Shung-Haur Yang

How Accurate is Magnetic Resonance Imaging in Restaging Rectal Cancer in Patients Receiving Preoperative Combined Chemoradiotherapy

PURPOSEPreoperative combined chemoradiotherapy is currently the main neoadjuvant therapy used to treat locally advanced middle and low rectal adenocarcinoma. A restaging work-up with magnetic resonance imaging was hoped to provide information about the effects related to combined chemoradiotherapy. The goal was to evaluate the correlation between pathologically verified tumor stages and clinical stages predicted by magnetic resonance imaging after combined chemoradiotherapy.METHODSBetween August 2000 and June 2003, 50 patients with biopsy-proven middle and lower rectal adenocarcinoma, with initial stage T3–T4 or N+, M0, were recruited in this series. Pelvic magnetic resonance imaging was used to stage the tumor before and after combined chemoradiotherapy. A protocol of the standard external radiation dose and oral combined uracil and 5-fluorouracil plus leucovorin was used. The results of magnetic resonance imaging restaging after combined chemoradiotherapy were correlated with the pathologic staging.RESULTSThe overall predictive accuracy in T stage was 52 percent, whereas overstaging and understaging occurred in 38 percent and 10 percent of patients, respectively. Most of the inaccurate T staging was a result of the overstaging of superficial tumors (T0–T2). In N stage, accurate staging was noted in 68 percent of all patients, whereas 24 percent were overstaged and 8 percent were understaged.CONCLUSIONIn restaging irradiated tumors, magnetic resonance imaging had the accuracy of 52 percent in T stage and 68 percent in N stage. Poor agreement between post–combined chemoradiotherapy magnetic resonance imaging and pathologic staging was observed in both T (k = 0.017) and N (k = 0.031) stages. Most of the inaccuracy in both T and N stages was caused by overstaging. The problem with magnetic resonance imaging was believed to be that it could not completely differentiate fibrosis from viable residual tumors.

Curative Resection of T1 Colorectal Carcinoma: Risk of Lymph Node Metastasis and Long-Term Prognosis

PURPOSEThe features of T1 colorectal adenocarcinoma and the risk determination of lymph node metastasis were reviewed. Prognostic factors were assessed to verify whether the risk of lymph node metastasis would influence the long-term prognosis.METHODSPatients undergoing curative resection 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’s t -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.RESULTSA 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.CONCLUSIONSVariables that predict lymph node metastasis in surgically resected T1 colorectal carcinoma may not impact the long-term prognosis.

Anti-angiogenic effect of silymarin on colon cancer lovo cell line

OBJECTIVE This study was designed to evaluate the anti-angiogenic effect of silymarin (SM) and its major pure component silibinin (SB), and also thalidomide (TH). MATERIALS AND METHODS A modified in vitro system using a coculture of endothelial (EA.hy 926) and colon cancer (LoVo) cell lines was adopted in this study. RESULTS In cytotoxicity assay, SM/SB/TH concentrations causing 20% (IC(20)) inhibition of cellular growth were 41.8 microg/ml/0.22 mM/0.088 mM for EA.hy 926 cells, and 16.1 microg/ml/0.12 mM/0.099 mM for LoVo cells, respectively. All 3 drugs showed concentration dependent inhibition of migration and differentiation assay. The IC(50) inhibiting chemotaxis migration of EA.hy 926 towards LoVo by SM/SB/TH was 1.15 microg/ml/0.66 microM/1.98 microM, respectively. In differentiation assay, SM/SB/TH inhibited in vitro capillary tube formation by 50% at 1.25 microg/ml/2.6 micro/6.3 microM, respectively. In an analysis of vascular endothelial growth factor secreted by LoVo cells, SM/SB/TH decreased 50% secretion at 6.52 microg/ml/6.6 microM/131.7 microM, respectively. CONCLUSION SM/SB has a strong anti-angiogenesis effect on the colon cancer cell line, and this might provide an alternative treatment option for anti-cancer treatment.

Transabdominal Anastomosis After Low Anterior Resection: A Prospective, Randomized, Controlled Trial Comparing Long-Term Results Between Side-to-End Anastomosis and Colonic J-Pouch

PURPOSEColonic J-pouch has been constructed to overcome reservoir dysfunction after restorative rectal surgery, whereas no effort has been made for sphincter dysfunction. We conducted a prospective, randomized study comparing surgical and functional outcomes between side-to-end anastomosis and colonic J-pouch after low anterior resection in which the anastomosis was constructed from the abdomen.METHODSFifty-six consecutive patients with middle-to-low rectal cancer undergoing low anterior resection were randomly assigned to side-to-end or colonic J-pouch group preoperatively. Surgical outcomes of all the patients were recorded. Patients underwent functional evaluation, including anorectal manometry and functional assessment, preoperatively and then 3 months, 6 months, 1 year, and 2 years postoperatively.RESULTSTwenty-four patients in each group completed the study. The demographic data and preoperative functional assessment did not differ between the two groups. There was no significant difference in surgical outcomes with regard to anastomotic height (5 cm), blood loss, protective colostomy, operative time, complications, and adjuvant therapy. Anal pressures showed no significant change postoperatively and during the follow-up period; there were no differences between the two groups. Temporal minor fecal incontinence was noted in the early postoperative period in both groups. With regard to bowel function, a significant reduction of volume of urgency and maximal tolerable volume was found postoperatively in both groups; however, a faster recovery was noted in the colonic J-pouch group. Stool frequency increased significantly after surgery in both groups; however, in contrast to rectal volume, a faster recovery was noted in the side-to-end group.CONCLUSIONSAnastomosis after low anterior resection for middle to low rectal cancer could be performed safely from the abdomen. It minimized sphincter injury and showed good continence preservation. On the other hand, the surgical outcomes and long-term functional results of side-to-end anastomosis were comparable with colonic J-pouch. Side-to-end anastomosis provides an easier, alternative way for reconstruction after restorative rectal surgery.

CIP2A is a predictor of poor prognosis in colon cancer.

PurposeThe cancerous inhibitor of protein phosphatase 2A (CIP2A) oncoprotein is overexpressed in colon cancer tissue compared to normal colon mucosa. We investigated the impact of CIP2A on colon cancer.MethodsA tissue microarray consisting of 167 colon cancer specimens was investigated. The association between CIP2A and clinicopathological parameters was analyzed using the χ2 test. Survival was analyzed using the Kaplan–Meier method. The impact of CIP2A on proliferation and drug resistance was evaluated using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide test. An anchorage-independent colony formation assay was also performed.ResultsCIP2A was an independent prognostic factor in colon cancer after controlling for other clinical confounding factors, such as stage and lymphovascular invasion, particularly in stages III and IV (hazard ratio = 2.974, P < 0.001). The knockdown of CIP2A reduced the proliferation and anchorage-independent colony formation of colon cancer cells. Knockdown of CIP2A decreased the resistance of the cells to 5-fluorouracil, oxaliplatin, and SN38 (an active metabolite of irinotecan). Treatment with 5-fluorouracil, oxaliplatin, and SN38 decreased CIP2A expression.ConclusionsCIP2A is a prognostic factor in colon cancer. The knockdown of CIP2A reduced proliferation and anchorage-independent colony formation and increased 5-fluorouracil, oxaliplatin, and SN38 efficacy in colon cancer cell lines.

BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy

In metastatic colorectal cancer, v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a predictive biomarker for anti‐epidermal growth factor receptor (EGFR) treatment and V‐raf murine sarcoma viral oncogene homolog B1 (BRAF) is a prognostic biomarker. We aimed to determine the impact of KRAS and BRAF mutation as determined from liver metastases specimens on overall survival (OS) in patients following colorectal liver metastasectomy.

The Influence of Fecal Diversion and Anastomotic Leakage on Survival after Resection of Rectal Cancer

BackgroundWe analyzed factors associated with the occurrence of anastomotic leakage (AL) and its impact on long-term survival in patients who have undergone resection for rectal cancer. We also investigated the effect of fecal diversion on survival.MethodClinical data of patients who received surgery for rectal cancer were reviewed. The difference in AL incidence among different groups was compared and survival rates were calculated. Cox’s proportional hazards model was used to compare survival in patients who developed AL or received diversion stoma with those who did not.ResultsOf 999 patients who received resection and anastomosis, 53 patients experienced AL. Multivariate analysis revealed advanced age (P = 0.009) and operative method (P = 0.002) were independent risk factors for AL. Anastomotic leakage was an independent risk factor for overall recurrence (HR 2.30; 95% CI 1.12–4.73). Anastomotic leakage and fecal diversion were independent prognostic factors of overall survival (P = 0.002 and P < 0.001, respectively), cancer-specific survival (P = 0.002 and P < 0.001, respectively), and disease-free survival (P < 0.001, respectively).ConclusionsPatients who are older and have anastomosis at the anorectal junction or dentate line have an increased risk of AL. A diversion stoma does not appear to decrease the incidence of anastomotic leakage, but may decrease the need of reoperation when leakage occurred. Anastomotic leakage and fecal diversion are independent prognostic factors of overall, cancer-specific, and disease-free survival.

Analysis of the seventh edition of American Joint Committee on colon cancer staging

PurposeThe seventh edition of the American Joint Committee on Cancer (AJCC) staging system has new substages for colon cancer. We used survival data from a single medical center to analyze this new AJCC edition.MethodsThe colon cancer database of Taipei Veterans General Hospital provided 1,865 patient records covering from 1999 to 2005. Survival rates were evaluated using the Kaplan–Meier method.ResultsThere were 268, 607, 561, and 421 patients in stages I, II, III, and IV disease with 5-year observed survival rates of 86.3%, 79.2%, 65.4%, and 12.8%, respectively. Survival rates were not significantly different between those with T4a and T4b disease (P = 0.806). The outcome of N1c disease was similar to N1a and N1b but worse than N0 (P = 0.004). Survival rates for M1a and M1b disease became different after reclassifying solely peritoneal seeding as M1a (P < 0.001). No discrepancy of outcomes between stage IIIA and stage IIB/IIC remained in the seventh edition.ConclusionsEvolution from the fifth to seventh edition of the AJCC staging system is successful in separating prognostic groups by substaging. But some issues remain unresolved, including the subdivision of T4, N1, and M1.

Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

BackgroundTo investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT).MethodsBetween 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).ResultsFive-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%).ConclusionsIn 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.

Mutations in the RAS and PI3K pathways are associated with metastatic location in colorectal cancers.

Identification of mutations in the downstream epidermal growth factor receptor (EGFR) signaling pathway could provide important insights of EGFR‐targeted therapies in colorectal cancers. We analyzed the mutation spectra of the PI3K/PTEN/AKT and RAS/RAF/MAPK pathways in colorectal cancers and the associations of these mutations with sites of metastases or recurrence.