Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity.

BACKGROUND: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. METHODS: Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. RESULTS: We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. CONCLUSIONS: Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents.

Review: Cell Dynamics in Malignant Pleural Effusions.

Malignant pleural effusions (MPEs) are a common manifestation found in patients with lung cancer. After cytological and histological confirmation of malignancy, talc pleurodesis still remains the treatment of choice in patients with MPEs resistant to chemotherapy. Despite this, primary challenges include reduced quality of life and life expectancy in general. Therefore, a better understanding of the cell biology of MPEs, along with improvements in treatment is greatly needed. It has recently been demonstrated that MPEs may represent an excellent source for identification of molecular mechanisms within the tumor and its environment. The present review summarizes the current understanding of MPEs cells and tumor microenvironment, and particularly focuses on dissecting the cross-talk between MPEs and epithelial to mesenchymal transition (EMT), inflammation and cancer stem cells.

Integration of tablet technologies in the e-laboratory of cytology: a health technology assessment.

INTRODUCTION: Although tablet systems are becoming a powerful technology, particularly useful in every application of medical imaging, to date no one has investigated the acceptance and performance of this technology in digital cytology. The specific aims of the work were (1) to design a health technology assessment (HTA) tool to assess, in terms of performance and acceptance, the introduction of tablet technologies (wearable, portable, and non portable) in the e-laboratories of cytology and (2) to test the tool in a first significant application of digital cytology. MATERIALS AND METHODS: An HTA tool was proposed operating on a domain of five dimensions of investigation comprising the basic information of the product of digital cytology, the perceived subjective quality of images, the assessment of the virtual navigation on the e-slide, the assessment of the information and communication technologies features, and the diagnostic power. Six e-slides regarding studies of cervicovaginal cytology digitalized by means of an Aperio ( www.aperio.com ) scanner and uploaded onto the www.digitalslide.it Web site were used for testing the methodology on three different network connections. RESULTS: Three experts of cytology successfully tested the methodology on seven tablets found suitable for the study in their own standard configuration. Specific indexes furnished by the tool indicated both a high degree of performance and subjective acceptance of the investigated technology. CONCLUSIONS: The HTA tool thus could be useful to investigate new tablet technologies in digital cytology and furnish stakeholders with useful information that may help them make decisions involving the healthcare system. From a global point of view the study demonstrates the feasibility of using the tablet technology in digital cytology.

EMT markers in lung adenocarcinoma pleural effusion spheroid cells.

Epithelial-to-mesenchymal transition (EMT) is a process in which cells undergo a developmental switch from epithelial to mesenchymal phenotype. This process has been related to embryologic morphogenesis but also to cancer progression and metastasis. The aim of the current study was to investigate the expression of EMT-related markers in adherent and spheroid cell cultures derived from malignant pleural effusions (MPEs) of patients affected by lung adenocarcinoma. On the basis of efficient in vitro propagation, six cases of MPEs were selected and analyzed by immunocytochemistry staining for EMT markers and by RT-PCR for transcription factors known to orchestrate EMT. EMT markers immunostaining showed in spheroids a statistically significant correlation between the loss of E-cadherin immunoreactivity and overexpression of N-cadherin (P < 0.001). Likewise loss of EpCAM epithelial marker was coincident with Vimentin overexpression (P < 0.001). RT-PCR analysis of transcription factors Snail, Slug, and Twist showed a highly variable expression, although a general trend to increase was observed. Importantly, in some selected cases it was possible to establish a precise relationship between spheroid formation, EMT switch and increased upregulation of the marker related to cancer stemness such as ALDH positivity. Therefore, MPE-derived cell cultures, while recapitulating the heterogeneity of lung cancer, are a suitable system to study the mechanisms at the basis of EMT and to understand its relationship with the generation of cancer stem cells.

Artificial Intelligence in Digital Pathology: What Is the Future? Part 1: From the Digital Slide Onwards.

This commentary aims to address the field of Artificial intelligence (AI) in Digital Pathology (DP) both in terms of the global situation and research perspectives. It has four polarities. First, it revisits the evolutions of digital pathology with particular care to the two fields of the digital cytology and the digital histology. Second, it illustrates the main fields in the employment of AI in DP. Third, it looks at the future directions of the research challenges from both a clinical and technological point of view. Fourth, it discusses the transversal problems among these challenges and implications and introduces the immediate work to implement.

Artificial Intelligence in Digital Pathology: What Is the Future? Part 2: An Investigation on the Insiders.

Motivation: This study deals with the introduction of artificial intelligence (AI) in digital pathology (DP). The study starts from the highlights of a companion paper. Objective: The aim was to investigate the consensus and acceptance of the insiders on this issue. Procedure: An electronic survey based on the standardized package Microsoft Forms (Microsoft, Redmond, WA, USA) was proposed to a sample of biomedical laboratory technicians (149 admitted in the study, 76 males, 73 females, mean age 44.2 years). Results: The survey showed no criticality. It highlighted (a) the good perception of the basic training on both groups, and (b) a uniformly low perceived knowledge of AI (as arisen from the graded questions). Expectations, perceived general impact, perceived changes in the work-flow, and worries clearly emerged in the study. Conclusions: The of AI in DP is an unstoppable process, as well as the increase of the digitalization in the health domain. Stakeholders must not look with suspicion towards AI, which can represent an important resource, but should invest in monitoring and consensus training initiatives based also on electronic surveys.

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

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.

Elevated Gastric Juice Carbohydrate Antigen 72.4 (Ca 72.4) Is an Independent Prognostic Factor of Poor Survival for Gastric Cancer Patients.

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.

Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study.

BACKGROUND: In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate. METHODS: 544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology. FINDINGS: 31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method. INTERPRETATION: Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate.

Advances in Intraluminal Exfoliative Cytology of Gastric Cancer: Oncologic Implication of the Sixth Metastatic Route (Metastasis VI).

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.

Gastric Lavage Malignant Cells (yGL) and Hypohemoglobinemia (yAnemia) as New Systems of Tumor Regression Grading and Prognostic Prediction for Gastric Cancer After Neoadjuvant Treatment.

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.

Tissue inhibitor of metalloproteinase 2 (TIMP-2) expression in adenocarcinoma pleural effusions.

Serous effusions are frequently a clinical manifestation of metastatic disease, with lung, breast and ovarian carcinoma and mesothelioma leading the list. The diagnosis of malignant effusion signifies disease progression and is associated with a worsening patient prognosis. The ability to grow in a dense exudative fluid suggests that the malignant cells are capable of acquiring nutrients, surviving and proliferating, despite the lack of a solid-phase scaffold. During proliferation, neoplastic cells release ligands and matrix metalloproteinases (MMPs) into their environment, which dissolve the extracellular matrix (ECM). Tissue inhibitors of metalloproteinase (TIMPs) are endogenous regulators of MMPs, the principal enzymes responsible for the degradation of ECM in metastasis, and reduce their proteolytic activity. TIMP-2 has demonstrated an association between high tumor tissue expression levels and poor prognosis. The purpose of this preliminary study is to investigate, by immunocytochemistry, TIMP-2 expression in non-neoplastic and metastatic adenocarcinoma pleural effusions. We selected 16 cases of reactive mesothelio, 7 of normal mesothelio, 14 of lung adenocarcinoma, 9 from the ovary, 4 from the gastrointestinal tract and 3 from the breast. In 23/30 cases (76%), we detected adenocarcinoma cells with strong TIMP-2 expression. Positive TIMP-2 expression was found in 2/7 cases (28%) of normal and 2/16 (12%) of reactive mesothelio. A statistical association was detected between TIMP-2 expression and metastatic adenocarcinoma cells compared to reactive and normal mesothelial cells (p<0.00003). The calculated sensitivities for TIMP-2 compared to CEA and Ber-EP4 were, respectively, 76.7, 80.0 and 93.3%, and the specificities 82.6, 95.7 and 87.0%. In conclusion, immunocytochemical detection of TIMP-2 could be considered an interesting marker in metastatic adenocarcinoma pleural effusions, and could possibly be used as a component of an antibody panel in diagnostic cytopathology.

The design of a health technology assessment system in telepathology.

Up to a few years ago, the management of the information on the slides (virtual slides) in telepathology applications was principally based on the design and construction of a few identical and expensive platforms with microscope units and software tools for the display and for electronic control (zooming, moving, and cutting of images). The development of information technology tools allows the diffusion of new visualization strategies and the availability of low cost or free visualization proprietary tools. New competitive systems such as client-server architectures are available in telepathology today. The investigation of the new technologies for telepathology is a basic and core aspect in telemedicine technology assessment. A new interactive environment to investigate the health technology assessment of a telepathology system has been studied. In particular, in consideration of previous experience the methodology focused both on the senior pathologist and younger student pathologist. Two interactive forms were created by a working group: a feedback form and a diagnostic form. The first was designed to investigate the technology characteristics and acceptance of the telepathology systems. The second tool was designed to investigate the diagnostic accuracy on a significant sample of virtual slides by two different groups of pathologists (senior and younger students). The acceptance of the methodology was very high.

Telepathology requires specific training for the technician in the biomedical laboratory.

The Italian Laurea for Health Care Professionals furnishes a high level of learning to technical personnel who will be involved in the healthcare system. It also represents a test for new models of learning in e-health and telemedicine applications. The purpose of this work was to investigate the changes in the biomedical laboratory curriculum in the healthcare system as a result of the introduction of telepathology (TP). Changes were categorized in two stages. The first stage was the inclusion of the TP as a support methodology using external furnishers to digitize the glass slides. The second is the inclusion of the TP as a consolidated routine methodology using a dedicated internal scanner to digitize the glass slides. New modules of learning have been designed to run on the wide area network to allow a better familiarization with new technologies. These new methodologies have been tested and present three tangible advantages: (1) A high level of knowledge for the student; (2) A cost-benefit advantage to the student; and (3) A cost-benefit advantage to the hospital. As the biomedical laboratories are freed up from academic applications, they thus become more available for clinical use.

Gastric Cancer Cells in Peritoneal Lavage Fluid: A Systematic Review Comparing Cytological with Molecular Detection for Diagnosis of Peritoneal Metastases and Prediction of Peritoneal Recurrences.

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.

Long non-coding RNAs in the gastric juice of gastric cancer patients.

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.

Gastric Juice MicroRNAs as Potential Biomarkers for Screening Gastric Cancer: A Systematic Review.

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.

Utility of Nasogastric Tube for Medical and Surgical Oncology of Gastric Cancer: A Prospective Institutional Study on a New and Precious Application of an Old and Economic Device.

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.

Laparoscopic Intragastric Surgery for Treating Early Gastric Cancer.

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.