Inhibition of LPS-mediated TLR4 activation abrogates gastric adenocarcinoma-associated peritoneal metastasis

Bacground/Aim. Peritoneal metastasis is a leading cause of therapeutic failure after an operative treatment of patients with gastric adenocarcinoma. Free cancer cells might induce or indicate an early peritoneal seeding with a subsequent peritoneal metastasis. The aim of this study was to determine the frequency of the presence of free cancer cells in the peritoneal cavity in the patients surgically treated for gastric adenocarcinoma, and its relation to certain clinical, operative and pathohistological parameters. Methods. Inside a period from April 2000, and April 2004, the total of 100 patients underwent intraoperative peritoneal lavage for cytological examination. Immediately after the laparotomy, 200 ml physiologic saline, heated to 37 ?C, was introduced into the abdominal cavity, manually dispersed and collected from the region around the gastric tumor and the pouch of Douglas. The nucleated cell layer was smeared on four glass slides for every patient and dyed with May-Gr?nwald-Giemsa stain. The cytological findings were defined as positive or negative according to the presence of cancer cells. The frequency of positive cytological findings was compared to the location and the diameter of the cancer, pathohistological type of carcinoma, pathohistological stage of the disease, lymph node and the liver and/or peritoneal metastases and the type of surgical procedure. Results. Free cancer cells were found in 24 (24%) of the patients, while in 76 (76%) of them cytological findings were negative. A statistically highly significant difference (p ? 0.001) in the frequency of positive cytological finding was found between the groups of patients with and without cancer invasion of serosa, with cancer diameters > 5 cm and ? 5 cm, in the stage of disease I, II and III, IV, with macroscopically present and without metastases, with resection and D2 lymphadenectomy and palliative procedure. Free cancer cells were statistically more frequently (p ? 0.05) detected in the patients with lymph nodes metastases comparing to the patients without lymph nodes involvement. The results of the univariate analysis showed that the cancer diameter > 5 cm, tumor invasion of serosa, pathohistological stage of the disease III and IV and macroscopically visible metastases were the most important risk factors for the free cancer cells detection. Conclusion. Peritoneal lavage cytology was shown to be a useful tool for the detection of the group of patients with greatest risk of peritoneal dissemination. The frequency of positive cytological findings was highly associated with the diameter of the tumor and the cancer invasion of serosa. Cytological examination of peritoneal lavage fluid improved the accuracy of staging and selection of patients who might have benefit from neoadjuvant chemotherapy.

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Whole-Exome Sequencing Reveals Molecular Characterization of Early-Onset and Peritoneal Metastasis in Gastric Cancers

10.21203/rs.3.rs-880086/v1 ◽

2021 ◽

Author(s):

Zhi-wei Zhou ◽

Hai-bo Qiu ◽

Xu-jun Wang ◽

Wei Wang ◽

Ting Wu ◽

...

Keyword(s):

Exome Sequencing ◽

Molecular Characterization ◽

Gastric Adenocarcinoma ◽

Peritoneal Metastasis ◽

Early Onset ◽

Somatic Mutations ◽

Cancer Center ◽

Gastric Cancers ◽

Younger Age ◽

Cancer Aggressiveness

Abstract Background: Increasing numbers of Gastric cancer(GC) patients were diagnosed at younger age with aggressive behavior including early disease recurrence, more frequent peritoneal metastasis and poor overall survival. To investigate the driver genes and mechanisms of the early-onset and more aggressive nature of the GC.Methods: Gastric adenocarcinoma and matched germline samples were obtained from patients in Sun Yat-sen University Cancer Center between 2007 and 2013. Exome sequencing were performed for 198 pairs of primary gastric adenocarcinoma fresh tissue and blood samples from young or elder patients. Besides, matched tumor / blood exome sequencing was performed in 80 patients with peritoneal seeding and 51 patients without. Then bioinformatics analysis was performed to find genomic variants and their clinical meanings.Results: Early-onset gastric cancers (EOGCs) have fewer somatic mutations but some deleterious germline variates in FAT genes, patients carried none, one, two, three of the 4 Single nucleotide polymorphisms (SNPs), the mean ages of diagnosis are 60, 50, 40 and 35 respectively. Somatic mutations in CDH1, TGFBR1 and CTNNB1 are related to early-onset cancers. These variants are all linked to WNT pathways. Somatic mutations in genes involved in cancer aggressiveness like MAP2K7, CDH1 and RhoA are related to cancer progression and metastasis. Patients carrying RhoA, ITGAV, TGFBR1, CDH1, CTNNB1, MYO9B, VAV1, SALL1, CDX4 somatic mutations or simultaneously carrying three FAT germline SNPs have been diagnosed at younger age than those have only TP53 mutations.Conclusions: The molecular characterization gives us a novel insight into the carcinogenesis and tumor progression mechanisms and may provide a guide to developing novel targeted therapy in GC.

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