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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Lessons learned analyzing complications after laparoscopic total gastrectomy for gastric cancer / Lições aprendidas analisando complicações da gastrectomia total laparoscópica para câncer gástrico

ABSTRACT 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.

RESUMO Racional: A cirurgia laparoscópica tem sido gradualmente aceita como opção para o tratamento cirúrgico do câncer gástrico. Ainda existem pontos controversos ou situações eventualmente associadas a dificuldades intra-operatórias ou complicações pós-operatórias. Objetivo: Estabelecer a relação entre as dificuldades durante a execução da gastrectomia total e a ocorrência de eventuais complicações pós-operatórias. Método: Foram revisados ​​os protocolos operatórios e a evolução pós-operatória de 74 pacientes operados por câncer gástrico, submetidos à gastrectomia total laparoscópica (critérios de inclusão). Foram analisadas as dificuldades intraoperatórias registradas no protocolo operatório e as complicações pós-operatórias de natureza cirúrgica (critérios de inclusão). As complicações médicas pós-operatórias foram excluídas (critérios de exclusão). Para a discussão, foi realizada extensa revisão bibliográfica. Resultados: Dificuldades ou complicações intraoperatórias relatadas corresponderam a 33/74 e destas 18 (54,5%) foram relacionadas com complicações pós-operatórias e seis absolutamente inesperadas. As mais frequentes foram vazamentos da anastomose e do coto duodenal; no entretanto, outras complicações raras foram observadas. Sete foram tratados com medidas conservadoras e 17 (22,9%) necessitaram de re-exploração cirúrgica, com mortalidade pós-operatória de dois pacientes (2,7%). Conclusão: Aprendemos que existem complicações infrequentes e inesperadas; a equipe de tratamento deve estar atenta e diante da suspeita de complicação, decisão apropriada pode incluir uma nova exploração precoce. Finalmente, após a experiência relatada, algumas complicações devem ser evitadas.

Lymphoparietal index in esophageal cancer is stronger than tnm staging in long-term survival prognosis in a latin-american country / índice linfoparietal no câncer esofágico é mais forte do que tnm no prognóstico de sobrevivência em longo prazo em um país latinoamericano

ABSTRACT 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.

RESUMO Racional: A identificação de fatores prognósticos do câncer de esôfago permitiu prever a evolução dos pacientes. Objetivo: Avaliar diferentes fatores prognósticos da sobrevida em longo prazo do câncer de esôfago e avaliar um novo fator prognóstico da sobrevida em longo prazo chamado índice linfoparietal (N+/T). Método: Estudo prospectivo do Hospital Clínico da Universidade do Chile, entre janeiro de 2004 e dezembro de 2013. Incluiu todas as operações de câncer de esôfago com intenção curativa e anastomose cervical. Os critérios de exclusão incluíram: câncer em estágio 4, ressecções R1, procedimentos paliativos e operações de emergência. Resultados: Cinquenta e oito pacientes foram incluídos, 62,1% eram homens, a idade média foi de 63,3 anos. Um total de 48,3% eram escamosos, 88% eram cânceres avançados, a colheita média de linfonodos foi de 17,1. A morbidade cirúrgica pós-operatória foi de 75%, com 17,2% de reoperações e 3,4% de mortalidade. A sobrevida global média foi de 41,3 meses, a sobrevida em três anos foi de 31%. A análise multivariada dos fatores prognósticos mostrou que variáveis significativas foram elevação pelo mediastinal anterior (p=0,01, OR: 6,7 [1,43-31,6]), fístula anastomótica (p=0,03, OR: 0,21 [0,05-0,87]), classificação N (p=0,02, OR: 3,8 [1,16-12,73]), estágio TNM (p=0,04, OR: 2,8 [1,01-9,26]) e índice linfoparietal (p=0,04, RR: 3,9 [1,01-15,17]. As curvas ROC do índice linfoparietal, classificação N e estádio TNM apresentam áreas abaixo da curva de 0,71, 0,63 e 0,64, respectivamente, com diferença estatística significativa (p=0,01). Conclusão: Os fatores prognósticos independentes de sobrevida em longo prazo no câncer de esôfago são a elevação mediastinal anterior, fístula anastomótica, classificação N, estágio TNM e índice linfoparietal. No câncer de esôfago, o novo índice linfoparietal é mais forte que o estágio TNM no prognóstico de sobrevida em longo prazo.

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.

Introduction of the new lymphoparietal index for gastric cancer patients / Introdução de novo índice linfoparietal para pacientes de câncer gástrico

ABSTRACT 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.

RESUMO Racional: A identificação de fatores prognósticos do câncer gástrico (GC) permitiu predizer a evolução dos pacientes. Objetivo: Avaliar a confiabilidade do índice linfoparietal na predição de sobrevida em longo prazo em pacientes tratados com intenção curativa. Método: Estudo prospectivo do Hospital das Clínicas da Universidade de Chile, entre maio de 2004 e maio de 2012. Todas as operações de câncer gástrico foram com intenção curativa. Os critérios de exclusão foram: gastrectomia por lesões benignas, cânceres estágio 4, ressecções R1, procedimentos paliativos, esofagogastrectomias completas e operações de emergência. Resultados: Foi incluído um total de 284 pacientes; da amostra 65,4% eram homens, com média de idade de 64,5 anos, 75% eram cânceres avançados, 72,5% necessitaram de gastrectomia total e 30 coletas de linfonodos. A morbimortalidade cirúrgica foi de 17,2% e 1,7%. Sobrevida em cinco anos foi de 56,9%. O índice N +/T pôde predizer a sobrevida em longo prazo em todos os subgrupos (p<0,0001), embora tivesse previsão confiável em GC precoce (p=0,005), GC avançado (p<0,0001), célula GC de anel de sinete (p< 0,0001), GC proximal (p<0,0001) e GC distal (p<0,0001). As curvas ROC N +/T, LNR e T apresentaram áreas abaixo da curva de 0,789, 0,786 e 0,790, respectivamente, sem diferença estatística significativa (p=0,96 ). Conclusão: O índice N +/T é um quociente confiável no prognóstico na avaliação de pacientes com adenocarcinoma gástrico que foram ressecados com intenção curativa.

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.

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.

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.

Resultados del tratamiento quirúrgico en pacientes con cáncer gástrico de 80 o más años / Results of surgical treatment of gastric cancer in patients with 80 or more years of age

Introducción: La población chilena, al igual que la mundial, ha presentado un importante envejecimiento en los últimos 25 años. El cáncer gástrico ocupa la primera causa de mortalidad por tumores malignos en Chile. Objetivo: Determinar la mortalidad operatoria de la gastrectomía total o subtotal en pacientes con cáncer gástrico de 80 o más años y la sobrevida a 5 años. Material y método: Estudio retrospectivo y prospectivo de todos los pacientes sometidos a resección gástrica por cáncer gástrico entre 1988 y 2016, con 80 o más años. Se excluyeron los pacientes sometidos a técnicas quirúrgicas no resectivas. Se analizaron las siguientes variables: síntomas y signos, comorbilidades, características anatomopatológicas, mortalidad según el tipo de gastrectomía y sobrevida global a 5 años. Resultados: En el periodo de tiempo analizado hubo 70 pacientes con cáncer gástrico y edad igual o mayor de 80 años, que representan al 7,4% del total de pacientes con resección gástrica. Los síntomas más frecuentes fueron dolor, baja de peso y anemia crónica microcítica. Hubo un 66% de pacientes con comorbilidades. El cáncer se ubicó preferentemente en el tercio superior, siendo un adenocarcinoma en 66 pacientes. En 4 pacientes hubo 2 linfomas, un GIST maligno y un carcinoide maligno. El carcinoma incipiente correspondió al 12% de los adenocarcinomas. La mortalidad global de la gastrectomía fue del 17%, siendo el 5% para la subtotal y el 22% para la total. La sobrevida promedio a 5 años fue del 26%. Conclusiones: La gastrectomía subtotal o total en pacientes con cáncer gástrico sobre 80 años es factible de realizar en pacientes seleccionados, pero el riesgo de mortalidad operatoria es de 7 a 10 veces mayor que en pacientes bajo los 75 años.

Introduction: The longevity of Chilean population has increased greatly in the last 25 years, similar to world population. Gastric cancer in Chile is the first cause of death due to malignant tumors. Purpose: To determine operative mortality of subtotal or total gastrectomy in patients with gastric cancer older than 80 years, and the rate 5 year-survival. Material and method: This is an retrospective-prospective study of all patients with 80 years of age or more submitted to gastric resection due to gastric cancer between 1988 and 2016. Patients submitted to non-resective procedures were excluded. The following parameters were analized: symptoms and signs, comorbidities, pathologic features of the gastric cancer, operative mortality according to the gastrectomy and 5-year survival rate. Results: There were 70 patients with gastric cancer older than 80 years of age, which represented 7.4% of all patients with gastric cancer submitted to gastric resection in the same period of time. Most frequent symptoms were epigastric pain, loss of weight and chronic microcitic anemia. There were 66% of the patients with comorbidities. The tumor was located mainly in the upper third of the stomach, being an adenocarcinoma in 66 patients (94%). There were also 2 linfomas, one GIST and one patient with a malignant carcinoid. Early cancer was observed in 12% of the adenocarcinomas. Global operative mortality was 17% being 5% for subtotal and 22% for total gastrectomy. Mean 5-year survival rate was 26%. Conclusions: Subtotal or total gastrectomy in patients with gastric cancer with 80 years of age or more is possible to perform in selected patients, but the risk of operative mortality is 7 to 10 times greater than below 75 years of age.

Ressonância corporal: uma proposta de intervenção psicodramática / Body resonance: a proposal for a psychodramatic intervention / Resonancia del cuerpo: una propuesta psicodramática para intervención

Para este trabalho, especificamente apresentamos uma proposta de intervenção grupal psicodramática intitulada de "Ressonância Corporal", fundamentada no estudo e na prática de ações que utilizam a linguagem não verbal - comunicação corporal -, objetivando desvelar aquilo que é falado e sentido, bem como potencializar a capacidade expressiva do corpo inerente às pessoas. A vivência apresentada promove o resgate e a consciência da linguagem corporal, a partir da prática e da reflexão da relação comunicação-corpo. A ressonância corporal pode ser classificada como uma intervenção psicodramática que implica duas ou mais pessoas "ressoarem" a mensagem emitida por um indivíduo ou um grupo por meio de uma ação corporal executada.

This paper introduces a specific psychodramatic group intervention, namely "Body Resonance", which has its foundations in the study and practice of action using non-verbal language - body communication - and aims to unveil what is spoken and felt, as well as enhance the body's inherent expressive power in people. The here described experience promotes the revival and awareness of body language, by exercising and reflecting on the relationship between body and communication. Body resonance can be understood as a psychodramatic intervention that involves two or more people "resonating" the messages issued by an individual or group, through performing bodily action.

Para este trabajo, proponemos un psicodrama de la intervención de grupo específico que titulado "Resonancia corporal" basado en las acciones del estudio y la práctica que utilizan lenguaje no verbal - comunicación corporal - desvelando así lo que se habla y dirección, así como mejoran el cuerpo de fuerza expresiva inherente en las personas. La experiencia presentada promueve el rescate y conocimiento del lenguaje corporal, de práctica y reflexión de la comunicación de la relación del cuerpo. La resonancia del cuerpo se puede clasificar como una intervención de psicodrama que consiste en dos o más personas "resuenan" el mensaje emitido por un individuo o grupo a través de una acción corporal.