Association Between DCE-MRI Perfusion Histogram Parameters and EGFR and VEGF Expressions in Different Lauren Classifications of Advanced Gastric Cancer

Objective: To investigate the correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion histogram parameters and vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions in advanced gastric cancer (AGC).Methods: This retrospective study included 80 pathologically confirmed patients with AGC who underwent DCE-MRI before surgery from February 2017 to May 2021. The DCE-MRI perfusion histogram parameters were calculated by Omni Kinetics software in four quantitative parameter maps. Immunohistochemical methods were used to detect VEGF and EGFR expressions and calculate the immunohistochemical score.Results: VEGF expression was relatively lower in patients with intestinal-type AGC than those with diffuse-type AGC (p < 0.05). For VEGF, Receiver operating characteristics (ROC) curve analysis revealed that Quantile 90 of Ktrans, Meanvalue of Kep and Quantile 50 of Ve provided the perfect combination of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for distinguishing high and low VEGF expression, For EGFR, Skewness of Ktrans, Energy of Kep and Entropy of Vp provided the perfect combination of sensitivity, specificity, PPV and NPV for distinguishing high and low EGFR expression. Ktrans (Quantile 90, Entropy) showed the strongest correlation with VEGF and EGFR in patients with intestinal-type AGC (r = 0.854 and r = 0.627, respectively); Ktrans (Mean value, Entropy) had the strongest correlation with VEGF and EGFR in patients with diffuse-type AGC (r = 0.635 and 0.656, respectively).Conclusion: DCE-MRI perfusion histogram parameters can serve as imaging biomarkers to reflect VEGF and EGFR expressions and estimate their difference in different Lauren classifications of AGC.

Age-Related Macular Degeneration Eyes Presenting with Cuticular Drusen and Reticular Pseudodrusen

This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). The clinical records of 13 eyes of seven patients diagnosed with CD and RPD were retrospectively reviewed. All patients underwent a complete ocular examination and multimodal imaging. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.

Higher Lymph Node Metastasis Rate and Poorer Prognosis of Intestinal-Type Gastric Cancer Compared to Diffuse-Type Gastric Cancer in Early-Onset Early-Stage Gastric Cancer: A Retrospective Study

Background: The incidence of early-onset gastric cancer (GC) that was diagnosed at <50 years is increasing, but there is a knowledge gap on early-onset early-stage GC (EEGC) that was defined as early-onset GC limited to the mucosa or submucosa. Therefore, we comprehensively analysed the clinical features based on Lauren type.Methods: Logistic and Cox analyses were used to investigate risk factors for lymph node metastasis (LNM) and prognosis, respectively. Propensity score matching (PSM) was used to adjust confounding factors. Protein mass spectrometry analysis was used to explore the molecular mechanism of LNM.Result: Our study included 581 patients with EEGC from the Surveillance, Epidemiology, and End Results (SEER) database and 226 patients with EEGC from our own centre. We identified intestinal type, T1b stage, and tumour size (>3 cm) as risk factors for LNM using SEER and our own data. We also found that the prognosis of patients with intestinal-type EEGC was poorer than patients with diffuse-type EEGC, and T1b stage and positive LNM were hazard factors for survival. After analysing the expression of proteins between positive and negative LNM in the intestinal or diffuse type, we found no similar proteins between these groups. The differentially expressed genes (DEGs) in the intestinal type functioned as epithelial cell signalling in Helicobacter pylori. The DEGs in the diffuse type functioned in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation.Conclusion: For EEGC, our study was the first report to demonstrate that the intestinal type was a risk factor for LNM and survival compared to the diffuse type, and the oncogenic expression promoting the occurrence of LNM was different. These findings suggest that clinicians should pay more attention to intestinal-type EEGC than diffuse-type EEGC.

Cell Cycle Regulation and DNA Damage Response Networks in Diffuse- and Intestinal-Type Gastric Cancer

Dynamic regulation in molecular networks including cell cycle regulation and DNA damage response play an important role in cancer. To reveal the feature of cancer malignancy, gene expression and network regulation were profiled in diffuse- and intestinal-type gastric cancer (GC). The results of the network analysis with Ingenuity Pathway Analysis (IPA) showed that the activation states of several canonical pathways related to cell cycle regulation were altered. The G1/S checkpoint regulation pathway was activated in diffuse-type GC compared to intestinal-type GC, while canonical pathways of the cell cycle control of chromosomal replication, and the cyclin and cell cycle regulation, were activated in intestinal-type GC compared to diffuse-type GC. A canonical pathway on the role of BRCA1 in the DNA damage response was activated in intestinal-type GC compared to diffuse-type GC, where gene expression of BRCA1, which is related to G1/S phase transition, was upregulated in intestinal-type GC compared to diffuse-type GC. Several microRNAs (miRNAs), such as mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451 and mir-605, were identified to have direct relationships in the G1/S cell cycle checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in epithelial-mesenchymal transition (EMT) conditions. The alterations in the activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC highlighted the significance of cell cycle regulation in EMT.

Gastric Cancers Missed at Upper Endoscopy in Central Norway 2007 to 2016—A Population-Based Study

Background: The rates of missed gastric cancers (MGC) at upper endoscopy (UE) has been reported at 5–10% in Western countries. We aimed to calculate the rate of MGC and identify factors associated with MGC. Methods: Retrospective population-based cohort study including 730 patients diagnosed with gastric adenocarcinoma in Central Norway 2007–2016. MGCs were incident gastric adenocarcinomas diagnosed 6–36 months after a previous UE. Factors associated with MGC were examined. Definitely missed (UE 6–12 months prior) and potentially missed (UE 12–36 months prior) MGCs were compared. Results: Sixty-seven (9.2%) of 730 gastric cancers were MGC. MGC were associated with localization (p = 0.009) and more frequent in the corpus, Lauren’s histological type (p = 0.028) and diffuse type more prevalent, and previous Billroth 2-operation (14.9% vs. 4.7%, p = 0.001). MGCs were diagnosed at earlier stages (p = 0.037). An ulceration was more common in patients with definitely missed than potentially MGC (40.9% vs. 17.8%, p = 0.041). Conclusions: MGC accounted for 9.2% of gastric cancers in Central Norway. MGC were associated with localization in the corpus, Lauren´s diffuse type and previous Billroth-2-operation. Intensified follow-up and adequate biopsy sampling of patients with gastric ulcerations could reduce the rate of missed gastric cancers.

Metastatic Gastric Adenocarcinoma of the Uterine Cervix – A Case Report and Review of the Literature

Background: Poorly differentiated diffuse-type gastric adenocarcinoma typically presents at an advanced stage, however, metastasis to the uterine cervix is extremely rare. To our knowledge, less than forty cases have been described worldwide. Case presentation: We report a case of a 47-year-old woman who presented to us with symptomatic uterine fibroids and subsequently underwent a successful total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. The diagnosis of metastatic cancer involving the cervix was established incidentally on histopathology, which showed atypical signet ring cells in the lymphovascular spaces of the cervix. Further investigations for a primary malignancy revealed a poorly differentiated diffuse-type gastric adenocarcinoma. Conclusion: Gastric cancer involving the uterine cervix is rare and associated with a poor prognosis. When presented with isolated cervical metastases, the gastrointestinal tract should be considered as a possible primary source. Due to the limited publications on this clinical entity, we expect to raise awareness and study of this unique manifestation of gastric cancer by presenting our case.

Computed tomographic pneumogastrography in determining the types of gastric cancer according to the Lauren classification

Objective. To assess the capabilities of computed tomographic pneumogastrography in determining the types of gastric cancer according to the Lauren classification at the stage of clinical staging.Materials and methods. This study is a single-center retrospective study with 202 patients with gastric cancer included who was treated at the National Medical Research Center of Oncology named after N. N. Petrov from 2015 to 2018. All patients underwent subtotal gastric resection or gastrectomy and computed tomographic pneumogastrography at the stage of clinical staging. For patients undergoing neoadjuvant chemotherapy, CT was performed twice: before chemotherapy and after, immediately before surgery. We studied quantitative and qualitative imaging biomarkers, measured densitometric indices of stomach tumor density in the arterial, portal and delayed phases of scanning at five different points. For patients receiving NACT, all density indices were recorded twice — both before the start of therapeutic treatment, and after, immediately before the surgery.Results. The distribution of gastric cancer types according to Lauren»s classification was as follows: in 59 (29,2 %) intestinal type, 69 (34,2 %) — diffuse, 16 (7,9 %) — mixed, 58 (28,7 %) — indeterminate type. Based on visual characteristics, taking into account the characteristics of tumor growth, 3 main CT-PGG of the gastric cancer type were identified: 1 — tuberous (n = 68, 34,0 %), 2 — intramural (n = 57,3 %) and 3 — mixed (n = 77,4 %). CT-PGG tumor type is associated with Lauren type (χ2 = 185,19, p <0,001). With a tuberous CT-PGG type, it is possible to assume that the tumor is of an intestinal or indeterminate Lauren type; sensitivity 0,58 (95% CI: 0,49-0,67), specificity 0,1 (95% CI: 0,96-0,1). With an intramural CT-PGG type, the diffuse type of tumor according to Lauren is most likely; sensitivity 0,75 (95% CI: 0,64-0,85), specificity 0,96 (95% CI: 0,91-0,99). With a mixed CT-PGG type, the definition of the type according to Lauren is difficult. In the definition of mixed tumor type according to Lauren, the sensitivity and specificity of mixed CT-PGG tumor type are 0,94 (95% CI: 0,70% -0,1) and 0,67 (95% CI: 0,59-0,73) respectively.Conclusion. The shape of the stomach tumor, determined by CT-PGG, has a high diagnostic efficiency in determining the types of gastric cancer according to Lauren. The tuberous CT-PGG type is typical for tumors of the intestinal type according to Lauren, and the intramural CT-PGG type is typical for tumors of the diffuse type according to Lauren. Tumors of indeterminate Lauren type have any CT-PGG type and contrast pattern. For tumors of a mixed type according to Lauren, a mixed type according to CT-PGG is characteristic, but differential diagnosis with tumors of a tuberous and diffuse type according to Lauren of an atypical form for them is impossible. Tumors of the intestinal and diffuse Lauren type of the CT-PGG type, which is not typical for them, have an atypical contrast pattern.