Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer.

BACKGROUND: Postoperative minimal residual disease (MRD) detection using circulating-tumour DNA (ctDNA) requires a highly sensitive analysis platform. We have developed a tumour-informed, hybrid-capture ctDNA sequencing MRD assay. METHODS: Personalised target-capture panels for ctDNA detection were designed using individual variants identified in tumour whole-exome sequencing of each patient. MRD status was determined using ultra-high-depth sequencing data of plasma cell-free DNA. The MRD positivity and its association with clinical outcome were analysed in Stage II or III colorectal cancer (CRC). RESULTS: In 98 CRC patients, personalised panels for ctDNA sequencing were built from tumour data, including a median of 185 variants per patient. In silico simulation showed that increasing the number of target variants increases MRD detection sensitivity in low fractions (<0.01%). At postoperative 3-week, 21.4% of patients were positive for MRD by ctDNA. Postoperative positive MRD was strongly associated with poor disease-free survival (DFS) (adjusted hazard ratio 8.40, 95% confidence interval 3.49-20.2). Patients with a negative conversion of MRD after adjuvant therapy showed significantly better DFS (P < 0.001). CONCLUSION: Tumour-informed, hybrid-capture-based ctDNA assay monitoring a large number of patient-specific mutations is a sensitive strategy for MRD detection to predict recurrence in CRC.

Short-Term Impact of Temporary Shutdown of a University-Affiliated Hospital on Patients With Colorectal Cancer During the Coronavirus Disease 2019 Pandemic.

Owing to in-hospital transmission of coronavirus disease 2019 (COVID-19), Uijeongbu St. Mary's Hospital, a university-affiliated hospital in South Korea, was temporarily closed for disinfection in March 2020. This study aimed to investigate the impact of both the hospital shutdown and the prolonged COVID-19 pandemic on short-term outcomes of colorectal cancer (CRC) patients. We retrospectively reviewed the clinicopathologic data of 607 patients who were surgically treated for CRC from May 2018 to September 2021. Nodal upstaging, higher lymphatic invasion and abdominoperineal resection rates for 3 months after the hospital resumed surgery following the shutdown in the first wave of the COVID-19 pandemic were detected, without worse short-term morbidity or mortality. The incidence of adverse pathologic features of CRC such as lymphatic, venous, and perineural invasion was higher throughout the COVID-19 pandemic era. Further follow-up of CRC patients treated in the pandemic era for long-term oncologic outcomes is needed.

The development and validation of a predictive model for recurrence in rectal cancer based on radiological and clinicopathological data.

OBJECTIVE: To develop a prediction model for recurrence by incorporating radiological and clinicopathological prognostic factors in rectal cancer patients. METHODS: All radiologic and clinicopathologic data of 489 patients with rectal cancer, retrospectively collected from a single institution between 2009 and 2013, were used to develop a predictive model for recurrence using the Cox regression. The model performance was validated on an independent cohort between 2015 and 2017 (N = 168). RESULTS: Out of 489 derivative patients, 103 showed recurrence after surgery. The prediction model was constructed with the following four significant predictors: distance from anal verge, MR-based extramural venous invasion, pathologic nodal stage, and perineural invasion (HR: 1.69, 2.09, 2.59, 2.29, respectively). Each factor was assigned a risk score corresponding to HR. The derivation and validation cohort were classified by sum of risk scores into 3 groups: low, intermediate, and high risk. Each of these groups showed significantly different recurrence rates (derivation cohort: 13.4%, 35.3%, 61.5 %; validation cohort: 6.2%, 23.7%, 64.7%). Our new model showed better performance in risk stratification, compared to recurrence rates of tumor node metastasis (TNM) staging in the validation cohort (stage I: 3.6%, II: 12%, III: 30.2%). The area under the receiver operating characteristic curve of the new prediction model was higher than TNM staging at 3-year recurrence in the validation cohort (0.853 vs. 0.731; p = .009). CONCLUSIONS: The new risk prediction model was strongly correlated with a recurrence rate after rectal cancer surgery and excellent for selection of high-risk group, who needs more active surveillance. KEY POINTS: • Multivariate analysis revealed four significant risk factors to be MR-based extramural venous invasion, perineural invasion, nodal metastasis, and the short distance from anal verge among the radiologic and clinicopathologic data. • Our new recurrence prediction model including radiologic data as well as clinicopathologic data showed high predictive performance of disease recurrence. • This model can be used as a comprehensive approach to evaluate individual prognosis and helpful for the selection of highly recurrent group who needs more active surveillance.

Routine colonoscopy may be needed for uncomplicated acute right colonic diverticulitis.

BACKGROUND: Routine colonoscopy is recommended to determine the coexistence of colon cancer after medical treatment for colon diverticulitis. However, in the case of uncomplicated diverticulitis diagnosed by computed tomography, the clinical relevance of routine follow-up colonoscopy has recently been debated. Yet, the role of follow-up colonoscopy for right colon diverticulitis, which tends to develop at a younger age than left colon diverticulitis, has not been specifically evaluated. Therefore, we aimed to evaluate the incidence of right colon cancer or colonic adenomatous polyps, detected by routine colonoscopy, after conservative management of acute uncomplicated right colon diverticulitis. METHODS: Patients with uncomplicated right colon diverticulitis (modified Hinchey stage Ia) diagnosed by computed tomography imaging, between 2011 and 2017, and who underwent follow-up colonoscopy surveillance after treatment were included. The primary outcome was the incidence of colon cancer, with the detection rate of adenoma being the secondary outcome. Information for analysis was retrieved retrospectively from patients' medical records. RESULTS: The study group included 330 consecutive patients, with a mean age of 41.9 years, and 51.9% being men. For the primary outcome, the rate of colon cancer on follow-up colonoscopy was 0.3% (1/330 cases). The rate of adenoma detection was 20.9% (69/330 cases) and advanced adenoma (> 10 mm in diameter; or exhibiting a > 25% villous component or severe dysplasia), including colon cancer, was observed in 9 patients (2.7%). CONCLUSIONS: In patients with acute uncomplicated right colonic diverticulitis, routine colonoscopy after conservative treatment may be necessary because although the colon cancer detection rate is low, it is possible to detect advanced colon adenoma.

Survival outcomes after isolated local recurrence of rectal cancer and risk analysis affecting its resectability.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the clinical course and prognostic factors after isolated local recurrence (iLR) and to identify the predictive factors for R0 resection of locally recurrent rectal cancer (LRRC). METHODS: We retrospectively reviewed the medical records of 76 patients with iLR who had undergone radical surgery for a primary tumor from 2003 to 2015. RESULTS: The iLR rate was 2.5%. From 76 patients, 39 patients underwent R0 resection for iLR. Multivariate analysis revealed that initial open surgery, neoadjuvant chemoradiation, and p/ypT ≥ 3 were poor prognostic factors after iLR as regard to the variables related to the primary tumor; and symptom presence at the time of iLR diagnosis, higher fixity, and no chemotherapy after iLR were associated with shorter overall survival after iLR, and R0 resection of LRRC was the only favorable prognostic factor for progression-free survival after iLR as regard to the variables related to LRRC. Higher tumor level, negative pathologic circumferential margin of the primary tumor, and low fixity of LRRC were favorable factors in achieving R0 resection of LRRC. CONCLUSIONS: Early detection of iLR before symptom development, use of chemotherapy after iLR and R0 resection of LRRC should be considered to improve survival outcomes after iLR.

Prognostic role of pre-sarcopenia and body composition with long-term outcomes in obstructive colorectal cancer: a retrospective cohort study.

BACKGROUND: The clinical significance of pre-sarcopenia in colorectal cancer obstruction has not yet been described. The present study aimed to determine the short- and long-term oncologic impacts of pre-sarcopenia in obstructive colorectal cancer. METHODS: We retrospectively analyzed 214 patients with obstructive colon cancer between January 2004 and December 2013. Initial staging computed tomography (CT) scans identified pre-sarcopenia and visceral obesity by measuring the muscle and visceral fat areas at the third lumbar vertebra level. Both short-term postoperative and long-term oncologic outcomes were analyzed. RESULTS: Among all 214 patients, 71 (33.2%) were diagnosed with pre-sarcopenia. Pre-sarcopenia had a negative oncologic impact in both disease-free survival (DFS) and overall survival (OS), (hazard ratio [HR] = 1.86, 95% confidence interval [CI] 1.04-3.13, p = 0.037, and HR = 1.92, CI 1.02-3.60, p = 0.043, respectively). Visceral adiposity, body mass index (BMI), and neutrophil-lymphocyte ratio (NLR) did not significantly impact DFS and OS. CONCLUSION: Pre-sarcopenia is a clinical factor significantly associated with OS and DFS but not with short-term complications in obstructive colorectal cancer. In future, prospective studies should incorporate body composition data in patient risk assessments and oncologic prediction tools.

Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo.

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 µg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.

Chebulinic acid attenuates glutamate-induced HT22 cell death by inhibiting oxidative stress, calcium influx and MAPKs phosphorylation.

Glutamate-induced excitotoxicity and oxidative stress is a major causative factor in neuronal cell death in acute brain injuries and chronic neurodegenerative diseases. The prevention of oxidative stress is a potential therapeutic strategy. Therefore, in the present study, we aimed to examine a potential therapeutic agent and its protective mechanism against glutamate-mediated cell death. We first found that chebulinic acid isolated from extracts of the fruit of Terminalia chebula prevented glutamate-induced HT22 cell death. Chebulinic acid significantly reduced intracellular reactive oxygen species (ROS) production and Ca2+ influx induced by glutamate. We further demonstrated that chebulinic acid significantly decreased the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, and p38, as well as inhibiting pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 protein expression. Moreover, we demonstrated that chebulinic acid significantly reduced the apoptosis induced by glutamate in HT22 cells. In conclusion, our results in this study suggest that chebulinic acid is a potent protectant against glutamate-induced neuronal cell death via inhibiting ROS production, Ca2+ influx, and phosphorylation of MAPKs, as well as reducing the ratio of Bax to Bcl-2, which contribute to oxidative stress-mediated neuronal cell death.

7α,15-Dihydroxydehydroabietic acid from Pinus koraiensis inhibits the promotion of angiogenesis through downregulation of VEGF, p-Akt and p-ERK in HUVECs.

Pinus koraiensis pinecones are considered an undesired waste by-product of the processing of seeds. However, recent studies of the potential anti-tumor effects of the pinecones have led to increasing interest in their chemical constituents. The present study examined the potential antiangiogenic effects of the constituents of pinecones and further characterized their underlying mechanisms of action. Chemical investigation of a water extract of P. koraiensis pinecones led to the isolation and identification of the eight main components including five diterpenoids (1-5), two monoterpenes (6,7) and a phenolic acid (8). The structure of the compounds was determined by spectroscopic analysis of NMR spectra and LC/MS analysis. Of the isolated compounds, 7α,15-dihydroxydehydroabietic acid (5) significantly inhibited the promotion of angiogenesis in human umbilical vein endothelial cells (HUVECs). Compound 5 inhibited angiogenesis through downregulation of the VEGF, p-Akt and p-ERK signaling pathways. These results provide experimental evidence of a novel biological activity of 7α,15-dihydroxydehydroabietic acid (5) as a potential antiangiogenic substance. This study also suggests that compound 5 could potentially be a useful adjuvant therapeutic substance for cancer prevention and treatment.

The prognostic significance of KRAS and BRAF mutation status in Korean colorectal cancer patients.

BACKGROUND: BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients. METHODS: From July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary's Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status. All data were reviewed retrospectively. RESULTS: Among 1096 patients, 401 (36.7%) had KRAS mutations and 44 (4.0%) had BRAF mutations. Of 83 patients, 77 (92.8%) had microsatellite stable (MSS) or MSI low (MSI-L) status while 6 (7.2%) patients had MSI high (MSI-H) status. Patients with BRAF mutation demonstrated a worse disease-free survival (DFS, HR 1.990, CI 1.080-3.660, P = 0.02) and overall survival (OS, HR 3.470, CI 1.900-6.330, P < 0.0001). Regarding KRAS status, no significant difference was noted in DFS (P = 0.0548) or OS (P = 0.107). Comparing the MSS/MSI-L and MSI-H groups there were no significant differences in either DFS (P = 0.294) or OS (P = 0.557). CONCLUSIONS: BRAF mutation, rather than KRAS, was a significant prognostic factor in Korean CRC patients at both early and advanced stages. The subgroup analysis for MSI did not show significant differences in clinical outcome. BRAF should be included in future larger prospective biomarker studies on CRC.

The positive impact of surgical quality control on adequate lymph node harvest by standardized laparoscopic surgery and national quality assessment program in colorectal cancer.

PURPOSE: We aimed to present the factors associated with lymph node harvest (LNH) and seek whether surgical quality control measures can improve LNH. METHODS: From a prospectively collected data at a single institution, 874 CRC patients who underwent curative surgery between 2004 and 2013 were included. Factor and survival analyses were performed regarding LNH. Subgroup analysis was performed according to LNH group (LNH ≥ 12 vs LNH < 12) and year of surgery (2004-2008, 2009-2011, and 2012-2013 group). RESULTS: In the multivariate analysis, tumor location (OR 0.6, p < 0.001), stage (OR 1.95, p < 0.001), and year of surgery (OR 3.86, p < 0.001) showed an association with adequate LNH. In the subgroup analysis categorized by the year of surgery, surgical quality control measures by standardized laparoscopic surgery (OR 52.91, p < 0.001) showed notable association with adequate LNH. Comparing the 2009-2011 and 2012-2013 group, the national quality assessment program additionally improved adequate LNH percentage (83.9 vs 94.3%). In the survival analysis, disease-free survival (DFS) differed according to year of surgery, standardized laparoscopic surgery with high vascular ligation, and adequate LNH by stage. In the overall survival (OS) analysis, the LNH-related factors did not show significant difference. CONCLUSIONS: Through standardized laparoscopic surgery with high vascular ligation and national quality assessment program, surgical quality control had a positive impact on the increase of adequate LNH. Improving the modifiable LNH factors resulted in the enhancement of adequate LNH and related DFS.

Comparison of Long-Term Outcomes Between Emergency Surgery and Bridge to Surgery for Malignant Obstruction in Right-Sided Colon Cancer: A Multicenter Retrospective Study.

BACKGROUND: Malignant obstruction in right-sided colon (MORC) has traditionally been treated by emergency resection with primary anastomosis. The aim of this study was to evaluate short-term postoperative and long-term oncologic outcomes according to the surgical approach adopted for MORC. METHODS: A total of 1785 patients who underwent curative surgery for stage II or III colon cancer in seven hospitals were reviewed retrospectively. Seventy-four of 1785 patients had MORC. We compared the postoperative outcome and long-term oncologic outcome between the emergency surgery (ES) group (49 patients) and the bridge to surgery (BS) group (25 patients) for 74 patients with MORC. RESULTS: There were no differences in the length of the distal and proximal resection margin (p = 0.820 and p = 0.620) or the number of metastatic lymph nodes (p = 0.221). There were no differences in flatus passage (p = 0.242), start of diet (p = 0.336), hospital stay (p = 0.444), or postoperative morbidity (p = 0.762). The 5-year overall survival rates were 73.2 % in the ES group and 90.7 % in the BS group (p = 0.172). Moreover, the 5-year disease-free survival rates were 71.9 % in the ES group and 76.2 % in the BS group (p = 0.929). CONCLUSIONS: On the basis of the above results, the postoperative course of the ES group was similar to that of the BS group. In addition, the long-term oncologic outcome of the BS group was similar or slightly better than that of the ES group. BS after colonic stent may be an alternative option for MORC.

Effect of time delays for appendectomy as observed on computed tomography in patients with noncomplicated appendicitis.

OBJECTIVES: Delaying appendectomy is a controversial issue. This study aimed at identifying the effect of time delays in surgery, especially for patients with noncomplicated appendicitis on computed tomography (CT). METHODS: Postappendectomy patients were analyzed from October 2013 to August 2014. Among the patients, data of those with findings of noncomplicated appendicitis on CT were gathered and the following time parameters were reviewed: CT examination time and appendectomy time. Other basic information and postoperative complications were checked. Patients were divided into a noncomplicated appendicitis group and a complicated appendicitis group. Perforated appendicitis and periappendiceal abscesses were regarded as complicated appendicitis. All other appendicitis from simple, focal to suppurative, and gangrenous appendicitis were regarded as noncomplicated appendicitis. RESULTS: In total, 397 patients were enrolled. The mean age was 33.2 years and the number of male/female patients was 216:181, respectively. The mean times from CT to operation were 5.9 vs 6.3hours for both the noncomplicated and complicated appendicitis groups (P=.758). The time from CT to operation showed no statistical relation to occurrences of complicated appendicitis, or postoperative complications such as ileuses, wound complications, and length of hospital stay. CONCLUSIONS: The time from CT to operation has no effect on the results of appendicitis. Further study in large-scaled, multicenter setting might yield more reliable results.

Correlation of dynamic contrast-enhanced MRI perfusion parameters with angiogenesis and biologic aggressiveness of rectal cancer: Preliminary results.

PURPOSE: To investigate whether quantitative parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are correlated with angiogenesis and biologic aggressiveness of rectal cancer. MATERIALS AND METHODS: A total of 46 patients with rectal cancer underwent DCE-MRI. Using a two-compartmental model, quantitative parameters (K(trans) , kep , ve , and iAUC) were calculated from the whole-transverse region of interest (ROI) and high K(trans) area ROI of entire tumors. Histological specimens were analyzed for tumor size; T/N stage; lymphatic, vascular, perineural invasion; expression of epidermal growth factor receptor (EGFR); and KRAS gene mutations. Tumor angiogenesis was evaluated based on the microvessel density (MVD) and the expression level of the vascular endothelial growth factor. Correlations of the DCE-MRI parameters with histological markers and angiogenesis were determined using Student's t-test and analysis of variance (ANOVA). RESULTS: The mean kep from high K(trans) area ROIs showed a significantly positive correlation with MVD (P = 0.030, r = 0.514, R(2) = 0.264). The mean kep from the whole-transverse ROIs showed a significant inverse correlation with T stage (T1 vs. T2-4, P = 0.021). EGFR-positive cancer displayed higher mean K(trans) (P = 0.045) and kep (P = 0.038) than EGFR-negative cancer in whole-transverse ROIs. CONCLUSION: These preliminary results suggest that the determination of kep of high K(trans) area permits the noninvasive estimation of tumor angiogenesis in rectal cancer and that DCE-MRI parameters can be used as imaging biomarkers to predict the biologic aggressiveness of the tumor and patient prognosis.

Stromal expression of miR-21 in T3-4a colorectal cancer is an independent predictor of early tumor relapse.

BACKGROUND: MicroRNA-21 (miR-21) is an oncogenic microRNA that regulates the expression of multiple cancer-related target genes. miR-21 has been associated with progression of some types of cancer. Metastasis-associated protein1 expression and loss of E-cadherin expression are correlated with cancer progression and metastasis in many cancer types. In advanced colorectal cancer, the clinical significance of miR-21 expression remains unclear. We aimed to investigate the impact of miR-21 expression in advanced colorectal cancer and its correlation with target proteins associated with colorectal cancer progression. METHODS: From 2004 to 2007, 277 consecutive patients with T3-4a colorectal cancer treated with R0 surgical resection were included. Patients with neoadjuvant therapy and distant metastasis at presentation were excluded. The expression of miR-21 was investigated by in situ hybridization. Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression. RESULTS: High stromal expression of miR-21 was found in 76 of 277 (27.4%) colorectal cancer samples and was correlated with low E-cadherin expression (P = 0.019) and high metastasis-associated protein1 expression (P = 0.004). T3-4a colorectal cancer patients with high miR-21 expression had significantly shorter recurrence-free survival than those with low miR-21 expression. When analyzing colon and rectal cancer separately, high expression of miR-21 was an independent prognostic factor of unfavorable recurrence-free survival in T3-4a colon cancer patients (P = 0.038, HR = 2.45; 95% CI = 1.05-5.72) but not in T3-4a rectal cancer patients. In a sub-classification analysis, high miR-21 expression was associated with shorter recurrence-free survival in the stage II cancer (P = 0.001) but not in the stage III subgroup (P = 0.267). CONCLUSIONS: Stromal miR-21 expression is related to the expression of E-cadherin and metastasis-associated protein1 in colorectal cancer. Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

Wnt3a expression is associated with MMP-9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer.

BACKGROUND: The wnt/ß-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2). METHODS: Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, ß-catenin, MMP-9 and VEGFR-2. RESULTS: Wnt3a, wnt5a, ß-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and ß-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p = 0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p = 0.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, ß-catenin expression was significantly correlated with overall survival (p = 0.05). CONCLUSIONS: Wnt3a and wnt5a expression had a concordance rate higher than 60% with a high concordance rate between the primary tumor and metastatic site. Wnt3a expression is associated with the expression of MMP-9 in primary tumor tissue adjacent mesenchymal tissue, and at the metastatic site. As a prognostic marker, only ß-catenin expression showed significant relation with survival outcome.

Quantitative detection of target cells using unghosted cells (UGCs) of DxH 800 (Beckman Coulter).

BACKGROUND: In the Retic channel of DxH 800 (Beckman Coulter), the red blood cells (RBCs) resistant to hemoglobin clearing are counted as unghosted cells (UGCs). The aim of this study was to evaluate that the UGC is a surrogate marker for both the detection and counting of target cells. METHODS: In total, 1181 samples including 22 from iron deficiency anemia (IDA) patients, 95 from jaundice, 2 from sickle cell anemia, 3 from thalassemia, 1 cord blood, and 269 from normal controls were analyzed. Slides were prepared from all samples except normal controls and target cells were counted for correlation analysis of target cell counts to UGCs. RESULTS: The normal control samples showed 0.01% (0%-0.01%) UGCs, and the reference range was set at ≤0.02%. The IDA samples showed 0.015% (0.01%-0.03%) UGC count and 0.05% (0%-0.2%) target cell count. The jaundice samples showed 0.98% (0.1%-5.36%) UGC count, and 1.4% (0.1%-7.0%) target cell count. The two sickle cell anemia samples showed 0.41% and 3.74% UGC counts and 0.4% and 11.5% target cell counts. A cord blood sample showed 0.01% UGCs and 0% target cells. The three thalassemia samples showed 0.01%, 1.99%, and 7.82% UGC counts and 0%, 1.4%, and 15.5% target cell counts. The samples showing poikilocytosis other than target cells showed normal UGC count (≤0.02%). The positive predictive value of UGCs was 58.2% (124/213) and the negative predictive value was 96.8% (674/696). The UGC counts were well correlated to the manual target cell counts (r=0.944, p=0.000). CONCLUSIONS: This study demonstrates for the first time in the literature that a hematological parameter obtained automatically every time a reticulocyte counting is performed can be used to both screen for the presence of target cells and reliably quantify them.

Prediction and management of recurrent right colon diverticulitis.

PURPOSE: While the incidence of right colonic diverticulitis (RCD) is rare in Western countries, the right colon is the most common site of diverticulitis in Asian countries. However, its recurrent pattern and management were rarely studied. This study was designed to elucidate the pattern of recurrence in RCD. METHODS: Of the 154 patients admitted as right colonic diverticulitis between February 2004 and March 2012, 104 patients were enrolled, prospectively. The recurrence rate, size, multiplicity, location, diagnostic criteria score, and predisposing factors were evaluated based on Hinchey's classification of diverticulitis. RESULTS: There were 104 patients with right colonic diverticulitis in this study, and 20 patients (19.2 %) recurred after medical treatment. When the diverticula were not located in the right colon, the recurrence rate was significantly higher than the diverticula located only in the right colon (p = 0.004). The recurrence rate of diverticulitis for a single diverticulum was significantly lower than that for multiple diverticula (p = 0.02). Of the 20 patients with recurrence, 1 (5 %) patient underwent laparoscopic diverticulectomy due to a misdiagnosis of diverticulitis as appendicitis. The remaining 19 patients (95 %) received nonoperative management and recovered without any sequelae. CONCLUSIONS: The recurrence rate was 19.2 %, and the predisposing factors were the location of diverticula and the multiplicity of primary diverticula. The re-recurrence rate of recurred patients was 26.3 %. The recurred lesions were controlled simply by nonoperative management. Elective surgery was also a treatment option.

High ligation with posterior wall repair for inguinal hernia repair in young adults: a nationwide cohort study.

Purpose: This study evaluated the difference in the recurrence of inguinal hernia in young adult patients who underwent either high ligation alone or high ligation with posterior wall repair using nationwide data. Methods: This retrospective study included young adult patients (aged 16-30 years) who underwent surgery for inguinal hernia between June 1, 2013 and December 31, 2020. Data from the National Health Information Database from the Korea Health Insurance Service were used for this study. Patients were divided into 2 groups (high ligation alone and posterior wall repair). The primary outcome was the difference in recurrent inguinal hernia surgeries between the 2 groups. Results: Among the 10,803 patients included in the study, 947 underwent high ligation alone, and 9,856 underwent high ligation with posterior wall repair. Recurrence was observed in 18 patients (1.9%) in the high ligation only group and 84 (0.85%) in the high ligation with posterior wall repair group. Log-rank test findings revealed that recurrence was less frequent in the high ligation with posterior wall repair group than in the high ligation only group (P = 0.003). In the multivariate analysis of factors influencing recurrence, posterior wall repair (hazard ratio, 0.241; P = 0.001) was shown to significantly lower the recurrence. Conclusion: Posterior wall repair might be necessary for inguinal hernia repair in young adults.

Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers.

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis. [BMB Reports 2024; 57(3): 161-166].