High visceral to subcutaneous fat area ratio predicts early postoperative small bowel obstruction after surgery for colorectal cancer.

PURPOSE: Risks for postoperative small bowel obstruction have been demonstrated in several reports, most of which indicated male sex was a risk factor, but with the reason remaining unknown. We tested the hypothesis that it could be because males have more visceral fat than females. This prospective observational study aims to examine risks of early postoperative small bowel obstruction (EPSBO) after colorectal cancer surgery and the association between visceral to subcutaneous fat area ratio (V/S ratio) and EPSBO. METHODS: Four hundred and seventy-four patients who underwent colectomy for colorectal cancer in our hospital were enrolled in this study. The influence of several factors including V/S ratio on the development of EPSBO was analyzed. RESULTS: Thirty-one of the 474 patients (6.5%) developed EPSBO. EPSBO occurred more frequently in males (p = 0.03) and cases who developed postoperative anastomotic leakage (p < 0.001) or wound infection (p = 0.02). Higher V/S ratio was strongly related to male sex (p < 0.001). Multivariate analysis revealed higher V/S ratio (OR 2.25; p = 0.049) and anastomotic leakage (OR 5.86; p < 0.001) were independent risk factors for EPSBO. CONCLUSION: Higher V/S ratio was significantly related to EPSBO, suggesting that one of the reasons EPSBO was more likely to occur in males because they have more visceral fat than females. Preoperative identification of this risk factor could help us watch out for this potential complication.

Impact of the post/preoperative serum CEA ratio on the survival of patients with rectal cancer.

PURPOSE: This study demonstrated the usefulness of the post/preoperative serum carcinoembryonic antigen (CEA) ratio as a predictor of survival after surgery for stage III rectal cancer patients. METHODS: One hundred and four patients with stage III rectal cancer who underwent surgery between 1991 and 2000 were enrolled. The ratio of the postoperative serum CEA value divided by the preoperative serum CEA value was defined as post/preoperative serum CEA ratio, and the patients were separated into two groups: post/preoperative serum CEA ratio ≤ 1 (n = 86) and >1 (n = 18). RESULTS: The multivariate analyses demonstrated that the intraoperative blood loss, lack of a sphincter-saving procedure and a post/preoperative serum CEA ratio >1 were independent factors predicting a poor prognosis for the overall and disease-free survival. The overall and disease-free survival rates among patients with a high preoperative serum CEA level (>5 ng/ml) or patients with a high postoperative serum CEA (>5 ng/ml) were longer in patients with a post/preoperative serum CEA ratio ≤ 1, in comparison to those with a post/preoperative serum CEA ratio >1. Liver metastasis was observed more frequently in patients with a post/preoperative serum CEA ratio >1. CONCLUSIONS: The post/preoperative serum CEA ratio may be a predictor of the prognosis after surgery for stage III rectal cancer patients.

Predicting lymph node metastasis in early colorectal cancer using the CITED1 expression.

BACKGROUND: The identification of molecular markers that are useful for predicting lymph node metastasis is urgently needed to determine treatment strategies for T1 colorectal cancer (CRC). We previously showed that 10 candidate genes are correlated with de-differentiation at the invasion front of CRC using a gene expression analysis. These 10 genes are potential markers that may predict lymph node metastasis by CRC. MATERIALS AND METHODS: Samples were obtained from 161 patients with CRC. Quantitative real-time reverse transcription-polymerase chain reaction assays were performed using 66 T3 samples in order to extract genes correlated with lymph node metastasis. Immunohistochemical studies of the extracted genes were performed on 66 T3 and 95 T1 samples. A univariate analysis followed by a multivariate logistic regression model was used to examine independent risk factors for lymph node metastasis. RESULTS: The CITED1 messenger RNA expression was found to be an independent risk factor for lymph node metastasis in T3 CRC patients (P = 0.040). A high CITED1 protein expression, as detected with immunohistochemistry, was also an independent risk factor in T3 CRC patients (P = 0.035). In T1 colorectal cancer patients, a high CITED1 protein expression was found to be an independent risk factor for lymph node metastasis (P = 0.010). The positive predictive and negative predictive values in the T1 colorectal cancer patients were 27.5% and 95.5%, respectively. CONCLUSIONS: The CITED1 expression is correlated with lymph node metastasis in patients with CRC. In T1 colorectal cancer patients, CITED1 has the potential ability to predict the presence of lymph node metastasis.

Clinical outcome of up-front surgery in patients with asymptomatic, incurable synchronous peritoneal carcinomatosis.

PURPOSES: The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC. METHODS: Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively. RESULTS: A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p < 0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001). CONCLUSION: Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.

Re-expression of CEACAM1 long cytoplasmic domain isoform is associated with invasion and migration of colorectal cancer.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is known to be downregulated at the transcriptional level in adenoma and carcinoma. Recent reports have shown that CEACAM1 is overexpressed at protein level in colorectal cancer and correlated with clinical stage. The reason why colorectal cancer cells re-expressed CEACAM1 remains unclear. The aim of our study was to clarify the implication of CEACAM1 re-expression in colorectal cancer. Immunohistochemical analyses were conducted with CEACAM1 long (CEACAM1-L) or short (CEACAM1-S) cytoplasmic domain-specific antibodies on clinical samples from 164 patients with colorectal cancer. The risk factors for metastasis and survival were calculated for clinical implication of CEACAM1 re-expression. Invasion chamber and wound healing assays were performed for the effect of CEACAM1 expression on invasion and migration of colorectal cancer cells. CEACAM1-L and CEACAM1-S stained with greater intensity at the invasion front than at the luminal surface of tumors. Differences between the long and short cytoplasmic isoform expression levels were observed at the invasion front. Multivariate analysis showed that CEACAM1-L dominance was an independent risk factor for lymph node metastasis, hematogenous metastasis and short survival. The Kaplan-Meier evaluation demonstrated that CEACAM1-L dominance was associated with shorter survival time (p < 0.0001). In the invasion chamber and wound healing assays, CEACAM1-L promoted invasion and migration. Re-expression of CEACAM1 is observed at the invasion front of colorectal cancer. CEACAM1-L dominance is associated with metastasis and shorter survival of the patients with colorectal cancer. CEACAM1-L dominance is important for colorectal cancer cells invasion and migration.

Rectal transection by the Nelaton catheter pulling method during a laparoscopic low anterior resection.

BACKGROUND: A laparoscopic low anterior resection with double-stapling technique for lower rectal cancer is considered to be technically challenging because it is difficult to perform rectal transection and anastomosis in the narrow pelvic cavity. METHODS: We developed a new method for transecting the rectum with stapling a small number of cartridges. In laparoscopic low anterior resection, a 70-mm endovascular clip clamps the rectal wall at the anal side of the tumor. An endolinear stapler is applied at the rectal wall parallel and caudal to the 70-mm endovascular clip. A Nelaton catheter of 3.5 to 4.5 mm in outer diameter is inserted, and the loop of the Nelaton catheter is made behind the rectum. The Nelaton catheter loop is applied at the rectal wall parallel and caudal to the endolinear stapler and is pulled parallel the endolinear stapler toward the anterior side of the rectum. The endolinear stapler with opened jaws can be pushed deeper into the space, then the jaws can be closed in a position that can transect the rectum with one firing using only one cartridge. RESULTS: Curative low anterior resection with rectal transection using the Nelaton catheter pulling method was performed in 13 patients with rectal cancer. The median value and range of tumor distance from the anal verge were 6.0 and 4.5 to 10.0 cm. The median duration of the operation was 284 minutes, and median blood loss was 10 mL. The number of stapling cartridges used for rectal transection was 1 in all cases, and there were no major complications. CONCLUSIONS: We have demonstrated a safe, easy, and effective new transection method for rectal cancer resection using one firing with a Nelaton catheter.

Intraoperative maneuvers may affect the development of early postoperative small bowel obstruction after laparoscopic colorectal cancer surgery: Multicenter prospective cohort study.

BACKGROUND: Early postoperative small bowel obstruction (EPSBO) is one of the most common complications after colorectal cancer (CRC) surgery, and clarification of its causes is desired. Several reports have demonstrated the risks of EPSBO, but few have focused on laparoscopic surgery for CRC and intraoperative maneuvers. We therefore prospectively examined the risk factors for EPSBO after laparoscopic CRC resection. METHODS: We prospectively enrolled 706 patients with CRC that underwent laparoscopic CRC resection in our hospital and affiliated hospitals. We analyzed several factors concerning EPSBO including intraoperative procedures. RESULTS: EPSBO developed in 43 of the 706 cases (6.1%). Univariate analysis showed that risk factors for EPSBO were male sex, increased operative time, repositioning of the small intestine before wound closure and anastomotic leakage. Risk factors for EPSBO according to multivariate analysis were increased operative time (odds ratio (OR) 2.41; P = 0.032), repositioning of the small intestine before wound closure (OR 3.58; P = 0.005) and anastomotic leakage (OR 3.91; P = 0.006). CONCLUSION: To reduce EPSBO after laparoscopic CRC surgery, the operation should be finished as soon as possible without performing optional maneuvers. To avoid development to EPSBO, particular care is required in cases where the risk of anastomotic leakage is predicted to be high.

Combination of p53 codon 72 polymorphism and inactive p53 mutation predicts chemosensitivity to 5-fluorouracil in colorectal cancer.

There are increasing reports showing the clinical significance of the p53 polymorphism status in terms of the response to chemotherapy. We investigated whether p53 polymorphism and mutation were associated with in vitro sensitivity to 5-fluorouracil (5-FU) in patients with colorectal cancer. Chemosensitivity to 5-FU was evaluated by the collagen gel droplet embedded culture drug sensitivity test. 5-FU sensitivity of tumor cells without inactive p53 mutation in the arginine/arginine (Arg/Arg) variant was significantly higher than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.022), whereas the 5-FU sensitivity of tumor cells with inactive p53 mutation in the Arg/Arg variant was significantly lower than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.002). In the Arg/Arg variant, apoptotic cells induced by 5-FU treatment in patients without inactive p53 mutation were more markedly increased than those in patients with inactive p53 mutation (p = 0.037). Bax and Bcl-2 protein expressions in tumor tissue treated with 5-FU were associated with both 5-FU sensitivity and the apoptotic cell count. Our data show that the Arg/Arg genotype without inactive p53 mutation could be predictive of a more favorable response and the Arg/Arg genotype with inactive p53 mutation a less favorable response to chemotherapy using 5-FU in CRC. The combination of the p53 codon 72 polymorphism and p53 mutation status is a potential predictive marker of sensitivity to 5-FU in CRC.

Clinicopathological features of anastomotic recurrence after an anterior resection for rectal cancer.

PURPOSE: Anastomotic recurrence after an anterior resection for rectal cancer has not been analyzed in detail in the era of total mesorectal excision. This study tried to clarify the characteristics of patients with anastomotic recurrence when compared to the pelvic recurrence. METHODS: This study compared the clinicopathological data of 21 isolated recurrent patients that were treated between 1998 and 2007, including eight with anastomotic recurrence and 13 with pelvic recurrence. RESULTS: The rate of positive serum carcinoembryonic antigen level at the time of recurrence is 0% in the anastomotic recurrence group and 85% in the pelvic recurrence group (p < 0.001). The clinical symptoms presented in 13% in the anastomotic recurrence group, in comparison to 69% in the pelvic recurrence group (p = 0.024). The median time from the initial resection until recurrence was 14 months in the anastomotic recurrence group, whereas it was 12 months in the pelvic recurrence group (p = 0.992). The survival rate of patients with anastomotic recurrence was higher than those with pelvic recurrence (p = 0.005). CONCLUSION: A difference was observed in the serum carcinoembryonic antigen, clinical symptom, and survival between patients with anastomotic and pelvic recurrence. Furthermore, according to these results, we should pay attention to these clinical features in the follow-up period.

Moderately differentiated colorectal adenocarcinoma as a lymph node metastatic phenotype: comparison with well differentiated counterparts.

BACKGROUND: The differences between the metastatic property of moderately (Mod) and well (Wel) differentiated colorectal adenocarcinoma remain unclear. Since Mod is unable to form complete acini, therefore an epithelial-mesenchymal transition (EMT) can occur in that structure. Herein, we hypothesized that Mod metastasizes more easily than the Wel counterparts. METHODS: The medical records of 283 consecutive patients with Mod (n = 71) or Wel (n = 212) who underwent surgery were reviewed between January 1, 2001, and December 31, 2003, for actual 5-year overall survival. We examined the differences between the clinicopathological characteristics of the Mod and the Wel groups. RESULTS: The lymph node involvement (p < 0.0001), lymphatic permeation, venous permeation, depth of invasion, liver metastasis, and carcinomatous peritonitis were significantly higher in the Mod group in comparison to the Wel group. The independent risk factors by a logistic regression analysis for lymph node involvement were as follows: lymphatic permeation, liver metastasis, and Mod (p = 0.0291, Relative Risk of 1.991: 95% Confidence Interval: 1.073-3.697). A Kaplan-Meier survival curve showed that Mod had a trend towards a poor survival (p = 0.0517). CONCLUSION: Mod metastasizes to the lymph nodes more easily in comparison to Wel. Therefore, patients with Mod may be considered the existence of lymph node involvement.

Identification of a compound heterozygous inactivating ABCC8 gene mutation responsible for young-onset diabetes with exome sequencing.

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years-of-age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes.

Identification of the molecular mechanisms for dedifferentiation at the invasion front of colorectal cancer by a gene expression analysis.

PURPOSE: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer. EXPERIMENTAL DESIGN: Two types of colorectal cancer were selected. Both types were well-differentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (type A, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers. RESULTS: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-beta, Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification. CONCLUSIONS: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-beta, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.

Long-term comorbidity of diabetes mellitus is a risk factor for perineal wound complications after an abdominoperineal resection.

BACKGROUND: This report is an attempt to clarify the effect of diabetes mellitus on perineal wound complications including infectious entities and delayed wound healing after abdominoperineal resection and also tried to show the risk factors for perineal wound complications. MATERIAL AND METHODS: The data of 80 patients who underwent an abdominoperineal resection were reviewed from April 1996 to March 2006. RESULTS: The rate of perineal wound complications is higher in diabetics (67%) than in nondiabetics (18%, p = 0.005). In a multivariate analysis, diabetes mellitus and operation time (> or =420 min) were the risk factors for perineal wound complications (p = 0.040, p = 0.027, respectively). Infectious perineal wound complication was associated with diabetes mellitus (p < 0.001) but not with the operation time (p = 0.097). Furthermore, a longer comorbid duration of diabetes (> or =10 years) was a significant predictor for perineal wound complications (p = 0.008). CONCLUSION: This study demonstrated diabetes mellitus to be independently associated with perineal wound complications, and when the patients have diabetes mellitus, especially with a longer comorbid duration and longer operation time, the clinical path should be changed to reduce perineal wound complications.

Survival of patients with T3 stage III rectal cancer is significantly worse than T2 stage III rectal cancer. A new proposal of a subdivision of stage III rectal cancer.

BACKGROUND: The prognosis of T1 plus T2 stage III rectal cancer patients is better than that of T3 stage III rectal cancer patients. However, it is thought that T1 rectal cancer patients have a better prognosis than T2 rectal cancer patients. AIM: This study attempted to clarify the difference of the short- and long-term outcomes in T2 and T3 stage III rectal cancer patients deleting T1 cancer. METHODS: The study demonstrated the potential predictors of the survival after surgery, the factors associated with T3 and T2, and the recurrence sites in 134 patients with stage III rectal cancer who underwent surgery, including 111 patients with T3 and 23 patients with T2. RESULTS: The disease-free survival (DFS) of the T3 stage III patients was worse than the T2 stage III patients (5-year DFS rates, 52 vs. 78%; 10-year DFS rates, 43 vs. 78%; p =0.044). The maximum tumor size and operative blood loss were significant tumor characteristics associated with the depth of invasion (p =0.007,p =0.011,respectively). There was no significant difference in the recurrence sites after surgery between the two groups. CONCLUSION: As a result, a more detailed subdivision for stage III rectal cancer is considered necessary.

Repeat reduction surgery after an initial hepatectomy for patients with colorectal cancer.

A hepatectomy is the only treatment offering long-term survival in patients with colorectal liver metastases. However, 70-80% of the patients with a complete resection develop recurrent disease after an initial hepatectomy. Sixty-one patients who underwent metastases from colorectal carcinoma with a curative hepatectomy were entered into this study. Recurrence after hepatectomy was observed in 41 patients (67.2%). We reviewed the outcome of these 41 patients. Repeat reduction surgery was performed on 16 out of 41 patients (39.0%). According to a multivariate analysis, repeat reduction surgery and tumor size were found to be independent prognostic factors for the survival rate (p=0.007, p=0.018). Furthermore, in the group that underwent repeat reduction surgery, the rate of positive lymph nodes was significantly lower in the primary lesions, and the disease-free interval (DFI) was also significantly longer than in the group that did not undergo repeat reduction surgery (p=0.023, p=0.045), respectively. Repeat reduction surgery was found to be the most important prognostic factor. Patients with a longer DFI and with negative lymph node findings at the primary site may therefore be considered to be good candidates for repeat reduction surgery.

Rectal cancer surgery in the elderly: analysis of consecutive 158 patients with stage III rectal cancer.

BACKGROUND: It is difficult to establish a clear-cut indication for rectal surgery in elderly patients because of greater risk. We tried to clarify the factors associated with the short-term and long-term outcomes between elderly and younger patients. MATERIALS AND METHODS: We clarified the potential predictors of the cancer-related and disease-free survivals after surgery, the factors associated with the elderly, preoperative comorbid conditions, and postoperative complications in 158 patients with stage III rectal cancer who underwent surgery, including 33 elderly patients (>or=75 years) and 125 younger patients (<75 years). RESULTS: An old age and macroscopic types 3 and 4 were independent poor prognostic factors of cancer-related survival, whereas the disease-free survival of the younger patients was not longer than for the elderly patients. Interestingly, the survival rate in the elderly patients with recurrence was shorter than that in the younger patients. Histopathological type except well differentiated and without chemotherapy were significant tumor characteristics associated with the elderly patients. On preoperative comorbid conditions, elderly patients have more cardiovascular diseases than younger patients, whereas there were no significant differences in the postoperative complications. CONCLUSION: Strength of the adjuvant and intensive therapies after recurrence may contribute to gain long-term survival in the elderly rectal cancer patients.

Potential predictors of survival after surgery for colorectal cancer patients with synchronous unresectable liver metastases.

Liver resection has been recognized as the best treatment for patients with colorectal liver metastases, but as a curative resection for multiple and bilobar colorectal liver metastases (MBCLM) it is definitely less effective. We clarify predictors of survival for unresectable MBCLM. Potential predictors of overall survival, and the correlation between tumor marker and survival were evaluated for patients with synchronous unresectable MBCLM, including 6 rectal and 17 colon cancers. In univariate analysis, survival in patients with the following parameters were longer than those without them: number of liver metastases (10) and a >1.0 ratio of postoperative CEA/preoperative CEA were factors of poor prognosis, and patients with two such factors had an even worse prognosis. There was a tendency for correlation between the ratio of postoperative CEA/pre-operative CEA and survival (R=-0.492, P=0.053; y=17.388-3.733x). Thus, we clarified some of the predictors of survival for MBCLM, and the usefulness of serum CEA.

The relationship between survival and the expression of dihydropyrimidine dehydrogenase in patients with colorectal cancer.

Dihydropyrimidine dehydrogenase (DPD) is considered to be a key enzyme affecting the prognosis for patients with colorectal cancer. We investigated whether a correlation exists between the expression of DPD and survival in patients with colorectal cancer. The present study was designed to quantify the DPD level using an enzyme-linked immunosorbent assay in tumors and normal tissue specimens obtained from 22 colorectal cancer patients. There were no significant differences in the preoperative features, neither in the intra- and post-operative findings of patients between the high DPD and low DPD groups in tumor tissue. In patients showing an expression of DPD in tumor tissue, the overall survival in the low DPD group tended to be longer than that in the high DPD group (P = 0.076). In contrast, in patients showing an expression of DPD in normal tissue, no significant difference was observed in the overall survival between the high DPD and low DPD groups (P = 0.358). In patients showing an expression of DPD in tumor tissue, the disease-free survival in the low DPD group was longer than that in the high DPD group (P = 0.046), whereas in patients showing an expression of DPD in normal tissue, no significant difference was seen in the disease-free survival between the high DPD and low DPD groups (P = 0.473). There tended to be a correlation between the DPD expression in tumor tissue and that in adjacent normal tissue (R = 0.390, P = 0.073). Based on these findings, we demonstrated the importance of DPD expression in tumor tissue as a prognostic factor in patients with colorectal cancer.

Potential predictors of long-term survival after surgery for patients with stage IV colorectal cancer.

BACKGROUND: The prognosis of patients with colorectal cancer is considered to be affected by several factors. Recently, chemotherapy for this disease has been demonstrated to be effective for long-term survival. In this study, the potential predictors, including chemotherapy regimens for survival after surgery, in patients with stage IV colorectal cancer are presented. PATIENTS AND METHODS: Univariate and multivariate analyses of potential predictors of survival after surgery were carried out for 56 patients with stage IV colorectal cancer who had undergone surgery, including 22 with rectal and 34 with colon cancer. RESULTS: The survival in patients who had had a primary liver resection was longer than that in patients who had not (p=0.007). There was a significant difference among chemotherapy regimens (p=0.021). The survival in patients who were administered l-leucovorin/5-fluorouracil (l-LV/5FU) was longer than that in patients who received uracil-tegafur (UFT) and cisplatin (CDDP)/5FU (p=0.024, p=0.004, respectively). In multivariate analyses, there were 5 favorable factors that influenced overall survival after surgery: lymph node metastasis (p=0.029), no bone metastasis (p=0.012), no peritoneal invasion (p=0.018), no primary liver resection (p=0.004) and the chemotherapy regimen (p=0.008). Furthermore, the survival in patients with a continued l-LV/5FU plus modified IFL regimen (additional irinotecan) was longer than for those patients who received other regimens, in both univariate and multivariate analyses. CONCLUSION: Five factors, namely lymph node metastasis, bone metastasis, peritoneal invasion, primary liver resection and chemotherapy, are potential predictors of survival after surgery for patients with stage IV colorectal cancer.

Clinical impact of adjuvant chemotherapy on patients with stage III colorectal cancer: l-LV/5FU chemotherapy as a modified RPMI regimen is an independent prognostic factor for survival.

BACKGROUND: Patients with stage III colorectal cancer have a substantial risk of microscopic metastatic disease at the time of resection. Treatment with leucovorin (LV)/5-Fluorouracil (5FU) has been demonstrated to be effective for advanced colorectal cancer; however, the clinical impact of l-LV/5FU is still unclear. 1-LV/5FU for patients with stage III colorectal cancer may play an important role, as an adjuvant chemotherapy, in improving survival. PATIENTS AND METHODS: The clinicopathological features of 36 patients receiving adjuvant l-LV/54 administration and 16 not, univariate analysis of potential predictors of overall survival and disease-free survival, relative risk of overall survival and disease-free survival by multivariate analysis and the occurrence of chemotherapy-induced toxic effects were studied in 52 patients with stage III colorectal cancer, including 30 with rectal and 22 with colon cancer, who had undergone surgery. RESULTS: No significant differences were found in the clinicopathological features of the 2 groups. On univariate analysis, there were no significant differences in overall survival in either group; disease-free survival in patients with adjuvant I-LV/5FU was longer than that in patients without it (p<0.001). Moreover, multivariate analysis demonstrated that I-LV/5FU adjuvant chemotherapy was an independent prognostic factor in terms of disease-free survival (p =0.001; RR, 17.492; 95% CI, 3.298-92.778). CONCLUSION: I-LV/5FU adjuvant chemotherapy in patients with stage III colorectal cancer is important as an independent prognostic factor in terms of disease-free survival.