Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer.

Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. MICA gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study MICA gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of MICA gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA*002 (*A9) as the most frequent allele in both, patients and controls, followed by MICA*008 allele (*A5.1). MICA*009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39-18.74], p = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA*A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12-0.98], p = 0.046). Survival analysis after gastrectomy showed that patients with MICA*002/002 or MICA*002/004 alleles had significantly higher survival rates than those patients bearing MICA*002/008 (p = 0.014) or MICA*002/009 (MICA*002/049) alleles (p = 0.040). The presence of threonine in the position MICA-181 (MICA*009/049 allele) was more frequent in GC patients than controls (p = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA*004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori.

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

Polymorphisms PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in a high risk population.

Genetic variants are considered risk factors for gastric cancer. To date, 61 polymorphisms have been identified as associated with this disease. The aim of the present study was to analyze the association of some of those polymorphisms with GC in Chile. We performed a case-control study including 310 gastric cancer cases and 311 controls to assess the association of 36 single-nucleotide polymorphisms genotyped by Global Screening Array (GSA). Three polymorphisms was significantly associated: PSCA rs2294008 (allele model, OR = 1.49, 95%CI 1.17-1.88, P = 1.08 × 10-3), IL-4 rs2243250 (allele model, OR = 1.28, 95%CI 1.01-1.62, P = 0.04), and MUC1 rs4072037 (allele model, OR = 0.78, 95%CI 0.61-0.99, P = 0.04).PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in Chile. It suggests that those polymorphisms could be used as biomarkers to assess the genetic risk for this cancer outside of the previously studied populations, not only for East Asians and Caucasians populations.

Decreased invariant natural killer T-cell-mediated antitumor immune response in patients with gastric cancer.

Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Invariant natural killer T (iNKT) cells are innate-like cytotoxic T lymphocytes involved in tumor immune surveillance. They can be activated either through CD1d-presented glycolipid antigens recognized by their invariant T-cell receptor, cytokines or by sensing tumor-associated stress-induced ligands through the natural killer group 2, member D (NKG2D) receptor. Although the number and functionality of iNKT cells may be decreased in several types of cancer, here we show that GC patients presented a mild increase in iNKT cell frequencies and numbers in the blood compared with healthy donors. In GC patients, iNKT cells, expanded in vitro with α-galactosyl ceramide and stimulated with phorbol 12-myristate 13-acetate and ionomycin, produced higher levels of interleukin-2 and transforming growth factor-beta, while their capacity to degranulate remained preserved. Because tumor-derived epithelial cell adhesion molecule-positive epithelial cells did not display surface CD1d, and NKG2D ligands (NKG2DLs) were detected in the gastric tumor milieu, we envisioned a role for NKG2D in iNKT cell functions. Peripheral iNKT cells from GC patients and controls presented similar levels of NKG2D; nevertheless, the percentages of interferon-γ-producing and CD107a-positive iNKT cells from patients were reduced upon challenge with CD1d-negative, NKG2DL-positive K562 cells, suggesting a compromised response by iNKT cells in GC patients, which may not result from impaired NKG2D/NKG2DL signaling. The decreased response of iNKT cells may explain the fact that higher frequencies of circulating iNKT cells did not confer a survival benefit for GC patients. Therefore, functional impairment of iNKT cells in GC may contribute to tumor immune escape and favor disease progression.

Long responders to estramustine monophosphate. Report of two cases and literature review. / Repondedores a largo plazo a Estramustina monofosfato. A propósito de dos casos. Revisión bibliográfica.

OBJECTIVE: Estramustine is an stable estradiol and nitrogenated mustard conjugatewith antymicotic properties. Currently, with the appearance of chemotherapy and new molecules, estramustin acetate is not a drug of choice for castration resistant prostate cancer. METHODS: We describe two patients with castration resistant prostate cancer under treatment with estramustine acetate and complete biochemical response and stable disease. We review the literature to elucidate if the drug should be stopped and changed for the new molecules that have demonstrated survival increase. RESULTS: To our knowledge, there are not data in the literature to either solve the questions posed or shed light regarding cumulative toxicity due to prolongued use of estramustine acetate. CONCLUSIONS: We recognize that these clinical cases do not translate that estramustine acetate is a first line treatment for patients with CRPC. Nevertheless, they translate the heterogeneity of CRPC. It would be interesting to investigate the combination of new agents with estramustine acetate as well as the search of biomarkers that enable selection of candidates who could respond to estramustine acetate.

OBJETIVO: La estramustina es un conjugado estable de estradiol y una mostaza nitrogenada que tiene propiedades antimitóticas. Actualmente, con la aparición de la quimioterpia y las nuevas moléculas, el acetato de estramustina -no es un fármaco de elección en el cáncer de próstata resistente a castración.MÉTODO: Describimos dos pacientes con cáncer de próstata resistente a la castración en tratamiento con acetato de estramustina, y con una respuesta bioquímica completa y enfermedad estable. Revisamos la literatura para dilucidar si se debería retirar el acetato de estramustina y cambiar por las nuevas moléculas que han demostrado un aumento de supervivencia. RESULTADO: Hasta donde llega nuestro conocimiento, no hay datos en la literatura que resuelvan las dudas planteadas y tampoco que aporten luz en cuanto a la toxicidad acumulada por el uso prolongado del acetato de estramustina.CONCLUSIÓN: Somos conscientes de que estos casos clínicos no traducen que el acetato de estramustina sea un tratamiento de primera línea para los pacientes con cáncer de próstata resistente a la castración. Sin embargo, traducen la heterogeneidad del CPRC. Sería interesante investigar la combinación de los nuevos agentes con el acetato de estramustina así como la búsqueda de biomarcadores que permitan la selección de los candidatos que podrían responder al acetato de estramustina.

Endoscopic imaging techniques for detecting early colorectal cancer.

PURPOSE OF REVIEW: The detection of early colorectal cancer has improved notably since the introduction of bowel cancer screening programmes. This has created new challenges from endoscopic, histological and therapeutic perspectives. Here, we outline the limitations of current clinical practice and ways of implementing optical diagnosis to overcome these limitations. RECENT FINDINGS: Virtual chromoendoscopy without magnification for predicting or ruling out deep submucosal invasion is useful in real clinical practice for most lesions. However, magnifying virtual chromoendoscopy is needed to make an accurate diagnosis in nonulcerated narrow-band imaging international colorectal endoscopic (NICE) type 3 lesions or NICE type 2 lesions with depressed areas or of nodular mixed type. Finally, dye-based magnifying chromoendoscopy is needed in Japanese NBI Expert Team 2B lesions assessed with magnifying virtual chromoendoscopy. SUMMARY: A four-step strategy is proposed, combining white-light assessment, virtual chromoendoscopy without magnification, virtual chromoendoscopy with magnification and dye-based chromoendoscopy with magnification.

A long-term prospective study of the efficacy and safety of endoscopic septotomy using the LigaSure® system for the treatment of Zenker's diverticulum.

BACKGROUND AND OBJECTIVES: endoscopic septotomy of the cricopharyngeal muscle (ESCM) is a technique used for the treatment of Zenker's diverticulum (ZD). The experience with computerized vascular sealing systems (LigaSure® type) is limited. The objective of this study was to evaluate the efficacy and safety of ESCM using LigaSure®. METHODS: this was a long-term prospective study of 18 patients with ZD, who were referred to our hospital due to ESCM between 2010 and 2016. The severity of the symptoms was determined using the Dakkak-Bennett validated scale for dysphagia and the rest with numerical scales. The rates of relapse and retreatment were evaluated. RESULTS: ESCM with LigaSure® was performed in 17 cases, one case was excluded due to technical difficulties. The median age was 72 years and regurgitation, dysphagia and respiratory symptoms were found in 100%, 89% and 56% of cases, respectively. The median size of the diverticulum was 28 mm (20-60 mm). The median time of the procedure was 35 minutes (25-45 minutes). There were four complications, two hemorrhages and two perforations. The median follow-up was 13 months (range: 12-82 months). Clinical improvements were observed for all symptoms and were maintained 12 months after treatment (p < 0.05). There was no relapse during follow-up in 13 patients. A complete section was not achieved and clinical relapse occurred after a median time of seven months that required retreatment in the remaining patients. CONCLUSIONS: ESCM with LigaSure® may be a safe and effective technique in long-term follow-up situations, with low rates of relapse.

Endoscopic surveillance after colonic polyps and colorrectal cancer resection. 2018 update. / Vigilancia tras resección de pólipos de colon y de cáncer colorrectal. Actualización 2018.

There is limited scientific evidence available to stratify the risk of developing metachronous colorectal cancer after resection of colonic polyps and to determine surveillance intervals and is mostly based on observational studies. However, while awaiting further evidence, the criteria of endoscopic follow-up needs to be unified in our setting. Therefore, the Spanish Association of Gastroenterology, the Spanish Society of Family and Community Medicine, the Spanish Society of Digestive Endoscopy, and the Colorectal Cancer Screening Group of the Spanish Society of Epidemiology, have written this consensus document, which is included in chapter 10 of the "Clinical Practice Guideline for Diagnosis and Prevention of Colorectal Cancer. 2018 Update". Important developments will also be presented as regards the previous edition published in 2009. First of all, situations that require and do not require endoscopic surveillance are established, and the need of endoscopic surveillance of individuals who do not present a special risk of metachronous colon cancer is eliminated. Secondly, endoscopic surveillance recommendations are established in individuals with serrated polyps. Finally, unlike the previous edition, endoscopic surveillance recommendations are given in patients operated on for colorectal cancer. At the same time, it represents an advance on the European guideline for quality assurance in colorectal cancer screening, since it eliminates the division between intermediate risk group and high risk group, which means the elimination of a considerable proportion of colonoscopies of early surveillance. Finally, clear recommendations are given on the absence of need for follow-up in the low risk group, for which the European guidelines maintained some ambiguity.

IL-8-251T>A (rs4073) Polymorphism Is Associated with Prognosis in Gastric Cancer Patients.

BACKGROUND/AIM: Inflammation is a key process in gastric carcinogenesis. Cytokines are mediators of inflammation and are involved in metastasis and tumorigenicity. We previously assessed the role of cytokine gene polymorphisms in gastric cancer risk in Chile. In the present study, we aimed to analyze whether these polymorphisms are associated with overall survival (OS) in gastric cancer (GC) patients. PATIENTS AND METHODS: A total of 153 individuals with GC diagnosis were followed-up for at least 2 years. Hazard ratios (HR) were estimated from Cox regression models using SNPs as predictor variables. The following SNPs were genotyped for study using a TaqMan assay: rs16944 (IL1B -511C>T); rs4073 (IL8 -251 T>A); rs2275913 (IL-17 -197G>A); rs1800872 (IL10 -592 C>A); rs1800896 (IL10 -1082A>G); rs28372698 (IL32). RESULTS: Interleukin-8 rs4073 (IL-8 -251T>A) showed association with OS under the dominant model (TA + AA) only when adjusted by clinicopathological variables (HR=1.64, 95%CI=1.05-2.55, p=0.030, q-value=0.18), but not with the univariate model (HR=1.51, 95%CI=0.98-2.31, p=0.062, q-value=0.37). No significant differences were observed after adjusting for population stratification (PC1 and PC2 from Principal Component Analysis using genotypes from Infinium Global Screening Array). After stratification by clinicopathological variables, the association with shorter overall survival was higher among patients with diffuse-type tumors (HR=2.24, 95%CI=1.16-4.45) and patients with tumor size >5 cm (HR=1.79, 95%CI=1.08-2.97). CONCLUSION: These results suggest a role of IL-8 rs4073 in cancer prognosis. Its use as a prognostic marker of GC survival warrants further investigation.

Polymorphisms in TWIST1 and ZEB1 Are Associated with Prognosis of Gastric Cancer Patients.

BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) program has been linked as a driver of metastatic dissemination by conferring migratory and invasive capacity to cancer cells. Gastric cancer (GC) patients with tumors expressing altered levels of EMT markers have low survival. This study aimed to assess if polymorphisms of CDH1, TWIST1, SNAIL2, ZEB1 and ZEB2 genes are associated with survival in GC patients. PATIENTS AND METHODS: A total of 153 individuals with diagnosis of GC were recruited in Santiago, Chile. All patients were genotyped using Infinium Global Screening Array (GSA). Twenty Tag SNPs of the studied genes were retrieved. RESULTS: Three SNPs were associated with survival: rs2526614 (TWIST1) (genotype CA + AA, adjusted HR=0.58, 95%CI=0.37-0.93), rs6953766 (TWIST1) (genotype GG, crude HR=2.02, 95%CI=1.06-3.82, adjusted HR=2.14, 95%CI=1.07-4.25), and rs431073 (ZEB1) (genotype AC + CC, crude HR=1.62, 95%CI=1.01-2.59, adjusted HR=1.96, 95%CI=1.18-3.25). CONCLUSION: To the best of our knowledge, this is the first study proposing a role of these SNPs in cancer prognosis. Their use as prognostic markers of GC survival warrants further investigation.

Ghost Ileostomy in Advanced Ovarian Cancer: A Reliable Option.

OBJECTIVE: Diverting ileostomy (DI) has been proposed to reduce the incidence and consequences anastomotic leakage after bowel resection. In colorectal cancer treatment, ghost ileostomy (GI) has been proposed as an alternative to DI. Our objective was to report the results of GI associated with colorectal resection in the treatment of ovarian cancer. MATERIALS AND METHODS: This is an observational pilot study performed in a single institution. The main objective sought was to report the results of GI associated with colorectal resection in the treatment of ovarian cancer: 26 patients were included. RESULTS: Modified posterior exenteration was performed in 24 cases (92.3%) and rectum resection in the 2 cases of relapse (7.7%). After the main procedure GI was created, to check up the anastomosis status, a sequential postoperative rectoscopy was performed on postoperative day 5 ± 1 (range, 4-7). Serum levels were monitored in first and third postoperative days just with a descriptive intention to establish its relationship with the rectoscopy findings. In 2 cases, rectoscopy demonstrated a leakage. During postoperative course, no other complication related with the GI or DI was observed. No case of clinical anastomotic leakage was found. CONCLUSIONS: To the extent of our knowledge, this is the first study in which GI has been performed for the treatment of patients with ovarian cancer. Ghost ileostomy represents a real option that may reduce the number of ileostomies performed in ovarian cancer without increasing the morbimortality. Ghost ileostomy presents the advantages of DI while avoiding its drawbacks. It also seems to be a safe, feasible, and reproducible technique that does not add significant costs to the surgery.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions. / Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Polymorphisms in RAS/RAF/MEK/ERK Pathway Are Associated with Gastric Cancer.

The RAS/RAF/MEK/ERK pathway regulates certain cellular functions, including cell proliferation, differentiation, survival, and apoptosis. Dysregulation of this pathway leads to the occurrence and progression of cancers mainly by somatic mutations. This study aimed to assess if polymorphisms of the RAS/RAF/MEK/ERK pathway are associated with gastric cancer. A case-control study of 242 gastric cancer patients and 242 controls was performed to assess the association of 27 single nucleotide polymorphisms (SNPs) in the RAS/RAF/MEK/ERK pathway genes with gastric cancer. Analyses performed under the additive model (allele) showed four significantly associated SNPs: RAF1 rs3729931 (Odds ratio (OR) = 1.54, 95%, confidence interval (CI): 1.20⁻1.98, p-value = 7.95 × 10-4), HRAS rs45604736 (OR = 1.60, 95% CI: 1.16⁻2.22, p-value = 4.68 × 10-3), MAPK1 rs2283792 (OR = 1.45, 95% CI: 1.12⁻1.87, p-value = 4.91 × 10-3), and MAPK1 rs9610417 (OR = 0.60, 95% CI: 0.42⁻0.87, p-value = 6.64 × 10-3). Functional annotation suggested that those variants or their proxy variants may have a functional effect. In conclusion, this study suggests that RAF1 rs3729931, HRAS rs45604736, MAPK1 rs2283792, and MAPK1 rs9610417 are associated with gastric cancer.

The Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Hispanics Undergoing Endoscopy Is Infrequent Compared to Caucasians: A Cross-Sectional Study.

INTRODUCTION: The prevalence of eosinophilic esophagitis (EoE), a chronic, immune-mediated, clinicopathologic, inflammatory disorder, has been well described in the pediatric and adult Caucasian population but not as well studied in the Hispanic population. The major aims of this study are to determine the prevalence and gene expression profile of EoE in these populations. METHODS: This is a retrospective cohort study of patients from two institutions predominantly serving a Hispanic population. Patients included at Los Angeles County Hospital (LACH) had an esophagogastroduodenoscopy (EGD) and esophageal biopsies performed for evaluation of dysphagia and/or food impaction, while patients included from the University Hospital Medical Center of El Paso (UHMCEP) had an EGD and esophageal biopsies performed for any appropriate clinical indication. Gene expression analysis which has been shown to accurately diagnose EOE in Caucasians was performed for 9 patients at UHMCEP to determine its accuracy in Hispanics. RESULTS: At LACH, 234 patients were included in the study of whom 155 (66.3%) were Hispanic and 22 (9.4%) were Caucasian. 3.2% of the Hispanic patients and 9.1% of the Caucasian patients were diagnosed with EOE with threefold difference. At UHMCEP 1700 patients were included of whom 1350 (79.4%) were Hispanic and 179 (10.5%) were Caucasian. 0.96% of the Hispanic patients and 7.26% of the Caucasian patients were diagnosed with EOE with a sevenfold difference. Gene expression accurately diagnosed EOE in a small number of both Hispanics and Caucasians who underwent analysis. CONCLUSIONS: Hispanic patients at LAC and UMHCEP had a significantly lower prevalence of EOE as compared to Caucasians at these two institutions and a lower prevalence as compared to Caucasians with EOE previously reported in the literature. Gene expression analysis, which has previously been shown to accurately diagnose EOE in Caucasian patients, accurately diagnosed EOE in a small sample of this Hispanic population. Based on this similar gene expression, other factors such as environmental, ethnic, and cultural causes should be investigated to explain the markedly lower prevalence of EOE in Hispanics.

Beneficio de la bursectomía en gastrectomía D2 para el cáncer gástrico: una revisión sistemática / Benefit of bursectomy in gastrectomy D2 for gastric cancer: a systematic review

Resumen Introducción: La resección quirúrgica ha demostrado ser la única opción curativa para el cáncer gástrico, al incluir linfadenectomía D2 como estándar de seguridad. Sin embargo, el beneficio de extender la resección a la bursa omentalis sigue siendo controvertido. La investigación publicada no ha arrojado evidencia categórica definiendo la eficacia. Realizamos una revisión sistemática de ensayos clínicos aleatorizados publicados (ECA), para evaluar el beneficio de la bursectomía en la sobrevida global (OS) y la sobrevida libre de enfermedad (SLE) de los pacientes. Como resultado secundario se consideró la seguridad del procedimiento. Métodos: Se realizó una búsqueda bibliográfica en las bases de datos de Pubmed, Cochrane, Scielo, Metabuscador PUC, Epistemonikos, Tripdatabase, Sciencedirect y Lilacs para ECA que compararan la bursectomía con la no bursectomía, publicados antes de marzo de 2016. Se establecieron y aplicaron criterios de inclusión y exclusión. Resultados: Se encontraron 3 ECA correspondientes a diferentes informes de la misma cohorte de pacientes. Se incluyeron 210 pacientes (104 en el grupo de bursectomía y 106 en el grupo de no bursectomía). La bursectomía no tuvo un efecto significativo ni en la OS a 5 años (HR: 1,4; IC del 95%: 0,87-2,25) ni en la SLE (HR: 1,25; IC del 95% 0,80-1,97). No se observó diferencia estadísticamente significativa en la tasa de complicaciones al comparar el grupo de bursectomía y el grupo de no bursectomía. Conclusión: La gastrectomía con bursectomía no es superior a la no bursectomía, ya sea en términos de OS a 5 años o de SLE.

Abstract Introduction: The surgical resection has proved to be the only curative option for Gastric Cancer, when including D2 linfadenectomy as security standard. The benefit of extending the resection to the bursa omentalis, however, is still controversial. The published research has not yielded categorical evidence on defining the efficacy of bursectomy. We conducted a systematic review of published randomized controlled trials (RCT), to evaluate the benefit of bursectomy in the overall survival (OS) and disease-free survival (DFS) of patients. As secondary outcome, was considered the safety of the procedure. Methods: A literature search was conducted in Pubmed, Cochrane library databases, Scielo, Metabuscador PUC, Epistemonikos, Tripdatabase, Sciencedirect, and Lilacs for randomized clinical trials comparing bursectomy with non-bursectomy, published before March 2016. Inclusion and exclusion criteria were established and applied. Results: We found three RCT corresponding to different reports of the same cohort of randomized patients. They included 210 patients (104 in the bursectomy group, and 106 in the non-bursectomy group). The bursectomy did not have a significant effect either on 5-years OS (HR: 1.4; 95%CI: 0,87-2,25), or on DFS (HR: 1.25; 95% CI: 0,80-1,97). No statistically significant difference was observed in the rate of complications, when comparing the bursectomy group and the non-bursectomy group. Conclusion: Gastrectomy with bursectomy is not superior to non-bursectomy either in terms of 5 years OS or on DFS.

STAT3 inhibition by STA21 increases cell surface expression of MICB and the release of soluble MICB by gastric adenocarcinoma cells.

NKG2D is an activating receptor expressed on NK cells that binds to a variety of ligands, including MICA and MICB. These cell surface glycoproteins are overexpressed under cellular transformation, thus playing an important role in cell-mediated immune response to tumors. STAT3 is a transcription factor that is constitutively active in cancer. It negatively regulates MICA expression on target cells, while its inhibition enhances NK cell cytotoxicity against tumors. In this work, we aimed to describe the effect of STAT3 signaling inhibition by STA21 on the regulation of MICB expression in gastric adenocarcinoma cells and its effect on the cytotoxic function of NK cells. Treatment of gastric adenocarcinoma cells with STA21 induced an increase in MICB expression and soluble MICB secretion, as well as a variable pattern on effector cell degranulation. Soluble MICB secretion by gastric adenocarcinoma cells was not affected by metalloprotease inhibition. We also observed that primary gastric adenocarcinoma tissue released soluble MICB into the extracellular milieu. Recombinant MICB induced a significant decrease in the levels of NKG2D receptor on effector NK and CD8+ T cells, which correlated with an impaired cytotoxic function. Altogether, our data provide evidence that STAT3 signaling pathway regulates MICB expression on gastric adenocarcinoma cells and that recombinant soluble MICB compromises the cytolytic activity of NK cells.

Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients.

Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57% of tumors (13/23) and 44% of mucosal samples (10/23), while MICB was detected in 50% of tumors (10/20) and 45% of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.

[Influence of learning curve in the diagnosis of prostate cancer by ultrasound guided biopsy]. / INFLUENCIA DE LA CURVA DE APRENDIZAJE EN EL DIAGNÓSTICO DEL CÁNCER DE PRÓSTATA MEDIANTE BIOPSIA ECODIRIGIDA.

OBJECTIVE: To analyze if there is a learning curve to get to perform high quality ultrasound guided prostate biopsies that enable to effectively perform the diagnosis of prostate cancer, taking the pathological result of the samples into consideration. METHODS: We retrospectively reviewed data from 790 ultrasound-guided biopsies performed consecutively in our center between May 2009 and December 2012 by four surgeons. We reviewed the following data: Surgeon, date of intervention, patient age, PSA, rectal digital examination (DRE), ultrasound, prostate volume, number of cores obtained, pathology result of the biopsy. The surgeons were residents in Urology in their first year in the department. For statistical analysis the biopsies were grouped in blocks of 25 and 75 cases performed by a surgeon, in a chronological order. To evaluate the influence of the learning curve on diagnosis we performed univariate and multivariate analysis between the different variables and pathological report. RESULTS: Median age was 67 years (42-90). 300 biopsies (38%) were positive for prostate cancer. On univariate analysis, regarding cancer detection rate, the variables surgeon, PSA, DRE, ultrasound result, prostate volume, number of cores and groups of 75 showed statistically significant differences, this latter showing 32% in the first 75 biopsies and 43.2% in the last group. The variables age (p=0.11) and groups of 25 patients (p=0.07) did not show differences. Nevertheless, on multivariate analysis only PSA, DRE, prostate volume and groups of 75 patients were statistically significant, this latter with an OR of 1.35 (95%CI 1.09-1.66). CONCLUSIONS: The results obtained in our study show that the number of procedures performed, namely surgeon experience, does have an influence to achieve an optimal diagnostic yield in ultrasound guided prostatic biopsies.