Linfócitos e volume plaquetário estão associados a complicações pós-esofagectomia por câncer: um estudo de coorte / Lymphocyte count and platelet volume predicts postoperative complications in esophagectomy for cancer: a cohort study

ABSTRACT BACKGROUND: Biomarkers from routine complete blood count are known predictive factors of long-term outcomes in cancer patients. The value of these biomarkers in the setting of trimodal therapy for esophageal cancer in predicting early postoperative outcomes is not studied. OBJECTIVE: The present study evaluated the value of cellular blood components changes during neoadjuvant chemoradiotherapy followed by curative intent esophagectomy for cancer in predicting postoperative mortality and morbidity. METHODS: A cohort of 149 consecutive patients that underwent chemoradiotherapy using platinum- and taxane-based regimens followed by esophagectomy was analyzed. Cellular components of blood collected before neoadjuvant therapy (period A) and before surgery (period B) were assessed for postoperative mortality and complications. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of blood count variables. RESULTS: Postoperative morbidity was present in 46% of the patients. On multiple regression analysis platelet volume (B) (OR: 1.53; 95% CI: 1.2-2.33) was an independent predictor of general complications. Severe postoperative surgical complications were present in 17% of the patients. On multiple regression analysis, lymphocyte decrease between B-A periods (OR: 0.992; 95% CI: 0.990-0.997) was related to higher risk for severe complications. Cervical anastomotic leakage was present in 25.6% of the patients. On univariate analysis eosinophil count in A and B periods was related to cervical anastomotic leakage. For this outcome, multivariate joint model could not identify independent risk variables of cellular components of blood. The 30-day mortality rate was 7.4%. On univariate analysis, platelet count in period B was associated to higher risk for mortality. The multivariate joint model could not accurately predict mortality due to the few number of patients in the mortality group. CONCLUSION: This is the first study to assess the relationship between peripheral blood count variables changes during neoadjuvant chemoradiotherapy using a platinum- and taxane-based regimen followed by curative intent esophagectomy for cancer in predicting postoperative complications. The platelet volume prior to surgery is related to postoperative complications and the lymphocyte count change prior to surgery predicts severe postoperative complications in the setting of trimodal therapy for esophageal cancer.

RESUMO CONTEXTO: Os biomarcadores obtidos do hemograma completo são fatores prognósticos a longo prazo em pacientes com câncer. No entanto, o valor desses biomarcadores no contexto da terapia trimodal para o câncer de esôfago na predição de resultados pós-operatórios precoces não é estudado. OBJETIVO: O presente estudo avaliou o papel dos componentes celulares do sangue na predição de mortalidade e morbidade pós-operatória. MÉTODOS: Uma coorte de 149 pacientes consecutivos submetidos à quimiorradioterapia usando esquemas baseados em platina e taxano seguidos por esofagectomia foi analisada. Os componentes celulares do sangue coletados antes da terapia neoadjuvante (período A) e antes da cirurgia (período B) foram avaliados quanto à mortalidade e complicações pós-operatórias. Modelos de regressão de Cox univariada e multivariada foram aplicados para avaliar a significância prognóstica independente das variáveis da contagem sanguínea. RESULTADOS: A morbidade pós-operatória esteve presente em 46% dos pacientes. Na análise de regressão múltipla, o volume plaquetário (B) (OR: 1,53; IC95%: 1,2-2,33) foi um preditor independente de complicações gerais. Complicações cirúrgicas pós-operatórias graves estavam presentes em 17% dos pacientes. Na análise de regressão múltipla, a diminuição de linfócitos entre os períodos B-A (OR: 0,992; 95% CI: 0,990-0,997) esteve relacionada ao maior risco de complicações graves. Fístula da anastomose cervical esteve presente em 25,6% dos pacientes. Na análise univariada, a contagem de eosinófilos nos períodos A e B relacionou-se com a fístula da anastomose cervical. Para este resultado, o modelo multivariado de articulação não conseguiu identificar variáveis de risco independentes entre os componentes celulares do sangue. A taxa de mortalidade em 30 dias foi de 7,4%. Na análise univariada, a contagem no período B foi associada a maior risco de mortalidade. O modelo multivariado de articulação não pôde predizer mortalidade devido ao pequeno número de pacientes no grupo de mortalidade. CONCLUSÃO: Este é o primeiro estudo a avaliar o papel das variáveis do hemograma durante a quimiorradioterapia neoadjuvante para câncer na predição de complicações pós-operatórias. Volume plaquetário e variação da contagem de linfócitos séricos antes da cirurgia podem ser utilizados como biomarcadores preditivos de complicações pós-operatórias nos pacientes com neoplasia de esôfago submetidos a terapia trimodal.

Câncer gástrico em adultos jovens: um grupo de pior prognóstico? / Gastric cancer in young adults: a worse prognosis group?

RESUMO Objetivo: avaliar as características clínico-patológicas e sobrevivência de pacientes jovens, portadores de câncer gástrico, independentemente da intenção de tratamento. Métodos: análise retrospectiva de todos os pacientes com câncer gástrico submetidos a qualquer tratamento cirúrgico entre 2008 e 2017. Pacientes com idade inferior a 45 anos foram considerados adultos jovens, e aqueles com mais de 45 anos foram definidos como grupo com idade avançada. Resultados: dos 875 pacientes avaliados, 84 (9,6%) eram adultos jovens e 791 (90,4%) tinham idade avançada. Jovens associaram-se ao sexo feminino (p<0,001), menor escore de Charlson (p=0,002), ASA I/II (p<0,001), tipo difuso de Lauren (p<0,001) e tumores pouco diferenciados (p<0,001). Não houve diferença entre os grupos quanto à intenção de tratamento (paliativo versus curativo) (p=0,267) e estádio clínico cTNM (p=0,120). A sobrevida livre de doença foi pior nos jovens (p=0,049), mas a sobrevida global foi semelhante entre os grupos (p=0,578). A análise multivariada identificou gastrectomia total, pT3/T4, pN+ e tipo difuso de Lauren como fatores prognósticos associados a pior sobrevida livre de doença e sobrevida global. A idade não foi um fator independente associado a pior prognóstico. Conclusão: apesar de os jovens apresentarem uma menor sobrevida livre de doença, a sobrevida global foi semelhante entre os grupos, e a idade não demonstrou ser um fator prognóstico independente significativo.

ABSTRACT Objective: to evaluate the clinical and pathological characteristics and survival of young patients with gastric cancer, regardless of the intention of treatment. Methods: we conducted a retrospective analysis of all gastric cancer patients undergoing any surgical treatment between 2008 and 2017. We considered patients under 45 years old as young adults and those over 45 years old, as of advanced age. Results: of the 875 patients evaluated, 84 (9.6%) were young adults and 791 (90.4%) were older. Younger patients were associated with female gender (p<0.001), lower Charlson score (p=0.002), ASA I/II (p<0.001), diffuse Lauren type (p<0.001) and poorly differentiated tumors (p<0.001). There was no difference between groups regarding treatment intention (palliative versus curative) (p=0.267) and cTNM clinical stage (p=0.120). Disease-free survival was worse in younger individuals (p=0.049), but overall survival was similar between groups (p=0.578). Multivariate analysis identified total gastrectomy, pT3/T4, pN+, and diffuse Lauren type as prognostic factors associated with worse disease-free survival and overall survival. Age was not an independent factor associated with worse prognosis. Conclusion: although younger patients had lower disease-free survival, overall survival was similar between groups, and age was not a significant independent prognostic factor.

Transhiatal esophagectomy is not associated with poor quality lymphadenectomy / Esofagectomia trans-hiatal não está associada com linfadenectomia de baixa qualidade

ABSTRACT Background: Esophageal cancer neoadjuvant therapy followed by surgery increases the likelihood of treatment success. Aim: To evaluate variables that can influence the number of retrieved lymph nodes, the number of retrieved metastatic lymph nodes and lymphnodal recurrence in esophagectomy after neoadjuvant chemoradiotherapy. Methods: Patients of a single institute were evaluated after completion of trimodal therapy. Univariate and multivariate analyses were performed to evaluate variables that can influence in the number of retrieved lymph nodes and retrieved metastatic lymph nodes. Results: One hundred and forty-nine patients were included. Thoracoscopy access was considered an independent factor for the number of lymph nodes retrieved, but was neither related to the number of positive lymph nodes retrieved nor to lymphnodal recurrence. Pathological complete response on the primary tumor and male were independent variables associated with the number of positive lymph node retrieved. Pathological complete response on the primary tumor site did not statistically influence the likelihood of a lower number of lymph nodes retrieved. Conclusion: Patients submitted to esophagectomy after neoadjuvant chemoradiotherapy, thoracoscopic access is more accurate for pathological staging, even in a complete pathological response. With a proper patient selection, transhiatal surgery may preserve the quality of lymphadenectomy of the positive lymph nodes.

RESUMO Racional: No câncer esofágico a terapia neoadjuvante seguida de procedimento cirúrgico aumenta a probabilidade de sucesso do tratamento. Objetivo: Avaliar variáveis que podem influenciar o número de linfonodos recuperados, o número de linfonodos metastáticos recuperados e a recorrência linfonodal na esofagectomia após quimiorradioterapia neoadjuvante. Métodos: Os pacientes incluídos foram aqueles que terminaram terapia trimodal. Análises univariadas e multivariadas foram realizadas para avaliar as variáveis que pudessem influenciar no número de linfonodos recuperados e nos metastáticos recuperados. Resultados: Cento e quarenta e nove pacientes foram incluídos. O acesso por toracoscopia foi considerado fator independente para o número de linfonodos recuperados, mas não teve relação com o número de linfonodos positivos recuperados, nem com recorrência linfonodal. Resposta patológica completa no tumor primário e homens foram variáveis independentes associadas ao número de linfonodos positivos recuperados. A resposta patológica completa do tumor primário não acarretou em número menor de linfonodos recuperados. Conclusão: Em pacientes submetidos à esofagectomia após quimiorradioterapia neoadjuvante o acesso toracoscópico é mais preciso para estadiamento patológico, mesmo em resposta patológica completa. Com seleção adequada a esofagectomia trans-hiatal pode preservar a qualidade da linfadenectomia dos linfonodos positivos.

Conversion therapy for gastric cancer: expanding the treatment possibilities / Terapia de conversão no câncer gástrico: ampliando as possibilidades de tratamento

ABSTRACT Background: Conversion therapy in gastric cancer (GC) is defined as the use of chemotherapy/radiotherapy followed by surgical resection with curative intent of a tumor that was prior considered unresectable or oncologically incurable. Aim: To evaluate the results of conversion therapy in the treatment of GC. Methods: Retrospective analysis of all GC surgeries between 2009 and 2018. Patients who received any therapy before surgery were further identified to define the conversion group. Results: Out of 1003 surgeries performed for GC, 113 cases underwent neoadjuvant treatment and 16 (1.6%) were considered as conversion therapy. The main indication for treatment was: T4b lesions (n=10), lymph node metastasis (n=4), peritoneal carcinomatosis and hepatic metastasis in one case each. The diagnosis was made by imaging in 14 cases (75%) and during surgical procedure in four (25%). The most commonly used chemotherapy regimens were XP and mFLOX. Major surgical complications occurred in four cases (25%) and one (6.3%) died. After an average follow-up of 20 months, 11 patients (68.7%) had recurrence and nine (56.3%) died. Prolonged recurrence-free survival over 40 months occurred in two cases. Conclusion: Conversion therapy may offer the possibility of prolonged survival for a group of GC patients initially considered beyond therapeutic possibility.

RESUMO Racional : A terapia de conversão no câncer gástrico (CG) é definida como o uso de quimio/radioterapia seguida de ressecção cirúrgica com intenção curativa de um tumor que era considerado irressecável ou oncologicamente incurável. Objetivo : Avaliar os resultados da terapia de conversão no tratamento do CG. Métodos : Análise retrospectiva de todas as operações de CG entre 2009 e 2018. Os pacientes que receberam alguma terapia antes da operação foram também identificados para definir o grupo de conversão. Resultados : Entre 1003 operações realizadas para o CG, 113 foram submetidos ao tratamento neoadjuvante e 16 (1,6%) considerados como terapia de conversão. As principais indicações para o tratamento foram: lesões T4b (n=10), metástase linfonodal (n=4), carcinomatose peritoneal e metástase hepática em 1 caso cada. O diagnóstico foi feito por exame de imagem em 14 casos (75%) e durante o procedimento cirúrgico em 4 casos (25%). Os esquemas quimioterápicos mais utilizados foram XP e mFLOX. Complicações cirúrgicas maiores ocorreram em 4 casos (25%) e 1 (6,3%) foi a óbito. Após seguimento médio de 20 meses, 11 pacientes (68,7%) apresentaram recidiva e 9 (56,3%) morreram. Sobrevida livre de recidiva prolongada acima de 40 meses ocorreu em dois casos. Conclusão : A terapia de conversão pode oferecer possibilidade de sobrevida prolongada para um grupo de pacientes com CG considerados inicialmente fora das possibilidades terapêuticas.

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

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

Validation of classic and expanded criteria for endoscopic submucosal dissection of early gastric cancer: 7 years of experience in a Western tertiary cancer center

OBJECTIVE: Our aim was to evaluate the Japan Gastroenterological Endoscopy Society criteria for endoscopic submucosal resection of early gastric cancer (EGC) based on the experience in a Brazilian cancer center. METHODS: We included all patients who underwent endoscopic submucosal resection for gastric lesions between February 2009 and October 2016. Demographic data and information regarding the endoscopic resection, pathological report and follow-up were obtained. Statistical calculations were performed with Fisher's exact test and chi-square tests, with 95% confidence intervals. RESULTS: In total, 76% of the 51 lesions were adenocarcinomas, 16% were adenomas, and 8% had other diagnoses. The average size was 19.9 mm (±11.7). The average procedure length was 113.9 minutes (±71.4). The complication rate was 21.3%, with only one patient who needed surgical treatment (transmural perforation). Among the adenocarcinomas, 39.5% met the classic criteria for curability, 31.6% met the expanded criteria and 28.9% met the criteria for noncurative resection. Analysis of the indication criteria and curability revealed differences among cases with "only-by-size" expanded criteria (64.28%), other expanded criteria (40%) and classic criteria (89.47%), with a p-value of 0.049. During follow-up (15.8 months; ±14.3), 86.1% of the EGC patients had no recurrence. When well-differentiated and poorly differentiated lesions or lesions included in the classic and expanded criteria were compared, there were no differences in recurrence. The noncurative group presented a higher recurrence rate than the classic group (p=0.014). CONCLUSION: These results suggest that the Japanese endoscopic submucosal resection criteria might be useful for endoscopic treatment of EGC in Western countries.

Prognostic factors affecting outcomes in multivisceral en bloc resection for colorectal cancer

OBJECTIVES: This study sought to determine the clinical and pathological factors associated with perioperative morbidity, mortality and oncological outcomes after multivisceral en bloc resection in patients with colorectal cancer. METHODS: Between January 2009 and February 2014, 105 patients with primary colorectal cancer selected for multivisceral resection were identified from a prospective database. Clinical and pathological factors, perioperative morbidity and mortality and outcomes were obtained from medical records. Estimated local recurrence and overall survival were compared using the log-rank method, and Cox regression analysis was used to determine the independence of the studied parameters. ClinicalTrials.gov: NCT02859155. RESULTS: The median age of the patients was 60 (range 23-86) years, 66.7% were female, 80% of tumors were located in the rectum, 11.4% had stage-IV disease, and 54.3% received neoadjuvant chemoradiotherapy. The organs most frequently resected were ovaries and annexes (37%). Additionally, 30.5% of patients received abdominoperineal resection. Invasion of other organs was confirmed histologically in 53.5% of patients, and R0 resection was obtained in 72% of patients. The overall morbidity rate of patients in this study was 37.1%. Ureter resection and intraoperative blood transfusion were independently associated with an increased number of complications. The 30-day postoperative mortality rate was 1.9%. After 27 (range 5-57) months of follow-up, the mortality and local recurrence rates were 23% and 15%, respectively. Positive margins were associated with a higher recurrence rate. Positive margins, lymph node involvement, stage III/IV disease, and stage IV disease alone were associated with lower overall survival rates. On multivariate analysis, the only factor associated with reduced survival was lymph node involvement. CONCLUSIONS: Multivisceral en bloc resection for primary colorectal cancer can be performed with acceptable rates of morbidity and mortality and may lead to favorable oncological outcomes.

Gastric stump mucosa: is there a risk for carcinoma?

Patients who underwent partial gastric resections are at an increased risk for the development of cancer in the gastric remnant. AIM: To assess the long-term patients who underwent surgical treatment for peptic ulcer disease through endoscopic and pathologic evaluation of the gastric stump mucosal alterations. PATIENTS AND METHODS: Between 1987 and 1990, 154 patients (mean = 20.4 years after gastrectomy) were evaluated by upper digestive endoscopy with multiple biopsies and pathological examination. RESULTS: Endoscopic alterations were present in 111 patients (72.1%). The commonest pathologic alterations were foveolar hyperplasia, intestinal metaplasia and cystic dilation. Severe dysplasia was noted in two (1.25%) and carcinoma in 13 (8.4%) of the cases. In four patients (3.8%) the endoscopic findings did not show any evidence of tumors, however they were detected due to multiple biopsies and histologic studies. CONCLUSIONS: Surveillance of these patients with endoscopy and multiple biopsies may provide the means to diagnose tumors at an early stage, but the cost benefit ratio of surveillance requires further study