Is the prognosis of T1-2N1 colon cancer the same as that of T1-2N0 colon cancer after curative surgery?

Objectives: The prognoses of T1-2N0 and T1-2N1 colon cancer after curative surgery remain unclear. This study compared the prognoses of patients with T1-2N0 and T1-2N1 colon cancer after curative surgery.Materials and methods: We retrospectively evaluated 307 consecutive patients with T1-2N0/1 colon cancer who underwent radical surgery at our hospital between January 2010 and December 2016. There were 266 patients with T1-2N0 colon cancer and 41 patients with T1-2N1 colon cancer. After excluding patients with <12 retrieved lymph nodes, 179 patients with T1-2N0 and 32 with T1-2N1 colon cancer were included in the cohort.Results: Overall survival and disease-free survival did not differ between the T1-2N0 and T1-2N1 groups (p = 0.498 and p = 0.681, respectively). Overall survival and disease-free survival were not significantly different between the T1-2N1 + no chemotherapy and T1-2N1 + chemotherapy groups (p = 0.740 and p = 0.765, respectively). Additionally, overall survival and disease-free survival did not differ between the T1-2N0, T1-2N1 + no chemotherapy, and T1-2N1 + chemotherapy groups (p = 0.757 and p = 0.877, respectively), even after excluding patients with <12 retrieved lymph nodes.Conclusions: T1-2N1 has a prognosis as good as that of T1-2N0 colon cancer after curative surgery. Moreover, further research is needed to investigate the efficacy of adjuvant FOLFOX chemotherapy in T1-2N1.

Comparison of nutritional and immunological scoring systems predicting prognosis in T1-2N0 colorectal cancer.

PURPOSE: Previous studies have shown that the new nutritional and immunological status scoring systems of the Naples prognostic score (NPS), controlling nutritional status score (CONUT), and the older prognostic nutritional index (PNI) are independent predictors in colorectal cancer. This study compares the prognostic value of NPS, CONUT, and PNI in T1-2N0 colorectal cancer. METHODS: We retrospectively evaluated 305 consecutive stage I (T1-2N0M0) colorectal cancer patients who underwent radical surgery from January 2010 to December 2015 at our hospital. The NPS results were divided into 3 groups (0, 1, and 2 groups), and the PNI and CONUT results were divided into 2 groups (low and high groups). RESULTS: The patients with low PNI had worse overall survival (OS) and disease-free survival (DFS) than those with high PNI (P < 0.001 and P < 0.001, respectively). Multivariate analysis showed that PNI was independently associated with OS and DFS (P < 0.001 and P < 0.001, respectively), but NPS and CONUT results were not. CONCLUSION: The PNI is an independent predictor in stage I colorectal cancer, but NPS and CONUT results are not.

Clinical Significance of Surgical Resection Timing from Endoscopic Stenting for Left-Sided Large-Bowel Obstruction in Colorectal Cancer.

BACKGROUND: The optimal interval between self-expanding metallic stent (SEMS) insertion and surgery remains controversial in malignant left-sided large-bowel obstruction (MLLO), especially with respect to oncologic aspects. AIMS: The aim of this study is to examine whether the time interval to surgery is related to oncologic outcomes. METHODS: Prospectively collected database of MLLO between January 2005 and December 2017 were reviewed. They were divided according to established cut-off value of 14 days for the time interval to surgery. The two groups (early and late groups) were compared with respect to disease-free survival (DFS) and overall survival (OS). Additional subgroup analysis was performed using the established cut-off values for patients with stage II and III tumors. RESULTS: A total of 149 patients underwent surgery after SEMS insertion. There were no significant differences between the early and late groups in the 5-year DFS (78.0% vs 72.4%; P = 0.513) and the OS (74.2% vs 75.7%; P = 0.864) rates in all MLLO. Subgroup analysis showed that there were significant differences between the two groups for DFS and OS in stage II MLLO. The multivariate Cox regression analysis in stage II MLLO demonstrated that the time to surgery was a prognostic factor for DFS (HR, 2.051; 95% CI, 1.528-42.136; P = 0.014) and for OS (HR, 4.947; 95% CI, 1.520-16.107; P = 0.008). CONCLUSIONS: The time to surgery was demonstrated not to be a significant prognostic factor in all MLLO. However, it was a prognostic factor for patients with stage II MLLO.

Endoscopic Stenting for Malignant Left-Sided Large-Bowel Obstruction in Patients with Colorectal Cancer: Evaluation according to Pathological Stage.

INTRODUCTION: Self-expandable metallic stents (SEMSs) are widely used in patients with malignant left-sided large-bowel obstruction (MLLO) to convert an emergency situation into an elective one. However, the effects of endoscopic stenting on oncological outcomes remain unclear. This study aimed to analyze the oncological outcomes of SEMS placement in patients with MLLO stratified by pathological stage. METHODS: We reviewed the data of patients with MLLO that were prospectively collected between January 2005 and December 2016. Patients were divided into those who underwent SEMS placement as a bridge to surgery and those who underwent emergency surgery. Disease-free survival (DFS) and overall survival (OS) were compared between groups, and their prognostic factors were determined by pathological stage. RESULTS: SEMS placement and emergency surgery were performed in 130 and 45 patients, respectively. There was no difference in the 5-year DFS and OS rate between two groups. Subgroup analysis revealed a significant difference in the 5-year DFS and OS rate in patients with stage III MLLO, but was not observed in patients with stage II MLLO. Multivariate Cox regression analysis for stage III MLLO revealed endoscopic stenting (hazard ratio [HR], 2.051; 95% confidence interval [CI], 1.018-4.131; p = 0.044) as the only prognostic factor for DFS. Age, tumor differentiation, perineural invasion, and endoscopic stenting (HR, 3.189; 95% CI, 1.346-7.556; p = 0.008) were prognostic factors for OS. CONCLUSION: In terms of oncologic outcomes, endoscopic stenting might be more beneficial than ES in patients with stage III MLLO.

Clinical Implications of Combined Lymphocyte and Neutrophil Count in Locally Advanced Rectal Cancer After Preoperative Chemoradiotherapy.

BACKGROUND: There are controversies about the ability of neutrophil to lymphocyte ratio to predict the recurrence and survival in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation. The objective of this study is to investigate the prognostic potential of combined lymphocyte count (LC) and neutrophil count (NC) in LARC patients treated with chemoradiotherapy (CRT) followed by curative surgery. METHODS: Patients with LARC who underwent surgical resection between January 2010 and December 2017 were reviewed retrospectively. We divided the patients into three groups: high LC and low NC, low LC and high NC, and the remaining patients. The cut-off values of LC and NC were determined by receiver operating characteristic curve analysis and log-rank test statistics. We compared the disease-free survival (DFS) rate between the groups. RESULTS: A total of 176 consecutive patients were included in this study. The 5 year DFS rate was significantly different among the three groups in pathologic node (pN)+ patients (73.2% vs. 61.9% vs. 14.2%; P = 0.025). Cox multivariate analysis for pN+ patients demonstrated that combination of low LC and high NC (hazard ratio, 3.630; 95% confidence interval [CI], 1.306-10.093; P = 0.013) was significantly correlated with decreased DFS. CONCLUSIONS: This study showed that the combination of LC and NC is a powerful predictive factor for disease recurrence in pN+ LARC patients who underwent CRT.

Ultralow Anterior Resection and Coloanal Anastomosis for Low-Lying Rectal Cancer: An Appraisal Based on Bowel Function.

BACKGROUNDS/AIMS: On the basis of acceptable oncologic results, ultralow anterior resection (ULAR) and colo-anal anastomosis plus hand-sewn coloanal anastomosis have been performed for treating very low-lying rectal cancer. However, many patients experience bowel dysfunction after ULAR. Studies have provided inadequate data on bowel dysfunctions and only a few functional studies have focused on low rectal cancer. Therefore, we aimed to elucidate the severity of bowel dysfunction after ULAR in a single-surgeon cohort. METHODS: In this prospective observational study, we analyzed data of 203 patients who underwent sphincter-preserving surgery for low-lying rectal cancer (tumor located within 5 cm from the anus) between January 2011 and December 2014. During routine follow-up, examinations (3-6 months interval) after ileostomy closure, patients were asked about their bowel functions based on the Wexner incontinence and LAR syndrome (LARS) scores. Patients were divided into 2 groups: LAR group (LAR with double-stapled anastomosis) and ULAR group (ULAR with coloanal anastomosis), and functional scores were compared between 6 and 36 months. Seven risk factors for major LARS were analyzed. RESULTS: At 36 months after surgery, 94.2 and 70.6% of patients in the ULAR group still had moderate to severe incontinence and major LARS respectively. Fecal incontinence improved significantly over time (ULAR group, 14.4 vs. 7.2, p = 0.045; LAR group, 13.9 vs. 5.4, p < 0.05). However, improvement in LARS over time was observed in the LAR group only (26.5 vs. 19.7, p = 0.045). In the ULAR group, the difference did not reach a statistical significance (33.6 vs. 26.0, p = 0.10). Major LARS and moderate incontinence were significantly higher in the ULAR group than in the LAR group (70.6 vs. 47.6%, p = 0.001; 82.4 vs. 32.0%, p = 0.012 respectively). Among the 7 factors evaluated in multivariable analysis, old age (> 70), male sex, ULAR per se, and chemoradiation therapy were found to be meaningful risk factors for major LARS. CONCLUSION: In patients with low rectal cancers undergoing ULAR plus coloanal anastomosis, bowel dysfunctions were severe. Bowel dysfunctions improved over time, but most patients still experienced major bowel dysfunctions even 36 months after surgery. Risk factors for bowel dysfunctions were old age, male sex, adjuvant chemoradiation therapy, and ULAR. Therefore, ULAR should be performed in carefully selected patients with low-lying rectal cancer.

Prognostic significance of systemic inflammatory response in stage II colorectal cancer.

BACKGROUND: It is considered that stage II colorectal cancers have heterogeneous oncological outcomes. It remains to be determined whether inflammatory markers can predict survival after curative surgery in these patients. The aim of this study was to investigate the prognostic impact of preoperative inflammatory markers after curative surgery in stage II colorectal cancers. METHODS: Two hundred sixty-one patients with stage II colorectal cancers who underwent curative surgery between January 2006 and December 2011 were reviewed. Oncologic outcomes were analyzed with neutrophil count, lymphocyte count, monocyte count, neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio. RESULTS: Univariate analysis showed that high NLR (hazard ratio (HR), 3.506; 95% confidence interval [CI], 1.415-8.688; P = 0.007) and low LMR (HR, 2.436; 95% CI, 1.010-5.880; P = 0.048) were associated with worse disease-free survival (DFS), and high NLR (HR, 2.834; 95% CI, 1.419-5.662; P = 0.003) and low LMR (HR, 2.374; 95% CI, 1.188-4.742; P = 0.014) were associated with worse overall survival (OS) in stage II colorectal cancer. Cox multivariate analysis demonstrated that high NLR was independently associated with worse DFS (HR, 3.163; 95% CI, 1.058-9.455; P = 0.004) and OS (HR, 3.018; 95% CI, 1.467-6.207; P = 0.003) in stage II colorectal cancer. CONCLUSION: Among the systemic inflammatory markers, NLR is a strong predictor of worse DFS and OS in stage II colorectal cancer.

Prognostic Significance of Lymphocyte Counts in Colon Cancer Patients Treated with FOLFOX Chemotherapy.

PURPOSE: There is increasing interest in immune function in combination with chemotherapy for cancer treatment. However, the effects of chemotherapy on the human immune system remain to be determined. The aim of this study was to investigate the prognostic impact of lymphocyte and neutrophil counts in colon cancer patients who were treated with curative surgery and adjuvant chemotherapy. METHODS: Two hundred thirty-one patients with colon cancers who underwent curative surgery and FOLFOX adjuvant chemotherapy between November 2005 and December 2011 were included. Oncologic outcomes were analyzed with neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR) before and after chemotherapy. RESULTS: The 5-year DFS rate was lower in colon cancer patients with low lymphocyte count during chemotherapy (61.9 vs. 76.7%, P = 0.026). Cox multivariate analysis demonstrated that low lymphocyte count during chemotherapy was independently associated with poor disease-free survival (HR 1.829; 95% CI 1.096-3.050; P = 0.021) in colon cancer patients who underwent FOLFOX adjuvant chemotherapy. CONCLUSION: Lymphocyte count during chemotherapy is a strong predictor of worse disease-free survival in colon cancer patients who have undergone FOLFOX adjuvant chemotherapy.

Clinical Significance of the Endoscopic Finding in Predicting Complete Tumor Response to Preoperative Chemoradiation Therapy in Rectal Cancer.

BACKGROUND: There are reports that suggest conservative treatment when a tumor shows clinically complete response (CR) after preoperative chemoradiotherapy in rectal cancer. The aim of this study is to investigate the association between endoscopic complete response (E-CR) and pathologic CR (pCR) and to determine the sensitivity and specificity of E-CR and its clinical utility after preoperative chemoradiotherapy in rectal cancer. METHODS: We analyzed prospectively collected data of patients with middle and lower rectal cancers who underwent preoperative chemoradiotherapy, between January 2010 and January 2015. RESULTS: Nineteen patients (17.9 %) showed E-CR, and 87 patients showed E-non CR. Twenty-three patients (21.7 %) were confirmed to have pCR. E-CR was closely associated with pCR (p < 0.001). E-CR reflected pCR with an accuracy of 88.7 %, sensitivity of 65.2 %, specificity of 95.2 %, PPV of 78.9 %, NPV of 90.8 %, and a p value of <0.001. CONCLUSIONS: E-CR after preoperative chemoradiotherapy in rectal cancer is significantly associated with pCR. However, a wait and see policy should be performed carefully with current endoscopic prediction for pCR to avoid inadequate treatment in patients who show E-CR after preoperative chemoradiotherapy.

Preoperative neutrophil to lymphocyte ratio predicts survival in patients with T1-2N0 colorectal cancer.

PURPOSE: Neutrophil to lymphocyte ratio (NLR) is reported to be associated with prognosis of colorectal cancer. The aim of this study is to determine whether the NLR is a predictor of oncological outcomes in patients with stage I colorectal cancer who underwent curative surgery. METHODS: Two hundred sixty-nine patients with stage I colorectal cancer who underwent surgical resection between December 2003 and December 2011 were retrospectively reviewed. The cutoff for NLR was defined as three by maximizing log-rank test statistics. We compared patients with a low NLR and those with a high NLR in terms of survival. RESULTS: The 5-year disease-free survival (DFS) and cancer-specific survival (CSS) rates were lower in patients with a high NLR compared to those with a low NLR in stage I colorectal cancer (89.5% vs. 97.4%, P = 0.006; 94.0% vs. 98.9%, P = 0.022). Cox multivariate analysis demonstrated that preoperative NLR was independently associated with DFS (HR, 5.216; 95%CI, 1.400-19.431; P = 0.014) and CSS (HR, 6.190; 95%CI, 1.034-37.047; P = 0.046) in patients with stage I colorectal cancer. CONCLUSION: The preoperative NLR is a prognostic factor predicting DFS and CSS in patients with stage I colorectal cancer who underwent curative surgery.

ALDH1 is a prognostic factor for patients treated with neoadjuvant chemoradiotherapy and radical resection for stage III rectal cancer.

BACKGROUND AND OBJECTIVES: The factors relating to changes within a tumor after preoperative chemoradiotherapy associated with rectal cancer prognosis remain to be determined. The aim of this study was to investigate the expression of CD133 and ALDH1 and to analyze the predictive and prognostic roles in patients with rectal cancer after chemoradiotherapy. METHODS: We analyzed the expression levels of ALDH1 and CD133 in patients with middle and lower rectal cancers who underwent preoperative chemoradiotherapy between March 2005 and December 2011. RESULTS: The expression of CD133 was not associated with survival. The 5-year overall survival rates were lower in patients with high ALDH1 expression compared to low ALDH1 expression in stage III rectal cancer (61.0% vs. 89.7%, P=0.031). Cox multivariate analysis demonstrated that high ALDH1 expression (HR, 5.425; 95% CI, 1.116-26.373; P=0.036), cT (HR, 12.861; 95% CI, 2.188-75.591; P=0.005), and pN2 (HR, 28.481; 95% CI, 4.757-170.518; P<0.001) were independently associated with overall survival in 51 patients with stage III rectal cancer. CONCLUSIONS: Expression of ALDH1 indicates a more aggressive feature of stage III rectal cancer and can stratify stage III rectal cancer into different survival groups.

Pretreatment selection of regimen according to genetic analysis improves the efficacy of chemotherapy in the first line treatment of metastatic colorectal cancer.

BACKGROUND AND OBJECTIVES: Metastatic colon cancer patients are treated with the chemotherapy regimens, FOLFOX and FOLFIRI, in either order. So far, we cannot predict the response of chemotherapeutic agent, so it is necessary to find which regimen is adequate before starting chemotherapy. METHODS: Enrolled patients are randomized into either conventional treatment or planned treatment preceded by pretreatment genetic analysis. Blood samples of patients in planned treatment group (N = 53) were analyzed for the genetic polymorphism before selection of chemotherapeutic agents. Target genes were XPD-751, GSTP-1-105, XRCC1-399 for oxaliplatin, UGT1A1 for irinotecan. The response was measured by computed tomographic scan after completion of three cycles of chemotherapy. RESULTS: Overall response rate was significantly higher in planned group (67.9% vs. 46.3%, P = 0.020). In FOLFOX group, response rate was significantly improved in the planned patients(77.1% vs. 50%, P = 0.018). In FOLFIRI group, the difference didn't reach statistical significance (50% vs. 42.5%, P = 0.776). CONCLUSIONS: We found significantly improved response rates in the chemotherapy of metastatic colon cancer by pretreatment genetic analysis, especially in FOLFOX group.

Comparison of oncological outcomes between neoadjuvant and adjuvant chemotherapy combined with surgery for resectable synchronous colorectal liver metastases.

BACKGROUND: The role of neoadjuvant chemotherapy for resectable colorectal liver metastases is a subject of debate. We compared the oncologic outcomes between neoadjuvant chemotherapy and adjuvant chemotherapy combined with surgery for resectable synchronous colorectal liver metastases. METHODS: We analyzed 30 patients who underwent liver resection for resectable colorectal liver metastases combined with oxaliplatin-based neoadjuvant or adjuvant chemotherapy between May 2003 and August 2010. We assessed recurrence-free and overall survival in patients treated using neoadjuvant chemotherapy compared with those who received adjuvant chemotherapy. RESULTS: Of the 30 patients with colorectal liver metastases, 15 underwent neoadjuvant chemotherapy and 15 underwent adjuvant chemotherapy. Nine (60%) patients in the adjuvant group relapsed and nine (60%) patients in the neoadjuvant group relapsed. The neoadjuvant chemotherapy group had no significant difference in recurrence-free and overall 3-y survival (37.5% versus 45.0%, P = 0.938; 44.0% versus 66.7 %, P = 0.466) compared with the adjuvant chemotherapy group. CONCLUSION: Our results indicate that neoadjuvant chemotherapy is not inferior to adjuvant chemotherapy for resectable colorectal liver metastases, although the study was not randomized and included a limited number of patients.

Oncologic outcomes after adjuvant chemotherapy using FOLFOX in MSI-H sporadic stage III colon cancer.

BACKGROUND: Little is known of the oncological outcomes after adjuvant FOLFOX chemotherapy in patients with stage III colon cancer showing microsatellite instability high (MSI-H). In the present study we investigated the prognostic impact of MSI-H in patients with stage III colon cancer receiving FOLFOX chemotherapy. METHODS: We analyzed the MSI status in 127 patients with stage III colon cancer who underwent curative surgical resection followed by FOLFOX chemotherapy between January 2003 and December 2010. We assessed disease-free and overall survival (OS) in patients with MSI-H colon cancer compared with those showing microsatellite instability low or microsatellite stable (MSI-L/MSS) disease. RESULTS: Sixteen of the patients (12.6 %) were MSI-H, and 111 patients (87.4 %) were MSI-L/MSS. There was no significant difference between patients showing MSI-H and MSI-L/MSS except for age (P = 0.030), tumor location (P < 0.001), and differentiation (P = 0.031). Compared with MSI-L/MSS colon cancer, patients with MSI-H colon cancer had no significant difference in 5-year disease-free and OS (72.2 vs 68.5 %, P = 0.874; 68.1 vs 71.1 %, P = 0.437). CONCLUSIONS: Our study indicates that FOLFOX chemotherapy can be considered to treat stage III colon cancer patients with MSI-H after surgery, although the study was not randomized and included only a limited number of patients.

Effectiveness of Self-Assessment, TAilored Information, and Lifestyle Management for Cancer Patients' Returning to Work (START): A Multi-center, Randomized Controlled Trial.

PURPOSE: We developed a comprehensive return to work (RTW) intervention covering physical, psycho-social and practical issues for patients newly diagnosed and evaluated its efficacy in terms of RTW. Materials and Methods: A multi-center randomized controlled trial was done to evaluate the efficacy of the intervention conducted at two university-based cancer centers in Korea. The intervention program comprised educational material at diagnosis, a face-to-face educational session at completion of active treatment, and three individualized telephone counseling sessions. The control group received other education at enrollment. RESULTS: At 1-month post-intervention (T2), the intervention group was more likely to be working compared to the control group after controlling working status at diagnosis (65.4% vs. 55.9%, p=0.037). Among patients who did not work at baseline, the intervention group was 1.99-times more likely to be working at T2. The mean of knowledge score was higher in the intervention group compared to the control group (7.4 vs. 6.8, p=0.029). At the 1-year follow-up, the intervention group was 65% (95% confidence interval, 0.78 to 3.48) more likely to have higher odds for having work. CONCLUSION: The intervention improved work-related knowledge and was effective in facilitating cancer patients' RTW.

Prognostic impact of fascin-1 expression is more significant in advanced colorectal cancer.

BACKGROUND: Fascin-1 is not expressed in normal colorectal epithelium, but is up-regulated in colorectal cancer. However, its exact biological mechanism remains unknown. The purpose of this study was to investigate the relationship of fascin-1 expression with the clinicopathologic parameters and its prognostic impact in advanced colorectal cancer. MATERIALS AND METHODS: The immunohistochemical stainings for fascin-1, ß-catenin, and Ki-67 labeling index were performed with 126 stage III colorectal cancer specimens. RESULTS: Fascin-1 was found to be expressed in 74 (58.7%) of the 126 colorectal cancer specimens. Five-year survival rate was significantly low, whereas the distant recurrence rate was significantly high in patients with fascin-positive stage III colorectal cancer. There was no significant correlation between fascin-1 expression and clinicopathologic factors such as tumor size, nodal metastasis, pathologic stage, ß-catenin expression, and Ki-67 labeling index. However, fascin-1 expression was an independent prognostic factor in multivariate analysis. Patients with N1 showed no significant difference in 5-y DFS and OS according to the fascin-1 expression (79.0% versus 60.5%, P = 0.113; 86.5% versus 78.8%, P = 0.566). Patients with N2 showed marginal difference in 5-y DFS and significant difference in 5-y OS according to the fascin-1 expression (59.4% versus 32.4%, P = 0.088; 81.2% versus 39.5%, P = 0.002). CONCLUSIONS: This study suggests that fascin-1 expression in colorectal cancer may be clinically useful in predicting distant metastasis and poor survival, and we demonstrated that fascin-1 expression and N stage are significant independent prognostic factors for survival of colorectal cancer patients.

Prognostic value of advanced lung cancer inflammation index in patients with colorectal cancer liver metastases undergoing surgery.

INTRODUCTION: Recently, a new inflammatory marker, the advanced lung cancer inflammation index (ALI), was reported as a prognostic marker in patients with several cancers. We aimed to investigate the prognostic value of ALI in patients with colorectal cancer liver metastases (CLM) undergoing surgery. METHODS: From June 2009 to June 2018, 141 patients underwent a surgery for CLM at Ajou University Hospital, of whom 132 without extrahepatic metastases, systemic inflammatory diseases, or immune system diseases were enrolled in this study. The ALI was calculated using the following formula: ALI = body mass index × serum albumin/neutrophil-to-lymphocyte ratio. The patients were divided into high (n = 32) and low (n = 100) ALI groups according to the preoperative optimal cutoff value of 70.40 that was determined by X-tile software. RESULTS: Patients with low ALI had a significantly worse overall survival (OS) compared to the high ALI group (p = 0.010). Multivariate analysis showed that ALI and carcinoembryonic antigen (CEA) were independently associated with OS (p = 0.009 and p = 0.042, respectively). Among the patients with CEA >5 ng/mL, the low ALI group had a significantly worse OS compared to the high ALI group (p = 0.013). CONCLUSION: Preoperative ALI was a prognostic factor in patients with CLM undergoing surgery. In particular, the prognostic impact of ALI was more prominent in the patients with CEA >5 ng/mL.

Does total mesorectal excision require a learning curve? Analysis from the database of a single surgeon's experience.

BACKGROUND: The procedure of total mesorectal excision (TME) is the gold standard in the treatment of rectal cancer. However, quality control of TME is still under debate. The present study was conducted to determine whether TME requires a learning curve to allow the surgeon to grasp the necessary technical expertise. METHODS: We performed a retrospective review of patients with rectal cancer who underwent TME with curative intention between August 1998 and December 2003; 195 consecutive patients were enrolled. From the first patient of the cohort, the first 50 patients were categorized into group 1, the next 50 into group 2, the next 50 into group 3, and the final 45 patients into group 4. Local recurrence rates were compared between the four groups. RESULTS: No significant difference in clinicopathological features was observed between the four groups, except for age, operative time, and grade of mesorectum. The local recurrence (LR) rate decreased from 22.3% in the inadequate TME group (G1) to 9.1% in the adequate TME group (G2-4) (p=0.035). In multivariate analysis, regional lymph node metastasis, mesorectal grade (incomplete or nearly complete), and early period of learning curve were independent predictors of local recurrence. CONCLUSIONS: Our results suggest that a learning curve is necessary for the development of technical expertise in the performance of TME for treatment of rectal cancer.

Prognostic Reappraisal of Postoperative Carcinoembryonic Antigen in T1-2N0 Colorectal Cancer.

BACKGROUND/AIM: The purpose of this study was to compare the prognostic value of preoperative carcinoembryonic antigen (CEA), preoperative CEA/tumor size and postoperative CEA in stage I colorectal cancer. PATIENTS AND METHODS: We analyzed a total of 305 consecutive stage I colorectal cancer patients who underwent a radical surgery at our Department. The patients were divided into low and high preoperative CEA groups, low and high preoperative CEA/tumor size groups, and low and high postoperative CEA groups according to the optimal cut-off values. RESULTS: Multivariate analysis showed that postoperative CEA was independently associated with OS and DFS. However, the preoperative CEA and preoperative CEA/tumor size were not. CONCLUSION: The prognostic value of postoperative CEA is better than preoperative CEA and preoperative CEA/tumor size in patients with stage I colorectal cancer. Moreover, the common 5 ng/ml cut-off was not optimal for risk stratification in stage I colorectal cancer.

Senescent Tumor Cells Build a Cytokine Shield in Colorectal Cancer.

Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8+ T cells is negatively associated with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C-X-C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8+ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti-PD1 antibody in allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells enhances T cell infiltration and results in reducing the number and size of tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC. These findings suggest senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack and provide a new target for overcoming the immunotherapy resistance of CRC.