RESUMO
BACKGROUND: Transthoracic esophagectomy for cancer triggers a massive inflammatory reaction. The data whether a minimally invasive esophagectomy (MIE) leads to less pronounced inflammatory response compared to open right-sided transthoracic esophagectomy (OE) are scarce. The aim of this study was to evaluate the extent of the inflammatory reaction, represented by levels of the pro-inflammatory interleukins IL-6 and IL-8, the anti-inflammatory IL-1 RA and the chemokines CINC-1 and MCP-1 in the right pleural fluid and the blood from patients undergoing standard OE or MIE. METHODS: Pleural drainage fluid and blood was collected at five different time points during the first 72 h following surgery, and the concentrations of IL-6, IL-8, IL-1 RA, CINC-1 and MCP-1 were analyzed using enzyme-linked immune-sorbent assays in 24 patients undergoing MIE or OE. RESULTS: The groups were matched for cancer stage and comorbidities. Pro- and anti-inflammatory mediator levels in the pleural fluid were markedly increased at the end of surgery and on postoperative days 1-3. The pleural inflammatory response of all cyto- and chemokines was lower in the MIE group, reaching significance at some time points. Cyto- and chemokine response levels measured in the blood were overall lower compared to those in the pleural fluid. The chemokines CINC-1 and MCP-1 reacted less pronounced or not at all. Preoperative pulmonary comorbidity, postoperative pulmonary morbidity and length of surgery were associated with an increased reaction in selected mediators. CONCLUSIONS: The minimally invasive technique attenuates the inflammatory response, especially locally in the thoracic compartment. Length of procedure, preoperative pulmonary comorbidity and postoperative pulmonary complications are mirrored in an increase in individual inflammatory markers in the pleural fluid. The value of the chemokines CINC-1 and MCP-1 as markers of inflammation in the setting of esophagectomy is unclear.
Assuntos
Citocinas/biossíntese , Neoplasias Esofágicas/cirurgia , Esofagectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Pleura/imunologia , Idoso , Citocinas/sangue , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: The CXCL12-CXCR4 chemokine axis plays an important role in cell trafficking as well as in tumor progression. In colorectal cancer (CRC), the chemokine receptor CXCR4 has been shown to be an unfavorable prognostic factor in some studies, however, the role of its activated (phosphorylated) form, pCXCR4, has not yet been evaluated. Here, we aimed to investigate the prognostic value of CXCR4 and pCXCR4 in a large cohort of CRC patients. PATIENTS AND METHODS: A tissue microarray (TMA) of 684 patient specimens of primary CRCs was analyzed by immunohistochemistry (IHC) for the expression of CXCR4 and pCXCR4 by tumor cells and tumor-infiltrating immune cells (TICs). RESULTS: The combined high expression of CXCR4 and pCXCR4 showed a favorable 5-year overall survival rate (68%; 95%CI = 59-76%) compared to tumors showing a high expression of CXCR4 only (48%; 95%CI = 41-54%). High expression of pCXCR4 was significantly associated with a favorable prognosis in a test and validation group (p = 0.015 and p = 0.0001). Moreover, we found that CRCs with a high density of pCXCR4+ tumor-infiltrating immune cells (TICs) also showed a favorable prognosis in a test and validation group (p = 0.054 and p = 0.004). Univariate Cox regression analysis for TICs revealed that a high density of pCXCR4+ TICs was a favorable prognostic marker for overall survival (HR = 0.97,95%CI = 0.96-1.00; p = 0.01). In multivariate Cox regression survival analyses a high expression of pCXCR4 in tumor cells lost its association with a better overall survival (HR = 0.99; 95%CI = 0.99-1.00, p = 0.098). CONCLUSION: Our results show that high densities of CXCR4 and pCXCR4 positive TICs are favorable prognostic factors in CRC.
Assuntos
Neoplasias Colorretais/metabolismo , Receptores CXCR4/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Intervalos de Confiança , Humanos , Imuno-Histoquímica , Fosforilação/genética , Fosforilação/fisiologia , Modelos de Riscos Proporcionais , Receptores CXCR4/genética , Estudos Retrospectivos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Software , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
Roux-en-Y gastric bypass (RYGB) is the gold standard in bariatric surgery. The effect of the procedure is based on restriction, malabsorption and changes in hormonal axis. Ghrelin is an important appetite hormone which is produced mainly in the gastric fundus. By adding a resection of the gastric fundus, we hypothesized that excessive weight loss will be more prominent and the satiety feelings less pronounced compared to standard RYGB. A total of 73 patients with standard very very long limb (VVLL) RYGB (group A) were compared with 44 patients with VVLL RYGB with resection of the fundus (group B). Outcome measures were excessive weight loss (EWL), body mass index (BMI), early postoperative morbidity, change of co-morbidities, and appetite reduction as assessed by an appetite questionnaire over a postoperative period of 24 months. Groups were comparable in basic preoperative descriptions. Additional fundus resection did not influence EWL (group A 66.1 % vs. group B 70.6 %, p = 0.383) or BMI (group A 29 kg/m(2) vs. group B 27 kg/m(2), p = 0.199). No significant difference in morbidity or change of co-morbidities occurred. The appetite and satiety questionnaire showed no difference between group A and group B, respectively. Adding a resection of the gastric fundus in RYGB did not alter the clinical results, i.e., increased excessive weight loss, decrease of appetite, or increase of satiety. The value of removing a part of the ghrelin-producing cells might be overestimated.