Scirrhous Gastric Cancer Research Articles

Necessity of splenectomy for antral-type scirrhous gastric cancer

BackgroundTotal gastrectomy with splenic hilar nodal dissection by splenectomy is frequently selected for resectable scirrhous gastric cancer (GC), irrespective of the whether it is of the antral or body type. However, whether splenectomy is necessary for antral-type scirrhous GC remains unclear. MethodsWe retrospectively reviewed the data of patients treated at National Cancer Center Hospital in Japan between 2000 and 2018. We selected patients with type IV GC in which the predominant location could be identified, who received D2 or more total gastrectomy with splenectomy, and in whom R0 or R1 resection was achieved. The therapeutic value index was evaluated by multiplying the metastatic rate of each nodal station by the five-year overall survival (OS) rate of patients with metastasis to each node. ResultsIn total, 180 patients were included in this study (antral type, n=19 [10.6%]; body type, n=161 [89.4%]). Both types showed similar and frequent invasion of the greater curvature of the upper stomach. Metastasis to the splenic hilar nodes (#10) was not observed in the antral type (0/19) but was observed in the body type (35/161, 21.7%); the difference was statistically significant (p=0.027). The therapeutic value index of #10 was 0 in the antral type but was >7, the fourth highest, in the body type. The only nodes with an index >0 in the antral type were #4d, #3, #4sb, #6, #7, and #1. ConclusionsSplenectomy may therefore be unnecessary for antral-type scirrhous GC.

Impact of D2 Total Gastrectomy Including Splenectomy for Scirrhous Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

Total gastrectomy with D2 dissection including splenectomy (TGS) is usually selected for locally resectable scirrhous gastric cancer (SGC), which was established in the era of surgery alone. However, it remains unclear whether TGS for SGC is justified in the era of effective adjuvant chemotherapy. This study included 112 SGC patients, consisting of 60 cases treated between January 2000 and December 2006 (Former group), and 52 cases treated between January 2007 and December 2016 (Latter group). We collected clinicopathological data and then examined the survival and the therapeutic value indexes. The background characteristics were well-balanced, except for sex and physical status. The Latter group might be characterized by frequent female (P = 0.037) and poorer physical status (P = 0.048). Adjuvant chemotherapy was administered to 86.5% of the Latter group and was 11.7% of the Former group (P < 0.001). The 5-year-overall survival rate of the Latter group was 58.7% (95% confidence interval: 43.5-71.1), seems better than that of the Former group (44.5%; 95% confidence interval 31.7-56.6) (hazard ratio = 0.758, P = 0.291). Improvement of the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between two groups was 1.42 at the D1 station and 1.67 at the D2 station. Index of splenic hilar node ranked similarly high in both groups. The therapeutic value index was improved in almost all nodal stations by S-1 adjuvant chemotherapy, especially in D2 nodes. TGS would be more important for locally resectable SGC in the era of effective adjuvant chemotherapy.

Retraction Note to: Mesothelial cells differentiate into fibroblast-like cells under the scirrhous gastric cancer microenvironment and promote peritoneal carcinomatosis in vitro and in vivo.

Retraction Note to: Mesothelial cells differentiate into fibroblast-like cells under the scirrhous gastric cancer microenvironment and promote peritoneal carcinomatosis in vitro and in vivo.

CCDC85A is regulated by miR-224-3p and augments cancer cell resistance to endoplasmic reticulum stress.

MicroRNAs (miRNAs) play pivotal roles in the tumor microenvironment. Here, we analyzed miRNAs in tumor stromal fibroblasts. Expression of miR-224-3p in cancer-associated fibroblasts (CAF) from scirrhous gastric cancer patients was lower than in normal fibroblasts (NF). Introduction of a miR-224-3p mimic attenuated migration and invasion of CAF. Coiled-coil domain containing 85A (CCDC85A), whose function in tumors is not understood, was the target gene of miR-224-3p. Immunohistological analysis revealed that CCDC85A is expressed to varying degrees by cancer cells and CAFs in gastric and pancreatic carcinomas. Downregulation of CCDC85A in cancer cells revealed that these cells are vulnerable to endoplasmic reticulum (ER) stress induced by thapsigargin or tunicamycin, which were ameliorated after addback of CCDC85A. Injection of NF-derived exosomes containing miR-224-3p into the xenograft tumor increased tumor shrinkage by cisplatin treatment. Mechanistically, CCDC85A associated with the molecular chaperone GRP78 and GRP94, thereby inhibiting association of these negative regulators of the unfolded protein response (UPR), leading to sustained activation of PERK and downstream eIF2〈 and ATF4 upon ER stress. These data suggest a novel miR-224-3p-mediated function for CCDC85A: protection from ER stress and cisplatin resistance.

Efficacy for diagnoses of scirrhous gastric cancer and safety of endoscopic ultrasound-guided fine-needle aspiration: A systematic review and meta-analysis.

Scirrhous gastric cancer (SGC) is diagnosed using endoscopy and/or biopsy; however, SGC diagnosis remains challenging owing to its special growth form and morphologic features. Hence, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is minimally invasive and has a high proportion of diagnostic tissue, may be an alternative investigative modality for patients with suspected SGC. This systematic review and meta-analysis aimed to identify and evaluate the evidence for the efficacy and safety of EUS-FNA in patients with suspected SGC. We conducted a systematic review using the PubMed (MEDLINE) and Ichushi-Web (NPO Japan Medical Abstracts Society) databases and included all entries in which SGC was evaluated using EUS-FNA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the databases' inception to October 10, 2022. The primary outcome was the proportion of SGC diagnosed using EUS-FNA. In addition, we analyzed the proportion of adverse events associated with EUS-FNA. The electronic search identified 1890 studies; overall, four studies met the selection criteria and reported data on EUS-FNA performed on 114 patients with suspected SGC. The overall diagnostic yield of EUS-FNA for SGC was 82.6% (95% confidence interval, 74.6-90.6%) and the statistical heterogeneity was 0% (I 2 = 0%), indicating a low heterogeneity. Furthermore, the EUS-FNA diagnostic proportion for SGC lymph node metastasis was 75-100%, indicating a high diagnostic performance. The adverse event rate of EUS-FNA was 0%. EUS-FNA may be an alternative investigation mode for SGC patients with negative esophagogastroduodenoscopy-biopsy results.

Combined intraperitoneal and systemic chemotherapy as adjuvant or perioperative chemotherapy for patients with type 4 scirrhous gastric cancer: PHOENIX-GC2 trial.

TPS477 Background: Despite recent progress in adjuvant and perioperative chemotherapy, the prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combination chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a multicenter, open-label, randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Methods: Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled from 40 hospitals throughout Japan. Clinical trial information: jRCT2031200087 .

Diffusely infiltrative squamous cell carcinoma of the esophagus resembling scirrhous gastric cancer: a case report.

The patient was a 75-year-old woman whose chief complaints were dysphagia and upper abdominal pain. Esophagogastroduodenoscopy and biopsy revealed squamous cell carcinoma at the abdominal esophagus. After neoadjuvant chemotherapy, esophagogastroduodenoscopy showed diffuse thickening and poor distensibility of the stomach wall. We suspected scirrhous gastric cancer and performed multiple biopsies, which revealed no evidence of malignancy. We then performed staging laparoscopy. There were no apparent changes in the serous membrane of the stomach, but peritoneal lavage cytology revealed squamous cell carcinoma. Thus, we made a diagnosis of squamous cell carcinoma of the esophagus with diffuse invasion of the stomach. Intraoperative pathological diagnosis revealed that there was greater diffuse submucosal invasion of the oral esophagus than we expected, and we had to resect the esophagus at the level of the middle thoracic esophagus. Despite multidisciplinary treatment (surgery, chemotherapy, and radiotherapy), the patient died 20 months after the initial diagnosis. In this case, although biopsy did not lead to a diagnosis, peritoneal lavage cytology led to the correct diagnosis. Moreover, it was impossible to preoperatively predict the exact extent of the expansion because of diffuse submucosal invasion. When diffusely infiltrative squamous cell carcinoma of the esophagus is suspected, peritoneal lavage cytology may be useful for confirming the diagnosis; however, it should be assumed that accurate preoperative evaluation of the range of diffusely infiltrative squamous cell carcinoma is difficult.

Elevated METTL9 is associated with peritoneal dissemination in human scirrhous gastric cancers

Methylation, the most common chemical modification of cellular components such as DNA, RNA, and proteins, impacts biological processes including transcription, RNA processing, and protein dynamics. Although abnormal expression of methyltransferase can lead to various diseases including cancers, little is known about the relationship between methyltransferase and cancers. Here we aimed to understand the role of methyltransferase in cancer metastasis. We found that elevated methyltransferase-like 9 (METTL9) is closely associated with the acquisition of metastatic activity in human scirrhous gastric cancers. The stable knockdown of METTL9 via an shRNA vector technique in our original metastatic cells from scirrhous gastric cancer patients significantly inhibited migration and invasion. In metastatic cells, METTL9 protein is predominantly localized in mitochondria, and the METTL9 knockdown significantly reduced mitochondrial Complex I activity. METTL9 can be a candidate of molecular targets to inhibit peritoneal dissemination of scirrhous gastric cancers. This report is the first to describe the relationship between METTL9 and cancer metastasis.

Dual blockade of MET and VEGFR2 signaling pathways as a potential therapeutic maneuver for peritoneal carcinomatosis in scirrhous gastric cancer

Scirrhous gastric cancer frequently develops into peritoneal carcinomatosis with malignant ascites, leading to an extremely poor prognosis. We had demonstrated that paracrine hepatocyte growth factor (HGF)-induced MET activation promotes peritoneal carcinomatosis with ascites formation. The vascular endothelial growth factor (VEGF) receptor (VEGFR)/VEGF axis facilitates tumor progression and formation of malignant ascites. This study investigated the role of MET and VEGFR2 in the development of peritoneal carcinomatosis with malignant ascites. Cabozantinib is a dual inhibitor of MET and VEGFR2. We examined the effects of cabozantinib on MET- and VEGFR2-mediated progression of peritoneal carcinomatosis in human scirrhous gastric cancer in vitro and in vivo. Cabozantinib inhibited HGF-stimulated proliferation of scirrhous cancer cell lines NUGC4 and GCIY, with a high potential to generate peritoneal carcinomatosis with ascites fluid, as well as the constitutive proliferation of MKN45 cells with MET amplification. Cabozantinib also inhibited the phosphorylation of both MET and VEGFR2 in scirrhous cancer cells and HGF- or VEGF-stimulated HUVECs. It effectively reduced ascitic fluid and prolonged the survival of NUGC4-inoculated nude mice. In clinical specimens, malignant ascites fluid from patients with peritoneal carcinomatosis contained high levels of HGF and VEGF. Our results strongly suggest that MET- and VEGFR2-mediated signaling pathways play pivotal roles in the pathogenesis of peritoneal carcinomatosis in scirrhous gastric cancer. Thus, the dual blockade of MET and VEGFR2 signaling may be a potential therapeutic maneuver for peritoneal carcinomatosis in scirrhous gastric cancer.

Crosstalk of tumor stromal cells orchestrates invasion and spreading of gastric cancer.

Tumors contain various stromal cells that support cancer progression. Some types of cancer, such as scirrhous gastric cancer, are characterized by large areas of fibrosis accompanied by cancer-associated fibroblasts (CAFs). Asporin (ASPN) is a small leucine-rich proteoglycan highly expressed in CAFs of various tumors. ASPN accelerates CAF migration and invasion, resulting in CAF-led cancer cell invasion. In addition, ASPN further upregulated the expression of genes specific to a characteristic subgroup of fibroblasts in tumors. These cells were preferentially located at the tumor periphery and could be generated by a unique mechanism involving the CAF-mediated education of normal fibroblasts (CEFs). In this review, we at first describe recent findings regarding the function of ASPN in the tumor microenvironment, as well as the mechanism involved in the generation of CEFs. CAFs are derived from heterogeneous origins besides resident normal fibroblasts. Among them, CAFs derived from mesothelial cells (mesothelial cell-derived CAF [MC-CAFs]) play pivotal roles in peritoneal carcinomatosis. We observed that MC-CAFs on the surfaces of organs also participate in tumor formation by infiltrating into the parenchyma, promoting local invasion by gastric cancers. This review also highlights the potential functions of macrophages in the formation of MC-CAFs in gastric cancers, by transfer the contents of cancer cell-derived extracellular vesicles.

Soluble podoplanin as a biomarker in diffuse‑type gastric cancer.

Diffuse‑type gastric cancer, also known as scirrhous gastric cancer, is characterized by a larger number of stromal cells, referred to as cancer‑associated fibroblasts (CAFs), than the number of cancer cells in the tissue. The present study focused on CAFs in gastric cancer and examined their potential as a blood biomarker. A total of 46and84patients with gastric cancer were respectively included in a development and an independent validation cohort to assess the clinicopathological characteristics of plasma podoplanin (PDPN) levels. The prognostic impact of plasma PDPN was also investigated in the validation cohort. The cut‑off value of the plasma‑PDPN concentration was set to the median plasma PDPN concentration in the development cohort that was then divided into the high‑PDPN and low‑PDPN groups. The high‑PDPN group tended to have more diffuse‑type disease (P=0.079), which was further confirmed through logistic regression analysis (P=0.008). Kaplan‑Meier survival estimates indicated that the recurrence‑free survival rate was significantly lower in the high‑PDPN group (P=0.029). In conclusion, plasma soluble PDPN was demonstrated to be a marker for diffuse gastric cancer and may reflect the prognosis of this disease.

Dipeptidyl Peptidase-4 from Cancer-associated Fibroblasts Stimulates the Proliferation of Scirrhous-type Gastric Cancer Cells.

Cancer-associated fibroblasts (CAFs) may promote the malignancy of human scirrhous gastric cancer (SGC) cells. We conducted the present study to identify novel growth factors from CAFs. OCUM-12 and 2 CAF cell lines were used. The proliferation of cancer cells was determined by the number of cancer cells or the MTT assay. The growth factor(s) were purified and characterized by the gel filtration chromatography and protein array. The molecular weight of the growth-stimulating factor was estimated to be approximately 66-669 kDa. Protein array of conditioned medium (CM) from CAFs indicated that dipeptidyl peptidase-4 (DPP-4) was one of the growth factors. The addition of CM increased the phosphorylation of C-X-C chemokine receptor 4 (CXCR4). The DPP-4 inhibitor significantly inhibited the growth-stimulating activity of CM. DPP-4 from CAFs might be one of the growth-stimulating factors for SGC through CXCR4.

Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial.

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

Telmisartan Exerts Cytotoxicity in Scirrhous Gastric Cancer Cells by Inducing G0/G1 Cell Cycle Arrest.

This study aimed to assess the effects of telmisartan (TEL), a potential antitumor agent, and its mechanism of action in the regulation of apoptosis, autophagy, and cell cycle in scirrhous gastric cancer (SGC). The effect of TEL on the viability and chromatin condensation of OCUM-2M and OCUM-12 cells was assessed. Protein expression and the cell cycle were analysed using western blotting and flow cytometry, respectively. TEL inhibited cell proliferation in a dose-dependent manner and increased chromatin condensation and autophagy marker LC3-II levels in OCUM-12 cells. TEL also increased the proportion of cells in the G0/G1 phase transition. Apoptosis and autophagy are partially involved in the inhibitory effect of TEL on cell proliferation. Additionally, TEL caused G0/G1 cell cycle arrest. Therefore, TEL could be a promising treatment for SGC.

Phlegmonous gastritis: a case series

BackgroundPhlegmonous gastritis is a rare and fatal infectious disease of the stomach, presenting varied and nonspecific endoscopic images, which are therefore difficult to diagnose. This report discusses three cases of phlegmonous gastritis, each with unique endoscopic images, and considers the differential diagnosis of this disease. These cases were initially suspected of scirrhous gastric cancer, gastric syphilis, and acute gastric mucosal lesion.Case presentationCase 1 A 32-year-old Asian man visited our hospital complaining of upper abdominal pain. Endoscopy raised suspicion of scirrhous gastric cancer. However, a histopathological examination showed no malignant cells, thus leading to the diagnosis of phlegmonous gastritis. The patient was started on antibiotic therapy, which was effective.Case 2 A 33-year-old Asian man visited our hospital complaining of epigastralgia. Endoscopy raised suspicion of gastric syphilis. However, the serum test for syphilis was negative, and Streptococcus viridans was detected in the biopsy specimen culture, which led to the diagnosis of phlegmonous gastritis.The patient was started on antibiotic therapy, resulting in significant improvement in the endoscopic image after 2 weeks.Case 3 A 19-year-old Asian man visited our hospital complaining of epigastric pain. Endoscopy raised suspicion of acute gastric mucosal lesion. A gastric juice culture showed Pseudomonas aeruginosa and Streptococcus viridans, thus leading to the diagnosis of phlegmonous gastritis. The patient was started on antibiotic therapy, resulting in the disappearance of the gastric lesions.ConclusionIn severe cases of phlegmonous gastritis, immediate surgical treatment is generally required. However, the endoscopic images are varied and nonspecific. These three cases suggest that clinicians need to consider the differential diagnosis of phlegmonous gastritis and make accurate diagnoses at an early stage.

Abstract 258: Identification of characteristic genes of scirrhous-type gastric cancer cells by RNAseq

Abstract Introduction: Scirrhous gastric cancer shows an extremely poor prognosis with rapid growth and infiltration activity. One of the reasons for poor prognosis is a lack of the identification of driver gene for scirrhous gastric cancer. FGFR2 (fibroblast growth factor receptor 2), E-cadherin, TGFβR (transforming growth factor β receptor), CD44/IGFIR (insulin-like growth factor I receptor), have been reported as candidates of driver for scirrhous-type of gastric cancer, however useful molecular-targeted therapeutic agents against these driver molecules have not yet been clinically approved. In this study, we identified the characteristic genes of scirrhous-type gastric cancer by RNA-seq of gastric cancer cell lines. Methods: RNA-seq was performed using 6 scirrhous gastric cancer cell lines (OCUM1, OCUM2MLN, OCUM8, OCUM12, OCUM13, OCUM14) using a next-generation sequencer (ION S5 system, Thermo Fisher Scientific). Furthermore, RNA-seq public data of 4 strains of scirrhous gastric cancer cell lines (KATO3, NUGC4, SNU601, SNU668) and 10 strains of non-scirrhous gastric cancer cell lines (MKN7, MKN45, MKN74, HS746T, SNU1, SNU16, SNU638, AZ521, HGC27, TMK1) on the Sequence Read Archive were added, and the genes expressed in scirrhous gastric cancer were compared and examined. The analysis tools used were kallisto and sleuth. We set p-value &amp;lt; 0.05 and log2 (fold change) &amp;gt; 2 as the cut-offs to screen out differentially expressed genes (DEGs). Pathway enrichment and protein-protein interaction (PPI) network analysis were performed based on metascape databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed for the genes. Results: A total of 234 DEGs were identified from this analysis. A gene co-expression network was constructed containing 8 DEGs. The genes were mainly associated with response to chemokine, and cytokine-mediated signaling pathway. Several critical genes were disclosed, such as C-C motif chemokine ligand 20 (CCL20) and C-X-C subfamiliy. Genes highly expressed in scirrhous gastric cancer cell lines were CCL20 (10.6-fold change, p=9.89×10-4) and C-X-C Motif Chemokine Ligand 3 (CXCL3, 19.5-fold change, p=1.67×10-5). The mean of abundances across samples (=log(counts+0.5)), which represent the average expression levels of all samples, were CCL20 and CXCL3, 4.04 and 4.53, respectively. KEGG pathway enrichment analysis showed that viral protein interaction with cytokine and cytokine receptor, Cytokine-cytokine receptor interaction and IL-17 signaling pathway were significantly over-represented. Conclusion: CCL20 and CXCL3 might be characteristic genes for scirrhous-type of gastric cancer. Citation Format: Tomohiro Sera, Masakazu Yashiro, Gen Tsujio, Yurie Yamamoto, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Masaichi Ohira. Identification of characteristic genes of scirrhous-type gastric cancer cells by RNAseq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 258.

Comparative Outcomes of Laparoscopic Gastrectomy and Open Gastrectomy for Scirrhous Gastric Cancer: A Multicenter Retrospective Cohort Study.

A multicenter retrospective cohort study was performed to compare the outcomes of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for scirrhous gastric cancer (GC) as a unique subtype also known as type 4 gastric cancer or linitis plastica. Although data on the efficacy and safety of LG as an alternative to OG are emerging, the applicability of LG to scirrhous GC remains unclear. Patients with clinical type 4 GC undergoing gastrectomy at 13 hospitals from 2005 to 2015 were retrospectively reviewed. As the primary endpoint, we compared overall survival (OS) between the LG and OG groups. To adjust for confounding factors, we used multivariate Cox regression analysis for the main analyses and propensity-score matching for sensitivity analysis. Short-term outcomes and recurrence-free survival were also compared. A total of 288 patients (LG, 62; OG, 226) were included in the main analysis. Postoperative complications occurred in 25.8% and 30.1%, respectively (P = 0.44). No significant difference in recurrence-free survival was observed (P = 0.72). The 5-year OS rates were 32.4% and 31.6% in the LG and OG groups, respectively (P = 0.60). The hazard ratio (LG/OG) for OS was 0.98 (95% confidence interval [CI], 0.65-1.43) in the multivariate regression analysis. In the sensitivity analyses after propensity-score matching, the hazard ratio for OS was 0.92 (95% CI, 0.58-1.45). Considering the hazard ratios and 95% CIs for OS, LG for scirrhous GC was not associated with worse survival than that for OG.

A case of small 0-IIc-like scirrhous gastric cancer that developed 5 years after &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication placement: A case report

A case of small 0-IIc-like scirrhous gastric cancer that developed 5 years after &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication placement: A case report

Long Noncoding RNA HOTAIR Promotes Epithelial-Mesenchymal Transition and Is a Suitable Target to Inhibit Peritoneal Dissemination in Human Scirrhous Gastric Cancers

Objectives: Scirrhous gastric cancer, which accounts for approximately 10% of all gastric cancers, often disseminates to the peritoneum, leading to intractable cases with poor prognosis. There is an urgent need for new treatment approaches for this difficult cancer. Methods: We previously established an original cell line, HSC-60, from a scirrhous gastric cancer patient and isolated a peritoneal-metastatic cell line, 60As6, in nude mice following orthotopic inoculations. In the present study, we focused on the expression of long noncoding ribonucleic acid (RNA) (lncRNA) in the cell lines and investigated the mechanism on peritoneal dissemination. Results: We demonstrated that an lncRNA, HOX transcript antisense RNA (HOTAIR), is expressed significantly more highly in 60As6 than HSC-60 cells. Then, using both HOTAIR knockdown and overexpression experiments, we showed that high-level expression of HOTAIR promotes epithelial-mesenchymal transition (EMT) in 60As6 cells. By luciferase assay, we found that HOTAIR directly targets and binds to miR-217, and that miR-217 directly binds to Zinc finger E-box-binding homeobox 1 (ZEB1). The knockdown of HOTAIR in 60As6 cells significantly reduced the invasion activity and peritoneal dissemination – and significantly prolonged the survival – in the orthotopic tumor mouse model. Conclusion: An EMT-associated pathway (the HOTAIR-miR-217-ZEB1 axis) appears to inhibit peritoneal dissemination and could lead to a novel therapeutic strategy against scirrhous gastric cancer in humans.

Three Cases of Scirrhous Gastric Cancer After Eradication of &lt;i&gt;Helicobacter Pylori&lt;/i&gt;

The incidence of gastric cancer after eradication of Helicobacter pylori (HP) is expected to increase in the future. Although reports of early gastric cancer after the eradication account for the majority of cases, scirrhous gastric cancer is rare. Herein, we report three cases of scirrhous gastric cancer after eradication of HP. Case 1: A 50-year-old woman had been treated with eradication of HP and was followed up by esophagogastroduodenoscopy (EGD) on a regular basis. Two years after the eradication, EGD revealed advanced type 4 gastric cancer. Case 2: A 50-year-old woman had been treated with eradication and was followed up by EGD on a regular basis. Twenty-four years after the eradication, EGD revealed advanced type 4 gastric cancer. Case 3: A 50-year-old man had been treated with eradication and was followed up every year by EGD. Five years after the eradication, EGD revealed advanced type 4 gastric cancer. Despite performing regular EGD, cases of scirrhous gastric cancer can be found after eradication. We report our encountered cases, along with relevant literature.