Type Of Gastric Adenocarcinoma Research Articles

Phase I/II study of nab-paclitaxel combined with S-1 as adjuvant chemotherapy in diffuse type of stage III gastric or gastroesophageal junction adenocarcinoma.

e16064 Background: Diffuse type (Lauren's classification) of gastric adenocarcinoma (GAC) or gastroesophageal junction adenocarcinoma (GEJ) has a poorer prognosis than intestinal type of GAC or GEJ. Studies have shown that nab-paclitaxel combined with S-1 has a synergistic anti-tumor effect on advanced gastric cancer. We designed this trial to evaluate the efficacy and safety of nab-paclitaxel plus S-1 as adjuvant chemotherapy in diffuse type of stage III GAC or GEJ. Methods: This study was a multi-center, open-label, phase I/II study. The results of the phase I dose escalation study have already been reported, and the recommended phase II dose (RP2D) of nab-paclitaxel is 260mg/m2. Patients with stage III diffuse type GAC or GEJ after D2 dissection and achieved R0 resection were included in this study. S-1 monotherapy was used as adjuvant therapy in the first cycle. If absence of grade3/4 treatment-related adverse events (AEs) of S-1 monotherapy, nab-paclitaxel (260mg/m2, d1, q3w) and S-1 [body surface area (BSA) <1.25 m2, 80mg/d; BSA 1.25–1.5 m2, 100mg/d; BSA >1.5 m2, 120mg/d; d1-14, q3w] were administered for 6 cycles. Then patients still received S-1 monotherapy for 8 cycles. In phase II study, the primary endpoint was 1-year disease free survival (DFS) rate, and the secondary endpoints were 3-year DFS rate and safety. Results: From January 2021 to February 2023, a total of 42 patients were enrolled in this analysis (3 patients in nab-paclitaxel 260mg/m2 dose group in phase I and 39 patients in phase II). The median age (range) was 53 (29~69) years, 18 patients (42.86%) were stage IIIA, 10 patients (23.81%) were stage IIIB and 14 patients (33.33%) were stage IIIC. The median follow-up time was 13.26 months. As of January 2023, 12 patients experienced recurrence. The 1-year-DFS rate was 74.07%, median DFS and 3-year-DFS rate were not reached. The incidence of adverse effects (AEs) was 78.57% (33/42), and the rate of grade 3-4 AEs was 42.86% (18/42). The most common AEs were neutropenia and leukopenia. In addition, we performed next generation sequencing (NGS) for 5 relapsed patients, and 5 non-relapsed patients who were matched to the relapsed patients. The results showed that the mutant rates of tumor supressor gene CDH1, ARID1A, KMT2D, and TP53 in non-relapsed patients were higher than that in relapsed patients. The positive rate of ctDNA were 60% in relapsed patients, but no ctDNA was detected in non-relapsed patients. Conclusions: Adjuvant chemotherapy with nab-paclitaxel and S-1 followed by S-1 monotherapy exhibited promising clinical efficacy, with acceptable tolerability. This study deserves further investigation and follow up for diffuse type of GAC or GEJ. Clinical trial information: NCT03977220 .

Clinical and pathological characteristics of gastric adenocarcinoma of fundic gland type

To analyze the clinical, endoscopic and pathological feature of gastric adenocarcinoma of fundic gland type (GA-FG) (18 cases) collected from Sir Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine and Taizhou Hospital of Zhejiang Province from January 2019 to July 2022. There were 18 cases of patient of GA-FG, including male 12 cases, female 6 cases, aged from 38 to 78 years old, with average age of 60.5 years old. Gastroscopy showed that bulging or flat lesions of gastric fundus were 0.2-5.5 cm in size, and the mucosal surface was smooth, redness or rough. Histologic examination showed that tumor cells were dominated by chief cells and scattered with a few oxyntic cells, formed a complex gland that anastomoses each other, and infiltrated to the submucosa. The results of immunohistochemistry showed that tumor cells were positive for the expression of mucin-6 (MUC6) and Pepsinogen 1, and partial expression of synaptophysin (Syn). GA-FG is a rare type of gastric adenocarcinoma with good differentiation, and currently only a few cases have been reported, and often easily been misdiagnosed or missed. Therefore, to master the characteristics of clinic and pathology is helpful to improve the ability of clinical pathologists in differential diagnosis.

Abstract 1194: Evolution of immune and stromal cell states during the gastric cancer continuum

Abstract Introduction: Gastric adenocarcinoma (GAC), a global health burden, lacks detail understanding of the evolution-driven cellular/molecular programs that lead to GAC tumorigenesis followed by progression/metastases. How the TME is orchestrated by precancerous lesions, primary GAC, and in metastatic niches, when well understood, may propel us into an entirely new dimension with the hopes of novel therapeutics. However, only a few studies have investigated the immune/stromal subtypes of GAC with the limitation of scope, cohort size, and/or depth or mainly focused on the primary GACs. Here, we present an atlas of transcriptionally diverse TME across the full continuum of GAC by including peripheral blood, normal gastric tissues, premalignant lesions, localized, and metastatic GACs. Methods: We performed a comprehensive single-cell profiling of 68 specimens collected from 43 subjects including a total of 77,392 high-quality cells which revealed 62 unique cell states uncovering varying profiles. We defined alterations in TMEs that underscore initiation of tumorigenesis to eventual progression. Results: We found a striking preponderance of B lineage cells, primarily the IgA+ plasma cells, in TMEs of the precancerous lesions, whereas 3 immunosuppressive myeloid subsets dominated in advanced GACs. Fractions of GZMK+ effector CD8 T cells and progenitor exhausted CD8 T cells gradually increased as GACs progressed to advanced stages. In addition, our analysis revealed extensive stromal remodeling along the GAC continuum, which may have contributed to enhanced angiogenesis and immune suppressive signaling. The observations in the primary tumors could be validated in an independent scRNA-seq dataset. Notably, we uncovered 3 unique TME interactomes and defined 6 cellular environtypes inhabited by 62 TME cell subsets giving GAC to a novel landscape not yet defined. The two distinct environtypes in GAC primaries are validated in three independent large-scale GAC cohorts, giving credence and definition to previously established histopathological variables, genomic/molecular subtypes and clinical outcomes. The analysis of tumor associated stromal cells discovered SDC2 as an exploitable target to pursue. SDC2 was abundant in cancer associated fibroblasts (CAFs), and the abundance is validated in 3 independent single-cell GAC cohorts as well as at the protein level. SDC2 expression was significantly higher in advanced (vs. early) stages and diffuse (vs. intestinal) type of GAC, and SDC2 overexpression was associated with shorter survival in all 5 large-scale GAC cohorts. Lastly, we assessed the functional effects of SDC2 expression in CAFs on tumor growth in vivo in xenograft models and found SDC2 overexpression in CAFs contributes to tumor growth. Conclusion: This study provides an atlas of GAC TMEs from tumorigenesis to advanced GAC that could be further developed for novel therapeutics but also serves as a community resource. Citation Format: Ruiping Wang, Shumei Song, Jiangjiang Qin, Katsuhiro Yoshimura, Fuduan Peng, Yanshuo Chu, Yuan Li, Yibo Fan, Jiankang Jin, Minghao Dang, Enyu Dai, Guangsheng Pei, Guangchun Han, Yating Li, Deyali Chatterjee, Melissa P. Pizzi, Ailing W. Scott, Ghia Tatlonghari, Xinmiao Yan, Matheus Da Silva Sewastjanow, Ahmed Adel Fouad Abdelhakeem, Pawel K. Mazur, Xiangdong Cheng, Jaffer A. Ajani, Linghua Wang. Evolution of immune and stromal cell states during the gastric cancer continuum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1194.

Further prognostic stratification of intestinal type of gastric adenocarcinoma by CDX2 expression pattern

Gastric cancer is one of the most deadly malignancies worldwide. It is routinely divided into 2 common histologic subtypes by the Lauren classification, intestinal type and diffuse type. In recent years, the intestinal type of gastric cancer has been found to represent a heterogeneous disease with divergent prognosis. Our objective was to investigate the CDX2/CK7 immunohistochemical pattern and its role in further stratifying this type of gastric cancer. Gastrectomy cases with a diagnosis of the intestinal type of gastric adenocarcinoma from a single large institution between 2008 and 2022 were collected. Forty-four cases with available blocks and enough tumor tissue were included in this study. Four different immunohistochemical patterns were identified: CDX2+/CK7+ (40.9%), CDX2-/CK7+ (34.1%), CDX2+/CK7- (18.2%), and CDX2-/CK7- (6.8%). Compared to CDX2-negative cases, CDX2-positive ones are more likely to present better prognostic histopathological features including early stage, less perineural and lymphovascular invasion, and lower nodal metastasis. In addition, CDX2 expression was associated with specific molecular features like HER2 overexpression and genetic alterations of receptor tyrosine kinase (TRK) genes including EGFR, ERBB2, ERBB3, DDR2, and MET. In conclusion, according to the CDX2 expression pattern, the intestinal type of gastric cancer could be further divided into 2 subgroups, which have different histopathological and molecular features and different prognosis.

Clinicopathological characteristics and prognosis of gastric signet ring cell carcinoma.

BACKGROUNDThe clinicopathological features and prognosis of gastric signet ring cell carcinoma (GSRC) remain controversial, particularly with regard to sensitivity to postoperative adjuvant therapy.AIMTo compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.METHODSBy screening gastric cancer patients from 2010 to 2015 in the database of Surveillance, Epidemiology and End Results, and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University, we analyzed the general pathological characteristics of GSRC by the chi-square test. Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma. The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma. The prognosis model of advanced GSRC was established with R software, and the area under curve (AUC) and C-index were used to assess the accuracy of the model.RESULTSAnalysis of pathological features revealed that signet ring-cell carcinoma (SRC) was more frequently seen in younger (< 60 years), female, and White patients compared to non-SRC patients. SRC was less commonly associated with early gastric cancer (EGC) (23.60% vs 39.10%), lower N0 (38.61% vs 61.03%), and larger tumour sizes > 5 cm (31.15% vs 27.10%) compared to the differentiated type, while the opposite was true compared to the undifferentiated type. Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients. In contrast, among advanced gastric cancer (AGC) patients, the prognosis of SRC patients was correlated with age, race, tumour size, AJCC stage, T-stage, and postoperative adjuvant therapy. The predictive model showed that the 3-year AUC was 0.787, 5-year AUC was 0.806, and C-index was 0.766. Compared to non-SRC patients, patients with SRC had a better prognosis in EGC [hazard ratio (HR): 0.626, 95% confidence interval (CI): 0.427-0.919, P < 0.05] and a worse prognosis in AGC (HR: 1.139, 95%CI: 1.030-1.258, P < 0.05). When non-SRC was divided into differentiated and undifferentiated types for comparison, it was found that in EGC, SRC had a better prognosis than differentiated and undifferentiated types, while there was no significant difference between differentiated and undifferentiated types. In AGC, there was no significant difference in prognosis between SRC and undifferentiated types, both of which were worse than differentiated types. A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival (34.6% and 36.2% vs 18.6%, P < 0.05).CONCLUSIONThe prognosis of SRC is better than that of undifferentiated type, especially in EGC, and its prognosis is even better than that of differentiated type. SRC patients can benefit from early detection, surgical resection, and aggressive adjuvant therapy.

S3614 Gastric Linitis Plastica - An Easily Missed Diagnosis

Introduction: Gastric cancer remains one of the most common malignancies worldwide, with large variations based on genetic, ethnic, geographic, and socioeconomic factors. Patients can present with nonspecific abdominal pain, weight loss, early satiety, or anemia from occult gastrointestinal bleeding. Gastric linitis plastica, a diffuse type of gastric adenocarcinoma, results in proliferation of fibrous tissue in the submucosa and muscle layers of the stomach wall. Biopsy will show classic signet ring cells or poorly differentiated tumor cells. Case Description/Methods: A 54-year-old Caucasian male with a past medical history of end stage renal disease, hypertension, type II diabetes mellitus presented to the hospital for fatigue and melena. His hemoglobin was 7.3 g/dL, which was approximately 3g lower than his most recent hospitalization two weeks prior. He underwent upper endoscopy, which revealed a well-demarcated region of severely congested, erythematous, and friable mucosa with a reticular appearance localized to the gastric cardia, fundus, and body (Figure A and B). Histopathology revealed intramucosal adenocarcinoma with high-grade signet ring features (Figure C), consistent with gastric linitis plastica. Staining for Helicobacter pylori was negative. He was treated with acid suppression. The patient had a prolonged hospital course complicated by hypoxic respiratory failure and eventual cardiac arrest resulting in his death. Discussion: We present here a case of gastric linitis plastica. This is a diffuse type of gastric adenocarcinoma that involves the deeper layers of the stomach wall, making the stomach firm and non-distensible. It is not associated with Helicobacter pylori infection. Diagnostic upper endoscopy remains the gold standard for evaluation, however such malignancies that spare the mucosa can be easily missed on endoscopy or histopathology. The lack of mucosal involvement decreases the yield of endoscopy and biopsy, and findings on computed tomography imaging of the abdomen lack specificity. Early diagnosis remains challenging, as endoscopic findings are less sensitive. Clinicians should maintain a high index of suspicion for this condition with findings of localized congested-appearing gastric mucosa, especially with distinct demarcation and regional non-distensibility of the gastric lumen. Deeper biopsies using “bite-on-bite” technique or endoscopic ultrasound guided fine needle biopsy should be considered.Figure 1.: A and B. Reticular appearance of gastric mucosa in linitis plastica. Figure C. Pathology of gastric biopsy demonstrating the classic appearance of signet ring cells in linitis plastica.

The expression of SOX10 and its value for predicting tumor biological behaviors in patients suffering gastric adenocarcinoma, cross sectional study

BackgroundSpecial attention has been recently paid to the expression of the SOX10 marker, which is actually responsible for coordinating the signaling process of the Wnt/B-catenin evolutionary pathway and therefore responsible for cell proliferation and differentiation in tumor cells. We aimed to study the expression of this marker in different types of gastric adenocarcinomas and to find its relationship with histopathologic features of the tumor. MethodsThis cross-sectional study was performed on patients with gastric adenocarcinoma (diffuse or intestinal type) whose malignancy could be confirmed by tissue. Subjects were classified according to CAP criteria based on pathology results. Patients underwent immunohistochemical staining to evaluate SOX10 expression. Tumor behavior was determined based on histological studies. ResultsSOX10 positivity was reported in 22.5% of all tissue samples assessed. The assessment of relationship between SOX10 expression and baseline and tumor characteristics showed no significant association of SOX10 expression and patients’ gender, age, tumor location, tumor size, its type and also lymphovascular and perineural invasions. ConclusionThe expression of the SOX10 marker is expected only in 22.5% of patients diagnosed with gastric cancer. In our society, the expression of this marker has nothing to do with the biological and aggressive behaviors of this tumor.

Abstract 6377: Developing combination therapy with SHP2 inhibition for CIN-type gastroesophageal adenocarcinoma with KRAS amplification

Abstract Recent studies from the cancer genome atlas (TCGA. Nature. 2014) (TCGA. Nature. 2017) and other groups showed that a molecular subtype with chromosomal instability (CIN) is the most common subtype of gastroesophageal adenocarcinoma (GEA) and is characterized by aneuploidy without somatic hypermutation. The oncogene KRAS is frequently amplified in CIN type gastric cancer (14.3%) and esophageal adenocarcinoma (10.4%). SHP2 is a phosphatase which is a part of a machinery activating KRAS from GDP-bound inactive status to GTP-bound active status, and our group previously reported that KRAS-amplified gastric tumors are relatively resistant to MEK inhibition but sensitive to MEK/SHP2 co-inhibition. While the combination of MEK and SHP2 inhibitors showed efficacy in pre-clinical models, the translation of this combination has been challenging, in part due to on-target toxicity from inhibitors of the MAPK pathway (Auliac, et al. Cancers. 2020). Therefore, we sought better combination strategy with SHP2 inhibition, using genome-wide CRISPR screen. We conducted primary CRISPR screening with two GEA cell lines (KE-39 and HUG1-N) and CRISPR-KO lentivirus library (Brunello CRISPR knockout pooled library, 77,741 sgRNAs/19,114 genes, Broad Institute Genomic Perturbation Platform) and identified candidate targets both within the MAPK pathway and among upstream tyrosine kinases that may enhance the efficacy of a SHP2 inhibitor in KRAS-amplified GEA. Prior to detailed analyses of potential hits from the screen, we performed the secondary screen with additional KRAS-amplified and -mutant cell lines (CAT12, YCC-1, and GSU) using a custom CRISPR-Cas9 sgRNA library targeting 509 genes of interest including top hits in each cell line data set, and confirmed that knockout of KRAS upstream and downstream genes have additive cytotoxicity to SHP2 inhibition. Given our focus on finding targets that could be readily translated into therapeutics, we focused our analysis on those of most ready translational relevance and specifically chose ERBBs, FAK, SRC, RAFs, ERK1/2, and CDK4/6 as candidate targets. Further analyses showed the potent cytotoxicity of SHP2 inhibition with a pan-ERBB kinase inhibitior (Afatinib) and with a CDK4/6 inhibitor (Ribociclib), with greater efficacy of this combination in KRAS-amplified tumors compared to KRAS-mutant tumors, both in vitro and in vivo experiments. Overall, these results suggest co-inhibition of SHP2 and upstream/downstream of KRAS as a promising treatment strategy against KRAS-amplified CIN-type GEA. Citation Format: Osamu Kikuchi, Tianxia Li, Jin Zhou, Yichen Wang, Klavdija Bastl, Prafulla C. Gokhale, Aine Knott, Yanxi Zhang, John G. Doench, Zandra Ho, Daniel V. Catenacci, Adam J. Bass. Developing combination therapy with SHP2 inhibition for CIN-type gastroesophageal adenocarcinoma with KRAS amplification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6377.

Dysplastic Stem Cell Plasticity Functions as a Driving Force for Neoplastic Transformation of Precancerous Gastric Mucosa

Dysplasia carries a high risk of cancer development; however, the cellular mechanisms for dysplasia evolution to cancer are obscure. We have previously identified 2 putative dysplastic stem cell (DSC) populations, CD44v6neg/CD133+/CD166+ (double positive [DP]) and CD44v6+/CD133+/CD166+ (triple positive [TP]), which may contribute to cellular heterogeneity of gastric dysplasia. Here, we investigated functional roles and cell plasticity of noncancerous Trop2+/CD133+/CD166+ DSCs initially developed in the transition from precancerous metaplasia to dysplasia in the stomach. Dysplastic organoids established from active Kras-induced mouse stomachs were used for transcriptome analysis, invitro differentiation, and invivo tumorigenicity assessments of DSCs. Cell heterogeneity and genetic alterations during clonal evolution of DSCs were examined by next-generation sequencing. Tissue microarrays were used to identify DSCs in human dysplasia. We additionally evaluated the effect of casein kinase 1 alpha (CK1α) regulation on the DSC activities using both mouse and human dysplastic organoids. We identified a high similarity of molecular profiles between DP- and TP-DSCs, but more dynamic activities of DP-DSCs in differentiation and survival for maintaining dysplastic cell lineages through Wnt ligand-independent CK1α/β-catenin signaling. Xenograft studies demonstrated that the DP-DSCs clonally evolve toward multiple types of gastric adenocarcinomas and promote cancer cell heterogeneity by acquiring additional genetic mutations and recruiting the tumor microenvironment. Last, growth and survival of both mouse and human dysplastic organoids were controlled by targeting CK1α. These findings indicate that the DSCs are de novo gastric cancer-initiating cells responsible for neoplastic transformation and a promising target for intervention in early induction of gastric cancer.

Interval gastric cancer: A call to attentiveness and action

Introduction and aimsEndoscopy is the most effective method for identifying gastric adenocarcinoma (GAC). Interval gastric cancer (IGC) is GAC that is diagnosed 2–3 years after a normal endoscopy. Its characteristics are unknown in the Colombian environment. The clinical, histopathologic, and endoscopic characteristics were evaluated, along with the presentation rate, proton pump inhibitor (PPI) use, and IGC survival rate, and compared with other types of GAC. MethodsA retrospective, analytic study was conducted on a prospective cohort. It evaluated 513 patients with GAC treated at our institution, within the time frame of January 2012 and June 2018. The patients had endoscopic diagnosis of GAC and endoscopy within the past three years that was negative for tumor. ResultsA total of 513 patients diagnosed with GAC were evaluated. Forty-two of the patients had IGC (8.2%): 9 early lesions and 33 advanced lesions (79%). The IGCs were smaller (31 vs. 41 mm; P < .01), as well as flatter and more depressed (P < .01). There was no association with PPI use, but there was an association with a history of gastrectomy and anastomosis (P = .02), as well as the absence of red flags (P < .003). The most frequent locations were the gastric body (52%) and the antrum (26%). Overall two-year survival was similar between IGC and GAC (37.1 vs. 39.3%, P = .72). ConclusionA total of 8.2% of recently diagnosed GAC were cases of IGC. The presence of anastomosis and the absence of red flags were related to IGC. Overall survival was poor and there were no differences from the other types of GAC detected.

Endoscopic ultrasound guided fine needle biopsy in patients with suspected gastric linitis plastica

BackgroundGastric linitis plastica (GLP) is a diffuse infiltrating type of gastric adenocarcinoma. It is associated with a poor prognosis and a five-year survival of 3–10%. The infiltrating profile of this tumor explains the low yield of the superficial mucosal biospies. The objective of this study was to investigate the role of endoscopic ultrasound-fine needle biopsy (EUS-FNB) in the diagnosis of GLP. MethodsWe performed a retrospective analysis including all patients who had an EUS-FNB, at a tertiary referral center, over the last 3 years. The primary outcome was the sensitivity of EUS-FNB in patients with suspected GLP. ResultsBetween January 2017 and December 2020, 34 patients had an EUS-FNB for suspected GLP. Ten patients had a diagnostic of GLP. This diagnosis was obtained by EUS-FNB in 90% (9/10) of the cases. Eight patients had at least one previous esophagogastroduodenoscopy (EGD) with negative mucosal biopsies. Gastric EUS-FNB helped diagnose other serious conditions in 47% (16/34) of cases with inconclusive mucosal biopsies. ConclusionGastric EUS-FNB in patients with suspected GLP and normal endoscopic mucosal biopsies may lead to a positive diagnosis of GLP in 90% of cases without notable adverse events. This technique should be considered as a second step in the setting of suspicion of GLP after inconclusive mucosal biopsies.

Cáncer gástrico de intervalo: un llamado a la atención y a la acción

Introduction and aimsEndoscopy is the most effective method for identifying gastric adenocarcinoma (GAC). Interval gastric cancer (IGC) is GAC that is diagnosed 2–3 years after a normal endoscopy. Its characteristics are unknown in the Colombian environment. The clinical, histopathologic, and endoscopic characteristics were evaluated, along with the presentation rate, proton pump inhibitor (PPI) use, and IGC survival rate, and compared with other types of GAC. MethodsA retrospective, analytic study was conducted on a prospective cohort. It evaluated 513 patients with GAC treated at our institution, within the time frame of January 2012 and June 2018. The patients had endoscopic diagnosis of GAC and endoscopy within the past three years that was negative for tumor. ResultsA total of 513 patients diagnosed with GAC were evaluated. Forty-two of the patients had IGC (8.2%): 9 early lesions and 33 advanced lesions (79%). The IGCs were smaller (31 vs. 41mm; P<.01), as well as flatter and more depressed (P<.01). There was no association with PPI use, but there was an association with a history of gastrectomy and anastomosis (P=.02), as well as the absence of red flags (P<.003). The most frequent locations were the gastric body (52%) and the antrum (26%). Overall two-year survival was similar between IGC and GAC (37.1 vs. 39.3%, P=.72). ConclusionA total of 8.2% of recently diagnosed GAC were cases of IGC. The presence of anastomosis and the absence of red flags were related to IGC. Overall survival was poor and there were no differences from the other types of GAC detected.

Research on the Histological Features and Pathological Types of Gastric Adenocarcinoma With Mucinous Differentiation.

ObjectiveTo discuss the histological features, pathological types, and prognosis of gastric adenocarcinoma with mucinous differentiation.MethodsSpecimens of 189 cases of gastric adenocarcinoma with mucinous differentiation were collected for detailed histomorphology, immunohistochemistry, fluorescence in situ hybridization, and follow-up.ResultsIn accordance with the morphological and histological structural features of the cancer cells as well as the area ratio of the mucus, gastric adenocarcinoma with mucinous differentiation was divided into four types, namely pure mucinous carcinoma, intraductal papillary mucinous carcinoma, signet ring cell type mucinous carcinoma, and mixed cell type mucinous carcinoma. Based on the macroscopic types according to Bormann's classification, pure mucinous carcinoma was mostly Type I, intraductal papillary mucinous carcinoma was mostly Type II, signet ring cell type mucinous carcinoma was mostly Type IV, and mixed cell type mucinous carcinoma was mostly Type III. The 5-year survival rate was 69.2, 64.2, 0, and 31.5%, respectively. There was a statistical difference in the lymph node metastasis rate and survival rate of the four carcinoma types. The invasion features of pure mucinous carcinoma entailed penetrating corrosively in a push-in form, without blood vessel or lymphatic metastasis and with few lymphocytes and lymphatic nodules in the marginal area. Thus, there was little lymph node metastasis and invasion of nerves. The HER2 protein expression rate was 40.2% (76/189), the HER2 gene amplification detected by FISH technology was 16.9% (32/189).ConclusionThe independent histological type, four subtypes, and histopathological classification of gastric mucinous adenocarcinoma are important for the prognosis evaluation and precise treatment of this disease.

OLGA- and OLGIM-Based Staging in the Patients with Gastritis and Endoscopy Indications.

Gastric cancer is one of the most common cancers with high mortality. In Iran, the high-risk regions include Northern and Northwestern parts. The aim of this study was to assess the operative link on gastritis assessment- and operative link on gastric intestinal metaplasia-based staging in patients with upper gastrointestinal symptoms. Totally, 345 patients underwent upper gastrointestinal endoscopy. Also, the status of Helicobacter pylori infection was evaluated using rapid urease test and histological method. Moreover, histological changes were assessed using the Update Sydney System. The operative link on gastritis assessment- and operative link on gastric intestinal metaplasia-based stages of 0-II were considered as low-risk stages and stages III and IV were considered as high-risk stages. Most of the patients were lower than 60 years (245 patients, 71%), and 71.9% of our patients had H. pylori infection. The frequency of atrophic gastritis and intestinal metaplasia was 44.9% and 25.2%, respectively (P < .001). Eleven patients (73.7%) with gastric adenocarcinoma had a low risk and 2 patients with low-grade dysplasia had a high risk of operative link on gastritis assessment and operative link on gastric intestinal metaplasia. Almost, 62.5% of gastric cancer patients with an intestinal type of gastric adenocarcinoma were at low-risk stages. Although high stages of operative link on gastritis assessment and operative link on gastric intestinal metaplasia need further follow-up, lower stages of atrophy or intestinal metaplasia also require follow-up. Furthermore, operative link on gastritis assessment method in detecting a greater number of patients who need follow-up is more successful and profitable.

Clinicopathological features of gastric adenocarcinoma with enteroblastic differentiation: a report of twelve cases

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED). Methods: Twelve cases of GAED diagnosed in Fujian Provincial Hospital from August 2019 to August 2020 were collected. HE staining, immunohistochemistry and HER2 gene amplification were evaluated. In addition, 343 cases of gastric adenocarcinoma diagnosed in the same period were used as the control group to compare the clinicopathological differences between them. Results: The 12 cases of GAED included 10 males and 2 females, aged 59-75 years (median 66.5 years). The main clinical manifestations were abdominal pain, melena with hematemesis; nine tumors were ulcerative and three were protuberant. The tumor diameter ranged from 1.5 to 9.5 cm (median 6.0 cm). Histologically, the tumor cells were arranged in tubular, papillary, cribriform, or adenoid structures. The cells were cuboidal to columnar, with relatively distinct cell boundaries and abundant clear or slightly eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for SALL4 (12/12), glypican-3 (9/12), AFP (5/12), CDX2 (8/12), CD10 (3/12), p53 mutated (10/12), HER2 (2/12, 3+), and both cases showed HER2 gene amplification by fluorescence in situ hybridization. Compared with common gastric adenocarcinoma, GAED showed higher rate of vascular invasion and tumor progression (P<0.05), but there were no significant differences in age, sex, degree of differentiation, nerve invasion, lymph node metastasis, pT stage, pN stage and pM stage (P>0.05). Conclusions: GAED is a rare type of gastric adenocarcinoma. Pathologically, GAED has both embryonal and intestinal phenotypes. In terms of biological behavior, it is more invasive. GAED needs to be distinguished from common gastric adenocarcinoma in clinical diagnosis.

In vivo assessment of Lauren classification for gastric adenocarcinoma using diffusion MRI with a fractional order calculus model.

To evaluate the performance of a fractional order calculus (FROC) diffusion model for imaging-based assessment of Lauren classification in gastric adenocarcinoma. In this study, 43 patients (15 females, 28 males) with gastric adenocarcinoma underwent MRI at 1.5 T. According to pathology-based Lauren classification, 10 patients had diffuse-type, 20 had intestinal-type, and 13 had mixed-type lesions. The diffuse and mixed types were combined as diffuse-and-mixed type to be differentiated from the intestinal type using diffusion MRI. Diffusion-weighted images were acquired by using eleven b-values (0-2000 s/mm2). Three FROC model parameters comprising diffusion coefficient D, intravoxel diffusion heterogeneity β, and a microstructural quantity μ, together with a conventional apparent diffusion coefficient (ADC), were estimated. The mean parameter values in the tumour were computed by using a percentile histogram analysis. Individual or linear combinations of the mean parameters in the tumour were used to differentiate the diffuse-and-mixed type from the intestinal type using descriptive statistics and receiver operating characteristic (ROC) analyses. Significant differences were observed between diffuse-and-mixed-type and intestinal-type lesions in D (0.99 ± 0.20 μm2/ms vs. 1.11 ± 0.23 μm2/ms; p = 0.036), β (0.37 ± 0.08 vs. 0.43 ± 0.11; p = 0.043), μ (7.92 ± 2.79 μm vs. 9.87 ± 1.52 μm; p = 0.038), and ADC (0.81 ± 0.34 μm2/ms vs. 0.96 ± 0.19 μm2/ms; p = 0.033). Among the individual parameters, μ produced the largest area under the ROC curve (0.739). The combinations of (D, β, μ) and (β and μ) produced the best overall performance with a sensitivity of 0.739, specificity of 0.750, accuracy of 0.744, and area under the curve of 0.793 (95% confidence interval: 0.657-0.929). Diffusion MRI with the FROC model holds promise for non-invasive assessment of Lauren classification for gastric adenocarcinoma. • High b-value diffusion MRI with a FROC model that is sensitive to tissue microstructures can differentiate the diffuse-and-mixed type from intestinal type of gastric adenocarcinoma. • The combination of FROC parameters produced the best result for distinguishing the diffuse-and-mixed type from the intestinal type with an area under the receiver operating characteristic curve of 0.793. • The FROC model parameters, individually or conjointly, hold promise for repeated, non-invasive evaluations of gastric adenocarcinoma at various time points throughout disease progression or regression to complement conventional Lauren classification.

Preoperatively Treated Diffuse-Type Gastric Adenocarcinoma: Glucose vs. Other Energy Sources Substantially Influence Prognosis and Therapy Response.

Simple SummaryThe diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity of the primary on baseline FDG-PET. Our data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding.Diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity (high with standardized uptake value (SUV) > 3.5 or low with SUV ≤ 3.5) of the primary on baseline FDG-PET. We retrospectively selected 111 localized dGAC patients who had baseline FDG-PET (all were treated with preoperative chemotherapy and chemoradiation). FDG-PET avidity was compared with overall survival (OS) and response to therapy. The mean age was 59.4 years and with many females (47.7%). The high-SUV group (58 (52.3%) patients) and the low-SUV group (53 (47.7%) patients) were equally divided. While the median OS for all patients was 49.5 months (95% CI: 38.5–98.8 months), it was 98.0 months (95% CI: 49.5–NE months) for the low-SUV group and 36.0 months for the high-SUV (p = 0.003). While the median DFS for all patients was 38.2 months (95% CI: 27.7–97.6 months), it was 98.0 (95% CI: 36.9–NE months) months for the low-SUV group was and only 27.0 months (95% CI: 15.2–63.2 months) for the high-SUV group (p = 0.005). Clinical responses before surgery were more common in the low-SUV group but overall we observed only 4 pathologic complete responses in 111 patients. Our unique data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding.

Localized diffuse-type gastric adenocarcinoma: Influence of baseline positron emission tomography on survival and therapy response.

176 Background: Diffuse type of gastric adenocarcinoma (dGAC) confers a poor but variable prognosis compared to intestinal type of GAC. The value of baseline uptake of FDG-PET in localized dGAC is unclear and ~40% are not FDG-PET avid. We analyzed outcomes based on the avidity (high with SUV &gt; 3.5 or low with SUV ≤3.5) of the primary on baseline FDG-PET. Methods: We retrospectively selected 111 localized dGAC cases who had baseline FDG-PET for staging. We compared the FDG-PET avidity with overall survival (OS) and response to preoperative therapy. Standard statistical methods were utilized. Results: The mean age was 59.4 years and with many female patients (47.7%). All patients had dGAC. The high-SUV group (58 [52.3%] patients) and the low-SUV group (53 [47.7%] patients) were equally divided. While the median OS for all patients was 49.5 months (95% CI: 38.5 – 98.8 months), it was 98.0 months for the low-SUV group and 36.0 months for the high-SUV ( p value = 0.003). While the median PFS for all patients was 38.2 months (95%CI: 27.7 – 97.6 months), it was 98.0 months for the low-SUV group was and 27.0 months for the high-SUV group ( p value = 0.005). Clinical responses before surgery were more common in the low-SUV group but there were only 4 patients with pathologic complete response in the entire cohort. Conclusions: Our unique data suggest that localized dGAC patients with low SUV fare better than those with high SUV meaning highly metabolic GACs consuming glucose confer poor prognosis and overall all dGACs seem resistant to therapy.

An analysis of clinicopathological characteristics and prognosis on hepatoid adenocarcinoma of stomach.

e16558 Background: Hepatoid adenocarcinoma of the stomach(HAS) is a rare type of gastric adenocarcinoma(GAC). At present, histopathology is the gold standard for the diagnosis of HAS, however, HAS is easy to be missed diagnosis, and lack of a perfect diagnosis system and effective treatment strategy. In this research, clinical pathological features will be analyzed to improve the diagnostic system, judge prognosis and provide clues for exploration of pathogenesis and targeted therapy of HAS. Methods: 576 cases including 5 confirmed patients with HAS were enrolled onto this study from 1320 patients with GAC. 10 cases of HAS were diagnosed by the second histopathological examination from the other 571 enrolled cases. 30 cases from the remaining 561 enrolled patients were randomly selected as the control group. The information of the two group cases were completed by collecting the existing case data, detecting the missed immunohistochemical indicators and telephone follow-up. The clinicopathological features of the two group cases were compared, and the treatment and prognosis of 15 HAS cases were analyzed. Results: In this study, 15 cases of HAS were found in 576 patients with GAC, including 5 cases from the 1st pathological diagnosis and 10 cases from the 2nd pathological diagnosis. There was no significant difference in age, gender, HP positive rate, serum CEA or CA19-9 level, tumor size, TNM stage, tumor invasion depth, lymph node invasion, distant metastasis rate, differentiation degree, nerve/vascular invasion, and Ki-67 expression level between the two groups( P&gt; 0.05). Compared with the control group, the serum AFP level, and the expression level of GPC3, AFP, EGFR and VEGF protein of patients in HAS group were significantly high, as well as the patients in the HAS group were more likely to develop liver metastasis( P&lt; 0.05). The mOS was 12 mo vs 42 mo for HAS group vs control group( P&lt; 0.05). Multivariate analysis showed immunohistochemical AFP staining intensity was an independent risk factor for prognosis of HAS. Conclusions: As a special type of GAC, HAS is prone to developing liver metastasis with poor prognosis. Based on the higher missed diagnosis rate of HAS, it is suggested to make 2nd cancer histopathological diagnosis including immunohistochemical detection of AFP and GPC3 for GAC patients with significantly increased serum AFP level. The intensity of immunohistochemical AFP staining is an independent risk factor for the prognosis of patients with HAS. VEGF, EGFR and PD-1 / PDL-1 may be potential therapeutic targets of HAS, which is worth further study.

Tumor Budding and Prognosis in Gastric Adenocarcinoma.

Tumor budding has been associated with poor prognosis in several cancer types, but its significance in gastric cancer is unknown. The aim of this study was to assess the prognostic significance of tumor budding in gastric adenocarcinoma, and its main histologic types. Some 583 gastric adenocarcinoma patients who underwent surgery in Oulu University Hospital during the years 1983-2016 were included in this retrospective cohort study. Tumor budding was counted per 0.785 mm fields from the slides originally used for diagnostic purposes. Patients were divided into low-budding (<10 buds) and high-budding (≥10 buds) groups. Tumor budding was analyzed in relation to 5-year survival and overall survival. Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders. Determining tumor budding was difficult in diffuse-type cancer due to the uncohesive growth pattern of these tumors. Patients with high tumor budding had worse 5-year survival compared with patients with low tumor budding (adjusted HR, 1.55; 95% CI, 1.20-2.01). In intestinal-type adenocarcinomas, the high-budding group had significantly poorer 5-year survival compared with the low-budding group (adjusted HR, 1.57; 95% CI, 1.14-2.15). There were no differences in 5-year survival between the budding groups in the diffuse type adenocarcinoma. In conclusion, high tumor budding is an independent prognostic factor in gastric adenocarcinoma, but its value is limited to the intestinal type of gastric adenocarcinoma. In diffuse type gastric adenocarcinoma, the assessment of tumor budding is hardly feasible, and it does not have prognostic relevance.