Hae-Ran Yun

Pulmonary resection for metastases from colorectal cancer: prognostic factors and survival

BackgroundsPulmonary metastases occur in up to 10% of all patients who undergo curative resection. Surgical resection is an important part in the treatment of pulmonary metastasis from colorectal cancer. We analyzed the treatment outcome and prognostic factors affecting survival in this subset of patients.Materials and methodsBetween October 1994 and December 2004, 59 patients underwent curative resection for pulmonary metastases of colorectal cancer. Uncontrollable synchronous liver and lung metastasis or synchronous colorectal cancer with isolated lung metastasis were excluded from this study. A retrospective review of patient characteristics and factors influencing survival was performed. Survival was analyzed by the Kaplan–Meier method. Comparison between groups were performed by a log-rank analysis and the Cox proportional hazard model.ResultsThe 5-year overall survival rate of all patients who received pulmonary resection was 50.3%. The number of pulmonary metastases was significantly related with survival in univariate analysis, but not in multivariate analysis (pu2009=u20090.032). Prethoracotomy carcinoembryonic antigen (CEA) level exceeding 5xa0ng/ml was related with poor survival (pu2009=u20090.001). A disease-free interval of greater than 2xa0years did not correlate with survival after thoracotomy (pu2009=u20090.3).ConclusionThe prethoracotomy CEA level and the number of metastases were independent prognostic factors. Resection of pulmonary metastasis from colorectal cancer may result in improved survival or even healing in selected patients. Pulmonary resection of colorectal cancer is regarded as a safe and effective treatment with low morbidity and mortality rates.

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

PurposeColon 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 designWe 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.ResultsThere 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 (Pxa0=xa00.56) or OS (Pxa0=xa00.61) in patients with colon cancer (nxa0=xa0135) receiving adjuvant FOLFOX. According to p53 status, there was also no significant difference for DFS (Pxa0=xa00.11) and OS (Pxa0=xa00.94). For patients with genotyping/IHC agreement (nxa0=xa0108), there was no difference in DFS (Pxa0=xa00.57) and OS (Pxa0=xa00.98) between patients with MSI-H/MMR-D and MSI-L/S/MMR-I tumors.ConclusionThe 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.

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

Background and aimsThere 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 methodsA 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 3xa0years.ResultsThere were 994 patients with colon cancer and 844 patients with rectal cancer. The median duration of follow-up was 60.9u2009±u200924.5xa0months. 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 (pu2009<u20090.001). 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 3xa0years in 59.9% and 82.4% of the patients, respectively. In patients with colon and rectal cancer, the pathologic T stage (pu2009=u20090.044 and pu2009=u20090.034, respectively), pathologic N stage (pu2009=u20090.001 and pu2009<u20090.001, respectively), and lymphovascular invasion (pu2009=u20090.013 and pu2009=u20090.004, respectively) were adverse risk factors for local recurrence. The level of the anastomosis from the anal verge was an additional prognostic factor (pu2009=u20090.007) in patients with rectal cancer.ConclusionCompulsive follow-up care of patients with colon and rectal cancers is needed for 3xa0years after curative resection, especially in patients who have adverse risk factors for local recurrence.

Treatment outcomes of hepatic and pulmonary metastases from colorectal carcinoma

Background and Aim:u2002 The resection of synchronous or metachronous pulmonary and liver metastasis is an aggressive treatment option for patients with stage IV colorectal cancer and has been shown to yield acceptable long‐term survival. We reviewed our experience with colorectal cancer patients with both liver and lung resections to determine the efficacy of surgical resections.

Double primary malignancy in colorectal cancer patients—MSI is the useful marker for predicting double primary tumors

Background and aimsThe incidence of double primary malignancies (DPM) is known to be higher in colorectal cancer patients than the general population. And, the role of microsatellite instability (MSI) in DPM has been previously studied. We evaluated the clinical features and association between MSI and colorectal cancer patients with DPM.Materials and methodsFrom September 1994 to May 2004, we reviewed 2,301 colorectal cancer patients with regard to secondary primary malignancies. A subgroup analysis was performed for MSI after January 2003.ResultsOne hundred forty-five patients (6.3%) had a DPM identified. In DPM group, 57 patients had a synchronous DPM (39.3%), and 88 patients had a metachronous malignancy (60.7%). Male gender (pu2009<u20090.001) and colon cancer (pu2009<u20090.001) were the factors related with the development of the DPM. Most of the second malignancies occurred within 3xa0years after the primary operation. The common second malignancies were stomach (58 patients, 40%) and lung (21 patients, 14.5%). In the subgroup analysis, there was a higher frequency of DPM in the MSI group when compared to the microsatellite stable group (pu2009=u20090.021).ConclusionsThe careful pre- and postoperative evaluation should be paid for detecting DPM as well as for detecting recurrence in colorectal cancer patients. The results of this study suggest that MSI might be a useful marker for the detection of DPM in colorectal cancer patients.

The effect of DNA mismatch repair (MMR) status on oxaliplatin-based first-line chemotherapy as in recurrent or metastatic colon cancer

Colon cancer with DNA mismatch repair (MMR) defects reveals distinct clinical and pathologic features, including a better prognosis but reduced response to 5-fluorouracil (5-FU)-based chemotherapy. A current standard treatment for recurrent or metastatic colon cancer uses capecitabine plus oxaliplatin (CAPOX), or continuous-infusion fluorouracil plus oxaliplatin (FOLFOX). This study investigated the effect of MMR status on the treatment outcomes for CAPOX and FOLFOX as first-line combination chemotherapy in recurrent or metastatic colon cancer. We analyzed 171 patients who had been treated with CAPOX or FOLFOX as first-line combination chemotherapy in recurrent or metastatic colon adenocarcinoma between February 2004 and July 2008. Tumor expression of the MMR proteins, MLH1 and MSH2, was detected by immunohistochemistry (IHC) in surgically resected tumor specimens. The microsatellite instability (MSI) was analyzed by polymerase chain reaction (PCR) amplification, using fluorescent dye-labeled primers specific to microsatellite loci. Tumors with MMR defect were defined as those demonstrating a loss of MMR protein expression (MMR-D) and/or a microsatellite instability-high (MSI-H) genotype. In all, 75 patients (44%) received FOLFOX, and 96 patients (56%) received CAPOX as first-line combination chemotherapy. The incidence of colon cancer with MMR defect was 10/171 (6%). Colon cancers with MMR defect (MSI-H and/or MMR-D) are more commonly located in proximal to the splenic flexure (pxa0=xa00.03). The MMR status did not significantly influence the overall response (pxa0=xa00.95) to first-line CAPOX or FOLFOX treatment in patients with recurrent or metastatic colon cancer. According to the MMR status, there was no significant difference for PFS (pxa0=xa00.50) and OS (pxa0=xa00.47) in patients with recurrent or metastatic colon cancer treated with first-line CAPOX or FOLFOX. In colon cancers with MMR defect, there was no significant difference for PFS (pxa0=xa00.48) and OS (pxa0=xa00.56) between CAPOX and FOLFOX as first-line combination chemotherapy. However, in MMR intact, there was significant difference for OS between CAPOX and FOLFOX (pxa0=xa00.04). OS was significantly better in patients treated with CAPOX when compared to patients with FOLFOX. The MMR status does not predict the effect of oxaliplatin-based combination chemotherapy as 1st line in recurrent or metastatic colon cancers. CAPOX in the first-line treatment of recurrent or metastatic colon cancer with MMR intacts showed a superior OS compared with FOLFOX unlike colon cancer with MMR defects.

Clinical usefulness of chest radiography in detection of pulmonary metastases after curative resection for colorectal cancer.

PurposeThe purpose of this study was to evaluate the effectiveness of chest radiography (CXR) and abdominal computed tomography (CT) for detecting pulmonary metastases after curative surgery for colorectal cancer.MethodsWe performed a retrospective analysis of the records of all patients with pulmonary metastasis from colorectal cancer who underwent curative resection between 1994 and 2004 at our institution. ResultsPulmonary metastases were detected in 193 patients by either CXR or abdominal CT. They were initially detected by CXR in 87 patients (45.1%) and by abdominal CT in 106 patients (54.9%). In the CXR group, the patterns of pulmonary recurrence were as follows: solitary (n = 38, 43.7%), multiple unilateral (n = 11, 12.6%), and multiple bilateral (n = 38, 43.7%). In the CT group, there were 22 patients (20.8%) with a solitary nodule, 17 patients (16.0%) with multiple unilateral nodules, and 67 (63.2%) with multiple bilateral nodules. The overall survivals of the CXR group and abdominal CT group were 34.6% and 31.7%, respectively (p = 0.312). There was no difference in the median disease-free interval between the CXR group and the abdominal CT group (23.8 vs. 23.2 months, p = 0.428).ConclusionsAlthough this study is limited by its small sample size, it can be speculated that abdominal CT with lower thorax images may replace CXR in surveillance programs.

An Alternative Pathway in Colorectal Carcinogenesis Based on the Mismatch Repair System and p53 Expression in Korean Patients with Sporadic Colorectal Cancer

PurposeMicrosatellite instability (MSI) and chromosomal instability are main mechanisms underlying colorectal carcinogenesis. We determined the features and prognosis of colorectal cancer based on MSI including mismatch repair genes and expression of p53.MethodsBetween 1999 and 2008, a total of 2,649 colorectal cancer patients were analyzed using a prospective database. A mismatch repair defect (MMR-D) was defined as a loss of expression of more than one MMR protein and/or MSI-high. MMR-proficiency (MMR-P) was defined as expression of all MMR proteins and microsatellite stable (MSS)/MSI-low. Groups 1 (G1), 2 (G2), 3 (G3), and 4 (G4) were defined as MMR-D and p53-positive expression, MMR-D and p53-negative expression, MMR-P and p53-positive expression, MMR-P and p53-negative expression, respectively.ResultsEighty-two (3.0xa0%), 181 (6.8xa0%), 1,368 (51.7xa0%), and 1,018 (38.5xa0%) patients were classified into groups 1–4, respectively. Comparison between G1 and G2 showed differences in location (pxa0<xa00.001), size (pxa0=xa00.030), node metastasis (pxa0=xa00.027), distant metastasis (pxa0=xa00.009), and stage (pxa0=xa00.040). Comparison between G3 and G4 showed differences in location (pxa0<xa00.001) and histology (pxa0<xa00.001). Comparison between G1 and G3 showed differences in location (pxa0<xa00.001) and histology (pxa0<xa00.001). Comparison between G2 and G4 showed differences in age (pxa0<xa00.001), location (pxa0<xa00.001), size (pxa0=xa00.006), histology (pxa0<xa00.001), node metastasis (pxa0<xa00.001), distant metastasis (pxa0<xa00.001), and stage (pxa0<xa00.001). On multivariate analysis, stage (pxa0=xa00.007) and histology (pxa0<xa00.001) were associated with improved overall survival, and stage (pxa0<xa00.001) was associated with disease-free survival.ConclusionsAccording to the MSI and p53 subsets, colorectal cancers showed different clinicopathologic features, but these subsets had no prognostic impact on overall and disease-free survival rate.

Curved cutter stapler vs. linear stapler in rectal cancer surgery: a pilot prospective randomized study

ObjectiveThis study aimed to compare the safety and technical accessibility of linear stapler and curved cutter stapler (CCS) during mid to low rectal cancer surgery.Materials and methodsBetween April and November 2006, 60 patients were randomly assigned to either linear staplers (DST TA®; United States Surgical, Tyco Healthcare Group LP, Norwalk, CT) or the CCS (Contour Curved Cutter Stapler®; Ethicon Endo-Surgery, Inc., Cincinnati, OH) during low anterior resection for mid to low rectal cancers.ResultsThere were no significant differences in age, gender, body mass index, and mean carcinoembryonic antigen level between the two groups. Distal resection margin was longer in the CCS group as compared with the linear stapler group but did not reach statistical significance (24.7 vs. 20.8xa0mm, Pu2009=u20090.065). There was no difference in the incidence of postoperative complications.ConclusionIn this study, both the CCS and linear staplers were satisfactory devices for securing the distal rectum during low anterior resection in mid to low rectal cancers.

Early surgical outcomes of NiTi endoluminal compression anastomotic clip (NiTi CAC 30) use in patients with gastrointestinal malignancy.

BACKGROUNDnThe NiTi endoluminal Compression Anastomotic Clip (CAC™) 30 (NiTi CAC 30) (NiTi Alloys Technologies, Ltd., Netanya, Israel) is a new device with shape-memory characteristics. We aimed to investigate the safety and early surgical outcomes of NiTi CAC 30 for intestinal anastomosis in patients with gastrointestinal malignancy.nnnSUBJECTS AND METHODSnFifty patients operated on with NiTi CAC 30 were matched for sex, age, body mass index, operation type (open versus laparoscopy), operation name, and anastomosis type with patients in a control group operated on with a stapling device between November 2009 and May 2010. Early clinical outcomes were investigated.nnnRESULTSnOne misfired case of NiTi CAC 30 was excluded. Between the two groups, no significant differences were observed in demographics except for previous abdominal operation history. The results of early clinical outcomes were investigated, including operation time, estimated blood loss, time to first flatus, first defecation, and discharge, and complications. No differences were noted. Postoperatively, migration started in 1 patient between 3 and 5 days, 11 patients between 6 to 7 days, and 37 patients after 8 days. The expulsion of 31 cases occurred between 2 and 3 weeks, postoperatively. The NiTi CAC 30 was expulsed within 1 week in 4 patients and between 1 to 2 weeks in 8 patients. An expulsion occurred in 1 case at over 4 weeks. No problems related to early migration and expulsion were observed, and no anastomotic leakage and bleeding occurred.nnnCONCLUSIONSnIntestinal anastomosis with the NiTi CAC 30 was safe and feasible without anastomotic leakage and reoperation compared with the stapling technique.