There has been worldwide debate on lymphadenectomy for gastric cancer, with increasing consensus on performing an extended (D2) resection. There is a paucity of data in Australia. Our aim is to compare overall outcomes between a D1 and D2 lymphadenectomy for gastric cancer in a single specialist unit. We performed a retrospective analysis on patients who underwent a curative primary gastric resection for gastric adenocarcinoma between January 1996 and April 2016, primary outcomes included overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) analysis was used to balance covariates between D1/D1+ and D2 groups. Kaplan-Meier survival curves of D1/D1+ versus D2 were constructed and evaluated using the log-rank test with subgroup analyses for pathological node (pN) status. Multiple Cox proportional hazards model was used to determine predictors of overall survival. Two hundred four patients underwent a gastrectomy, 54 had D1/D1+, and 150 had a D2 lymphadenectomy. After PSM, there were 39 patients in each group, the 10-year OS for D1/D1+ was 52.1 and 76.2% for D2 (p = 0.008), and 10-year DFS was 35% for D1 and 58.1% for D2 (p = 0.058). Subgroup analysis showed that node-negative (N0) patients had improved 5-year OS for D2 (90.9%), compared to D1/D1+ (76.4%) (p = 0.028). There was no difference in operative mortality between the groups (D1 vs D2: 2 vs 0%, p = 0.314), nor in post-operative complications (p = 0.227). Multiple Cox analysis showed advanced tumor stage (stages III and IV), and lymphadenectomy type (D1) and the presence of postoperative complications were independent predictors of poor overall survival. D2 lymphadenectomy with spleen and pancreas preservation can be performed safely on patients with gastric adenocarcinoma. Significant improvement in overall survival is observed in patients with N0 disease who underwent D2 lymphadenectomy without increasing operative morbidity or mortality. This paper supports the notion of a global consensus for a D2 lymphadenectomy, particularly in the Western context.

Background: HCC develops in the context of chronic inflammation; however, the opposing roles the immune system plays in both the development and control of tumors are not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumors. Methods: A 39-parameter imaging mass cytometry panel was optimized with markers targeting immune cells, stromal cells, endothelial cells, hepatocytes, and tumor cells. We mapped the immune landscape of tumor, invasive margin, and adjacent nontumor regions across 16 resected tumors comprising 144 regions of interest. X-shift clustering and manual gating were used to characterize cell subsets, and Spectre quantified the spatial environment to identify cellular neighborhoods. Ligand-receptor communication was quantified on 2 single-cell RNA-sequencing data sets and 1 spatial transcriptomic data set. Results: We show immune cell densities remain largely consistent across these 3 regions, except for subsets of monocyte-derived macrophages, which are enriched within the tumors. Mapping cellular interactions across these regions in an unbiased manner identifies immune neighborhoods comprised of tissue-resident T cells, dendritic cells, and various macrophage populations around perivascular spaces. Importantly, we identify multiple immune cells within these neighborhoods interacting with VEGFA⁺ perivascular macrophages. VEGFA was further identified as a ligand for communication between perivascular macrophages and CD34⁺ endothelial cells. Conclusions: Immune cell neighborhood interactions, but not cell densities, differ between intratumoral and adjacent nontumor regions in HCC. Unique intratumoral immune neighborhoods around the perivascular space point to an altered landscape within tumors. Enrichment of VEGFA⁺ perivascular macrophages within these tumors could play a key role in angiogenesis and vascular permeability.