Increased Morbidity and Mortality in COVID-19 Patients with Liver Injury.

BACKGROUND: There is a high prevalence of liver injury (LI) in patients with coronavirus disease 2019 (COVID-19); however, few large-scale studies assessing risk factors and clinical outcomes in these patients have been done. AIMS: To evaluate the risk factors and clinical outcomes associated with LI in a large inpatient cohort of COVID-19 patients. METHODS: Adult patients with COVID-19 between March 1 and April 30, 2020, were included. LI was defined as peak levels of alanine aminotransferase/aspartate aminotransferase that were 3 times the ULN or peak levels in alkaline phosphatase/total bilirubin that were 2 times the ULN. Mild elevation in liver enzymes (MEL) was defined as abnormal peak liver enzyme levels lower than the threshold for LI. Patients with MEL and LI were compared to a control group comprising patients with normal liver enzymes throughout hospitalization. RESULTS: Of 1935 hospitalized COVID-19 patients, 1031 (53.2%) had MEL and 396 (20.5%) had LI. Compared to control patients, MEL and LI groups contained proportionately more men. Patients in the MEL cohort were older compared to control, and African-Americans were more highly represented in the LI group. Patients with LI had an increased risk of mortality (relative risk [RR] 4.26), intensive care unit admission (RR, 5.52), intubation (RR, 11.01), 30-day readmission (RR, 1.81), length of hospitalization, and intensive care unit stay (10.49 and 10.06 days, respectively) compared to control. CONCLUSION: Our study showed that patients with COVID-19 who presented with LI had a significantly increased risk of mortality and poor clinical outcomes.

Observational medical treatment or surgery for giant paraesophageal hiatal hernia in elderly patients.

Giant paraesophageal hernias (GPHH) occur frequently in the elderly and account for about 5-10% of all hiatal hernias. Up to now controversy persists between expected medical treatment and surgical treatment. To assess if an indication for surgical repair of GPHH is possible in elderly patients. A prospective study that includes patients over 70 years of age hospitalized from January 2015 to December 2019 with GPHH. Patients were separated into Group A and Group B. Group A consisted of a cohort of 23 patients in whom observation and medical treatment were performed. Group B consisted of 44 patients submitted to elective laparoscopic hiatal hernia repair. Symptomatic patients were observed in both groups (20/23 in Group A and 38/44 in Group B). Charlson's score >6 and ASA II or III were more frequent in Group A. Patients in Group A presented symptoms many years before their hospitalization in comparison to Group B (21.8+7.8 vs. 6.2+3.5 years, respectively) (P=0.0001). Emergency hospitalization was observed exclusively in Group A. Acute complications were frequently observed and hospital stays were significantly longer in Group A, 14 patients were subjected to medical management and 6 to emergency surgery. In-hospital mortality occurred in 13/20 patients (65%) versus 1/38 patients (2.6%) in Group B (P=0.0001). Laparoscopic paraesophageal hiatal hernia repair can be done safely, effectively, and in a timely manner in elderly patients at specialized surgical teams. Advanced age alone should not be a limiting factor for the repair of paraesophageal hernias.

P059 Impact of PHQ-9 Screen on Early Identification of Depression in IBD Clinic.

BACKGROUND: Over the past two decades there has been significant research linking inflammatory bowel disease (IBD) to depression. The chronicity of symptoms coupled with the financial burden of treatment costs, missed days of work/school and interpersonal relationship stress are contributing factors in the diagnosis of depression. The prevalence of depression within the IBD community is 15% and depressive symptoms are noted in 20% of patients. Furthermore, IBD patients with severe uncontrolled disease have higher rates of depression (40.7%) than those in remission (16.5%). The association between IBD and depression is linked to lower quality of life, poor medication compliance, worse disease outcomes, increased hospitalization, and higher suicidal risk. Early diagnosis and treatment of depression in IBD patients is paramount in achieving and maintaining IBD disease remission. While the association between IBD and depression is well-known, identifying depression can be a challenge. Review of recent literature shows that depression is under screened in IBD clinics. We present a prospective quality improvement study at a robust IBD center evaluating the impact of a validated depression screen (PHQ-9) on identifying depression compared to standard of care. METHODS: We compared the prevalence of depression in the IBD clinic in the control group using the history and diagnosis of depression and compared it against the intervention group after HQ-9 screening. Control group patient data was collected from June 2020 to July 2020 via virtual and in person visits. Intervention group PHQ-9 data was collected in person visits from January - March 2020 and post-intervention data collection was placed on hold until November 2020 due to the COVID pandemic. One randomly selected patient from each clinic session was asked to participate in the study at the time of visit. The primary end point was to compare the rates of depression and identify any barriers in providing early treatment for depression. The secondary endpoint was to identify high risk patients that are prone to depression. Categorical variables were analyzed by chi square analysis or fischer exact tests. Numerical data were analyzed using T-test. RESULTS: A total of 111 patients were screened. 60 patients were randomized to the control group (i.e. EMR based review for depression) and 51 patients were screened via survey during in person clinic visit. The identified depression rate from control vs intervention group is 20% vs. 35% (p = 0.071). Rates of depression were 15% in non-fistulizing Crohn's disease vs. 41.4% in fistulizing Crohn's disease (p = 0.003). Multivariate model for predicting depression noted to be significant for extra-intestinal manifestations OR of 3.06 (1.03, 9.12) p = 0.045 and age OR of 0.97 (0.94, 1.00) p = 0.042. Control vs. intervention identification of depression in patients with extra-intestinal manifestations is notable for OR of 3.31 (1.15, 9.52) p = 0.026 in the univariate model and OR of 3.30 (1.07, 10.16) p = 0.038 in the multivariate model. CONCLUSION: Key findings including identification of depression is higher in the intervention group compared to the control group. Though the data is not statistically significant, this is likely secondary to the small sample size in the setting of the pandemic. In addition, univariate analysis revealed a statistically significant finding that the older the age of the patient, the less likely they are to have depression. Our data showed that the mean age of depressed patients was 38.3 compared to nondepressed patients whose mean age is 47.1. Further analysis can help elucidate this finding, for example identifying if older patients are being treated for depression or more likely to seek out therapists compared to younger patients. Univariate analysis also revealed that intestinal Crohn's disease was a risk factor for depression. This is possibly secondary to the severity of disease in these individuals, especially if their IBD is causing an impact on their quality of life. Looking into the number of hospitalizations, days off from work or school, and coexisting medical diagnoses can allow us to further understand if depression stems from their disease. Given preliminary findings, we plan to continue this study for a larger sample size and further determine if there is a significant delay in identifying depression with the current standard of care.

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.

Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population.

Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.

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.

Prevalence of clarithromycin resistance in Helicobacter pylori in Santiago, Chile, estimated by real-time PCR directly from gastric mucosa.

BACKGROUND: Current available treatments for Helicobacter pylori eradication are chosen according to local clarithromycin and metronidazole resistance prevalence. The aim of this study was to estimate, by means of molecular methods, both clarithromycin and metronidazole resistance in gastric mucosa from patients infected with H.pylori. METHODS: A total of 191 DNA samples were analyzed. DNA was purified from gastric mucosa obtained from patients who underwent an upper gastrointestinal endoscopy at an university hospital from Santiago, Chile, between 2011 and 2014. H.pylori was detected by real-time PCR. A 5'exonuclease assay was developed to detect A2142G and A2143G mutations among H.pylori-positive samples. rdxA gene was sequenced in samples harboring A2142G and A2143G mutations in order to detect mutations that potentially confer dual clarithromycin and metronidazole resistance. RESULTS: Ninety-three (93) out of 191 DNA samples obtained from gastric mucosa were H.pylori-positive (48.7%). Clarithromycin-resistance was detected in 29 samples (31.2% [95%CI 22.0-41.6%]). The sequencing of rdxA gene revealed that two samples harbored truncating mutations in rdxA, one sample had an in-frame deletion, and 11 had amino acid changes that likely cause metronidazole resistance. CONCLUSIONS: We estimated a prevalence of clarithomycin-resistance of 31.8% in Santiago, Chile. Three of them harbor inactivating mutations in rdxA and 11 had missense mutations likely conferring metronidazole resistance. Our results require further confirmation. Nevertheless, they are significant as an initial approximation in re-evaluating the guidelines for H.pylori eradication currently used in Chile.

National Trend in Laparoscopic Gastrectomy for Gastric Cancer: Analysis of the National Register in Chile.

INTRODUCTION: The laparoscopic approach for the treatment of gastric cancer has many advantages. However, outside Asia there are few large case series. AIM: To evaluate postoperative morbidity, long-term survival, changes in indication, and the results of laparoscopic gastrectomy. METHODS: We included all patients treated with a laparoscopic gastrectomy from 2005 to 2014. We compared results across 2 time periods: 2005-2011 and 2012-2014. Median follow-up was 39 months. RESULTS: Two hundred and eleven patients underwent a laparoscopic gastrectomy (median age 64 years, 55% male patients). In 135 (64%) patients, a total gastrectomy was performed. Postoperative morbidity occurred in 29%. A significant increase in the indication of laparoscopic surgery for stages II-III (32 vs. 45%; p = 0.04) and higher lymph node count (27 vs. 33; p = 0.002) were observed between the 2 periods. The 5-year overall survival was 72%. According to the stage, the 5-year overall survival was 85, 63, and 54% for stage I, II, and III respectively (p < 0.001). CONCLUSIONS: There was an acceptable rate of postoperative complications and the long-term survival was in accordance with the disease stage. There was a higher indication of laparoscopic surgery in stages II-III disease, and higher lymph node count in the latter period of this study.

[Esophageal sarcomatoid squamous carcinoma: report of one case]. / Carcinoma escamoso sarcomatoide de la unión gastroesofágica: caso clínico.

Sarcomatoid squamous carcinoma (ESC) is a rare esophageal neoplasm, with a clinical, etiological and pathological behavior that differs from squamous cancer. From the histological point of view it has a dual configuration. The squamous epithelial component is usually limited to small areas, while the major part is constituted by mesenchymatous (sarcomatoid) polypoid tissue. Treatment is esophagectomy or total esophagogastrectomy depending on the tumor location. Early detection is critical in terms of survival. For large lesions, preoperative chemo-radiotherapy can be considered. We report a 78-year-old male presenting with dysphagia. An upper gastrointestinal endoscopy showed a tumor located below the cardia. The patient was subjected to a total esophageal and gastric resection. In a second operation, the digestive transit was reconstituted in 2 steps. The pathology report informed a sarcomatoid squamous carcinoma. After 18 months of follow up, the patient is ambulatory.

[Hiatal hernias: why and how should they be surgically treated]. / Hernias hiatales: ¿cuándo y por qué deben ser operadas?

INTRODUCTION: There is controversy in the literature about the choice of expectant medical treatment versus surgical treatment of hiatal hernias, depending on the presence or absence of symptoms. This study presents the results obtained by our group, considering disease duration and postoperative results. PATIENTS AND METHOD: A total of 121 patients were included and divided by age, disease duration, type of hiatal hernia and postoperative outcome. RESULTS: In 32% of the patients younger than 70 years, symptom duration was longer than 11 years and 68% of those aged more than 71 years had long-term symptoms (p<.05). Type iv hernias (complex) and those with diameters measuring more than 16 cm were observed in the group with longer symptom duration. Complications were more frequent in the older age group, in those with longer symptom duration and in those with type iv complex hernias. There was no postoperative mortality and only one patient (0.8%) with a type iii hernia and severe oesophagitis required reoperation. CONCLUSION: We recommend that patients with hiatal hernia undergo surgery at diagnosis to avoid complications and risks. Older patients should not be excluded from surgical indication but should undergo a complete multidisciplinary evaluation to avoid complications and postoperative mortality.

TOMOGRAPHIC SARCOPENIA PREDICTS ANASTOMOTIC LEAKS AND LONG-TERM SURVIVAL IN GASTRIC CANCER PATIENTS OPERATED WITH CURATIVE INTENT.

BACKGROUND: The preoperative nutritional state has prognostic postoperative value. Tomographic density and area of psoas muscle are validated tools for assessing nutritional status. There are few reports assessing the utility of staging tomography in gastric cancer patients in this field. AIMS: This study aimed to determine the influence of sarcopenia, measured by a preoperative staging computed tomography scan, on postoperative morbimortality and long-term survival in patients operated on for gastric cancer with curative intent. METHODS: This retrospective study was conducted from 2007 to 2013. The definition of radiological sarcopenia was by measurement of cross-sectional area and density of psoas muscle at the L3 (third lumbar vertebra) level in an axial cut of an abdominopelvic computed tomography scan (in the selection without intravascular contrast media). The software used was OsirixX version 10.0.2, with the tool "propagate segmentation", and all muscle seen in the image was manually adjusted. RESULTS: We included 70 patients, 77% men, with a mean cross-sectional in L3 of 16.6 cm2 (standard deviation+6.1) and mean density of psoas muscle in L3 of 36.1 mean muscle density (standard deviation+7.1). Advanced cancers were 86, 28.6% had signet-ring cells, 78.6% required a total gastrectomy, postoperative surgical morbidity and mortality were 22.8 and 2.8%, respectively, and overall 5-year long-term survival was 57.1%. In the multivariate analysis, cross-sectional area failed to predict surgical morbidity (p=0.4) and 5-year long-term survival (p=0.34), while density of psoas muscle was able to predict anastomotic fistulas (p=0.009; OR 0.86; 95%CI 0.76-0.96) and 5-year long-term survival (p=0.04; OR 2.9; 95%CI 1.04-8.15). CONCLUSIONS: Tomographic diagnosis of sarcopenia from density of psoas muscle can predict anastomotic fistulas and long-term survival in gastric cancer patients treated with curative intent.

LYMPHOPARIETAL INDEX IN ESOPHAGEAL CANCER IS STRONGER THAN TNM STAGING IN LONG-TERM SURVIVAL PROGNOSIS IN A LATIN-AMERICAN COUNTRY.

BACKGROUND: The identification of prognostic factors of esophageal cancer has allowed to predict the evolution of patients. AIM: Assess different prognostic factors of long-term survival of esophageal cancer and evaluate a new prognostic factor of long-term survival called lymphoparietal index (N+/T). METHOD: Prospective study of the Universidad de Chile Clinical Hospital, between January 2004 and December 2013. Included all esophageal cancer surgeries with curative intent and cervical anastomosis. Exclusion criteria included: stage 4 cancers, R1 resections, palliative procedures and emergency surgeries. RESULTS: Fifty-eight patients were included, 62.1% were men, the average age was 63.3 years. A total of 48.3% were squamous, 88% were advanced cancers, the average lymph node harvest was 17.1. Post-operative surgical morbidity was 75%, with a 17.2% of reoperations and 3.4% of mortality. The average overall survival was 41.3 months, the 3-year survival was 31%. Multivariate analysis of the prognostic factors showed that significant variables were anterior mediastinal ascent (p=0.01, OR: 6.7 [1.43-31.6]), anastomotic fistula (p=0.03, OR: 0.21 [0.05-0.87]), N classification (p=0.02, OR: 3.8 [1.16-12.73]), TNM stage (p=0.04, OR: 2.8 [1.01-9.26]), and lymphoparietal index (p=0.04, RR: 3.9 [1.01-15.17]. The ROC curves of lymphoparietal index, N classification and TNM stage have areas under the curve of 0.71, 0.63 and 0.64 respectively, with significant statistical difference (p=0.01). CONCLUSION: The independent prognostic factors of long-term survival in esophageal cancer are anterior mediastinal ascent, anastomotic fistula, N classification, TNM stage and lymphoparietal index. In esophageal cancer the new lymphoparietal index is stronger than TNM stage in long-term survival prognosis.

Prevalence of Helicobacter pylori Antimicrobial Resistance Among Chilean Patients.

BACKGROUND: Treatments for Helicobacter pylori (H. pylori) eradication include the use of antibiotics and a proton-pump inhibitor. Antibiotic resistance is a major concern for two drugs: levofloxacin and clarithromycin. The aim was to determine the prevalence of levofloxacin resistance (LevoR) and clarithromycin resistance (ClaR) in an urban population in Santiago, Chile. METHODS: Gastric mucosa biopsies were obtained for DNA isolation from 143 H. pylori-positive individuals aged 18-80 years. Direct sequencing of the quinolone-resistance determining region (QRDR) of the gyrA gene was used to determine LevoR. ClaR was determined using restriction-fragment length polymorphism or 5'exonuclease assay. RESULTS: The prevalences of LevoR and ClaR were 29 and 27%, respectively. LevoR was higher in women than in men (39 vs. 13%, p <0.001), while no sex difference was observed for ClaR (p = 0.123). The prevalence of LevoR increased with age (p-trend = 0.004) but not for ClaR (p-trend = 0.054). In sex-stratified analyses, both LevoR and ClaR increased with age only among women. Older women (>50 years) had a higher probability to carry LevoR strains as compared to men. The prevalence of dual LevoR and ClaR was 12.6%. CONCLUSIONS: The prevalence of ClaR and LevoR is high in Santiago, according to International guidelines that recommend avoiding schemes with antibiotic resistance >15%. Our findings provide evidence to re-evaluate current therapies and guide empirical first- and second-line eradication treatments in Chile.

LESSONS LEARNED ANALYZING COMPLICATIONS AFTER LAPAROSCOPIC TOTAL GASTRECTOMY FOR GASTRIC CANCER.

BACKGROUND: Laparoscopic surgery has been gradually accepted as an option for the surgical treatment ofgastric cancer. There are still points that are controversial or situations that are eventually associated with intra-operative difficulties or postoperative complications. AIM: To establish the relationship between the difficulties during the execution of total gastrectomy and the occurrence of eventual postoperative complications. METHOD: The operative protocols and postoperative evolution of 74 patients operated for gastriccancer, who were subjected to laparoscopic total gastrectomy (inclusion criteria) were reviewed. The intraoperative difficulties recorded in the operative protocol and postoperative complications of a surgical nature wereanalyzed (inclusion criteria). Postoperative medical complications were excluded (exclusion criteria). For the discussion, an extensive bibliographical review was carried out. RESULTS: Intra-operative difficulties or complications reported correspond to 33/74 and of these; 18 events (54.5%) were related to postoperative complications and six were absolutely unexpected. The more frequent were leaks of the anastomosis and leaks of the duodenal stump; however, other rare complications were observed. Seven were managed with conservative measures and 17 (22.9%) required surgical re-exploration, with a postoperative mortality of two patients (2.7%). CONCLUSION: We have learned that there are infrequent and unexpected complications; the treating team must be mindful of and, in front of suspicion of complications, anappropriate decision must be done which includes early re-exploration. Finally, after the experience reported, some complications should be avoided.

INTRODUCTION OF THE NEW LYMPHOPARIETAL INDEX FOR GASTRIC CANCER PATIENTS.

BACKGROUND: The identification of prognostic factors of gastric cancer (GC) has allowed to predict the evolution of patients. AIM: Assess the reliability of the lymphoparietal index in the prediction of long-term survival in GC treated with curative intent. METHOD: Prospective study of the Universidad de Chile Clinical Hospital, between May 2004 and May 2012. Included all gastric cancer surgeries with curative intent. Exclusion criteria were: gastrectomies due to benign lesions, stage 4 cancers, R1 resections, palliative procedures, complete esophagogastrectomies and emergency surgeries. RESULTS: A total of 284 patients were included; of the sample 65.4% were male,mean age of 64.5 years,75% were advanced cancers, 72.5% required a total gastrectomy, 30 lymph nodes harvest. Surgical morbidity and mortality were 17.2% and 1.7%. 5-year survival was 56.9%. The N+/T index could predict long-term survival in all de subgrups (p<0.0001), although had a reliable prediction in early GC (p=0.005), advanced GC (p<0.0001), signet ring cell GC (p<0.0001), proximal GC (p<0.0001) and distal GC (p<0.0001). The ROC curves N+/T index, LNR and T classification presented areas below the curve of 0.789, 0.786 and 0,790 respectively, without a significant statistical difference (p=0.96). CONCLUSION: The N+/T index is a reliable quotient in the prognostic evaluation of gastric adenocarcinoma patients who have been resected with curative intent.

Endoscopic ablation combined with fundoplication plus acid suppression-duodenal diversion procedure for long segment barrett´s esophagus: early and long-term outcome / Ablação endoscópica combinada com fundoplicatura associada a diversão duodenal no esôfago de barrett longo: resultados precoce e de longo prazo

ABSTRACT BACKGROUND: The addition of endoscopic ablative therapy plus proton pump inhibitors or fundoplication is postulated for the treatment of patients with long-segment Barrett´s esophagus (LSBE); however, it does not avoid acid and bile reflux in these patients. Fundoplication with distal gastrectomy and Roux-en-Y gastrojejunostomy is proposed as an acid suppression-duodenal diversion procedure demonstrating excellent results at long-term follow-up. There are no reports on therapeutic strategy with this combination. AIMS: To determine the early and long-term results observed in LSBE patients with or without low-grade dysplasia who underwent the acid suppression-duodenal diversion procedure combined with endoscopic therapy. METHODS: Prospective study including patients with endoscopic LSBE using the Prague classification for circumferential and maximal lengths and confirmed by histological study. Patients were submitted to argon plasma coagulation (21) or radiofrequency ablation (31). After receiving treatment, they were monitored at early and late follow-up (5-12 years) with endoscopic and histologic evaluation. RESULTS: Few complications (ulcers or strictures) were observed after the procedure. Re-treatment was required in both groups of patients. The reduction in length of metaplastic epithelium was significantly better after radiofrequency ablation compared to argon plasma coagulation (10.95 vs 21.15 mms for circumferential length; and 30.96 vs 44.41 mms for maximal length). Intestinal metaplasia disappeared in a high percentage of patients, and histological long-term results were quite similar in both groups. CONCLUSIONS: Endoscopic procedures combined with fundoplication plus acid suppression with duodenal diversion technique to eliminate metaplastic epithelium of distal esophagus could be considered a good alternative option for LSBE treatment.

RESUMO RACIONAL: A adição de terapia ablativa endoscópica associado a inibidores da bomba de prótons ou fundoplicatura tem sido postulada para o tratamento de pacientes com esôfago de Barrett de segmento longo (EBSL), no entanto, essa conduta não evita o refluxo ácido/biliar nesses pacientes. A fundoplicatura com gastrectomia distal e gastrojejunostomia em Y de Roux (FGD-Y) foi proposta como procedimento de supressão de ácido, demonstrando excelentes resultados no seguimento a longo prazo. Não há relatos na literature com a combinação dessa estratégia terapêutica. OBJETIVOS: Determinar os resultados precoces e a longo prazo observados em pacientes com EBSL com ou sem dysplasia de baixo grau, submetidos a FGD-Y, combinado com terapia endoscópica. MÉTODOS: Estudo prospectivo incluindo pacientes com EBSL, empregando a classificação de Praga, sendo o comprimento circunferencial (C) e máximo (M) e confirmado por estudo histológico. Os pacientes foram submetidos à coagulação com plasma de argônio (CPA, 21 pacientes) ou ablação por radiofrequência (ARF, 31 pacientes). Após o tratamento, eles foram seguidos precoce e tardiamente (5-12 anos), mediante avaliação endoscópica e histológica. RESULTADOS: Foram observadas poucas complicações após o procedimento (úlcera ou estenose). Re-tratamento foi necessário em ambos os grupos de pacientes. A redução do comprimento do epitélio metaplásico foi significativamente melhor após ARF em comparação com CPA (10,95 versus 21,15 mm para C e 30,96 versus 44,41 mm para M). A metaplasia intestinal desapareceu em elevada porcentagem de pacientes, e os resultados histológicos a longo prazo foram bastante semelhantes em ambos os grupos. CONCLUSÕES: Procedimentos endoscópicos combinados com fundoplicatura e gastrectomia distal e gastrojejunostomia em Y de Roux, para eliminar o epitélio metaplásico do esôfago distal podem ser considerados uma boa opção alternativa para o tratamento da EBSL.

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.

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 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.

Tomographic sarcopenia predicts anastomotic leaks and long-term survival in gastric cancer patients operated with curative intent / Sarcopenia tomográfica prevê fístulas de anastomoses e sobrevida a longo prazo em pacientes com câncer gástrico operados com intenção curativa

ABSTRACT BACKGROUND: The preoperative nutritional state has prognostic postoperative value. Tomographic density and area of psoas muscle are validated tools for assessing nutritional status. There are few reports assessing the utility of staging tomography in gastric cancer patients in this field. AIMS: This study aimed to determine the influence of sarcopenia, measured by a preoperative staging computed tomography scan, on postoperative morbimortality and long-term survival in patients operated on for gastric cancer with curative intent. METHODS: This retrospective study was conducted from 2007 to 2013. The definition of radiological sarcopenia was by measurement of cross-sectional area and density of psoas muscle at the L3 (third lumbar vertebra) level in an axial cut of an abdominopelvic computed tomography scan (in the selection without intravascular contrast media). The software used was OsirixX version 10.0.2, with the tool "propagate segmentation", and all muscle seen in the image was manually adjusted. RESULTS: We included 70 patients, 77% men, with a mean cross-sectional in L3 of 16.6 cm2 (standard deviation+6.1) and mean density of psoas muscle in L3 of 36.1 mean muscle density (standard deviation+7.1). Advanced cancers were 86, 28.6% had signet-ring cells, 78.6% required a total gastrectomy, postoperative surgical morbidity and mortality were 22.8 and 2.8%, respectively, and overall 5-year long-term survival was 57.1%. In the multivariate analysis, cross-sectional area failed to predict surgical morbidity (p=0.4) and 5-year long-term survival (p=0.34), while density of psoas muscle was able to predict anastomotic fistulas (p=0.009; OR 0.86; 95%CI 0.76-0.96) and 5-year long-term survival (p=0.04; OR 2.9; 95%CI 1.04-8.15). CONCLUSIONS: Tomographic diagnosis of sarcopenia from density of psoas muscle can predict anastomotic fistulas and long-term survival in gastric cancer patients treated with curative intent.

RESUMO RACIONAL: O estado nutricional pré-operatório tem valor prognóstico pós-operatório. A densidade tomográfica e a área do músculo psoas é uma ferramenta validada para o estado nutricional. Existem poucos estudos avaliando a utilidade da tomografia de estadiamento em pacientes com câncer gástrico neste campo. OBJETIVOS: Determinar a influência da sarcopenia, medida por tomografia computadorizada de estadiamento pré-operatório, na morbimortalidade pós-operatória e sobrevida em longo prazo em pacientes operados de câncer gástrico com intenção curativa. MÉTODOS: Estudo retrospectivo de 2007 a 2013. A definição de sarcopenia radiológica foi pela medida da área (PA) e densidade do músculo psoas (PD) a nível de L3 (Terceira vertebra lombar), em um corte axial de tomografia computadorizada abdominopélvica (na seleção sem meio de contraste intravascular). O Software utilizado foi o OsirixX v 10.0.2, com a ferramenta "propagar segmentação", ajustando manualmente todos os músculos vistos na imagem. RESULTADOS: Foram incluídos 70 pacientes, 77% homens, PA média em L3: 16,6 cm2 (desvio padrão+6,1), PD média em L3: 36,1 mean muscle density (desvio padrão+7,1). Os cânceres avançados foram de 86, 28,6% tinham células em anel de sinete, 78,6% necessitaram de gastrectomia total, a morbidade e mortalidade cirúrgica pós-operatória foi de 22,8 e 2,8%, respectivamente, a sobrevida global de 5 anos a longo prazo (SV5) foi de 57,1%. Na análise multivariada, PA falhou em prever morbidade cirúrgica (p=0,4) e sobrevida global de 5 anos (p=0,34), enquanto PD foi capaz de prever fístulas anastomóticas (p=0,009; OR 0,86; IC95% 0,76-0,96) e SV5 (p=0,04; OR 2,9; IC95% 1,04-8,15). CONCLUSÕES: O diagnóstico tomográfico de sarcopenia por desvio padrão é capaz de predizer fístulas anastomóticas e sobrevida a longo prazo em pacientes com câncer gástrico tratados com intenção curativa.