Marcus Fernando Kodama Pertille Ramos

MINIMALLY INVASIVE SURGERY FOR GASTRIC CANCER: TIME TO CHANGE THE PARADIGM

ABSTRACT Introduction: Minimally invasive surgery widely used to treat benign disorders of the digestive system, has become the focus of intense study in recent years in the field of surgical oncology. Since then, the experience with this kind of approach has grown, aiming to provide the same oncological outcomes and survival to conventional surgery. Regarding gastric cancer, surgery is still considered the only curative treatment, considering the extent of resection and lymphadenectomy performed. Conventional surgery remains the main modality performed worldwide. Notwithstanding, the role of the minimally invasive access is yet to be clarified. Objective: To evaluate and summarize the current status of minimally invasive resection of gastric cancer. Methods: A literature review was performed using Medline/PubMed, Cochrane Library and SciELO with the following headings: gastric cancer, minimally invasive surgery, robotic gastrectomy, laparoscopic gastrectomy, stomach cancer. The language used for the research was English. Results: 28 articles were considered, including randomized controlled trials, meta-analyzes, prospective and retrospective cohort studies. Conclusion: Minimally invasive gastrectomy may be considered as a technical option in the treatment of early gastric cancer. As for advanced cancer, recent studies have demonstrated the safety and feasibility of the laparoscopic approach. Robotic gastrectomy will probably improve outcomes obtained with laparoscopy. However, high cost is still a barrier to its use on a large scale.

Risk Factors for Lymph Node Metastasis in Western Early Gastric Cancer After Optimal Surgical Treatment

BackgroundLymph node metastasis (LNM) has a strong influence on the prognosis of patients with early gastric cancer (EGC). As minimally invasive treatments are considered appropriate for EGC, and lymphadenectomy may be restricted or even eliminated in some cases; it is imperative to identify the main risk factors for LNM to individualize the therapeutic approach. This study aims to evaluate the risk factors for LNM in EGC and to determine the adequacy of the endoscopic resection criteria in a western population.MethodsEGC patients who underwent gastrectomy with lymphadenectomy were retrospectively analyzed utilizing a prospective database. The clinicopathological variables were assessed to determine which factors were associated to LNM.ResultsAmong 474 enrolled patients, 105 had EGC (22.1%). LNM occurred in 13.3% of all EGC (10% T1a; 15.4% T1b). Tumor size, venous, lymphatic, and perineural invasions were confirmed as independent predictors of LNM by multivariate analysis. Expanded criteria were safely adopted only in selected cases, and 13.6% of patients who matched expanded indication had LNM.ConclusionsTumor size, venous, lymphatic, and perineural invasions were associated with LNM and should be considered as surrogate markers for surgical treatment of EGC. Expanded criteria for endoscopic resection can be safely adopted only in selected cases.

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

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 patients prognosis.

GASTRIC NEUROENDOCRINE TUMOR: REVIEW AND UPDATE

INTRODUCTION The frequency of gastric neuroendocrine tumors is increasing. Reasons are the popularization of endoscopy and its technical refinements. Despite this, they are still poorly understood and have complex management. AIM Update the knowledge on gastric neuroendocrine tumor and expose the future perspectives on the diagnosis and treatment of this disease. METHOD Literature review using the following databases: Medline/PubMed, Cochrane Library and SciELO. Search terms were: gastric carcinoid, gastric neuroendocrine tumor, treatment. From the selected articles, 38 were included in this review. RESULTS Gastric neuroendocrine tumors are classified in four clinical types. Correct identification of the clinical type and histological grade is fundamental, since treatment varies accordingly and defines survival. CONCLUSION Gastric neuroendocrine tumors comprise different subtypes with distinct management and prognosis. Correct identification allows for a tailored therapy. Further studies will clarify the diseases biology and improve its treatment.

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

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.

Duodenal fistula: The most lethal surgical complication in a case series of radical gastrectomy

BACKGROUND Despite all advances regarding the surgical treatment of gastric cancer (GC), duodenal stump fistula (DF) continues to negatively affect postoperative outcomes. This study aimed to assess DF regarding its incidence, risk factors, management and impact on overall survival. METHODS We retrospectively analyzed 562 consecutive patients who underwent gastrectomy for GC between 2009 and 2017. Clinicopathological characteristics analysis was performed comparing DF, other surgical fistulas and patients with uneventful postoperative course. RESULTS DF occurred in 15 (2.7%) cases, and 51 (9%) patients had other surgical fistulas. Tumor located in the lower third of the stomach (p = 0.021) and subtotal gastrectomy (p = 0.002) were associated with occurrence of DF. The overall mortality rate was 40% for DF and 15.7% for others surgical fistulas (p = 0.043). The median time of DF onset was on postoperative day 9 (range 1-75). Conservative approach was performed in 8 patients and surgical intervention in 7 cases. Age (OR 7.41, p = 0.012) and DF (OR 9.06, p=0.020) were found to be independent risk factors for surgical mortality. Furthermore, patients without fistula had better long-term survival outcomes comparing to patients with any type of fistulas (p = 0.006). CONCLUSION DF is related with distal tumors and patients submitted to subtotal gastrectomy. It affects not only the postoperative period with high morbidity and mortality rates, but may also have a negative impact on long-term survival.

Prognostic Role of Neutrophil/Lymphocyte Ratio in Resected Gastric Cancer: A Systematic Review and Meta-analysis

High levels of inflammatory markers and the neutrophil-lymphocyte ratio appear to be associated with worse overall survival in solid tumors. However, few studies have analyzed the role of the neutrophil-lymphocyte ratio in gastric cancer patients scheduled to undergo curative resection. In the present study, a systematic review and meta-analysis was performed to analyze the relationship between the neutrophil-lymphocyte ratio and overall survival in patients with gastric cancer submitted to curative resection and to identify the clinicopathological features (age, gender, tumor depth, nodal involvement and tumor differentiation) that are correlated with high neutrophil-lymphocyte ratios. A literature search of PubMed, Scopus, Cochrane and EMBASE through November 2017 was conducted. Articles that included gastric cancer patients submitted to curative resection and preoperatory neutrophil-lymphocyte ratio values were included. A total of 7 studies comprising 3264 patients from 5 different countries were included. The meta-analysis revealed an association of high neutrophil-lymphocyte ratios with older age, male gender, lower 5-year overall survival, increased depth of tumor invasion, positive nodal involvement but not with histological differentiation. Evaluation of the neutrophil-lymphocyte ratio is a cost-effective method that is widely available in preoperatory settings. Furthermore, it can effectively predict prognosis, as high values of this biomarker are related to more aggressive tumor characteristics. This ratio can also be used to stratify risk in patients within the same disease stage and may be used to assist in individualized follow-up and treatment.

DETECTION OF OCCULT LYMPH NODE TUMOR CELLS IN NODE-NEGATIVE GASTRIC CANCER PATIENTS

ABSTRACT Background: The presence of lymph nodes metastasis is one of the most important prognostic indicators in gastric cancer. The micrometastases have been studied as prognostic factor in gastric cancer, which are related to decrease overall survival and increased risk of recurrence. However, their identification is limited by conventional methodology, since they can be overlooked after routine staining. Aim: To investigate the presence of occult tumor cells using cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically lymph node negative (pN0) by H&E. Methods: Forty patients (T1-T4N0) submitted to a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The results for metastases, micrometastases and isolated tumor cells were also associated to clinicopathological characteristics and their impact on stage grouping. Tumor deposits within lymph nodes were defined according to the tumor-node-metastases guidelines (7th TNM). Results: A total of 1439 lymph nodes were obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in 24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006) and perineural invasions (p=0.04), as well as peritumoral lymphocytic response (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally negative lymph nodes by H&E. The histologic stage of two patients was upstaged from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three among 12 CK-positive patients (25%) had disease recurrence (p=0.65). Conclusion: The CK-immunostaining is an effective method for detecting occult tumor cells in lymph nodes and may be recommended to precisely determine tumor stage. It may be useful as supplement to H&E routine to provide better pathological staging.

Risk factors associated with the development of gastric cancer — case-control study

INTRODUCTION It is estimated that about 1 million (952,000) new cases of gastric cancer occurred worldwide in 2012.1 Except for non-melanoma skin cancer, stomach cancer is currently the fifth most common cancer in the world. The National Cancer Institute (Inca)2 estimated for Brazil 12,920 new cases of stomach cancer in men and 7,600 in women in the biennium 2016-2017. Adenocarcinoma is the histological type most commonly found in gastric tumours. It accounts for more than 95% of gastric neoplasms, and is practically a synonym of gastric cancer. Other neoplasms found in the stomach include gastrointestinal stromal tumours, leiomyomas, lymphomas, and neuroendocrine tumours. Risk factors commonly associated with the development of gastric cancer include chronic infection with Helicobacter pylori (H. pylori), low fruit and vegetable intake, high salt intake, smoking, and alcohol consumption3. The World Health Organization (WHO) classifies H. pylori as a group 1 carcinogen

Reply to: “Association between neutrophil-lymphocyte ratio and prognosis after potentially curative resection for gastric cancer”

To the editor: We appreciate the interest of the authors of the letter in our research.1 It raised two questions regarding our study. The first one concerns the utilization of the Propensity Score Model (PSM) in order to obtain a more convincing statistical analysis. Propensity Score Model was first described in 1983, and since then has been utilized in observational studies, in order to reduce selection bias between treatment and control groups, by balancing the covariates.We decided to evaluate all patients who underwent potentially curative resection during the studied period, thus we did not utilized PSM in our research. Nonetheless, risk stratification according to neutrophil-lymphocyte ratio (NLR) value was done in same tumor depth (T4 and <T4), stage (III and <III) and lymph node status (N+ and N−) group of patients. Cox regression model demonstrated that NLR was an independent factor of worse OS (HR 1.50 95%CI 1.27-4.21, P = 0.048). Additionally, even if the necessity of a matching model would apply, PSM may be the wrong choice, as described by King et al.2 The second point was that the number of clinicopathological characteristics was low. We must also disagree with this affirmation. The range of covariates applied in a study does not imply necessarily a better quality or reliable results.We chose themain covariates allied to a large sample of patients. Once more, thank you very much for the comments.