Diffuse Histological Type Research Articles

Safety and efficacy of first-line nivolumab plus chemotherapy for HER2-negative advanced gastric cancer in real-world patients: Updated analysis.

341 Background: Based on the results of CheckMate-649 and ATTRACTION-4, nivolumab plus chemotherapy is the new standard of care as first-line treatment for patients with HER2-negative advanced gastric cancer (AGC) regardless of PD-L1 combined positive score (CPS) status in Japan. This study aimed to evaluate the safety and efficacy of this regimen in real-world patients with HER2-negative AGC with a longer follow-up. Methods: In this single-institutional retrospective study, patients with HER2-negative AGC who were treated with first-line nivolumab plus chemotherapy between September 2021 and April 2024 were consecutively enrolled and evaluated. Early tumor shrinkage (ETS) was defined as ≥20% tumor reduction at 8 ± 2 weeks. Results: Of 151 patients, median age was 66 years (range, 27–83); 58% were male; 81% had diffuse-type histology; the peritoneal metastasis was seen in 60%; PD-L1 CPS of <1, 1≤/<5, 5≤ was 30%/41%/29%; deficient mismatch repair and/or high microsatellite instability was 7%. At a median follow-up of 14.2 months, the median overall survival (OS) and progression-free survival (PFS) were 21.7 months (95% confidence interval [CI] 14.4–26.2) and 7.7 months (6.4–9.6), respectively. The median OS according to CPS subgroups (<1, 1≤/<5, 5≤) were 21.7 / not reached (NR) /25.0 months, respectively (log-rank P = 0.55). In patients with measurable lesions at baseline according to RECIST ver 1.1, the objective response rate and disease control rate were 62% and 87%, respectively, with a complete response rate of 10%. In the exploratory analysis by ETS, both median PFS and OS were significantly longer in the ETS group compared to the non-ETS group (PFS, NR vs. 6.2 months; hazard ratio [HR] 0.35; 95% CI 0.17–0.68; P = 0.001) (OS, 25.0 vs. 11.7 months; HR 0.44; 95% CI 0.20–0.93; P = 0.03). The immune-related adverse events (irAEs) of any grade were observed in 26% (grade 3–4 irAEs 12%), whereas no treatment-related death was documented. Conclusions: The updated analysis suggests that first-line nivolumab plus chemotherapy provides benefit in real-world patients with HER2-negative AGC regardless of PD-L1 status, and suggests that the magnitude of ETS may predict a significant impact on the duration of survival.

Early gastric cancer of young patients treated by endoscopic submucosal dissection: focusing on the different characteristics and prognosis of elderly patients.

A small portion of patients are diagnosed with early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at a young age. However, their clinical outcomes are rarely known. We investigated to identify the feasibility and clinical outcomes of ESD for EGC focusing on young patients. We analyzed the clinical characteristics and outscomes of patients who had undergone ESD for the treatment of EGC at < 50years of age. We enrolled patients who had been diagnosed with EGC and had undergone ESD between 2006 and 2020. We divided them by age as follows: ≤ 50 and > 50years into the young age (YA) and other age (OA) groups, respectively. Altogether, 1681 patients underwent ESD for EGC (YA group: 124 [7.4%], OA group: 1557 [92.6%]). The YA group had less severe atrophy and more undifferentiated (37.1% vs. 13.9%, P < 0.001) and diffuse type (25% vs. 7.7%, P < 0.001) histology. The curative resection rate was not significantly different between the groups. However, among 1075 patients who had achieved curative resection and had been followed-up for > 12months, the YA group had a lower incidence of MGN (5.2% vs. 17.5%, P = 0.004) and MGC (2.6% vs. 10.9%, P = 0.019) than those exhibited by the OA group. The YA group was a significant negative predictor of MGN (odds ratio [OR]: 2.983, 95% confidence interval [CI] 1.060-8.393, P = 0.038), and marginally negative predictor in MGC (OR: 3.909, 95% CI: 0.939-16.281, P = 0.061). ESD is a favorable and effective therapeutic modality for EGC patients aged < 50years, once curative resection is achieved.

Clinicopathological Characteristics and Risk Factors of Young-Onset Gastric Carcinoma: A Systematic Review and Meta-analysis.

The characteristics of gastric carcinoma in young individuals differ from that in older individuals. We conducted a systematic review and meta-analysis to explore the clinicopathological features and risk factors associated with young-onset (younger than 50 years) gastric carcinoma. We searched for studies published between January 1, 1990, and September 1, 2023, on patients with young-onset gastric carcinoma in PubMed, EMBASE, Web of Science, and MEDLINE to explore clinicopathological characteristics among this specific patient group. Extracted information included the proportion of patients with symptoms or family history of gastric cancer, tumor location, and histological features such as Lauren or World Health Organization histological classification and degree of differentiation. Additional analyses were conducted on risk factors such as positive family history, Helicobacter pylori infection, or high-risk nutritional or behavioral factors. The estimates were derived using random or fixed-effect models and included subgroup analyses based on different sex and age groups. This study was registered in PROSPERO (CRD42023466131). We identified 5,696 records, 1,292 were included in the quality assessment stage. Finally, 84 studies from 18 countries or regions including 89,447 patients with young-onset gastric carcinoma were included. Young-onset gastric carcinoma has slight female predominance (53.7%, 95% confidence interval [CI]: 51.6-55.7%), with most having symptoms (87.0%, 95% CI: 82.4%-91.7%). Family history was reported in 12.1% (95% CI: 9.5%-14.7%). H. pylori infection was detected in 60.0% of cases (95% CI: 47.1%-72.8%). Most of these carcinomas were in the non-cardia region (89.6%, 95% CI: 82.4%-96.8%), exhibiting Lauren diffuse-type histology (71.1%, 95% CI: 66.8%-75.3%) and poor/undifferentiated features (81.9%, 95% CI%: 79.7-84.2%). A positive family history of gastric cancer was the most important risk factor associated with the development of gastric carcinoma in young individuals (pooled odds ratios 4.0, 95% CI: 2.8-5.2), followed by H. pylori infection (odds ratio 2.3; 95% CI: 1.4-3.2) and dietary and other lifestyle risk factors. Young-onset gastric carcinoma exhibits specific clinicopathological characteristics, with positive family history being the most important risk factor. Most of the patients were symptomatic at diagnosis. These findings could help to inform future strategies for the early detection of gastric carcinoma among young individuals.

Risk Factors for Lymph Node Metastasis in a Western Series of Patients with Distal Early Gastric Cancer.

Background: Assessment of potential lymph node metastasis is mandatory in the appropriate treatment of early gastric cancers. This study analysed factors associated with lymph node metastasis to identify differences between node-negative and node-positive patients and between T1a and T1b cancers. Methods: The clinicopathological features of 129 early gastric cancer patients who had undergone radical gastrectomy were analysed to identify predictive factors for lymph node metastasis. Results: Lymph node metastasis was detected in 76 (59.0%) patients. Node-positive patients were younger (58.1 ± 11.3 years) than those without metastasis (61.9 ± 9.6 years, p = 0.02). Greater tumour sizes were observed in patients with lymph node metastasis (3.6 ± 1.0 cm) compared to node-negative patients (1.9 ± 0.5 cm, p = 0.00001). Depressed form, ulceration, diffuse histological type, and undifferentiated lesions were more frequent in node-positive patients than in the node-negative group. Tumour size > 3.0 cm showed a correlation with lymph node metastasis in both T1a (p = 0.0001) and T1b (p = 0.006) cancer. The male sex (p = 0.006) had a significant correlation with lymph node metastasis in T1a cancer. Depressed appearance (p = 0.02), ulceration (p = 0.03), differentiation (p = 0.0001), diffuse type (p = 0.0002), and lower third location (p = 0.005) were associated with lymph node metastasis in T1b cancer. Conclusions: Tumour size > 3 cm, undifferentiated lesions, ulceration, diffuse type, lower third location, and submucosal invasion are risk factors for lymph node metastasis in early gastric cancer.

Enhanced epithelial-mesenchymal transition signatures are linked with adverse tumor microenvironment, angiogenesis and worse survival in gastric cancer.

Epithelial-mesenchymal transition (EMT) is a crucial mechanism that facilitates cancer cell metastasis. Despite its importance, the clinical significance of EMT in gastric cancer (GC) patients has yet to be clearly demonstrated. For gauging the extent of EMT in GC, we employed gene set variation analysis to score 807 patient samples from two large cohorts: TCGA and GSE84437. In both cohorts, EMT high GC showed a significant association with worse overall survival (hazard ratio (HR) = 1.74, p = 0.011 and HR = 2.01, p < 0.001, respectively). This association was stronger when considering the EMT signature score compared to the individual expressions of EMT-related genes (CDH1, CDH2, VIM, and FN1). While the EMT signature level did not differ among various cancers, high EMT signature specifically correlated with survival in GC alone. Mucinous and diffuse histological types exhibited higher EMT levels compared to others (p < 0.001), and the EMT signature level was correlated with tumor depth and AJCC stage (all p < 0.001). Interestingly, the EMT score was an independent factor for overall and disease-specific survival (multivariate; p = 0.006 and 0.032, respectively). EMT high GC displayed a lower fraction of Th1 cells and a higher fraction of dendritic cells, M1 macrophages and several stromal cells. EMT high GC exhibited an inverse correlation with cell proliferation-related gene sets. While they significantly enriched multiple pro-cancerous gene sets, such as TGF-β signaling, hypoxia, and angiogenesis. The presence of EMT signature in a bulk tumor was linked to TGF-β signaling, hypoxia, and angiogenesis, and was also associated with poorer survival outcomes in GC patients.

Clinical outcomes of early gastric cancer resected by endoscopic submucosal dissection at young age.

314 Background: A small portion of patients are diagnosed as early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at young age, however, their clinical outcomes are rarely known. We investigated clinical characteristics and outcomes of patients who underwent ESD for treatment of EGC at age under 50. Methods: We enrolled patients who were diagnosed as EGC and underwent ESD during 2006 and 2020. We divided them either for young age (YA) group if age ≤ 50 years and other age (OA) group if &gt; 50 years. Results: We enrolled 1,349 patients (YA group: 105 patients [7.8%], OA group: 1244 [92.2%]). Compared with OA group, YA group contained more female patients (36.2 vs. 26.5%, P= 0.033), their tumor was located at middle third (41.0 vs. 29.6%, P= 0.006) and was depressed (40.0 vs. 28.8%, P= 0.001), and had more undifferentiated (30.5 vs. 12.1%, P&lt; 0.001) and diffuse type (22.9 vs. 7.3%, P&lt; 0.001) histology. However, synchronous tumor was less frequent in YA group (2.9 vs. 12.4%, P= 0.001). When we sorted 884 patients who achieved curative resection and were followed-up longer than 12 months, Kaplan-Meier analysis showed that metachronous neoplasm (dysplasia or cancer) and metachronous cancer were significantly less in YA group than OA group ( P= 0.003 and 0.013, respectively), however, local recurrence was not significantly different between two groups. Conclusions: ESD is a favorable and effective therapeutic modality for EGC patients who are aged under 50, once curative resection is achieved.

Early-onset gasrtric cancer (review)

Objective. Early-onset gastric cancer (EOGC) constitutes a serious medical and social problem. Early-onset gastric cancer accounts for approximately 6% of all malignant epithelial neoplasms.Material and Methods. We reviewed retrospective and prospective randomized trials using Medline and Elibrary databases.Results. The applied significance of the molecular genetic classifications consist in the formation of groups for evaluating prognosis of the disease using multifactorial analysis. This classification indicates that EOGC diagnosed at a locally advanced stage and primary dissemination is most often caused by GS (TCGA) and MSS/EMT(ACRG) subtypes and is characterized by mutations in CDH1, RhoA, CLDN18-ARHGAP genes. These changes are accompanied by the prevalence of diffuse histological type of gastric cancer according to the Lauren classification and ulcerated or infiltrative type according to the Borrmann classification (type III and IV) with the presence of high-grade adenocarcinoma with a signet ring cell component.Conclusion. Considering the aggressiveness of gastric cancer in young patients, who more frequently present with locally advanced and metastatic disease at the time of diagnosis, there is a need for increased cancer alertness among physicians of other specialties, early endoscopic controls to detect cancer at early stages and benefit from both surgical and multimodal treatment.

Diffuse-Type Histology Is Prognostic for All Siewert Types of Gastroesophageal Adenocarcinoma.

The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

OGC P19 Peritoneal metastases from gastric cancer in a nationwide cohort: incidence, treatment and survival

Abstract Background The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these patients using population-based data. Methods Patients diagnosed with gastric cancer in 2015-2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Results Of 2147 patients with gastric cancer, 656 (31%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n=675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs. 18% respectively, p&amp;lt;0.001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs. 2.3 months respectively, p=0.731). Conclusions Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3-year follow-up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated.

Clinicopathologic features and prognostic value of claudin 18.2 overexpression in patients with resectable gastric cancer

Claudin 18.2 has emerged as a promising therapeutic target in gastric cancer based on phase 3 studies. However, clinicopathologic features associated with claudin 18.2 overexpression have not been comprehensively studied specifically for patients with resectable gastric cancer. This retrospective study included 299 patients with stage I–III resectable gastric cancer who underwent curative surgical resection. Possible associations between claudin 18.2 overexpression (moderate-to-strong expression in ≥ 75% by the 43-14A clone) and clinicopathologic features and survival outcomes were analyzed. There were 90 (30.1%), 96 (32.1%), and 113 (37.8%) patients with stage I, II, and III disease, respectively. Claudin 18.2 overexpression was noted in 139 out of 299 patients (46.5%). Claudin 18.2 overexpression was associated with a younger age, a lower invasion depth limited to the mucosa/submucosa, and less frequent lymphovascular invasion. Claudin 18.2 overexpression was also associated with Borrmann type 4 among patients with advanced gastric cancer and the diffuse histological type. Claudin 18.2 overexpression was not an independent factor for survival outcomes. In conclusion, claudin 18.2 was overexpressed in almost half of resectable gastric cancer patients. Claudin 18.2 overexpression was associated with some clinicopathological characteristics, but was not an independent prognostic factor in a localized setting.

Peritoneal metastases from gastric cancer in a nationwide cohort: Incidence, treatment and survival.

The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these patients using population-based data. Patients diagnosed with gastric cancer in 2015 to 2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Of 2206 patients with gastric cancer, 741 (34%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n = 675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs 18%, respectively, P < .001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs 2.3 months, respectively, P = .731). Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3-year follow-up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated.

Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer.

Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11-1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98-1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06-2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60-0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46-0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.

Aggressive Histology and Extensive Metastasis Characteristic of Very Young Gastric Cancer (Less Than 30 Years): A Retrospective Clinical Audit

Objectives Gastric cancer (GC) is an aggressive disease and remains one of the most common causes of cancer-related mortality worldwide. Incidence of gastric cancer in young (GCY) varies between 2 and 8%. GCY faces unique challenges such as biological variation, diagnosis at an advanced stage, issues related to fertility preservation, and psychosocial considerations. This study aimed to find the differences in clinical characteristics and treatment outcomes of GCY compared to gastric cancer in older adults (GCO). Material and Methods This is a retrospective study from a tertiary care center. We screened records from 2015 to 2020, identified 33 records of GCY (less than 30 years), and compared the data with GCO (greater than 30 years) during 2015 and 2018. Results We identified 33 patients with GCY with a median age of 28 years (21–30) and a female to male ratio of 2:1. In GCY, 60% of patients presented with metastatic disease. Diffuse-type histology was more common in the GCY than in GCO (66.7% vs. 41.7%, p = 0.001). In patients with metastasis, multiple metastases were common in GCY compared to GCO (45% vs. 15%, p = 0.003). The median duration of follow-up for all patients was 27 (24–29) months. In GCY, the median OS was not reached for patients treated with curative intent, and it was 13 months for those treated with palliative intent. Conclusion The incidence of GCY in our study was like the western literature. Female patients with aggressive diffuse histology and multiple extensive metastases were characteristic of GCY. The survival outcomes were identical to GCO.

Current prognostic factors of advanced gastric cancer patients treated with chemotherapy: real world data from a Japanese 12 institutions.

Understanding the prognostic factors of advanced gastric cancer before starting chemotherapy is important to determine personalized treatment strategies. However, the details of chemotherapy and the prognosis of advanced gastric cancer patients have changed with the time and environment. The aim of this study was to understand the current reality of chemotherapy and to estimate the prognostic factors of advanced gastric cancer patients before starting chemotherapy at multiple centers. This includes specialized cancer hospitals and community hospitals, with the latest data under the Japanese insurance system. We evaluated the clinical parameters and treatment details of 1025 patients who received systemic chemotherapy for unresectable advanced gastric cancer from 2012 to 2018 at 12 institutions in Japan. Prognostic factors were analyzed using the Cox proportional hazards regression model. As of April 2021, 953 (93%) patients had died, while 72 (7%) patients survived. The median overall survival and progression-free survival of first-line chemotherapy was 11.8months (95% confidence interval, 10.8-12.3months) and 6.3months (95% confidence interval, 5.9-6.9months), respectively. Multivariate analysis revealed eight prognostic factors: age<40years, performance status ≥2, no gastrectomy, diffuse histological type, albumin <3.6, alkaline phosphatase ≥300, creatinine ≥1.0 and neutrophil-to-lymphocyte ratio>3.0. Patients using trastuzumab showed better survival than patients without (16.1months vs. 11.1months; P=0.0005). We identified eight prognostic factors for patients with advanced gastric cancer undergoing Japanese standard chemotherapy. Our results will help clinicians develop treatment strategies for every patient.

Exploring the Genetic Diversity of Epstein-Barr Virus among Patients with Gastric Cancer in Southern Chile.

The Epstein-Barr virus (EBV) has been associated with gastric cancer (GC), one of the deadliest malignancies in Chile and the world. Little is known about Chilean EBV strains. This study aims to investigate the frequency and genetic diversity of EBV in GC in patients in southern Chile. To evaluate the prevalence of EBV in GC patients from the Chilean population, we studied 54 GC samples using the gold standard detection method of EBV-encoded small RNA (EBER). The EBV-positive samples were subjected to amplification and sequencing of the Epstein-Barr virus nuclear protein 3A (EBNA3A) gene to evaluate the genetic diversity of EBV strains circulating in southern Chile. In total, 22.2% of the GC samples were EBV-positive and significantly associated with diffuse-type histology (p = 0.003). Phylogenetic analyses identified EBV-1 and EBV-2 in the GC samples, showing genetic diversity among Chilean isolates. This work provides important information for an epidemiological follow-up of the different EBV subtypes that may cause GC in southern Chile.

A Novel Hematological Inflammation-Nutrition Score (HINS) and Its Related Nomogram Model to Predict Survival Outcome in Advanced Gastric Cancer Patients Receiving First-Line Palliative Chemotherapy.

This study aims to construct a novel hematological inflammation-nutrition score (HINS) and investigate its prognostic value in patients with advanced gastric cancer (AGC). We investigated the risk stratification performance of HINS and developed a HINS-based nomogram model to predict overall survival by combining traditional predictors. We conducted a retrospective study on 812 AGC patients who received first-line platinum- or fluoropyrimidine-containing chemotherapy at The First Affiliated Hospital of Zhengzhou University Hospital between 2014 and 2019. Patients were randomly divided into a training cohort (N=609) and a validation cohort (N=203). HINS (0-2) was constructed based on a pre-chemotherapy systemic immune-inflammation index (SII) and albumin (ALB). Prognostic factors were screened by univariate and multivariate COX proportional regression models. Significant factors were used to construct a nomogram model. Internal validation was performed by calibration curves, time-dependent receiver operating characteristics (ROC) curves, and decision curve analysis (DCA), evaluating its prediction consistency, discrimination ability, and clinical net benefit. HINS was constructed based on SII and ALB. HINS showed a better stratification ability than JCOG prognostic index, with significant differences between groups. Multivariate analysis showed that ECOG ≥1 (HR: 1.379; P=0.005), Stage IV (HR: 1.581; P <0.001), diffuse-type histology (HR: 1.586; P <0.001), number of metastases ≥2 (HR: 1.274; P=0.038), without prior gastrectomy (HR: 1.830; P <0.001), ALP ≥ULN (HR: 1.335; P=0.034), HINS (P <0.001) were independent factors of OS. We successfully established a HINS-based nomogram model that showed a strong discriminative ability, accuracy, and clinical utility in training and validation cohorts. HINS shows a superior risk stratification ability, which might be a potential prognostic biomarker for AGC patients receiving palliative first-line palliative chemotherapy. The HINS-based nomogram model is a convenient and efficient tool for managing prognosis and follow-up treatments.

Clinicopathological Significance and Prognostic Role of Her2neu Protein Expression in Patients with Carcinoma Stomach: A Prospective Study from Northern India

Background and Aims Gastric cancer is the third most common cause of cancer-related mortality worldwide after lungs and colorectum. Although controversial, Her2neu overexpression by immunohistochemistry is usually associated with poor prognosis in patients with carcinoma stomach. We conducted a prospective study to evaluate the prognostic role of Her2neu and its correlation with clinical, pathologic type, and stage of the disease. Methods A prospective study was performed on paraffin blocks of 111 gastric cancer specimens (88 patients were biopsy specimens and 23 were gastrectomy specimens). The paraffin blocks were processed for Her2neu receptor immunohistochemical staining and fluorescence in situ hybridization, and scoring was done. Results Her2neu overexpression was detected in 30 out of 111 (27%) patients. The mean age was 57.68 ± 12.82 years, with males constituting two-thirds of total patients. Tobacco addiction was found in 44% of the patients and smoking in 33% of the patients. Her2neu expression was similar in Lauren's intestinal and diffuse histologic type; however, proximal gastric tumors overexpressed Her2neu as compared with distal tumors. Her2neu 2+ or 3 + (odds ratio: 2.52, 95% CI: 1.61–3.95, p = 0.001) was the only independent predictor of survival in gastric cancer patients. Kaplan–Meir survival analysis showed that the survival of gastric cancer patients with Her2neu overexpression (Her2neu 2+ or 3 + ) was significantly lower than that of those with Her2neu nonexpression (p = 0.001). Conclusion Her2neu positivity was a significant predictor of mortality in patients with carcinoma stomach, and Her2neu overexpression was associated with a lower overall survival rate compared with Her2neu nonexpression.

Association between INDELs in MicroRNAs and Susceptibility to Gastric Cancer in Amazonian Population.

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk.

Tertiary lymphoid structures and gastric cancer prognosis.

Tertiary lymphoid structures (TLSs) are part of immune response against cancer. Their high density and high diameter have been shown to be associated with prognosis in different cancer types. The aim of this study was to examine the prognostic significance of TLS density and diameter in gastric cancer and reproducibility of their assessments. TLS densities and maximal TLS diameter were assessed from hematoxylin-eosin (HE) stained slides of 721 surgically treated gastric cancer patients from two hospitals in Finland. Mortality hazard ratios (HRs) for TLS densities and maximal TLS diameter were analyzed. TLS densities and maximal TLS diameter were assessed with moderate interobserver agreement (Cohen's kappa 0.50-0.62). Maximal TLS density was not associated with survival (adjusted HR 0.85, 95% CI 0.70-1.02) and neither was hotspot TLS density (adjusted HR 0.85, 95% CI 0.70-1.02). High maximal TLS diameter was associated with longer survival in overall study population (adjusted HR 0.74, 95% CI 0.61-0.89) and in diffuse type subgroup (adjusted HR 0.65, 95% CI 0.50-0.85). In conclusion, high maximal TLS diameter is associated with improved survival in gastric cancer and can be assessed from HE-stained slides. Its prognostic value might be limited to diffuse histological type.

Extent of Surgical Resection for Gastric Cancer: The Safety Distance Between the Tumor and the Proximal Resection Margin.

A potentially curative treatment scheme for gastric cancer is considered futile without a proper surgical resection. An oncological, surgical resection for gastric cancer prerequisites a proper resection of the stomach, and a D2 lymph node dissection followed by reconstruction of the gastrointestinal tract continuity. Recently, as the favorable impact of organ preserving surgery on functional outcomes has been increasingly appreciated; distal gastrectomy represents a valid alternative to total gastrectomy provided that the proper oncological principles are not violated. However, the appropriateness of distal gastrectomy as a valid type of resection becomes synonymous with achieving a negative proximal resection margin. The purpose of the present study was to assess the optimal distance between the tumor and the resection margin in a gastrectomy with curative intent, performed for gastric cancer, by reviewing the relevant literature. Having in mind, the well documented discrepancy between the gross and the pathologic boundaries of the tumor, pitfalls might be encountered. Current published guidelines have used a "safety distance" i.e., >4 or 5 cm between the proximal macroscopic tumor border and the proximal resection margin in order to guarantee a negative resection margin on pathology. An increased distance of safety is currently proposed in high-risk tumors such as tumors of the diffuse histological type.