Nuri Faruk Aykan

Red meat and colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented.

Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer.

The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid-phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24–84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P-values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC.

Red meat subtypes and colorectal cancer risk.

Dear Editor, I read with a great interest the manuscript of “Meat subtypes and their association with colorectal cancer: Systematic review and meta-analysis” reported by Prudence R. Carr and colleagues. I want to point out that I identified some errors and missing points in this article. First, in the “subgroup analysis by geographic location” on page 6; the association between beef consumption and colon cancer risk was mentioned as statistically significant in European studies although p value was 0.079, as seen in Table 1. This error should be corrected or clarified. Second, although there is a significant association between pork consumption and rectal cancer in European studies, as shown again in Table 1 (RR5 1.08, p5 0.007), this result was not mentioned neither in the article, nor in the abstract. Conversely, the abstract contains a lack of relationship between pork consumption and colorectal cancer (CRC). I think that the general statements may be overlooked important details. As the authors evaluated colon and rectal cancer separately beside CRC, new data support the existence of two categories of CRC based on site of origin. The aim of this meta-analysis is essentially to summarize and quantify the associations between meat subtypes and CRC. But, when we look at the Sato’s study, not only for meat subtypes but also there is not any significant association between total meat consumption and the risk of CRC. Because, the meat consumption is very low in the participants of this study; 70.4 g/day for highest quartile, which is the upper limit of recommended level (500 g/week) for healthy people according to guidelines. So, I think that it is questionable to take this type of completely negative study into specific meta-analyses. In addition, Figure 3 contains some minor different data than those of original publications such as upper limits of confidence intervals (CIs) in Norat’s and Sato’s articles, respectively; 1.47 for colorectal cancer and 2.63 (for colon), 1.41 (for rectal) should be 1.48 and 2.62, 1.42 according to the original data. Finally, it seems that the relative risk (RR) for colorectal cancer in the Netherlands cohort study, RRs for colon and rectal cancer in Takachi’s article were calculated from pooled data mentioned in material and methods. But, RRs for colon and rectal cancer separately from Norat’s study which is the largest European cohort study (EPIC) were not included into Figure 2 and 3. In fact, the original article does not contain these data, but I am wondering if it was not possible to have and/or calculate them from EPIC Study Group in which they were two authors from Heidelberg, Germany.

Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study

PURPOSE We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC). METHODS We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens. RESULTS The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients. CONCLUSION Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.

Evaluation of epidermal growth factor receptor serum levels and their association with clinicopathological characteristics in patients with colorectal cancer

Colorectal cancer (CRC) is a major public health concern and one of the leading causes of cancer-related mortality worldwide. The aim of the present study was to determine the serum epidermal growth factor receptor (sEGFR) levels in healthy volunteers and patients with CRC, to determine the association between tumor marker levels and clinicopathological findings, and investigate its prognostic value. A total of 140 patients with CRC were enrolled in the present study. Pre-treatment sEGFR levels were determined using ELISA. A total of 40 age- and sex-matched healthy controls were included in the analysis. The median age of patients was 60 years (range, 24–84 years); the majority of the tumor localization was to the colon (n=81, 58%). The median follow-up time was 14 months, while 43 (31%) patients experienced disease progression and 31 (22%) succumbed to the disease. A total of 81 patients (58%) were in the early stages of disease (stage II and III), and 42% of the patients had stage IV disease. The estimated 2-year overall and 1-year progression-free survival rates for the whole patient group were 70% [95% confidence interval (CI): 58.8–81.2] and 26.2% (95% CI: 12.9–39.5), respectively. The number of patients who received neoadjuvant treatment was 37. Of the patients who were administered palliative treatment, 24 received oxaliplatin, whereas 22 received irinotecan and 9 received fluorouracil/capecitabine. A total of 36 and 15 of the patients who received targeted therapy were administered bevacizumab and cetuximab, respectively. Of the 55 patients with metastatic disease who received palliative chemotherapy (CTx), 31% were CTx-responsive. The baseline median sEGFR levels were significantly higher in patients with CRC compared with the healthy control group (P=0.002). In addition, established clinical variables, including no surgical resection, metastatic stage, higher pathological tumor stage, poorer regression score (3–4) and higher lactate dehydrogenase levels, were found to be associated with higher sEGFR levels (P=0.03, P=0.009, P=0.05, P=0.05 and P=0.05, respectively). The results of the present study did not reveal statistically significant associations between sEGFR concentrations and overall and progression-free survival rates. In conclusion, sEGFR concentrations may be diagnostic markers in patients with CRC; however, their predictive and prognostic values were not determined.

Clinical significance of serum vascular cell adhesion molecule-1(VCAM-1) in colorectal cancer.

550 Background: Vascular cell adhesion molecule-1 (VCAM-1) is a transmembrane glycoprotein, which is expressed on endothelium and contributes in leukocyte adhesion and extravasation during inflammation. It has been demonstrated that VCAM-1 is over-expressed on colorectal cancer (CRC) cells and plays role in metastasis development and angiogenesis. We aimed to compare serum VCAM-1 levels of CRC patients with heathy controls and evaluate its relationship with clinicopathologic parameters, treatment response and overall survival (OS). Methods: The study enrolled 111 patients with histopathologically confirmed CRC followed up between February 2010-September 2013 in Institute of Oncology, Istanbul University and 30 sex- and age-matched healthy controls. Pre-treatment serum VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Results: The cancer localisation was rectum in 40% and colon in 60% of patients. Metastatic disease was present in 51.4%. Forty percent of 40 metastatic patients who rec...

Serum neural precursor cell-expressed, developmentally down regulated 9 (NEDD9) level may have a prognostic role in patients with gastric cancer.

BACKGROUND Neural precursor cell-expressed, developmentally down regulated 9 (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved in cancer cell adhesion, migration and invasion. The prognostic value of NEDD9 has been evaluated before and its expression is a predictor of poor prognosis in cancer patients. The objective of this study was to determine the clinical significance of the serum levels of NEDD9 in gastric cancer (GC) patients. PATIENTS AND METHODS A total of 68 patients with a pathologically confirmed diagnosis of GC were enrolled into this study. Serum NEDD9 concentrations were determined by the solid-phase sandwich (ELISA) method. Twenty-eight healthy age- and sex-matched controls were included into the analysis. RESULTS The median age at diagnosis was 60years, range 21 to 84years. Forty-nine (72%) patients were male and cardia was the most common tumor localization (n=37, 77%) in GC patients. The most frequent histologic subtype was adenocarcinoma (n=45, 66%). Liver was the most common metastatic site in 32 patients with metastasis (n=14, 44%). Sixty-one percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. The median follow-up time was 8months (range 1 to 23months). At the end of the observation period, 17 patients (25%) experienced disease progression and 28 of the remaining patients (41%) died. Median progression-free survival (PFS) and overall survival (OS) of the whole group were 4.0±0.7months [95% confidence interval (CI)=3-5months] and 14.6±1.2months (95% CI=12-17months), respectively. One-year and 2-year OS rates were 54.4% (95% CI=41.3-67.5) and 51.2% (95% CI=37.3-65.1), respectively. The median serum NEDD9 levels of GC patients were significantly higher than controls (1339.51 vs. 1187.91pg/mL, P=0.02). There was no significant difference according to known disease-related clinicopathological or laboratory parameters (P>0.05). Serum NEDD9 levels had a significant impact on PFS (P=0.04). On the other hand, serum NEDD9 levels showed no significantly adverse effect on OS (P=0.50). CONCLUSION Serum NEDD9 level may be a diagnostic marker for GC patients. Moreover, our study results showed that it was elevated in GC patients and had an unfavorable prognostic effect. However, it has no predictive role on CTx response.

Clinical significance of serum protein and mRNA level of insulin-like growth factor-1 (IGF-1) in patients with hepatocellular carcinoma.

203 Background: The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. The aim of this study was to assess the usefulness of serum protein and circulating mRNA of insulin-likegrowth factor-1 (IGF-1) as a diagnostic and prognostic tool in HCC. Methods: Fifty-four HCC patients were enrolled into this study. Age and sex matched 20 healthy controls were also included in the study. Serum IGF-1 levels were determined by the solid-phase sandwich ELISA method. Serum IGF-1 mRNA levels were determined by quantitative RT-PCR. Results: The median age at diagnosis was 60 years, range 16–88 years; 48 patients were men. All of patients had cirrhotic history. Fourty-six percent (n=25) of patients had Child-Pugh Score A, 30% (n=16) had Score B or C. All of the patients were preformed with local therapies but no...