Prognostic factors associated with primary cancer in curatively resected stage IV colorectal cancer.

PURPOSE: The aim of this study is to evaluate the prognostic factors associated with primary cancer in patients with curatively resected stage IV colorectal cancer, based on lymph node status. METHODS: A total of 468 consecutive patients with curatively resected stage IV colorectal cancer from October 1994 to December 2010 were prospectively enrolled. Survival curves were constructed using the Kaplan-Meier method, and multivariate analysis assessed independent prognostic factors. RESULTS: During the median follow-up period of this study, which was 37 months (range 1-177), the 3- and 5-year overall survival rates were 66.5 and 52.1%, respectively, and the 3- and 5-year disease-free survival rates were 43.0 and 38.2%, respectively. According to multivariate analysis, adjuvant chemotherapy and the preoperative serum carcinoembryonic antigen (CEA) level were independent prognostic factors for overall survival, and primary tumor location and preoperative serum CEA level were independent variables for disease-free survival. For the patients with N0 and N1 tumors, the overall survival curves in the preoperative CEA groups differed significantly (P = 0.046 and P < 0.013, respectively). However, for patients with pN2 tumors, the overall survival did not differ significantly according to the preoperative CEA (P = 0.948). CONCLUSION: The preoperative serum CEA level is a reliable predictor of recurrence and survival after curative surgery in patients with metastatic colorectal cancer. A multidisciplinary approach that combines both complete resection and adjuvant chemotherapy may achieve improved overall survival in these patients.

The effect of postoperative pelvic irradiation after complete resection of metastatic rectal cancer.

BACKGROUND AND OBJECTIVES: The 2010 NCCN clinical practice guidelines recommend radiation as a part of the standard adjuvant or neoadjuvant treatment for stage IV rectal cancer patients. This study evaluated the oncologic efficacy of postoperative radiotherapy (RTx) in loco-regional control after complete removal of primary and metastatic lesions in stage IV rectal cancer. METHODS: Sixty-eight patients with metastatic rectal cancer were enrolled and analyzed. Twenty-eight of the enrolled patients received concurrent postoperative RTx with chemotherapy (RTx group) and the remaining 40 received only postoperative systemic chemotherapy (CTx) without RTx (non-RTx group). The eligibility criteria were as follows: a primary rectal tumor located in the low or mid-rectum, no postoperative macroscopic and microscopic evidence of residual tumor in primary and metastatic sites, and no history of prior CTx or pelvic RTx. RESULTS: The recurrence rates were 75.0% in the RTx group and 72.5% in the non-RTx group. Local recurrence rates were 7.1% (RTx group) and 22.5% (non-RTx group) (P = 0.108). There were no differences in overall survival (OS), local recurrence-free survival, and disease-free survival between the two groups. The 2-year OS rates were 78.9% (RTx group) and 74.1% (non-RTx group) (P = 0.395). CONCLUSIONS: Survival benefit of postoperative RTx in stage IV rectal cancer after complete removal of tumors was not apparent. RTx could be recommended for selected patients at high risk of local recurrence or for palliation of symptoms.

Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy.

PURPOSE: Colon cancer with DNA mismatch repair (MMR) defects reveals indistinguishable clinical and pathologic aspects, including better prognosis and reduced response to 5-fluorouracil (5-FU)-based chemotherapy. There has been no consensus for p53 as a prognostic marker in colorectal cancer. This study investigated the clinical implication of MSI-H/MMR-D and p53 expression in R0-resected colon cancer patients who received adjuvant oxaliplatin/5-FU/leucovorin (FOLFOX) therapy. EXPERIMENTAL DESIGN: We analyzed 135 patients, who had been treated by adjuvant chemotherapy containing 5-FU and oxaliplatin (FOLFOX) after curative resection (R0) for colon adenocarcinoma between May 2004 and November 2007. Tumor expression of the MMR proteins, MLH1 and MSH2, was detected by immunohistochemistry (IHC) in surgically resected tumor specimens. MSI was analyzed by polymerase chain reaction (PCR) amplification using fluorescent dye-labeled primers specific for microsatellite loci. Tumors with MMR defects were defined as those demonstrating loss of MMR protein expression (MMR-D) and/or microsatellite instability high (MSI-H) genotype. Expression patterns of p53 were determined in a semiquantitative manner by light microscopy. RESULTS: There were 13 (9.6%) patients with stage II, 108 (80%) with stage III, and 14 (10.4%) with stage IV. Fourteen patients with stage IV (10.3%) had metastases to liver only, all of whom underwent complete metastasectomy for liver metastases. In total, 134 tumor specimens were genotyped, 115 specimens were tested by IHC and 113 cases had both genotyping and IHC results available for analysis. Genotyping results demonstrated that 12 (9.0%) cases were MSI-H and 122 (91.0%) were MSI-L/S. By IHC, 11 (9.6%) patients were MMR-D and 104 (90.4%) were MMR-I. The methods were in agreement in 108 patients (94.7%). We assessed 114 patients for p53 expression by immunostaining. MMR status was not significantly associated with DFS (P = 0.56) or OS (P = 0.61) in patients with colon cancer (n = 135) receiving adjuvant FOLFOX. According to p53 status, there was also no significant difference for DFS (P = 0.11) and OS (P = 0.94). For patients with genotyping/IHC agreement (n = 108), there was no difference in DFS (P = 0.57) and OS (P = 0.98) between patients with MSI-H/MMR-D and MSI-L/S/MMR-I tumors. CONCLUSION: The MMR status or p53 positivity was not significantly associated with outcomes to FOLFOX as adjuvant chemotherapy in colon cancer patients with R0 resection. Adding oxaliplatin in adjuvant chemotherapy may overcome negative impact of 5-FU on colon cancers with MSI-H/MMR-D.

Relationship of polymorphism of the tandem repeat sequence in the thymidylate synthase gene and the survival of stage III colorectal cancer patients receiving adjuvant 5-flurouracil-based chemotherapy.

BACKGROUND: The aim of this study was to determine whether the different polymorphisms in the thymidylate synthase (TS) gene, novel G>C single nucleotide polymorphism (SNP) and variable number of tandem repeat (VNTR), may be related with disease-free survival (DFS) in patients with stage III colorectal cancer receiving adjuvant chemotherapy. METHODS: The study included 201 patients with pathologic TNM stage III colon cancer who received adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgery. DNA was extracted from fresh tumor tissue and sequenced. Patients with TS genotypes of 2R3G, 3C3G, or 3G3G were assigned to a high expression group, and those with 2R2R, 2R3C, or 3C3C, to a low expression group. RESULTS: Frequencies of the TS tandem repeat polymorphisms among the tumor genotypes were 6.0% in 2R2R, 25.4% in 2R3R, and 68.7% in 3R3R. The low expression group included 52 patients (25.9%), and the high expression group included 149 patients (74.1%). Groups classified according to possession of VNTR, SNP, and low- or high-expression genotypes did not differ significantly in DFS. In multivariate analysis, only tumor stage showed significant prognostic value (hazard ratio (HR) 2.05, 95% CI = 1.24-3.37, P = 0.005). CONCLUSIONS: TS polymorphisms do not predict clinical outcome of colorectal cancer patients treated with adjuvant 5-FU-based chemotherapy.

Compliance and effective management of the hand-foot syndrome in colon cancer patients receiving capecitabine as adjuvant chemotherapy.

PURPOSE: Physicians and oncology nurses must continue to update their knowledge on treatment and treatment-related side effects, while searching for effective methods to prevent or manage side effects. The objective of our study was to describe the incidence and response to treatment of the hand-foot syndrome (HFS) and the compliance with treatment of patients with stage IIB, IIIA, IIIB, and IIIC colon cancer that were treated with capecitabine alone as adjuvant therapy. MATERIALS AND METHODS: Between September 2005 and September 2006, 84 patients fulfilled the inclusion criteria and were included in this retrospective analysis of prospectively collected data. RESULTS: The treatment compliance rate was 90.5% (76 out of the 84 patients). The HFS developed in 65 patients (77.4%). Thirty-three patients (50.7%) had grade 1 HFS, 22 patients (33.8%) had grade 2 HFS and 10 patients (15.5%) had grade 3 HFS, as their most severe episode. For Grade 1 patients, the dose was maintained, and skin barrier cream and moist exposed burn ointment (MEBO) were applied. For Grade 2 patients, either the dose was maintained or 25% of the dose was reduced; MEBO and supportive care were provided. For Grade 3 patients, one cycle of chemotherapy was interrupted followed by dose adjustment; MEBO and supportive care were provided. CONCLUSION: HFS is manageable if both patients and oncology care teams are educated about HFS associated with capecitabine. The HFS is treated by patient education, preventive management, ointment application, conservative management, dose reduction, and interruption of chemotherapy administration.

En bloc resection for right colon cancer directly invading duodenum or pancreatic head.

PURPOSE: We undertook this study to analyze clinical features and surgical outcome of en bloc resections of the right side colon cancer directly invading duodenum and/or pancreatic head. MATERIALS AND METHODS: The records of all patients who underwent en bloc resection of duodenum and/or pancreas for right colon cancers were analyzed retrospectively. From September 1994 to September 2006, 1,016 patients underwent curative right hemicolectomy. Nine patients (0.9%) had en bloc resection of a right side colon cancer with duodenum or pancreatic head invasion. RESULTS: The median operative time was 320 minutes (range, 200-420) and the median blood loss was 700 mL (range, 100-2,000). The mean size of tumor was 6.6 cm (range, 3.2-10.7). The mean preoperative carcinoembryonic antigen (CEA) was 10.6 ng/mL (range, 0.2-50.8). There was no 30 day perioperative mortality. The median disease-free survival was 23.5 months [95% confidence interval (CI) 5.2-41.8] and the median overall survival was 28.1 months (95% CI 9.7-46.5). CONCLUSION: In patients with locally advanced right side colon cancer that directly invades the duodenum or pancreas can be safely resected with curative potential with minimum morbidity and mortality. Long term disease free survival can occur in a significant number of patients undergoing curative en bloc resection in this particular subset of patients.

Tumor localization for laparoscopic colorectal surgery.

BACKGROUND: Because palpating colonic tumors during laparoscopy is impossible, the precise location of a tumor must be identified before operation. The aim of this study was to evaluate the accuracy of various diagnostic methods that are used to localize colorectal tumors and to propose an adequate localization protocol for laparoscopic colorectal surgery. METHODS: A total of 310 patients underwent laparoscopy-assisted colectomy between April 2000 and March 2006. We investigated if the locations of the tumors that were estimated preoperatively were consistent with the actual locations according to the operation. RESULTS: All the tumors were correctly localized and resected. Altogether, 203 patients had complete endoscopic reports available. Colonoscopy was inaccurate for tumor localization in 23 cases (11.3%). In total, 104 patients (33.5%) underwent barium enema; five tumors (4.8%) were not visualized, and three tumors were incorrectly localized. Another group of 94 patients (30.3%) underwent computed tomography (CT) colonography, which identified 91 of 94 lesions (96.8%). Finally, 96 patients (31.0%) underwent endoscopic tattooing; 2 patients (2.1%) did not have tattoos visualized laparoscopically and required intraoperative colonoscopy to localize their lesions during resection. Dye spillage was found in six patients intraoperatively, but only one patient experienced clinical symptoms. Intraoperative colonoscopy was performed in four patients; two of the four were followed by endoscopic tattooing, and the other two underwent intraoperative colonoscopy for localization. All lesions were correctly localized by intraoperative colonoscopy. The accuracy of tumor localization was as follows: colonoscopy (180/203, 88.7%), barium enema (97/104, 93.3%), CT colonography (89/94, 94.7%), endoscopic tattooing (94/96, 97.9%), and intraoperative colonoscopy (4/4, 100%). CONCLUSIONS: With a combination of methods, localization of tumors for laparoscopic surgery did not seem very different from that during open surgery. Preoperative endoscopic tattooing is a safe, highly effective method for localization. In the case of tattoo failure, intraoperative colonoscopy can be used for accurate localization.