Gastric ectopic pancreas combined with synchronous multiple early gastric cancer: A rare case report.

BACKGROUND: A large percentage of patients with ectopic pancreas are asymptomatic. When present, the symptoms are typically non-specific. These lesions are predominantly located in the stomach and benign in nature. Synchronous multiple early gastric cancer (SMEGC) (two or more simultaneous malignant lesions with early gastric cancer) is relatively rare and particularly easy to overlook during endoscopic examination. The prognosis of SMEGC is generally poor. We report a rare case of ectopic pancreas with concomitant SMEGC. CASE SUMMARY: A 74-year-old woman presented with paroxysmal upper abdominal pain. On initial investigations, she tested positive for Helicobacter pylori (H. pylori). She underwent esophagogastroduodenoscopy which revealed a 1.5 cm × 2 cm major lesion at the greater curvature and a 1 cm minor lesion at the lesser curvature of the stomach. On endoscopic ultrasound, the major lesion showed hypoechoic changes, uneven internal echoes and unclear boundaries between some areas and the muscularis propria. Endoscopic submucosal dissection was performed to excise the minor lesion. A laparoscopic resection was chosen for the major lesion. On histopathological examination, the major lesion contained high grade intraepithelial neoplasia with a small focus of cancer. A separate underlying ectopic pancreas was found under this lesion. The minor lesion contained high grade intraepithelial neoplasia. In this case, the patient was diagnosed with SMEGC with concomitant ectopic pancreas in the stomach. CONCLUSION: Patients with atrophy, H. pylori, and other risk factors should be carefully investigated to avoid missing other lesions including SMEGC and ectopic pancreas.

Role of CARD9 in inflammatory signal pathway of peritoneal macrophages in severe acute pancreatitis.

Previous studies revealed that caspase recruitment domain protein 9 (CARD9) was involved in severe acute pancreatitis (SAP) inflammation and that interfering with its expression in vivo could inhibit inflammation. However, the specific mechanism is unknown. This study aimed to discover the related signal pathways of CARD9 in macrophages. SiRNA interference technology was used in vivo and in vitro to detect CARD9-related signal pathways in peritoneal macrophages. Furthermore, Toll-like receptor 4 (TLR4) and membrane-associated C-type lectin-1 (Dectin-1) pathways in macrophages were activated specially to looking for the upstream signal path of CARD9. Results showed up-regulation of CARD9 expression in peritoneal macrophages of SAP rats (P < .05). CARD9 siRNA alleviated inflammatory cytokines, and inhibited the phosphorylation of NF-κB and p38MAPK in peritoneal macrophages in vivo or in vitro. Meanwhile, CARD9 siRNA reduced the concentration of CARD9 and Bcl10 in peritoneal macrophages, and TLR4 and Dectin-1 took part in CARD9 signal pathways in macrophages. In conclusion, there is an inflammation signal pathway comprised of TLR4/Dectin-1-CARD9-NF-κB/p38MAPK activated in macrophages in SAP. Blockade of CARD9 expression in macrophages can effectively alleviate SAP inflammation.

Phosphoinositide 3­kinase/protein kinase B regulates inflammation severity via signaling of Toll­like receptor 4 in severe acute pancreatitis.

Phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) has been indicated to serve an important role in the pathogenesis of inflammatory diseases. It was previously demonstrated that the PI3K/Akt inhibitor wortmannin alleviated the severity of inflammation and improved the survival rate in rats with induced severe acute pancreatitis (SAP), which indicates that PI3K/Akt may serve a role in the pathogenesis of acute pancreatitis. To date, the mechanism by which PI3K/Akt regulates inflammation has not been elucidated. In the present study, it was hypothesized that PI3K/Akt may be invovled in SAP inflammation via regulation of the Toll­like receptor 4 (TLR4) signaling pathway. Rats with SAP were treated with the PI3K/Akt agonist insulin­like growth factor (IGF)­1, which alleviated the severity of inflammation in a dose­dependent manner. Furthermore, to better understand the role of PI3K/Akt in inflammation, RAW264.7 murine macrophages were stimulated with IGF­1 and wortmannin alone or together before the induction of inflammation by treatment with lipopolysaccharide (LPS). The results indicated that LPS stimulated overexpression of TLR4, myeloid differentiation primary response gene 88 (MyD88), PI3K, Akt, p38MAPK and NF­κBp65 mRNA, and increased the levels of tumor necrosis factor (TNF)­α and interleukin (IL)­6 in RAW264.7 cells compared with the control group. The levels of all detected factors were increased by stimulation with IGF­1, whereas these levels were decreased following treatment with wortmannin alone, and the effect of IGF­1 was abolished by wortmannin in RAW264.7 cells. In vivo studies indicated that IGF­1 produced the same anti­inflammatory effect as wortmannin and that expression of TLR4, p38MAPK and NF­κBp65 decreased following treatment with IGF­1. These findings indicate that PI3K/Akt may take part in the progression of SAP by regulating the TLR4 signaling pathway and that IGF­1 can inhibit inflammation in SAP rats.

15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric carcinoma.

AIM: To investigate the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle arrest. METHODS: Expression of 15-PGDH mRNA and protein was examined by immunohistochemistry, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting in tissue from human gastric cancer, gastric precancerous state (gastric polyps and atrophic gastritis), normal stomach, and gastric cancer cell lines. The relationship between gastric cancer, gastric precancerous state and 15-PGDH expression was determined. The association between expression of 15-PGDH and various clinicopathological parameters in gastric cancer was evaluated. Human gastric cancer cell line SGC-7901 was transfected with 15-PGDH expression plasmids. The effect of 15-PGDH on the cell cycle was examined by flow cytometry. The effect of 15-PGDH on apoptosis was examined by transmission electron microscopy, flow cytometry and transferase mediated nick end labeling (TUNEL) assay. Expression of cell cycle (p21, p27, p16 and p53) and apoptosis (Survivin, BCL-2, BCL-X(L), BAK and BAX) genes was analyzed by RT-PCR. RESULTS: Expression of 15-PGDH mRNA and protein in human gastric cancer tissues was significantly lower than in normal gastric tissues (P < 0.01). Expression in human gastric cancer cell lines MKN-28 and MKN-45 was reduced, and absent in SGC-7901 cells (P < 0.05). Reduction of 15-PGDH expression was also found in precancerous tissues, such as gastric polyps and atrophic gastritis (P < 0.01). There was a significant difference in expression of 15-PGDH among various gastric cancer pathological types (P < 0.05), with or without distant metastasis (P < 0.05) and different TNM stage (P < 0.01). Flow cytometry demonstrated a significant increase in apoptotic cells in SGC-7901 cells transfected with pcDNA3/15-PGDH plasmid for 24 h and 48 h (P < 0.01), and an increased fraction of sub-G1 phase after transfection (P < 0.05). TUNEL assay showed an increased apoptotic index in cells overexpressing 15-PGDH (P < 0.01). After transfection, expression of proapoptotic genes, such as BAK (P < 0.05), BAX and p53 (P < 0.01), was increased. Expression of antiapoptotic genes was decreased, such as Survivin, BCL-2 and BCL-X(L) (P < 0.01). Expression of cyclin-dependent kinase inhibitors p21 and p16 (P < 0.01) was significantly upregulated in cells overexpressing 15-PGDH. CONCLUSION: Reduction of 15-PGDH is associated with carcinogenesis and development of gastric carcinoma. 15-PGDH induces apoptosis and cell cycle arrest in SGC-7901 cells.