Identification of Patients with High-Risk Stage II Colon Cancer for Adjuvant Therapy

Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. Methods We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. Results With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1–6.2; P = 0.02), preoperative carcinoembryonic antigen >5 ng/ml (HR, 2.1; 95 percent CI, 1.1–4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1–4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent. Conclusions Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not avaliable.     

Tumor Budding as an Index to Identify High-Risk Patients with Stage II Colon Cancer

Purpose High-risk patients with Stage II colon cancer may benefit from adjuvant chemotherapy, but they are difficult to identify. We assessed the value of tumor budding, defined as small clusters of undifferentiated cancer cells at invasive margins, as a predictor of outcomes in patients with Stage II colon cancer. Methods We studied a total of 200 patients with Stage II colon cancer who underwent curative surgery. With hematoxylin and eosin-stained specimens, the degree of tumor budding was classified as low-grade or high-grade. The survival rate of patients who had Stage II disease with low-grade or high-grade tumor budding was compared with that of 226 patients who had Stage III colon cancer. Results Univariate analysis revealed that serosal surface involvement (P = 0.04) and tumor budding (P < 0.001) were significantly related to survival. Cumulative five- and ten-year survival rates differed significantly between patients with low-grade tumor budding (93.9 and 90.6 percent, respectively) and those with high-grade (73.9 and 67.8 percent, respectively). Survival rates did not differ significantly between patients with Stage II disease who had high-grade tumor budding and patients with Stage III disease. Cox’s regression analysis demonstrated that tumor budding (hazard ratio, 4.89; P < 0.001) and serosal surface involvement (hazard ratio, 2.561; P = 0.023) were independent prognostic factors. Liver (P < 0.001) and peritoneal (P = 0.003) metastases were more frequent in the patients with high-grade tumor budding than in those with low-grade. Conclusions Tumor budding is useful for prognosis and identifying patients with Stage II colon cancer who have a high risk of disease recurrence after curative surgery.     

DNA Ploidy Status and Prognosis in Colorectal Cancer: A Meta-Analysis of Published Data

Purpose In colorectal cancer, the negative effect of aneuploidy has been a controversy for more than 20 years. Studies to determine a survival-deoxyribonucleic acid content relationship have conflicting results. A systematic literature search followed by a meta-analysis of published studies addressing prognostic effect of aneuploidy for patients who underwent surgical treatment of colon and rectal cancer was conducted. Methods The main outcome measure was the five-year overall mortality rate after surgical resection. For the selected studies, we estimated this outcome for three subsets of patients through separate meta-analyses: 1) for all patients with colorectal cancer; 2) only between patients with Stage II colon cancer; and 3) only for studies in which follow-up losses were declared. The presence of publication bias was assessed with a funnel plot for asymmetry. Results A total of 5,478 patients with colorectal cancer were represented in 32 studies (Group 1), we estimated a reduction in the five-year overall mortality from 43.2 percent for aneuploid tumors to 29.2 percent for diploid tumors (combined relative risk = 1.44; 95 percent confidence interval = 1.34–1.55; P < 0.001). In addition, 357 patients with Stage II colon cancer (Group 2) extracted from three studies had an absolute reduction of 14.3 percent in five-year overall mortality favoring diploid tumors (combined relative risk = 1.93; 95 percent confidence interval = 1.29–2.89; P = 0.001). Lastly, of 14 studies in which follow-up losses were declared (Group 3), 2,221 patients were represented and a 15.7 percent mortality reduction was measured favoring patients with diploid tumors (combined relative risk = 1.44; 95 percent confidence interval = 1.3–1.61; P < 0.001). Conclusions Patients who undergo an aneuploid colorectal cancer surgical resection have a higher risk of death after five years. This finding may ultimately impact survival of patients with node-negative colon cancer through adjuvant therapy. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 3 to 7, 2006.     

Local recurrence after curative resection in patients with colon and rectal cancers

Background and aims  There are a range of rates and a number of prognostic factors associated with the local recurrence of colorectal cancer after curative resection. The aim of this study was to identify the potential prognostic factors of local recurrence in patients with colon and rectal cancers. Materials and methods  A retrospective review of 1,838 patients who underwent curative resection of non-metastatic colorectal cancer was conducted. The patients were treated between 1994 and 2004, and had a minimum follow-up of 3 years. Results  There were 994 patients with colon cancer and 844 patients with rectal cancer. The median duration of follow-up was 60.9 ± 24.5 months. With respect to colon cancer, the local recurrence rate was 6.1% (61 patients). With respect to rectal cancer, 95 patients had a local recurrence (11.3%), the rate of which was statistically greater than the local recurrence rate for colon cancer (p < 0.001). The overall recurrence rate was 16.4% (301 patients), and the local recurrence rate, with or without systemic metastases, was 8.5% (156 patients). Local recurrences occurred within 2 and 3 years in 59.9% and 82.4% of the patients, respectively. In patients with colon and rectal cancer, the pathologic T stage (p = 0.044 and p = 0.034, respectively), pathologic N stage (p = 0.001 and p < 0.001, respectively), and lymphovascular invasion (p = 0.013 and p = 0.004, respectively) were adverse risk factors for local recurrence. The level of the anastomosis from the anal verge was an additional prognostic factor (p = 0.007) in patients with rectal cancer. Conclusion  Compulsive follow-up care of patients with colon and rectal cancers is needed for 3 years after curative resection, especially in patients who have adverse risk factors for local recurrence.     

The prognostic factors of stage IV colorectal cancer and assessment of proper treatment according to the patient’s status

Background and aims Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV. The majority has non-curative metastases, and their chances of survival are pitiful. This study evaluated the prognostic factors of survival and the access to the effective treatment in accordance with patients. Materials and methods We retrospectively analyzed 503 patients for demographics, tumor characteristics, the treatment modality, and the survival outcome. Curative operation was performed in 127 patients and palliative operation in 376 patients. Results For the curative operation group, the 5-year survival rate was 34.5%, and the prognostic factors of survival and recurrence were male gender (p = 0.003, 0.009), pathologic N stage (p < 0.001, p = 0.002), and perineural invasion (p = 0.003, p = 0.026), respectively. For the non-curative operation group, the 5-year survival rate was 0%, and the median survival duration was 16.5 months. The potential predictors of survival for the palliative operation group were carcinoembryonic antigen level (p = 0.013), differentiation of tumor (p = 0.011), resection of primary tumor (p < 0.001), and chemotherapy (p < 0.001). But for the 131 patients with asymptomatic incurable disease, only chemotherapy was related to survival (p < 0.001). Conclusions The potential predictors of survival for curative stage IV colorectal cancer were male gender, pathologic N stage, and perineural invasion. Resection of the primary tumor and chemotherapy showed benefit for the incurable patients. But for the asymptomatic incurable patients, only chemotherapy prolonged the survival. This study was presented at the 21st Biennial Congress of International Society of the University of Colon and Rectal Surgeons held in Istanbul, Turkey in June 2006.     

Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer

Background and aims The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy. Materials and methods We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA] > 5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed. Results Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p = 0.001), showing a statistically significant correlation (r = 0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR = 3.53 [1.13–10.90], p = 0.02), age (OR = 1.09 [1.01–1.18], p = 0.03), Dukes stage (OR = 1.93 [1.01–3.70]), caspase-3 activity in normal mucosa (OR = 1.02 [1.01–1.04], p = 0.017) and caspase-3 activity in tumour (OR = 1.02 [1.01–1.03], p = 0.013). Conclusion Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.     

Prognostic Significance of Receptor-Binding Cancer Antigen Expressed on SiSo Cells (RCAS1) Expression in Relation to Cadherin Expression in Patients with Colorectal Carcinoma

Purpose This study was designed to assess the prognostic value of receptor-binding cancer antigen expressed on SiSo cells expression and its relationship with cadherin expression in patients with colorectal cancer. Methods The expressions of receptor-binding cancer antigen expressed on SiSo cells and E-cadherin were analyzed with special reference to prognosis in 105 patients with colorectal cancer. Results Receptor-binding cancer antigen expressed on SiSo cells immunoreactivity was detected in the membrane and cytoplasm of tumor cells and considered to be positive in 48 patients (45.7 percent). The expression of receptor-binding cancer antigen expressed on SiSo cells was significantly correlated with lymph node metastasis (P = 0.0004), venous invasion (P = 0.0062), Dukes stages (P < 0.0001), and serum levels of carcinoembryonic antigen (P = 0.014). Furthermore, receptor-binding cancer antigen expressed on SiSo cells expression was significantly correlated with a poor prognosis (P < 0.001), and multivariate analysis indicated that it was an independent prognostic indicator. The expression of receptor-binding cancer antigen expressed on SiSo cells was more frequently found in tumors with reduced or abnormal expression of E-cadherin. The survival time of patients with reduced/abnormal E-cadherin expression was significantly shorter than that of patients with normal E-cadherin expression among patients with receptor-binding cancer antigen expressed on SiSo cells expression (P = 0.0043) but did not differ for those without receptor-binding cancer antigen expressed on SiSo cells expression (P = 0.17). Furthermore, multivariate analysis revealed that reduced/abnormal expression of E-cadherin was an independent prognostic factor in patients with receptor-binding cancer antigen expressed on SiSo cells expression but not in those without receptor-binding cancer antigen expressed on SiSo cells expression. Conclusions Receptor-binding cancer antigen expressed on SiSo cells expression is significantly correlated with tumor progression and poor prognosis in patients with colorectal cancer. Both reduced E-cadherin and enhanced receptor-binding cancer antigen expressed on SiSo cells expression may be critical for the mechanism of metastasis and recurrence in human colorectal cancer.     

Prognostic factors in node-negative colorectal cancer: a retrospective study from a prospective database

Purpose  

There is a need to identify a subgroup of high-risk patients with node-negative colorectal cancer who have a poor long-term prognosis and may benefit from adjuvant therapies. The aim of this study was to evaluate the prognostic impact of clinical and pathological parameters in a retrospective study from a prospective, continuous database of homogenously treated patients.     

Survival Stratification Panel of Colorectal Carcinoma with Combined Expression of Carcinoembryonic Antigen,Matrix Metalloproteinases-2, and p27<Superscript>kip1</Superscript>

Purpose The prognosis varies greatly in colorectal carcinoma patients, even in the same stage. We examined the association between the expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27^kip1, and clinicopathologic features in patients with colorectal carcinoma to identify a possible panel of tumor markers in predicting prognosis of colorectal carcinoma. Methods The expressions of three individual markers in 127 colorectal carcinoma cases were analyzed by immunohistochemistry method. Univariate and multivariate analysis were performed to analyze the expression with the disease-free survival time in colorectal carcinoma. Results High expression of matrix metalloproteinases-2, carcinoembryonic antigen, and low expression of p27^kip1 were related to poor prognosis in univariate analysis (P = 0.0002; P < 0.0001; P = 0.0008). The expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27^kip1, and tumor differentiation were independent prognostic factors for disease-free survival by Cox regression analysis. The coexpression panel of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip had significant prognostic value in all patients (P_AB = 0.0103; P_BC = 0.0068; P_CD = 0.0117). Multivariate analysis with Cox regression reveals that coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 were independent prognostic factors as tumor differentiation in colorectal carcinoma. In different stages, coexpression tumor markers functioned in Stages II and III but not in the 19 cases of Stage I. The reason might be the number of patients was too small. Conclusions The results of this study provided further evidence that the combination of tumor markers of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 was more informative than any single tumor marker alone for the disease-free survival stratification of colorectal carcinoma. Coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 might be a useful survival stratification panel for clinical management. Supported by the Research fund of the Beijing Municipal Science & Technology Commission (Grant H020920030390); Beijing New Star Project on Science & Technology (Grant 2006B55). Poster presentation at Digestive Disease Week, Los Angeles, California, May 20 to 25, 2006.     

Lymphatic Microvessel Density is an Independent Prognostic Factor in Colorectal Cancer

Purpose Although lymph node metastasis via lymphatic vessels often is related with an adverse outcome, it is not well known whether lymphatic spread to lymph node needs the development of the new lymphatic formation. In addition, the correlation between lymphangiogenesis and prognosis has not been well documented. This study was designed to assess the prognostic value of lymphangiogenesis and lymphatic vessel invasion in colorectal cancer. Methods We examined 106 colorectal cancer specimens by immunostaining for podoplanin, lymphatic endothelial specific marker. We evaluated lymphangiogenesis, as measured by lymphatic microvessel density, and lymphatic vessel invasion. We next investigated the association of these two parameters with the clinicopathologic findings and prognosis. Results A significant correlation was observed between high lymphatic microvessel density and positive lymphatic vessel invasion (P = 0.0003). Positive lymphatic vessel invasion was significantly associated with the presence of lymph node metastasis (P = 0.0071). The survival curves demonstrated that both high lymphatic microvessel density and positive lymphatic vessel invasion were correlated with an adverse outcome (P = 0.0004 and P = 0.009, respectively). In a univariate analysis, high lymphatic microvessel density and positive lymphatic vessel invasion were negatively associated with the overall survival (P = 0.0011 and P = 0.0118, respectively). Furthermore, high lymphatic microvessel density, but not lymphatic vessel invasion, correlated with a poor outcome in a multivariate analysis (P = 0.0114). Conclusions Our data suggested that lymphatic vessel invasion was related with lymph node metastasis and that both lymphatic microvessel density and lymphatic vessel invasion were related with an adverse outcome in colorectal cancer. Furthermore, lymphatic microvessel density may be a useful prognostic factor in colorectal cancer. *Deceased. The Poster presentation at the meeting of the Japanese Society of Gastroenterology, Sapporo, Japan, October 11 to 14, 2006. Reprints are not available.     

Cancer Invasion to Auerbach’s Plexus is an Important Prognostic Factor in Patients with pT3-pT4 Colorectal Cancer

Purpose By defining perineural invasion of colorectal cancer as invasion to Auerbach’s plexus, we examined the usefulness of this pathologic finding as a prognostic factor. Methods A total of 509 consecutive patients who underwent curative surgery for pT3 or pT4 colorectal cancer between May 1997 and December 2001 were reviewed. All the surviving patients were followed for more than five years. All the pathologic findings, including perineural invasion, were described prospectively in the pathology report forms. Results Perineural invasion was detected in 132 of 509 patients (26 percent) and was significantly associated with lymph node status, lymphatic invasion, and venous invasion. Incidences of local and systemic recurrence were significantly higher in patients with perineural invasion than in those without perineural invasion. The disease-free survival of the perineural invasion-positive group was significantly poorer than that of the perineural invasion-negative group for Stages II and III colon cancer, irrespective of the use of adjuvant chemotherapy. This improved disease-free survival also was seen in patients with Stage II rectal cancer not treated with adjuvant chemotherapy. There was a nonsignificant difference in disease-free survival for Stage II rectal cancer and Stage III rectal cancer treated with chemotherapy, that of the perineural invasion-positive group being poorer. Multivariate analysis showed that lymph node status, perineural invasion, depth of invasion, and cancer site were significant prognostic factors. Conclusions Perineural invasion defined as cancer invasion to Auerbach’s plexus is an important prognostic factor for colorectal cancer. Supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan.     

Anti-p53 autoantibody in colorectal cancer: prognostic significance in long-term follow-up

Background The prognostic significance of anti-53 autoantibody in colorectal cancer (CRC) patients is unclear due to measurement of overall rather than disease-specific survival and generally short follow-up periods in many studies. We aim to investigate prognostic significance of anti-p53 auto-antibodies in a study with long-term follow-up (minimum 5 years). Methods ELISA for anti-p53 autoantibody was assayed in serum from 92 patients with CRC and 28 controls. Results Anti-p53 autoantibody was found in 20 patients (21.7%) and none of the controls. No difference in Dukes’ (A/B vs. C/D), Stage (I/II vs. III/IV), T1/2 vs. T3/4, N0 vs. N1/2, M0 vs. M1, poor vs. well/moderate differentiation and proximal vs. distal CRC was observed. Median overall survival was 62 months and median disease-specific survival was 73 months. Dukes’ C/D, Stage III/IV, N1/2 and M1 were associated with poor disease-specific survival in univariate analysis. Stage III/IV was an independent prognostic factor in overall and disease-free survival in multivariate analysis. Anti-p53 autoantibody sero-positivity did not influence overall (p = 0.980) or disease-specific survival (p = 0.874). Median overall survival in anti-p53 autoantibody positive patients was 62 months vs. 60 months in anti-53 autoantibody negative patients. Median disease-specific survival in anti-p53 autoantibody positive patients was 73 months vs. 82 months. Conclusion Anti-p53 autoantibody is not related to clinical parameters of CRC and has no prognostic significance in long-term follow-up.     

Bacterial Translocation May Influence the Long-Term Survival in Colorectal Cancer Patients

Purpose The purpose of this study was to investigate the association of bacterial translocation with long-term disease-specific and disease-free survival in colorectal cancer patients. Methods This was a prospective cohort study in which 128 and 30 colorectal cancer patients undergoing curative and palliative resections, respectively, were recruited between 1992 and 1997. Samples of mesenteric lymph nodes were harvested for culture before administration of prophylactic antibiotics. Median follow-up for patients without cancer death was 103 (range, 72–147) months. This cohort of patients was internally validated by Dukes staging. Results The cumulative disease-specific survival (time to death) and disease-free survival (time to recurrence) for all patients at five years of follow-up was 55 percent (standard error [SE], 4.4 percent) and 65 percent (SE, 4.8 percent), respectively. Bacteria were isolated from the mesenteric nodes of 23 (15 percent) patients. There was no association between bacterial translocation and nodal metastases, bowel obstruction, and septic complications. Patients with confirmed bacterial translocation had a worse disease-specific survival (n=158, 5-year survivorship estimates±SE, 38 percent±12 percent vs. 58 percent±4.7 percent; P < 0.01) and disease-free survival (n=128, 5-year survivorship estimates±SE, 46 percent±14 percent vs. 66 percent±5 percent; P = 0.004) than those without. Using multivariate Cox regression analysis, bacterial translocation was a predictor of disease-specific survival (P = 0.011) and disease-free survival (P = 0.02) independent of other pathologic prognostic indicators. Conclusion Colorectal cancer patients with bacterial translocation in the mesenteric lymph nodes have a worse outcome. Presented at the meeting of the Society of Academic and Research Surgery, Belfast, Northern Ireland, January 14 to 16, 2004.     

Absence of Prognostic Value of Nuclear Shape Factor Analysis in Colorectal Carcinoma: Relevance of Interobserver and Intraobserver Variability

Purpose  Several retrospective studies, including our previous investigation, have shown a prognostic value of nuclear shape factor in colorectal carcinomas. This prospective study was designed to assess the reliability of nuclear shape factor determined by nuclear morphometry and to confirm its prognostic value. Methods  Ninety-eight patients who underwent colorectal carcinoma resection were prospectively enrolled. Measurement of nuclear shape factor was performed by using a computer-based image analysis system. Nuclear shape factor was defined as the degree of circularity of the nucleus (1.0 for a perfect circle and <1.0 for any other elliptical shape). The prognostic impact of nuclear shape factor on ten-year survival and the intraobserver and interobserver agreement were assessed. Results  The nuclear shape factor mean values by American Joint Committee on Cancer stage were: 0.73 (0.07) in Stage I, 0.74 (0.06) in Stage II, and 0.75 (0.05) in Stage III carcinomas (P = 0.78, ANOVA). The intraobserver agreement was poor for observer A (r = 0.28) and practically nonexistent for observer B (r = −0.004, Pearson correlation). The intraclass coefficient for interobserver agreement was practically nonexistent. No significant association between nuclear shape factor and ten-year survival was found. Conclusions  Our prospective results, as opposed to our previous retrospective results, suggest that the reliability for nuclear shape factor morphometric analysis is very poor. We failed to confirm a prognostic value for nuclear shape factor in colorectal carcinoma. Supported by a grant from the Research Foundation of The American Society of Colon and Rectal Surgeons. Reprints are not available.     

Expression of blood group antigens A, B and H in carcinoma tissue correlates with a poor prognosis for colorectal cancer patients

The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy. Received: 20 August 1999 / Accepted: 16 December 1999     

Tumor Invasion of Lymph Node Capsules in Patients with Dukes C Colorectal Adenocarcinoma

Purpose The objective of this study was to investigate the correlation between the microscopic findings of positive lymph nodes, especially focusing on capsular invasion, and the outcome after curative surgical resection of colorectal cancer. Methods We analyzed 480 positive lymph nodes from 155 consecutive patients with Stage III colorectal cancer to determine the frequency and significance of lymph node capsular invasion. Recurrence-free and cancer-specific survival rates were assessed in the patients with and without lymph node capsular invasion. Results Between April 1995 and December 2000, 406 consecutive patients with primary colorectal cancer underwent curative resection. Regional lymph node metastases were present in 155 cases (38.2 percent). During the median follow-up period of 4.8 years, 41 patients (26.5 percent) developed recurrent disease and 28 patients died of cancer. Lymph node capsular invasion was detected in one or more lymph nodes from 75 cases (48.3 percent). The five-year recurrence-free rate was 56.1 percent in this group, whereas in the 80 patients without lymph node capsular invasion the rate was 88 percent (P<0.01). Features that were associated with recurrent disease were greater number of positive lymph nodes, venous invasion in primary tumor, infiltrative growth pattern of intranodal tumor, and presence of lymph node capsular invasion. Multivariate analysis identified lymph node capsular invasion as the only significant prognostic factor for recurrence. In multivariate analysis with regard to survival, lymph node capsular invasion, venous invasion, and number of positive nodes remained as significant prognostic factors. Conclusions Lymph node capsular invasion, determined by routine hematoxylin-eosin staining, is a potent prognostic factor in Stage III colorectal cancer. Read in part at the meeting of The International Society of University Colon and Rectal Surgeons, Budapest, Hungary, June 9, 2004. Reprints are not available.     

Number and Size of Lymph Nodes Recovered From Dukes B Rectal Cancers: Correlation with Prognosis and Histologic Antitumor Immune Response

Purpose In rectal cancer variation in lymph node recovery influences the detection of nodal metastases and prognosis among Dukes B (Stage II) cases. However, the possible prognostic importance of node size and inherent patient/tumor characteristics in determining node recovery has not been studied. Methods We examined 269 Dukes B (Stage II) rectal tumors, with a mean of 12 nodes per case. Primary tumor characteristics were correlated with the number and size of recovered nodes. Clinical follow-up permitted determination of long-term survival. Results The five-year survival of 94 Dukes B cases with nine or fewer nodes was 69.4 percent vs. 87.6 percent in 175 cases with ten or more nodes (P = 0.001). Lymph nodes were smaller in patients dying of recurrence; among 130 Dukes B patients whose mean node diameter was <4 mm, survival was 73.3 vs. 88 percent when mean nodal diameter was ≥4 mm. The number and size of recovered nodes was related to patient age, histologic antitumor immune response, and tumor growth pattern. By combining the number and size of nodes, a poor prognosis subgroup of 98 Dukes B patients with relatively few large nodes (no more than 5 measuring ≥4 mm) was identified with a five-year survival of 65.6 percent compared with 89.6 percent for the remaining 158 Dukes B cases (P < 0.0001). Conclusions In Dukes B rectal tumors, the number and size of lymph nodes are related to inherent patient and tumor characteristics and permit the identification of Dukes B cases at increased risk of recurrence. A valid comparison of nodal sampling efficiency between centers necessitates measuring and counting harvested lymph nodes. Supported by Cancer Research Appeal Mercy Hospital, Cork, Ireland and Cancer Research, United Kingdom     

Predictive clinicopathologic factors for limited response of T3 rectal cancer to combined modality therapy

Purpose The response of T3 rectal cancer to combined modality therapy (CMT) is highly predictive of long-term outcome following surgery. The aim of this study was to identify pretreatment factors associated with poor tumor response to neoadjuvant chemoradiation. Methods A prospective institutional database at Memorial Sloan-Kettering Cancer Center was queried for endorectal ultrasound (ERUS) stage T3N0–2 rectal cancer patients, treated with CMT followed by surgical resection, between 1998 and 2003. Preoperative clinicopathologic factors determined by biopsy, ERUS, proctoscopy, and digital rectal examination were correlated with the degree of downstaging of the primary mural lesion (tumor downstaging) in response to neoadjuvant therapy. Associations were analyzed by chi-square, Kaplan–Meier, and logistic regression. Results Of 274 patients, 51% obtained tumor downstaging in response to preoperative treatment, i.e., lower pathologic T-stage compared with pretreatment ERUS. Five-year recurrence-free survival was 89% in the cohort that obtained tumor downstaging compared with only 45% in the cohort that obtained no tumor downstaging. Factors significantly associated with limited or lack of tumor downstaging after CMT included: fixed tumor on digital rectal examination (p < 0.021), near-circumferential tumor (p < 0.011), tumor stenosis (p < 0.025), metastatic disease (p < 0.012), biopsy-proven poorly differentiated pathology (p < 0.002), and radial extension >2.5 mm on ERUS (p < 0.031). On multivariate analysis, deep radial extension on ERUS, metastatic disease, and poorly differentiated pathology were in each, independently associated with limited or lack of tumor downstaging. Conclusions Pretreatment evaluation with biopsy, proctoscopy, and ERUS can identify T3 rectal cancer patients unlikely to respond well to CMT. These patients may be considered for alternative protocols and their tumors studied to ascertain the molecular events responsible for resistance to chemoradiation. Presented at Presented at the 2006 annual meeting of The American Society of Colon and Rectal Surgeons, June 3–7, 2006, Seattle, WA, USA.     

Long-Term Outcome After Operative Intervention for Rectal Cancer in Patients Aged Over 80 Years: Analysis of 9,501 Patients

Introduction Perceptions of poor outcome may detract caregivers from offering standard therapies to patients over 80 years who have been diagnosed with rectal cancer. We evaluate the effect of operative intervention on their survival. Methods Demographics, tumor characteristics, treatment, and survival for patients over 80 years with rectal and rectosigmoid cancer from 1993 to 2002 in the Surveillance, Epidemiology and End Results Program of the National Cancer Institute were examined. Survival was determined by using the Kaplan-Meier method. Patients who underwent operation (Group A) were compared with those who did not undergo surgery (Group B). Fisher's exact, chi-squared, analysis of variance, and log-rank tests were used as appropriate, and P < 0.05 was considered statistically significant. Results A total of 9,501 patients (19 percent) were aged older than 80 years. Mean age was 85 years, and median survival was 24 months. Stage of disease was unknown for 2,915 patients. Median survival was 58, 53, 39, 27, and 5 months for Stages 0 (n=163), I (n=1,878), II (n=1,796), III (n=1,536), and IV (n=1,213), respectively. A total of 6,900 patients (81 percent) underwent surgery. Median survival for operated patients was significantly longer for all stages (36 vs. 5 months, P < 0.00001), Stage 0 (60 vs. 7 months, P < 0.01), Stage I (55 vs. 11 months, P < 0.0001), Stage II (41 vs. 13 months, P < 0.0001), Stage III (28 vs. 14 months, P < 0.05), and Stage IV (8 vs. 3 months, P < 0.0001). For patients with rectal cancer, local therapy also significantly improved median survival compared with nonoperated patients (P < 0.0001). Conclusions Operative intervention provides sustained benefit in terms of survival to patients aged >80 years with rectal cancer at all stages who are assessed to be a good operative risk. Age older than 80 years should not detract surgeons from offering optimal therapy to good-risk patients. Reprints are not available.     

Simultaneous versus staged liver resection of synchronous liver metastases from colorectal cancer

Background and aims The surgical strategy for treatment of synchronous liver metastases from colorectal cancer remains controversial. This retrospective analysis was conducted to compare the postoperative outcome and survival of patients receiving simultaneous resection of liver metastases and primary colorectal cancer to those receiving staged resection. Materials and methods Between January 1988 and September 2005, 219 patients underwent liver resection for synchronous colorectal liver metastases, of whom, 40 patients received simultaneous resection of liver metastases and primary colorectal cancer, and 179 patients staged resections. Patients were identified from a prospective database, and records were retrospectively reviewed. Patient, tumor, and operative parameters were analyzed for their influence on postoperative morbidity and mortality as well as on long-term survival. Results Simultaneous liver resections tend to be performed for colon primaries rather than for rectal cancer (p = 0.004) and used less extensive liver resections (p < 0.001). The postoperative morbidity was comparable between both groups, whereas the mortality was significantly higher in patients with simultaneous liver resection (p = 0.012). The mortality after simultaneous liver resection (n = 4) occurred after major hepatectomies, and three of these four patients were 70 years of age or older. There was no significant difference in long-term survival after formally curative simultaneous and staged liver resection. Conclusion Simultaneous liver and colorectal resection is as efficient as staged resections in the treatment of patients with colorectal cancer and synchronous liver metastases. To perform simultaneous resections safely a careful patient selection is necessary. The most important criteria to select patients for simultaneous liver resection are age of the patient and extent of liver resection.