Robotic versus laparoscopic gastrectomy for gastric cancer: A Western propensity score matched analysis.

BACKGROUND: Robot-assisted gastrectomy (RG) has been shown to be safe and feasible in the treatment of gastric cancer (GC). However, it is unclear whether RG is equivalent to laparoscopic gastrectomy (LG), especially in the Western world. Our objective was to compare the outcomes of RG and LG in GC patients. METHODS: We reviewed all gastric adenocarcinoma patients who underwent curative gastrectomy by minimally invasive approach in our institution from 2009 to 2022. Propensity score matching (PSM) analysis was conducted to reduce selection bias. DaVinci Si platform was used for RG. RESULTS: A total of 156 patients were eligible for inclusion (48 RG and 108 LG). Total gastrectomy was performed in 21.3% and 25% of cases in LG and RG, respectively. The frequency of stage pTNM II/III was 48.1%, and 54.2% in the LG and RG groups (p = 0.488). After PSM, 48 patients were matched in each group. LG and RG had a similar number of dissected lymph nodes (p = 0.759), operative time (p = 0.421), and hospital stay (p = 0.353). Blood loss was lower in the RG group (p = 0.042). The major postoperative complications rate was 16.7% for LG and 6.2% for RG (p = 0.109). The 30-day mortality rate was 2.1% and 0% for LG and RG, respectively (p = 1.0). There was no significant difference between the LG and RG groups for disease-free survival (79.6% vs. 61.2%, respectively; p = 0.155) and overall survival (75.9% vs. 65.7%, respectively; p = 0.422). CONCLUSION: RG had similar surgical and long-term outcomes compared to LG, with less blood loss observed in RG.

Gastric cancer with microsatellite instability displays increased thymidylate synthase expression.

BACKGROUND: Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. METHODS: We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). RESULTS: Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. CONCLUSION: MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT.

Preoperative chemotherapy is a better strategy than upfront surgery in cT4 gastric cancer.

BACKGROUND: Chemotherapy (CMT) followed by surgery is recommended by Western countries for advanced gastric cancer (GC). However, cT4 GC usually undergoes upfront surgery, due to symptoms. This study aimed to evaluate if preoperative CMT is a better strategy than upfront surgery in cT4 GC. METHODS: All cT4 GCs who underwent curative gastrectomy were included. Patients were divided according to their initial treatment: upfront surgery (SURG) or CMT + SURG. RESULTS: Among the 226 GC initially staged as cT4, 150 underwent SURG and 76 CMT + SURG. Groups were similar concerning age, comorbidities, American Society of Anesthesiologists, gastrectomy performed, and postoperative complications. The CMT + SURG group had less advanced pTNM. Median overall survival (OS) was 32 and 58.5 months for SURG and CMT + SURG, respectively (p = 0.04). Patients who received perioperative or adjuvant CMT had better OS compared to surgery alone (49.4 vs. 15.9 months, p < 0.001). OS was similar for those receiving preoperative and adjuvant CMT. Non-CMT, pN+, and R1 resection were independent risk factors for worse OS. CONCLUSION: Multimodal treatment associating CMT with surgery, regardless of whether the approach is pre- or postoperative, is essential to improve the survival of cT4 GC. As tolerance to adjuvant treatment is reduced, preoperative CMT is a better strategy than upfront surgery in these patients.

Gastrectomy for elderly gastric cancer patients: A propensity score-matching analysis.

BACKGROUND: Although D2-gastrectomy is the most effective treatment for resectable gastric cancer (GC), it is unclear whether elderly patients have increased risk of morbidity and worse survival. This study aimed to compare the short- and long-term outcomes of older age (OA) patients with those of less advanced age (LAA). METHODS: GC patients undergoing curative gastrectomy were retrospectively analyzed and divided into two groups: OA (>75 years) and LAA (<75 years). Propensity score-matching (PSM) analysis using seven variables was conducted to reduce selection bias. RESULTS: Among 586 patients, 494 (84.3%) were classified as LAA and 92 (15.7%) as OA. OA patients had worse clinical status, higher rates of D1-lymphadenectomy, subtotal gastrectomy, and Lauren type; higher mortality and worse survival. No difference in pathological tumor-node-metastasis (pTNM) stage was observed between groups. Preoperative chemotherapy was performed more frequently in the LAA group. After PSM (92 OA: 92 LAA), all variables included in PSM were matched, and mortality rates and survival became similar between groups. In multivariate analysis, American Society of Anaesthesiologists score III/IV was an independent factor associated with a 90-day mortality after PSM. CONCLUSION: Gastrectomy in elderly GC patients has similar outcomes compared with younger ones. Clinical status and disease stage are more important than the patient's age.

Multivisceral resection vs standard gastrectomy for gastric adenocarcinoma.

INTRODUCTION: Multivisceral resection (MVR) is potentially curative for selected gastric cancer patients, supposedly at the cost of increased complications. However, current data comparing MVR to standard gastrectomy (SG) is lacking. OBJECTIVES: Compare complications and survival after MVR and SG. METHODS: In a retrospective cohort of 1015 patients with gastric adenocarcinoma, 58 underwent MVR and 466 SG. Groups were compared concerning their characteristics, complications, and survival. RESULTS: One hundred seventy-six patients had postoperative complications. Major complications were more frequent after MVR (P = .002). Surgical mortality was 8.6% and 4.9% for MVR and SG (P = .221). Older age, higher morbidities, and MVR were independent risk factors for major complications. The odds ratio for major complications was 5.89 for MVR with one or two organs and 38.01 for MVR with three or more organs. The pancreas was the most commonly removed organ and pT4b disease were confirmed in 34 (58.6%) of the MVR cases. Disease-free survival (DFS) was lower in MVR patients (51% vs 77.8%; P < .001), being worse according to the number of organs resected. In pN+ patients, DFS was worse after MVR. DFS was equivalent to pT4b and non-pT4b in the MVR group. CONCLUSIONS: Increased morbidity and lower survival are expected for gastric cancer patients undergoing MVR.

Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?

BACKGROUND: Gastric cancer (GC) has been defined in distinct molecular subtypes with different therapeutic implications. However, its clinical significance and prognosis regarding standard chemotherapy (CMT) remains unclear. This study aimed to analyze the impact of perioperative or adjuvant treatment among subtypes of GC. METHODS: We retrospectively evaluated all stage II/III patients with GC who underwent a curative gastrectomy. Based on immunohistochemistry and in situ hybridization techniques, GC was classified into five subtypes: Epstein-Barr virus (EBV) positive, microsatellite instability (MSI), e-cadherin aberrant, p53-aberrant, and p53-normal. RESULTS: Among the 178 CG included, 111 patients received CMT and 67 were treated with surgery alone. Survival analysis showed that p53-aberrant GC treated with CMT had better disease-free survival (DFS) compared with surgery alone (P = .001).There was no significant difference in DFS between patients who received CMT and those with surgery alone for EBV, MSI, E-cadherin, and p53-normal GC. An improvement in overall survival was observed only for E-cadherin (P = .001) and p53-aberrant (P < .001) patients who received CMT. CONCLUSIONS: CMT showed different impact on the survival of CG according to the molecular subtype. No survival benefit was observed for EBV and MSI groups who received CMT. GC with p53-aberrant had a significant benefit in survival with standard therapy.

Association between Polymorphisms in Inflammatory Response-Related Genes and the Susceptibility, Progression and Prognosis of the Diffuse Histological Subtype of Gastric Cancer.

The chronic inflammatory microenvironment and immune cell dysfunction have been described as critical components for gastric tumor initiation and progression. The diffuse subtype is related to poor clinical outcomes, pronounced inflammation, and the worst prognosis. We investigated the association of polymorphisms in inflammatory response-related genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB, and TP53) with gastric cancer susceptibility, progression and prognosis in a Brazilian sample, focusing on the diffuse subtype. We also performed the analysis regarding the total sample of cases (not stratified for tumor subtypes), allowing the comparison between the findings. We further investigated the polymorphisms in linkage disequilibrium and performed haplotype association analyses. In the case-control study, rs1042522 (TP53) was associated with a stronger risk for developing gastric cancer in the sample stratified for diffuse subtype patients when compared to the risk observed for the total cases; CTC haplotype (rs699947/rs833061/rs2010963 VEGFA) was associated with risk while rs699947 was associated with protection for gastric malignancy in the total sample. Regarding the associations with the clinicopathological features of gastric cancer, for the diffuse subtype we found that rs699947 and rs833061 (VEGFA) were associated with outcomes related to a worse progression while rs5275 (COX-2), rs909253 (TNFB), and rs2227956 (HSPA1L) were associated to a better progression of the disease. In the total sample, rs699947 and rs833061 (VEGFA), rs4644 (LGALS3), and rs1042522 (TP53) were able to predict a worse progression while rs5275 (COX-2), rs2227956 (HSPA1L), and rs3025039 (VEGFA) a better progression. Besides, rs909253 (TNFB) predicted protection for the overall and disease-free survivals for gastric cancer. In conclusion, these results helped us to clarify the potential role of these polymorphisms in genes involved in the modulation of the inflammatory response in the pathogenesis of gastric cancer.

Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. METHODS: We evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. RESULTS: EBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P = 0.032), proximal location (P < 0.001), undetermined Lauren type (P < 0.001), poorly differentiated histology (P = 0.043) and severe inflammatory infiltrate (P < 0.001). MSI-tumors were associated to older age (P = 0.002), subtotal gastrectomy (P = 0.004), pN0 (P = 0.024) and earlier TNM stage (P = 0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P < 0.001). MSI was associated to better survival outcomes. CONCLUSION: EBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.

Neutrophil-lymphocyte ratio is associated with prognosis in patients who underwent potentially curative resection for gastric cancer.

BACKGROUND AND OBJECTIVES: The role of inflammation in cancer development is a well-known phenomenon that may be represented by the neutrophil-lymphocyte ratio (NLR). The present research intends to determine the impact of NLR on the survival outcome of patients with gastric cancer (GC), and to evaluate its use as a stratification factor for the staging groups. METHODS: Data regarding clinical characteristics, surgery, pathology, and follow-up were retrospectively collected from our single-center prospective database. Blood samples were obtained before surgery. RESULTS: A total of 383 patients (231 males) who underwent gastrectomy with lymphadenectomy were evaluated between 2009 and 2016. NLR established cutoff was 2.44, and patients were divided in NLR ≥2.44 (hNLR) and <2.44 (lNLR). hNLR patients (38.4% of the cases) had lower disease-free survival and overall survival (OS) compared to lNLR patients (P = 0.047 and P = 0.045, respectively). Risk stratification according to NLR value was done in same tumor depth (T4 and