Search

The complexity in the molecular mechanism of the internal anal sphincter (IAS) limits preclinical or clinical outcomes of fecal incontinence (FI) treatment. So far, there are no systematic reviews of IAS translation and experimental studies that have been reported. This systematic review aims to provide a comprehensive understanding of IAS critical role in FI. Previous studies revealed the key pathway for basal tone and relaxation of IAS in different properties as follows; calcium, Rho-associated, coiled-coil containing serine/threonine kinase, aging-associated IAS dysfunction, oxidative stress, renin-angiotensin-aldosterone, cyclooxygenase, and inhibitory neurotransmitters. Previous studies have reported improved functional outcomes of cellular treatment for regeneration of dysfunctional IAS, using various stem cells, but did not demonstrate the interrelationship between those results and basal tone or relaxation-related molecular pathway of IAS. Furthermore, these results have lower specificity for IAS-incontinence due to the included external anal sphincter or nerve injury regardless of the cell type. An acellular approach using bioengineered IAS showed a physiologic response of basal tone and relaxation response similar to human IAS. However, in both cellular and acellular approaches, the lack of human IAS data still hampers clinical application. Therefore, the IAS regeneration presents more challenges and warrants more advances.

Since the da Vinci SP (dVSP) surgical system was introduced, single-incision robotic surgery (SIRS) for colorectal diseases has gained increasing acceptance. We compared the short-term outcomes of SIRS using dVSP with those of conventional multiport laparoscopic surgery (CMLS) to verify its efficacy and safety in colon cancer. The medical records of 237 patients who underwent curative resection for colon cancer by a single surgeon were retrospectively reviewed. Patients were divided into two groups according to surgical modality: SIRS (RS group) and CMLS (LS group). Intra- and postoperative outcomes were analyzed. Of the 237 patients, 140 were included in the analysis. Patients in the RS group (n = 43) were predominantly female, younger, and had better general performance than those in the LS group (n = 97). The total operation time was longer in the RS group than in the LS group (232.8 ± 46.0 vs. 204.1 ± 41.7 min, P

Supplementary Table S1. Read mapping information of CRC samples

Supplementary Figure 1. Survival plot using Kaplan-Meier survival analysis between two patient groups with high- and low-heterogeneity.

Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis.Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated.Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53, and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors.Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. Clin Cancer Res; 23(23); 7209–16. ©2017 AACR.

Objective: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model. Materials and Methods: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague–Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson’s trichrome staining, and quantitative RT–PCR. Results: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs. Conclusions: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.

Cancer cell-derived exosomes deliver oncogenic factors to other cells and their tumour microenvironment. We aimed to investigate the role of cancer cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines HT-29, SW480, and LoVo. Subsequently, HT-29 cells were treated with these exosomes to evaluate the effect of exosomes on cancer progression. MTT and wound-healing assays were performed to evaluate the effect of exosomes on cellular viability and migration. Moreover, we obtained cancer-associated fibroblasts (CAFs) from patients with colorectal cancer to analyse the effects of cancer cell-derived exosomes on the tumour microenvironment. We performed RNA sequencing to evaluate changes in the mRNA components of the CAFs after exosome treatment. Compared with control cells, exosome-treated cells showed significantly increased proliferation. Regarding western blotting for epithelial-mesenchymal transition markers, exosome-treated cells showed N-cadherin upregulation followed by E-cadherin downregulation. In the wound-healing assay, exosome-treated cells exhibited increased mobile properties. Additionally, exosome-treated CAFs showed increased downregulated genes. In the functional enrichment analysis, exosomes derived from each cell affected different gene regulation pathways. Our findings suggest that cancer cell-derived exosomes are crucially involved in tumour progression and metastasis by affecting the tumour microenvironment.

Although Hartmann’s procedure (HP) is commonly used as emergency treatment for colorectal disease, the reversal of HP (HR) is infrequently performed. The aims were to evaluate the rate of HR and determine the factors predictive of achieving HR. We retrospectively reviewed the medical records of patients who underwent HP between January 2007 and June 2019 at six Hallym University-affiliated hospitals. Multivariable analysis was performed to identify which factors were independently associated with HR. In the study period, 437 patients underwent HP, and 127 (29.0%) subsequently underwent HR. Of these, 46 (35.9%) patients experienced post-HR complications. In multivariable analysis, an interval between HP and HR of > 6 months was associated with the only lower rate of post-HR complications. Multivariate analysis showed that HR was less likely in patients aged > 70 years, those with American Society of Anesthesiologists (ASA) class III or IV, elective surgery, those experiencing more than two HP-related complications, and those with a malignancy (an indication for HP). One-third of the patients underwent HR. Age > 70 years, ASA class III or IV, elective surgery, more than two HP-related complications, and malignancy were associated with a non-HR rate.

Colorectal cancer is a devastating disease with a low 5-year survival rate. Recently, many researchers have studied the mechanisms of tumor progression related to the tumor microenvironment. Here, we addressed the prognostic value of tumor-associated macrophages (TAMs) using a total of 232 CRC patient tissue samples and investigated the mechanisms underlying TAM-related colon cancer progression with respect to PI3Kγ regulation using in vitro, in vivo, and ex vivo approaches. Patients with M2/M1 3. M1 and M2 macrophages elicited opposite effects on colon cancer progression via the FBW7-MCL-1 axis. Blocking macrophage PI3Kγ had cytotoxic effects on colon cancer cells and inhibited epithelial–mesenchymal transition features by regulating the FBW7-MCL-1 axis. The results of this study suggest that macrophage PI3Kγ may be a promising target for immunotherapy in colon cancer., Cancer treatment: turning the tide against colon cancer Drugs that target a specific subset of immune cells could render colorectal tumors more susceptible to immunological destruction by the host. The cellular composition of a tumor profoundly affects the odds of progression or survival, and some immune cell types can stall the antitumor response rather than strengthening it. Researchers led by Yong Beom Cho of Sungkyunkwan University, Seoul, South Korea, explored the impact of various subpopulations of macrophages, cells that help coordinate the immune counterattack against cancer. The researchers learned that the relative balance between M2 and M1 subtypes of macrophages correlates with colorectal cancer outcomes, patients with less M2 and more M1 activity generally faring better. They also uncovered a strategy for inhibiting M2 activity, which unleashes a more-aggressive response against the tumor and could thus offer a useful therapeutic approach.

Purpose Carcinoembryonic antigen (CEA) is a useful marker for rectal cancer. The aim of this study was to investigate the prognostic impact of CEA level according to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients who underwent radical surgery. Methods A total of 245 patients with rectal cancer who underwent radical surgery were retrospectively evaluated. Serum CEA level was measured preoperatively and postoperatively. We compared survival outcomes based on CEA level before and after surgery according to nCRT. Results Of the 245 patients, elevation of CEA level was observed preoperatively in 79 and postoperatively in 30, respectively. Eighty-seven (35.5%) patients received nCRT, and elevated CEA level was a significant prognostic factor both before and after surgery. In patients who had not received nCRT, an elevated CEA level was a significant prognostic factor before surgery but was not significant after surgery. In a multivariate analysis for prognostic factors, elevation of preoperative CEA level was an independent prognostic factor of disease-free survival (DFS) regardless of nCRT. Postoperative CEA level was an independent prognostic factor of DFS in patients who had received nCRT but was not a factor in patients who had not received nCRT. Conclusions Serum CEA level was an independent prognostic factor both preoperatively and postoperatively in rectal cancer patients who had received nCRT.

Purpose CEA is a useful tumor marker for colon cancer. The aim of this study was to investigate the prognostic value of changes in CEA levels before and after surgery in colon cancer patients who underwent radical surgery. Methods A total of 601 colon cancer patients who underwent radical surgery from January 2007 to December 2017 at a single institution were evaluated. Patients were categorized according to preoperative and postoperative CEA levels. We adjusted patient characteristics using propensity score matched analysis between groups and compared survival outcomes according to changes in CEA levels before and after surgery. Results According to the preoperative and postoperative CEA levels, patients were classified into 3 groups: group 1, ≤5 and ≤5 ng/mL, respectively (n = 407); group 2, >5 and ≤5 ng/mL, respectively (n = 127); and group 3 (>5 and >5 ng/mL, respectively (n = 67). Postoperative CEA elevation was associated with adverse clinical features. Before and after matching, the patients in group 3 showed significantly lower disease-free survival and overall survival rates compared to the patients in group 1 and group 2. In multivariate analysis, changes in CEA levels were an independent prognostic factor of overall survival (P = 0.041). Conclusion The changes in CEA levels before and after surgery can be a useful prognostic factor for disease-free survival and overall survival in colon cancer patients.

We conducted this study to compare the perioperative outcomes of laparoscopic surgery (LS) vs. open surgery (OS) for repairing colonoscopic perforation, and to evaluate the possible predictors of complications. We reviewed the medical records of patients who underwent surgical repair of colonoscopic perforation by LS or OS between January 2005 and June 2019 at six Hallym University-affiliated hospitals. Multivariable analysis was performed to identify the predictors of postoperative complications. Of the total 99 patients, 40 underwent OS and 59 underwent LS. The postoperative hospital stay and the time to resuming a soft diet were shorter in the LS group than in the OS group (P = 0.017 and 0.026, respectively). The complication rate and Clavien–Dindo classification were not significantly different between the two groups. Multivariable analysis revealed that an American Society of Anesthesiologists score (ASA) ≥ 3 and switching from non-operative management to surgical treatment were independently associated with complications (P = 0.025 and 0.010, respectively). LS may be a safe alternative to OS for repairing colonoscopic perforation with a shorter postoperative hospital stay and time to resuming a soft diet. Patients with an ASA score ≥ 3 and those with changes to their planned treatment should be monitored carefully to minimize their risk of complications.

Purpose Meckel diverticulum (MD), caused by an obliteration defect of the omphalomesenteric duct, is one of the most common congenital anomalies of small intestines. The objective of this study was to review surgical outcomes of MD and evaluate the feasibility of minimally invasive surgery (MIS) in MD. Methods We performed a retrospective analysis of the medical records of patients who underwent diverticulectomy for MD at 6 Hallym University-affiliated hospitals between January 2008 and December 2017. All patients underwent either open surgery or MIS. Patients who underwent MIS were subdivided into laparoscopic only diverticulectomy (LOD) or laparoscopic-assisted diverticulectomy (LAD). Results Of 64 patients, 21 underwent open surgery and 43 underwent MIS. Time to flatus, time to soft food intake, and length of hospital stay were shorter in the MIS group than in the open surgery group (P = 0.047, P = 0.005, and P = 0.015, respectively). Among patients who underwent MIS, the time to flatus and time to soft food intake were longer in the LAD group than in the LOD group (0.3 and 0.9 days, respectively). Multivariate analysis showed that old age and preoperative ileus were independent predictors of complications (P = 0.030 and P = 0.013, respectively). Operation type (open surgery, LOD, or LAD) was not associated with complications. Conclusion The present study showed that MIS is associated with quicker recovery without increasing complications. Therefore, MIS may be a safe alternative to open surgery for MD. An old age and preoperative ileus were associated with a risk of postoperative complications.

The prognostic impact of anastomotic leakage (AL) in rectal cancer remains uncertain. We investigated the prognostic significance of AL in rectal cancer patients who underwent curative surgery, especially in terms of chemoradiotherapy.A total of 1,818 rectal cancer patients who underwent radical surgery from 2011 to 2015 were retrospectively evaluated. We categorized patients according to AL and compared survival outcomes between the groups before and after matching. In locally advanced rectal cancer patients, we classified patients according to neoadjuvant chemoradiotherapy (nCRT) or adjuvant chemotherapy (aCTx) and analyzed survival outcomes according to AL in each group.Before matching, overall survival (OS) was significantly worse in the AL (+) group compared to the AL (-) group (P = 0.004). In matched patients, there were no differences in disease-free survival (DFS) and OS between groups (P = 0.423 and P = 0.083, respectively). In subgroup analysis for locally advanced rectal cancer, patients were classified as follows: nCRT (+) and aCTx (+) group; nCRT (+) and aCTx (-) group; nCRT (-) and aCTx (+) group; and nCRT (-) and aCTx (-) group. In the nCRT (-) and aCTx (+) group, patients with AL exhibited significantly worse DFS than patients without AL (P = 0.040). In the other 3 groups, there were no differences in DFS according to AL.In locally advanced rectal cancer, AL had an adverse effect on oncologic outcome in patients receiving aCTx without nCRT but not in patients receiving nCRT.

BACKGROUND: Signet-ring cell carcinoma (SRCC) is a very rare subtype of colorectal adenocarcinoma (COAD) with a poor clinical prognosis. Although understanding key mechanisms of tumor progression in SRCCs is critical for precise treatment, a comprehensive view of genomic alterations is lacking. MATERIALS AND METHODS: We performed whole-exome sequencing of tumors and matched normal blood as well as RNA sequencing of tumors and matched normal colonic tissues from five patients with SRCC. RESULTS: We identified major somatic alterations and characterized transcriptional changes at the gene and pathway level. Based on high-throughput sequencing, the pattern of mutations and copy number variations was overall similar to that of COAD. Transcriptome analysis revealed that major transcription factors, such as SRF, HNF4A, ZEB1, and RUNX1, with potential regulatory roles in key pathways, including focal adhesion, the PI3K-Akt signaling pathway, and the MAPK signaling pathway, may play a role in the tumorigenesis of SRCC. Furthermore, significantly upregulated genes in SRCCs were enriched for epithelial-mesenchymal transition genes, and accumulation of mucin in intracytoplasm was associated with the overexpression of MUC2. CONCLUSION: The results indicate that the molecular basis of colorectal SRCC exhibits key differences from that of consensus COAD. Our findings clarify important genetic features of particular abnormalities in SRCCs.

It remains unclear whether old age is a poor prognostic factor in colorectal cancer (CRC). We compared oncologic outcomes in CRC patients according to age, using 80 as the dividing point. CRC patients who underwent radical surgery from 2000 to 2011 were evaluated. We performed matched and adjusted analyses comparing oncologic outcomes between patients with ≥ 80 and

Background Understanding the genomic determinants associated with metastasis in colorectal cancers (CRCs) provides crucial clues for improving patient care. Patients and methods In this study, we performed whole-exome sequencing as well as RNA sequencing analyses on five pairs of primary and liver metastasized samples from CRC patients together with blood/normal control samples for each pair. Results We identified genomic deletions in the region of 8p21-23 (q value Conclusion Taken together, our findings uncovered various genomic alterations potentially leading to metastasis in CRC and provide important insights into the development of potential therapeutic targets for preventing metastatic progression of CRC.

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay., High-throughput sequencing is used to identify somatic variants in cancer patients. Here, the authors perform panel-based profiling of 5095 clinical samples and demonstrate that many clinically-actionable variants have low variant allele fractions, requiring assays with high detection sensitivity.

Background Circulating tumor cells (CTCs) might play a significant role in cancer progression and metastasis. However, the ability to detect CTCs is limited, especially in cells undergoing epithelial-mesenchymal transition. In this study, we evaluated a new size-based CTC detection platform and its clinical efficacy in colorectal cancer. Patients and Methods Blood samples were obtained from 76 patients with colorectal cancer and 20 healthy control subjects for CTC analysis. CTCs were enriched using a high-density microporous chip filter and were detected using a 4-color staining protocol including 4′,6-diamidino-2-phenylindole (DAPI) for nucleated cells, CD45 monoclonal antibody (mAb) as a leukocyte marker, and epithelial cell adhesion molecule (EpCAM) mAb or cytokeratin (CK) mAb as an epithelial cell marker. CTC positivity was defined as DAPI-positive (DAPI+)/CD45−/EpCAM+ or CK+ cells and clinical outcomes of patients were analyzed according to CTC counts. Results CTCs were detected in 50 patients using this size-based filtration platform. CTC+ patients were more frequently identified with a high level of carcinoembryonic antigen and advanced stage cancer (P = .038 and P = .017, respectively). CTC counts for patients with stage IV cancer (12.47 ± 24.00) were significantly higher than those for patients with cancers that were stage I to III (2.84 ± 5.29; P = .005) and healthy control subjects (0.25 ± 0.55; P Conclusion CTC positivity was found to correlate with clinical features of colorectal cancer patients. Our results suggest that this new size-based platform has potential for determining prognosis and therapeutic response in colorectal cancer patients.

Liver metastasis is a leading cause of death in patients with colorectal cancer. Investigating the mechanisms of liver metastasis and control of disease progression are important strategies for improving survival of these patients. Liver metastasis is a multi-step process and relevant models representing these steps are necessary to understand the mechanism of liver metastasis and establish appropriate treatments. Recently, the development of animal models for use in metastasis research has greatly increased; however, there is still a lack of models that sufficiently represent human cancer. Thus, in order to select an optimal model for of a given study, it is necessary to fully understand the characteristics of each animal model. In this review, we describe the mouse models currently used for colorectal cancer with liver metastasis, their characteristics, and their pros and cons. This may help us specify the mechanism of liver metastasis and provide evidence relevant to clinical applications.

Background The da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) was introduced to overcome the limitations of single-incision laparoscopic surgery, which is challenging due to its restrictions regarding triangulation and retraction. The purpose of this article is to describe the initial experience with single-incision surgery using the da Vinvci Single-Port Platform (dVSP). Methods The medical records of patients with colorectal disease, who underwent single-incision robotic surgery using the dVSP, were retrospectively reviewed. Results Five patients with appendiceal and colorectal cancer, and two with diverticulitis were enrolled. All procedures were completed using a pure single-incision approach, with an exception for low anterior resection. There were two minor complications. For patients with colorectal cancer, the number of retrieved lymph nodes and status of the resection margin were acceptable, and cosmetic results were satisfactory. Conclusion The dVSP is a novel surgical platform that can be used as an alternative surgical modality for colorectal surgery.

Tumor genetic heterogeneity may underlie poor clinical outcomes because diverse subclones could be comprised of metastatic and drug resistant cells. Targeted deep sequencing has been used widely as a diagnostic tool to identify actionable mutations in cancer patients. In this study, we evaluated the clinical utility of estimating tumor heterogeneity using targeted panel sequencing data. We investigated the prognostic impact of a tumor heterogeneity (TH) index on clinical outcomes, using mutational profiles from targeted deep sequencing data acquired from 1,352 patients across 8 cancer types. The TH index tended to be increased in high pathological stage disease in several cancer types, indicating clonal expansion of cancer cells as tumor progression proceeds. In colorectal cancer patients, TH index values also correlated significantly with clinical prognosis. Integration of the TH index with genomic and clinical features could improve the power of risk prediction for clinical outcomes. In conclusion, deep sequencing to determine the TH index could serve as a promising prognostic indicator in cancer patients.

Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit impaired epithelial-mesenchymal transition (EMT), but little is known about the underlying mechanisms of this phenomenon. In this study, we investigated the role of Twist1 and its downstream signaling cascades in EMT induction according to MSI status. To investigate the effects of Twist1 on EMT induction according to MSI status, MSS LS513 and MSI LoVo colon cancer cell lines, which overexpress human Twist1, were generated. Twist1-induced EMT and its downstream signaling pathways were evaluated via in vitro and in vivo experiments. We found that Twist1 induced EMT markers and stem cell-like characteristics via AKT signaling pathways. Twist1 induced activation of AKT and suppression of glycogen synthase kinase (GSK)-3β, which resulted in the activation of β-catenin, increasing CD44 expression. In addition, Twist1 activated the AKT-induced NF-κB pathway, increasing CD44 and CD166 expression. Activation of both the AKT/GSK-3β/β-catenin and AKT/NF-κB pathways occurred in MSS LS513 cells, while only the AKT/GSK-3β/β-catenin pathway was activated in MSI LoVo cells. In conclusion, Twist1 induces stem cell-like characteristics in colon cancer cell lines related to EMT via AKT signaling pathways, and those pathways depend on MSI status.

The type of surgery performed for primary transverse colon cancer varies based on tumor characteristics and surgeon perspective. The optimal oncological outcome following different surgical options has not been clearly established, and transverse colectomy has shown oncological equivalence only in small cohort studies.Our aim was to compare long-term oncological outcomes after transverse colectomy versus extended resection for transverse colon cancer.This study is a retrospective review of prospectively collected data.This study was conducted at a tertiary care hospital.All patients treated for transverse colon cancer at the Samsung Medical Center between 1995 and 2013 were included.Oncological outcomes were compared between 2 groups of patients: a transverse colectomy group and an extended colectomy group (which included extended right hemicolectomy and left hemicolectomy).A total of 1066 patients were included, of whom 750 (70.4%) underwent extended right hemicolectomy, 127 (11.9%) underwent transverse colectomy, and 189 (17.7%) underwent left hemicolectomy. According to univariate analysis, surgical approach, histological type, tumor morphology, cancer T and N stage, cancer size, and lymphovascular invasion were significant factors contributing to disease-free survival (DFS). However, as seen in multivariate analysis, only node-positive disease (HR = 2.035 (1.188-3.484)), tumors with ulcerative morphology (HR = 3.643 (1.132-11.725)), and the presence of vascular invasion (HR = 2.569 (1.455-4.538)) were significant factors for DFS. Further analysis with a propensity-matched cohort between the transverse and extended colectomy groups demonstrated no significant differences in DFS and overall survival.This study was limited because it was performed at a single institution and it was retrospective in nature.In terms of perioperative and oncological outcomes, transverse colectomy and extended colectomy did not differ despite a shorter specimen length and fewer lymph nodes harvested in the transverse colectomy group. Independent prognostic factors for DFS were node-positive disease, the presence of vascular invasion, and ulcerative morphology.

Coastal ecosystems, play critical ecological roles of which tidal flats are a significant component of coastal wetlands, such as habitat and nutrient cycling in aquatic biology. Microbial communities in tidal flats are known to play vital roles of self-purification. And the microbial ecology of the sediment is easily affected by human activities and pollution. In this paper, we applied pyrosequencing technology to investigate microbial communities in three different tidal flats (Ganghwa Island, Ongnyeon land region and Yeongjong Island) on the Incheon, Korea peninsula. A total of 16,906 sequences were obtained. We used these sequences to identify the dominant phyla in the three tidal flats: Proteobacteria, Chloroflexi, Actinobacteria, and Bacteroidetes. The composition of the bacterial community of Ganghwa Island and the Ongnyeon region were more similar to each other than they were to the bacterial community of Yeongjong Island. Simpson's dominance index of Yeongjong Island was higher than that of the other regions, and the Shannon diversity index of this region was the lowest. Previous research of samples in these regions indicated that the three tidal flats had similar geochemical characteristics. However, their bacterial communities were rather distinct. This might be because the analysis of microbial communities and physiochemical analysis have different perspectives. Therefore, the pyrosequencing of a bacterial community with physiochemical analysis is recommended as an effective monitoring tool for the comprehensive management of tidal flats.

Purpose There are patients who do not undergo surgery, regardless of tumor response for neoadjuvant chemoradiotherapy (nCRT) in rectal cancer. However, there have been few reports focused on how oncologic outcomes are worse in these patients. We sought to investigate oncologic outcomes for these non-operated patients with rectal cancer after nCRT. Materials and Methods A total of 1,063 records of patients with rectal cancer who were treated with nCRT from January 2002 to December 2013 were retrospectively reviewed. We categorized patients into the non-operated group (n=77), transanal local excision (TLE) group (n=54), ortotal mesorectal excision (TME) group (n=932) and compared each group using propensity score matching. Results In the non-operated group, the most common reason for no surgery was patient refusal (n=64). Eleven patients were considered to have achieve clinical complete response (cCR), which was an independent prognostic factor of progression-free survival (p=0.045). In patients with disease progression in the non-operated group, the overall survival did not improved according to salvage treatments (p=0.451). The non-operated group showed worse survivals compared to the TLE or TME group before and after matching (p < 0.001). This finding was also noted in the analysis of survival only in patients with cCR. Conclusion In this study, non-operated patients did not secure oncologic safety regardless of cCR after nCRT. Our results suggest that a non-operative management must be carefully considered even if cCR is achieved.

Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis. Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated. Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53, and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors. Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. Clin Cancer Res; 23(23); 7209–16. ©2017 AACR.

Indigenous microorganisms play decisive roles in biodegradation. In this study, eighty strains of hydrocarbon-degrading microbes were isolated from Incheon Bay. Among them, 12 strains were selected by an oil film collapsing method. The bacterial strain ‘Incheon9’ was eventually selected based on its relatively higher lipase and emulsification activities, and was identified as Acinetobacter sp. (NCBI accession code: KF54854). The optimum condition for the growth and emulsification activity of Acinetobacter sp. Incheon9 was 20°C, pH 7, and 1% NaCl. The optimum time for the best production of biosurfactant was 72 hrs. The oil degradation ability of Acinetobacter sp. Incheon9 was investigated by measuring the residual oils in the culture medium by gas chromatography (FID). This research provides foundational data for eco-friendly environmental remediation by microorganisms.

Purpose Local anesthetic wound infusion has been previously investigated in postoperative pain management. However, a limited number of studies have evaluated its use in laparoscopic colorectal surgery. This study aims to evaluate whether ropivacaine wound infusion is effective for postoperative pain management after laparoscopic surgery in patients with colorectal cancer. Methods This prospective study included 184 patients who underwent laparoscopic surgery for colorectal cancer between July 2012 and June 2013. The patients were grouped as the combined group (intravenous patient-controlled analgesia [IV-PCA] plus continuous wound infusion with ropivacaine, n = 92) and the PCA group (IV-PCA only, n = 92). Efficacy and safety were assessed in terms of numeric rating scale (NRS) pain score, opioid consumption, postoperative recovery, and complications. Results The total quantity of PCA fentanyl was significantly less in the combined group than in the PCA group (P < 0.001). The NRS score of the combined group was not higher than in the PCA group, despite less opioid consumption. There were no differences between groups for postoperative recovery and most complications, including wound complications. However, the rate of nausea and vomiting was significantly lower in the combined group (P = 0.022). Conclusion Ropivacaine wound infusion significantly reduced postoperative opioid requirements and the rate of nausea/vomiting. This study showed clinical efficacy of ropivacaine wound infusion for postoperative pain control in colorectal cancer patients undergoing laparoscopic surgery.

Purpose : Laparoscopic surgery has been shown to be useful modality to be compared with conventional open surgery. However, it has been raised several limitations such as absence of tactile sense, long operative time, technically complexity, and limited operative field. Hand-assisted laparoscopic surgery (HALS) has been proposed as an alternative to these limitations of laparoscopic surgery. The aim of this study is to compare HALS with conventional open surgery(OS) in rectal cancer patients. Methods : We reviewed 36 rectal cancer patients who underwent operation between Jan 2009 and Oct 2011, retro- spectively. Patients were diagnosed with rectal cancer and underwent HALS AR/LAR or open AR/LAR by the same surgical team. Patients were excluded from this study when visceral peritoneum was invaded (T4), the largest lesion was bigger than 5 cm, there were synchronous metastasis of other organs other than the rectum, resection of other organs in addition to rectum were accompanied during operation, and HALS was converted to OS. Patients were classified into two groups with either HALS or OS. We compared perioperative outcomes of each group. Results : Out of 36 patients, 14 underwent HALS AR/LAR and 22 underwent open AR/LAR. There was no significant difference between these two groups in age, sex, BMI, and comorbidities. HALS group had significantly longer operative time than OS group (243.9 min vs. 201.1 min, p= 0.014). HALS group had significantly shorter skin incision (7.5 cm vs. 19.5 cm, p=0.000) and less estimated blood loss (112.0 ml vs. 342.3 ml, p=0.001) than OS group. In histopathologic reports, HALS group had significantly earlier stage (1.5 vs. 2.3, p=0.009) than OS group, but there was no significant difference in number of harvested lymph nodes and length of resection margin. In post- operative course, there was no significant difference in date of first gas out, date of starting diet, number of parenteral opioid analgesics administered, and amount of RBC transfused, but HALS group was shown shorter length of hospital stay (10.4 days vs. 13.3 days, p=0.011) than OS group. Also post-operative morbidity or mortality did not shown significant differences between the two groups. Conclusion : This study showed that HALS AR/LAR seems to be minimally invasive and oncologically feasible. Therefore, it is also useful alternative modality as laparoscopic surgery or open surgery in rectal cancer patients.

Rotavirus is the main cause of severe diarrhea in infants and young children of the world. However, the frequency of genetic alterations makes it hard to control the prophylaxis. Therefore, continuous monitoring of the rotavirus’s genetic change is inevitable to prevent disease prevalence and is useful in inventing an efficient vaccine. From January 2005 to December 2010, we investigated 11,607 stool samples of acute gastroenteritis patients in the Incheon metropolitan area. About 13.18% (1,530 stool samples) of all samples had a positive reaction against rotavirus using an antigen capture enzyme- linked immunosorbent assay (ELISA). Then, the 160 stool samples were searched for subtypes of group A rotavirus by using a reverse transcription polymerase chain reaction (RT-PCR) and a nested multiplex RCR. In P sub-typing, P8 (56.3%) was an extremely prevalent genotype, followed by P6 (21.3%), and P1A (10.0%). G1 (39.4%) was most widespread in the G subtype, followed by G4 (25.0%) and G3 (18.8%). G1P8 (35.5%) was the most common G and P subtype combination, followed by G4P6 (19.3%) and G3P8 (13.1%). These results might be useful data for understanding the epidemiological status of group A-rotavirus dispersion in the Incheon metropolitan area.

Metformin may have anticancer effects and could improve response to radiotherapy in several malignancies. We aimed to investigate the effect of metformin on response to radiotherapy in rectal cancer. A total of 543 rectal cancer patients who were treated with neoadjuvant chemoradiotherapy followed by radical surgery from January 2007 to December 2011 were reviewed. Patients were divided into three groups: diabetics taking metformin (n = 42), diabetics not taking metformin (n = 29), and non-diabetics (n = 472). Tumor response and survival were compared between groups. The rates of N downstaging and tumor regression grades (TRG) 3–4 were significantly higher in diabetics taking metformin (p = 0.006 and p = 0.029, respectively). There were no significant differences between groups in terms of T downstaging and pathologic complete response. On multivariate analysis, metformin use was associated with increased rates of N downstaging and TRG 3–4 (p = 0.003 and p = 0.019, respectively). Recurrence-free survival, disease-free survival, and overall survival rates were not significantly different between groups. Metformin is associated with higher tumor response rates to radiotherapy in rectal cancer, especially in patients with diabetes.

The inhibitory effect of the food processing agent on growth of Escherichia coli O157:H7, Salmonella Enteritidis, and Listeria monocytogenes was performed with organic acid, and combination of citric acid, acetic acid, propionic acid and vanillic acid. The minimun inhibitory concentration(MIC) of propionic acid was 5,000 ppm in E. coli O157:H7, 2,500 ppm in Salmonella Enteritidis and Listeria monocytogenes. MIC of citric acid was 10,000 ppm in E. coli O157:H7 and Salmonella Enteritidis, 2,500 ppm in Listeria monocytogenes. MIC of acetic acid was 2,500ppm, while in vanillic acid was 5,000 ppm in Escherichia coli O157:H7, Salmonella Enteritidis, and Listeria monocytogenes. MIC of combined organc acid in E. coli O157:H7 were 2,500ppm in PC, 1,250 ppm in PA, PV, CA, CV and AV. MIC of combined organc acid in Salmonella Enteritidis were 2,500 ppm in PC, PA, PV, CA, and CV, 1,250 ppm in AV. MIC of combined organc acid in Listeria monocytogenes were 1,250 ppm in all treatment group. MIC of combined treatment of three organc acid in E. coli O157:H7, S. Enteritidis and L. monocytogenes were 1,250 ppm in PCA, PCV, PAV and CAV. The inhibitory effect of organc acid in E. coli O157:H7, S. Enteritidis and L. monocytogenes could be confirmed from the result of this experiment. Therefore, it was expected that the food process would increase or maintain by using organic acid.

BACKGROUND Transanal local excision has recently received attention as an alternative to radical surgery for early rectal cancer. Recurrence usually occurs within 5 years after surgery, but recurrences later than this have also been reported. OBJECTIVE The aim of this study was to investigate the incidence and risk factors of recurrence in patients who have early rectal cancer 10 years after transanal local excision. DESIGN Patients with early rectal cancer who underwent transanal local excision from October 1994 to December 2010 were retrospectively reviewed. We reviewed the demographics and clinicopathologic features of primary lesions and analyzed the incidence and risk factors of recurrence. SETTINGS This investigation was conducted at a tertiary university hospital. PATIENTS A total of 295 patients who underwent transanal local excision for pTis (n = 155) or pT1 (n = 140) early rectal cancer were included in the analysis. INTERVENTION Transanal local excision was performed for each patient to excise primary rectal lesions. MAIN OUTCOME MEASURES The primary end point of this study was the incidence of recurrence, especially late recurrence. The secondary end point was risk factors for recurrence. RESULTS The 10-year cumulative local recurrence rate was 6.7% in pTis and 18.0% in pT1 patients. The rate of late local recurrence was 2.8% in pTis and 3.7% in pT1 patients. There was no evidence of late systemic recurrence 5 years after transanal local excision. In pT1 patients, a higher risk of recurrence was associated with an invasion depth of sm3, the presence of lymphovascular invasion, and a positive resection margin. LIMITATION The main limitation of this study is its retrospective nature. CONCLUSIONS Late recurrence can occur in patients with early rectal cancer who have undergone transanal local excision. Transanal local excision can be performed in selective patients with biologically favorable tumors, and 10-year postoperative surveillance should be considered for these patients.

The microsatellite instability-high (MSI-H) phenotype of colon cancer has a good prognosis and limited response to chemotherapy. We aimed to investigate prognostic factors and oncologic outcomes in patients with MSI-H sporadic colon cancer.A total of 329 patients with MSI-H sporadic colon cancer who underwent radical surgery from January 2004 to December 2012 at a single institution were included. We analyzed prognostic factors and oncologic outcomes according to chemotherapy in these patients compared with patients with MSI-low/microsatellite stable colon cancer.Among the 329 patients, 174 were male and 155 were female. The median age was 59 years. The population consisted of 220 patients with stage II, 97 with stage III, and 12 with stage IV disease. Old age and advanced stage were independent poor prognostic factors of overall survival (OS; P = .014 and P = .040, respectively) and advanced stage and presence of perineural invasion were independent poor prognostic factors of disease-free survival (DFS; P = .004 and P = .001, respectively). In addition, a greater number of poor prognostic factors were associated with worse survival (P.001). Patients with stage II disease showed no differences in OS and DFS according to receiving or not receiving chemotherapy (P = .140 and P = .694, respectively).Old age, advanced stage, and presence of perineural invasion were independent and poor prognostic factors in patients with MSI-H sporadic colon cancer. Survival rates of MSI-H colon cancer patients with stage II disease were not improved by adjuvant chemotherapy.