Current evidence on the surgical and oncological safety of laparoscopic surgery in patients with Borrmann type IV (B-IV) advanced gastric cancer (AGC) remains insufficient. This study aimed to compare the surgical and prognostic outcomes of laparoscopic gastrectomy (LG) and open gastrectomy (OG) in patients with B-IV AGC.

Patients with primary B-IV gastric cancer who underwent LG or OG between 2003 and 2019 were retrospectively analyzed. We conducted 1:1 propensity score matching using covariates including sex, age, body mass index, operation type, clinical T and N stages, pathological TNM stage, tumor size, and tumor location. Surgical outcomes, postoperative complications, 5-year survival and recurrence outcomes, and risk factors for peritoneal recurrence were compared between the two groups.

Of 401 patients enrolled, 106 from each of the LG and OG groups were matched, with all standardized differences < 0.1. The LG had significantly fewer wound infections (P = 0.029), intra-abdominal abscesses (P = 0.035) and a lower peritoneal recurrence rate (5-year cumulative incidence: 48.8% vs. 62.8%, P = 0.032; hazard ratio, 0.66; 95% confidence interval, 0.45-0.96) compared to the OG group, along with a trend toward improved 5-year overall survival (LG vs. OG: 37.0% vs. 26.2%, P = 0.174; hazard ratio, 0.78; 95% confidence interval, 0.55-1.11). Multivariate analyses revealed a 32.6% decrease in the hazard ratio for peritoneal recurrence in the LG group (P = 0.048).

LG significantly reduced peritoneal recurrence with fewer wound and intra-abdominal infectious complications in patients with B-IV AGC.

Adolescents and young adults (AYA) with germline CDH1 variants are at risk of overtreatment when precancer lesions are detected with endoscopic screening. We characterize diffuse-type gastric cancer prevalence and survival in AYA managed with prophylactic total gastrectomy (PTG) or endoscopic surveillance.

Prospective cohort study of 188 individuals aged 39 and younger enrolled from January 27, 2017, to May 1, 2023. Clinicopathological data, prevalence of early gastric signet ring cell (SRC) lesions, advanced gastric cancer diagnoses, and cancer-specific survival were measured.

Among 188 AYA patients, 104 chose surveillance and 67 pursued PTG for management of elevated gastric cancer risk. AYA who enrolled early in the study period and had SRC lesions detected on preoperative endoscopy were more likely to elect for PTG compared with surveillance. SRC lesions were detected on preoperative endoscopy in 48% of patients who subsequently had PTG, and yet nearly all (93%, 62/67) had multifocal SRC (pT1aN0) on final pathology. Median age at enrollment (30 vs 31 years, P = .21), biological sex (P = .17), and median number of family members with gastric cancer (3 vs 4, P = .14) were not different between groups. No patients under surveillance developed advanced cancer or developed cancer recurrence after PTG with a median follow-up of 2.5 years (IQR = 1.6-4.0) from initial endoscopy.

Cancer-specific outcomes were not different in AYA who harbored SRC and were managed with surveillance or PTG. Lack of cancer-specific deaths and low prevalence of advanced gastric cancer underscore the risk of overtreatment of SRC lesions and suggest that active surveillance is warranted.

Identifying therapeutic targets for signet ring cell carcinoma (SRCC) of the colon and rectum is a clinical challenge because of the lack of patient-derived organoids (PDO) or patient-derived xenografts (PDX). To address this unmet need, we present a robust method for establishing PDO and PDX models. We demonstrate that these models identify novel therapeutic strategies targeting therapy resistance and peritoneal metastasis.

We derived nine PDO and PDX models from patients with colorectal SRCC. Detailed histopathologic characterization confirmed the fidelity of these models to the original tumors. Drug sensitivity assays were conducted in vitro and in vivo to assess the therapeutic efficacy and impact on peritoneal metastasis. An RNA sequencing analysis was performed to identify critical pathways contributing to therapy resistance and metastatic progression.

We successfully developed and characterized PDO and PDX models from nine patients with SRCC. The SRCC PDO and PDX models exhibited histopathologic features consistent with those of the original tumors, including high mucin content and eccentric nuclei. They demonstrated increased sensitivity to FOLFIRI combined with paclitaxel or vincristine, reducing peritoneal metastasis. RNA sequencing analysis revealed the upregulation of autophagy genes in SRCC. Treatment with chloroquine alone resulted in decreased tumor growth and peritoneal metastasis.

Our study establishes PDO and PDX models as robust platforms for studying SRCC and identifying potential therapeutic strategies. Combining FOLFIRI with paclitaxel/vincristine or chloroquine alone inhibits tumor growth and prevents peritoneal metastasis, showing promise for clinical translation. These findings suggest that combining FOLFIRI with intraperitoneal paclitaxel warrants further investigation in phase I clinical trials for patients with SRCC.

Large type 3 (≥ 8 cm) and type 4 gastric cancers (GCs) have poor prognoses and necessitate multidisciplinary treatment. A multi-institutional phase II study (OGSG1902) was conducted to assess the efficacy and safety of neoadjuvant chemotherapy (NAC) with docetaxel, oxaliplatin, and S-1 (DOS) in these patients.

Patients with large type 3 or type 4 GC without distant metastasis, except for positive peritoneal cytology (CY), were enrolled. Patients received three courses of neoadjuvant DOS therapy (docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 via intravenous infusion, and S-1 80 mg/m2 orally for 14 days, repeated every 3 weeks) followed by gastrectomy. After R0 resection, adjuvant docetaxel/S-1 therapy was administered for 1 year.

From October 2019 to February 2022, 48 patients were enrolled. NAC was completed in 91.7% of patients. The R0 resection rate was 89.6%. The pathological response rate (Grade 1b-3) was 66.7%. Among patients with measurable lesions, the response rate was 50.0%. The CY-negative conversion rate was 80.0%, and the protocol completion rate was 45.8%. Grade 3 or 4 adverse events during NAC, including neutropenia and appetite loss, occurred in 37.5% of patients. Major postoperative complications (Clavien-Dindo Grade IIIa or higher) were observed in 2.1% of patients.

NAC with DOS for large type 3 or type 4 GC followed by gastrectomy demonstrated promising efficacy, high pathological response rates, and an acceptable toxicity profile. Further evaluation of long-term survival outcomes is ongoing.

In recent years, the global prevalence of gastric cancer (GC) has witnessed a progressive decrease, accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma (GSRCC). As precision medicine concepts progress, GSRCC, a distinct sub-type of GC, has drawn considerable attention from researchers. However, there still persist some controversies regarding the associated research findings.

To summarize the current obstacles and potential future directions for research on GSRCC.

To begin with, all literature related to GSRCC published from January 1, 2004 to December 31, 2023 was subjected to bibliometric analysis in this article. Additionally, this paper analyzed the research data using CiteSpace, GraphPad Prism v8.0.2, and VOSviewer, which was obtained from the Web of Science Core Collection database. The analysis results were visually represented.

This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC, including cited references, authors, journals, countries, institutions, and keywords. The popular keywords and clusters contain "prognosis", "survival", "expression", "histology", and "chemotherapy".

The prognosis, precise definition and classification, as well as chemoresistance of GSRCC, continue to be crucial areas of ongoing research, whose directions are closely tied to advancements in molecular biology research on GSRCC.

Recent research suggests that neoadjuvant chemotherapy is not effective for gastric cancer with signet ring cells.

The present study performs a scoping review of research that seeks to determine whether neoadjuvant chemotherapy is more effective than upfront surgery in the survival of locally advanced signet ring gastric adenocarcinoma.

Online databases such as Pubmed, scopus and embase were used to identify articles from the last 20 years that used survival, as an initial or secondary outcome variable, after upfront surgery or neoadjuvant chemotherapy as initial treatment in locally advanced gastric signet ring cells adenocarcinoma.

After a systematic selection process, five primary studies were selected that evaluated neoadjuvant chemotherapy compared to primary surgery.

Neoadjuvant chemotherapy does not appear to have greater benefit than initial surgery in gastric adenocarcinoma with locally advanced sign ring cells, it is necessary to define which is the most appropriate qt scheme for adenocarcinoma with sign ring cells, clinical trials type studies are required to improve the evidence. Finally, a national clinical practice guide is required as an interpretative map for the management of gastric cancer which may be appropriate as a first step to know the reality.

This study reviews the findings of a recent study by Li et al, which demonstrated that perioperative chemotherapy benefits patients with diffuse-type gastric cancer compared to surgery alone. Despite potential biases, the study supports the inclusion of perioperative chemotherapy in treatment guidelines. Neoadjuvant and adjuvant chemotherapy may also provide similar survival outcomes, allowing for flexible treatment planning.

Signet ring cell (SRC) gastric carcinoma is traditionally associated with a poor prognosis. However, the literature has presented contradictory results. Linear models are the standard statistical tools typically used to study these conditions. However, machine learning (ML) models have the potential to replace or even outperform linear models in terms of predictive performance.

This study analyzed 608 patients diagnosed with gastric cancer at our institution. The analysis compared traditional linear models and ML models. Variables examined included demographic data, presence of an SRC component, lymph nodes (LNs) resected and affected (ratio), stage of the disease, body mass index, pathologic features, type of surgery, tumor location, and carcinoembryonic antigen levels to evaluate their influence on 5-year mortality and 2-year recurrence rates.

SRC carcinoma was associated with poorer prognosis in terms of 5-year overall survival than non-SRC carcinoma. In addition, SRC exhibited higher rates of LN metastasis and a higher LN ratio (resected/affected) and was more prevalent in younger patients (<65 years). However, SRC was not an independent factor in the multivariate analysis. Linear models showed worse predictions for 5-year mortality and 2-year recurrence than ML models. The ML models did not consider the presence of the SRC component as an important variable.

SRC gastric carcinoma continues to present an uncertain prognosis. ML models can evaluate prognosis more accurately than traditional linear models. Large-scale studies using ML algorithms are necessary to elucidate the predictive potential of such models.

This study aimed to predict metastasis risk and identify prognostic factors of gastrointestinal signet ring cell carcinoma (SRCC) using data from the SEER database, the largest cancer dataset in North America.

Data were obtained from the SEER database, covering 17 cancer registries from 2004 to 2020. Demographic and clinical data included sex, age, race, tumor location, size, pathological grade, stage, overall survival time, and treatment modalities. Statistical analyses were conducted using SPSS and R software. Propensity Score Matching (PSM) ensured comparable baseline characteristics between gastric cancer (GC) and colorectal cancer (CRC) groups. LASSO regression analysis identified predictors of metastasis, leading to the construction of predictive models using the lrm function in R. Nomograms were visualized with the "rms" package and assessed via ROC curves, calibration curves, and decision curve analysis (DCA). Cox regression analyses identified prognostic indicators for overall survival (OS), and Kaplan-Meier curves compared OS between high-risk and low-risk groups.

From 2004 to 2020, 7680 SRCC patients were identified, including 4980 GC and 2700 CRC patients. CRC patients were older and had larger tumors, higher staging, and worse differentiation. Nomograms demonstrated good discriminative ability, with AUCs of 0.704 and 0.694 for GC, and 0.694 and 0.701 for CRC in training and validation cohorts, respectively. The DCA curve indicates that this predictive model has a high gain in predicting metastasis and OS.

The nomograms effectively predicted metastasis risk and OS in metastatic SRCC patients, offering clinical utility in stratifying patients and guiding treatment decisions, thereby enhancing personalized treatment approaches.

Signet ring cell carcinoma (SRCC) is defined as carcinoma composed of epithelial cells with intracytoplasmic mucin that causes peripheral displacement of the nucleus, creating a crescent-shaped morphology. It can arise in many organs; however, pure primary SRCC of the breast is very rare. The WHO classification of tumours placed SRCC of the breast under mucin-producing carcinomas; however, nowadays, it is no longer regarded as a histological variant of invasive carcinoma. To date, only few cases have been reported in the literature. This report presents a woman in her 70s with primary pure SRCC of the breast. The patient underwent right lumpectomy with sentinel lymph node dissection and was proposed adjuvant chemotherapy followed by radiotherapy and hormonal treatment. She had no disease relapse until today. The histological features and treatment approach of this rare entity are debated in light of relevant literature.

Poor prognosis in patients with distant metastasis of gastric signet ring cell carcinoma (GSRC), and there are few studies on the development and validation of the diagnosis and prognosis of distant metastasis of GSRC. The Surveillance, Epidemiology, and End Results database was used to identify patients with GSRC from 2004 to 2019. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for distant metastasis of GSRC, while univariate and multivariate Cox proportional hazard regression analysis were used to determine independent prognostic factors for patients with distant metastasis of GSRC. Two nomograms were established, and model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis. A total of 9703 cases with GSRC were enrolled, among which 2307 cases (23.78%) were diagnosed with distant metastasis at the time of diagnosis. Independent risk factors for distant metastasis included age, race, and T stage. Independent prognostic factors included T stage, chemotherapy, and surgery. The receiver operating characteristic curve, calibration curve, decision curve analysis curve, and Kaplan-Meier survival curve of the training set and validation set confirmed that the 2 nomograms could accurately predict the occurrence and prognosis of distant metastasis in GSRC. Two nomograms can serve as effective prediction tools for predicting distant metastasis in GSRC patients and the prognosis of patients with distant metastasis. They have a certain clinical reference value.

Whether patients with diffuse gastric cancer, which is insensitive to chemotherapy, can benefit from neoadjuvant or adjuvant chemotherapy has long been controversial.

To investigate whether perioperative chemotherapy can improve survival of patients with locally advanced diffuse gastric cancer.

A total of 2684 patients with locally advanced diffuse gastric cancer from 18 population-based cancer registries in the United States were analyzed.

Compared with surgery alone, perioperative chemotherapy improved the prognosis of patients with locally advanced gastric cancer. Before stabilized inverse probability of treatment weighting (IPTW), the median overall survival (OS) times were 40.0 months and 13.0 months (P < 0.001), respectively. After IPTW, the median OS times were 33.0 months and 17.0 months (P < 0.001), respectively. Neoadjuvant chemotherapy did not improve the prognosis of patients with locally advanced gastric cancer compared with adjuvant chemotherapy after IPTW. After IPTW, the median OS times were 38.0 months in the neoadjuvant chemotherapy group and 42.0 months in the adjuvant chemotherapy group (P = 0.472).

Patients with diffuse gastric cancer can benefit from perioperative chemotherapy. There was no significant difference in survival between patients who received neoadjuvant chemotherapy and those who received adjuvant chemotherapy.

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

Upper gastrointestinal (GI) signet ring cell carcinomas (SRCC) confer a poor prognosis. The benefit of operative intervention for this patient group is controversial in terms of overall survival.

To investigate factors relating to survival in patients with upper GI SRCC.

A retrospective, tertiary, single-centre review of patients who were diagnosed with oesophageal, gastroesophageal junction and gastric SRCC was performed. The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management. Secondary outcomes included assessing the relationship between demographic and histopathological factors, and survival.

One hundred and thirty-one patients were included. The one-year survival for the operative group was 81% and for the nonoperative group was 19.1%. The five-year survival in the operative group was 28.6% vs 1.5% in the nonoperative group. The difference in overall survival between groups was statistically significant (HR 0.19, 95%CI (0.13-0.30), P < 0.001). There was no difference in survival when adjusting for age, smoking status or gender. On multivariate analysis, patients who underwent surgical management, those with a lower stage of disease, and those with a lower Charlson Comorbidity Index (CCI) had significantly improved survival.

Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery. Offering surgery to a carefully selected patient group may improve the outcome for this disease.

The impact of neoadjuvant chemotherapy (nCTX) on survival and tumor response in patients with esophagogastric signet ring cell carcinoma (SRCC) is still controversial.

Two independent reviewers performed a systematic literature search in Medline, CENTRAL, and Web of Science including prospective and retrospective two-arm non-randomized and randomized controlled studies (RCTs). Data was extracted on overall survival (OS) and tumor regression in resected esophagogastric SRCC patients with or without nCTX. Survival data was analyzed using published hazard ratios (HR) if available or determined it from other survival data or survival curves. OS and histopathological response rates by type of tumor (SRCC vs. non-SRCC) were also investigated.

Out of 559 studies, ten (1 RCT, 9 non-RCTs) were included in this meta-analysis (PROSPERO CRD42022298743) investigating 3,653 patients in total. The four studies investigating survival in SRCC patients treated with nCTX + surgery vs. surgery alone showed no survival benefit for neither intervention, but heterogeneity was considerable (HR, 1.01; 95% CI, 0.61-1.67; p = 0.98; I2 = 89%). In patients treated by nCTX + surgery SRCC patients showed worse survival (HR, 1.45; 95% CI, 1.21-1.74; p < 0.01) and lower rate of major histopathological response than non-SRCC patients (OR, 2.47; 95% CI, 1.78-3.44; p < 0.01).

The current meta-analysis could not demonstrate beneficial effects of nCTX for SRCC patients. Histopathological response to and survival benefits of non-taxane-based nCTX seem to be lower in comparison to non-SRC esophagogastric cancer. However, certainty of evidence is low due to the scarcity of high-quality trials. Further research is necessary to determine optimal treatment for SRCC patients.

https://www.crd.york.ac.uk/, PROSPERO (CRD42022298743).

The clinical impact of SMARCA4 mutations (SMARCA4ms) in gastroesophageal adenocarcinoma (GEA) remains underexplored. This study aimed to examine the association of SMARCA4ms with clinical outcomes and co-occurrence with other gene mutations identified through a next-generation sequencing (NGS) panel in GEA patients.

A total of 256 patients with metastatic or recurrent GEA who underwent NGS panel profiling at the MD Anderson Cancer Center between 2016 and 2022 were included. Comparative analyses were performed to assess clinical outcomes related to SMARCA4ms. The frequency and types of SMARCA4ms and their co-occurrence with other gene mutations were also examined.

SMARCA4ms were identified in 19 patients (7.4%). These SMARCA4ms were significantly associated with non-signet ring cell subtype (p = 0.044) and PD-L1 positive expression (p = 0.046). No difference in survival between the SMARCA4m and SMARCA4-normal group was observed (p = 0.84). There were significant associations between SMARCA4ms and FANCA, IGF1R, KRAS, FANCL, and PTEN alterations. Notably, 15 of the 19 SMARCA4m cases involved SNV missense mutations, with frequent co-occurrences noted with TP53, KRAS, ARID1A, and ERBB2 mutations.

These results serve as the first comprehensive examination of the relationship between SMARCA4ms and clinical outcomes in GEA.

Diffuse type adenocarcinoma and, more specifically, signet ring cell carcinoma (SRCC) of the stomach and gastroesophageal junction (GEJ) have a poor prognosis and the value of neoadjuvant chemo(radio)therapy (nCRT) is unclear.

All patients who underwent surgery for diffuse type gastric and GEJ carcinoma between 2004 and 2015 were retrospectively included from the Netherlands Cancer Registry. The primary outcome was overall survival after surgery. Kaplan-Meier curves were plotted. Furthermore, multivariable Poisson and Cox regressions were performed, correcting for confounders. To comply with the Cox regression proportional hazard assumption, gastric cancer survival was split into two groups, i.e. <90 days and >90 days, postoperatively by adding an interaction variable.

Analyses included 2046 patients with diffuse type cancer: 1728 gastric cancers (50% SRCC) and 318 GEJ cancers (39% SRCC). In the gastric cancer group, 49% received neoadjuvant chemotherapy (nCT) and 51% received primary surgery (PS). All-cause mortality within 90 days postoperatively was lower after nCT (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.20-0.44; p < 0.001). Also after 90 days, mortality was lower in the nCT group (HR for the interaction variable 2.84, 95% CI 1.87-4.30, p < 0.001; total HR 0.29*2.84 = 0.84). In the GEJ group, 38% received nCT, 22% received nCRT, and 39% received PS. All-cause mortality was lower after nCT (HR 0.63, 95% CI 0.43-0.93; p = 0.020) compared with PS. The nCRT group was removed from the Cox regression analysis since the Kaplan-Meier curves of nCRT and PS intersected. The results for gastric and GEJ carcinomas were similar between the SRCC and non-SRCC subgroups.

For gastric and GEJ diffuse type cancer, including SRCC, nCT was associated with increased survival.

Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy.

A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS.

The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34).

At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer.

Mucin glycans are an important component of the mucus barrier and a vital defence against physical and chemical damage as well as pathogens. There are 20 mucins in the human body, which can be classified into secreted mucins and transmembrane mucins according to their distributions. The major difference between them is that secreted mucins do not have transmembrane structural domains, and the expression of each mucin is organ and cell-specific. Under physiological conditions, mucin glycans are involved in the composition of the mucus barrier and thus protect the body from infection and injury. However, abnormal expression of mucin glycans can lead to the occurrence of diseases, especially cancer, through various mechanisms. Therefore, targeting mucin glycans for the diagnosis and treatment of cancer has always been a promising research direction. Here, we first summarize the main types of glycosylation (O-GalNAc glycosylation and N-glycosylation) on mucins and the mechanisms by which abnormal mucin glycans occur. Next, how abnormal mucin glycans contribute to cancer development is described. Finally, we summarize MUC1-based antibodies, vaccines, radio-pharmaceuticals, and CAR-T therapies using the best characterized MUC1 as an example. In this section, we specifically elaborate on the recent new cancer therapy CAR-M, which may bring new hope to cancer patients.

Adenocarcinoma of the gastroesophageal junction (AEG) has become increasingly common in Western and Asian populations. Surgical resection is the mainstay of treatment for AEG; however, determining the distance from the upper edge of the tumor to the esophageal margin (PM) is essential for accurate prognosis. Despite the relevance of these studies, most have been retrospective and vary widely in their conclusions. The PM is now widely accepted to have an impact on patient outcomes but can be masked by TNM at later stages. Extended PM is associated with improved outcomes, but the optimal PM is uncertain. Academics continue to debate the surgical route, extent of lymphadenectomy, preoperative tumor size assessment, intraoperative cryosection, neoadjuvant therapy, and other aspects to further ensure a negative margin in patients with gastroesophageal adenocarcinoma. This review summarizes and evaluates the findings from these studies and suggests that the choice of approach for patients with adenocarcinoma of the esophagogastric junction should take into account the extent of esophagectomy and lymphadenectomy. Although several guidelines and reviews recommend the routine use of intraoperative cryosections to evaluate surgical margins, its generalizability is limited. Furthermore, neoadjuvant chemotherapy and radiotherapy are more likely to increase the R0 resection rate. In particular, intraoperative cryosections and neoadjuvant chemoradiotherapy were found to be more effective for achieving negative resection margins in signet ring cell carcinoma.

Diffuse-type gastric cancer (DTGC) is associated with poor outcome. Surgical resection margin status (R) is an important prognostic factor, but its exact impact on DTGC patients remains unknown. The aim of this study was to assess the prognostic value of microscopically positive margins (R1) after gastrectomy on survival and tumour recurrence in DTGC patients.

All consecutive DTGC patients from two tertiary centers who underwent curative oncologic gastrectomy from 2005 to 2018 were analyzed. The primary endpoint was overall survival (OS) for R0 versus R1 patients. Secondary endpoints included disease-free survival (DFS), recurrence patterns as well as the overall survival benefit of chemotherapy in this DTGC patient cohort.

Overall, 108 patients were analysed, 88 with R0 and 20 with R1 resection. Patients with negative lymph nodes and negative margins (pN0R0) had the best OS (median 102 months, 95% CI 1-207), whereas pN + R0 patients had better median OS than pN + R1 patients (36 months 95% CI 13-59, versus 7 months, 95% CI 1-13, p < 0.001). Similar findings were observed for DFS. Perioperative chemotherapy offered a median OS of 46 months (95% CI 24-68) versus 9 months (95% CI 1-25) after upfront surgery (p = 0.022). R1 patients presented more often early recurrence (< 12 postoperative months, 30% vs 8%, p = 0.002), however, no differences were observed in recurrence location.

DTGC patients with microscopically positive margins (R1) presented poorer OS and DFS, and early tumour recurrence in the present series. R0 resection should be obtained whenever possible, even if other adverse biological features are present.

Locally advanced gastric cancer (LAGC) represents a therapeutic challenge, particularly as it often involves adjacent organs. The necessity of neoadjuvant treatments for LAGC patients is still controversial. The aim of this study was to analyze the factors affecting prognosis and survival in patients with LAGC with particular regard to the effect of neoadjuvant therapies.

Between January 2005 and December 2018, the medical records of 113 patients with LAGC who underwent curative resection were retrospectively reviewed. Patient characteristics, related complications, long-term survival, and prognostic factors were analyzed at uni- and multivariate analyses.

Postoperative mortality and morbidity rates of patients undergoing neo-adjuvant therapies were 2.3% and 43.2%, respectively. Whereas in patients undergoing upfront surgery were 4.6% and 26.1%, respectively. R0 resection was achieved 79.5% and in 73.9% of patients undergoing neoadjuvant therapy and upfront surgery, respectively (P<0.001). Multivariate analysis revealed that neoadjuvant therapy, completeness of resection (R0), number of lymph nodes retrieved, N status and the adoption of hyperthermic intraperitoneal chemotherapy were independent prognostic factors associated with longer survival. Five-year overall survival for NAC group and upfront surgery group was 46% and 32%, respectively (P=0.04). Five-year disease-free survival for NAC group and upfront surgery group was 38% and 25%, respectively (P=0.02).

Patients with LAGC undergoing surgery plus neoadjuvant therapy had a better OS and DFS with respect to patients treated with surgery alone.

Poorly cohesive cells-gastric cancer (PCC-GC) represents distinct features within the GC spectrum. The present study investigated the clinicopathologic characteristics and chemo-sensitivity for a relatively large cohort of PCC-GC patients.

A total of 268 patients diagnosed with stage II or III PCC-GC were included. GC cell lines were also analyzed for drug sensitivity to 5-fluorouracil (5-FU) and oxaliplatin in vitro.

One hundred fifteen (42.9%) patients were stage II and 153 (57.1%) were stage III. Two hundred twenty-three (83.2%) patients received adjuvant therapy. Among these patients, 139 (62.3%) received CAPOX and 84 (37.7%) received S-1. With a median follow-up of 38.9 (1.6-137.8) months, the estimated 5-year disease-free survival (DFS) and overall survival (OS) rates were 52.3% and 61.0%, respectively. In the univariate analysis, survival was significantly better in the adjuvant chemotherapy group than in the surgery only group. In the subgroup analysis, there was no significant difference in DFS or OS between the types of adjuvant chemotherapy for either disease stage. In vitro cell line analysis, different responses to 5-FU and oxaliplatin were observed in SRC and non-SRC, where the treatment in KATOIII cell lines with oxaliplatin had less effect at a higher concentration compared to non-SRC cell lines.

The current study found that adjuvant chemotherapy was not significantly associated with survival benefit for patients with resected stage II and III PCC-GC. Plus, S-1 showed numerically longer DFS and OS compared to CAPOX in PCC-GC patients, although no significant in the multivariate analysis.

Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA-YAP axis in these mechanisms. The present observational multicenter retrospective study included 133 patients with PC GC treated at two dedicated European surgical centers between 2004 and 2014. YAP nuclear localization was measured by immunohistochemical (IHC) analysis of tissue biopsies. The complete absence of nuclear reactivity was coded as negative expression; we considered "any positive" as low nuclear expression (>0% but <10% of cells) and high nuclear expression (≥10% of cells). Women represented about half of the present series (52%), and the median age was 64 years (p25-p75 range: 53-75). Neoadjuvant and adjuvant treatments were administered to 10% and 54% of the cases, respectively. Extended systemic lymphadenectomy (D2) was the most common (54%). In nearly all cases, the number of retrieved nodes was ≥15, i.e., adequate for tumor staging (94%). An R0 resection was achieved in 80% of the cases. Most patients were pathological T stage 3 and 4 (pT3/pT4 = 79.0%) and pathological N stage 2, 3a, and 3b (pN2/pN3a/pN3b = 47.0%) at the pathological examination. Twenty patients (15%) presented distant metastases. Five-year overall survival (OS) was significantly higher (p = 0.029) in patients with negative YAP (46%, 95% CI 31.1-60.0%) than in the other patients (27%, 17.5-38.1%). Moreover, when controlling for sex, age, pT, pN, and percentage of signet ring cells in the multivariable analysis, YAP expression was a significant predictor of OS (HR 2.03, 95% CI: 1.18-3.51, p = 0.011). Our results provide new insights into the role of the YAP signaling cascade, as its activation was associated with a worse prognosis in PC GC.

Signet ring cell carcinoma accounts for 35% to 45% of all gastric cancer. Despite the acknowledgment of its more aggressive pathological features, various controversies surrounding this topic still exist. Thus, we investigate the clinical pathological characteristics and survival prognostic significance of signet ring cell components in patients affected by gastric cancer.

From January 2004 to December 2020, in a retrospective study, we enrolled 404 patients with gastric cancer who were curatively treated in our department. The male-to-female ratio was 249/142, and the median age was 75 (range 37-94). We dichotomized patients into two groups (75 patients vs. 316 patients) based on the signet ring cell presence; according to preoperative, operative, and postoperative characteristics, we performed a univariate and multivariate analysis for overall survival.

Signet ring cell carcinoma indicated an increasing incidence trend over the time analyzed. Overall median survival of signet ring cell and non-signet ring cell carcinoma were, respectively, 16 vs. 35 months, p < 0.05. In early gastric cancer, the prognosis of the signet ring cell is better than that of the non-signet ring cell, as opposed to advanced cancer. Among the entire population in the multivariate analysis, the only independent factors were preoperative serum albumin level, complete surgical resection, level of lymphadenectomy, and pathological stage. Recurrence occurred more frequently in patients affected by signet ring cell, but in our data, we could not identify a peculiar site of recurrence.

Signet ring cell carcinoma has a specific oncogenetic phenotype and treatment resistance heterogeneity; however, it is not always associated with poor prognosis. According to our results, a radical surgical procedure associated with an adequate lymphadenectomy should be advocated to improve patients survival. Gastric cancer patients with signet ring cell components should draw clinicians' attention.

Evidence specifically comparing the clinicopathology of Borrmann type IV (B-IV) gastric cancer with that of other Borrmann types is insufficient.

A total of 3130 patients with advanced gastric cancer who underwent gastrectomy from January 2001 to September 2017 were enrolled in the analysis. Logistic regression and survival analysis methodology were used to investigate factors associated with peritoneal metastasis and overall survival (OS).

Of the total cohort, 264 (8.43%) patients were B-IV type, 1752 (55.97%) were small-size other Borrmann types, and 1114 (35.59%) were large-size other Borrmann types. Signet ring cell carcinoma (SRC) was more common in B-IV types than in other Borrmann types (33.71% vs 11.42% vs 12.66%, P < 0.001). In B-IV gastric cancers, SRC was significantly associated with peritoneal metastasis (HR = 1.898, 95% CI = 1.112 ~ 3.241, P = 0.019) and poorer OS (HR = 1.492, 95% CI = 1.088 ~ 2.045, P = 0.013) in multivariable analysis. Furthermore, stratified analysis revealed that SRC had worse survival than adenocarcinoma in the B-IV subgroups, with locally advanced stages (stages II ~ III) or negative surgical margins (all P < 0.05). In contrast, SRC failed to be significantly associated with peritoneal metastasis and poor OS in other Borrmann types (all P > 0.05).

SRC was more common in B-IV gastric cancer than in other Borrmann types. It was significantly associated with peritoneal metastasis and poorer OS in the B-IV type but not in other Borrmann types. As a unique prognostic factor for B-IV gastric cancer, SRC might help evaluate risk stratification and optimize treatment for this entity, especially for patients with locally advanced stages or R0 resection.

Signet-ring cell carcinoma (SRCC) was previously thought to have a worse prognosis than other differentiated gastric cancer (GC), however, recent studies have shown that the prognosis of SRCC is related to pathological type. We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis (LNM).

To establish models to predict LNM in early GC (EGC), including early gastric SRCC.

Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed. The patients were divided into three groups based on type: Pure SRCC, mixed SRCC, and non-signet ring cell carcinoma (NSRC). The risk factors were identified through statistical tests using SPSS 23.0, R, and Em-powerStats software.

A total of 1922 subjects with EGC were enrolled in this study, and included 249 SRCC patients and 1673 NSRC patients, while 278 of the patients (14.46%) presented with LNM. Multivariable analysis showed that gender, tumor size, depth of invasion, lymphovascular invasion, ulceration, and histological subtype were independent risk factors for LNM in EGC. Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy (98.0% vs 58.1%, P = 0.034; 88.4% vs 86.8%, P < 0.001, respectively). Among the 249 SRCC patients, LNM was more common in mixed (35.06%) rather than in pure SRCC (8.42%, P < 0.001). The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760 (95%CI: 0.682-0.843), while the area under the operating characteristic curve of the internal validation set was 0.734 (95%CI: 0.643-0.826). The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size > 2 cm (OR = 5.422, P = 0.038).

A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC, which can aid in pre-surgical decision making of the best method of treatment for patients.

FLOT perioperative chemotherapy represents the standard of care in non-metastatic gastric cancer patients. Signet-ring cell positivity is associated with a worse prognosis in patients with gastric cancer treated with chemotherapy. Comparison between FLOT perioperative chemotherapy vs. surgery followed by adjuvant chemotherapy based on signet-ring cell positivity is lacking. The aim of the analysis was to compare perioperative FLOT with adjuvant chemotherapy in gastric cancer patients stratified by signet-ring cell positivity.

We conducted a retrospective multicenter analysis based on disease-free survival (DFS) and overall survival (OS) in patients with gastric cancer who received perioperative chemotherapy with a FLOT regimen and compared their survival with a historical cohort of patients treated with adjuvant chemotherapy, matched by cT and cN stage and by tumor histological features.

Seventy-six patients were enrolled and 24 (32%) were signet-ring cell positive. At a median follow-up time of 39 months, the median DFS was 26.3 months and the median OS was 37.3 months. Signet-ring cell positivity was associated with a shorter OS (median OS: 20.4 vs. 46.9 months, HR: 3.30, 95%CI: 1.56-6.99, p = 0.0018) and DFS (mDFS: 15.2 vs. 38.6 months, HR: 3.18, 95%CI: 1.55-6.54, p = 0.0016). This was confirmed by multivariate analysis for DFS (Exp(B): 2.55) and OS (Exp(B): 2.68). After propensity score matching, statistically significant shorter DFS (HR: 3.30, 95%CI: 1.50-7.35, p = 0.003) and OS (HR: 5.25, 95%CI: 2.18-12-68, p = 0.0002) were observed for patients with signet-ring cell positivity who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy.

Signet-ring positivity was associated with shorter DFS and OS in patients who received perioperative treatment with FLOT compared with surgery followed by adjuvant therapy. These data suggest that for patients with signet-ring cell histology, FLOT perioperative treatment might not always be the best choice of treatment, and further research should be focused on this group of patients.

In the last few decades, the treatment strategy for locally advanced resectable gastric cancer (GC) has shifted to a multimodal approach, which potentially decreases recurrence risk and improves survival rates. Perioperative therapy leads to downstaging, increased curative resection rates, and prolonged disease-free and overall survival, by preventing micrometastases in patients with resectable GC. Application of neoadjuvant therapy provides information about tumor biology and in vivo sensitivity. A consensus regarding the therapeutic approach for non-metastatic GC does not exist, and many clinical trials aim to clarify this aspect. Advances in precision medicine and the role of immunotherapy have been the focus of research in GC treatment. Herein, the current status and possible future developments of perioperative therapy for locally advanced resectable GC are reviewed, based on the most recent randomized clinical trials.

Gastric adenocarcinoma remains associated with a poor long-term survival, despite recent therapeutical advances. In most parts of the world where systematic screening programs do not exist, diagnosis is often made at advanced stages, affecting long-term prognosis. In recent years, there is increasing evidence that a large bundle of factors, ranging from the tumor microenvironment to patient ethnicity and variations in therapeutic strategy, play an important role in patient outcome. A more thorough understanding of these multi-faceted parameters is needed in order to provide a better assessment of long-term prognosis in these patients, which probably also require the refinement of current staging systems. This study aims to review existing knowledge on the clinical, biomolecular and treatment-related parameters that have some prognostic value in patients with gastric adenocarcinoma.

Despite its decreasing incidence, gastric cancer remains an important global healthcare problem due to its overall high prevalence and high mortality rate. Since the MAGIC and FNLCC/FFCD trials, the neoadjuvant chemotherapy has been recommended throughout Europe in gastric cancer. Potential benefits of preoperative treatments include a higher rate of R0 resection achieved by downstaging the primary tumor, a likely effect on micrometastases and isolated tumor cells in the lymph nodes, and, as a result, improved cancer-related survival. Nevertheless, distortion of anatomical planes of dissection, interstitial fibrosis, and sclerotic tissue changes may increase surgical difficulty. The collection of at least twenty-five lymph nodes after neoadjuvant therapy would seem to ensure removal of undetectable node metastasis and reduce the likelihood of locoregional recurrence. It is not what you take but what you leave behind that defines survival. Therefore, para-aortic lymph node dissection is safe and effective after neoadjuvant chemotherapy, in both therapeutic and prophylactic settings. In this review, the efficacy of adequate lymph node dissection, also in a neoadjuvant setting, has been investigated in the key studies conducted to date on the topic.

Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj).

Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005-2014). Multivariable Cox regression analyses were performed on propensity score-matched (PSM) cohorts stratified by stage to compare overall survival (OS).

We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04-1.38) and improved survival for SII (HR 0.93 CI 0.87-0.998) and SIII (HR 0.75, CI 0.68-0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004-1.402). SII patients had no difference in OS (HR 0.98, CI 0.91-1.07) and SIII patients had improved OS (HR 0.78, CI 0.69-0.90).

In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

Gastric signet ring cell carcinoma (SRCC) has shown a growth growing trend worldwide, but its clinicopathological features and prognostic-related risk factors have not been systematically studied. This systematic review was devoted to this.

PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved, and retrospective cohort studies comparing clinicopathological features and related risk factors in SRCC patients were included.

In SRCC patient population, males were more than females (male, OR = 1.38, 95% CI: 1.20-1.60); N3 patients were more than N0-2 patients (N0-2, OR = 3.19, 95% CI: 1.98-5.15); M1 patients were more than M0 patients (M0, OR = 3.30, 95% CI: 1.88-5.80); patients with tumor > 5 cm were more than those with tumor (≤5 cm, OR = 7.36, 95% CI: 1.33-40.60). Patients with age < 60 years (age ≥ 60 years, OR = 1.03, 95% CI: 1.01-1.05), lymphatic vessel invasion (no, OR = 1.74, 95% CI: 1.03-2.45), T2 (T1, OR = 1.17, 95% CI: 1.07-1.28) and T4 (T1, OR = 2.55, 95% CI: 2.30-2.81) stages, and N1 (N0, OR = 1.73, 95% CI: 1.08-2.38), N2 (N0, OR = 2.24, 95% CI: 1.12-3.36), and N3 (N0, OR = 3.45, 95% CI: 1.58-5.32) stages had higher hazard ratio (HR).

SRCC may occur frequently in male. Age, lymphatic vessel invasion, TN, and M stage may be risk factors for poor prognoses of SRCC patients.

Signet-ring cell carcinoma of the stomach (SRCC) is a particular gastric cancer entity. Its incidence is increasing. Its diagnosis is pathological; it corresponds to adenocarcinoma with a majority of signet-ring cells component (> 50%). These histological features give it its aggressiveness characteristics. This has repercussions on the prognostic level and implications for the alternatives of therapy, especially since some authors suggest a potential chemoresistance. This survey aimed to identify the epidemiological, pathological, therapeutic, and prognostic characteristics of SRCC as a separate disease entity.

This was a retrospective study of 123 patients admitted for gastric adenocarcinoma to Habib Thameur Hospital in Tunis over 11 years from January 2006 to December 2016. A comparative study was performed between 2 groups: the SRCC group with 62 patients and the non-SRCC (non-signet-ring cell carcinoma of the stomach) with 61 patients.

The prevalence of SRCC in our series was 50%. SRCC affected significantly younger patients (55 vs 62 years; p = 0.004). The infiltrative character was more common in SRCC tumors (30.6 vs 14.8%; p = 0.060), whereas the budding character was more often noted in non-SRCC tumors (78.7 vs 58.1%; p = 0.039). There was no significant difference in tumor localization between both groups. Linitis plastica was noted in 14 patients with SRCC against a single patient with non-SRCC (p = 0.001). The tumor size was more important in the non-SRCC group (6.84 vs 6.39 cm; p = 0.551). Peritoneal carcinomatosis was noted in 4.3% of cases in the SRCC group versus 2.2% of cases in the NSRCC group (p = 0.570). Total gastrectomy was more often performed in the SRCC group (87 vs 56%; p = 0.001). Resection was more often curative in the non-SRCC group (84.4 vs 78.3%; p = 0.063). Postoperative chemotherapy was more commonly indicated in the SRCC group (67.4 vs 53.3%; p = 0.339). Tumor recurrence was more common in the non-SRCC group (35.7 vs 32%; p = 0.776). The most common type of recurrence was peritoneal carcinomatosis in the SRCC group (62.5%) and hepatic metastasis in the non-SRCC group (60%; p = 0.096). The overall 5-year survival in the SRCC group was lower than in the non-SRCC group, with no statistically significant difference (47.1 vs 51.5%; p = 0.715). The overall survival was more important for SRCC in early cancer (100 vs 80%; p = 0.408), whereas it was higher for non-SRCC in advanced cancer (48.1 vs 41.9%; p = 0.635).

Apart from its epidemiological and pathological features, SRCC seems to have a worse prognosis. Indeed, it is diagnosed at a more advanced stage and has a worse prognosis in advanced cancer than non-SRCC. It is therefore to be considered as a particular entity of gastric adenocarcinoma requiring a specific therapeutic protocol where the place of chemotherapy remains to be more investigated.

Purpose: Hypergastrinemia increases the risk of developing proximal gastric adenocarcinoma. However, it is unclear if hypergastrinemia affects the survival in patients with gastric adenocarcinoma. This study aimed to examine the hypothesis that hypergastrinemia is associated with increased risk of mortality in patients with gastric adenocarcinoma.Materials and methods: This prospective population-based cohort study based on the Trøndelag Health Study (HUNT) included 78,962 adult individuals (≥20 years). During the baseline assessment period (1995-2008) of these participants, serum samples were collected and frozen. All participants with a newly diagnosed gastric adenocarcinoma in the cohort in 1995-2015 were identified and their gastrin levels were measured in the pre-diagnostic serum samples. Gastrin levels were analysed in relation to all-cause mortality until year 2020 using multivariable Cox regression providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for sex, age, body mass index (BMI), tobacco smoking, tumour stage, completeness of surgical resection, and peri-operative chemotherapy.Results: Among 172 patients with gastric adenocarcinoma, 81 (47%) had hypergastrinemia (serum gastrin >60 pmol/L) and 91 (53%) had normal gastrin level. The tumour location was proximal in 83 patients (43%) and distal in 78 (41%). Hypergastrinemia was not associated with any increased risk of all-cause mortality in all patients (adjusted HR 0.8, 95% CI 0.5-1.1), or in sub-groups of patients with proximal tumour location (HR 0.9, 95% CI 0.4-2.2) or distal tumour location (HR 0.9, 95% CI 0.5-1.7).Conclusion: This population-based cohort study indicates that hypergastrinemia may not increase the risk of mortality in patients with gastric adenocarcinoma.