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.

Phlegmonous gastritis: a case series

Background Phlegmonous 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 presentation Case 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. Conclusion In 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.

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

<b><i>Objectives:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.