Yong Beom Cho

Tumor localization for laparoscopic colorectal surgery

BackgroundBecause 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.MethodsA 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.ResultsAll 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%).ConclusionsWith 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.

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.

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

Background and aimsApproximately 20% of patients with colorectal cancer are initially diagnosed with stage IV. The majority has non-curative metastases, and their chances of survival are pitiful. This study evaluated the prognostic factors of survival and the access to the effective treatment in accordance with patients.Materials and methodsWe retrospectively analyzed 503 patients for demographics, tumor characteristics, the treatment modality, and the survival outcome. Curative operation was performed in 127 patients and palliative operation in 376 patients.ResultsFor the curative operation group, the 5-year survival rate was 34.5%, and the prognostic factors of survival and recurrence were male gender (pu2009=u20090.003, 0.009), pathologic N stage (pu2009<u20090.001, pu2009=u20090.002), and perineural invasion (pu2009=u20090.003, pu2009=u20090.026), respectively. For the non-curative operation group, the 5-year survival rate was 0%, and the median survival duration was 16.5xa0months. The potential predictors of survival for the palliative operation group were carcinoembryonic antigen level (pu2009=u20090.013), differentiation of tumor (pu2009=u20090.011), resection of primary tumor (pu2009<u20090.001), and chemotherapy (pu2009<u20090.001). But for the 131 patients with asymptomatic incurable disease, only chemotherapy was related to survival (pu2009<u20090.001).ConclusionsThe potential predictors of survival for curative stage IV colorectal cancer were male gender, pathologic N stage, and perineural invasion. Resection of the primary tumor and chemotherapy showed benefit for the incurable patients. But for the asymptomatic incurable patients, only chemotherapy prolonged the survival.

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.

Accuracy of MRI and 18F-FDG PET/CT for restaging after preoperative concurrent chemoradiotherapy for rectal cancer.

BackgroundPerforming a restaging work-up with magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) can provide information about the effects that are related to preoperative concurrent chemoradiotherapy (CCRT). The purpose of the present study was to investigate the accuracy of MRI and 18F-FDG PET/CT for restaging after preoperative CCRT for rectal cancer.MethodsBetween April 2005 and February 2006, 30 patients with histologically proven rectal adenocarcinoma were included in this study. Pelvic MRI and 18F-FDG PET/CT were performed to clinically restage the tumor after CCRT. The results of the pathologic staging were correlated with those of the MRI and 18F-FDG PET/CT after CCRT. Two patients underwent transanal endoscopic microsurgery after CCRT, and they were excluded when the N category was evaluated.ResultsThe overall accuracy of MRI for the T category was 67% (κxa0=xa00.422, Pxa0=xa00.003), whereas overstaging and understaging occurred in 30 and 3% of the patients, respectively. For the N category, accurate staging was noted in 75% (κxa0=xa00.410, Pxa0=xa00.030) of all the patients, whereas 14% were overstaged and 11% were understaged. The overall accuracy rates for the T and N categories with performing 18F-FDG PET/CT were 60% (κxa0=xa00.372, Pxa0=xa00.004) and 71% (κxa0=xa00.097, Pxa0=xa00.549), respectively. While MRI could not predict any patient who showed a pathologic complete response, 18F-FDG PET/CT predicted three of the four patients who showed a pathologic complete response after preoperative CCRT. Furthermore, 18F-FDG PET/CT identified distant metastases with an accuracy rate of 97%.ConclusionsFor restaging patients with rectal cancer after preoperative CCRT, MRI is a useful diagnostic modality to predict both the T and N categories. 18F-FDG PET/CT is helpful in predicting a pathologic complete response and in finding metastasis after preoperative CCRT.

The role of palliative resection for asymptomatic primary tumor in patients with unresectable stage IV colorectal cancer.

BACKGROUND: The prognostic role of surgical resection of primary tumors is not well established in patients with asymptomatic unresectable stage IV colorectal cancer. OBJECTIVE: The aims of this study were to reveal the prognostic role of surgical resection of primary tumors and to define prognostic factors affecting long-term oncological outcomes in patients with asymptomatic unresectable synchronous metastases. DESIGN: This study was a retrospective analysis of prospectively collected data. PATIENTS: Between 2000 and 2008, a total of 416 patients with asymptomatic unresectable stage IV colorectal cancer were analyzed with propensity score matching. MAIN OUTCOME MEASURES: Prematching baseline characteristics were compared by bivariate analysis, and 113 pairs were selected after 1:1 matching with propensity scores estimated from logistic regression. The primary end point was overall survival. RESULTS: Among 416 patients, 218 (52.4%) underwent palliative resection of the primary tumor. Before propensity score matching, palliative resection resulted in a better survival rate than nonresection in univariate analysis (p < 0.001), but not in multivariate analysis (p = 0.08). After matching, the 5-year overall survival rate was significantly lower for patients with peritoneal metastasis and clinical M1b stage tumors in univariate analysis (p = 0.004 and p = 0.02). However, neither peritoneal metastasis nor clinical M1b stage showed any prognostic significance in multivariate analysis. The overall 5-year survival rate of the postmatching group was 4.9% and 3.5% in the palliative resection and nonresection groups. Consequently, palliative resection was not associated with a significant increase in survival compared with nonresection (p = 0.27). A subgroup analysis performed according to the site of metastasis also did not show any significant survival benefit of palliative resection after matching. LIMITATIONS: Selection bias and potential confounders were limitations of this study. CONCLUSIONS: Resection of the primary tumor in patients with asymptomatic unresectable stage IV colorectal cancer was not associated with an improvement in overall survival after propensity score matching.

Oxaliplatin-Induced Chronic Peripheral Neurotoxicity: A Prospective Analysis in Patients with Colorectal Cancer

Purpose Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients. Materials and Methods This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model. Results Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m2 (range, 85 to 1,583 mg/m2). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age ≥55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN. Conclusion We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.

Predicting tumor response after preoperative chemoradiation using clinical parameters in rectal cancer

AIMnTo evaluate the clinical parameters and identify a better method of predicting pathological complete response (pCR).nnnMETHODSnWe enrolled 249 patients from a database of 544 consecutive rectal cancer patients who underwent surgical resection after preoperative chemoradiation therapy (PCRT). A retrospective review of morphological characteristics was then performed to collect data regarding rectal examination findings. A scoring model to predict pCR was then created. To validate the ability of the scoring model to predict complete regression.nnnRESULTSnSeventy patients (12.9%) achieved a pCR. A multivariate analysis found that pre-CRT movability (P = 0.024), post-CRT size (P = 0.018), post-CRT morphology (P = 0.023), and gross change (P = 0.009) were independent predictors of pCR. The accuracy of the scoring model was 76.8% for predicting pCR with the threshold set at 4.5. In the validation set, the accuracy was 86.7%.nnnCONCLUSIONnGross changes and morphological findings are important predictors of pathological response. Accordingly, PCRT response is best predicted by a combination of clinical, laboratory and metabolic information.

Clinical and Pathologic Evaluation of Patients with Recurrence of Colorectal Cancer Five or More Years After Curative Resection

PurposeThis study was designed to evaluate the characteristics of recurrences that occur five or more years after curative resection for colorectal cancer.MethodsThis study included a total of 352 patients who were confirmed as having recurrence after curative resection for colorectal cancer during the period from January 1995 to December 2000. Of the 352 patients, 231 had early recurrence (less than 2xa0years after operation), 103 had intermediate recurrence (2–5xa0years after operation), and 18 had late recurrence (more than 5xa0years after operation). The clinicopathologic findings of the patients with late recurrence were compared with those of the other two recurrence groups, with special reference to the pattern of recurrence.ResultsThe rate of late recurrence was 1.2 percent. In the late recurrence group, males outnumbered females by a ratio of 3.5:1 and the mean level of preoperative carcinoembryonic antigen was 4.5xa0ng/ml, whereas that of the early recurrence group was 30.5xa0ng/ml. All the lesions in the cases with late recurrence except one lesion were located in the left colon or rectum, the tumors were small-sized and polypoid, and well-differentiated adenocarcinomas were more frequently observed. Distant metastasis, especially lung metastasis, was most frequently observed.ConclusionsLate recurrent colorectal cancer has some characteristics compared with early or intermediate recurrence. Although recurrence at more than five years postoperatively is not common, its possibility should be considered whenever performing follow-up, and surveillance for lung metastasis is recommended after more than five years of surgery.

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.