IL-17 receptor A functions to help maintain barrier integrity and limit activation of immunopathogenic response to H. pylori infection.

Activation of Th17 cell responses, including the production of IL-17A and IL-21, contributes to host defense and inflammatory responses by coordinating adaptive and innate immune responses. IL-17A and IL-17F signal through a multimeric receptor, which includes the IL-17 receptor A (IL-17RA) subunit and the IL-17RC subunit. IL-17RA is expressed by many cell types, and data from previous studies suggest that loss of IL-17 receptor is required to limit immunopathology in the Helicobacter pylori model of infection. Here, an Il17ra-/- mouse was generated on the FVB/n background, and the role of IL-17 signaling in the maintenance of barrier responses to H. pylori was investigated. Generating the Il17ra-/- on the FVB/n background allowed for the examination of responses in the paragastric lymph node and will allow for future investigation into carcinogenesis. While uninfected Il17ra-/- mice do not develop spontaneous gastritis following H. pylori infection, Il17ra-/- mice develop severe gastric inflammation accompanied by lymphoid follicle production and exacerbated production of Th17 cytokines. Increased inflammation in the tissue, increased IgA levels in the lumen, and reduced production of Muc5ac in the corpus correlate with increased H. pylori-induced paragastric lymph node activation. These data suggest that the cross talk between immune cells and epithelial cells regulates mucin production, IgA production, and translocation, impacting the integrity of the gastric mucosa and therefore activating of the adaptive immune response.

Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer?

Gastric intestinal metaplasia (GIM), which denotes conversion of gastric mucosa into an intestinal phenotype, can occur in all regions of the stomach, including cardiac, fundic, and pyloric mucosa. Since the earliest description of GIM, its association with gastric cancer of the differentiated (intestinal) type has been a well-recognized concern. Many epidemiologic studies have confirmed GIM to be significantly associated with subsequent gastric cancer development. Helicobacter pylori, the principal etiologic factor for gastric cancer, plays the most important role in predisposing to GIM. Although the role of GIM in the stepwise progression model of gastric carcinogenesis (the so-called "Correa cascade") has come into question recently, we review the scientific evidence that strongly supports this long-standing model and propose a new progression model that builds on the Correa cascade. Eradication of H pylori is the most important method for preventing gastric cancer globally, but the effect of eradication on established GIM, is limited, if any. Endoscopic surveillance for GIM may, therefore, be necessary, especially when there is extensive corpus GIM. Recent advances in image-enhanced endoscopy with integrated artificial intelligence have facilitated the identification of GIM and neoplastic lesions, which will impact preventive strategies in the near future.

Gastric dysplasia in random biopsies: the influence of Helicobacter pylori infection and alcohol consumption in the presence of a lesion.

BACKGROUND: Gastric dysplasia in the absence of an endoscopically defined lesion is rare, usually either a false positive diagnosis or a previously unidentified precancerous lesion during esophagogastroduodenoscopy (EGD). AIMS: Evaluate factors associated with the presence of an endoscopically visible lesion during follow-up in patients with histologic diagnosis of gastric dysplasia in random biopsies. METHODS: Retrospective cohort study including patients referred to our institution for gastric dysplasia in random biopsies during Index EGD. Endoscopic evaluation was performed with a high-definition endoscope using narrow band imaging (HD EGD-0). If no lesion was detected, endoscopic surveillance (HD EGD-FU) was conducted within 6 months for high grade dysplasia (HGD) or 12 months for low grade (LGD) or indefinite for dysplasia (IFD). RESULTS: From a total sample of 96 patients, 5 (5.2%) presented with an endoscopically visible lesion during HD EGD-0, while 10 lesions (10.4%) were identified during HD EGD-FU. Patients with Helicobacter pylori infection at Index EDG and with regular alcohol consumption (≥25 g/day) were 8 and 4 times more likely to have an endoscopically visible lesion on HD EGD-FU (p = 0.012 and p = 0.047). In binary logistic regression, both factors were independent predictors of the presence of gastric lesion on HD EGD-FU (OR 9.284, p = 0.009 and OR 5.025, p = 0.033). CONCLUSIONS: The presence of an endoscopically visible lesion after the histologic diagnosis of gastric dysplasia in random biopsies was more frequent during HD EGD-FU. H. pylori infection at Index EGD and regular alcohol consumption were significant predictors of the presence of gastric lesion on HD EGD-FU.

Gastric dysplastic lesions in Helicobacter pylori-naïve stomach: Foveolar-type adenoma and intestinal-type dysplasia.

Reports of Helicobacter pylori (Hp)-naïve gastric neoplasm (HpNGN) cases have been rapidly increasing due to the recent increase in the Hp-naïve population in Japan. Most HpNGNs exhibit the gastric immunophenotype and a low malignant potential regardless of histological type. Especially, foveolar-type gastric adenoma (FGA) and intestinal-type gastric dysplasia (IGD) rarely progress to invasive carcinoma. FGA is a foveolar epithelial neoplasm that occurs in the fundic gland (oxyntic gland) mucosa and is classified as the flat type or raspberry type (FGA-RA). The flat type is a large, whitish flatly elevated lesion while FGA-RA is a small reddish polyp. Genomically, the flat type is characterized by APC and KRAS gene mutations and FGA-RA by a common single nucleotide variant in the KLF4 gene. This KLF4 single-nucleotide variant reportedly induces gastric foveolar epithelial tumorigenesis and activates both cell proliferation and apoptosis, leading to its slow-growing nature. IGD consists of an intestinalized epithelial dysplasia that develops in the pyloric gland mucosa, characterized as a superficial depressed lesion surrounded by raised mucosa showing a gastritis-like appearance. Immunohistochemically, it exhibits an intestinal or gastrointestinal phenotype and, frequently, p53 overexpression. Thus, IGD shows unique characteristics in HpNGNs and a potential multistep tumorigenic process.

Image-enhanced endoscopy in the diagnosis of gastric premalignant conditions and gastric cancer. / Técnicas de imagen avanzada en la detección y caracterización de las lesiones precursoras del cáncer gástrico y del cáncer gástrico precoz.

Diagnosis of early gastric cancer and its precancerous lesions remains a challenge for great part of western endoscopists. Changes seen in the mucosal pattern are generally subtle and hence difficult to identify. In this article, we will review the usefulness of conventional and virtual chromoendoscopy and magnification endoscopy in the recognition and classification of these lesions.

Long-Term Outcome of Gastric Mild-Moderate Dysplasia: A Real-World Clinical Experience.

BACKGROUND & AIMS: The natural course of gastric mild-moderate dysplasia in a country with high incidence of gastric cancer (GC) is relatively unknown. We aimed to determine the long-term cumulative incidence of and risk factors for advanced neoplasia in patients with gastric dysplasia. METHODS: This was a single-center observational study including all consecutive patients diagnosed with gastric mild-moderate dysplasia between 2000 and 2017. Follow-up data were collected until December 2019. We determined the cumulative incidence of advanced neoplasia and identified risk factors with Cox regression. RESULTS: A total of 3489 consecutive participants were followed for a median of 4.19 years from initial mild-moderate dysplasia diagnosis. The median surveillance interval between index endoscopy and next follow-up endoscopy was 1.08 years, and more than half of patients had at least 3 surveillance gastroscopies. During the study period, the majority of participants did not show disease progression, either with dysplasia not detected (51.4%) or with persistent dysplasia (46.1%). There were 88 (2.9%) patients (5.13 per 1000 patient-years) who progressed to advanced neoplasia within a median of 4.3 years. The annual incidence of advanced neoplasia and GC were 0.43% and 0.26%, respectively, within 5 years of mild-moderate dysplasia diagnosis. Increasing age, male sex, moderate dysplasia, dysplasia detected in fundus or cardia at index endoscopy, and persistent Helicobacter pylori infection during follow-up were independent risk factors for developing advanced neoplasia. CONCLUSIONS: Even in a country with high incidence of GC, the majority of patients with gastric mild-moderate dysplasia did not experience disease progression in the long term. Intensified surveillance during the first 5 years after mild-moderate dysplasia detection is suggested.

Deep learning for automatic diagnosis of gastric dysplasia using whole-slide histopathology images in endoscopic specimens.

BACKGROUND: Distinguishing gastric epithelial regeneration change from dysplasia and histopathological diagnosis of dysplasia is subject to interobserver disagreement in endoscopic specimens. In this study, we developed a method to distinguish gastric epithelial regeneration change from dysplasia and further subclassify dysplasia. Meanwhile, optimized the cross-hospital diagnosis using domain adaption (DA). METHODS: 897 whole slide images (WSIs) of endoscopic specimens from two hospitals were divided into training, internal validation, and external validation cohorts. We developed a deep learning (DL) with DA (DLDA) model to classify gastric dysplasia and epithelial regeneration change into three categories: negative for dysplasia (NFD), low-grade dysplasia (LGD), and high-grade dysplasia (HGD)/intramucosal invasion neoplasia (IMN). The diagnosis based on the DLDA model was compared to 12 pathologists using 100 gastric biopsy cases. RESULTS: In the internal validation cohort, the diagnostic performance measured by the macro-averaged area under the receiver operating characteristic curve (AUC) was 0.97. In the independent external validation cohort, our DLDA models increased macro-averaged AUC from 0.67 to 0.82. In terms of the NFD and HGD cases, our model's diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were significantly higher than junior and senior pathologists. Our model's diagnostic sensitivity, NPV, was higher than specialist pathologists. CONCLUSIONS: We demonstrated that our DLDA model could distinguish gastric epithelial regeneration change from dysplasia and further subclassify dysplasia in endoscopic specimens. Meanwhile, achieved significant improvement of diagnosis cross-hospital.

Kimura-Takemoto Classification: A Tool to Predict Gastric Intestinal Metaplasia Progression to Advanced Gastric Neoplasia.

BACKGROUND AND AIMS: Gastric cancer is a leading cause of morbidity and mortality worldwide. Gastric intestinal metaplasia (GIM) has been described as a key histologic step in the development of gastric adenocarcinoma. However, not all people with GIM develop malignancy. We studied the factors associated with progression to dysplasia and advanced gastric neoplasia (aGN) in patients with baseline GIM. METHODS: Retrospective cohort analysis of patients with baseline GIM and subsequent endoscopic evaluation at Cleveland Clinic Florida and Ohio Main Campus between 2005 and 2017. Demographic and exposure risk factors, as well as Kimura-Takemoto classification (KTc), were used as variables for hazards ratio (HR) and Kaplan-Meier survival-free analysis for aGN and any form of dysplasia progression. RESULTS: There were 708 patients identified with GIM; 29 patients (4.1%) progressed to any degree of dysplasia. From these, LGD was present in 12 cases (1.7%), HGD in 4 cases (0.6%), and gastric cancer in 13 cases (1.8%), for a total of 17 aGN cases. KTc was associated with dysplasia and aGN progression (p < 0.001), and no cases progressed if KTc findings were absent. Open-type KTc was associated with aGN (HR 6.36, p < 0.001) and any dysplasia progression (HR 13.34, p < 0.001) compared to closed-type or absent KTc features. No other factors were associated with aGN or dysplasia progression. Open-type KTc was also associated with shorter cancer survival-free progression. CONCLUSION: Patients with baseline GIM present a higher progression risk to aGN, dysplasia, or cancer if concomitant KTc findings are present, particularly an open-type KTc pattern.

Cell polarity (the 'four lines') distinguishes gastric dysplasia from epithelial changes in reactive gastropathy.

AIMS: Gastric dysplasia is a risk factor for synchronous and subsequent gastric carcinoma. Distinguishing gastric dysplasia from reactive changes is subject to interobserver disagreement and is a frequent reason for expert consultation. We previously used assessment of surface cell polarity (the 'four lines') as a key feature to decrease equivocal diagnoses in Barrett oesophagus. In the current study, we examined for the presence or absence of the four lines in gastric dysplasia and reactive gastropathy. MATERIALS AND METHODS: The study includes all (n = 91) in-house biopsies with at least gastric dysplasia from the surgical pathology archives of two academic institutions during a 5-year period from 2008 to 2012. A reactive gastropathy group (n = 60) was created for comparison. RESULTS: The dysplasia/neoplasia group was comprised of 14 biopsies of gastric foveolar-type dysplasia, 59 of intestinal-type dysplasia, 14 with dysplasia in fundic gland polyps, three pyloric gland adenomas and one oxyntic gland adenoma. Loss of surface cell polarity was seen in all 88 dysplasia cases with evaluable surface epithelium. All 57 reactive gastropathy cases with evaluable surface epithelium showed intact surface cell polarity except in focal areas directly adjacent to erosions in 17 cases, where the thin wisp of residual surface mucin could not be appreciated on haematoxylin and eosin. CONCLUSION: Surface cell polarity (the four lines) was lost in all gastric dysplasia biopsies with evaluable surface epithelium and maintained in all biopsies of reactive gastropathy. Caution should be taken in using this feature adjacent to erosions in reactive gastropathy.

Long-term natural history after endoscopic resection for gastric dysplasia.

BACKGROUND AND STUDY AIMS: Natural history after endoscopic resection (ER) for gastric dysplasia is still unclear. The aim of this study was to evaluate the long-term clinical outcomes and risk factors after ER for gastric dysplasia between control and cases with synchronous or metachronous gastric neoplasm. METHODS: A total of 1090 patients who had undergone ER for gastric dysplasia and been followed up for at least one year from December 2002 to December 2013 were finally analyzed. Risk factors affecting the development of synchronous or metachronous neoplasm (SMN) and long-term clinical outcomes after ER for gastric dysplasia were evaluated. RESULTS: Synchronous and metachronous neoplasms had developed in 126 (11.6%) and 133 patients (12.2%) during the mean follow-up duration of 63.6 months, respectively. Five-year and 10-year risk of metachronous neoplasm were 9.8% and 27.2%, respectively. Median duration to the development of metachronous neoplasm was 103.1 months. While age (P < 0.001) and mucosal atrophy (P = 0.09) of index cases were associated with the development of synchronous neoplasm, age (P = 0.017), incomplete resection (P = 0.025), and intestinal metaplasia (P = 0.017) of background mucosa of index cases were significantly related to the development of metachronous neoplasm in multivariate analysis. Cumulative incidence of SMN was not significantly different among H. pylori negative, eradicated, and persistent group. CONCLUSIONS: Age, incomplete ER, and background intestinal metaplasia of index gastric dysplasia were significantly associated with metachronous recurrence. Endoscopic surveillance for metachronous recurrence after ER for gastric dysplasia is mandatory for longer than 10 years.

Analysis of factors associated with local recurrence after endoscopic resection of gastric epithelial dysplasia: a retrospective study.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely used techniques for the treatment of gastric epithelial dysplasia. Previous studies have compared the clinical outcome of endoscopic resection for early gastric cancer, but few studies have focused on gastric dysplasia alone. This study aimed to evaluate the long-term prognosis following endoscopic procedures for gastric epithelial dysplasia, investigate differences in local recurrence rates according to the treatment modality, and identify risk factors associated with local recurrence. METHODS: In this retrospective study, local recurrence rates and risk factors associated with local recurrence were compared between 599 patients who underwent EMR and 306 who underwent ESD for gastric epithelial dysplasia from January 2011 to December 2015. RESULTS: The en bloc resection rate (32.2% vs. 100%, p < 0.001) and complete resection rate (94.8% vs. 99.0%, p = 0.003) were significantly lower in the EMR group than in the ESD group. The local recurrence rate was significantly lower in the ESD group (1.3%) than in the EMR group (4.2%; p = 0.026). There was a significantly increased risk of local recurrence, regardless of lesion location or histologic grade, in patients with lesions > 2 cm (p = 0.002) or red in color (p = 0.03). The ESD group had a significantly lower local recurrence rate, with a higher complete resection rate, than that in the EMR group (p < 0.05). In the case of recurrence after endoscopic resection, most of the recurred lesions were removed through additional endoscopic procedures; there was no difference between the two groups (p = 0.153). CONCLUSIONS: The complete resection rate was significantly higher, and the local recurrence rate was significantly lower, in patients with gastric epithelial dysplasia treated with ESD. Therefore, ESD should be considered the preferred treatment in patients with lesions > 2 cm or showing redness due to an increased risk of local recurrence and EMR may be possible for low-grade dysplasia that is less than 2 cm without surface changes such as redness, depression and nodularity.

Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes.

Gastric cancer accounts for about 6% of cancers worldwide, being the fifth most frequently diagnosed malignancy and the third leading cause of cancer related death. Gastric carcinogenesis is a multistep and multifactorial process and is the result of the complex interplay between genetic susceptibility and environmental factors. The identification of predisposing conditions and of precancerous lesions is the basis for screening programs and early stage treatment. Furthermore, although most gastric cancers are sporadic, familial clustering is observed in up to 10% of patients. Among them, hereditary cases, related to known cancer susceptibility syndromes and/or genetic causes are thought to account for 1-3% of all gastric cancers. The pathology report of gastric resections specimens therefore requires a standardized approach as well as in depth knowledge of prognostic and treatment associated factors.

[Morphological and immunohistochemical features of severe gastric dysplasia and early gastric cancer]. / Morfologicheskie i immunogistokhimicheskie osobennosti tiazheloi displazii i rannego raka zheludka.

AIM: to investigate the morphological and immunohistochemical features of severe gastric dysplasia (SGD) and early gastric cancer (EGC). MATERIAL AND METHODS: The fragments of gastric tumor tissue with adjacent mucosal portions from 50 patients aged from 34 to 79 years (mean age 63.8 years), which had been removed during organ-sparing endoscopic surgery, were histologically, histochemical, and immunohistochemically (IHC) examined. RESULTS: In EGC, there was a preponderance of intestinal-type cancer; the adjacent mucosal areas showed foci of SGD and colonic metaplasia in 100%. Cancer emboli were absent in the lumen of blood and lymphatic vessels in EGC at a рТ1а stage. Relapse of cancer occurred in 10% of the patients with EGC within 6-24 months after endoscopic dissection. CONCLUSION: Complex morphological and IHC examination allows timely diagnosis of SGD and EGC, namely: the ability to assess the histologic type and depth of invasion of EGC, the presence or absence of cancer emboli in the blood and lymphatic vessels, which is crucial in determining treatment policy and prognosis. The immunophenotype of SGD and EGC with a number of antibodies (Abs) (cytokeratins 7, 8/18, mucins 1, 2 and 5AC, and p53) was assessed, the most significant ones of which were, in our opinion, Abs to p53 and mucin 5AC.

Relationship between body mass index and the risk of early gastric cancer and dysplasia regardless of Helicobacter pylori infection.

BACKGROUND: Obesity is known to be associated with an increased risk of gastric cardia cancer but not with noncardia cancer. In terms of gastric dysplasia, few studies have evaluated its relationship with obesity. In addition, no study on the relationship between obesity and the risk of gastric cancer has analyzed the status of Helicobacter pylori infection. METHODS: A case-control study was designed to investigate the relationship between obesity and the risk of gastric cancer and dysplasia adjusted for the status of H. pylori infection in Koreans. Nine hundred ninety-eight gastric cancer patients, 313 gastric dysplasia patients, and 1,288 subjects with normal endoscopic findings were included. RESULTS: As gender differences could be the largest confounding factor, the risk of gastric cancer and dysplasia with an increasing body mass index (BMI) was analyzed in men and women, separately, and was adjusted for age, smoking, drinking, family history of gastric cancer, H. pylori infection, atrophic gastritis, intestinal metaplasia, and serum pepsinogen I/pepsinogen II ratio. Obesity (BMI 25 kg/m(2) or greater but less than 30 kg/m(2)) was associated with increased risk of early gastric cancer [adjusted odds ratio (aOR) 1.657; 95 % confidence interval (CI) 1.086-2.528; P = 0.019] and well or moderately differentiated adenocarcinoma (aOR 1.566; 95 % CI 1.011-2.424; P = 0.044) compared with normal BMI status (BMI < 23 kg/m(2)) in men. Obesity was related to gastric dysplasia (aOR 2.086; 95 % CI 1.011-4.302; P = 0.047) in women. CONCLUSIONS: The effect of obesity on gastric cancer showed a gender difference. That is, in men it was related to increased risk of early gastric cancer and well or moderately differentiated adenocarcinoma, but it was associated with gastric dysplasia in women regardless of H. pylori infection in Korea. Further research into this difference is necessary.

Comparative study of the endoscope-based bevelled and volume fiber-optic Raman probes for optical diagnosis of gastric dysplasia in vivo at endoscopy.

This study aims to compare the diagnostic performance of the two different endoscope-based fiber-optic Raman probe designs (i.e., bevelled and volume Raman probes) for real-time, in vivo detection of gastric dysplasia at endoscopy. To conduct the clinical comparison, a total of 1,050 in vivo tissue Raman spectra (normal: n = 864; dysplasia: n = 186) were acquired from 66 gastric patients (normal: n = 48; dysplasia: n = 18) by using bevelled Raman probe, while a total of 1,913 in vivo tissue Raman spectra (normal: n = 1,786; dysplasia: n = 127) were acquired from 98 gastric patients (normal: n = 87; dysplasia: n = 11) by using volume Raman probe. The bevelled Raman probe provides approximately twofold improvements in tissue Raman-to-autofluorescence intensity ratios as compared to the use of volume Raman probe. Partial least squares discriminant analysis together with leave-one patient-out cross-validation on in vivo tissue Raman spectra acquired yields a diagnostic accuracy of 93.0 % (sensitivity of 92.5 %; specificity of 93.1 %) for differentiating gastric dysplasia from normal gastric tissue by using the bevelled fiber-optic Raman probe, which is superior to the diagnostic performance (accuracy of 88.4 %; sensitivity of 85.8 %; specificity of 88.6 %) by using the volume Raman probe. This work demonstrates that the Raman spectroscopic technique coupled with bevelled fiber-optic Raman probe has great potential to enhance in vivo diagnosis of gastric precancer and early cancer at endoscopy. Graphical Abstract Comparison of in vivo gastric tissue Raman spectra acquired by using bevelled and volume fiber-optic Raman probes.

Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis.

BACKGROUND: The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp-infected population in Japan. We investigated the clinicopathologic differences between Hp-infected gastric neoplasms (HpIGNs) and Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. METHODS: This retrospective multicenter study investigated 966 consecutive patients with 1131 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinicopathologic features were compared between HpIGN and HpNGN cases. RESULTS: One thousand and sixty-eight HpIGNs in 916 patients included 877 differentiated types and 191 undifferentiated types. Sixty-three HpNGNs in 50 patients included 57 differentiated types (35 foveolar types, 15 intestinal types, 6 fundic-gland types, and 1 other differentiated type) and 6 undifferentiated types. HpNGNs occurred in younger (59.5 vs. 71.8 years, p < 0.05) and female patients (40.0% vs. 26.5%, p < 0.05), were found more frequently in the proximal compartment (p < 0.05), and had smaller size (median 4.0 vs. 20.0 mm, p < 0.05). Histologically, HpNGNs and HpIGNs both primarily consisted of differentiated type (90.5% vs. 82.1%, p = 0.089) and HpNGNs showed lower prevalence of invasive cancer (11.1% vs. 37.6%, p < 0.05) and lymphovascular invasion (1.6% vs. 31.6%, p < 0.05). Nearly all HpNGNs (62/63, 98.4%) were diagnosed in early pathological stage, while 16.1% (172/1068) of HpIGNs were diagnosed in advanced stage (p < 0.05). CONCLUSIONS: HpNGNs is recently on the increase but shows lower malignant nature regardless of histologic type than HpIGN. Endoscopic gastric cancer screening will be reviewed via cost effectiveness for Hp-naïve individuals in future.

Diagnostic Usefulness of p53 Immunostaining in Gastric Cancer and Dysplasia: A Real-world Clinical Experience.

BACKGROUND/AIM: Gastric cancer and its precancerous lesions represent a significant public health concern. A subset of gastric cancers exhibits mutations in the TP53 gene, often accompanying distinctive morphologic alterations. This study aimed to assess the diagnostic efficacy of p53 immunostaining in real-world clinical settings. PATIENTS AND METHODS: A retrospective analysis was conducted on 50 cases of gastric tumors and tumor-like lesions, wherein p53 immunostaining played a pivotal diagnostic role. The staining pattern of p53 was examined in conjunction with clinicopathologic parameters. RESULTS: Mutant p53 staining pattern demonstrated a significant association with high-grade nuclear atypia (p<0.001), high-grade dysplasia, and tubular adenocarcinoma (p<0.001), as well as microsatellite instability status (p=0.034). Furthermore, the diagnostic utility of p53 immunostaining was evident in scenarios where: 1) biopsy specimens contained few tumor cells, 2) pathologic evaluation of resection margins was limited by cauterization artifacts, and 3) distinction between low-grade and high-grade gastric dysplasia was challenging. CONCLUSION: P53 immunostaining can be helpful for the diagnosis of gastric tumor and tumor-like lesions, and accurate pathologic margin evaluation, particularly in lesions demonstrating intestinal-type differentiation and some degree of nuclear atypia.

A Rare Intersection: A Case of Gastric Adenocarcinoma With Yolk Sac Differentiation.

This case report presents a rare instance of a 73-year-old male diagnosed with a yolk sac tumor (YST) coexisting with adenocarcinoma components in the stomach. YSTs are primarily gonadal and seldom occur in extragonadal sites such as the gastrointestinal tract. The patient underwent curative resection followed by chemotherapy, resulting in long-term survival without recurrence. This case contributes to the limited existing literature on gastric YSTs, emphasizing the importance of early diagnosis and effective treatment for this aggressive malignancy. It serves as a valuable addition to our understanding of the pathophysiology, diagnosis, and management of this rare condition.

Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions.

Background:Helicobacter pylori infection is characterized by an inflammatory infiltrate that might be an important antecedent of gastric cancer. The purpose of this study was to evaluate whether interleukin (IL)-17 inflammation is elicited by gastric T cells in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia (IM/DYS). We also investigated the serum IL-17A levels in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia, and patients with Helicobacter pylori non-atrophic gastritis (NAG). Methods: the IL-17 cytokine profile of gastric T cells was investigated in six patients with IM/DYS and Helicobacter pylori infection. Serum IL-17A levels were measured in 45 Helicobacter pylori-infected IM/DYS patients, 45 Helicobacter pylori-infected patients without IM/DYS and in 45 healthy controls (HC). Results: gastric T cells from all IM/DYS patients with Helicobacter pylori were able to proliferate in response to Helicobacter pylori and to produce IL-17A. The Luminex analysis revealed that IL-17A levels were significantly increased in Helicobacter pylori IM/DYS patients compared to healthy controls and to Helicobacter pylori gastritis patients without IM/DYS (452.34 ± 369.13 pg/mL, 246.82 ± 156.06 pg/mL, 169.26 ± 73.82 pg/mL, respectively; p < 0.01, p < 0.05). Conclusions: the results obtained indicate that Helicobacter pylori is able to drive gastric IL-17 inflammation in IM/DYS Helicobacter pylori-infected patients, and that IL-17A serum levels are significantly increased in Helicobacter pylori-infected patients with IM/DYS.

The pattern of metachronous recurrence after endoscopic submucosal dissection for gastric adenocarcinoma and dysplasias.

BACKGROUND/AIMS: Metachronous recurrence incidences and risk factors following endoscopic submucosal dissection (ESD) for gastric adenocarcinoma and dysplasias were investigated. METHODS: Retrospective review of electronic medical records of patients who underwent gastric ESD at The Catholic University of Korea, Yeouido St. Mary's Hospital. RESULTS: A total of 190 subjects were enrolled for analysis during the study period. The mean age was 64.4 years-old and the male sex occupied 73.7%. The mean observation period following ESD was 3.45 years. The annual incidence rate of metachronous gastric neoplasms (MGN) was about 3.96%. The annual incidence rate was 5.36% for the low-grade dysplasia group, 6.47% for the high-grade dysplasia group, and 2.74% for the EGC group. MGN was more frequent in the dysplasia group than in the EGC group (p<0.05). For those with MGN development, the mean time interval from ESD to MGN was 4.1 (±1.8) years. By using the Kaplan-Meier model, the estimated mean MGN free survival time was 9.97 years (95% confidence interval, 8.53-11.40) The histological types of MGN were not related to the primary histology types. CONCLUSION: MGN following ESD developed in 3.96% annually and MGN was more frequent in the dysplasia group. The histological types of MGN did not correlate with those of primary neoplasm.