Presence of cancer cells in gastric lavage of gastric cancer patients as an indicator of advanced disease, predictor of tumour aggressive phenotype and independent prognostic factor for poor survival: The endoluminal metastatic pathway of gastric cancer and GL0/GL1 classification

Abstract

Objective: As of 2017, the pathobiology of gastric cancer (GC) is far from fully understood; consequently, new methods of basic and advanced research have been proposed and tested. The presence (GL1) vs absence (GL0) of malignant cells exfoliated in gastric lavage (GL) of GC patients was formerly evaluated with diagnostic intent but not for staging or prognostic assessment. We investigated this hitherto unreported application of cytopathology.Methods: GL was preoperatively and prospectively collected from 80 GC patients and cytologically analysed. The results were compared with the classic clinicopathological features of GC and related to survival. The prognostic value of GL1 was assessed through univariate and multivariate analyses.Results: GL1 was detected in 36 samples (45%) and correlated with advanced tumour depth (T3-T4), lymphatic metastasis (N+), distant metastasis (M1) and lymphovascular invasion (LVI1; P=.0317, .0024, .003 and .0028, respectively). Overall survival (OS) was significantly shorter for GL1 (23 months) vs GL0 patients (42 months; P=.005) and GL1 vs GL0 T1 subjects (12.6 vs 47.8 months, P=.0029). Univariate analysis revealed that GL1, N+, M1, LVI1 and advanced stage were significantly associated with OS. Multivariate analysis assessed GL1 as the only independent prognostic factor for worse OS and progression-free survival (P=.0013 and .0107). Conclusions:In the present study, GL1 was correlated with advanced disease, aggressive tumour behaviour and poor prognosis. Although additional studies are needed to confirm these findings, the GL0/GL1 classification can be applied to GC patients to achieve higher accuracy in staging, prognostic stratification and treatment selection. K E Y W O R D Sgastric adenocarcinoma, gastric cancer, gastric cytopathology, gastric lavage, gastric washing

Combined Analysis of Intragastric Malignant Exfoliation and Ca 72.4 Concentration in Stomach Adenocarcinoma: The “GL1 Ca 72.4” Parameter

“…In this regard, recently numerous studies on cytologic and molecular analyses of the intragastric environment have provided interesting results [10-25, 33-35]. On the one hand, compared to the GL0 counterpart, the presence of cancer cells exfoliated into the gastric lumen (GL1) has been associated with an aggressive GC phenotype and credited as an independent prognostic factor of bad prognosis of affected patients [17-19]. On the other hand, intragastric molecules from traditional tumor antigens (CEA, CA 19.9, Ca 72.4, and Ca 50) to newer biomarkers (miRNAs, lnc­RNAs, and other noncoding segments) are currently demonstrating an important role in diagnosis and prognosis [20-27].…”

“…The findings derived from the GJ/GL of GC subjects have prompted us to identify this biologic fluid as a distinct route of tumor spreading, naming it “endoluminal pathway” or “metastasis VI” (Fig. 9) [16, 17]. Substantially, we followed the example given by Xie and colleagues [36-38] when they found malignant cells in the mesogastrium of resected GC specimens, assessing the gastric mesentery as the fifth metastatic route (“Metastasis V”) used by GC.…”

“…Ca 72.4 was measured using an electrochemiluminescence sandwich immunoassay method with an Elecsys 2010 analyzer (Roche Diagnostics, Mannheim, Germany). Metastatic lymph node ratio (LNR) was classified into a 4-tier system: LNR0 (0.0), LNR1 (>0–0.3), LNR2 (>0.3–0.6), and LNR3 (>0.6) [17, 18]. The following cytomorphological criteria were considered pathognomonic of malignancy: nuclear changes (atypia and anisokaryosis), increased and/or abnormal mitotic figures, high nucleus-to-cytoplasm ratio, nucleolar hypertrophy or multiplicity, highly condensed nuclear chromatin, cytosolic vacuoles (signet-ring cells), pleomorphism, hypertrophy, presence of aggregates, and pseudopapillary arrangements (Fig.…”

“…The following cytomorphological criteria were considered pathognomonic of malignancy: nuclear changes (atypia and anisokaryosis), increased and/or abnormal mitotic figures, high nucleus-to-cytoplasm ratio, nucleolar hypertrophy or multiplicity, highly condensed nuclear chromatin, cytosolic vacuoles (signet-ring cells), pleomorphism, hypertrophy, presence of aggregates, and pseudopapillary arrangements (Fig. 1) [17]. The pathology of surgical specimens was described following the 8th edition of the AJCC TNM Staging System [29].…”

Gastric washing by distilled water can reduce free gastric cancer cells exfoliated into the stomach lumen

“…During EFTR, an intentional perforation is essential; therefore, free cancer cells in the gastric content may spill into the peritoneal cavity, leading to iatrogenic tumor-cell seeding [1]. However, cytologic evidence of cancer-cell exfoliation from the lesion into the gastric lumen has rarely been studied [3][4][5]. Therefore, we conducted this study to examine the free cancer cells in the stomach having gastric cancer.…”