Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer

doi:10.1016/0960-7404(92)90034-I

Surgical Oncology

Volume 1, Issue 5, October 1992, Pages 341-346

https://doi.org/10.1016/0960-7404(92)90034-I Get rights and content

Abstract

The objective of the study was to define risk factors for peritoneal dissemination and haematogenous metastasis after curative resection of patients with an advanced gastric cancer. In retrospective analyses of 405 patients, 168 died of a tumour recurrence. Patients who died of gastric cancer were more likely to have large, invasive tumours which had spread throughout the stomach, metastasized to lymph nodes, and vessel invasion by gastric cancerous cells (P < 0.01 or P < 0.05). Of the 168 deaths, 60 (35.7%) were secondary to haematogenous recurrence, 53 (31.5%) were related to peritoneal dissemination, and 19 (11.3%) were related to a local recurrence. To determine the independent risk factors related to peritoneal dissemination and haematogenous metastasis, multivariate analyses using a stepwise logistic model suggested that serosal invasion (P < 0.01, relative risk = 2.57) and Borrmann type 4 (P < 0.01, relative risk = 1.95) were the greatest risk factors for peritoneal dissemination. The presence of lymph node metastasis (P < 0.01, relative risk = 2.62) and presence of vessel invasion by cancerous cells (P < 0.05, relative risk = 1.59) were the greatest risk factors for a haematogenous metastasis.

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Prediction of the peritoneal recurrence via the macroscopic diagnosis of the serosal invasion in patients with gastric cancer: Supplementary analysis of JCOG0110
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Citation Excerpt :
Discrepancies exist between the intraoperative macroscopic diagnosis of serosal invasion and pathological diagnosis. The risk of peritoneal recurrence and survival is important during the treatment of patients with serosa-positive gastric cancer, and the predictability of peritoneal recurrence and survival by macroscopic diagnosis is reported to be equal to or better than that by pathological diagnosis [3–8]. However, these data have been reported in retrospective case series from single institutions, with relatively small sample sizes; only few multicenter prospective studies have investigated the use of macroscopic diagnoses for predicting peritoneal recurrence and survival in patients with gastric cancer [9].
Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence.
This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates.
A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively.
Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended.
Long-term prognosis of patients with cancer-related genes detected in postoperative peritoneal washings obtained during curative gastrectomy
2022, European Journal of Surgical Oncology
Cancer cells in intraoperative peritoneal washings (PW) indicate increased peritoneal recurrence. Detection of CEA or CK20 genes indicates poor prognosis. We assessed long-term prognosis of patients with amplification of cancer-related genes in PW obtained intraoperatively during curative gastric cancer surgery.
PW was collected before and immediately after curative gastrectomy. CEA, CK20, TFF1, MUC2, and FABP1-mRNA were selected as marker genes for reverse transcription polymerase chain reaction. Peritoneal recurrence-free survival (PRFS) and overall survival (OS) after >7-year follow-up were examined using the Kaplan–Meier method.
Of 138 patients who underwent gastrectomy with negative cytological findings at laparotomy, 80 patients showed negative cancer-related gene amplification in preoperative PW. Fifty-eight patients were excluded due to positive gene amplification, which suggested presence of preoperative peritoneal cancer cells. The 80 patients had mRNA amplification in PW after surgery. Amplification of multiple and single cancer-related marker genes was observed in 38 and 21 patients; 21 cases had marker-negative results. Five-year PRFS was 69.1%, 95.2%, and 100% in multi-marker-positive, single marker-positive, and marker-negative cases, respectively. Multi-marker-positive patients had significantly worse PRFS than the other groups (p < 0.05). Multivariate analysis in the Cox proportional hazards model identified multi-marker-positivity as an independent prognostic factor for PRFS (hazard ratio, 7.6; 95% confidence interval, 1.07–62.63; p = 0.046), and multi-marker-positive patients had significantly worse OS than other groups (p < 0.01).
Multi-marker cancer-related gene amplification in PW is associated with worse prognosis in PRFS and OS even after a long follow-up; PRFS can be stratified by the number of genes amplified.
Antitumor Effect of AZD4547 in a Fibroblast Growth Factor Receptor 2–Amplified Gastric Cancer Patient–Derived Cell Model
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BACKGROUND: FGFR2 amplification is associated with aggressive gastric cancer (GC), and targeted drugs have been developed for treatment of GC. We evaluated the antitumor activity of an FGFR inhibitor in FGFR2-amplified GC patients with peritoneal carcinomatosis. METHODS: Two GC patients with FGFR2 amplification confirmed by fluorescence in situ hybridization showed peritoneal seeding and malignant ascites. We used the patient-derived xenograft model; patient-derived cells (PDCs) from malignant ascites were used to assess FGFR2 expression and its downstream pathway using immunofluorescence analysis and immunoblot assay in vitro. Apoptosis and cell cycle arrest after treatment of FGFR inhibitor were analyzed by Annexin V-FITC assay and cell cycle analysis. RESULTS: FGFR2 amplification was verified in both PDC lines. AZD4547 as an FGFR inhibitor decreased proliferation of PDCs, and the IC₅₀ value was estimated to be 250 nM in PDC#1 and 210 nM in PDC#2. FGFR inhibitor also significantly decreased levels of phosphorylated FGFR2 and downstream signaling molecules in FGFR2-amplified PDC lines. In cell cycle analysis, apoptosis was significantly increased in AZD4547-treated cells compared with nontreated cells. The proportion of cells in the sub-G1 stage was significantly higher in AZD4547-treated PDCs than in control cells. CONCLUSION: Our findings suggest that FGFR2 amplification is a relevant therapeutic target in GC with peritoneal carcinomatosis.
Extragastric recurrence in patients who underwent surgical resection of stage i gastric cancer: Incidence, risk factors, and value of abdominal computed tomography as a postoperative surveillance method
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Gastric and gastroesophageal junction cancer: Risk factors and prophylactic treatments for prevention of peritoneal recurrence after curative intent surgery
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Actual 3-Year Survival After Reduced-Port Laparoscopic Distal Gastrectomy for Gastric Cancer (RpLDG): a Propensity Score Matching Analysis
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Original articleRisk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer

Abstract

Am J Surg

Pathological characteristics of gastric cancer that develop hematogenous recurrence, with special reference to the site of recurrence

J Surg Oncol

Blood vessel invasion in gastric carcinoma

Surgery

Clinical and pathological factors influencing ultimate prognosis and following resection for carcinoma of the stomach

Ann Surg

Clinicopathological analysis of the intestinal type and diffuse type of gastric carcinoma

Jpn J Surg

Relationship between area of serosal invasion and prognosis in patients with gastric carcinoma

Cancer

Histologic features of gastric cancer in relation to pattern of spread

Acta Chir Scand

Original article
Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer