Development of an Algorithm to Predict Recurrences After Resection of Liver Metastases in Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. PATIENTS AND METHODS: Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. RESULTS: In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. CONCLUSION: Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.

Investigation of clinicopathological characters and gene expression features in colorectal signet-ring cell carcinoma utilizing CMS classification.

Signet ring cell carcinoma (SRCC) is a rare pathological type of colorectal cancer, of which the clinicopathological features and genetic background have not yet been fully investigated. Previous research has focused on the optimization of colorectal cancer treatment utilizing consensus molecular subtyping (CMS). However, it is not known what type of CMS would be designated to SRCC treatment. In the current study, of 1,350 patients diagnosed with colorectal cancer who underwent surgery, 14 were diagnosed with SRCC. The case-control cohort that fit the clinical background of the SRCC case was constructed. Statistical comparison between the SRCC group and the case-control cohort was performed among clinicopathological variables. SRCC and well to moderately adenocarcinoma case mRNA were submitted to microarray analysis and CMS analysis. Compared with the case-control cohort, the SRCC group was located more in the right-sided colon, the lymphatic invasion was more severe and the peritoneal dissemination was more frequent. The cancer-specific survival and the progression-free survival were significantly worse in the SRCC group compared with the case-control cohort. Microarray and CMS analysis identified that one SRCC case was significantly well assigned in the CMS 4 group and the other case was assigned in the CMS 1 group. Gene set analysis revealed the upregulation of EMT related genes and the downregulation of fatty acid, glycolysis, differentiation, MYC, HNF4A, DNA repair genes. In conclusion, the clinical characteristics of SRCC are severe but there is a possibility of the presence of different phenotypes according to CMS analysis.

[A Case of Postoperative Recurrence of Rectal Cancer in Which Desensitization Therapy Was Effective against Oxaliplatin Allergy in L-OHP].

The case involved a 44-year-old man who underwent intersphincteric resection and lateral lymph node dissection for rectal cancer. Pathological diagnosis revealed a well-differentiated adenocarcinoma comprising KRAS wild type, and pT2N0M0 (pathological Stage I). CapeOX (capecitabine plus oxaliplatin[L-OHP]), and bevacizumab therapy was initiated because of local recurrence. Although a partial response (PR) was observed, the therapy was terminated after 6 courses because of the development of hand-foot syndrome. FOLFIRI and cetuximab therapy was initiated after cancer recurrence was observed during a follow up. As the therapeutic efficiency is characterized by stability (stable disease: SD), and the tumor reduction effect observed was not sufficient, we performed an abdominoperineal resection to achieve local control. However, a left hydronephrosis occurred due to the pelvic recurrence, necessitating the emergency hospitalization of the patient. Because resistance to L-OHP was not confirmed, mFOLFOX6 and bevacizumab therapy was introduced in hopes of the effect of the former. As Grade 2 allergy (erythema) appeared immediately after the L-OHP was administered during the 3 courses, treatment was discontinued. We the reinitiated the treatment along with the desensitization therapy from the 4 courses. A total of 27 courses of mFOLFOX6 and bevacizumab therapy were administered until the state of disease progression (progression disease: PD) was determined. PR was defined as the best therapeutic efficiency. In some cases, discontinuation of treatment is necessary as observed in the present case due to the onset of L-OHP allergies, even if the overall effect of the treatment is expected to be good. Our case is essentialas it demonstrates the successfulness of desensitization therapy for L-OHP allergies.

Mina53 nuclear localization is an important indicator of prognosis in patients with colorectal cancer after adjuvant chemotherapy.

The aim of this study was to investigate the status of the c­Myc­related molecule Mina53 and the clinical impact of Mina53 nuclear localization in patients with stage II and III colorectal cancer (CRC). Patients (n=250) who underwent complete resection of CRC at our department were enrolled in this study, and tissue microarray samples were constructed from resected specimens. Mina53 expression in the nuclei of tumor cells was analyzed using immunohistochemistry (IHC). Patients were classified into Mina53 nuclear localization­-positive and ­negative groups, and statistical correlations with clinicopathological factors were investigated. Relapse­free survival (RFS) was compared using the Kaplan­Meier method and the Cox proportional hazard model. Tumor recurrence was significantly higher in the Mina53­positive group than in the Mina53­negative group. Moreover, in RFS analysis, patients in the Mina53­positive group exhibited significantly poorer prognosis than patients in the Mina53­negative group. In the univariate analysis, histological type, adjuvant chemotherapy status, carcinoembryonic antigen (CEA) status, and Mina53 status were prognostic factors for RFS. Furthermore, in the subgroup analysis, patients in the Mina53­positive group with stage III disease treated with adjuvant chemotherapy exhibited significantly poorer prognosis in RFS than patients in the Mina53­negative group. In the univariate and multivariate analyses, histological type and Mina53 status were significantly associated with RFS. Thus, our findings revealed that Mina53 was an important indicator of prognosis in patients with stage III CRC treated with adjuvant chemotherapy.

Nuclear Y-Box-binding Protein-1 Expression Predicts Poor Clinical Outcome in Stage III Colorectal Cancer.

BACKGROUND/AIM: Y-Box-binding protein-1 (YB-1), a DNA/RNA-binding protein, is an important oncogenic transcription and translation factor. We aimed to evaluate the relationships between nuclear YB-1 expression, epidermal growth factor receptor (EGFR) status, and poor clinical outcomes in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Nuclear YB-1 expression was immunohistochemically analyzed in CRC tissues obtained from 124 patients who underwent curative resection between 2005 and 2008. Correlations between nuclear YB-1 expression, various clinicopathological characteristics, EGFR status, and prognostic factors were evaluated. RESULTS: High-grade nuclear YB-1 expression was detected in 62.9% of cases and was found to be an independent predictor of poorer overall survival (p<0.001) and relapse-free survival (p<0.001). A trend was also observed towards a positive correlation between nuclear YB-1 expression and EGFR status (p=0.051). CONCLUSION: Nuclear YB-1 expression is a useful prognostic biomarker that correlates with EGFR status in patients with CRC.

A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells).

BACKGROUND: Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis. METHODS: The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed. RESULTS: A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45). CONCLUSIONS: This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.

Analysis of Wnt and ß-catenin Expression in Advanced Colorectal Cancer.

BACKGROUND: Wnt/ß-catenin signaling plays an important role in colorectal cancer (CRC). Wnt has many sub-types and it is uncertain which of them affect progression of CRC. PATIENTS AND METHODS: We analysed 201 patients who underwent curative surgery for CRC. We investigated the relationship between the expression of Wnt and ß-catenin proteins and prognosis using immunohistochemistry. RESULTS: The high expression of Wnt1 correlated with high expression of nuclear and cytoplasmic ß-catenin (p=0.0004, p=0.02). The high expression of Wnt5a also correlated with high expression of membrane ß-catenin (p=0.03). In multivariate analysis, lymph node metastasis (p=0.046) and high expression of nuclear ß-catenin (p=0.04) were independent prognostic factors for survival. CONCLUSION: The expression of nuclear ß-catenin is a useful predictive marker in CRC. It is suggested that Wnt1 may be the main activator of the ß-catenin signaling pathway and that Wnt5a may stabilize adherens junctions, thereby suppressing the epithelial-mesenchymal transition.

Successful treatment with s-1 and oxaliplatin combination therapy in an elderly patient with metastatic colorectal cancer initially presenting with membranous nephropathy.

The incidence, morbidity, and mortality of colorectal cancer are increasing, largely owing to an increasingly aging population. Additionally, along with the increasing age of cancer patients, the number of patients with various comorbidities such as membranous nephropathy is also rising, and problems associated with the administration of chemotherapy to elderly patients with these conditions are becoming more common. Herein, we describe a case involving an 80-year-old woman who presented with general malaise, edematous limbs, and pleural effusion. An abdominal CT revealed multiple, relatively large, metastatic lesions in a wide area of the liver and left pleural effusion, and she was accordingly diagnosed with membranous nephropathy secondary to ascending colon cancer and multiple liver metastases. Despite her advanced age and the presence of membranous nephropathy, her general condition was favorable and chemotherapy was hence administered. Taking the toxicity profiles and the patient's preference into consideration, S-1 and oxaliplatin (SOX) therapy was selected, which showed a good tolerability. An abdominal CT after 8 cycles of SOX therapy revealed a marked reduction in the metastatic lesions in the liver and a decrease in the left pleural effusion, and the levels of tumor markers also decreased (partial response). At the latest follow-up, after the completion of 16 cycles, the condition of the patient remained stable, without any apparent signs of progressive disease. Based on this case, we conclude that, even for elderly patients with systemic complications or comorbid diseases, standard treatments should be considered after their general conditions, and therapeutic regimens have been sufficiently examined.