Huann-Sheng Wang

Purpose: Traditionally, Deficient Mismatch Repair(dMMR) has been associated with a favorable prognosis in early-stage colorectal cancer (CRC). dMMR acts as a predictive biomarker for immunotherapy response in metastatic CRC while its role in earlier-stage disease is still being evaluated in ongoing clinical trials. This study aims to re-evaluate the independent prognostic value of MMR status in stage II/III CRC within the framework of standardized modern clinical care. Methods We identified 972 patients with Stage II/III CRC (2017–2019) who underwent curative resection in a tertiary center. A 1:3 propensity score matching (PSM) was performed to balance age, gender, tumor location, pathological stage and chemotherapy. The endpoint was 5-year overall survival (OS), presented using the Kaplan-Meier analysis, compared via log-rank test and Multivariable Cox proportional hazards models were used to identify independent prognostic factors. Results After PSM, 5-year overall survival (OS) showed no significant difference for stage II(p = 0.79) and stage III (p = 0.99). Multivariate analysis confirmed that MMR status was not an independent predictor of OS (HR0.85, p = 0.70), whereas tumor-infiltrating lymphocytes (TILs), tumor location and patient age remained significant independent factors. Conclusion In the current treatment era, the use of oxaliplatin-based regimens has narrowed the survival gap between dMMR and proficient mismatch repair(pMMR) and dMMR has lost its role as an independent predictor of survival. Risk stratification should incorporate TILs, age and tumor location rather than relying on MMR status alone.

The incidence, site distribution, and mortality rates of patients with colorectal cancer differ according to gender. We investigated gene mutations in colorectal patients and wanted to examine gender-specific differences. A total of 1505 patients who underwent surgical intervention for colorectal cancer were recruited from March 2000 to January 2010 at Taipei Veterans’ General Hospital and investigated for gene mutations in K-ras, N-ras, H-ras, BRAF, loss of 18q, APC, p53, SMAD4, TGF-β, PIK3CA, PTEN, FBXW7, AKT1, and MSI. There were significant differences between male and female patients in terms of tumor location (p < 0.0001) and pathological stage (p = 0.011). The female patients had significantly more gene mutations in BRAF (6.4 vs. 3.3%, OR 1.985, p = 0.006), TGF-β (4.7 vs. 2.5%, OR 1.887, p = 0.027), and revealed a MSI-high status (14.0 vs. 8.3%, OR 1.800, p = 0.001) than male patients. Male patients had significantly more gene mutations in N-ras (5.1 vs. 2.3%, OR 2.227, p = 0.012); however, the significance was maintained only for mutations in BRAF (OR 2.104, p = 0.038), MSI-high status (OR 2.003 p = 0.001), and N-ras (OR 3.000, p = 0.010) after the groups were divided by tumor site. Gene mutations in BRAF, MSI-high status, and N-ras differ according to gender among patients with colorectal cancer.

This study aimed to investigate the clinicopathological characteristics of synchronous and metachronous colorectal cancers (CRCs). From January 1, 2001 to December 31, 2010, 5898 patients who underwent surgical resection for CRCs were enrolled. Synchronous CRC was defined as presence of more than one primary CRC within 6 months of resection of the primary tumor; while CRC that occurred at least 6 months later was regarded as metachronous CRC. 5346 patients were eligible for the study and divided into three groups: solitary, synchronous and metachronous CRC. The overall prevalence of the synchronous CRC was 2.2% and the 10-year cumulative incidence of metachronous cancer was 0.84%. 29 (64%) metachronous cancers were diagnosed within 3 years of the index cancer and the mean time interval was 3.2 years. Male gender and presence of associated adenoma were significant risk factors for both synchronous and metachronous CRC. Synchronous and metachronous CRC patients shared similar clinicopathological features except that the former were older than the latter by 3.7 years. The five-year survival rates were not different among the three groups. Our study indicates that synchronous and metachronous CRC might represent similar disease entity with different courses.

Colorectal carcinoid tumors are often described as being low-grade malignant. The objective of the current study was to address the clinicopathological features and outcomes of patients with colorectal carcinoid tumors. A total of 63 patients with colorectal carcinoid tumors were identified and evaluated using surgical pathology files and medical records between January 2000 and June 2012 at the Veterans General Hospital, Taipei, Taiwan. The median age of the 63 patients was 57.0 years; 38 (60.3%) were male and 25 (39.7%) female. The rectum was the most common tumor site (90.5%). Tumor size was 10.8 ± 7.4 mm, ranging from 2 to 50 mm in diameter. There were 40 patients (63.5%) who received endoscopic treatment for a tumor size of 7.7 ± 4.0 mm, 15 (23.8%) who underwent transanal excision for a mean size of 9.2 ± 4.5 mm and eight (12.7%) who underwent radical surgical resection (mean size: 29.5 ± 13.0 mm). Lymph node metastasis was significantly associated with tumor size. Totally distant metastases (liver) were demonstrated in four (6.3%), patients with mean tumor size of 31.3 ± 9.4 mm (20 to 50 mm). The extent of the disease was associated with survival and the five-year overall survival rate was 92.1%. With widespread colorectal cancer screening, heightened awareness and improved diagnostic modalities, the incidence of colorectal carcinoid tumors will continue to increase. We demonstrated that small-sized colorectal carcinoid tumors and those localized in the mucosa or submucosa may be safely and effectively removed via endoscopic or transanal local excision.

We evaluated the prognostic significance of clinicopathologic features recommended by the majority of guidelines for identifying high-risk stage it colon cancer patients. We enrolled 665 stage II colorectal cancer patients at Taipei Veterans General Hospital in 2002-2006. Patients who received preoperative or postoperative chemotherapy were excluded (124). The measured endpoint was disease-free survival. Of 541 patients, 59 showed stage T4 tumors; 35, lymphovascular invasion; 19, poor differentiation, and 251, carcinoembryonic antigen levels of > 5 ng/mL; 53 underwent emergent operations. Colorectal cancer recurred in 84 patients. The 5-year disease-free survival rate was 84.5%. Univariate and multivariate analyses revealed 3 independent factors affecting the prognosis significantly tumor stage T4, high carcinoembryonic antigen level, and presence of lymphovascular invasion. Considering the cumulative effect of risk factors, the 5-year disease-free survival rate of patients with tumors without any risk factor was 90.2%, which was significantly better than that of patients with 1 or 2 risk factors (82.3%, 61.6%). Stage II colorectal cancer patients had excellent outcome. Ad juvant chemotherapy may be warranted for patients with multiple risk factors.

Background: To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). Methods: Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). Results: Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). Conclusions: In patients with pre-CRT serum CEA ≥6 ng/ml, those with “normalized” CEA levels after CRT may have similar DFS to those with “normal” (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml.

SummaryIntroductionThe outcome of stage I colorectal cancer (CRC) patients is excellent. However, even after radical surgery, 10% of patients develop tumor recurrence or metastasis.AimThe aim of this study was to evaluate the prognostic significance of clinicopathologic features to identify high-risk stage I CRC patients.MethodsA total of 292 stage I CRC patients undergoing curative-intention surgery at Taipei Veterans General Hospital between 2000 and 2006 were enrolled. The measured end point was the postoperative disease-free survival (DFS).ResultsOf 292 cases, 185 (63.4%) had tumors of T2 stage, 16 (5.5%) had lymphovascular invasion (LVI), and 68 (23.3%) had a carcinoembryonic antigen (CEA) level of higher than 5 ng/mL. With a median follow-up period of 60 months (range, 6–130 months), CRC recurred in 23 patients. Overall, 5-year DFS was 88.7% in stage I disease patients. In the univariate analysis, 5-year DFS of patients with LVI was 52.7%, which was significantly poorer than that of patients without LVI (90.9%). Patients with a high CEA level or T2 lesion had a poor 5-year DFS, but the difference did not reach statistical significance. In the multivariate analysis, the only important independent factor affecting the 5-year DFS was LVI (hazard ratio = 4.27; 95% confidence interval: 1.88–9.68; p = 0.001). In the T1 disease, 5-year DFS of patients with LVI was 60.0%, significantly poorer than that of patients without LVI (93.4%; p = 0.045). In the T2 disease, the difference of 5-year DFS between patients with and without LVI was more significant (50.5% vs. 85.1%; p = 0.003).ConclusionStage I CRC patients in this study had an excellent outcome. Prognosis of patients having tumor with LVI was poor and should receive an aggressive follow-up protocol

The prognostic role of serum carcinoembryonic antigen (CEA) in colorectal cancer patients with normal preoperative level is questionable. We evaluate the perioperative change of serum CEA to elucidate its prognostic effect in these patients. We reviewed patients who received curative resection of colorectal cancer during 2000 and 2004 at Taipei Veterans General Hospital. The serum CEA level at diagnosis and one month after curative surgery were recorded. Levels higher than 5ng/mL were defined as abnormal. We divided patients with normal preoperative CEA level into two groups depending on the perioperative change. They were analyzed with clinicopathological factors and disease free survival rate. In patients with stage I to III colorectal cancer, there were 738 patients with normal preoperative CEA level (55.7%). Patients with increased post-operative CEA than pre-operative ones had higher percentage of colon cancer (p=0.007) and more lymphovascular invasion (p=0.038). Besides they also had higher disease recurrent rate (p=0.032) and worse disease-free survival (p=0.019). In multivariate analysis, perioperative CEA change, lymph node metastasis and tumor invasion depth remained independent prognostic factors (p=0.015). When preoperative CEA level is normal, perioperative change is a prognostic factor of colorectal cancer.

Background Preoperative chemoradiotherapy (CCRT) followed by radical resection is an option for advanced low rectal cancer. This study was aimed to clarify the impact of CCRT on patients' outcome. Patients and Methods One hundred thirty-six patients with rectal cancer (P = 0.125). The 5-year overall survival and disease-free survival (DFS) percentage were 88.4% and 76.8% for patients with preoperative CCRT, and 65.7% and 58.2% for patients without CCRT, respectively. Patients with preoperative CCRT had a higher overall survival rate and DFS (P = 0.001 and 0.015). Conclusions In patients with advanced low rectal cancer, preoperative CCRT followed by radical surgery significantly improved overall survival and DFS compared with surgery alone. The effect of sphincter preservation with preoperative CCRT is questionable. J. Surg. Oncol. 2010;102:771–777.

Ction of T1 colorectal adenocarcinoma at the Taipei Veterans General Hospital from December 1969 to August 2002 were retrospectively studied. Patients with synchronous colorectal cancer, distant metastasis, familiar adenomatous polyposis, or inflammatory bowel disease were excluded. The associations between lymph node metastasis and clinicopathologic variables were evaluated univariately using chi-squared test, Fisher's exact test, or Student'st-test, and multivariately using logistic regression. Univariate analysis by the log-rank test and multivariate analysis by Cox regression hazards model determined the factors influencing the overall survival. RESULTS: A total of 159 patients were included. Sixteen patients (10.1 percent) had lymph node metastasis. The risk of lymph node metastasis included histologic grade (P= 0.005), lymphatic vessel invasion (P= 0.023), inflammation around cancer (P= 0.049), and budding at the invasive front of tumor (P= 0.022). Age (P= 0.001) and number of total sampling lymph nodes (P< 0.0001) were found to be the factors influencing the overall survival. CONCLUSIONS: Variables that predict lymph node metastasis in surgically resected T1 colorectal carcinoma may not impact the long-term prognosis. Supported by a grant from the Research Foundation of Taipei Veterans General Hospital. aNo. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan, 11217, Republic of China, e-mail: hswang@vghtpe.gov.tw © The ASCRS 2005...