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BACKGROUND/AIM: Liquid biopsy (LB) is a promising non-invasive tool to detect cancer. Over the last few years, exosomes recruited from LB have attracted the attention of researchers for their involvement in cancer. We focused on the role of LB exosomes in gastric cancer (GC). MATERIALS AND METHODS: We investigated the world literature on exosome-encapsulated functional biomarkers (non-coding RNAs and DNAs) taken from GC patients' LBs. Only the studies exploring serum, intraperitoneal fluid or gastric lavage were included. RESULTS: As of 2022, fifty articles with an overall count of 3552 GC patients were investigated. Given the statistically significant associations with the clinicopathological categories of tumor depth, lymph node metastasis, staging class and tumor size, most exosome-mediated microRNAs, long non-coding RNAs and circular RNAs proved to exert a potentially important bioclinical role in terms of diagnosis, screening, prognosis and therapeutic targets. CONCLUSION: In the future, resorting to exosomal biomarkers taken from LB of affected patients could revolutionize the non-invasive fight against GC.
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Exossomos , Neoplasias Gástricas , Biomarcadores Tumorais/genética , Exossomos/genética , Humanos , Biópsia Líquida , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: In the last decade, analysis of malignant cells and flora in gastric lavage (GL) has provided interesting data on pathogenesis of gastric cancer (GC). For this study, combining such two aspects into one cyto-microbiologic category, we tested the prognostic role of the presence/absence of cancer cells (GL1/GL0) and bacterial microbiota (MB1/MB0) in our GC population. MATERIAL AND METHODS: Between April 2012 and August 2019, 79 surgical patients with GC were prospectively investigated with the determination of GL MB. RESULTS: Compared with GL1 MB0, GL1 MB1 strongly correlated with advanced GC, portended poorer overall survival (OS) (45.8 months vs 20.5 months, P = 0.049), and resulted a significant (P = 0.008) and an independent (P = 0.013) prognostic factor unfavorable for OS. CONCLUSION: In the light of our results, the cyto-microbiologic parameter of GL MB should be used to gain a better prognosis of GC patients. Administration of antimicrobial treatment for MB1 subjects should be entertained because it could reduce the risk of oncogenesis.
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BACKGROUND/AIM: As of 2020, carbohydrate antigen 72.4 (Ca 72.4) has been rarely investigated in the gastric juice (GJ) of patients with gastric cancer (GC). Our aim was to analyze the significance and role of this tumor antigen in the GJ of our GC population. PATIENTS AND METHODS: Between April 2012 and July 2013, 37 patients with operable GC were prospectively investigated to determine the GJ Ca 72.4 levels before surgical manipulation. RESULTS: GJ Ca 72.4 ≥6.49 ng/ml strongly correlated with the traditional categories of aggressive cancer (advanced tumor depth and stage, lymph node invasion and metastatic lymphatic ratio, indication to adjuvant treatment). It also associated with shorter survival (p=0.049) and is, thus, suggested as an independent factor of poor prognosis in GC patients (p=0.047). CONCLUSION: The GJ Ca 72.4 parameter should be considered an indicator of an aggressive tumor phenotype and should be used in the prognostic assessment of GC patients.
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Antígenos Glicosídicos Associados a Tumores/metabolismo , Suco Gástrico/metabolismo , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
INTRODUCTION/OBJECTIVE: Differently from other digestive malignancies, gastric cancer (GC) pathobiology is still little known and understood. Recently, cytopathology and molecular biology on gastric juice/gastric lavage (GJ/GL) of GC patients have provided novel and interesting results in terms of screening, diagnosis, prognosis, and therapy. However, entertaining cytologic examination and molecular test as a unified solo-run test is previously unreported. Our aim was to assess the new parameter "GL Ca 72.4" for GC patients. METHODS: Between April 2012 and July 2013, GJ/GL obtained from 37 surgical GC patients were tested for the presence/absence (GL1/GL0) of exfoliated malignant cells along with the intragastric concentration of Ca 72.4 (normal value <6.49 ng/mL: Ca 72.4n; elevated level ≥6.49 ng/mL: Ca 72.4+). RESULTS: At a median follow-up of 79.3 months, all the GC alive patients were "GL0 Ca 72.4n." The "GL1 Ca 72.4+" parameter, in comparison with GL0 Ca 72.4n, strongly correlated with deeper tumor invasion (p = 0.027), severe nodal metastasis (p = 0.012), worst metastatic node ratio (p = 0.041), higher number of metastatic lymph nodes (30 vs. 20 nodes, p = 0.014), angiolymphatic invasion (p = 0.044), advanced stage (p = 0.034), and adjuvant therapy (p = 0.044). The Kaplan-Meier model showed that GL1 Ca 72.4+ subjects had shorter overall survival (OS) than GL0 Ca 72.4n cases (9.7 vs. 43.2 months, respectively, p = 0.042). At univariate analysis, the GL1 Ca 72.4+ parameter resulted a significant prognostic factor for OS (p = 0.023). CONCLUSIONS: The combined cyto-molecular parameter "GL1 Ca 72.4+" appears to be a strong indicator of aggressive tumor behavior and a significant prognostic factor of poor survival for GC patients.
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Adenocarcinoma/patologia , Linfonodos/patologia , Neoplasias Gástricas/patologia , Estômago/patologia , Adenocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Lavagem Gástrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Neoplasias Gástricas/diagnósticoRESUMO
Historically, analysis of intragastric exfoliative cytology (IEC) of gastric cancer (GC) was used with a diagnostic intent only. With the successful advent of endoscopic biopsy, the rate of detection of GC has improved worldwide and, as a consequence, IEC has been progressively abandoned. Today, however, there is a renewed interest in this field of research, as witnessed by several pertinent publications. As discussed in this review, in fact, currently the importance of analyzing IEC in patients with early and advanced GC seems to reside in its clinicopathological and prognostic significance. In fact, compared to non-sloughing tumors, GC exhibiting intragastric exfoliation was recently associated with an aggressive tumor phenotype (characterized by deeper infiltration of the gastric wall, lymph nodal or distant metastases, angiolymphatic and perineural invasion) and poorer prognosis. Adoption of IEC examination in routine practice might help identify patients at higher risk of developing local recurrence and peritoneal metastasis from early and advanced GC, optimizing their treatment and improving quality of life and life expectancy.
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Citodiagnóstico/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Estômago/diagnóstico por imagem , Endoscopia , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Peritônio/diagnóstico por imagem , Peritônio/patologia , Prognóstico , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND/AIM: Although reckoned necessary for survival benefit, neoadjuvant chemotherapy (NAC) of gastric cancer (GC) patients has so far provided questionable results. Consequently, searching for new and clearer systems of response to NAC, post-NAC re-evaluation and prognostic prediction appears essential. The purpose of this study was to examine endogastric cytopathology and hemoglobin level count as new features, potentially useful for GC patients after NAC. PATIENTS AND METHODS: Between April 2012 and October 2018, 21 of 116 patients with resectable GC received NAC and were investigated for the presence of free-floating malignant cells in their gastric lavage (yGL1) and the development of hypohemoglobinia (yAnemia). RESULTS: yGL1 and yAnemia were found in 11 and 12 patients, respectively. yGL1 correlated with the traditional parameters of tumor regression (p=0.0424). Both yGL1 and yAnemia were found to be independent predictive factors of overall and progression-free survival (p≤0.0364). CONCLUSION: In the light of our results, the yGL1 and yAnemia appear two promising, simple and interesting clinicopathological features which should always be examined for better clarifying GC patients' response to NAC.
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Anemia/complicações , Lavagem Gástrica , Hemoglobinas/análise , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Período Perioperatório , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapiaRESUMO
Differently from other digestive malignancies, gastric cancer (GC) carcinogenesis seems more heterogeneous and unclear. This entails failing in identification of reliable serum tumor markers for screening early GC (EGC) as well as persisting ominous prognosis of this disease. Recently, investigation of human noncoding genome, especially long noncoding molecules (lncRNAs), has provided promising data. As for GC, however, since the current information on GC-specific lncRNAs is still scarce and comes largely from analyses performed on tissue or serum of affected patients, we decided to review the current literature dealing with expression of such molecules in the gastric juice (GJ) of GC patients. In the case of GC, in fact, several cytological and molecular works have already demonstrated GJ to be an interesting biological material for improving clinicopathologic and prognostic knowledge of this cancer. For this review, we burrowed into the literature on lncRNAs expressed in GJ of GC patients. PubMed, Science Direct, Scopus, Web of Science, Google Scholar and ResearchGate were the search engines entertained. As of 2018, only seven studies have been reported. LINC00152, AA174084, UCA1, RMRP, ABHD11-AS1, LINC00982 and H19 were the GJ lncRNAs examined. Following our review, we can conclude that, due to their high specificity and reliability, GJ lncRNAs should deserve a prominent role in the field of GC research: importantly, they could be used for screening EGC, ameliorating the existing methods of staging (which are still far from being completely accurate), improving the prognostic capacity of the current diagnostic armamentarium and, finally, providing new and valuable therapeutic targets.
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Biomarcadores Tumorais/análise , Suco Gástrico/química , RNA Longo não Codificante/análise , Neoplasias Gástricas/diagnóstico , Biomarcadores Tumorais/genética , Humanos , Sensibilidade e Especificidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND/AIM: Detecting free tumor cells in the peritoneal lavage fluid of gastric cancer patients permits to assess a more accurate prognosis, predict peritoneal recurrence and select cases for a more aggressive treatment. Currently, cytology and molecular biology comprise the two most popular methods of detection that are under constant study by researchers. MATERIALS AND METHODS: We burrowed into the available literature comparing cytological with molecular detection of free intraperitoneal gastric cancer cells. PubMed, Science Direct, Scopus and Google Scholar were the search engines investigated. RESULTS: As of 2017, 51 dedicated studies have been published. Messenger RNA of carcinoembryonic antigen was the genetic target most frequently described. The genetic technique is usually superior to cytology in sensitivity (38-100% vs. 12.3-67% respectively), whereas cytological examination tends to show a slight pre-eminence in specificity (approximately 100%). CONCLUSION: So far, given the imperfection of each method, employment of both cytology and molecular examination seem to be mandatory.
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Líquido Ascítico/patologia , Lavagem Peritoneal , Neoplasias Peritoneais/diagnóstico , Neoplasias Gástricas/patologia , Líquido Ascítico/metabolismo , Antígeno Carcinoembrionário/genética , Citodiagnóstico/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Recidiva Local de Neoplasia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND/AIM: Although there is an increasing number of studies on laparoscopic resection of early gastric cancer (EGC), as of 2018 no standardized strategy exists. We reviewed available literature dealing with laparoscopic intragastric (intraluminal) surgery (LIGS) conducted for patients with EGC to better define indications, benefits and limitations of this particular minimally invasive technique. MATERIALS AND METHODS: PubMed, MEDLINE, Science Direct, Scopus, Web of Science, Google Scholar and ResearchGate were the search engines investigated. Only LIGS for EGC was entertained; studies conducted for other gastric diseases were excluded. Suitable articles written in all languages were included in the review. RESULTS: As of 2018, we found 19 studies dealing with LIGS for EGC: studies on 72 humans and four pigs were identified. Among 72 human participants, there were 59 mucosal, five submucosal and one subserosal cancer. CONCLUSION: Based on our review, LIGS appears as a cogent option to endoscopic resection for treating superficial EGC.
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Neoplasias Gástricas/cirurgia , Humanos , Laparoscopia/métodosRESUMO
In addition to classical metastatic pathways, recently gastric cancer was described having an alternative route called "endoluminal exfoliation". Provisional analyses demonstrated, in fact, this kind of shedding is associated with several clinico-pathological features indicative of aggressive behavior and resulted to be an independent prognostic factor entailing poor prognosis. Compared with non-sowing counterparts, in fact, patients affected with exfoliating early and advanced gastric carcinomas met with shorter overall survival, disease free survival, progression free survival and time to tumor progression. In spite of these interesting results, however, the clinico-pathological and oncological significance of this unconventional metastatic route is still to be clarified. Such an investigation is further urged by the increasing widespread employment of minimally invasive treatments for gastric cancer which include a wide spectrum of intragastric interventions and maneuvers. Indeed, endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic full-thickness resection, intragastric laparoscopic surgery and hybrid procedures all take place inside of the stomach. However, iatrogenic perforations can occur during execution of these treatments leading to spillage of malignant cells from gastric to the peritoneal cavity or trocar insertion sites. Furthermore, many other gastric conditions and interventions can collide with endogastric presence of floating cancer cells: spontaneous ulceration or perforation, laparotomy surgery, gastrointestinal occlusion, diverticula. Viability, migration and intraluminal transportability of the intragastric floating cancer cells represents another original and intriguing topic. All these considerations led us to entertain the hypothesis that removing the exfoliated cancer cells from the gastric lumen could save patients from the dreaded potential risk of spillage. Performing gastric lavage before starting any kind of tumor intervention could be the most appropriate procedure to adopt with prophylactic intent. Should our speculation prove to be clinically significant, preoperative gastric lavage should be pointed out as a simple but cogent method useful for preventing oncological mishaps such as spillage of gastric cancer cells and development of related recurrences or metastases.
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Endoscopia , Lavagem Gástrica/métodos , Metástase Neoplásica , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Modelos Teóricos , Recidiva Local de Neoplasia , Peritônio/patologia , Período Pré-Operatório , Neoplasias Gástricas/diagnósticoRESUMO
BACKGROUND/AIM: To date, the combination of gastroscopy with biopsy remains the only test validated for screening gastric cancer (GC). Currently, analysis of circulating microRNAs (miRNAs or miRs) is providing interesting information on GC prognosis, but since these molecules are shared by several types of cancer, its clinical use could be questionable and difficult. MicroRNAs in gastric juice (GJ) could represent a cogent alternative to screening GC by biopsy. MATERIALS AND METHODS: We investigated the pertinent literature dealing with GC GJ microRNAs through four popular search engines (PubMed, Science Direct, Scopus and Google Scholar). RESULTS: As of 2017, only four studies had been published and were all from Chinese experience. MiR-421, miR-129, miR-21, miR-106a and miR-133a were the five molecules studied in the GJ of the enrolled patients. CONCLUSION: The GJ miRNA test is reliable and reproducible. The discussed GJ miRNAs appear to be new potential biomarkers for the screening of GC.
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Biomarcadores Tumorais/genética , Suco Gástrico , MicroRNAs/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Regulação Neoplásica da Expressão Gênica , HumanosRESUMO
BACKGROUND/AIM: Concerning gastric cancer (GC), nasogastric tube (NGT) is routinely employed for peri-operative decompression and palliative enteral nutrition. Additionally, we believe to have found a further application. PATIENTS AND METHODS: Between April 2012 and April 2017, 96 GC patients received preoperative nasogastric lavage (GL). All samples were cytologically examined to detect the presence (GL1) or absence (GL0) of malignant cells. Data were analyzed with classificatory, staging and prognostic purpose. RESULTS: GL1 was detected in 46 GC patients: association with tumor depth, lymph node and distant metastasis, lymphovascular and peri-neural invasion, diffuse type and signet-ring cells was significant (respectively p=0.0274, 0.0324, 0.0446, 0.0287, <0.0001, 0.0413, <0.0001). GL1 entailed significantly poorer overall (OS), progression-free, disease-free survival and tumor progression (18 vs. 32 months). At multivariate analysis, GL1 was an independent prognostic factor for worse OS (p=0.0287). CONCLUSION: NGT seems an economic oncologic measure useful for obtaining information on GC staging and prognosis.
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Lavagem Gástrica/métodos , Intubação Gastrointestinal/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/mortalidadeRESUMO
BACKGROUND/AIM: Early gastric cancer (EGC) is usually associated with excellent prognosis. Some cases, however, entail a poorer survival. Our aim was to assess if EGC exfoliating into gastric lavage (GL) has a more aggressive behavior than the non-exfoliative counterpart. PATIENTS AND METHODS: Between April 2012 and April 2017, 96 gastric cancer patients were prospectively submitted to preoperative GL to detect the presence (GL1) or absence (GL0) of exfoliated malignant cells. RESULTS: A total of 16 patients had EGC. T1b cases had significantly poorer overall (OS), progression-free (PFS) and disease-free survival (DFS) than their GL0 counterpart (16.3 vs. 61 months, p=0.0032). Similarly, the entire T1 class (T1a plus T1b EGCs) showed worse OS, PFS, DFS (15.5 vs. 61 months, p=0.0008) and time-to-tumor progression (17 vs. 61 months, p=0.0103). CONCLUSION: In the case of EGC, the GL0-GL1 classification should become a routine clinical practice to identify the aggressive tumor phenotypes requiring for closer follow-up or additional treatment.
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Lavagem Gástrica/métodos , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Detecção Precoce de Câncer , Feminino , Gastrectomia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológicoRESUMO
As of 2017, no serum tumor marker has shown high levels of sensitivity or specificity for early detection, classification, staging, prediction and prognosis of patients affected by gastric cancer. In this regard, since 1975 several authors have investigated the gastric juice or gastric lavage of patients with gastric adenocarcinoma in order to determine the concentrations of intragastric tumor markers and discover the perfect antigen for this cancer. To date, however, a systematic review of the literature on intragastric tumor markers is still unreported. After a thorough search, we found important as well as unimportant findings and have come to clearly defined conclusions. We believe that describing the current state of knowledge achieved by the scientific community in this particular field of research could augment information on the complex pathobiology of gastric cancer and entail a deeper understanding of its unpredictable malignant behavior.
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Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/metabolismo , Humanos , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: To investigate gastric lavage (GL) cytopathology and immunometric analysis as novel clinicopathologic and prognostic parameters for gastric cancer (GC). STUDY DESIGN: In 38 patients with gastric adenocarcinoma, we performed a cytopathologic analysis and an immunometric assay of GL using four tumor markers (CEA, CA 19.9, CA 72.4, and CA 50). The intragastric tumor marker levels were compared with a control group consisting of 41 non-GC patients to determine a statistically significant cutoff value. RESULTS: GL cytopathology demonstrated the presence of cancer cells in 13 (34.2%) of the 38 GC patients: such a finding correlated to the parameters pT and pN with a statistically significant validity (p < 0.0267 and p < 0.0306, respectively). Measurement of intragastric CA 19.9 and CA 50 attained a statistically significant cutoff value (p < 0.002 and p < 0.0096, respectively), which was invalidated by the low sensitivity of the ROC curve analysis. CONCLUSIONS: In contrast to determination of its tumor markers, GL cytopathology correlated well with pT and pN staging parameters. Should this and other features be corroborated by future studies, the GL cytology test could be routinely used to detect aggressive types of GC even at early stages and result in important progress in the knowledge, staging, prediction, as well as management and follow-up of this inauspicious type of cancer.
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Antígenos Glicosídicos Associados a Tumores/metabolismo , Antígeno CA-19-9/metabolismo , Antígeno Carcinoembrionário/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Lavagem Gástrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/metabolismoRESUMO
Although decreasing in the incidence over the last years, currently gastric adenocarcinoma represents the second cause of cancer related-death worldwide. Further knowledge and novel therapies are desperately needed in order to make the prognosis of these patients more acceptable. Infact, even though in recent years numerous staging parameters have been largely studied and unanimously recognized for their clinical and prognostic value, today too many shadows still exist around the capacity to predict exactly the natural history or post-treatment behavior of this cancer even among patients of the same stage. This study has identified the presence of isolated cancer cells as well as tumor markers (CEA, Ca 19.9, Ca 72.4 and Ca 50) from the gastric lavage of patients affected by gastric adenocarcinoma. Such findings led to the hypothesis that endoluminal exfoliation of neoplastic cells and the release of their products (tumor markers) into the gastric juice might be an expression of neoplastic behavior as well as aggressive malignancy. Should this hypothesis become a reality, some important progress could be made in the knowledge, staging, prediction as well as management and follow-up of this inauspicious type of cancer.