tract: a systematic review.

BACKGROUND AND AIMS: Obtaining adequate tissue samples in subepithelial lesions (SELs) remains challenging. Several biopsy techniques are available, but a systematic review including all available techniques to obtain a histologic diagnosis of SEL is lacking. The aim of this study was to evaluate the diagnostic yield and adverse event rates of endoscopic biopsies, EUS-guided FNA (EUS-FNA), EUS-guided fine-needle biopsy (FNB) (EUS-FNB), and mucosal incision-assisted biopsy (MIAB) for SELs in the upper GI tract. METHODS: A search strategy in multiple databases was performed. The primary outcome was diagnostic yield, defined as the percentage of procedures in which histology was obtained and resulted in a definitive histopathologic diagnosis. Secondary outcome measures included reported procedure-related adverse events, which were graded according to the AGREE (Adverse Events in Gastrointestinal Endoscopy) classification. RESULTS: A total of 94 original articles were included. Studies were classified per endoscopic technique to obtain histopathology. This resulted in 8 included studies for endoscopic biopsy methods, 55 studies for EUS-FNA, 33 studies for EUS-FNB, and 26 studies for MIAB. Pooled rates for diagnostic yield were 40.6% (95% confidence interval [CI], 30.8-51.2) for endoscopic biopsy, 74.6% (95% CI, 69.9-78.7) for EUS-FNA, 84.2% (95% CI, 80.7-87.2) for EUS-FNB, and 88.2% (95% CI, 84.7-91.1) for MIAB. Reported procedure-related adverse events graded AGREE II or higher were 2.8% to 3.9% for endoscopic biopsies, 1.0% to 4.5% for EUS-FNA, .9% to 7.7% for EUS-FNB, and 1.9% to 7.9% for MIAB. CONCLUSIONS: Based on the available evidence, MIAB and EUS-FNB seem to be most effective in terms of achieving a high diagnostic yield, with similar rates of adverse events.

Comparative diagnostic yield of different endoscopic techniques for tissue sampling of upper gastrointestinal subepithelial lesions: a network meta-analysis.

BACKGROUND: There is limited evidence on the comparative diagnostic performance of endoscopic tissue sampling techniques for subepithelial lesions. We performed a systematic review with network meta-analysis to compare these techniques. METHODS: A systematic literature review was conducted for randomized controlled trials (RCTs) comparing the sample adequacy and diagnostic accuracy of bite-on-bite biopsy, mucosal incision-assisted biopsy (MIAB), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and EUS-guided fine-needle biopsy (FNB). Results were expressed as relative risk (RR) and 95%CI. RESULTS: Eight RCTs were identified. EUS-FNB was significantly superior to EUS-FNA in terms of sample adequacy (RR 1.20 [95%CI 1.05-1.45]), whereas none of the other techniques significantly outperformed EUS-FNA. Additionally, bite-on-bite biopsy was significantly inferior to EUS-FNB (RR 0.55 [95%CI 0.33-0.98]). Overall, EUS-FNB appeared to be the best technique (surface under cumulative ranking [SUCRA] score 0.90) followed by MIAB (SUCRA 0.83), whereas bite-on-bite biopsy showed the poorest performance. When considering lesions <20 mm, MIAB, but not EUS-FNB, showed significantly higher accuracy rates compared with EUS-FNA (RR 1.68 [95%CI 1.02-2.88]). Overall, MIAB ranked as the best intervention for lesions <20 mm (SUCRA score 0.86 for adequacy and 0.91 for accuracy), with EUS-FNB only slightly superior to EUS-FNA. When rapid on-site cytological evaluation (ROSE) was available, no difference between EUS-FNB, EUS-FNA, and MIAB was observed. CONCLUSION: EUS-FNB and MIAB appeared to provide better performance, whereas bite-on-bite sampling was significantly inferior to the other techniques. MIAB seemed to be the best option for smaller lesions, whereas EUS-FNA remained competitive when ROSE was available.

Global epidemiology of early-onset upper gastrointestinal cancer: trend from the Global Burden of Disease Study 2019.

BACKGROUND AND AIM: In recent years, there has been a growing incidence of gastrointestinal cancer in young individuals. Despite its significant morbidity and mortality, research on upper gastrointestinal (UGI) cancer in young populations has been relatively limited. Therefore, studies on the epidemiological changes of this cancer are needed. METHODS: Using data from the Global Burden of Disease Study 2019, we examined the incidence, death, and disability-adjusted life years (DALYs) from UGI cancers in the young, namely, early-onset esophageal cancer (EOEC) and early-onset gastric cancer (EOGC). These results were stratified by sex, geographical region, country, and sociodemographic index. RESULTS: There was a total of 185 140 cases, 120 289 deaths, and 5.70 million DALYs attributable to early-onset UGI cancers globally. From 2010 to 2019, the global incidence, death, and DALYs rates of early-onset UGI cancers decreased. In contrast, the incidence rates increased in both EOEC (+1.15%) and EOGC (+0.21%) in the Eastern Mediterranean region. CONCLUSIONS: Over the past decade, the burden of UGI cancer in the young has decreased. However, it has increased in the Eastern Mediterranean region. Further research to elucidate the attributable risk factors in this population is warranted.

Upper Gastrointestinal Involvement in Crohn's Disease as an Independent Predictor of New-Onset Strictures: Insights from an Extensive Retrospective Cohort Analysis.

BACKGROUND/AIMS: Crohn's Disease (CD) can affect the entire gastrointestinal tract, including the upper sections (UGI), which is often overlooked, especially in Asian populations. There's a notable gap in research regarding the impact of UGI involvement on the intricate landscape of ensuing complications. This study aims to address this gap. METHODS: Conducting a retrospective study at Chang Gung Memorial Hospital from January 2001 to September 2023, we compared CD patients with UGI (Montreal L4) involvement against non-L4 counterparts, focusing on baseline characteristics, post-diagnosis complications, and overall outcomes. Routine UGI endoscopy was performed around the time of diagnosis in all patients followed in our inflammatory bowel disease (IBD) center, and all CD patients with adequate follow-up were included in this study. RESULTS: The study included 212 CD patients, 111 in the L4 group and 101 in the non-L4 group, with an average follow-up of 40.8 ± 15.1 months. At baseline, individuals in the L4 category demonstrated elevated smoking rates, increased Crohn's Disease Activity Index scores, a higher prevalence of strictures, and a more prevalent usage of biologics and proton pump inhibitors. Moreover, this group was characterized by reduced albumin levels. Upon concluding the follow-up, those with L4 involvement continued to show escalated CDAI scores and hospitalization frequencies, alongside heightened C-reactive protein levels and diminished albumin concentrations. Additionally, the occurrence of UGI involvement, stricturing disease at the time of diagnosis, and a younger age at the onset of CD were pinpointed as independent predictors for the development of new-onset strictures. CONCLUSIONS: CD patients with UGI involvement exhibit elevated disease activity and serve as independent predictors for the development of intestinal strictures. Thorough UGI evaluations at the time of diagnosis, coupled with assertive treatment strategies, are essential for managing these patients effectively.

Monocyte recruitment in venous pulmonary embolism at time of cancer diagnosis in upper gastrointestinal cancer patients.

Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system.

Efficacy and safety of endoscopic subserosal dissection treatment for gastrointetinal submucosal tumors in the upper gastrointestinal tract.

OBJECTIVE: To investigate the safety and efficacy of endoscopic subserosal dissection for patients with submucosal tumors in the upper gastrointestinal tract. METHODS: This retrospective single-center study included 16 patients who underwent ESSD. All patients were enrolled from July 2018 to Dec 2021. Parameters such as demographics, size, resection margin, complications, pathological features, procedure time and follow-up were investigated and analyzed. RESULTS: Our study achieved 100% en bloc resection and 100% R0 resection. The most common location was the corpus with a mean tumor size of 2.78 ± 1.56 cm. The mean age, procedure time, were 53.4 ± 10.3 years, 85.31 ± 46.64 min respectively. Acocording to National Institutes of Health classification, 7 (13, 53.85%), 5 (13, 38.46%) ,and 1 (13, 7.69%) objects belonged to the very low, low, and intermediate classification, respectively. Immunohistochemistry results showed a 100% positive rate of CD34, DOG-1, CD117, and Ki67. A mean follow-up of 9.3 ± 2.5 months showed no recurrence or metastasis. CONCLUSIONS: ESSD is effective and safe surgical procedure for curative removal of gastrointestinal submucosal tumors in the upper gastrointestinal tract, and it can be preferred for patients with no metastasis.

Artificial Intelligence and Deep Learning for Upper Gastrointestinal Neoplasia.

Upper gastrointestinal (GI) neoplasia account for 35% of GI cancers and 1.5 million cancer-related deaths every year. Despite its efficacy in preventing cancer mortality, diagnostic upper GI endoscopy is affected by a substantial miss rate of neoplastic lesions due to failure to recognize a visible lesion or imperfect navigation. This may be offset by the real-time application of artificial intelligence (AI) for detection (computer-aided detection [CADe]) and characterization (computer-aided diagnosis [CADx]) of upper GI neoplasia. Stand-alone performance of CADe for esophageal squamous cell neoplasia, Barrett's esophagus-related neoplasia, and gastric cancer showed promising accuracy, sensitivity ranging between 83% and 93%. However, incorporation of CADe/CADx in clinical practice depends on several factors, such as possible bias in the training or validation phases of these algorithms, its interaction with human endoscopists, and clinical implications of false-positive results. The aim of this review is to guide the clinician across the multiple steps of AI development in clinical practice.

Endoscopic screening of the upper gastrointestinal tract for second primary tumors in patients with head and neck cancer in a Western country.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival. METHODS: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma. RESULTS: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening. CONCLUSION: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities.

Iron pill-induced gastritis: an unrecognized side effect of iron-deficiency anemia.

Iron-deficiency anemia is a prevalent condition usually treated with iron supplementation. Iron pill-induced gastritis is an under-recognized, albeit serious potential complication of iron pill ingestion in the upper gastrointestinal tract. This entity must be identified by healthcare providers who prescribe iron. The diagnosis of this unusual drug-induced disease is based on endoscopic findings and histopathological examination, because the clinical symptoms are vague and non-specific. Herein we report a case of a 79-year-old woman with iron-deficiency anemia taking oral ferrous sulfate with multiple congestive and eroded polypoid lesions. Histology showed an H. pylori-negative erosive gastritis with iron deposition, confirming the diagnosis of iron pill-induced gastritis. The aim of this report is to highlight that iron pill-induced gastritis is an under-diagnosed entity that must be kept in mind when patients undergo chronic iron-pill therapy because it can lead to serious complications of the upper gastrointestinal tract.

Frequency and clinical significance of histologic upper gastrointestinal tract findings in children with inflammatory bowel disease.

OBJECTIVE: Assessment of the upper gastrointestinal tract (UGI) may enable more personalized treatment strategies in pediatric inflammatory bowel disease (IBD). However, data on the frequency and significance of these findings remain limited. METHODS: Data on 132 pediatric IBD patients with systematic UGI sampling were collected and the baseline characteristics and presence of complications compared between those with and without histological UGI findings. The control group comprised 162 children who received no diagnoses. RESULTS: Seventy-six children had ulcerative colitis (UC), 47 Crohn's disease (CD) and nine IBD unclassified. UGI findings were more common in IBD patients than controls (69.7% vs. 30.9%, respectively, p < .001), particularly in the stomach (62.1% vs. 16.8%; p < .001). Among IBD patients, findings were more common in CD than in UC (80.9% vs. 63.2%; p = .038), particularly in the duodenum (21.3% vs. 2.6%, p = .001). Four patients had UGI granulomas consistent with CD. Hypoalbuminemia (OR 3.22; 95% CI 1.18-8.79) and failure to thrive (2.82; 1.17-6.78) increased the likelihood of UGI findings in IBD. In CD, perianal morbidity was less common in those with than in those without UGI findings (13.2% vs. 44.4%; p = .032) whereas in UC, UGI findings increased the risk for co-morbidities (18.8% vs. 3.6%; p = .059). The long-term outcomes did not differ between patients with or without UGI findings. CONCLUSIONS: Histologic UGI findings were more common in children with IBD than in children with no gastrointestinal diagnoses. In CD, UGI findings were more frequent than in UC, especially in the duodenum. In UC, UGI findings were associated with more complex disease.

Infectious diseases of the upper gastrointestinal tract.

A broad spectrum of pathogens produce gastrointestinal disease. The ongoing spread of human immunodeficiency virus/acquired immune deficiency syndrome, the increased use of immunosuppressive therapy and the persistence of overcrowding and suboptimal sanitation in underdeveloped areas facilitate both disease transmission from environmental and foodborne sources and person-to-person transmission. Clinicians increasingly rely on endoscopic biopsy sample interpretation to diagnose gastrointestinal infections. Thus, pathologists must be aware of diagnostic features of a variety of microbial pathogens. Detection with molecular techniques also allows for correlation between infectious agents and their histopathological features, which has expanded our knowledge of the inflammatory changes produced by infectious agents. This review covers infectious disorders of the upper gastrointestinal tract encountered in surgical pathology. Clinical, endoscopic and pathological features are presented. The review emphasises morphological features of viruses, bacteria, fungi and parasites that may be found in tissue samples, and the inflammatory patterns that they produce. Differential diagnoses and useful ancillary techniques are discussed.

Recent advances upper gastrointestinal lymphomas: molecular updates and diagnostic implications.

Approximately one-third of extranodal non-Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T-cell neoplasms and the recommended diagnostic approach to aggressive B-cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases.

Characteristics and Prognostic Factors of Metachronous Second Primary Upper Gastrointestinal Cancer.

BACKGROUND: Patients with metachronous malignancies before carcinomas of the upper gastrointestinal tract were analyzed regarding clinical parameters, oncological outcome, and prognosis. METHODS: We analyzed the data of 1583 patients with gastroesophageal cancer who underwent oncological resections between 2002 and 2018. Of 1583 patients, 172 had a malignant tumor before the upper gastrointestinal cancer (second primary carcinomas) and 1411 without preceding malignancies served as the control group. The analyses were performed between both groups and within the subgroup of second primary carcinomas. RESULTS: Patients with second primary carcinomas were older (P < 0.0001), had more comorbidities (P < 0.0001), and underwent longer surgical resections (P = 0.0024). They had lower (y)pT-categories (P = 0.0427) and had longer stays in intensive care unit (P = 0.0002) and hospital (P = 0.0018). R0-resection was more frequent (P = 0.0275) while having more surgical complications (P = 0.0378). The median survival was 39.5 mo (primary carcinoma) versus 32.9 mo for (second primary carcinoma) and was not significantly different (P = 0.5359).In the subgroup analysis of second primaries, there were no significant survival differences depending on primary tumor entity (P = 0.4989). pT status (P = 0.0062), pN status (P < 0.0001), pM status (P < 0.0001), and R-status (P < 0.0001) were significant prognostic factors. A time period >9 y after the primary cancer could be identified as a novel and beneficial survival factor (P = 0.0496). Most patients with primary colorectal, prostate, hematogenous, or breast cancer had adenocarcinoma, whereas patients with initial otolaryngologic cancers mainly had squamous cell carcinoma. CONCLUSIONS: Second primary carcinomas of the upper gastrointestinal tract show distinct clinical and oncological characteristics. Common prognostic factors are applicable, and oncologic resection is recommended.

Aerodigestive adverse effects during intravenous pentamidine infusion for Pneumocystis jirovecii pneumonia prophylaxis.

Aerodigestive adverse effects (AD-AE) during intravenous pentamidine (IV-P) infusion for Pneumocystis jiroveci pneumonia prophylaxis are uncommon in retrospective chart review studies. We conducted a survey in patients on IV-P, which included 31 specific questions. Twenty-five patients were included in the analysis; AD-AE were observed in 22 (88%) with recurrence of symptoms in 88% participants with subsequent infusions. Five leading symptoms were congestion (48%), lip tingling (32%), nausea (28%), tongue tingling (24%), vomiting, and throat swelling (17%); multiple symptoms were reported in 72% of the patients. In conclusion, AD-AE of IV-P infusion are common, self-limited, and tend to be recurrent.

A conditional mouse expressing an activating mutation in NRF2 displays hyperplasia of the upper gastrointestinal tract and decreased white adipose tissue.

Activation of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) transcription factor is a critical and evolutionarily conserved cellular response to oxidative stress, metabolic stress, and xenobiotic insult. Deficiency of NRF2 results in hypersensitivity to a variety of stressors, whereas its aberrant activation contributes to several cancer types, most commonly squamous cell carcinomas of the esophagus, oral cavity, bladder, and lung. Between 10% and 35% of patients with squamous cell carcinomas display hyperactive NRF2 signaling, harboring activating mutations and copy number amplifications of the NFE2L2 oncogene or inactivating mutations or deletions of KEAP1 or CUL3, the proteins of which co-complex to ubiquitylate and degrade NRF2 protein. To better understand the role of NRF2 in tumorigenesis and more broadly in development, we engineered the endogenous Nfe2l2 genomic locus to create a conditional mutant LSL-Nrf2E79Q mouse model. The E79Q mutation, one of the most commonly observed NRF2-activating mutations in human squamous cancers, codes for a mutant protein that does not undergo KEAP1/CUL3-dependent degradation, resulting in its constitutive activity. Expression of NRF2 E79Q protein in keratin 14 (KRT14)-positive murine tissues resulted in hyperplasia of squamous cell tissues of the tongue, forestomach, and esophagus, a stunted body axis, decreased weight, and decreased visceral adipose depots. RNA-seq profiling and follow-up validation studies of cultured NRF2E79Q murine esophageal epithelial cells revealed known and novel NRF2-regulated transcriptional programs, including genes associated with squamous cell carcinoma (e.g. Myc), lipid and cellular metabolism (Hk2, Ppard), and growth factors (Areg, Bmp6, Vegfa). These data suggest that in addition to decreasing adipogenesis, KRT14-restricted NRF2 activation drives hyperplasia of the esophagus, forestomach, and tongue, but not formation of squamous cell carcinoma. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Cost-effectiveness of rapid on-site evaluation of endoscopic ultrasound fine needle aspiration in gastrointestinal lesions.

BACKGROUND AND AIM: Rapid on-site evaluation (ROSE) can improve adequacy rates of fine needle aspiration (FNA) and thus save operational costs. Our aim was to assess the cost-efficacy of ROSE performed during endoscopic ultrasound (EUS)-FNA of gastrointestinal lesions. METHOD: This was a retrospective cohort study of 156 patients who underwent EUS-FNA for pancreatic, submucosal upper gastrointestinal, and adjacent lesions at Galilee Medical Center between 2012 and 2017. The patient cohort was divided into group A (62 patients, 39.7%) who underwent EUS-FNA with ROSE, and group B (94 patients, 60.3%) without ROSE. Cost analysis was based on the additional expenditure of repeated EUS-FNA sessions needed to reach accurate and final diagnosis in the two groups. RESULTS: The overall cost was significantly higher in group B ($121 422) as compared to group A ($72 861), including the ROSE cost. Additional EUS-FNA sessions were needed in 11.3% and 23.4% in groups A and B, respectively. The additional cost to achieve final pathological diagnosis was $7203 and $24 696 in groups A and B, respectively (P = .02), yielding a savings of $252 per EUS-FNA case by adding ROSE. Notably, adding ROSE to the EUS-FNA exam for gastrointestinal non-pancreatic lesions resulted in even higher savings per case ($682.40). Moreover, adding ROSE improved specimen adequacy to achieve final pathological diagnosis (odds ratio = 7.13, P = .0005). CONCLUSIONS: EUS-FNA with ROSE was cost-effective. Incorporating ROSE into the clinical practice of EUS-FNA saves costs and improves specimen adequacy.

Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play.

Radiotherapy remains one of the contemporary cornerstones of cancer treatment in the neoadjuvant, curative, adjuvant and palliative settings, either in isolation or as a multimodal approach. Moreover, recent advances in targeted immune checkpoint therapy have firmly established immunotherapy as the fourth pillar in cancer therapy alongside surgery, chemotherapy and notably radiotherapy. There is emerging evidence to suggest both radioresistance and reduced efficacy of immune checkpoint blockade (ICB) are potentiated by the tumour microenvironment (TME) and in fact modulating aspects of this immunosuppressive milieu is instrumental to unlocking anti-tumour immunity. The response rates of Upper Gastrointestinal (UGI) malignancies to ICB remains modest at 10-15%, compared to melanoma at 20-40%. Harnessing the effects of radiotherapy through remodelling of the TME using ICB as a radiosensitisor is an avenue showing promise. Here we explore the rationale behind combining radiotherapy with ICB, as a symbiotic relationship in shifting the balance in favour of anti-tumour immunity. We discuss the effects of radiotherapy on immunogenic cell death, the concept of the abscopal effect, the importance of the cGAS STING pathway, and their relevance in the context of the tumour microenvironment. Furthermore, dosing and timing of radiotherapy and ICB is now being evaluated for its synergistic effects on host tumour immunity, and we review the ongoing efforts and current available literature for single agent and dual agent ICB in combination multimodal therapy for both locally advanced operable and metastatic disease of the upper gastrointestinal tract.

Helicobacter pylori and Upper Endoscopy in Systemic Sclerosis: A Cross-sectional Study in the Real World.

BACKGROUND/AIMS: A role for Helicobacter pylori in triggering systemic sclerosis (SSc) has been proposed, but data are conflicting. In previous studies, infection has been generally searched for by using serology. We designed this study to assess H. pylori prevalence in SSc patients with histology of gastric mucosa, considered the criterion standard for infection diagnosis. METHODS: This cross-sectional study enrolled 30 SSc patients who complained of upper gastrointestinal symptoms. All underwent upper endoscopy with gastric biopsies. Endoscopic alterations were recorded, and gastric mucosa biopsies were used for both histological examination and searching for H. pylori. The role for proton-pump inhibitor (PPI) therapy was considered. Fisher exact test was used for statistical analysis. RESULTS: Data of 28 SSc patients were available, 14 with ongoing PPI therapy. Helicobacter pylori infection at histology was detected in 14.3% patients, and it equally occurred in patients with or without PPI therapy. Erosive esophagitis/Barrett esophagus was detected in 26.6% of cases. Among patients with PPI therapy, 30% received half dose only. The prevalence of intestinal metaplasia was low (14.3%). Endoscopic esophageal alterations were significantly more frequent in those patients showing anti-Scl70 antibody positivity. CONCLUSIONS: This study showed that prevalence of H. pylori is very low in SSc patients, so that it seems not having a role in triggering SSc. Management of gastroesophageal diseases in SSc patients needs to be improved, and looking to the autoimmune profile may be of help. Thus, collaboration between rheumatologist and gastroenterologist is highly recommended.