Yasuhito Iseki

Impact of the Preoperative Controlling Nutritional Status (CONUT) Score on the Survival after Curative Surgery for Colorectal Cancer.

Background Recently, the preoperative immune-nutritional status has been reported to correlate with the survival rate in patients with colorectal cancer (CRC). However, there have been no reports on the relationship between the controlling nutritional status (CONUT) score and the clinical outcome after curative surgery for CRC. We herein evaluated the prognostic significance of the CONUT score in patients with CRC, and then compared the accuracy of the CONUT score and the prognostic nutritional index (PNI) as a predictor of survival. Methods We retrospectively reviewed a database of 204 patients who underwent curative surgery for Stage II/III CRC. Patients were divided into two groups according to the CONUT score and the PNI. Results The five-year cancer-specific survival (CSS) rate was significantly higher at 92.7% in the low CONUT group, compared to a rate of 81.0% in the high CONUT group (p=0.0016). The five-year CSS was 71.2% in the low PNI group and 92.3% in the high PNI group, which showed a significant difference (p=0.0155). A multivariate analysis showed that lymph node metastasis and the CONUT score were independent risk factors for CSS. Conclusion This study suggested that the CONUT score is a strong independent predictor of the survival among CRC patients.

The pretreatment albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer

BackgroundThe pretreatment albumin to globulin ratio (AGR) has been reported to correlate with the long-term survival in patients with various cancers. However, there are no reports regarding the correlation between the pretreatment AGR and chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer. The aim of this study was to evaluate the prognostic significance of the pretreatment AGR in patients with unresectable metastatic colorectal cancer.MethodsA total of 66 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy for metastatic tumors were enrolled. The AGR was calculated as follows: Albumin/(Total protein - Albumin).ResultsThe median pretreatment AGR was 1.254 (range: 0.849-1.840). We set 1.25 as the cut-off value based on the receiver operating characteristic curve. Based on the cut-off value of 1.25, 34 patients were classified into the high-AGR group and 32 patients were classified into the low-AGR group. The high-AGR group had a significantly higher chemotherapeutic disease control rate (p = 0.040) and better progression-free survival (p = 0.0171) and overall survival (p = 0.0360) rates than the low-AGR group. According to a multivariate analysis of survival, the AGR was identified to be an independent prognostic factor for progression-free survival (Hazard Ratio: 2.662, 95% Confidence Interval: 1.085-6.631, p = 0.033) and overall survival (Hazard Ratio: 2.247, 95% Confidence Interval: 1.069-4.722, p = 0.033).ConclusionsThe pretreatment AGR is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy.

Inflammation-based factors and prognosis in patients with colorectal cancer.

Several parameters for predicting survival in patients with colorectal cancer have been identified, including the performance status, age, gender and tumor-node-metastasis (TNM) stage. Although the TNM stage is important and useful for predicting the prognosis and determining the appropriate treatment, it is well known that the survival time varies widely, even in patients with the same stage of disease. Therefore, the identification of new parameters capable of more precisely predicting patient survival is needed to help select the optimal treatment, especially in patients in the advanced stage of disease. Although the TNM stage reflects the tumor characteristics, cancer progression and survival are not determined solely based on the local characteristics of the tumor, but also the host systemic immune/inflammatory response. Therefore, using a combination of parameters that reflect both tumor characteristics and the host systemic inflammatory status is thought to be important for accurately predicting patient survival.

The prognostic significance of a postoperative systemic inflammatory response in patients with colorectal cancer.

BackgroundRecently, a preoperative systemic inflammatory response has been reported to be a prognostic factor in patients with colorectal cancer (CRC). However, the prognostic significance of a systemic inflammatory response in the early stage after surgery in patients with CRC is unknown. The aim of this retrospective study was to evaluate the prognostic significance of a postoperative systemic inflammatory response in patients with CRC.MethodsTwo hundred and fifty-four patients who underwent potentially curative surgery for stage II/III CRC were enrolled in this study. Univariate and multivariate analyses were performed to evaluate the relationship between the prognosis and clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS), which were measured within two weeks before operation and at the first visit after leaving the hospital.ResultsThe overall survival rates were significantly worse in the high preoperative NLR/preoperative GPS/postoperative NLR group. A multivariate analysis indicated that only preoperative GPS, postoperative NLR, and the number of lymph node metastases were independent prognostic factors for a poor survival.ConclusionsThe postoperative NLR is an independent prognostic factor in patients with CRC who underwent potentially curative surgery.

The prognostic significance of the postoperative prognostic nutritional index in patients with colorectal cancer

BackgroundThe preoperative prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patents with various carcinomas. However, the prognostic significance of the postoperative PNI is unknown. The aim of this study was to evaluate the prognostic significance of the postoperative PNI in patients with colorectal cancer (CRC).MethodsTwo hundred and eighteen patients who underwent potentially curative surgery for stage II/III CRC were enrolled in this study. The PNI was calculated as 10 × serum albumin concentration (g/dl) + 0.005 × lymphocyte count (/mm3). The preoperative PNI was measured within two weeks before the operation and the postoperative PNI were measured at the first visit after leaving the hospital. We then examined the correlations between the preoperative/postoperative PNI and the prognosis for survival.ResultsIn the validation study, the median preoperative PNI was 47.90 (range: 32.45-61.36) and the median postoperative PNI was 48.69 (range: 32.62-66.96). According to the receiver operating characteristic (ROC) curve, we set 43.0 as the cut-off value in the validation study. For both the preoperative and postoperative PNI, the overall survival rates were significantly worse in the low PNI group in the validation study (preoperative PNI, p = 0.0374; postoperative PNI, p = 0.0005). In the multivariate analysis of the validation study, the combination of pre- and postoperative PNI was an independent predictor of poor overall survival (p = 0.006).ConclusionsThe postoperative PNI is, in addition to the preoperative PNI, a useful prognostic marker. The combination of pre- and postoperative PNI was an independent prognostic factor in patients with CRC who underwent potentially curative surgery and is important for considering the long-term outcome in patients with CRC.

Significance of E-cadherin and CD44 expression in patients with unresectable metastatic colorectal cancer

The loss of adhesion molecules is reported to be associated with tumor invasion and metastasis in numerous types of cancer. Epithelial (E)-cadherin is an important molecule for cell-to-cell adhesion, while cluster of differentiation (CD)44 is an important molecule for cell-to-extracellular matrix adhesion. The focus of the present study was to evaluate the significance of the expression of E-cadherin and CD44 in patients with the unresectable metastatic colorectal cancer (CRC) who are undergoing palliative chemotherapy. Formalin-fixed, paraffin-embedded samples were obtained from 49 patients who underwent primary tumor resection and who were receiving palliative chemotherapy for unresectable metastatic CRC. The expression of E-cadherin and CD44 was evaluated using immunohistochemistry. The expression of E-cadherin was not significantly associated with progression-free survival (PFS; P=0.2825) or overall survival (OS; P=0.6617). The expression of CD44 was not associated with PFS (P=0.4365), but it did exhibit a certain level of association with OS (P=0.0699). However, the combined low expression of E-cadherin and CD44 demonstrated a significant association with decreased PFS (P=0.0101) and OS (P=0.0009). The combined loss of E-cadherin and CD44 expression also led to a reduction in the objective response rate and disease control rate (P=0.0076 and P=0.0294, respectively). A univariate analysis indicated that the combined low expression of E-cadherin and CD44 (P=0.0474) and sex (P=0.0330) were significantly associated with decreased PFS, and multivariate analysis confirmed combined low expression of E-cadherin and CD44 as an independent risk factor for decreased PFS [hazard ratio (HR), 8.276; 95% confidence interval (CI), 1.383-43.311; P=0.0227]. Univariate and multivariate analyses also indicated that the combined low expression of E-cadherin and CD44 expression was a significant prognostic factor for poor OS (HR, 15.118; 95% CI, 2.645-77.490; P=0.0039). Therefore the current study suggests that the combined low expression of E-cadherin and CD44 is an effective independent predictor of decreased chemotherapeutic outcome and survival in patients with unresectable metastatic CRC.

Prognostic significance of the preoperative lymphocyte‑to‑monocyte ratio in patients with colorectal cancer

A correlation between the lymphocyte-to-monocyte ratio (LMR) and the survival of patients with hematological malignancies has been reported previously. However, there have been few studies investigating the prognostic significance of LMR in patients with solid tumors. The aim of the present study was to evaluate the prognostic significance of preoperative LMR in patients with colorectal cancer (CRC). A total of 189 patients undergoing potentially curative surgery for CRC were enrolled. The LMR was calculated from preoperative blood samples by dividing absolute lymphocyte count by absolute monocyte count. A cut-off value of 4.8 was set based on the receiver operating characteristic curve; 116 patients were classified as high-LMR, and 73 patients classified as low-LMR. The high-LMR group exhibited significantly better relapse-free survival (P=0.0018) and overall survival (P=0.0127) rates than the low-LMR group. According to the multivariate analysis of survival, preoperative LMR was identified as an independent prognostic factor for relapse-free survival (P=0.041) and overall survival (P=0.031). Therefore, preoperative LMR is a useful prognostic marker in patients with CRC.

The impact of the preoperative peripheral lymphocyte count and lymphocyte percentage in patients with colorectal cancer.

PurposeWe evaluated the prognostic significance of the peripheral lymphocyte count and lymphocyte percentage, which reflect the preoperative immune status, in patients with colorectal cancer (CRC) and then compared their accuracy as predictors of the survival.MethodsWe retrospectively reviewed a database of 362 patients. We classified the patients into high lymphocyte count and low lymphocyte count groups. We also classified the patients into high lymphocyte percentage and low lymphocyte percentage groups.ResultsThe 5-year relapse-free survival (RFS) rate in the high lymphocyte count group tended to be higher than that in the low lymphocyte count group. The 5-year overall survival (OS) rate in the high lymphocyte count group was significantly higher than that in the low lymphocyte count group. In contrast, the 5-year RFS and OS rates in the high lymphocyte percentage group were both significantly higher than those in the low lymphocyte percentage group. A multivariate analysis showed that the lymphocyte percentage was independently associated with the OS.ConclusionsThese findings suggest that the lymphocyte percentage is a good predictor of the OS and may be a stronger predictor of survival than the lymphocyte count in CRC patients.

The significance of the C-reactive protein to albumin ratio as a marker for predicting survival and monitoring chemotherapeutic effectiveness in patients with unresectable metastatic colorectal cancer

Inflammation has been reported to play an important role in cancer progression and various inflammatory markers have been reported to be useful prognostic markers. The aim of this retrospective study was to evaluate the significance of the C-reactive protein to albumin (CRP/ALB) ratio in colorectal cancer patients who received palliative chemotherapy. We performed a retrospective review of 99 patients who underwent palliative chemotherapy for unresectable colorectal cancer between 2005 and 2010. The cutoff value of the CRP/ALB ratio was determined based on a receiver operating characteristics curve analysis. The relationship between the CRP/ALB ratio and survival was assessed. The cutoff value for the CRP/ALB ratio was 0.183. The high pretreatment CRP/ALB ratio group showed significantly worse overall survival. Patients with a high pretreatment CRP/ALB ratio and in whom the CRP/ALB ratio normalized after chemotherapy tended to have better overall survival than those in whom both the pretreatment and posttreatment CRP/ALB ratios were high. The CRP/ALB ratio is a useful marker for predicting survival and monitoring chemotherapeutic effectiveness in patients with unresectable metastatic colorectal cancer.

A new method for evaluating tumor-infiltrating lymphocytes (TILs) in colorectal cancer using hematoxylin and eosin (H-E)-stained tumor sections

Purpose Numerous reports indicate that tumor-infiltrating lymphocytes (TILs) are a prognostic factor in various cancers and that they must be good biomarkers. However, the methods of evaluating TILs differ in each study; thus, there is not yet a standardized methodology for evaluating TILs. The purpose of this study is to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in patients with colorectal cancer (CRC) using the new method proposed by the International TILs Working Group in breast cancer and to standardize the method of evaluating TILs in CRC. Methods We retrospectively reviewed a database of 160 patients with Stage II or III CRC. The density of TILs was assessed by measuring the area occupied by mononuclear cells over the stromal area on hematoxylin and eosin (H-E)-stained sections. We set 42% as the cut-off percentage of the area occupied by TILs according to the receiver operating characteristic curve, and we classified patients into the high-TILs and the low-TILs groups. Results The rates of relapse-free survival (RFS) and overall survival (OS) in the high-TILs group were significantly higher than those in the low-TILs group. A multivariate analysis showed that the density of TILs was independently associated with RFS and OS. Moreover, the density of TILs assessed by an observer was significantly associated with the density of TILs assessed by the automated imaging software program. Conclusions The new method for evaluating TILs, which was recommended by the International TILs Working Group in breast cancer, might be a useful predictive factor in colorectal cancer patients.