Myong Hoon Ihn

Risk factors for bowel dysfunction after sphincter-preserving rectal cancer surgery: a prospective study using the Memorial Sloan Kettering Cancer Center bowel function instrument.

BACKGROUND: Until recently, no studies have prospectively evaluated bowel function after sphincter-preserving surgery for rectal cancer with the use of a validated bowel function scoring system. OBJECTIVE: The aim of this study was to investigate possible risk factors for altered bowel function after sphincter-preserving surgery. DESIGN: This was a prospective study. SETTINGS: The study was conducted between January 2006 and May 2012 at the authors’ institution. PATIENTS: Patients who underwent sphincter-preserving rectal cancer surgery were recruited. MAIN OUTCOME MEASURES: Bowel function was assessed 1 day before (baseline) and at 1 year after sphincter-preserving surgery or temporary ileostomy takedown with the use of the Memorial Sloan Kettering Cancer Center questionnaire. Multivariable analysis was performed to identify the factors associated with altered bowel function after surgery. RESULTS: Overall, 266 patients were eligible for the analysis. The tumor was located in the upper, middle, and lower rectum in 68 (25.5%), 113 (42.5%), and 85 (32.0%) patients. Intersphincteric resection and temporary ileostomy were performed in 18 (6.8%) and 129 (48.5%) patients. The mean Memorial Sloan Kettering Cancer Center score was 64.5 ± 7.6 at 1 year after sphincter-preserving surgery or temporary ileostomy takedown. The Memorial Sloan Kettering Cancer Center score decreased in 163/266 patients (61.3%) between baseline and 1 year after surgery. Tumor location (p = 0.01), operative method (p = 0.03), anastomotic type (p = 0.01), and temporary ileostomy (p = 0.01) were associated with altered bowel function after sphincter-preserving surgery in univariate analyses. In multivariable analysis, only tumor location was independently associated with impaired bowel function after sphincter-preserving rectal cancer surgery. LIMITATIONS: This study was limited by its nonrandomized design and the lack of measurement before preoperative chemoradiotherapy. CONCLUSION: We suggest that preoperative counseling should be implemented to inform patients of the risk of bowel dysfunction, especially in patients with lower rectal cancer, although this study cannot exclude the effect of chemoradiotherapy owing to the limitation of study.

Loss of AT-Rich Interactive Domain 1A Expression in Gastrointestinal Malignancies

Objective: AT-rich interactive domain 1A (ARID1A) has recently been identified as a novel tumor suppressor in various tumor types. This study was designed to explore the clinical relevance and prognostic impact of ARID1A expression loss in colorectal cancer (CRC) and gastric cancer (GC). Methods: Immunohistochemistry for ARID1A was performed using tissue microarray blocks containing 196 CRCs and 275 GCs, along with paired normal mucosa. Data on clinicopathologic variables and oncologic outcomes of patients were collected and analyzed. Results: We identified 6.1% (12/196) CRC and 8.0% (22/275) GC cases showing loss of ARID1A expression. Expression of ARID1A in paired mucosal epithelial cells was normal in all patients. Loss of ARID1A expression was significantly correlated with negative lymphatic invasion (p = 0.003) in CRC, with large tumor size (p = 0.037) in GC, and with expanding tumor border in both tumor types (CRC, p = 0.010; GC, p = 0.031). However, no association was evident between ARID1A expression and 5-year overall survival in both tumor types. Conclusions: Loss of ARID1A expression is uncommon and not associated with oncologic outcome but may be related to less invasive clinicopathologic features in CRC and GC. Further studies with a larger number of subjects are needed to establish the possible prognostic impact of ARID1A expression loss.

Curative Resection for Metachronous Pulmonary Metastases from Colorectal Cancer: Analysis of Survival Rates and Prognostic Factors

Purpose Prognostic factors in patients with pulmonary metastases (PM) from colorectal cancer (CRC) are still controversial. This study assessed oncologic outcomes and prognostic factors in patients with metachronous PM from CRC. Materials and Methods Between June 2003 and December 2011, 122 patients with CRC underwent curative resection of PM detected at least 4 months after CRC resection. Clinico-pathological factors selected from the prospectively maintained database were analyzed retrospectively. Results The median disease-free interval (DFI) between resection of the primary tumor and detection of PM was 22.0 months (range, 4 to 85 months). Solitary PM were detected in 77 patients (63.1%), with a median maximal tumor diameter of 12.0 mm (range, 2 to 70 mm). Of 52 patients who underwent mediastinal lymph node (LN) dissection, eight patients had LN involvement. Five-year overall survival and disease-free survival (DFS) rates after initial pulmonary metastasectomy were 66.4% and 50.9%, respectively. DFI, mediastinal LN involvement, and the number and distribution of PM were significantly prognostic factors for DFS. In multivariable analysis DFI ≥ 12 months, solitary lesion, and absence of mediastinal LN involvement were independently prognostic for DFS. Of the 122 patients, 48 patients (39.3%) developed recurrent PM a median 13.0 months after initial pulmonary metastasectomy. Recurrent DFI was independently prognostic of DFS in patients who underwent repeated pulmonary metastasectomy. Conclusion There is a potential survival benefit for patients with metachronous PM from CRC who undergo pulmonary metastasectomy, even those with recurrent PM. Pulmonary metastasectomy should be considered in selected patients, particularly those with longer DFI, solitary lesions, and absence of mediastinal LN involvement.

Prospective Study on the Incidence of Postoperative Venous Thromboembolism in Korean Patients with Colorectal Cancer.

Purpose Pharmacologic thromboprophylaxis is routinely recommended for Western cancer patients undergoing major surgery for prevention of venous thromboembolism (VTE). However, it is uncertainwhetherroutine administration of pharmacologic thromboprophylaxis is necessary in all Asian surgical cancer patients. This prospective study was conducted to examine the incidence of and risk factors for postoperative VTE in Korean colorectal cancer (CRC) patients undergoing major abdominal surgery. Materials and Methods This study comprised two cohorts, and none of patients received perioperative pharmacologic thromboprophylaxis. In cohort A (n=400), patients were routinely screened for VTE using lower-extremity Doppler ultrasonography (DUS) on postoperative days 5-14. In cohort B (n=148), routine DUS was not performed, and imaging was only performed when there were symptoms or signs that were suspicious for VTE. The primary endpoint was the VTE incidence at 4 weeks postoperatively in cohort A. Results The postoperative incidence of VTE was 3.0% (n=12) in cohort A. Among the 12 patients, eight had distal calf vein thromboses and one had symptomatic thrombosis. Age ≥ 70 years (odds ratio [OR], 5.61), ≥ 2 comorbidities (OR, 13.42), and white blood cell counts of > 10,000/μL (OR, 17.43) were independent risk factors for postoperative VTE (p < 0.05). In cohort B, there was one case of VTE (0.7%). Conclusion The postoperative incidence of VTE, which included asymptomatic cases, was 3.0% in Korean CRC patients who did not receive pharmacologic thromboprophylaxis. Perioperative pharmacologic thromboprophylaxis should be administered to Asian CRC patients on a risk-stratified basis.

Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans

Purpose Lynch syndrome, the commonest hereditary colorectal cancer syndrome, is caused by germline mutations in mismatch repair (MMR) genes. Three recently developed prediction models for MMR gene mutations based on family history and clinical features (MMRPredict, PREMM1,2,6, and MMRPro) have been validated only in Western countries. In this study, we propose validating these prediction models in the Korean population. Materials and Methods We collected MMR gene analysis data from 188 individuals in the Korean Hereditary Tumor Registry. The probability of gene mutation was calculated using three prediction models, and the overall diagnostic value of each model compared using receiver operator characteristic (ROC) curves and area under the ROC curve (AUC). Quantitative test characteristics were calculated at sensitivities of 90%, 95%, and 98%. Results Of the individuals analyzed, 101 satisfied Amsterdam criteria II, and 87 were suspected hereditary nonpolyposis colorectal cancer. MMR mutations were identified in 62 of the 188 subjects (33.0%). All three prediction models showed a poor predictive value of AUC (MMRPredict, 0.683; PREMM1,2,6, 0.709; MMRPro, 0.590). Within the range of acceptable sensitivity (> 90%), PREMM1,2,6 demonstrated higher specificity than the other models. Conclusion In the Korean population, overall predictive values of the three models (MMRPredict, PREMM1,2,6, MMRPro) for MMR gene mutations are poor, compared with their performance in Western populations. A new prediction model is therefore required for the Korean population to detect MMR mutation carriers, reflecting ethnic differences in genotype-phenotype associations.

Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer.

AbstractAlthough microsatellite instability-high (MSI-H) colorectal cancers (CRCs) have been shown to exhibit a distinct phenotype, the clinical value of MSI-low (MSI-L) in CRC remains unclear. We designed this study to examine the clinicopathologic characteristics and oncologic implications associated with MSI-L CRCs.We retrospectively reviewed data of CRC patients from 3 tertiary referral hospitals in Korea, who underwent surgical resection between January 2003 and December 2009 and had available MSI testing results. MSI testing was performed using the pentaplex Bethesda panel. Clinicopathologic features and oncologic outcomes were compared between MSI-L and microsatellite stable (MSS) CRCs; prognostic factors for survival were also examined.Of the 3019 patients reviewed, 2621 (86.8%) were MSS, and 200 (6.6%) were MSI-L; the remaining 198 (6.6%) were MSI-H. MSI-L and MSS CRCs were comparable in terms of their clinicopathologic features, with the exception of proximal tumor location (MSI-L 30.0% vs MSS 22.1%, P = 0.024) and tumor size (MSI-L 5.2 ± 2.6 cm vs MSS 4.6 ± 2.1 cm, P = 0.001). No differences were detected in either 3-year disease-free survival (MSI-L 87.2% vs MSS 82.6%, P = 0.121) or 5-year overall survival (OS) (MSI-L 74.2% vs MSS 78.3%, P = 0.131) by univariable analysis. However, MSI-L was an independent prognostic factor for poor OS by Cox regression analysis (hazard ratio 1.358, 95% confidence interval 1.014–1.819, P = 0.040).MSI-L may be an independent prognostic factor for OS in sporadic CRCs despite their clinicopathologic similarity to MSS. Further studies investigating the significance of MSI-L in the genesis and prognosis of CRCs are needed.

Cultural adaptation and validation of the Korean version of the EORTC QLQ-CR29 in patients with colorectal cancer.

PurposeWe aimed to evaluate the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR29), based on a sample of patients with colorectal cancer.MethodsA total of 123 patients treated for colorectal cancer participated in the validation study. Test–retest reliability was assessed using intra-class correlations from a random sample. Internal consistency reliability was estimated using Cronbach’s α coefficient. Convergent and discriminant validity was analyzed with multi-trait scaling. Clinical validity was assessed in terms of clinical differences using known-group comparisons. Concurrent validity was determined by correlations with the EORTC QLQ-C30, which was a generic core questionnaire to evaluate issues common to different cancer sites and treatments.ResultsThe test–retest, administered to 35 patients, showed acceptable reproducibility (0.62–1.00) except the constipation scale of the QLQ-C30 (0.43). Cronbach’s α coefficient (0.70–0.87) exceeded the 0.7 criterion. Multi-trait scaling analysis showed that multi-item scales met standards of convergent and discriminant validity. The known-group comparisons showed quality of life (QOL) differences between groups of patients based on tumor location, receipt of neoadjuvant therapy, and with/without a stoma. Correlations between the scales of the QLQ-CR29 and QLQ-C30 were low in most areas, whereas correlations in several areas with related content were higher.ConclusionThis study shows that the Korean version of the EORTC QLQ-CR29 is a reliable and valid tool for measuring QOL, as determined by application to a sample of Korean colorectal cancer patients.

Clinicopathological Features and Type of Surgery for Lynch Syndrome: Changes during the Past Two Decades.

Purpose The Korean Hereditary Tumor Registry, the first and one of the largest registries of hereditary tumors in Korea, has registered about 500 families with hereditary cancer syndromes. This study evaluates the temporal changes in clinicopathologic features and surgical patterns of Lynch syndrome (LS) patients. Materials and Methods Data on 182 unrelated LS patients were collected retrospectively. The patients were divided into the period 1 group (registered in 1990-2004) and 2 (registered in 2005-2014). The clinical characteristics of the two groups were compared to identify changes over time. Results The period 1 group included 76 patients; the period 2 group, 106 patients. The mean ages at diagnosis were 45.1 years (range, 13 to 85 years) for group 1 and 49.7 years (range, 20 to 84 years) for group 2 (p=0.015). The TNM stage at diagnosis did not differ significantly—period 1 group: stage 0-I (n=18, 23.7%), II (n=37, 48.7%), III (n=19, 25.0%), and IV (n=2, 2.6%); period 2 group: stage 0-I (n=30, 28.3%), II (n=35, 33.0%), III (n=37, 34.9%), and IV (n=4, 3.8%). Extended resection was more frequently performed (55/76, 72.4%) in the period 1 group than period 2 (49/106, 46.2%) (p=0.001). Conclusion Colorectal cancer in patients with LS registered at the Korean Hereditary Tumor Registry is still diagnosed at an advanced stage, more than two decades after registry’s establishment. Segmental resection was more frequently performed in the past decade. A prompt nationwide effort to raise public awareness of hereditary colorectal cancer and to support hereditary cancer registries is required in Korea.

Comparison of long-term oncological outcomes of appendiceal cancer and colon cancer: A multicenter retrospective study.

BACKGROUND There has been no comparative study of the long-term oncological outcomes of appendiceal cancer and colon cancer. We hypothesized that the oncological outcome is worse in appendiceal cancer because perforation is more frequent than in colon cancer. METHODS Patients with stage I-III were selected from 5046 patients with appendiceal or colon cancer, between September 2001 and June 2010. The 5-year disease-free survival (DFS) was the primary endpoint. Multivariate analyses with Cox proportional hazards model for DFS and logistic regression model for perforation were conducted. A matching model was used to compensate for the heterogeneity between groups. RESULTS The perforation rate was 44.7% in appendiceal cancer (n = 47), but 1.1% in colon cancer (n = 2828) (p = 0.001). The 5-year DFS rate was lower in appendiceal cancer than in colon cancer (57.9% vs. 85.2%, p = 0.001; matching model, 54.2% vs. 78.4%, p = 0.038), with a higher rate of peritoneal seeding (25.5% vs. 2.5%, p = 0.001; matching model, 24.0% vs. 4.0%, p = 0.007). Multivariate Cox regression showed that appendiceal cancer was an independent prognostic factor for poor DFS (hazard ratio = 2.602, 95% confidence interval = 1.26-5.35, p = 0.009), and logistic regression confirmed that appendiceal cancer was the risk factor associated with perforation (odds ratio = 66.265, 95% confidence interval = 28.21-155.61, p = 0.001). CONCLUSIONS This study suggested that the long-term oncological outcomes are worse for appendiceal cancer than for colon cancer, attributed to higher perforation rate in appendiceal cancer.

Incidental Cholecystectomy in Patients with Asymptomatic Gallstones Undergoing Surgery for Colorectal Cancer

Background and Aims: The feasibility of incidental cholecystectomy during colorectal cancer (CRC) surgery has not been determined as yet. We aimed to investigate the feasibility of incidental cholecystectomy during CRC surgery. Methods: The clinicopathologic data of patients who underwent CRC surgery between January 2004 and May 2011 were assessed. Patients with asymptomatic cholelithiasis were divided into groups that did and did not undergo incidental cholecystectomy. Their in-hospital morbidity and long-term biliary complications were compared. Results: Of the 282 patients identified, 143 (50.7%) underwent incidental cholecystectomy and 139 (49.3%) were observed without cholecystectomy. The two groups were similar in clinical characteristics, except for gender and operation time. Only one patient (0.7%) in the cholecystectomy group experienced an intraoperative biliary complication. There was no significant difference in overall in-hospital morbidity between the two groups. After a median follow-up period of 33 months, long-term biliary complications developed in 12 patients (8.6%) in the observation group, with 9 undergoing cholecystectomy. Conclusions: Incidental cholecystectomy was not associated with increased postoperative morbidity, whereas previously asymptomatic patients were at substantial long-term risk of becoming symptomatic. Thus, in the absence of clear contraindications, concomitant cholecystectomy might be a desirable treatment option during CRC surgery in patients with asymptomatic gallstones.