• Biomarkers
• Gastroesophageal cancer
• Heterogeneity
• Targeted therapy

• PRIN2022 Ministero dell'Istruzione, dell'Università e della Ricerca

• Humans
• Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods
• Linitis Plastica/diagnostic imaging
• Linitis Plastica/pathology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/diagnostic imaging
• Stomach Neoplasms/diagnosis

Early-onset gastric cancer (EOGC, ≤45 years old) is characterized with increasing incidence and more malignant phenotypes compared with late-onset gastric cancer, which exhibits remarkable immune cell infiltration and is potential immunotherapeutic population. Till now, restricted survival information of EOGC is available due to limited case numbers. This study established a novel nomogram to help evaluate cancer-specific survival (CSS) of EOGC patients who underwent gastrectomy, and may provide evidence for predicting patients’ survival.

We retrospectively enrolled a cohort containing 555 EOGC cases from five independent medical centers in China, among which 388 cases were randomly selected into a training set while the other 167 cases were assigned into the internal validation set. Asian or Pacific Islander (API) patients diagnosed with EOGC during 1975-2016 were retrieved from the SEER database (n=299) and utilized as the external validation cohort. Univariate and multivariate analyses were conducted to test prognostic significances of clinicopathological factors in the training set. Accordingly, two survival nomogram models were established and compared by concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curves and decision curve analyses (DCA).

The 5-year CSS rate of training cohort was 61.3% with a median survival time as 97.2 months. High consistency was observed on calibration curves in all three cohorts. Preferred nomogram was selected due to its better performance on ROC and DCA results. Accordingly, a novel predicative risk model was introduced to better stratify high-risk EOGC patients with low-risk patients. In brief, the 5-year CSS rates for low-risk groups were 92.9% in training set, 83.1% in internal validation set, 89.9% in combined NQSQS cohort, and 85.3% in SEER-API cohort. In contrast, the 5-year CSS rates decreased to 38.5%, 44.3%, 40.5%, and 36.9% in the high-risk groups of the four cohorts above, respectively. The significant survival difference between high-risk group (HRG) and low-risk group (LRG) indicated the precise accuracy of our risk model. Furthermore, the risk model was validated in patients with different TNM stages, respectively. Finally, an EOGC web-based survival calculator was established with public access, which can help predict prognosis.

Our data provided a precise nomogram on predicting CSS of EOGC patients with potential clinical applicability.

• Gastrectomy
• Humans
• Nomograms
• Prognosis
• Retrospective Studies
• Stomach Neoplasms/diagnosis

• Gastric cancer
• Glycan
• Lectin
• Signet ring cell carcinoma

While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

• Poorly cohesive cells gastric carcinoma
• Review
• Definition
• Classification
• Therapeutic management

Gastric linitis plastica (GLP) is a descriptive term but lacks a quantitative definition. Several relatively quantitative criteria had been proposed, such as tumor involving a limit of one-third or two-thirds of the gastric surface. However, these criteria needed doctors to subjectively judge tumor infiltration area, which made diagnosis difficult to be objective and reproducible. This study aimed to propose a quantitative diagnostic criterion for distinguishing GLP. We performed a retrospective cohort study of 2,907 patients with Borrmann III and IV gastric cancer (GC) who underwent gastrectomy between 2011 and 2018 in our center. The Kaplan–Meier curves showed that patients with an observed tumor size more than 8 cm had obviously lower overall survival (OS) and disease-free survival (DFS) rates than those with a size less than 8 cm(p < 0.001; p < 0.001). However, there was no significantly different prognosis of patients with tumor sizes between more than 8 cm and more than 10 cm (p = 0.248; p = 0.534). Moreover, patients with tumor sizes greater than 8 cm more presented with advanced stage and had extremely poor 3-year OS and DFS (31.4%; 29.3%), with a stronger propensity toward peritoneal metastasis. Therefore, we considered patients’ observed tumor size more than 8 cm as a critical value for distinguishing the prognosis of Borrmann III and IV GC. Furthermore, we proposed an observed tumor size more than 8 cm as a quantitative diagnostic criterion for GLP on the premise of satisfying the originally descriptive and pathological definition regardless of Borrmann type.

• CT
• linitis plastica
• neoadjuvant therapy
• quantitative definition
• tumor size

• Gastric cancer (GC)
• adjuvant treatment
• linitis plastica
• risk prediction

• Case report
• Gastric cancer
• Ovarian tumor
• Peritoneal carcinomatosis
• Signet-ring cell carcinoma

Type 4 gastric cancer (GC) has a very poor prognosis even after curative resection, and the survival benefit of splenectomy for splenic hilar lymph node (LN; #10) dissection in type 4 GC remains equivocal. This study aimed to clarify the clinical significance of splenectomy for #10 dissection in patients with type 4 GC.

The data of a total of 56 patients with type 4 GC who underwent total gastrectomy with splenectomy were retrospectively analyzed. Postoperative morbidity, state of LN metastasis, survival outcomes, and therapeutic value index (TVI) of each LN station were evaluated. TVI was calculated by multiplying the incidence of LN metastasis at each nodal station and the 5-year overall survival (OS) of patients who had metastasis to each node.

Overall, the postoperative morbidity rate was 28.6%, and the incidence of #10 metastasis in the patients was 28.6%. The 5-year OS rate for all patients was 29.9%, and most patients developed peritoneal recurrence. Moreover, the 5-year OS rates with and without #10 metastasis were 6.7% and 39.1% (median survival time, 20.4 vs. 46.0 months; P=0.006). The TVI of #10 was as low as 1.92.

The clinical significance of splenectomy in the dissection of #10 for type 4 GC is limited and splenectomy for splenic hilar dissection alone should be omitted.

• Gastric cancer
• linitis plastica
• surgery
• survival

• Diagnostic score
• Gastrectomy
• Linitis plastica

• Borrmann type IV
• Diffuse
• Gastrectomy
• Gastric cancer
• Linitis plastica
• Scirrhous carcinoma
• Signet ring

• Adenocarcinoma/surgery
• Gastrectomy
• Humans
• Linitis Plastica/diagnostic imaging
• Linitis Plastica/pathology
• Linitis Plastica/therapy
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Stomach Neoplasms/surgery
• Survival Rate

• P30 CA016672 NCI NIH HHS

• Malignancy
• maternal mortality
• pregnancy
• preventability

The value of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy in the gastric linitis plastica (GLP) with negative malignant endoscopy biopsies was investigated. Forty-six patients with linitis plastica who had undergone EUS-FNA were retrospectively studied, and their clinicopathological data were examined. Among the 46 eligible patients, 38 cases were diagnosed clearly by EUS-FNA. There were 24 cases with lymph node metastasis in the 38 patients. Both the lymph nodes and gastric lesions were punctured by EUS-FNA in the 24 cases. We compared the diagnostic accuracy in different sites, and the results showed that the diagnostic accuracy in lymph nodes was significantly higher than that in gastric lesions (P<0.05). Among them, 16 patients underwent surgical resection, and the accuracy of the pathological diagnosis by EUS-FNA was 87.5% (14/16). The preoperative diagnostic accuracy of T and N staging by endoscopic ultrasound (EUS) were both 75%. Neither severe hemorrhage nor perforation occurred in any patient. In conclusion, EUS-FNA is a safe and effective procedure for the diagnosis of indefinite linitis plastica, and puncturing metastatic lymph nodes can improve the diagnostic accuracy.

• diagnosis
• endoscopic biopsy
• endoscopic ultrasonography
• fine needle aspiration
• gastric linitis plastica

CLDN18-ARHGAP26/6 fusions have been identified in gastric cancers, with a predominance in diffuse-type gastric cancers (DGCs). Although in vitro experiments have suggested an oncogenic role for CLDN18-ARHGAP26/6 fusions, the exact frequencies and clinicopathological characteristics of the fusion-positive cases are poorly understood. We analyzed 254 cases of gastric cancer (172 diffuse-type and 82 intestinal-type) using RT-PCR and FISH, and also analyzed TCGA transcriptome datasets to identify genes that are related to the aggressive behaviors of fusion-positive cancers. Our assays identified 26 fusion-positive cases, 22 of which were DGCs (22/172, 12.8%). Unlike fusion-negative DGCs, almost all fusion-positive DGCs retained E-cadherin expression (P = 0.036). Fusion-positive DGCs also showed a higher prevalence of lymphatic and distant organ metastases, and these trends were only significant in the younger age group (< 60 years). In this group, the majority of cases with distant organ metastases (4 of 6 cases) were fusion-positive, and the multivariate regression analysis revealed that fusion status was an independent predictive marker for distant organ metastases (P = 0.002). In the TCGA dataset analysis, carbonic anhydrase 9 was postulated to be a potential modulator of the age-specific effects of the fusion protein, compatible with the immunohistochemical analysis of our cohort. Therefore, CLDN18-ARHGAP26/6 fusion-positive DGCs are considered biologically distinct entities that will require more advanced therapeutic options.

• CA9
• CLDN18-ARHGAP fusion
• E-cadherin
• RHOA
• diffuse-type gastric cancer

Linitis plastica due to gastric adenocarcinoma is a condition with a long history, but still lacks a standardized definition and is commonly confused with Borrmann type IV, Lauren diffuse, and signet-cell type gastric cancer. The absence of a clear definition is a problem when investigating its biological characteristics and role as a possible independent factor for prognosis. Nevertheless, the biological behavior for linitis plastica, which is unique, may be valuable in risk stratification and have implications for treatment. A definition of linitis plastica based on molecular or genomic criteria could represent a useful starting point for investigating new targeted therapies.

This literature review of linitis plastica will focus on the current classifications for gastric cancer, illustrating how the concept of linitis plastica relates to them in most cases and identifying a clear and reproducible definition. Moreover, the review will highlight the diagnostic challenges associated with linitis plastica, its prognostic implications, and the therapeutic options available. Future perspectives for its management are also addressed.

Linitis plastica is a carcinoma with a scirrhous stroma, involving the submucosal and muscular layers of the stomach even in the absence of mucosal alteration. In most cases, the primary cancer cells are signet-ring cells or scattered cells in the context of a poorly differentiated carcinoma. Diagnosis is challenging. Staging should be thorough, including diagnostic laparoscopy in all cases due to the high incidence of peritoneal involvement. The prognostic significance of linitis plastica is still controversial. Curative-intent surgery, when feasible, should be performed, with a multimodality treatment approach. Cancer-stroma interactions are important features of this disease, and represent attaining potential target for future therapies. Future pathologic assessments of gastric cancer should report the stromal reaction in order to allow better characterization of the tumor.

• Borrmann type IV
• Diffuse
• Gastric cancer
• Linitis plastica
• Scirrhous carcinoma
• Signet ring

We explored the prognostic value of the up-regulated carbohydrate antigen (CA19-9) in node-negative patients with gastric cancer as a surrogate marker for micrometastases.

Micrometastases were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for a subgroup of 30 node-negative patients. This group was used to determine the cut-off for preoperative CA19-9 serum levels as a surrogate marker for micrometastases. Then 187 node-negative T1 to T4 patients were selected to validate the predictive value of this CA19-9 threshold.

Patients with micrometastases had significantly higher preoperative CA19-9 serum levels compared to patients without micrometastases (p = 0.046). CA19-9 serum levels were significantly correlated with tumour site, tumour diameter, and perineural invasion. Although not reaching significance, subgroup analysis showed better five-year survival rates for patients with CA19-9 serum levels below the threshold, compared to patients with CA19-9 serum levels above the cut-off. The cumulative survival for T2 to T4 node-negative patients was significantly better with CA19-9 serum levels below the cut-off (p = 0.04).

Preoperative CA19-9 serum levels can be used to predict higher risk for haematogenous spread and micrometastases in node-negative patients. However, CA19-9 serum levels lack the necessary sensitivity and specificity to reliably predict micrometastases.

• CA19-9
• gastric cancer
• micrometastases