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Patients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

Objective The number of colon cancer patients is increasing worldwide. Malnutrition and comorbidities are frequently associated with these patients. The relationships between the preoperative malnutrition and the outcomes of colon cancer patients are unclear; this study aimed to clarify these issues. Methods A total of 3,849 consecutive colon cancer patients were enrolled in an analysis of short-term outcomes and 2,529 patients were included in an analysis of the long-term outcomes. These patients were divided into the hypoalbuminemic and normal groups according to the definition of hypoalbuminemia (serum albumin < 35 g/L). Results Advanced age, female gender, abnormal CEA levels, right colon or large tumors, mucinous adenocarcinoma, poor differentiation, stage II cancer, TNM advancing T stage, old cardiovascular accident, diabetes, and liver cirrhosis were more likely to be associated with hypoalbuminemia. Hypoalbuminemic patients had a higher rate of postoperative mortality and morbidity, including complications related to wounds, lungs, the urinary system, and anastomosis. The 5-year overall survival rates of patients with normal albumin and hypoalbuminemia were 78.0% and 60.0%, respectively (P < 0.0001), and the 5-year relapse-free survival rates were 78.9% and 73.5%, respectively (P = 0.0042). In a multivariate analysis, the albumin level was also significantly correlated with 5-year overall survival (<35 vs. ≥35, HR 1.75; 95% CI 1.49-2.08) and 5-year relapse-free survival (<35 vs. ≥35, HR 1.28; 95% CI 1.04-1.56). Conclusions Hypoalbuminemia is a predictor of poor surgical outcomes of colon cancer and is a poor prognosis factor for long-term survival of colon cancer after curative operation.

Background Preoperative carcinoembryonic antigen (CEA) has yet to be used as a prognostic or adjuvant chemotherapy factor for colorectal cancer (CRC). Methods This retrospective cohort study included all stage I–III CRC patients with different preoperative serum CEA levels (≤ 5, 5–10, and > 10 ng/ml) at a single center between 1995 and 2010. Propensity score matching was performed in a 1:1 ratio between the two elevated CEA groups (5–10 ng/ml and > 10 ng/ml) and in a 1:2 ratio between the elevated and non-elevated groups (≤ 5 ng/ml), with a caliper of 0.05. Results After exclusion and matching, 3857 patients had preoperative CEA levels ≤ 5 ng/ml, 1121 patients had CEA levels between 5 and 10 ng/ml, and 1121 patients had CEA levels > 10 ng/ml. Elevated preoperative CEA showed an increased risk of overall survival (5–10 ng/ml: hazard ratio [HR] 1.376; > 10 ng/ml: HR 1.523; both p  < 0.001), cancer-specific survival (5–10 ng/ml: HR 1.404; > 10 ng/ml: HR 1.712; both p  < 0.001), and recurrence free interval (5–10 ng/ml: HR 1.190; > 10 ng/ml: HR 1.468; both p  < 0.05). Patients with negative lymph node staging (LNs) and CEA > 10 ng/ml, as well as those with positive LNs and CEA ≤ 5 ng/ml, showed similar overall survival (5-year survival: 72% vs. 69%; p  = 0.542) and recurrence free intervals (19.9 vs. 21.72 months; p  = 0.662). Conclusions A preoperative CEA level can be an independent prognostic factor for stage I–III CRC after curative resection. Patients with negative LNs and preoperative CEA level > 10 ng/ml should be considered for intensive follow-up or adjuvant chemotherapy.

Purpose We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) on disease-free survival in patients with stages I to III colorectal cancer (CRC). Methods There were 3857 patients identified from our database. We used receiver operating characteristic (ROC) analysis to identify the best cutoff value of NLR. A 5-year disease-free survival was used as end point. Survival analysis was used to assess the NLR effect, after stratification by several clinopathologic factors. Results In the ROC analysis, NLR = 3 had the highest sensitivity and specificity. Elevated NLR (>3) in colon cancer seemed to accompany larger tumor size (≧5 cm) and more advanced T stage. By multivariate analysis, elevated NLR in colon cancer was associated with an increased risk of disease progression or cancer death [hazard ratio (HR) 1.377, 95  % confidence interval 1.104–1.717, P  = 0.014]. However, elevated NLR in rectal cancer lost its significance in multivariate analysis (HR 1.121, 95  % confidence interval 0.941–1.336, P  = 0.200). Patients with elevated NLR had worse outcome, especially for colon cancer. Conclusions Preoperative NLR influenced the disease-free survival in patients with stages I to III CRC. Elevated NLR (>3) was associated with worse outcome (5-year disease-free survival 66.3  % vs. 78.9  % in colon cancer, P  < 0.001; 60. 5 % vs. 66.2  % in rectal cancer, P  = 0.008). The difference was larger in colon cancer than in rectal cancer. NLR should be considered as a prognostic factor for stages I to III CRC patients after curative surgery.

Background The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection. Methods Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. Results Out of 956 patients with temporary stomas, 10.3% ( n  = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below ( p  < 0.001). Conclusion Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.

Background and aims Selection of appropriate stage II colon cancer patients for adjuvant chemotherapy is critical for improving survival outcome. With the aim of identifying more high risk factors for stage II colon cancer, this study aimed to determine whether the neutrophil–lymphocyte ratio (NLR) is a predictor of surgical outcomes in patients with stage II colon cancer who do not receive adjuvant chemotherapy. Materials and methods We enrolled 1,040 stage II colon cancer patients who had undergone colectomy at a single institution between January 1995 and December 2005 and did not receive adjuvant chemotherapy. Results Of these 1,040 patients, 785 (75.5%) patients had a normal NLR and 255 (24.5%) had an elevated NLR. Those with an elevated NLR included patients ≥65 years, T4b cancer, carcinoembryonic antigen ≥5 ng/mL, and tumor obstruction or perforation. Patients with an elevated NLR had a significantly worse overall survival (OS) and worse disease-free survival (DFS) than did patients with a normal NLR. Cox regression analysis revealed that elevated NLR was an independent predictor of OS ( P =0.012) but not DFS ( P =0.255). Conclusion An elevated NLR is an independent predictor of OS but not DFS in stage II colon cancer patients who did not receive adjuvant chemotherapy. Preoperative NLR measurement in stage II colon cancer patients may be a simple method for identifying patients with a poor prognosis who can be enrolled in further trials of adjuvant chemotherapy.

Purpose It remains controversial as to whether high ligation of the inferior mesenteric artery (IMA) should be performed during surgical treatment for sigmoid colon or rectal cancer. The purpose of this study is to attempt to clarify the extent of the oncologic benefit of high ligation of the IMA. Materials and methods From January 1995 to July 2001, a total of 1,389 patients underwent high ligation of the IMA; 387 patients featured non-disseminated sigmoid colon cancer and 1,002 patients had rectal cancer. Pathology of the primary tumors, IMA nodes, and clinical outcome were reviewed. Results Forty-three patients (3.1%) revealed IMA node metastasis. Of these 43 patients, 29 (67.4%) featured tumor recurrences/metastases. After a minimum 5-year follow-up, 11 of these 43 patients (25.6%) were alive and disease free. Of these 43 patients, the 5-year disease-free survival rate for patients featuring sigmoid cancer was 50% and for patients with rectal cancer 13.8%. The beneficial rate of high ligation of the IMA for non-disseminated sigmoid colon cancer and rectal cancer was 0.8%, for non-disseminated sigmoid colon cancer 1.8%, and for non-disseminated rectal cancer, the rate was only 0.4%. The rates of IMA metastasis in patients with T stage tumors were 0% (pT1), 1.0% (pT2), 2.6% (pT3), and 4.3% (pT4). Conclusions Although patients afflicted with IMA node metastasis revealed a rather high incidence of tumor recurrence/metastasis, 25.6% of these patients remained disease free following IMA node dissection after a minimum 5-year follow-up. We consider that IMA node dissection is more beneficial in patients with non-disseminated sigmoid pT4 tumor.

Background Local excision has become an alternative for radical resection in rectal cancer for selected patients. The purpose of this study was to assess the clinicopathologic factors determining lymph node metastasis (LNM) in patients with T1–2 rectal cancer. Methods Between January 1995 and December 2009, a total of 943 patients with pT1 or pT2 rectal adenocarcinoma received radical resection at a single institution. Clinicopathologic factors were evaluated by univariate and multivariate analyses to identify risk factors for LNM. Results A total of 943 patients (544 men and 399 women) treated for T1–2 rectal cancer were included in this study. LNM was found in 188 patients (19.9%). In multivariate analysis, lymphovascular invasion (LVI; P  < 0.001, hazard ratio 11.472), poor differentiation (PD; P  = 0.007, hazard ratio 3.218), and depth of invasion (presence of pT2; P  = 0.032, hazard ratio 1.694) were significantly related to nodal involvement. The incidence for LNM lesions in the presence of LVI, PD, and pT2 was 68.8, 50.0, and 23.1%, respectively, while that for pT1 carcinomas with no LVI or PD was 7.5%. Conclusions LVI, PD, and pT2 are independent risk factors predicting LNM in pT1–2 rectal carcinoma.

Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations. In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence. Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55) and 0.54 (95% CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O. The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.

TP53 encodes p53, which has a crucial role in modulating genes that regulate defense against cancer development. This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk. We identified 260 MLH1 and MSH2 germline mutation carriers from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association of TP53 polymorphisms with CRC development. The carriers of the variant C allele of rs1042522 were associated with a decreased CRC risk (GC genotype: HR = 0.35, 95% CI = 0.14-0.86; CC genotype: HR = 0.28, 95% CI = 0.13-0.57). In addition, the dominant model of rs1042522 was associated with a decreased CRC risk (HR = 0.32, 95% CI = 0.15-0.67). The CRC risk was decreased in carriers with the CT and TT genotypes of rs12947788 (HR = 0.20, 95% CI = 0.08-0.46 and HR = 0.25, 95% CI = 0.09-0.65, respectively). Moreover, the dominant model of rs12947788 was significantly associated with a decreased CRC risk (HR = 0.21, 95% CI = 0.09-0.46). A haplotype analysis indicated that compared with the most common GC haplotype, the CT haplotype was associated with a decreased CRC risk (HR = 0.26, 95% CI = 0.11-0.59). However, no significant interaction was observed between TP53 polymorphisms and lifestyle factors. The study results revealed that the rs1042522 genotype with the C allele and the rs12947788 genotype with the T allele in TP53 were associated with a decreased CRC risk in patients with Lynch syndrome in Taiwan.