Tumor Pathology and Long-Term Survival in Emergency Colorectal Cancer

PURPOSE Patients who have an emergency operation for colorectal cancer have poorer long-term survival outcomes compared with elective patients. This study was designed to define the role of tumor pathology as a basis for the differences in survival outcomes. METHODS There were 1,537 elective and 286 emergency patients who had an operation for bowel cancer from 1997 to 2003. Tumor pathology and survival data collected prospectively for these patients were compared by modes of presentation. RESULTS Excluding 30-day mortality, emergency patients as a whole had a five-year all-cause survival rate of 39.2 percent compared with 64.7 percent for elective patients P < 0.0001 they also had more advanced Dukes C and D tumors (P < 0.0001). The rates of early T1 and T2 cancers were 4.7 percent for the emergency and 25 percent for the elective group. Emergency cases had more lymph node-positive patients and N2 patients (57.1 vs. 41.8 percent and 26.6 vs. 15.9 percent, respectively; P < 0.0001). Curatively resected emergency colon patients again had more advanced Dukes staged tumors (P < 0.0001) with a five-year survival rate of 51.6 percent compared with 75.6 percent for elective patients P < 0.0001. On stage-for-stage analysis, the survival rates for curatively resected Dukes B and C colon cancers remained worse for emergency patients (P = 0.003 and P = 0.0002, respectively). Both emergency Dukes B and C groups had more T4 cases (21.5 vs. 10.6 percent; P = 0.017 and 26.4 vs. 15 percent; P = 0.016, respectively). CONCLUSION Advanced tumor pathology is a basis for poor long-term survival in emergency colorectal cancers. Reprints are not available.     

Predicting factors of postoperative relapse in T2-4N0M0 colorectal cancer patients via harvesting a minimum of 12 lymph nodes

Background and aim  The aim of this retrospective study was to determine which clinicopathological factors influenced the incidence of postoperative relapse and overall survival rates after radical resection of T_2-4N₀M₀ colorectal cancer (CRC) patients via harvesting a minimum of 12 lymph nodes. Materials and methods  Between January 2001 and June 2006, a total of 342 T_2-4N₀M₀ CRC patients who underwent radical resection were retrospectively analyzed in Kaohsiung Medical University Hospital. Of these 342 patients, 155 were observed by harvesting a minimum of 12 lymph nodes. These 155 patients were followed up intensively, and their outcomes were investigated retrospectively. Results  Of 155 patients, 83 were men (53.5%) and 72 (46.5%) were women. The mean age was 65.5 ± 11.1 years (range, 24–89 years). The median follow-up period was 49 months (range, 19–80 months). The present data showed invasive depth (P = 0.012), vascular invasion (P < 0.001), and perineural invasion (P = 0.009) as significantly prognostic factors for postoperative 5-year relapse rate by Kaplan–Meier analysis. Likewise, invasive depth (P = 0.013), vascular invasion (P < 0.001), and perineural invasion (P = 0.008) were significant factors for postoperative 5-year survival rate. Meanwhile, using a Cox proportional hazards analysis, depth of tumor invasion (P = 0.026) and vascular invasion (P = 0.001) were the independent predictors for postoperative relapse. Furthermore, the presence of vascular invasion was considerably correlated to the higher postoperative relapse rate and the poorer overall survival rates by survival analyses (P < 0.0001). Conclusions  Besides the conventional depth of tumor invasion, this study highlights the potential for using vascular invasion as a means of identifying a subgroup of T_2-4N₀M₀ CRC patients with adequate lymph node harvest at higher risk who would potential benefit from adjuvant therapy after surgery.     

Impact of Tumor Location on Nodal Evaluation for Colon Cancer

Purpose Adequate lymph node evaluation is important to stage colon cancers and make adjuvant treatment decisions. Studies have demonstrated improved survival when ≥ 12 nodes are examined. Our objective was to assess differences in the adequacy of nodal evaluation for right vs. left colon cancers. Methods From the National Cancer Data Base (1998–2004), 142,009 N0M0 colon cancer patients were identified. Logistic regression was used to evaluate the number of nodes examined for right vs. left colectomies. Multivariable modeling was used to determine the impact of examining ≥ 12 nodes on survival. Results Of 142,009 patients, 79,444 (56 percent) had right colectomies, and 62,565 (44 percent) patients had left colectomies. More nodes were examined during right colectomies than left (median 12 vs. 8, P < 0.0001). When adjusted for patient, tumor, and hospital factors, patients undergoing left colectomy were less likely to have ≥ 12 nodes identified (P < 0.0001). Patients were more likely to have ≥ 12 nodes identified for right and left colon cancers at high-volume hospitals. Survival was better with examination of ≥ 12 nodes for right and left colon cancers (P < 0.0001). Conclusions Evaluating ≥ 12 nodes for right and left colon cancers is a feasible, clinically relevant, and modifiable factor that will likely improve patient outcomes. Presented in part at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 7, 2007. Supported by a grant from the National Cancer Institute. Dr. Bilimoria is supported by the American College of Surgeons, Clinical Scholars in Residence program, and a research grant from the Department of Surgery, Feinberg School of Medicine, Northwestern University.     

Risk Factors for Occult Lymph Node Metastasis of Colorectal Cancer Invading the Submucosa and Indications for Endoscopic Mucosal Resection

Purpose Although risk factors for histologically overt lymph node metastasis in patients with early-stage colorectal cancer have been clarified, the risk factors for occult lymph node metastasis are not clear. This study was designed to clarify risk factors for lymph node metastasis, including occult metastasis, in patients with colorectal cancer invading the submucosa and to determine the criteria for endoscopic resection of early colorectal cancer. Methods The risk factors for lymph node metastasis, including occult metastasis, were analyzed in 86 cases of surgically resected colorectal cancer invading the submucosa. The lymph nodes were assessed by immunohistochemistry with cytokeratin antibody CAM5.2. Results The frequencies of overt and occult metastasis to the lymph nodes were 13 percent (11/86) and 13 percent (10/75), respectively. Multivariate analysis showed vascular invasion (P = 0.001) and tumor budding (P = 0.003) to be independent risk factors for lymph node metastasis, including occult metastasis. For tumors with submucosal invasion ≤1,000 μm, no lymph node metastasis was found. The frequencies of lymph node metastasis for tumors with submucosal invasion of 1,000 to 2,000 μm and >2,000 μm were 21 and 37 percent, respectively. In considering combinations of risk factors, there was no lymph node metastasis in tumors having neither vascular invasion nor tumor budding and submucosal invasion of ≤3,000 μm. Conclusions Vascular invasion, tumor budding, and the degree of submucosal invasion were significant risk factors for lymph node metastasis, including occult metastasis. These three factors can be used in combination to identify patients requiring additional surgery after endoscopic resection. Supported in part by a Grant-in-Aid for Scientific Research (no. 15390401) from the Japanese Ministry of Education, Science, and Culture. Presented at the Congress of Japan Surgery Society, Tokyo, Japan, March 29 to 31, 2006. Reprints are not available.     

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.     

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.     

Local Excision of Distal Rectal Cancer: An Update of Cancer and Leukemia Group B 8984

Purpose  The efficacy of local excision in the treatment of some early-stage distal rectal cancers is still being debated, because few high-quality, long-term prospective data on outcomes are available. Methods  Fifty-nine patients with T1 lesions were treated with local excision alone, whereas 51 patients with T2 lesions received external beam irradiation (5,400 cGY) and 5-fluorouracil (500 mg/m² intravenously Days 1–3, Days 29–31) after local excision. Kaplan-Meier curves were used to estimate the primary outcomes. The log-rank test and Cox’s proportional hazards model were used to compare subgroups relative to these outcomes. Results  With a median follow-up of 7.1 (range, 2.1–11.4) years, ten-year rates of overall survival were 84 percent for patients with T1 and 66 percent for T2 rectal cancer. Disease-free survival was 75 percent for T1 and 64 percent for T2 disease. Local recurrence rates for patients with T1 and T2 lesions were 8 and 18 percent, respectively, and rates of distant metastases were 5 percent for T1 and 12 percent for T2 lesions. T stage was a statistically significant predictor of overall survival (P = 0.04) and approached statistical significance as a predictor of disease-free survival (P = 0.07). Conclusions  Local excision alone for T1 rectal adenocarcinomas is associated with low recurrence and good survival rates that remain durable with long-term follow-up. T2 lesions treated via local excision and adjuvant therapy are associated with higher recurrence rates. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Vascular Invasion is Underrecognized in Colorectal Cancer Using Conventional Hematoxylin and Eosin Staining

Purpose This study was designed to test the hypothesis that highlighting vascular spaces with histochemical or immunohistochemical stains facilitates the identification of extramural and intramural vascular invasion in resected colorectal cancer specimens compared with routine hematoxylin and eosin staining. Methods Archival tumor sections from 50 resected colorectal cancers, in which extramural vascular invasion was not seen within the original tissue sections, were stained with hematoxylin and eosin, elastic van gieson histochemistry, and immunohistochemistry for CD31 and CD34. Two observers assessed the stained sections and the agreed incidence of vascular invasion using the four staining methods was compared. Results Vascular invasion was more commonly identified in Dukes C (pTanyN1/2) (vascular invasion seen in 24 of 25 cases by at least 1 method) than Dukes B tumors (pT3/4N0) (vascular invasion seen in 14 of 25 cases by at least 1 method). Vascular invasion was identified in significantly more cases using elastic van gieson (24 cases; P = 0.0001), CD31 (18 cases; P = 0.0064), and CD34 (21 cases; P < 0.0001) than with hematoxylin and eosin alone (5 cases). Conclusions This study was novel in that it compared both histochemical and immunohistochemical methods for identifying vascular invasion in cases of colorectal cancer in which vascular invasion had not been identified during initial reporting. Highlighting of endothelium significantly increases the observed incidence of vascular invasion in colorectal cancer compared with hematoxylin and eosin alone. Elastic van gieson seemed sensitive for the presence of vascular invasion but with uncertain specificity. The possibility that these immunohistochemical methods may identify a subset of patients with colorectal cancer who may benefit from chemotherapy warrants further study. Supported by The Institute of Biomedical Sciences, United Kingdom.     

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.     

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.     

Preoperative serum levels of serum VEGF-C is associated with distant metastasis in colorectal cancer patients

Purpose  Vascular endothelial growth factor-C (VEGF-C) is one of the most potent lymphangiogenic members of the VEGF family that has been associated with lymph node metastasis and poor prognosis in patients with colorectal cancer (CRC). In this study, we evaluated the relationship of preoperative serum VEGF-C (sVEGF-C) and survival in CRC patients. Materials and methods  sVEGF-C levels were determined, prior to resection, in a cohort of 120 newly presenting patients with CRC by quantitative ELISA. Results  Patients who had positive lymph node involvement and higher Dukes’ staging (C&D) were associated with shorter time to metastases as expected (p = 0.002 and 0.001, respectively). Patients with distant metastasis had significantly lower levels of sVEGF-C than those without histopathologically proven disease (p = 0.004). However, there was no significant difference in the median sVEGF-C level in patients with or without lymph node metastatic involvement (91 pg/ml vs. 124 pg/ml; p = 0.81). Patients with a sVEGF-C concentration less than the median value (103 pg/ml) showed a poorer overall survival than patients with sVEGF-C levels greater than the median; but this was not statistically significant. Conclusions  In this study, low sVEGF-C levels are associated with distant metastasis; hence, preoperative levels may aid in the selection of CRC patients who require further investigation.     

Follow-Up After Curative Resection of Colorectal Cancer: A Meta-Analysis

Purpose This is a systematic review to evaluate the impact of various follow-up intensities and strategies on the outcome of patients after curative surgery for colorectal cancer. Methods All randomized trials up to January 2007, comparing different follow-up intensities and strategies, were retrieved. Meta-analysis was performed by using the Forest plot review. Results Eight randomized, clinical trials with 2,923 patients with colorectal cancer undergoing curative resection were reviewed. There was a significant reduction in overall mortality in patients having intensive follow-up (intensive vs. less intensive follow-up: 21.8 vs. 25.7 percent; P = 0.01). Regular surveillance with serum carcinoembryonic antigen (P = 0.0002) and colonoscopy (P = 0.04) demonstrated a significant impact on overall mortality. However, cancer-related mortality did not show any significant difference. There was no significant difference in all-site recurrence and in local or distant metastasis. Detection of isolated local and hepatic recurrences was similar. Intensive follow-up detected asymptomatic recurrence more frequently (18.9 vs. 6.3 percent; P < 0.00001) and 5.91 months earlier than less intensive follow-up protocol; these were demonstrated with all investigation strategies used. Intensive surveillance program detected recurrences that were significantly more amenable to surgical reresection (10.7 vs. 5.7 percent; P = 0.0002). The chance of curative reresection were significantly better with more intensive follow-up (24.3 vs. 9.9 percent; P = 0.0001), independent of the investigation strategies used. Conclusions Intensive follow-up after curative resection of colorectal cancer improved overall survival and reresection rate for recurrent disease. However, the cancer-related mortality was not improved and the survival benefit was not related to earlier detection and treatment of recurrent disease. ^aDeceased. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 3 to 7, 2006.     

A novel role of serum cytochrome c as a tumor marker in patients with operable cancer

Purpose  This study aimed to evaluate serum cytochrome c (cyto-c) levels as a novel role of tumor marker in patients with operable malignant tumors. Methods  Serum cyto-c levels and lactate dehydrogenase (LD) activity were measured in a total of 257 cases (232 malignant and 25 benign). To identify the relationship between serum cyto-c and current tumor markers, six variables, such as gender, age, invasion, lymph node metastasis, distant metastasis, and LD, were analyzed by uni- and multivariate regression analysis methods. The test performance of serum cyto-c for the prediction of malignant behavior was evaluated by receiver operating characteristic (ROC) curves. Results  The serum cyto-c level was significantly higher in patients with malignant tumors than patients with benign tumors (20.6 vs. 15.5 ng/mL; P = 0.017, Mann–Whitney U test). No difference in the levels among subtypes of cancer was found, indicating that the change in serum cyto-c levels reflect cancer individually and not specific subtypes of cancer. The survival in patients with serum cyto-c levels over 40 ng/mL was poor (Kaplan–Meier test, P < 0.0001, Hazard ratio 16.76, 95% confidential interval 4.45–63.04). Multiple linear regression analyses disclosed the close association of serum cyto-c levels with invasion (P = 0.0004), metastasis (P = 0.0262) except for regional lymph node metastasis, and activity of serum LD (P < 0.0001), all of which are well known to represent malignant behavior. Conversely, the measurement of serum cyto-c was verified to have excellent diagnostic accuracy of 0.802 and 0.781 for the detection of invasion and metastasis (the area under curves of the constructed ROCs). Conclusion  Serum cyto-c is a potent tumor marker as a predictor for malignant potential in cancers.     

Postoperative Radiotherapy for Stage IIIA Rectal Cancer: Is It Justified?

Purpose  Adjuvant radiotherapy is currently recommended for all node-positive rectal cancers to reduce local recurrence. This study evaluated if an adequate mesorectal excision can obviate the need for radiotherapy in early node-positive cancer. Methods  Stage IIIA rectal cancer patients were identified in a prospectively maintained database. Patients who received postoperative radiotherapy (radiotherapy) and those who did not (no radiotherapy) were compared for recurrence, survival, bowel function, and quality of life. Quality of life was assessed using the Short Form-36 Medical Outcomes Survey. Results  Eighty-six patients underwent proctectomy for T1-T2,N1 rectal cancers from 1978 to 2004. Patients receiving radiotherapy (n = 34) were younger and had a higher percentage of T1 tumors than patients who did not receive radiotherapy (n = 52). Other tumor characteristics, type of surgery, and number of involved lymph nodes were comparable. Estimated 5-year local recurrence was radiotherapy 3.4 percent and no radiotherapy 4.7 percent; distant recurrence was radiotherapy 13.5 percent and no radiotherapy 16.5 percent; and disease-specific mortality rates were similar 13.5 vs. 11.3 percent, for radiotherapy and no radiotherapy (all P > .05). Patients receiving radiotherapy had higher frequency of daytime bowel movements, urgency, and usage of pads and antidiarrheal medications. Age adjusted quality of life parameters were comparable between treatments. Conclusion  Postoperative radiotherapy did not reduce recurrence or mortality. Function but not quality of life was adversely affected. Routine postoperative radiotherapy for Stage IIIA rectal cancer should be reconsidered. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Prognostic Analysis of Rectal Stromal Tumors by Reference of National Institutes of Health Risk Categories and Immunohistochemical Studies

Purpose  Prognostic analysis of stromal tumors focusing on the rectal area is rarely performed. This study elucidated prognostic factors by referencing biomarkers of Ki67 and p53. Methods  Forty-nine surgically resected rectal stromal tumors were collected from 1986 to 2006. Immunohistochemical studies were performed with antibodies of CD117, CD34, smooth muscle actin, desmin, S100, Ki67, and p53. Results  The immunoreactivities were: CD34, 83.6 percent; smooth muscle actin, 28.5 percent; S100, 4.1 percent; desmin,16.3 percent;, Ki67, 30.6 percent;, and p53 34.7 percent. Both p53+ and Ki67+ tumors were associated with increased tumor mitosis, increased tumor size, nonspindle cell type, and increased cell pleomorphism (P < 0.05). Increased National Institutes of Health risk was associated with old age, nonspindle cell types, and severe nuclear pleomorphism (P < 0.05). Survival analysis demonstrated that older patients (P = 0.0039), large tumor size (P = 0.003), high mitotic count (P < 0.001), increased risk categories (P < 0.001), high cell pleomorphism (P = 0.003), p53+ (P = 0.007), and Ki67 + (P = 0.002) were prognostic factors for poor disease-free survival. An independent prognostic factor was tumor mitotic count. Conclusions  This study demonstrated the prognostic role of Ki67 and p53 in rectal stromal tumors. Notably, tumor mitosis was superior for prognostic prediction compared to National Institutes of Health risk categories. This work was supported in part by grants from National Science Council, Taiwan (NSC 93-2314-B-182A-145- to T. H. H.)     

Absence of Lymph Nodes in the Resected Specimen After Radical Surgery for Distal Rectal Cancer and Neoadjuvant Chemoradiation Therapy: What does it Mean?

Purpose The number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen. Methods Patients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease. Results Thirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P < 0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P = 0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P = 0.2), and both were significantly better than patients with ypN+ disease (30 percent; P < 0.001). Conclusions Absence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality. Presented at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

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

PURPOSE The 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.METHODS Patients 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.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.     

MDM2 mRNA Expression in the p53 Pathway May Predict the Potential of Invasion and Liver Metastasis in Colorectal Cancer

Purpose  The p53/MDM2/p14ARF pathway is one of the major signaling cascades involved in the regulation of apoptosis. Although many tumors have been reported to show disruption of the p53/MDM2/p14ARF pathway, few studies have examined p53, MDM2, and p14ARF simultaneously in colorectal carcinoma. The present study was undertaken to clarify whether correlations exist among MDM2, p53, and p14ARF in colorectal cancer. Methods  We determined the presence of mutations in the p53 gene, MDM2 expression, and methylation status of the p14ARF in 97 primary colorectal carcinoma specimens. Associations with survival and clinicopathologic factors were investigated. Results  At least one abnormality of these three molecules was found in 82 (84 percent) tumors. We observed a significant inverse association between MDM2 expression and tumor invasion (P = 0.01). Furthermore, the presence of liver metastasis was also significantly associated with low MDM2 expression (P = 0.02). Conclusions  The results suggest that disruption of the p53/MDM2/p14ARF pathway may frequently participate in colonic carcinogenesis and that MDM2 expression status may be a factor in the prediction of potential invasion and liver metastasis of colorectal carcinomas. Reprints are not available.     

Pathologic Determinants of Survival After Resection of T3N0 (Stage IIA) Colorectal Cancer: Proposal for a New Prognostic Model

Purpose There is an increasing need for accurate prognostic stratification of patients with Stage II colorectal cancer to identify a subgroup of high-risk patients who may benefit from adjuvant therapies. This study was designed to evaluate the prognostic impact of a wide spectrum of pathologic parameters in a consecutive series of homogenously treated and well-characterized patients with Stage IIA (T3N0M0) colorectal cancer. Methods The study included 238 patients operated on by a single surgeon for Stage IIA colorectal tumors. The median postoperative follow-up was 110 (range, 96–120) months. At least 12 lymph nodes were harvested and examined in all the resection specimens. The prognostic value of 13 pathologic parameters, including lymph node occult disease (micrometastases) detected by immunohistochemistry, was investigated. Results Multivariate analysis identified tumor growth pattern (expanding or infiltrating; P = 0.01) and extent of tumor spread beyond muscularis propria (≤5 mm or >5 mm; P = 0.04) as the only factors having independent prognostic value. The combination of these two easily determined parameters allowed us to identify two groups of patients at low risk or high risk of tumor recurrence. The eight-year survival rates were 83.3 and 53.4 percent for the two groups, respectively. The high-risk group comprised those patients with infiltrating tumors and extramural tumor spread > 5 mm. Conclusions We propose a new and simple prognostic model to identify patients with high-risk Stage IIA colorectal cancer for whom adjuvant therapies may be justified and effective. Supported by grants from the Italian Ministry of University, Scientific and Technological Research, the Ente Cassa di Risparmio di Firenze, and the Associazione Italiana Ricerca sul Cancro.     

Hepatectomy for liver metastasis of colorectal cancer

Objective  The objective of this study was to investigate whether hepatic resection (HR) can increase the survival of liver metastasis of colorectal cancer (CRC). Materials and methods  CRC patients (n = 669) with liver metastasis treated at the Zhongshan Hospital, Fudan University from 1/2000 to 7/2007 were included in the study to investigate the relationship between HR and cancer survival. Results  CRC patients (n = 669) with liver metastases who had primary tumor resection were grouped in synchronous liver metastasis (SLM; 56.7%, n = 379) and metachronous liver metastasis (MLM) groups (43.3%, n = 290). Hepatic resection rates were lower (32.5%, n = 123) in the SLM than the MLM group (44.8%, n = 130, P < 0.05). The 30-day mortality rate in the MLM (2.3%) was significantly lower than SLM (2.4%) groups. The 5-year survival rates (36.6%) was same compared to SLM group (33.1%, P > 0.05). One-, 2-, and 3-year survival of stages I and II operation cases were 92.5% vs 86.5%, 0.7% vs 58.0%, and 42.1% vs 44.9% (P > 0.05) in the SLM group, respectively. Recurrence after first hepatic resection associated with a 2.23-fold increased risk of death (P < 0.01). Incision margins larger than 1 cm and HR for recurrence associated with 34% and 27% (P < 0.05) decreased death risk. Conclusions  Hepatic resection could help the survival of liver metastasis of colorectal cancer, and stage I surgery is safe for this disease. Xu Jianmin, Wei Ye, and Zhong Yunshi contributed equally to this paper.