Robotic versus laparoscopic gastrectomy for gastric cancer: A Western propensity score matched analysis.

BACKGROUND: Robot-assisted gastrectomy (RG) has been shown to be safe and feasible in the treatment of gastric cancer (GC). However, it is unclear whether RG is equivalent to laparoscopic gastrectomy (LG), especially in the Western world. Our objective was to compare the outcomes of RG and LG in GC patients. METHODS: We reviewed all gastric adenocarcinoma patients who underwent curative gastrectomy by minimally invasive approach in our institution from 2009 to 2022. Propensity score matching (PSM) analysis was conducted to reduce selection bias. DaVinci Si platform was used for RG. RESULTS: A total of 156 patients were eligible for inclusion (48 RG and 108 LG). Total gastrectomy was performed in 21.3% and 25% of cases in LG and RG, respectively. The frequency of stage pTNM II/III was 48.1%, and 54.2% in the LG and RG groups (p = 0.488). After PSM, 48 patients were matched in each group. LG and RG had a similar number of dissected lymph nodes (p = 0.759), operative time (p = 0.421), and hospital stay (p = 0.353). Blood loss was lower in the RG group (p = 0.042). The major postoperative complications rate was 16.7% for LG and 6.2% for RG (p = 0.109). The 30-day mortality rate was 2.1% and 0% for LG and RG, respectively (p = 1.0). There was no significant difference between the LG and RG groups for disease-free survival (79.6% vs. 61.2%, respectively; p = 0.155) and overall survival (75.9% vs. 65.7%, respectively; p = 0.422). CONCLUSION: RG had similar surgical and long-term outcomes compared to LG, with less blood loss observed in RG.

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

BACKGROUND AND OBJECTIVES: 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 patient's prognosis. METHODS: We evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. RESULTS: EBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P = 0.032), proximal location (P < 0.001), undetermined Lauren type (P < 0.001), poorly differentiated histology (P = 0.043) and severe inflammatory infiltrate (P < 0.001). MSI-tumors were associated to older age (P = 0.002), subtotal gastrectomy (P = 0.004), pN0 (P = 0.024) and earlier TNM stage (P = 0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P < 0.001). MSI was associated to better survival outcomes. CONCLUSION: EBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.

Do colorectal cancer resections improve diabetes in long-term survivors? A case-control study.

BACKGROUND: A clinical study was designed that aimed to analyze whether resection of the large bowel in cancer patients might benefit diabetes mellitus. METHODS: This prospective case-control study included retrospective information. Patients (n = 247) included diabetic and euglycemic groups with colorectal cancer operations (n = 60), cancer gastrectomy (n = 72), exclusive chemoradiotherapy for rectal cancer (n = 46), and noncancer clinical controls (n = 69). Follow-up periods were, respectively, 79.2 ± 27.4, 86.8 ± 25.1, 70.0 ± 26.3, and 85.1 ± 18.2 months (NS). Diabetes groups included patients with prediabetes. RESULTS: Diabetes remission, defined as conversion from diabetes to prediabetes or from this condition to normal, was documented in, respectively, 32.4 % (11 of 34), 41.2 % (14 of 34), 7.1 % (1 of 14), and 7.7 % (3 of 39) in the four cohorts (P = 0.004). Within the same period, progression of euglycemic participants to diabetes occurred in 30.8 % (8 of 26), 63.2 % (24 of 38), 25.0 (8 of 32), and 20.0 % (6 of 30) (P = 0.028). Diabetes amelioration was associated with weight loss in gastrectomy patients but not in the other groups. Dietary intake, estimated in the two surgical populations, did not predict outcome. CONCLUSIONS: Diabetes amelioration after colorectal interventions was demonstrated, but progression of euglycemic patients toward prediabetes was not changed in comparison with nonsurgical controls. It is speculated that reshaping of the bowel microbiome or hormone changes after colorectal interventions underlay the improvement in diabetes. Body weight fluctuations could not be incriminated in this investigation.

Does Roux-en-Y gastrectomy for gastric cancer influence glucose homeostasis in lean patients?

BACKGROUND: Cancer gastrectomy seems to benefit type 2 diabetes; however, results are conflicting. In a prospective protocol, including retrospective information, the aim was assessment of changes in glucose profile in patients with both normal and deranged preoperative glucose homeostasis. METHODS: Patients (N = 164) with curative subtotal or total Roux-en-Y gastrectomy for gastric cancer (n = 92), or Roux-en-Y gastric bypass for morbid obesity (RYGB, n = 72) were preoperatively classified into diabetes (including prediabetes) and control group. Postoperative diabetes outcome was stratified as responsive or refractory, and results in controls were correspondingly defined as stable or new-onset diabetes (NOD), according to fasting blood glucose and HbA1c. Dietary intake and biochemical profile was documented. Statistical methods included analysis of variance, multivariate logistic regression, and propensity score matching according to postoperative weight loss. RESULTS: Age of cancer cases was 67.9 ± 11.5 years, 56.5 % males, initial body mass index (BMI) 24.7 ± 3.7, current BMI 22.6 ± 3.8 kg/m(2), and follow-up 102.1 ± 51.0 months, whereas in bariatric individuals age was 51.4 ± 10.1 years, 15.3 % males, initial BMI 56.7 ± 12.2, current BMI 34.8 ± 8.1 kg/m(2), and follow-up 104.1 ± 29.7 months. Refractory disease corresponded to 62.5 % (cancer) versus 23.5 % (bariatric) (P = 0.019), whereas NOD represented 69.2 versus 23.8 % respectively (P = 0.016). Weight loss (ΔBMI) was associated with diabetes response in cancer patients but not with NOD. No difference between subtotal and total gastrectomy was detected. Divergent outcomes (refractory vs. responsive) were confirmed in BMI-similar, propensity-matched cancer gastrectomy patients with preoperative diabetes, consistent with weight-dependent and -independent benefits. CONCLUSIONS: Diabetes response was confirmed, however with more refractory cases than in bariatric controls, whereas high proportions of NOD occurred. Such dichotomous pattern seems unusual albeit consistent with previous studies.

Short-Term Surgical Outcomes of Robotic Gastrectomy Compared to Open Gastrectomy for Patients with Gastric Cancer: a Randomized Trial.

BACKGROUND: Robotic gastrectomy (RG) has been shown to be a safe and feasible method in gastric cancer (GC) treatment. However, most studies are in Eastern cohorts and there is great interest in knowing whether the method can be used routinely, especially in the West. OBJECTIVES: The aim of this study was to compare the short-term surgical outcomes of D2-gastrectomy by RG versus open gastrectomy (OG). METHODS: Single-institution, open-label, non-inferiority, randomized clinical trial performed between 2015 and 2020. GC patients were randomized (1:1 allocation) to surgical treatment by RG or OG. Da Vinci Si platform was used. INCLUSION CRITERIA: gastric adenocarcinoma, stage cT2-4 cN0-1, potentially curative surgery, age 18-80 years, and ECOG performance status 0-1. EXCLUSION CRITERIA: emergency surgery and previous gastric or major abdominal surgery. Primary endpoint was short-term surgical outcomes. The study is registered at clinicaltrials.gov (NCT02292914). RESULTS: Of 65 randomized patients, 5 were excluded (3 palliatives, 1 obstruction and emergency surgery, and 1 for material shortage). Consequently, 31 and 29 patients were included for final analysis in the OG and RG groups, respectively. No differences were observed between groups regarding age, sex, BMI, comorbidities, ASA, and frequency of total gastrectomy. RG had similar mean number of harvested lymph nodes (p = 0.805), longer surgical time (p < 0.001), and less bleeding (p < 0.001) compared to OG. Postoperative complications, length of hospital stay, and readmissions in 30 days were equivalent between OG and RG. CONCLUSIONS: RG reduces operative bleeding by more than 50%. The short-term outcomes were non-inferior to OG, although surgical time was longer in RG.

ROBOTIC GASTRECTOMY: TECHNIQUE STANDARDIZATION.

BACKGROUND: Trocars position for the Si model (position is similar for the Xi, although trocars stay more in line). Robotic gastrectomy is gaining popularity worldwide. It allows reduced blood loss and lesser pain. However, it widespread use is limited by the extensive learning curve and costs. AIM: To describe our standard technique with reduced use of robotic instruments. METHODS: We detail the steps involved in the procedure, including trocar placement, necessary robotic instruments, and meticulous surgical description. RESULTS: After standardizing the procedure, 28 patients were operated with this budget technique. For each procedure material used was: 1 (Xi model) or 2 disposable trocars (Si) and 4 robotic instruments. Stapling and clipping were performed by the assistant through an auxiliary port, limiting the use of robotic instruments and reducing the cost. CONCLUSION: This standardization helps implementing a robotic program for gastrectomy in the daily practice or in one`s institution.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of oesophageal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 2): UPDATE ON TREATMENT.

BACKGROUND: : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. AIM: : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. METHODS: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. CONCLUSION: : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 1): AN UPDATE ON DIAGNOSIS, STAGING, ENDOSCOPIC TREATMENT AND FOLLOW-UP.

BACKGROUND: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented. AIM: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients. METHODS: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3. CONCLUSION: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of gastric cancer.

Gastric cancer is among the ten most common types of cancer worldwide. Most cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of gastric carcinomas. The Brazilian Group of Gastrointestinal Tumors (GTG) invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy and follow-up, which was followed by presentation, discussion, and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of gastric carcinomas in several scenarios and clinical settings.

TOTAL OMENTECTOMY IN GASTRIC CANCER SURGERY: IS IT ALWAYS NECESSARY?

BACKGROUND: Traditionally, total omentectomy is performed along with gastric resection and extended lymphadenectomy in gastric cancer (GC) surgery. However, solid evidences regarding its oncologic benefit is still scarce. AIM: To evaluate the incidence of metastatic omental lymph nodes (LN) in patients undergoing curative gastrectomy for GC, as well as its risk factors and patients' outcomes. METHODS: All consecutive patients submitted to D2/modified D2 gastrectomy due to gastric adenocarcinoma from March 2009 to April 2016 were retrospectively reviewed from a prospective collected database. RESULTS: Of 284 patients included, five (1.8%) patients had metastatic omental LN (one: pT3N3bM0; two: pT4aN3bM0; one: pT4aN2M0 and one pT4bN3bM0). Four of them deceased and one was under palliative chemotherapy due relapse. LN metastases in the greater omentum significantly correlated with tumor's size (p=0.018), N stage (p<0.001), clinical stage (p=0.022), venous invasion growth (p=0.003), recurrence (p=0.006), site of recurrence (peritoneum: p=0.008; liver: p=0.023; ovary: p=0.035) and death (p=0.008). CONCLUSION: The incidence of metastatic omental LN of patients undergoing radical gastrectomy due to GC is extremely low. Total omentectomy may be avoided in tumors smaller than 5.25 cm and T1/T2 tumors. However, the presence of lymph node metastases in the greater omentum is associated with recurrence in the peritoneum, liver, ovary and death.

Laparoscopic D2 Gastrectomy for Gastric Cancer: Mid-Term Results and Current Evidence.

INTRODUCTION: Although the first laparoscopic gastrectomy was performed in 1991, there was a long delay until it was incorporated into the regular practice of western surgeons. In Brazil, there are only few case series reported and data on its safety and efficacy along with mid- and long-term results are desired. OBJECTIVE: Present the mid-term results of laparoscopic gastrectomy with curative intent in the treatment of gastric adenocarcinoma and review the current evidence on the therapy of this neoplasia with the laparoscopic access. METHODS: Patients who underwent D2 laparoscopic gastrectomy for gastric adenocarcinoma were retrospectively reviewed. RESULTS: Sixty-nine patients met the inclusion criteria. The mean age was 59.2 years and the mean body mass index was 24.2 kg/m2. Subtotal gastrectomy was performed in 73.9%. The mean number of harvested lymph nodes was 36.7, increased lymph node count and shorter operative time were observed in the last 34 cases. Median hospital stay was 8 days. Postoperative complications occurred in 22 (31.9%) cases. Surgical mortality was 4.3%. CONCLUSION: Laparoscopic gastrectomy can be performed safely with excellent short- and mid-term results. As experience increases, surgical duration is reduced and lymph node count rises.

Surgical outcomes of gastrectomy with D1 lymph node dissection performed for patients with unfavorable clinical conditions.

BACKGROUND: Gastric cancer (GC) patients with advanced age and/or multiple morbidities have limited expected survival and may not benefit from extended lymph node resection. The aim of this study was to evaluate the surgical outcomes of these GC patients who underwent gastrectomy with D1 dissection. METHODS: We retrospectively reviewed all GC patients who underwent gastrectomy with curative intent from 2009 to 2017. The decision to perform D1 was based on preoperative multidisciplinary meeting, and/or intraoperative clinical judgment. RESULTS: Among 460 enrolled patients, 73 (15.9%) underwent D1 lymphadenectomy and 387 (84.1%) D2 lymphadenectomy. Male gender, older age, American Society of Anesthesiologists score (ASA) III/IV, higher neutrophil-to-lymphocyte ratio (NLR) and higher Charlson Comorbidity Index (CCI) were more common in the D1 group. Postoperative major complications were significantly higher in D1 group (24.7% vs 12.4%, p < 0.001) and mostly related to clinical complications. Locoregional recurrence was higher in the D1 group (53.8% vs 39.5%, p = 0.330) however, without statistical significance. No difference was found in disease-free survival (DFS) between D1 and D2 patients with positive lymph nodes (p = 0.192), whereas overall survival was longer in the D2 group (p < 0.001). Multivariate analysis showed a statistically significant impact on survival of age ≥70 years, CCI ≥5, total gastrectomy, D1 lymphadenectomy and advanced stages (III/IV). CONCLUSIONS: Frail patients had high surgical mortality even when submitted to D1 dissection. DFS was comparable to D2. Extent of lymphadenectomy in high-risk patients should take in account the expectation of a decrease in surgical risk with the possibility of impairment of long-term survival.

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.

Surgical treatment of gastric cancer: a 10-year experience in a high-volume university hospital.

OBJECTIVES: Surgery remains the cornerstone treatment modality for gastric cancer, the fifth most common type of tumor in Brazil. The aim of this study was to analyze the surgical treatment outcomes of patients with gastric cancer who were referred to a high-volume university hospital. METHODS: We reviewed all consecutive patients who underwent any surgical procedure due to gastric cancer from a prospectively collected database. Clinicopathological characteristics, surgical and survival outcomes were evaluated, with emphasis on patients treated with curative intent. RESULTS: From 2008 to 2017, 934 patients with gastric tumors underwent surgical procedures in our center. Gastric adenocarcinoma accounted for the majority of cases. Of the 875 patients with gastric adenocarcinoma, resection with curative intent was performed in 63.5%, and palliative treatment was performed in 22.4%. The postoperative surgical mortality rate for resected cases was 5.3% and was related to D1 lymphadenectomy and the presence of comorbidities. Analysis of patients treated with curative intent showed that resection extent, pT category, pN category and final pTNM stage were related to disease-free survival (DFS) and overall survival (OS). The DFS rates for D1 and D2 lymphadenectomy were similar, but D2 lymphadenectomy significantly improved the OS rate. Additionally, clinical factors and the presence of comorbidities had influence on the OS. CONCLUSIONS: TNM stage and the type of lymphadenectomy were independent factors related to prognosis. Early diagnosis should be sought to offer the optimal surgical approach in patients with less-advanced disease.

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

BACKGROUND: Lymph 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. METHODS: EGC 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. RESULTS: Among 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. CONCLUSIONS: Tumor 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.

Clinicopathologic and immunohistochemistry characterization of synchronous multiple primary gastric adenocarcinoma.

The aim of this investigation was to evaluate clinicopathologic and immunohistochemical characteristics of synchronous primary gastric adenocarcinomas. Immunohistochemistry for p53 (suppressor pathway) and for hMLH1, hMSH2, and hMSH6 (mutator pathway) was performed using ABC-technique amplification by biotinylated tyramide. Synchronous primary gastric adenocarcinomas were detected in 19/553 (3.43%) of the patients. The tumors were localized in distal stomach in 22, body in 14, and proximal in five. There was a predominance of intestinal type in the group of synchronic tumors compared to the solitary lesions, 73.2 vs 37.3%, p = 0.001. Synchronous neoplasias were diagnosed in earlier stage than solitary neoplasias, T1-T2 = 60.9% vs T1-T2 = 28.4%, p = 0.0001; and N0 = 68.4% vs N0 = 26.2%, p = 0.001. p53 was detected in 52.6% of the patients with synchronous tumors. Altered hMLH1 immunoexpression occurred in 26.3% of the patients and hMSH6 in 5.3%. hMSH2 immunoreactivity was positive in all tumors. p53 was solely detected in 17 tumors, while hMLH1 was altered in 10/24 negative p53 tumors, p = 0.01. Synchronous gastric adenocarcinomas presented higher frequency of intestinal type and early gastric cancer in comparison to solitary gastric cancer. Two routes of carcinogenesis, mutator, and suppressor appear to be involved independently in the development of synchronous tumors.

Prognostic value of immunohistochemistry in gastric neuroendocrine (carcinoid) tumors.

UNLABELLED: Three subtypes of enterochromaffin-like cell tumors (carcinoids) have been described: type I, associated with chronic atrophic gastritis; type II, multiple endocrine neoplasia 1 and Zollinger-Ellison syndrome; and type III, sporadic tumors. OBJECTIVES: (i) To investigate the immunoexpression of Ki-67, p53 and Bcl-2 proteins in enterochromaffin-like cell (carcinoid) tumors and (ii) to evaluate the prognostic value of these markers. METHODS: Fifty-four samples from 21 patients with gastric carcinoid tumors were sectioned and immunostained using avidin-biotin peroxidase method. RESULTS: The mean age was 62.2+/-11.4 years (36-83 years-old) and 13 (61.9%) were women. Type I lesions were detected in 61.9% and type III in 38.1%. Tumors were single in 10 (47.6%) and were multiple and/or multicentric in 11 (52.4%). Nuclear p53 immunoreactivity was observed in 6/21 patients (28.6%), and all of them were type III tumors (6/8), compared with no p53 expression in type I (0/13), P=0.0002. p53 expression was also associated with high degree of cell proliferation (Ki-67-positive nuclear cells), P=0.00001. Bcl-2 expression was either unreactive or weakly positive in all tumor lesions. The mean follow-up period was 50.4 months (SD=45.2), varying from 6 to 144 months. Overall survival time of patients with positive p53 expression and high proliferative rate was significantly lower than that of negative patients (14.4 vs 123 months, P=0.0007). CONCLUSIONS: (i) p53 immunoexpression associated with high proliferative rate was useful to distinguish between type I and type III gastric carcinoid tumors and (ii) these markers were able to predict a shorter survival.

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

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.

Racional: A presença de metástase em linfonodos é um dos indicadores prognósticos mais importantes no câncer gástrico. As micrometástases têm sido estudadas como fator prognóstico no câncer gástrico, sendo relacionadas à diminuição da sobrevida global e aumento do risco de recidiva da doença. Entretanto, sua identificação é limitada pela metodologia convencional, uma vez que podem não ser identificadas pela rotina histopatológica por meio da coloração de H&E. Objetivos: Investigar a presença de células tumorais ocultas através de imunoistoquimica utilizando as citoqueratinas (CK) AE1/AE3 em pacientes com câncer gástrico com linfonodos histologicamente classificados como negativos por H&E. Métodos: Quarenta pacientes (T1-T4N0) submetidos à gastrectomia potencialmente curativa com linfadenectomia D2 foram avaliados. A presença de metástases, micrometástases e células tumorais isoladas foram correlacionadas com características clínicopatológicas e impacto no estadiamento. Os depósitos tumorais nos linfonodos foram classificados de acordo com o sistema TNM (7º TNM). Resultados: Um total de 1439 linfonodos foi obtido (~36 por paciente). Células tumorais foram detectadas por imunoistoquimica em 24 linfonodos de 12 pacientes (30%). As células neoplásicas estavam presentes na forma isolada ou em cluster. Invasão tumoral (p=0,002), venosa (p=0,016), linfática (p=0,006) e perineural (p=0,04), assim como resposta linfocítica peritumoral (p=0,012) foram correlacionadas com linfonodos CK-positivos que originalmente eram negativos à H&E. Dois pacientes tiveram o estadiamento alterado, migrando do estádio IB para IIA. Quatro dos 28 CK-negativos (14,3%) e três dos 12 CK-positivos (25%) tiveram recorrência da doença (p=0,65). Conclusão: A imunoistoquimica é meio eficaz para a detecção de células tumorais ocultas em linfonodos, podendo ser recomendada para melhor determinar o estágio do tumor. Ela pode ser útil como técnica complementar à rotina de H&E, de modo a fornecer melhor estadiamento patológico.

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.