Advanced glycation end products (AGEs) and their receptor RAGE emerge as important pathogenic contributors in colorectal carcinogenesis. However, their relationship to the detoxification enzyme Glyoxalase (GLO)-I and Adiponectin receptors (AdipoR1, AdipoR2) in colorectal carcinoma (CRC) is currently understudied. In the present study, we investigated the expression levels of the above molecules in CRC compared to adjacent non-tumoral tissue and their potential correlation with clinicopathological characteristics and patients’ survival. We analyzed the immunohistochemical expression of AGE, RAGE, GLO-1, AdipoR1 and AdipoR2 in 133 primary CRC cases, focusing on GLO-I. The tumour MSI status was further assessed in mucinous carcinomas. Western immunoblotting was employed for validation of immunohistochemical data in normal and tumoral tissues as well in three CRC cell lines. An independent set of 55 patients was also used to validate the results of univariate survival analysis regarding GLO-I. CRC tissue showed higher intensity of both AGE and RAGE expression compared with normal colonic mucosa which was negative for GLO-I in most cases (78 %). Western immunoblotting confirmed AGE, RAGE and GLO-I overexpression in tumoral tissue. GLO-I expression was directly related to RAGE and inversely related to AGE immunolabeling. There was a trend towards higher expression of all markers (except for RAGE) in the subgroup of mucinous carcinomas which, although of borderline significance, seemed to be more prominent for AdipoR1 and AGE. Additionally, AGE, AdipoR1 and Adipo R2 expression was related to tumor grade, whereas GLO-1 and AdipoR1 to T-category. In survival analysis, AdipoR2 and GLO-I overexpression predicted shortened survival in the entire cohort and in early stage cases, an effect which for GLO-I was reproduced in the validation cohort. Moreover, GLO-I emerged as an independent prognosticator of adverse significance in the patients’ cohort. We herein provide novel evidence regarding the possible interactions between the components of AGE-RAGE axis, GLO-I and adiponectin receptors in CRC. AGE and AdipoR1 are possibly involved in colorectal carcinogenesis, whereas AdipoR2 and GLO-I emerged as novel independent prognostic biomarkers of adverse significance for patients with early disease stage. Further studies are warranted to extend our observations and investigate their potential therapeutic significance.
Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance.
Background and Objectives: Laparoscopic procedures have become a routine approach in colorectal surgery. We aimed to evaluate intraoperative, postoperative and pathological outcomes of laparoscopic right hemicolectomy in comparison with open right hemicolectomy. Materials and Methods: We reviewed our database for colorectal surgery and collected data regarding right hemicolectomies performed over a period of 10 years regarding patient characteristics, operative outcomes and postoperative outcomes. We compared laparoscopic with open right hemicolectomies. All the anastomoses in the laparoscopic group were performed intracorporeally. Results: We included 384 cases, 74 (19.3%) laparoscopic and 310 (80.7%) open right hemicolectomies. Baseline characteristics were comparable between the two groups. Conversion rate was low (2.7%). A drain was placed more often in the open colectomies (p < 0.001). Laparoscopic colectomies lasted longer by 25 min on average in the entire cohort (p = 0.002) and by 30 min in cancer-only cases without concomitant procedures (p < 0.001). Laparoscopic procedures yielded more lymph nodes (p = 0.007), as well as longer distal resection margins (p < 0.001) and total specimen (p < 0.001). There was no difference between the two approaches concerning intraoperative complications (p = 0.36) or need for transfusion (p = 0.708). There was also no difference regarding overall (p = 0.361) or major complications (p = 1), as well as anastomotic leak (p = 0.475), surgical site infections (p = 0.275) or readmission rates (p = 1). Hospitalisation duration was shorter by 3 days after laparoscopic surgery in the entire cohort (p < 0.001), as well as when cancer-only cases without concomitant procedures were considered (p < 0.001). Conclusions: Laparoscopic right hemicolectomy with intracorporeal anastomosis provides perioperative safety and pathology outcomes comparable to open surgery, while significantly reducing hospital stay.