Hungdai Kim

HER-2/neu overexpression is an independent prognostic factor in colorectal cancer

Background and aimsThe HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth, as it is extensively homologous and is related to the epidermal growth factor receptor. This phenomenon has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease and poor prognoses, and also constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationships between the expression of HER-2/neu and the clinicopathological characteristics of colorectal cancer, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for colorectal cancer patients.Patients and methodsHER-2/neu overexpression and gene amplification were examined via semiquantitative standardized immunohistochemical staining and fluorescence in situ hybridization (FISH) in 137 colorectal cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital.ResultsSixty-five (47.4%) out of 137 patients were determined by immunohistochemistry to have overexpressed HER-2/neu protein. HER-2/neu gene amplification was detected in two patients by FISH. Tumors with HER-2/neu overexpression showed higher postoperative recurrence rate (39.3% vs 14.6%, p=0.013). Tumors with HER-2/neu overexpression were associated with poor 3-year (70.8% vs 83.7%) and 5-year survival rates (55.1% vs 78.3%, p<0.05). Advanced TNM stage, postoperative recurrence, and overexpression of HER-2/neu were found to be independently related to survival by multivariate analysis.ConclusionHER-2/neu overexpression may constitute an independent prognostic factor in colorectal cancer patients, and patients exhibiting HER-2/neu overexpression might constitute potential candidates for a new adjuvant therapy which involves the use of humanized monoclonal antibodies.

Field Cancerization in Sporadic Colon Cancer

Background/Aims Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients. Methods We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated using methylation-specific PCR. Results The methylation frequencies of the SFRP2, TFPI2, NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP,TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables. Conclusions The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa.

Age Over 80 is a Possible Risk Factor for Postoperative Morbidity After a Laparoscopic Resection of Colorectal Cancer.

Purpose With extended life expectancy, the mean age of patients at the time of diagnosis of colorectal cancer and its treatment, including radical resection, is increasing gradually. We aimed to evaluate the impact of age on postoperative clinical outcomes after a laparoscopic resection of colorectal cancers. Methods This is a retrospective review of prospectively collected data. Patients with primary colorectal malignancies or premalignant lesions who underwent laparoscopic colectomies between January 2009 and April 2013 were identified. Patients were divided into 6 groups by age using 70, 75, and 80 years as cutoffs: younger than 70, 70 or older, younger than 75, 75 or older, younger than 80, and 80 or older. Demographics, pathological parameters, and postoperative clinical outcomes, including postoperative morbidity, were compared between the younger and the older age groups. Results All 578 patients underwent a laparoscopic colorectal resection. The overall postoperative complication rate was 21.1% (n = 122). There were 4 cases of operative mortality (0.7%). Postoperative complication rates were consistently higher in the older groups at all three cutoffs; however, only the comparison with a cutoff at 80 years showed a statistically significant difference between the younger and the older groups. Conclusion Age over 80 is a possible risk factor for postoperative morbidity after a laparoscopic resection of colorectal cancer.

Early oral feeding following laparoscopic colorectal cancer surgery

Early oral feeding (EOF) following colorectal surgery can accelerate patient recovery and shorten hospital stay. However, some patients are intolerable to postoperative early oral feeding. The aim of this study was to evaluate the tolerability of EOF following laparoscopic colorectal cancer surgery and the effects of intravenous lidocaine.

Is methylation analysis of SFRP2, TFPI2, NDRG4, and BMP3 promoters suitable for colorectal cancer screening in the Korean population?

Background/Aims Colorectal cancer (CRC) screening using stool DNA was recently found to yield good detection rates. A multi-target stool DNA test (Cologuard®, Exact Sciences), including methylated genes has been recently approved by the U.S. Food and Drug Administration. The aim of this study was to validate these aberrantly methylated genes as stool-based DNA markers for detecting CRC and colorectal advanced adenoma (AA) in the Korean population. Methods A single-center study was conducted in 36 patients with AA; 35 patients with CRC; and 40 endoscopically diagnosed healthy controls using CRC screening colonoscopy. The methylation status of the SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated blindly using bisulfate-modified stool DNA obtained from 111 participants. Methylation status was investigated by methylation-specific polymerase chain reaction. Results Methylated SFRP2, TFPI2, NDRG4, and BMP3 promoters were detected in 60.0%, 31.4%, 68.8%, and 40.0% of CRC samples and in 27.8%, 27.8%, 27.8%, and 33.3% of AA samples, respectively. The sensitivities obtained using 4 markers to detect CRC and AA were 94.3% and 72.2%, respectively. The specificity was 55.0%. Conclusions Our results demonstrate that the SFRP2, TFPI2, NDRG4, and BMP3 promoter methylation analysis of stool sample DNA showed high sensitivity but low specificity for detecting CRC and AA. Because of the low specificity, 4 methylated markers might not be sufficient for CRC screening in the Korean population. Further large-scale studies are required to validate the methylation of these markers in the Asian population and to find new markers for the Asian population.

Obstructive Left Colon Cancer Should Be Managed by Using a Subtotal Colectomy Instead of Colonic Stenting

Purpose This study compared a subtotal colectomy to self-expandable metallic stent (SEMS) insertion as a bridge to surgery for patients with left colon-cancer obstruction. Methods Ninety-four consecutive patients with left colon-cancer obstruction underwent an emergency subtotal colectomy or elective SEMS insertion between January 2007 and August 2014. Using prospectively collected data, we performed a retrospective comparative analysis on an intention-to-treat basis. Results A subtotal colectomy and SEMS insertion were attempted in 24 and 70 patients, respectively. SEMS insertion technically failed in 5 patients (7.1%). The mean age and rate of obstruction in the descending colon were higher in the subtotal colectomy group than the SEMS group. Sex, underlying disease, American Society of Anesthesiologists physical status, and pathological stage showed no statistical difference. Laparoscopic surgery was performed more frequently in patients in the SEMS group (62 of 70, 88.6%) than in patients in the subtotal colectomy group (4 of 24, 16.7%). The overall rate of postoperative morbidity was higher in the SEMS group. No Clavien-Dindo grade III or IV complications occurred in the subtotal colectomy group, but 2 patients (2.9%) died from septic complications in the SEMS group. One patient (4.2%) in the subtotal colectomy group had synchronous cancer. The total hospital stay was shorter in the subtotal colectomy group. The median number of bowel movements in the subtotal colectomy group was twice per day at postoperative 3–6 months. Conclusion A subtotal colectomy for patients with obstructive left-colon cancer is a clinically and oncologically safer, 1-stage, surgical strategy compared to SEMS insertion as a bridge to surgery.

Microsatellite Instability Status of Interval Colorectal Cancers in a Korean Population.

Background/Aims A subset of patients may develop colorectal cancer after a colonoscopy that is negative for malignancy. These missed or de novo lesions are referred to as interval cancers. The aim of this study was to determine whether interval colon cancers are more likely to result from the loss of function of mismatch repair genes than sporadic cancers and to demonstrate microsatellite instability (MSI). Methods Interval cancer was defined as a cancer that was diagnosed within 5 years of a negative colonoscopy. Among the patients who underwent an operation for colorectal cancer from January 2013 to December 2014, archived cancer specimens were evaluated for MSI by sequencing microsatellite loci. Results Of the 286 colon cancers diagnosed during the study period, 25 (8.7%) represented interval cancer. MSI was found in eight of the 25 patients (32%) that presented interval cancers compared with 22 of the 261 patients (8.4%) that presented sporadic cancers (p=0.002). In the multivariable logistic regression model, MSI was associated with interval cancer (OR, 3.91; 95% confidence interval, 1.38 to 11.05). Conclusions Interval cancers were approximately four times more likely to show high MSI than sporadic cancers. Our findings indicate that certain interval cancers may occur because of distinct biological features.

Does Diabetes Really Impact on Postoperative Survival in Patients with Colorectal Cancer

See Article on Page 424-428 According to a recent cohort study, diabetic patients had a significantly greater risk of colorectal cancer (CRC) than non-diabetic patients [1]. This study went one-step further and analyzed the postoperative survival difference between diabetic and non-diabetic patients with comorbid colorectal cancer. The authors found that no relationship existed between the presence of diabetes and the recurrence of or the survival rate for colorectal cancer. However, many other studies have reported that diabetes significantly and negatively impacts overall survival (OS) and that the cancer-specific survival (CSS) and prognostic impact of diabetes on OS and CSS were particularly significant in patients with stage II colon cancer [2]. However, many articles report results different from what we know. For instance, in patients undergoing colorectal cancer surgery, those with diabetes had a 23% lower in hospital mortality and fewer postoperative complications compared to those without diabetics [3], but the reason for this finding is uncertain. There are many factors affecting the result of this study. An important bias is smoking. The association with colorectal cancer risk was significantly modified by smoking status [1]. Even though the presence of diabetes did not affect the overall survival in patients diagnosed with CRC, the quality of diabetes care prior to CRC diagnosis, which persisted after diagnosis, may have moderated the mortality in patients with diabetes [4]. Insulin itself, particularly insulin glargine, may play more of a mitogenic than a carcinogenic role in association with different types of cancer, suggesting an amplified rate of existing tumor growth in the presence of insulin analogs [5]. Thus, gaining confirmative data through a simple comparison between the presence and the absence of diabetics for estimating a prognosis for the disease is extremely difficult because it is hard to control so many kinds of biases. Furthermore, the reliability of the results is quite low because the number in the observation group was relatively small (67) compared with that in the control group (590) in this study. Therefore, a population-based prospective cohort study, rather than a case-control study, is needed to yield data in which one can have more confidence.