Oncological outcome of surgical site infection after colorectal cancer surgery.

BACKGROUND: This study evaluated the oncological outcome of surgical site infection (SSI) after colorectal cancer surgery. METHODS: A total of 3675 consecutive patients with colorectal cancer who underwent curative resection from January 2009 to December 2011 were analyzed. The prognostic significance of SSI was evaluated. Risk factors for SSI were also identified using multivariate regression analysis. RESULTS: Overall SSI rate was 9.6%, in which 5.5% was superficial or deep SSI and 4.1% was organ/space SSI. Incidence of SSI varied significantly with tumor location (P < 0.001): 7.1% in colon cancer and 14.0% in rectal cancer. With a median follow-up period of 49.8 months, the 5-year disease-free survival rates of patients without and with SSI were 87% and 83%, respectively (P = 0.018). SSI predicted disease-free survival in univariate analysis. However, SSI was not an independent predictor of survival in multivariate analysis. Body mass index, ASA score, preoperative WBC count, rectal tumor, open surgery, operation time, and transfusion during surgery were independent predictors of SSI. CONCLUSION: SSI predicted disease-free survival in colorectal cancer patients following curative surgery. Patient' demographics, tumor characteristics, and perioperative conditions were independently associated with an increased likelihood of SSI.

Prognostic Impact of Tumor-Budding Grade in Stages 1-3 Colon Cancer: A Retrospective Cohort Study.

BACKGROUND: Tumor budding is associated with adverse histology and is a predictor of lymph node metastasis. However, it remains unclear whether tumor budding is predictive of a poor prognosis for colon cancer patients. This study sought to investigate the prognostic significance of tumor budding in colon cancer. METHODS: This study evaluated 4196 colon cancer patients who underwent radical surgery from 2007 to 2013 at a single institution. The patients were categorized according to tumor-budding status. Adjustment was made for using propensity score-matched analysis, and both disease-free survival (DFS) and overall survival (OS) were compared between the groups. RESULTS: Among the 4196 patients, 2269 had low budding (< 5 buds), 1312 had intermediate budding (5-9 buds), and 615 had high budding (≥ 10 buds). High budding was associated with adverse histologic features such as elevated levels of preoperative carcinoembryonic antigen, advanced stage, poor histology, and the presence of lymphatic/vascular/perineural invasion. Before matching, DFS and OS decreased significantly with increasing tumor budding. After matching, the difference in survival between the low- and intermediate-budding groups disappeared. However, the OS and DFS rates for the high-budding group were significantly lower than for the other two groups. In the multivariate analysis of prognostic factors, high budding was an independent poor prognostic factor in DFS and OS, whereas tumor-budding positivity itself was not an independent prognostic factor. CONCLUSION: Tumor-budding grade rather than tumor-budding positivity was an independent prognostic factor in colon cancer.

Oncologic outcome of colorectal cancer patients over age 80: a propensity score-matched analysis.

PURPOSE: It remains unclear whether old age is a poor prognostic factor in colorectal cancer (CRC). We compared oncologic outcomes in CRC patients according to age, using 80 as the dividing point. METHODS: CRC patients who underwent radical surgery from 2000 to 2011 were evaluated. We performed matched and adjusted analyses comparing oncologic outcomes between patients with ≥ 80 and < 80 years old. RESULTS: Among 9562 patients, 222 were elderly. The median age was 82.0 years in elderly patients and 59.0 years in young patients. Elderly patients received less neoadjuvant or adjuvant therapy compared to young patients (p < 0.001). After recurrence, significantly fewer elderly patients received additional treatments (p < 0.001). Before matching, disease-free survival (DFS) and cancer-specific survival (CSS) were significantly lower for elderly patients compared to those for young patients (p < 0.001 and p < 0.001, respectively). After matching, DFS and CCS were not significantly different between the two groups (p = 0.400 and p = 0.267, respectively). In a multivariate analysis for prognostic factors, old age was not an independent poor prognostic factor of DFS and CCS (p = 0.619 and p = 0.137, respectively). CONCLUSIONS: Elderly patients aged ≥ 80 years with CRC had similar oncologic outcome to young patients, and age was not an independent prognostic factor.

Laparoscopic modified mesocolic excision with central vascular ligation in right-sided colon cancer shows better short- and long-term outcomes compared with the open approach in propensity score analysis.

BACKGROUND: The introduction of complete mesocolic excision (CME) with central vessel ligation (CVL) for right-sided colon cancer has improved oncologic outcomes. However, there is controversy over the oncologic safety of laparoscopic CME with CVL. This study compared short-term and long-term oncologic outcomes between laparoscopic and open modified CME (mCME) with CVL in patients with right-sided colon cancer. METHODS: We enrolled 1239 patients who underwent open mCME with CVL and 1010 patients treated by a laparoscopic approach for right-side colon cancer between 2000 and 2013 and used 1:1 propensity score matching to adjust for potential baseline confounders between two groups. RESULTS: After propensity score matching, 683 patients who underwent open mCME with CVL were compared with 683 patients treated with a laparoscopic approach. There were no significant differences between these groups in age, sex, ASA score, TNM stage, tumor size, lymphovascular invasion, and perineural invasion. Comparison of open and laparoscopic mCME groups showed no significant difference in postoperative morbidity (21.4 vs. 18.3%, p = 0.175) and mortality (0.1 vs. 0%, p = 1.000). The laparoscopic mCME group showed shorter length of hospital stay. The 5-year overall survival rate was 83.7% in the open group and 94.7% in the laparoscopic group (p < 0.001). The laparoscopic group also showed a significantly better 5-year disease-free survival rate (82.7 vs. 88.7%, p = 0.009) and 5-year disease-specific survival rate (83.7 vs. 94.7%, p < 0.001). CONCLUSION: Laparoscopic modified mesocolic excision with central vascular ligation is a safe and feasible approach with better short-term recovery profiles and potential oncologic benefits than the open approach for right-sided colon cancer.

Prospective analysis of delayed colorectal post-polypectomy bleeding.

BACKGROUNDS/AIMS: Although post-polypectomy bleeding is the most frequent complication after colonoscopic polypectomy, only few studies have investigated the incidence of bleeding prospectively. The aim of this study was to investigate the incidence of delayed post-polypectomy bleeding and its associated risk factors prospectively. METHODS: Patients who underwent colonoscopic polypectomy at Kangbuk Samsung Hospital from January 2013 to December 2014 were prospectively enrolled in this study. Trained nurses contacted patients via telephone 7 and 30 days after polypectomy and completed a standardized questionnaire regarding the development of bleeding. Delayed post-polypectomy bleeding was categorized as minor or major and early or late bleeding. Major delayed bleeding was defined as a > 2-g/dL drop in the hemoglobin level, requiring hospitalization for control of bleeding or blood transfusion; late delayed bleeding was defined as bleeding occurring later than 24 h after polypectomy. RESULTS: A total of 8175 colonoscopic polypectomies were performed in 3887 patients. Overall, 133 (3.4%) patients developed delayed post-polypectomy bleeding. Among them, 90 (2.3%) and 43 (1.1%) patients developed minor and major delayed bleeding, respectively, and 39 (1.0%) patients developed late delayed bleeding. In the polyp-based multivariate analysis, young age (< 50 years; odds ratio [OR] 2.10; 95% confidence interval [CI] 1.18-3.68), aspirin use (OR 2.78; 95% CI 1.23-6.31), and polyp size of > 10 mm (OR 2.45; 95% CI 1.38-4.36) were significant risk factors for major delayed bleeding, while young age (< 50 years; OR 2.6; 95% CI 1.35-5.12) and immediate bleeding (OR 3.3; 95% CI 1.49-7.30) were significant risk factors for late delayed bleeding. CONCLUSIONS: Young age, aspirin use, polyp size, and immediate bleeding were found to be independent risk factors for delayed post-polypectomy bleeding.

Prospective Analysis of Minor Adverse Events After Colon Polypectomy.

BACKGROUND: The risks of minor adverse events (MAEs) such as abdominal pain and bloating after colon polypectomy (CP) are less clearly documented than major adverse events. However, these complications may cause significant discomfort during the performance of normal activities. We aimed to estimate the incidence of MAE, associated risk factors, and healthcare resource utilization after CP. METHODS: Patients who underwent CP were prospectively enrolled in this study. Trained nurses contacted patients by telephone at 7 and 30 days after the CP and administered a standardized questionnaire to obtain information regarding the development of complications. MAEs were defined as any discomfort the patient experienced after CP excluding major bleeding, perforation, and post-polypectomy coagulation syndrome. RESULTS: Among a total of 2716 patients, 2253 patients completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%) before day 7, among which the most common were abdominal pain (4.5%), rectal bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267 patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.58-3.18) and use of meperidine (OR 1.54, 95% CI 1.04-2.27) were risk factors for the occurrence of MAEs. Two patients (0.7%) required hospital admission, 117 patients (43.8%) were treated medically in the outpatient clinic, and the majority at 148 patients (55.4%) experienced resolution of symptoms after observation. CONCLUSIONS: The post-CP MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven postoperative days and resulted in little use of healthcare resources.

Clinically suspected T4 colorectal cancer may be resected using a laparoscopic approach.

BACKGROUND: The role of laparoscopic resection in patients with clinically suspicious T4 colorectal cancer remains controversial. The aim of this study was to compare the long-term and oncologic outcomes of laparoscopic resection and the open approach in clinical T4 colorectal cancer. METHODS: Two hundred ninety-three consecutive patients undergoing curative surgery for colorectal cancer suspected to be T4 by computed tomography and/or magnetic resonance imaging were reviewed. RESULTS: Despite clinical suspicion of T4 disease in all cases, concordance with pathologic determination of T4 was only 37.9 %. Of the 71 patients in the laparoscopic group, four (5.6 %) were converted to the open technique. Patients in the laparoscopic group had significantly lower estimated blood loss (p < 0.001), fewer days to first flatus (p = 0.001), shorter length of hospital stay (p < 0.001), and fewer adverse events (14.1 % versus 31.5 %, p = 0.004). After a median follow-up of 36 months, 5-year disease-free survival was not significantly different between the two groups (81.8 % in laparoscopic versus 73.9 % in open surgery, p = 0.433). The clinical factors that predicted T4 staging on pathologic examination were found to be male sex (p = 0.038), preoperative carcinoembryonic antigen status (p = 0.021), clinical N status (p = 0.046), and clinical cancer perforation (p = 0.004). CONCLUSIONS: Laparoscopic colorectal resection for T4 colorectal cancer has perioperative and long-term oncologic outcomes similar to those of the open approach when performed by an experienced surgeon.

A comparison of hand-assisted laparoscopic surgery and conventional laparoscopic surgery in rectal cancer: a propensity score analysis.

PURPOSE: The aim of this study was to compare oncologic outcomes and perioperative variables following conventional laparoscopic surgery (LAP) versus hand-assisted laparoscopic surgery (HALS) for rectal cancer. METHODS: Between January 2008 and December 2012, 2680 consecutive patients who underwent curative resection for rectal cancer were analyzed. We used 1:1 propensity score matching to adjust for potential baseline confounders between groups including age, sex, body mass index, American Society of Anesthesiologists score, tumor distance from the anal verge, clinical T and N categories, pathologic T and N categories, preoperative carcinoembryonic antigen level, and the status of preoperative concurrent chemoradiotherapy. After matching, we analyzed 278 patients in each group (n = 556). RESULTS: The median follow-up period was 36.2 and 37.4 months in the HALS group and the conventional LAP group, respectively. Postoperative complications were not significantly different between the two groups (P = 0.531). The 5-year overall survival rate was 88.8 % in the HALS group and 91.2 % in the conventional LAP group (P = 0.329). The 5-year disease-free survival rate was 77.0 % in the HALS group and 79.7 % in the conventional LAP group (P = 0.591). CONCLUSIONS: HALS is considered a safe and feasible approach for rectal cancer treatment that enables the preservation of the advantages of conventional laparoscopic surgery.

Scoring Systems Used to Predict Bladder Dysfunction After Laparoscopic Rectal Cancer Surgery.

BACKGROUND: Postoperative bladder dysfunction often occurs after rectal cancer surgery, necessitating long-term urinary catheter drainage. The aim of this study was to evaluate the feasibility of early catheter removal and to propose scoring systems that may predict urinary dysfunction after laparoscopic rectal cancer surgery. METHODS: A total of 110 patients who underwent elective laparoscopic rectal cancer surgery were included in this prospective observational study. The urinary catheter was removed on the first postoperative day. RESULTS: The overall incidence of bladder dysfunction was 29.1 % (32/110). The incidence of bladder dysfunction was significantly higher in patients with an age of 65 years or older, male gender, and anastomosis levels from the anal verge of 6 cm or below (P = 0.03, 0.002, and 0.03, respectively). By setting a cut-off of two of the risk factors, this simple scoring system can predict postoperative bladder dysfunction with sensitivity of 96.9 %, specificity of 50.0 %, and accuracy of 63.6 %. A scoring system based on regression coefficients was also conducted according to the following formula: bladder dysfunction predicting score = 18 (1 for male or 0 for female) +0.5 (age, years) -2 (anastomosis level, cm). With this method, a cut-off value of 35+ points predicts postoperative bladder dysfunction with a sensitivity of 81.3 %, specificity of 71.8 %, and accuracy of 74.5 %. CONCLUSIONS: Bladder dysfunction after laparoscopic rectal cancer surgery following early catheter removal occurred in 29.1 % of patients. Two scoring systems using three risk factors (age, male gender, and anastomosis level) may predict postoperative bladder dysfunction.

Is Chemoradiotherapy Beneficial for Stage IV Rectal Cancer?

PURPOSE: The aim of this study was to investigate the oncologic impact of preoperative or postoperative chemoradiotherapy on stage IV rectal cancer. METHODS: A total of 140 consecutive patients with locally advanced mid-to-lower rectal cancer and resectable stage IV disease were prospectively enrolled. In total, 69 patients received chemoradiotherapy (26 preoperatively and 43 postoperatively); in contrast, 71 did not. Survival curves were constructed using the Kaplan-Meier method, and a multivariate analysis was performed to identify independent prognostic factors. RESULTS: According to the multivariate analysis, radiation therapy was not an independent factor associated with either survival or recurrence. The overall survival curves revealed that patients who underwent radiotherapy tended to have a better survival compared with patients who did not undergo radiotherapy; however, this trend was not statistically significant (p = 0.057). The disease-free, local recurrence-free, and distant metastasis-free survival curves did not differ significantly between the two groups. The local recurrence-free survival rates for patients who underwent preoperative radiotherapy were significantly higher than those for patients who underwent postoperative radiotherapy (p = 0.042). CONCLUSION: Preoperative radiotherapy, rather than postoperative radiotherapy, may improve local control of stage IV rectal cancer. However, chemoradiotherapy did not improve the survival of patients with stage IV rectal cancer in this study.

Features of Late Recurrence Following Transanal Local Excision for Early Rectal Cancer.

BACKGROUND: Transanal local excision has recently received attention as an alternative to radical surgery for early rectal cancer. Recurrence usually occurs within 5 years after surgery, but recurrences later than this have also been reported. OBJECTIVE: The aim of this study was to investigate the incidence and risk factors of recurrence in patients who have early rectal cancer 10 years after transanal local excision. DESIGN: Patients with early rectal cancer who underwent transanal local excision from October 1994 to December 2010 were retrospectively reviewed. We reviewed the demographics and clinicopathologic features of primary lesions and analyzed the incidence and risk factors of recurrence. SETTINGS: This investigation was conducted at a tertiary university hospital. PATIENTS: A total of 295 patients who underwent transanal local excision for pTis (n = 155) or pT1 (n = 140) early rectal cancer were included in the analysis. INTERVENTION: Transanal local excision was performed for each patient to excise primary rectal lesions. MAIN OUTCOME MEASURES: The primary end point of this study was the incidence of recurrence, especially late recurrence. The secondary end point was risk factors for recurrence. RESULTS: The 10-year cumulative local recurrence rate was 6.7% in pTis and 18.0% in pT1 patients. The rate of late local recurrence was 2.8% in pTis and 3.7% in pT1 patients. There was no evidence of late systemic recurrence 5 years after transanal local excision. In pT1 patients, a higher risk of recurrence was associated with an invasion depth of sm3, the presence of lymphovascular invasion, and a positive resection margin. LIMITATION: The main limitation of this study is its retrospective nature. CONCLUSIONS: Late recurrence can occur in patients with early rectal cancer who have undergone transanal local excision. Transanal local excision can be performed in selective patients with biologically favorable tumors, and 10-year postoperative surveillance should be considered for these patients.

Adjuvant chemotherapy after neoadjuvant chemoradiation and curative resection for rectal cancer: is it necessary for all patients?

BACKGROUND: The benefit of adjuvant chemotherapy for patients with locally advanced rectal cancer who have received neoadjuvant concurrent chemoradiation therapy (CCRT) and undergone curative resection remains unclear. METHODS: This study was a retrospective review of prospectively collected data. Patients with locally advanced rectal cancer who underwent curative surgery after neoadjuvant CCRT between January 2006 and March 2011 were identified. Four hundred forty-one patients who completed adjuvant chemotherapy (chemo group) were compared with 35 patients who did not receive any adjuvant treatment (nonchemo group). RESULTS: The 5-year disease-free survival (DFS) was significantly higher in the chemo group (78.5% vs. 63.1%, P = 0.016). After stratification of the patients according to nodal status, these differences were no longer significant, but there were trends toward inferior DFS in the nonchemo group in all survival curves. In multivariate Cox regression analysis, no adjuvant chemotherapy (HR, 2.306; 95% CI, 1.101-4.829; P = 0.027) emerged as an independent prognostic factor associated with decreased DFS. CONCLUSIONS: Adjuvant chemotherapy was significantly associated with increased DFS among patients who had undergone neoadjuvant CCRT and radical resection for locally advanced rectal cancer. Adjuvant chemotherapy should be considered in every patient after neoadjuvant CCRT irrespective of the final pathology stage.

Laparoscopic versus open reintervention for anastomotic leakage following minimally invasive colorectal surgery.

PURPOSE: The aim of this study is to evaluate the safety and feasibility of laparoscopic reintervention compared with open surgery in patients with anastomotic leakage after minimally invasive colorectal surgery. METHODS: Between January 2008 and December 2012, 77 patients who required surgical reintervention for anastomotic leakage following minimally invasive colorectal surgery were included in this study. Data on the patients' demographics, operative management, morbidity, hospital stay, and mortality were analyzed for differences based on whether they received laparoscopic or open surgery. RESULTS: Sixteen patients underwent open surgery following laparoscopy, and 61 patients received laparoscopic reintervention following laparoscopy. The conversion rate was 8.2 % (5/61). The median total hospital stay following reintervention was significantly shorter for laparoscopic surgery (16.0 days, range 9-117 days) than for open surgery (35.5 days, range 10-135 days, p < 0.001). The postoperative 30-day morbidity rate, including wound dehiscence (25.0 vs 3.3 %, p = 0.015) and intra-abdominal infection (31.3 vs 6.6 %, p = 0.016), was lower in the laparoscopic surgery group than in the open surgery group. The rate of stoma closure was lower in the open surgery group than in the laparoscopic surgery group (43.8 vs 80.5 %, p < 0.001). There was one in-hospital mortality in the open surgery group. CONCLUSIONS: Laparoscopic reintervention for anastomotic leakage following minimally invasive colorectal surgery is associated with a shorter hospital stay, fewer postoperative complications, and a higher stoma closure rate than open surgery. Laparoscopic reintervention for anastomotic leakage is feasible and safe.

Human Noxin is an anti-apoptotic protein in response to DNA damage of A549 non-small cell lung carcinoma.

Human Noxin (hNoxin, C11Orf82), a homolog of mouse noxin, is highly expressed in colorectal and lung cancer tissues. hNoxin contains a DNA-binding C-domain in RPA1, which mediates DNA metabolic processes, such as DNA replication and DNA repair. Expression of hNoxin is associated with S phase in cancer cells and in normal cells. Expression of hNoxin was induced by ultraviolet (UV) irradiation. Knockdown of hNoxin caused growth inhibition of colorectal and lung cancer cells. The comet assay and western blot analysis revealed that hNoxin knockdown induced apoptosis through activation of p38 mitogen-activated protein kinase (MAPK)/p53 in non-small cell lung carcinoma A549 cells. Furthermore, simultaneous hNoxin knockdown and treatment with DNA-damaging agents, such as camptothecin (CPT) and UV irradiation, enhanced apoptosis, whereas Trichostatin A (TSA) did not. However, transient overexpression of hNoxin rescued cells from DNA damage-induced apoptosis but did not block apoptosis in the absence of DNA damage. These results suggest that hNoxin may be associated with inhibition of apoptosis in response to DNA damage. An adenovirus expressing a short hairpin RNA against hNoxin transcripts significantly suppressed the growth of A549 tumor xenografts, indicating that hNoxin knockdown has in vivo anti-tumor efficacy. Thus, hNoxin is a DNA damage-induced anti-apoptotic protein and potential therapeutic target in cancer.

Should preoperative chest CT be recommended to all colon cancer patients?

OBJECTIVE: The aim of this study was to evaluate the efficacy of preoperative chest computed tomography (CT) and the risk factors for lung metastasis in colon cancer patients without liver metastasis who had negative findings on initial chest X-ray (CXR). BACKGROUND: Preoperative staging with chest CT is recommended in colon cancer patients. However, there have been only scant data on the clinical efficacy. METHODS: Three hundred nineteen consecutive colon cancer patients without liver metastasis were retrospectively reviewed and analyzed. The patients had negative findings on preoperative CXR, and they underwent surgery for colon cancer during the period of January 2008 to April 2010. RESULTS: Lung nodule on chest CT was found in 136 patients (42.6%). Twenty of those were definitely diagnosed with lung metastasis (6.3%) by follow-up chest CT or pathologic confirmation. There was no case of delay in surgery due to findings of lung nodule. Comparing the group with lung metastases to that without lung metastases, postoperative pathologic findings reported more advanced T and N status (P = 0.004, P < 0.001, respectively), and lymphatic invasion was more frequent (P = 0.003) in the group with lung metastasis. By multivariate analysis, CT-predicted lymph node metastases and pathologic lymph node metastases were risk factors for lung metastases. CONCLUSIONS: Preoperative staging chest CT is not beneficial to colon cancer patients without liver metastasis and lymph node metastasis suggested on abdominal and pelvic CT who had negative finding on initial CXR.

Recurrence pattern depends on the location of colon cancer in the patients with synchronous colorectal liver metastasis.

BACKGROUND: The veins from the lower rectum drain into the systemic venous system, while those from other parts of the colon drain into the portal venous system. The aim of this study was to investigate recurrence pattern and survival according to the anatomical differences in patients with colorectal liver metastases (CRLM). METHODS: From October 1994 to December 2009, synchronous CRLM patients who underwent surgery were identified from our prospectively collected database. The patients were excluded if there had been extrahepatic metastases. The patients were divided into two groups according to the location of the primary colorectal cancer: lower rectal cancer (group 1) and upper rectal or colon cancer (group 2). The recurrence patterns and survival were investigated. RESULTS: A total of 316 patients were included: 53 patients in group 1 and 263 patients in group 2. After a median follow-up of 37 months, the extrahepatic recurrence curve of group 1 was superior to that of group 2 (P < 0.001), although there was no difference between the hepatic recurrence curves (P = 0.93). The disease-free and overall survival curves of group 1 were inferior to those of group 2 (P = 0.004) (P < 0.001). Lower rectal cancer was a significant risk factor for extrahepatic recurrence in Cox proportional hazard model analysis (hazard ratio = 1.7, P = 0.04). CONCLUSIONS: The extrahepatic recurrence rate is high in lower rectal cancer patients after surgical treatment for synchronous CRLM.

Loss of E-Cadherin expression is associated with a poor prognosis in stage III colorectal cancer.

PURPOSE: The epithelial-mesenchymal transition (EMT) is known to be associated with tumor progression, invasion and metastasis in colorectal cancer (CRC). MATERIALS AND METHODS: Tissue samples obtained from 409 patients with stage III CRC treated from 2006 to 2007 were examined by immunohistochemistry to reveal the expression levels of E-cadherin, fibronectin, vimentin and α-smooth muscle actin (SMA). RESULTS: Among the 409 patients, 402 cases (98.3%) showed positive E-cadherin expression. Positive E-cadherin expression was associated with well or moderately differentiated cell types and a stable microsatellite status. In multivariate analysis, a preoperative carcinoembryonic antigen level >5 ng/ml (p = 0.021), advanced N stage (p = 0.017), positive vascular invasion (p = 0.048), positive perineural invasion (p = 0.002) and negative E-cadherin expression (p = 0.002, relative risk = 5.098, 95% CI = 1.801-14.430) were poor prognostic factors affecting disease-free survival. The declining E-cadherin expression was associated with a poor outcome in terms of overall survival in univariate (p = 0.016) but not in multivariate analyses (p = 0.303, relative risk = 1.984, 95% CI = 0.539-7.296). Fibronectin, vimentin and α-SMA were of no prognostic value in this study. CONCLUSION: The expression pattern of EMT markers in stage III CRC suggests that declining E-cadherin expression is a possible immunohistochemical predictor of patient prognosis.

Low expression of transforming growth factor beta-1 in cancer tissue predicts a poor prognosis for patients with stage III rectal cancers.

OBJECTIVE: Transforming growth factor beta (TGF-ß) plays an important role in tumorigenesis and metastasis. It works as a tumor suppressor in the normal colon, but acts as a cancer promoter during the late stages of colorectal carcinogenesis. High expression of TGF-ß is known to be associated with advanced stages, tumor recurrence and decreased survival of patients. We investigated the expression of TGF-ß and its signaling axis molecules and evaluated their prognostic significance in patients with stage III rectal cancers. METHODS: Tissues from 201 cases of stage III rectal cancer were subjected to immunohistochemistry for TGF-ß1, type II TGF-ß receptor, Smad3, Smad4 and Smad7 proteins. The immunoactivities of these molecules were evaluated and the results were compared with clinicopathological variables including patient survival. RESULTS: Low expression of TGF-ß1 protein was correlated with a decreased disease-free survival in univariate Kaplan-Meier (p = 0.003) and multivariate Cox regression (HR 9.188 and 95% CI 1.256-67.198, p = 0.029) analyses. The loss of Smad4 protein expression was associated with a reduction in disease-free survival in the univariate analysis, but this finding was not significant after the multivariate analysis. CONCLUSION: Low expression of TGF-ß1 protein is associated with a poor prognosis for patients with stage III rectal cancers.

The role of palliative resection for asymptomatic primary tumor in patients with unresectable stage IV colorectal cancer.

BACKGROUND: The prognostic role of surgical resection of primary tumors is not well established in patients with asymptomatic unresectable stage IV colorectal cancer. OBJECTIVE: The aims of this study were to reveal the prognostic role of surgical resection of primary tumors and to define prognostic factors affecting long-term oncological outcomes in patients with asymptomatic unresectable synchronous metastases. DESIGN: This study was a retrospective analysis of prospectively collected data. PATIENTS: Between 2000 and 2008, a total of 416 patients with asymptomatic unresectable stage IV colorectal cancer were analyzed with propensity score matching. MAIN OUTCOME MEASURES: Prematching baseline characteristics were compared by bivariate analysis, and 113 pairs were selected after 1:1 matching with propensity scores estimated from logistic regression. The primary end point was overall survival. RESULTS: Among 416 patients, 218 (52.4%) underwent palliative resection of the primary tumor. Before propensity score matching, palliative resection resulted in a better survival rate than nonresection in univariate analysis (p < 0.001), but not in multivariate analysis (p = 0.08). After matching, the 5-year overall survival rate was significantly lower for patients with peritoneal metastasis and clinical M1b stage tumors in univariate analysis (p = 0.004 and p = 0.02). However, neither peritoneal metastasis nor clinical M1b stage showed any prognostic significance in multivariate analysis. The overall 5-year survival rate of the postmatching group was 4.9% and 3.5% in the palliative resection and nonresection groups. Consequently, palliative resection was not associated with a significant increase in survival compared with nonresection (p = 0.27). A subgroup analysis performed according to the site of metastasis also did not show any significant survival benefit of palliative resection after matching. LIMITATIONS: Selection bias and potential confounders were limitations of this study. CONCLUSIONS: Resection of the primary tumor in patients with asymptomatic unresectable stage IV colorectal cancer was not associated with an improvement in overall survival after propensity score matching.

A circumferential resection margin of 1 mm is a negative prognostic factor in rectal cancer patients with and without neoadjuvant chemoradiotherapy.

BACKGROUND: There is ongoing debate about the appropriate criterion for defining a positive circumferential resection margin after radical surgery for rectal cancer. OBJECTIVE: The purpose of this work was to determine the importance of the extent of the circumferential resection margin with regard to outcomes in patients with rectal cancer who underwent total mesorectal excision with and without neoadjuvant chemoradiotherapy. DESIGN: This was a retrospective review of prospectively collected data. SETTINGS: The study was conducted in a tertiary care hospital. PATIENTS: We reviewed the medical charts of 780 patients with rectal cancer who underwent radical surgery from 2004 to 2009. There were 599 patients (76.8%) who did not receive neoadjuvant chemoradiotherapy and 181 patients (23.2%) who did. MAIN OUTCOME MEASURES: The relationship between the extent of the circumferential resection margin (0.5, 1.0, 2.0, and 3.0 mm) and recurrence and survival was assessed. RESULTS: Among circumferential resection margins ≤0.5, ≤1.0, ≤2.0, and ≤3.0 mm, the HR was highest and disease-free survival was longest for a circumferential resection margin ≤1 mm in both the chemoradiotherapy and nonchemoradiotherapy groups. A circumferential resection margin ≤1 mm, lymphatic invasion, histology, pathologic T category, pathologic N category, preoperative CEA, and adjuvant chemotherapy were independent predictors of disease-free survival in the nonchemoradiotherapy group. In the chemoradiotherapy group, a circumferential resection margin ≤1 mm and histology were independent predictors of disease-free survival. Multivariate analysis revealed that a circumferential resection margin ≤1 mm was an independent prognostic factor for overall survival in both of the 2 groups. LIMITATIONS: This was a single-institution, retrospective study. CONCLUSIONS: A circumferential resection margin of ≤1 mm had a strong association with disease-free survival compared with circumferential resection margins ≤0.5, ≤2.0, and ≤3 mm. A circumferential resection margin ≤1 mm was an independent predictor of a poor outcome in both the nonchemoradiotherapy and chemoradiotherapy groups.