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Abstract Background The efficacy of cell implantation via 3D-spheroids to treat basal tone in fecal incontinence remains unclear. To address this, in this study, we aimed to identify cell differentiation and assess the development of a contractile phenotype corresponding to smooth muscle cells (SMCs) following implantation of 3D-spheroid and 2D-cultured human adipose stem cells (hASCs) in an in vivo internal anal sphincter (IAS)-targeted mouse model. Methods We developed an IAS-targeted in vivo model via rapid freezing (at − 196 °C) of the dorsal layers of the region of interest (ROI) of the IAS ring posterior quarter, between the submucosal and muscular layers, following submucosal dissection (n = 60 rats). After implantation of tetramethylindocarbocyanine perchlorate (Dil)-stained 3D and 2D-cells into randomly allocated cryoinjured rats, the entire sphincter ring or only the cryoinjured ROI was harvested. Expression of SMC markers, RhoA/ROCKII and its downstream molecules, and fibrosis markers was analyzed. Dil, α-smooth muscle actin (α-SMA), and RhoA signals were used for cell tracking. Results In vitro, 3D-spheroids exhibited higher levels of SMC markers and RhoA/ROCKII-downstream molecules than 2D-hASCs. The IAS-targeted cryoinjured model exhibited substantial loss of SMC layers of the squamous epithelium lining of the anal canal, as well as reduced expression of SMC markers and RhoA-related downstream molecules. In vivo, 3D-spheroid implantation induced SMC markers and contractile molecules weakly at 1 week. At 2 weeks, the mRNA expression of aSma, Sm22a, Smoothelin, RhoA, Mypt1, Mlc 20 , Cpi17, and Pp1cd increased, whereas that of fibrosis markers reduced significantly in the 3D-spheroid implanted group compared to those in the sham, non-implanted, and 2D-hASC implanted groups. Protein levels of RhoA, p-MYPT1, and p-MLC20 were higher in the 3D-spheroid-implanted group than in the other groups. At 2 weeks, in the implanted groups, the cryoinjured tissues (which exhibited Dil, α-SMA, and RhoA signals) were restored, while they remained defective in the sham and non-implanted groups. Conclusions These findings demonstrate that, compared to 2D-cultured hASCs, 3D-spheroids more effectively induce a contractile phenotype that is initially weak but subsequently improves, inducing expression of RhoA/ROCKII-downstream molecules and SMC differentiation associated with IAS basal tone.

Objective:. We explored the oncological impact of tumor deposits (TDs) on colon cancer and proposed optimal modifications to the current staging system. Background:. In the existing American Joint Committee on Cancer colon cancer staging system, TDs are incorporated into the N category as N1c. When lymph node metastases (LNMs) are present, their number is considered to determine nodal stages, such as N1a/b or N2a/b, regardless of TDs. Methods:. 4212 patients with primary colon cancer who underwent surgical resection in the Seoul Colorectal Group (2010–2020) and 93,057 patients from the Surveillance, Epidemiology, and End Results*Stat database (2000–2017) were included in this study. Patients were classified according to the number of metastatic lymph nodes (LNs) (0/1–3/≥4) and the presence of TDs. Results:. TDs were significantly associated with left colon cancer, a higher T category, and vascular/perineural invasion. Patients with TDs had higher recurrence rates (23.1 vs 7.5%, P < 0.001). The TD-positive patients had notably worse overall survival (OS) and recurrence-free survival rates. The survival outcomes of TD-positive patients without LNM were inferior to those of TD-negative patients with LN1–3 (5-year OS: 78.9 vs 87.8%, P = 0.04). The survival outcomes of TD-positive patients with LN1–3 were similar to those of TD-negative patients with LN ≥4 (5-year OS: 87.0 vs 77.1%, P = 0.11). Survival outcomes obtained using the Surveillance, Epidemiology, and End Results *Stat database yielded consistent results. Conclusions:. TDs were associated with poor prognostic factors and had a significant impact on survival outcomes. The incorporation of tumor deposits into nodal classifications beyond the current N1c criteria may improve the staging system and more accurately reflect the recurrence and survival rates among patients with colon cancer. TD-positive in N1a or N1b could be categorized as N2.

Complete mesocolic excision and central vascular ligation with D3 lymphadenectomy are important surgical principles for improving oncological outcomes in colon cancer. The cranial-first approach is a colonic mobilization–first approach for radical right hemicolectomy, which has several advantages, including early feasibility assessment, safe dissection from surrounding organs, preestablished inferior margin of lymph node dissection, and revelation of the tangible anatomy of the tributaries of the gastrocolic trunk. This video demonstrates the cranial-first approach for laparoscopic extended right hemicolectomy in a 66-year-old man with locally advanced cecal cancer.

Abstract Tumor-infiltrating lymphocytes (TIL) have been suggested as an important prognostic marker in colorectal cancer, but assessment usually requires additional tissue processing and interpretational efforts. The aim of this study is to assess the clinical significance of artificial intelligence (AI)-powered spatial TIL analysis using only a hematoxylin and eosin (H&E)-stained whole-slide image (WSI) for the prediction of prognosis in stage II–III colon cancer treated with surgery and adjuvant therapy. In this retrospective study, we used Lunit SCOPE IO, an AI-powered H&E WSI analyzer, to assess intratumoral TIL (iTIL) and tumor-related stromal TIL (sTIL) densities from WSIs of 289 patients. The patients with confirmed recurrences had significantly lower sTIL densities (mean sTIL density 630.2/mm2 in cases with confirmed recurrence vs. 1021.3/mm2 in no recurrence, p

Background/Aims: Anorectal functions are influenced by gender and age. This study sought to define the normal anorectal pressure values measured with conventional anorectal manometry (ARM) and to evaluate the effects of age and gender on anorectal function in asymptomatic subjects. Methods: Conventional ARM was used to measure the anorectal pressures of 164 asymptomatic healthy subjects, including 86 males and 76 females. Results: The resting anal pressures of males and females aged >60 years were significantly lower than those ≤60 years (males, 44.09±14.22 vs. 57.45±17.69, p

Abstract Background Acute postoperative pain is a common complication of inguinal hernia repair. Pain management using local application of anesthetic agents over the skin surrounding the surgical incision may reduce the requirement for other pain medications. Targeted topical analgesics such as 5% lidocaine patches have been known to improve acute and chronic pain. However, the clinical effect of lidocaine patches on postoperative pain after inguinal hernia repair has not been studied, especially in patients undergoing surgery at day surgery units. Methods/design This is a single-center, prospective, double-blind, randomized, controlled clinical trial. Participants with unilateral inguinal hernia will be randomized to the lidocaine patch group or the placebo patch group. Based on the randomized allocation sequence, either lidocaine patches or placebo patches will be attached near each participant’s surgical wound after open hernia repair under general anesthesia. Participants will be asked to follow up at our outpatient clinic on the first postoperative day and at 1 week after surgery. The primary outcome is pain intensity, which will be measured using the visual analog scale (VAS) at the time of discharge from the day surgery unit. The secondary outcomes are VAS score at 24 h and 1 week after surgery. We will collect and analyze the participants’ clinical data (amount of intraoperative opioid use, time to recovery, and pain intensity at 30 min after surgery) and demographic characteristics (age, sex, body weight, and height). Discussion This trial may not only provide evidence on the efficacy of a 5% lidocaine patch for acute postoperative pain management after unilateral inguinal hernia repair, but also demonstrate the efficacy and safety of the patch for post-discharge pain management. Trial registration ClinicalTrials.gov NCT04754451. Registered on February 10, 2021.

IntroductionGlucose transporter-1 (GLUT-1) has been studied as a possible predictor for survival outcomes in locally advanced rectal cancer (LARC).MethodsWe aimed to investigate the prognostic role of GLUT-1 in LARC using the data of 208 patients with clinical T3–4 stage and/or node-positive rectal adenocarcinoma, all of whom underwent neoadjuvant chemoradiotherapy (CRT) and subsequent total mesorectal excision (TME). Both pre-CRT and post-CRT specimens were immunohistologically stained for GLUT-1. Patients were classified into GLUT-1-positive and GLUT-1-negative groups and distant metastasis-free survival (DMFS) and overall survival (OS) was analyzed and compared.ResultsAt a median follow-up of 74 months, post-CRT GLUT-1 status showed a significant correlation with worse DMFS (p=0.027, HR 2.26) and OS (p=0.030, HR 2.30). When patients were classified into 4 groups according to yp stage II/III status and post-CRT GLUT-1 positivity [yp stage II & GLUT-1 (-), yp stage II & GLUT-1 (+), yp stage III & GLUT-1 (-), yp stage III & GLUT-1 (+)], the 5-year DMFS rates were 92.3%, 63.9%, 65.4%, and 46.5%, respectively (p=0.013). GLUT-1 (-) groups showed markedly better outcomes for both yp stage II and III patients compared to GLUT-1 (+) groups. A similar tendency was observed for OS.DiscussionIn conclusion, post-CRT GLUT-1 may serve as a prognostic marker in LARC.

Abstract We aimed to compare the short- and long-term outcomes of simultaneous laparoscopic, hybrid, and open resection for colorectal cancer and synchronous liver metastases. We retrospectively analyzed the data of 647 patients with simultaneous resection of colorectal cancer and liver metastases between January 2006 and December 2018 at three tertiary referral hospitals. Patient’s baseline characteristics, perioperative outcomes, pathological examination results, liver-specific recurrence rate and survivals were compared between the propensity score-matched groups. Forty-two and 81 patients were selected for the laparoscopic vs. hybrid groups, and 48 and 136 patients for laparoscopic vs. open groups, respectively. The laparoscopic group had fewer wound complications (2.1 vs. 13.2%; p = 0.028) than the open group, and a shorter postoperative hospital stay than the hybrid and open groups (8 vs. 11 days, p

Purpose Local excision (LE) is an alternative initial treatment for clinical T1 rectal cancer, and has avoided potential morbidity. This study aimed to evaluate the clinical outcomes of LE compared with total mesorectal excision (TME) for clinical T1 rectal cancer. Methods Between January 2000 and December 2011, we retrospectively reviewed from multicenter data in patients with clinically suspected T1 rectal cancer treated with either LE or TME. Of 1,071 patients, 106 were treated with LE and 965 were treated with TME. The data were analyzed using propensity score matching, with each group comprising 91 patients. Results After propensity score matching, the median follow-up time was 60.8 months (range, 0.6–150.6 months). After adjustment for the necessary variables, patients who underwent LE showed a significantly higher local recurrence rate than did those who underwent TME; however, there were no differences in disease-free survival and overall survival. In the multivariate analysis, age (hazard ratio [HR], 9.620; 95% confidence interval [CI], 3.415–27.098; P

Abstract Epithelial–mesenchymal transition (EMT)-related cancers generally elicit low immune responses. EMT is regulated by several microRNAs (miRNAs) in cancers. Thus, this study aimed to evaluate the prognostic potential of EMT-related miRNAs as biomarkers in colorectal cancer (CRC). Formalin-fixed paraffin-embedded tumor and normal tissue and plasma samples were obtained from 65 patients with pathologically confirmed CRC. In addition, plasma samples were obtained from 30 healthy volunteers. Immunohistochemical staining for E-cadherin, ZEB1, PD-1, PD-L1, CD3, CD4, CD8, Foxp3, and CD68 was conducted on tissue samples. Droplet digital polymerase chain reaction (ddPCR) analysis was performed to evaluate miR-21-5p, 34a-5p, 138-5p, 200a-3p, 200b-5p, 200c-3p, 630, 1246, and 1290 expression in tissue samples and miR-630, 1246, and 1290 expression in plasma samples. miR-21-5p, 34a-5p, 630, 1246, and 1290 expression was higher in tumor tissues than in normal tissues (P

Background A laparoscopic approach is widely used in abdominal surgery. Although several studies have compared surgical and oncological outcomes between laparoscopic surgery (LS) and open surgery (OS) in rectal cancer patients, there have been few studies on postoperative renal outcomes. Methods We conducted a retrospective cohort study involving 1,633 patients who underwent rectal cancer surgery between 2003 and 2017. Postoperative acute kidney injury (AKI) was diagnosed according to the serum creatinine criteria of the Kidney Disease: Improving Global Outcomes classification. Results Among the 1,633 patients, 1,072 (65.6%) underwent LS. After matching propensity scores, 395 patients were included in each group. The incidence of postoperative AKI in the LS group was significantly lower than in the OS group (9.9% vs. 15.9%; p = 0.01). Operation time, estimated blood loss, and incidence of transfusion in the LS group were significantly lower than those in the OS group. Cox proportional hazard models revealed that LS was associated with decreased risk of postoperative AKI (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.402–0.893; p = 0.01) and postoperative transfusion was associated with increased risk of AKI (HR, 2.495; 95% CI, 1.529–4.072; p < 0.001). In the subgroup analysis, the incidence of postoperative AKI in patients with middle or high rectal cancer who underwent LS was much lower than in those who underwent OS (HR, 0.373; 95% CI, 0.197–0.705; p = 0.002). Conclusion This study showed that LS may have a favorable effect on the development of postoperative AKI in patients with rectal cancer.

Purpose This study aimed to evaluate the safety and feasibility of single-port laparoscopic surgery (SLS) for appendiceal mucinous neoplasm (AMN) when compared with conventional laparoscopic surgery (CLS). Methods This retrospective study enrolled patients who underwent surgery for AMN between July 2014 and June 2020 at Seoul National University Bundang Hospital. Patient demographics, surgical data, pathology, hospital stay, postoperative morbidity, and follow-up data were extracted from electronic records for analysis. Results We enrolled 18 patients who underwent SLS and 22 who underwent CLS. The SLS group included patients who underwent partial cecectomy (14 patients), ileocecectomy (3 patients), and right hemicolectomy (1 patient). The CLS group included patients who underwent appendectomy (4 patients), partial cecectomy (11 patients), ileocecectomy (5 patients), and right hemicolectomy (2 patients). Operation type was not significantly different between groups (P = 0.213). No patient required open surgery in the SLS group in contrast to the CLS group (13.6%; P = 0.238). The operative time tended to be shorter in the SLS group than the CLS group (median [interquartile range]: 52.5 minutes [40–65.2 minutes] and 60 minutes [40–120 minutes], respectively; P = 0.251). Morbidity was 5.5% in the SLS group and 9.0% in the CLS group (P = 0.692). Surgical margins were clear in all cases. The median duration of postoperative hospital stay was 2.0 and 4.0 days in the SLS and CLS groups, respectively (P = 0.013). No recurrence occurred in either group during follow-up. Conclusion This study indicates that SLS is a safe and feasible surgical approach for AMN.

PurposePresence of a long remnant sigmoid colon after left hemicolectomy with inferior mesenteric vein (IMV) ligation for distal transverse and descending colon cancers may be a risk factor for venous ischemia. This study aimed to evaluate the clinical impact of IMV preservation in patients who underwent left hemicolectomy with inferior mesenteric artery (IMA) preservation.MethodsWe included 155 patients who underwent left hemicolectomy with IMA preservation for distal transverse and descending colon cancers from 2003 to 2020. Technical success of IMV preservation was determined by assessing pre- and post-operative patency of the IMV on computed tomography (CT) by an abdominal radiologist. Intestinal complications comprising ulceration, stricture, venous engorgement, and colitis in remnant colon were compared between the IMV preservation and ligation groups.ResultsIMV was preserved in 22 (14.2%) and ligated in 133 (85.8%) patients. Surgical time, postoperative recovery outcomes, and number of harvested lymph nodes were similar in both groups. The technical success of IMV preservation was 81.8%. Intestinal complications were less common in the preservation group than in the IMV ligation group (4.5% vs. 23.3%, P=0.048). The complications in the IMV ligation group were anastomotic ulcer (n=2), anastomotic stricture (n=4), venous engorgement of the remnant distal colon (n=4), and colitis in the distal colon (n=21).ConclusionsIMV preservation may be beneficial after left hemicolectomy with IMA preservation for distal transverse and descending colon cancers. We suggest that IMV preservation might be considered when long remnant sigmoid colon is expected during left hemicolectomy with low ligation of IMA.

Purpose This study aimed to evaluate real-world clinical outcomes from surgically treated patients for sigmoid volvulus. Methods Five tertiary centers participated in this retrospective study with data collected from October 2003 through September 2018, including demographic information, preoperative clinical data, and information on laparoscopic/open and elective/emergency procedures. Outcome measurements included operation time, postoperative hospitalization, and postoperative morbidity. Results Among 74 patients, sigmoidectomy was the most common procedure (n = 46), followed by Hartmann’s procedure (n = 23), and subtotal colectomy (n = 5). Emergency surgery was performed in 35 cases (47.3%). Of the 35 emergency patients, 34 cases (97.1%) underwent open surgery, and a stoma was established for 26 patients (74.3%). Elective surgery was performed in 39 cases (52.7%), including 21 open procedures (53.8%), and 18 laparoscopic surgeries (46.2%). Median laparoscopic operation time was 180 minutes, while median open surgery time was 130 minutes (P < 0.001). Median postoperative hospitalization was 11 days for laparoscopy and 12 days for open surgery. There were 20 postoperative complications (27.0%), and all were resolved with conservative management. Emergency surgery cases had a higher complication rate than elective surgery cases (40.0% vs. 15.4%, P = 0.034). Conclusion Relative to elective surgery, emergency surgery had a higher rate of postoperative complications, open surgery, and stoma formation. As such, elective laparoscopic surgery after successful sigmoidoscopic decompression may be the optimal clinical option.

Abstract Background Laparoscopic surgery for T4 colon cancer may be safe in selected patients. We hypothesized that small tumor size might preoperatively predict a good laparoscopic surgery outcome. Herein, we compared the clinicopathologic and oncologic outcomes of laparoscopic and open surgery in small T4 colon cancer. Methods In a retrospective multicenter study, we reviewed the data of 449 patients, including 117 patients with tumors ≤ 4.0 cm who underwent surgery for T4 colon cancer between January 2014 and December 2017. We compared the clinicopathologic and 3-year oncologic outcomes between the laparoscopic and open groups. Survival curves were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. A p < 0.05 was considered statistically significant. Results Blood loss, length of hospital stay, and postoperative morbidity were lower in the laparoscopic group than in the open group (median [range], 50 [0–700] vs. 100 [0–4000] mL, p < 0.001; 8 vs. 10 days, p < 0.001; and 18.0 vs. 29.5%, p = 0.005, respectively). There were no intergroup differences in 3-year overall survival or disease-free survival (86.6 vs. 83.2%, p = 0.180, and 71.7 vs. 75.1%, p = 0.720, respectively). Among patients with tumor size ≤ 4.0 cm, blood loss was significantly lower in the laparoscopic group than in the open group (median [range], 50 [0–530] vs. 50 [0–1000] mL, p = 0.003). Despite no statistical difference observed in the 3-year overall survival rate (83.3 vs. 78.7%, p = 0.538), the laparoscopic group had a significantly higher 3-year disease-free survival rate (79.2 vs. 53.2%, p = 0.012). Conclusions Laparoscopic surgery showed similar outcomes to open surgery in T4 colon cancer patients and may have favorable short-term oncologic outcomes in patients with tumors ≤ 4.0 cm.

Abstract Background Frail older adults are at increased risk of post‐operative morbidity compared with robust counterparts. Simple methods testing frailty such as grip strength or gait speed have shown promising results for predicting post‐operative outcome, but there is a debate regarding the most appropriate and precise frailty assessment method. We compared the predictive value of multidimensional frailty score (MFS) with grip strength, gait speed, or conventional risk stratification tool for predicting post‐operative complications in older surgical patients. Methods From January 2016 to June 2017, 648 older surgical patients (age ≥ 65 years) were included for analysis. MFS was calculated based on the preoperative comprehensive geriatric assessment. Grip strength and gait speed were measured before surgery. The primary outcome was a composite of post‐operative complications (e.g. pneumonia, urinary tract infection, delirium, acute pulmonary thromboembolism, and unplanned intensive care unit admission). The secondary outcome was the 6 month all‐cause mortality. Results Among 648 patients (mean age 76.6 ± 5.4 years, 52.8% female), 66 (10.2%) patients experienced post‐operative complications, and the 6 month mortality was 3.9% (n = 25). Grip strength, gait speed, MFS, and American Society of Anesthesiologists (ASA) classification could predict post‐operative complication but only MFS (hazard ratio = 1.581, 95% confidence interval 1.276–1.959, P < 0.001) could predict 6 month mortality after adjustment. MFS (C‐index = 0.750) had a superior prognostic utility compared with age (0.638, P = 0.008), grip strength (0.566, P < 0.001), and ASA classification (0.649, P = 0.004). MFS improved the predictive value on age [C‐index of 0.638 (age) vs. 0.758 (age + MFS), P < 0.001] and ASA classification [C‐index of 0.649 (ASA) vs. 0.765 (ASA + MFS), P < 0.001] for post‐operative complication; however, gait speed or grip strength did not provide additional prognostic value in both age and ASA. Conclusions Multidimensional frailty score based on preoperative comprehensive geriatric assessment showed better utility than age, grip strength, gait speed, or ASA classification for predicting post‐operative complication and 6 month mortality. MFS also showed incremental predictive ability for post‐operative complications with the addition of age and ASA classification. Accordingly, MFS is superior to grip strength or gait speed for predicting complications among older surgical patients.

Purpose Single-port laparoscopic techniques can be optimized with confined incisions. This approach has an intraoperative advantage of excellent visualization of the correct intestinal segment for exteriorization, along with direct visual control of the extraction to avoid twisting. However, only a few studies have verified the efficacy of the technique. Thus, this study assessed the results of single-port laparoscopic stoma creation for fecal diversion, specifically focusing on feasibility, safety, and efficacy. Methods Patients who underwent single-incision enterostomy performed by a single surgeon were included. Data on demographics, indications for and chosen procedure, and operation results were retrospectively collected and analyzed. Results Between April 2015 and January 2018, a total of 13 patients (8 males, 5 females) with a mean age of 57.7 years (range, 41–83 years) underwent single-port ileostomy creation. The most common reason for diversion was palliative ileostomy for colon obstruction or fistula from peritoneal malignancy (n = 12), followed by colonic fistula with necrotizing pancreatitis (n = 1). There were no cases of conversion to open or multiport laparoscopic surgery. The mean operative time was 54 minutes (range, 37–118 minutes), and the median length of hospital stay was 8 days (range, 2–211 days). A postoperative complication, aspiration pneumonia, was documented in 1 patient and treated conservatively. The mean duration of bowel movement was 0.7 days (range, 0–4 days). All stomas had good function, and there was no 30-day mortality. Conclusion Single-port laparoscopic ileostomy in patients with a palliative setting could be a safe and feasible option for fecal diversion.

Abstract Background To develop and compare delta-radiomics signatures from 2- (2D) and 3-dimensional (3D) features that predict treatment outcomes following preoperative chemoradiotherapy (CCRT) and surgery for locally advanced rectal cancer. Methods In total, 101 patients (training cohort, n = 67; validation cohort, n = 34) with locally advanced rectal adenocarcinoma between 2008 and 2015 were included. We extracted 55 features from T2-weighted magnetic resonance imaging (MRI) scans. Delta-radiomics feature was defined as the difference in radiomics feature before and after CCRT. Signatures were developed to predict local recurrence (LR), distant metastasis (DM), and disease-free survival (DFS) from 2D and 3D features. The least absolute shrinkage and selection operator regression was used to select features and build signatures. The delta-radiomics signatures and clinical factors were integrated into Cox regression analysis to determine if the signatures were independent prognostic factors. Results The radiomics signatures for LR, DM, and DFS were developed and validated using both 2D and 3D features. Outcomes were significantly different in the low- and high-risk patients dichotomized by optimal cutoff in both the training and validation cohorts. In multivariate analysis, the signatures were independent prognostic factors even when considering the clinical parameters. There were no significant differences in C-index from 2D vs. 3D signatures. Conclusions This is the first study to develop delta-radiomics signatures for rectal cancer. The signatures successfully predicted the outcomes and were independent prognostic factors. External validation is warranted to ensure their performance.

Purpose Stage-IIIC colon cancer is an advanced disease; however, its oncologic outcomes and prognostic factors remain unclear. In this study, we aimed to determine the predictors of disease-free survival (DFS) in patients with stage-IIIC colon cancer. Methods From a multicenter database, we retrospectively enrolled 611 patients (355 men and 256 women) who had undergone a potentially curative resection for a stage-IIIC colon adenocarcinoma between 2003 and 2011. The primary end-point was the 5-year DFS. Results The median age was 62 years; 213 and 398 patients had right-sided colon cancer (RCC) and left-sided colon cancer (LCC), respectively. The 5-year DFS in all patients was 52.0%; median follow-up time was 35 months (range, 1–134 months). A multivariate Cox regression revealed that female sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.19–1.90; P < 0.01), right-sided tumor location (HR, 1.65; 95% CI, 1.29–2.11; P < 0.01), lymphatic invasion (HR, 1.52; 95% CI, 1.08–2.15; P < 0.01) and a high (≥0.4) metastatic lymph node ratio (HR, 3.72; 95% CI, 2.63–5.24; P < 0.01) were independent predictors of worse 5-year DFS. Female patients with RCC were 1.79 fold more likely to experience recurrence than male patients with LCC. Conclusion Female sex and right-sided tumor location are associated with higher tumor recurrence rates in patients with stage-IIIC colon cancers. Aggressive treatment and close surveillance should be planned for patients in these groups.

Summary: Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525). Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval [CI], −1•3 to 9•7, p = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6, p = 0•0052), micturition symptoms (−8•0 points; 95% CI, -14•1 to −1•8, p = 0•0108), male sexual problems (−19•9 points; 95% CI, -33•1 to -6•7, p = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8, p = 0•0155), and worse urinary symptoms (−5•4 points on a 35-point scale; 95% CI, −8•0 to −2•7, p

Purpose We aimed to investigate the extent of heterogeneity in medical terminology between South and North Korea by comparing medical terms related to the colorectal system. Methods North Korean medical terms were collected from the sections on diseases of the small intestine and colon in a surgery textbook from North Korea, and those terms were compared with their corresponding terms in a South Korean medical terminology textbook. The terms were categorized as either identical, similar, showing disparity, or not used in South Korea. In a subsection analysis, the terms were allocated to pathophysiology, diagnosis, symptoms and examination, drugs, testing, treatment, or others according to the categorization used in the textbook. Results We found 705 terms in the North Korean textbook, most of which were pathophysiological terms (206, 29.2%), followed by diagnostic terms (165, 23.4%) and symptom and examination terms (122, 17.3%). Treatment-, drug-, and testing-related terms constituted 15.5%, 5.8%, and 4.1% of the 705 terms, respectively. There were 331 identical terms (47.0%) and 146 similar terms (20.7%); 126 terms (17.9%) showed disparity. Another 102 terms (14.5%) were not used in South Korea. The pathophysiological terms were the least heterogeneous, with 61.2% being identical terms used in both countries. However, 26.8% of the terms in the drug category were not used in South Korea. Conclusion The present study showed that less than 50% of the terms for the colorectal system used in South and North Korea were identical. As the division between South and North Korea persists, the heterogeneity of medical terminology is expected to increase.

Purpose The purpose of this study was to categorize surgery-related medical terminologies used in South and North Korea and to compare and analyze discrepancies observed in the terms. Methods This study collected medical terminology used in the North Korean medical book “Surgery” and compared it to medical terminology found in the medical glossary of South Korea. The order of the subtitle was described according to the Instruction to Authors. Results In total, there were 2,168 individual medical terms, of which only 1,004 words (46.3%) were identical to South Korean medical terms. There were 581 similar terms (26.8%), 265 different terms (12.2%), and 318 terms that are nonexistent in South Korea (14.7%). Conclusion Less than half of the medical terms used in North Korea match those used in South Korea. It is expected that the prolongation of the current division of South and North Korea will only worsen this discrepancy. Further efforts to bridge the gap through academic exchange between South Korea and North Korea are required in preparation for an era of reunification.

BackgroundAnesthetic agents used for general anesthesia are emerging possible influential factors for surgical site infection (SSI). In this retrospective study, we evaluated the incidence of SSI after colorectal surgery according to the main anesthetic agents: volatile anesthetics vs. propofol.MethodsA total 1,934 adult patients, who underwent elective colorectal surgery under general anesthesia between January 2011 and December 2013, were surveyed to evaluate the incidence of SSI: 1,519 using volatile anesthetics and 415 using propofol for main anesthetic agents. Patient, surgery, and anesthesia-related factors were investigated from all patients. Propensity-score matching was performed to reduce the risk of confounding and produced 390 patients in each group.ResultsWithin the propensity-score matched groups, the incidence of SSI was higher in the volatile group compared with the propofol group (10 [2.6%] vs. 2 [0.5%], OR = 5.0 [95% CI = 1.1-2.8]). C-reactive protein was higher in the volatile group than in the propofol group (8.4 ± 5.6 vs. 7.1 ± 5.3 mg/dl, P = 0.001), and postoperative white blood cells count was higher in the volatile group than in the propofol group (9.2 ± 3.2 × 103/µl vs. 8.6 ± 3.4 × 103/µl, P = 0.041).ConclusionsThe results of this study suggest that intravenous anesthesia may have beneficial effects for reducing SSI in colorectal surgery compared to volatile anesthesia.

Background: The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis. Methods: miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry. Results: The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041). Conclusions: miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.

To retrospectively determine the sensitivity of preoperative CT in the detection of small (≤ 10 mm) colorectal liver metastasis (CRLM) nodules in patients undergoing liver resection.The institutional review board approved the study and waived informed consent. We included 461 pathologically confirmed CRLM nodules in 211 patients (including 71 women; mean age, 66.4 years) who underwent 229 liver resections following abdominal CT. Prior to 163 resections, gadoxetic acid-enhanced liver MR imaging was also performed. Nodules were matched between pathology reports and prospective CT reports following a predefined algorithm. Per-nodule sensitivity of CT was calculated by nodule-size category. Generalized estimating equations were used to adjust for within-case correlation.Fourteen nodule sizes were missing in the pathology report. Nodules of 1-5 mm and 6-10 mm accounted for 8.1% (n = 36) and 23.5% (n = 105) of the remaining 447 nodules, and the number of nodules gradually decreased as nodule size increased beyond 10 mm. The overall sensitivity of CT was 81.2% (95% confidence interval, 77.1%, 85.2%; 365/461). The sensitivity was 8% (0%, 17%; 3/36), 55% (45%, 65%; 59/105), 91%, 95%, and 100% for nodules of 1-5 mm, 6-10 mm, 11-15 mm, 16-20 mm, and >20 mm, respectively. The nodule-size distribution was similar between resections undergoing gadoxetic acid-enhanced MR imaging and those not undergoing the MR imaging.CT has limited sensitivity for nodules of ≤ 10 mm and particularly of ≤ 5 mm.

Anti-EGFR antibody-based treatment is an important therapeutic strategy for advanced colorectal cancer (CRC); despite this, several mutations--including KRAS, BRAF, and PIK3CA mutations, and HER2 amplification--are associated with the mechanisms underlying the development of resistance to anti-EGFR therapy. The aim of our study was to investigate the frequencies and clinical implications of these genetic alterations in advanced CRC.KRAS, BRAF, and PIK3CA mutations were determined by Cobas real-time polymerase chain reaction (PCR) in 191 advanced CRC patients with distant metastasis. Microsatellite instability (MSI) status was determined by a fragmentation assay and HER2 amplification was assessed by silver in situ hybridization. In addition, KRAS mutations were investigated by the Sanger sequencing method in 97 of 191 CRC cases.Mutations in KRAS, BRAF, and PIK3CA were found in 104 (54.5%), 6 (3.1%), and 25 (13.1%) cases of advanced CRC, respectively. MSI-high status and HER2 amplification were observed in 3 (1.6%) and 16 (8.4%) cases, respectively. PIK3CA mutations were more frequently found in KRAS mutant type (18.3%) than KRAS wild type (6.9%) (P = 0.020). In contrast, HER2 amplifications and BRAF mutations were associated with KRAS wild type with borderline significance (P = 0.052 and 0.094, respectively). In combined analyses with KRAS, BRAF and HER2 status, BRAF mutations or HER2 amplifications were associated with the worst prognosis in the wild type KRAS group (P = 0.004). When comparing the efficacy of detection methods, the results of real time PCR analysis revealed 56 of 97 (57.7%) CRC cases with KRAS mutations, whereas Sanger sequencing revealed 49 cases (50.5%).KRAS mutations were found in 54.5% of advanced CRC patients. Our results support that subgrouping using PIK3CA and BRAF mutation or HER2 amplification status, in addition to KRAS mutation status, is helpful for managing advanced CRC patients.

To evaluate the prognostic impact of the lymph node ratio (LNR) in ypStage III rectal cancer patients who were treated with neoadjuvant chemoradiotherapy (NCRT).We retrospectively reviewed the data of 638 consecutive patients who underwent NCRT followed by total mesorectal excision, and postoperative adjuvant chemotherapy for rectal cancer from 2004 to 2011. Of these, 125 patients were positive for lymph node (LN) metastasis and were analyzed in this study.The median numbers of examined and metastatic LNs were 17 and 2, respectively, and the median LNR was 0.143 (range, 0.02-1). Median follow-up time was 55 months. In multivariate analyses, LNR was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] 2.17, p = 0.041), disease-free survival (DFS) (HR 2.28, p = 0.005), and distant metastasis-free survival (DMFS) (HR 2.30, p = 0.010). When ypN1 patients were divided into low (low LNR ypN1 group) and high LNR (high LNR ypN1 group) according to a cut-off value of 0.152, the high LNR ypN1 group had poorer OS (p = 0.043) and DFS (p = 0.056) compared with the low LNR ypN1 group. And there were no differences between the high LNR ypN1 group and the ypN2 group in terms of the OS (p = 0.703) and DFS (p = 0.831).For ypN-positive rectal cancer patients, the LNR was a more effective prognostic marker than the ypN stage, circumferential resection margin, or tumor regression grade after NCRT, and could be used to discern the high-risk group among ypN1 patients.

The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients with primary colorectal cancer (CRC).The c-MYC GCN was investigated in 367 consecutive CRC patients (cohort 1) by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were investigated for mutations.In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 (8.4%) of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies/nucleus, was found in 63 (17.2%) patients and was associated with poor prognosis (P = 0.015). Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 (95% confidence interval, 1.453-3.802; P < 0.001). In a subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate (P = 0.034) and multivariate (P = 0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of 367 patients and weakly correlated with c-MYC GCN gain (ρ, 0.211). In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS.c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients' outcome and for managing CRC patients.

To compare the impact of postoperative chemoradiotherapy (CRT) versus adjuvant chemotherapy alone on recurrence and survival in patients with stage II and III upper rectal cancer undergoing curative resection.From our institutional database, 190 patients who underwent primary curative resection between 2003 and 2010 for stage II or III upper rectal cancer were identified. None of the patients received preoperative CRT. Of these, 136 patients received postoperative chemotherapy alone (the CTx group) and 54 patients received postoperative CRT (the CRT group). The CRT group had poorer prognostic features (pT4, pN2, poor differentiation, or involved resection margin) compared with the CTx group. To reduce the impact of treatment selection bias on treatment outcomes, propensity score-matching analysis was used.The matched cohort consisted of 50 CRT and 50 CTx patients with a median follow-up period of 76 and 63 months, respectively. In the matched cohort, CRT resulted in an improved 5-year local control (98.0% vs. 85.2%, p = 0.024) and overall survival rate (89.9% vs. 69.8%, p = 0.021) compared with CTx. In the subgroup analysis to identify subpopulations of patients that benefit most from receiving CRT, local recurrence did not occur in patients who did not have poor prognostic features regardless of the receipt of CRT. For patients with any poor prognostic features, CRT resulted in an improved 5-year local control compared with CTx (96.4% vs. 70.7%, p = 0.013).After adjusting for clinicopathologic factors by propensity score-matching, postoperative CRT was associated with improved local control and overall survival in stage II and III upper rectal cancer. Our results suggest that surgery followed by chemotherapy alone is acceptable for patients who did not have poor prognostic features, while additional radiotherapy should be given for patients who have any poor prognostic features.

This study aimed at determining the incidence and clinical implications of HER2 status in primary colorectal cancer (CRC). HER2 status was investigated in two retrospective cohorts of 365 consecutive CRC patients (cohort 1) and 174 advanced CRC patients with synchronous or metachronous distant metastasis (cohort 2). HER2 status was determined by performing dual-color silver in-situ hybridization (SISH), mRNA in-situ hybridization (ISH), and immunohistochemistry (IHC). The incidence of HER2 protein overexpression (IHC 2+/3+) was approximately 6% (22 of 365 in cohort 1; 10 of 174 in cohort 2). HER2 gene amplification was observed in 5.8% of the patients from cohort 1 and 6.3% of the patients from cohort 2. HER2 gene amplification was more frequently observed in CRCs located in the rectum than in the right and left colon (P = 0.013 in cohort 1; P = 0.009 in cohort 2). HER2 status, determined by IHC, ISH, and dual-color SISH, was not significantly associated with aggressive CRC behaviour or patients' prognosis in both the cohorts. Of the combined cohort with a total of 539 cases, the concordance rate was 95.5% between dual-color SISH and IHC detection methods. On excluding equivocally immunostained cases (IHC 2+), the concordance rate was 97.7%. HER2 mRNA overtranscription, detected by ISH, significantly correlated with protein overexpression and gene amplification (P

We aimed to evaluate the clinical significance of microvessel density (MVD), lymphatic vessel density (LVD), and cancer-associated fibroblasts (CAFs) in relation to tumor location in advanced colorectal cancer (CRC).Using immunohistochemistry, we examined 181 advanced CRC patients for CD31 and D2-40 to measure MVD and LVD, respectively, α-smooth muscle actin (SMA) and desmin to identify CAFs, and PTEN to examine genetic changes of CAFs. To evaluate the regional heterogeneity of these properties, we examined tissue from four sites (the center and periphery of the primary cancer, a distant metastasis, and a lymph node metastasis) in each patient.MVD, LVD, and CAFs showed significant heterogeneity with respect to the tumor location. LVD was the greatest in the center of the primary cancers and the amount of CAFs was the lowest in distant metastases. In distant metastases, those from the lung had higher LVD and MVD, but fewer CAFs than those from the liver, peritoneum, or ovary. Patients with low MVD and LVD in the center of the primary cancer had worse outcomes and patients with few CAFs in distant metastases and in the primary tumor had a lower survival rate. PTEN expression in CAFs in distant metastases was lost in 11 of 181 CRC patients (6.1%), which was associated with a worse prognosis.The microenvironment, including cancer-associated microvasculature and fibroblasts, is heterogeneous with respect to the tumor location in CRC patients. Therefore, heterogeneity of microenvironments should be taken into account when managing CRC patients.