PURPOSE: Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes. MATERIALS AND METHODS: In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review. RESULTS: In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap. CONCLUSION: These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.
Chemistry ; Colorectal Neoplasms* ; Demography ; Genomics ; Humans ; Microsatellite Instability ; Neoplasm Metastasis ; Retrospective Studies

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.
Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Lymph Nodes ; Metastasectomy ; Neoplasm Metastasis* ; Prospective Studies ; Retrospective Studies ; Survival Rate*

PURPOSE: Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RAS Mutational analysis using a high-throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing. MATERIALS AND METHODS: Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status. RESULTS: The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88). CONCLUSION: Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.
Cetuximab* ; Colorectal Neoplasms* ; Disease-Free Survival ; Exons ; Genes, ras ; High-Throughput Nucleotide Sequencing ; Humans ; Salvage Therapy

PURPOSE: Metformin is associated with an anticancer effect. However, the effects of metformin in rectal cancer are controversial. This study investigated the impact of metformin on the survival of patients with diabetes mellitus and nonmetastatic rectal cancer who underwent curative surgery. MATERIALS AND METHODS: The database was provided by the Korea Center Cancer Registry and National Health Insurance Service of the Republic of Korea. A cohort of patients with newly diagnosed rectal cancer between 2005 and 2011 was identified. Drug exposure was defined as receiving the oral hypoglycemic agent for at least 90 days over the period from 6 months before the initial diagnosis of rectal cancer to the last follow-up. RESULTS: A total of 4,503 patients were prescribed oral hypoglycemic agents and classified as the diabetic group, of which 3,694 patients received metformin for at least 90 days. Unadjusted analyses showed a significantly higher overall survival (hazard ratio, 0.596; 95% confidence interval, 0.506 to 0.702) and rectal cancer-specific survival (hazard ratio, 0.621; 95% confidence interval, 0.507 to 0.760) in the metformin group than in the nonmetformin group. The adjusted overall survival (hazard ratio, 0.631; 95% confidence interval, 0.527 to 0.755) and cancer-specific survival (hazard ratio, 0.598; 95% confidence interval, 0.479 to 0.746) in the group with a medication possession ratio of 80% or greater was significantly higher than in the group with a medication possession ratio of less than 80%. CONCLUSION: Metformin use is associated with overall and cancer-specific survival in diabetic patients with a nonmetastatic rectal cancer treated with a curative resection.
Cohort Studies ; Colorectal Surgery ; Diabetes Mellitus ; Diagnosis ; Follow-Up Studies ; Humans ; Hypoglycemic Agents ; Korea ; Metformin* ; National Health Programs ; Rectal Neoplasms* ; Republic of Korea

A 67-year-old man underwent two endoscopic submucosal dissection procedures, one for gastric adenoma and one for early gastric cancer. The follow-up endoscopy showed metachronous recurrence at the anterior wall of the lower body, for which he underwent a subtotal gastrectomy. Four first- or second-degree relatives in his family have been diagnosed with gastric or colon cancers. The patient underwent counseling and genetic testing to identify single nucleotide polymorphisms and indel variants for 31 genes by next generation sequencing. Five missense mutations were identified, one each in ATM, BRIP1, and EPCAM and two in BRCA2. These genetic alterations may be candidates for genetic causes of this familial cluster of gastric cancer. This study identified genes that, for the first time, can be potentially associated with an increased risk of familial gastric cancer among the Korean population. These results may be helpful in evaluating other genetic factors related to the etiology of gastric cancer.
Adenoma ; Aged ; Colonic Neoplasms ; Counseling ; Endoscopy ; Follow-Up Studies ; Gastrectomy ; Gastrointestinal Neoplasms* ; Genetic Testing ; Humans ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Recurrence ; Stomach Neoplasms*

PURPOSE: To demonstrate the feasibility, safety, and technical strategies of hand-assisted laparoscopic complete mesocolic excision (HAL-CME) and to compare oncological outcomes between HAL-CME and the open approach (O-CME) for right colon cancers. METHODS: Patients who were scheduled to undergo a right hemicolectomy were divided into HAL-CME and O-CME groups. Measured outcomes included demographic variables, perioperative parameters, and follow-up data. Demographic variables included age, sex distribution, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, previous abdominal surgery, tumor localization, and potential comorbidities. Perioperative parameters included incision length, operative time, blood loss, conversion rate, postoperative pain score, postoperative first passage of flatus, duration of hospital stay, total cost, number of lymph nodes retrieved, TNM classification, and postoperative complications. Follow-up data included follow-up time, use of chemotherapy, local recurrence rate, distant metastasis rate, and short-term survival rate. RESULTS: In total, 150 patients (HAL-CME, 78; O-CME, 72) were included. The groups were similar in age, sex distribution, BMI, ASA classification, history of previous abdominal surgeries, tumor localization, and potential comorbidities. Patients in the HAL-CME group had shorter incision lengths, longer operative times, less operative blood loss, lower pain scores, earlier first passage of flatus, shorter hospital stay, higher total costs, similar numbers of lymph nodes retrieved, similar TNM classifications, and a comparable incidence of postoperative complications. The 2 groups were also similar in local recurrence rate, distant metastasis rate, and short-term survival rate. CONCLUSION: The results demonstrate that the HAL-CME procedure is a safe, valid, and feasible surgical method for right hemicolon cancers.
Body Mass Index ; Classification ; Colectomy ; Colonic Neoplasms ; Comorbidity ; Drug Therapy ; Flatulence ; Follow-Up Studies ; Hand-Assisted Laparoscopy ; Humans ; Incidence ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Mesocolon ; Methods ; Neoplasm Metastasis ; Operative Time ; Pain, Postoperative ; Postoperative Complications ; Recurrence ; Sex Distribution ; Survival Rate

PURPOSE: Surgical resection of isolated hepatic or pulmonary metastases of colorectal cancer is an established procedure, with a 5-year survival rate of about 50%. However, the role of surgical resections in patients with both hepatic and pulmonary metastases is not well established. We aimed to analyze overall survival of these patients and associated factors. METHODS: Data retrospectively collected from 66 patients who underwent both hepatic and pulmonary metastasectomy after colorectal cancer surgery from August 2002 through August 2013 were analyzed. In univariate analysis, the log-rank test compared patient survival between groups. P < 0.1 was considered indicative of significance. Multivariate analysis of the significance data using a Cox proportional hazard model identified factors associated with overall survival. The synchronous group (n = 57) was defined as patients who had metastasectomy within 3 months from primary colorectal cancer surgery. The remaining nine patients constituted the metachronous group. RESULTS: Median follow-up was 126 months from the primary colorectal cancer surgery. The 5-year survival was 73.4%. There was no difference in overall survival between the synchronous and metachronous groups, consistent with previous studies. Distribution (involving one hemiliver or both, P = 0.010 in multivariate analysis) of liver metastases and multiplicity of the pulmonary metastasis (P = 0.039) were predictors of poor prognosis. CONCLUSION: Sequential or simultaneous resection of both hepatic and pulmonary metastasis of colorectal cancer resulted in good long-term survival in selected patients. Thus, an aggressive surgical approach and multidisciplinary decision making with surgeons seems to be justified.
Colorectal Neoplasms* ; Decision Making ; Follow-Up Studies ; Humans ; Liver* ; Lung* ; Metastasectomy ; Multivariate Analysis ; Neoplasm Metastasis* ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Surgeons ; Survival Rate

BACKGROUND/AIMS: Colonoscopy can detect precancerous lesions, which can subsequently be removed and reduce incidences of and mortality from colorectal cancer (CRC). However, recently published data have highlighted a significant rate of CRC in patients who previously underwent colonoscopy. Among many reasons, incomplete resection has been considered as a significant contributor. However, to date, there have only been a few studies regarding incompletely resected polyps, especially advanced colorectal adenoma (ACA). Hence, we aimed to evaluate the prognosis of incompletely resected ACA. METHODS: We retrospectively reviewed the medical records of patients with ACA who had underwent endoscopic treatment with incomplete resection. The primary outcomes were (1) the incomplete resection rate of ACA, as determined by a histopathologic examination and (2) the recurrence rate of incompletely resected ACA. We also investigated the probable contributing factors that may have led to a relapse of incompletely resected ACA. RESULTS: A total of 7,105 patients had their colorectal polyps resected by endoscopic treatment, and 2,233 of these were considered as ACA. Of these, 354 polyps (15.8%) were resected incompletely, and only 163 patients were followed-up. Of those followed-up, 31 patients (19.0%) experienced local recurrence. The risk factors for recurrence after incomplete resection were evaluated; age, morphology of adenoma, and use of rescue therapy, such as argon plasma coagulation, were found to be associated with adenoma recurrence. CONCLUSIONS: Incompletely resected ACA in older patients or in patients with sessile-type adenomas should be monitored strictly, and if incomplete resection is suspected, rescue therapy must be considered.
Adenoma* ; Argon Plasma Coagulation ; Colonic Polyps ; Colonoscopy ; Colorectal Neoplasms ; Humans ; Incidence ; Medical Records ; Mortality ; Polyps ; Prognosis ; Recurrence* ; Retrospective Studies* ; Risk Factors*

In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.
Colorectal Neoplasms* ; Humans ; Incidence ; Microsatellite Instability* ; Microsatellite Repeats* ; Mucins

Colorectal endoscopic submucosal dissection (ESD) is now a well-established endoscopic treatment for early-stage colorectal neoplasms, especially in Asian countries, including Japan. Despite the spread of colorectal ESD, there are still situations in which achieving successful submucosal dissection is difficult. Various novel techniques and devices have been developed to overcome these difficulties, and past reports have shown that some of these strategies can be applied to colorectal ESD. We review several recent developments in the field. The techniques reviewed include the pocket creation method and traction methods and the devices reviewed include the overtube with balloon and electrosurgical knives with water-jet function. These improved techniques and devices can facilitate safer, more reliable ESDs and expand its applicability and acceptability all over the world.
Asian Continental Ancestry Group ; Colorectal Neoplasms ; Humans ; Japan ; Methods ; Traction