International standardization and optimization group for intersphincteric resection (ISOG-ISR): modified Delphi consensus on anatomy, definition, indication, surgical technique, specimen description and functional outcome.

AIM: Intersphincteric resection (ISR) is an oncologically complex operation for very low-lying rectal cancers. Yet, definition, anatomical description, operative indications and operative approaches to ISR are not standardized. The aim of this study was to standardize the definition of ISR by reaching international consensus from the experts in the field. This standardization will allow meaningful comparison in the literature in the future. METHOD: A modified Delphi approach with three rounds of questionnaire was adopted. A total of 29 international experts from 11 countries were recruited for this study. Six domains with a total of 37 statements were examined, including anatomical definition; definition of intersphincteric dissection, intersphincteric resection (ISR) and ultra-low anterior resection (uLAR); indication for ISR; surgical technique of ISR; specimen description of ISR; and functional outcome assessment protocol. RESULTS: Three rounds of questionnaire were performed (response rate 100%, 89.6%, 89.6%). Agreement (≥80%) reached standardization on 36 statements. CONCLUSION: This study provides an international expert consensus-based definition and standardization of ISR. This is the first study standardizing terminology and definition of deep pelvis/anal canal anatomy from a surgical point of view. Intersphincteric dissection, ISR and uLAR were specifically defined for precise surgical description. Indication for ISR was determined by the rectal tumour's maximal radial infiltration (T stage) below the levator ani. A new surgical definition of T3isp was reached by consensus to define T3 low rectal tumours infiltrating the intersphincteric plane. A practical flowchart for surgical indication for uLAR/ISR/abdominoperineal resection was developed. A standardized ISR surgical technique and functional outcome assessment protocol was defined.

Clinical implication of tissue carcinoembryonic antigen expression in association with serum carcinoembryonic antigen in colorectal cancer.

This study aimed to evaluate the prognostic significance of carcinoembryonic antigen (CEA) expression in tumor tissues of patients with colorectal cancer (CRC). The cohort included 7,412 patients with CRC from January 2010 to December 2015. Survival outcomes were assessed based on tissue CEA (t-CEA) patterns and intensities. Three-year (76.7% versus 81.3%) and 5-year (71.7% versus 77.6%, p < 0.001) disease-free survival (DFS) rates were significantly (p < 0.001) poorer in patients with a diffuse-cytoplasmic pattern than an apicoluminal pattern. Three-year (79% versus 86.6%) and 5-year (74.6% versus 84.7%) DFS rates were also significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Three-year (84.6% versus 88.4%) and 5-year (77.3% versus 82.6%) overall survival (OS) rates were significantly (p < 0.001) poorer in patients with diffuse-cytoplasmic than apicoluminal pattern of CEA expression, and both 3-year (86.7% versus 91.2%) and 5-year (80.1% versus 87.7%) OS rates were significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Multivariate analyses showed that high-intensity t-CEA was independently associated with DFS (p = 0.02; hazard ratio [HR] = 1.233) and OS (p = 0.032; HR = 1.228). Therefore, high-intensity t-CEA is a significant prognostic factor in CRC, independent of serum CEA (s-CEA), and can complement s-CEA in predicting survival outcomes after CRC resection.

Interpretation and clinical utility of indocyanine-green fluorescence imaging (IFI) in robot-assisted anorectal-function saving operations (ASOs): A propensity-score matched analysis of 872 prospectively enroled patients undergoing IFI.

BACKGROUND: This study suggested a novel physiological evaluation of indocyanine-green fluorescence imaging (IFI), and its utility associated with anastomotic leakage/stricture (AL/AS) and prognosis. METHODS: This study focussed on the utility of IFI, comparing IFI + versus IFI- groups (n = 878 vs. 339), optimised by propensity-score matching. After intravenous injection of indocyanine green, maximal perfusion was separately assessed at the vasa recta (VR) and colonic wall (CW), by determining intensities at the VR (VRI) and CW (CWI) and respective time. RESULTS: Although IFI did not significantly reduce either AL or AS, which occurred approximately 3-fold frequently in patients with lower than higher intensity of VRI. IFI was found as an independent parameter for both disease-free [DFS: hazard ratio (HR) = 0.489; p = 0.002] and overall survival (OS: HR = 0.519; p = 0.021). CONCLUSIONS: Although IFI did not significantly reduce AL/AS, IFI independently reduced 5-year systemic recurrence and increased 5-year DFS and OS.

Partial mesorectal excision can be a primary option for middle rectal cancer: a propensity-score matched retrospective analysis.

Purpose: Although partial and total mesorectal excision (PME and TME) is primarily indicated for the upper and lower rectal cancer, respectively, few studies have evaluated whether PME or TME is more optimal for middle rectal cancer. Methods: This study included 671 patients with middle and upper rectal cancer who underwent robot-assisted PME or TME. The 2 groups were optimized by propensity-score matching of sex, age, clinical stage, tumor location, and neoadjuvant treatment. Results: Complete mesorectal excision was achieved in 617 of 671 patients (92.0%), without showing a difference between the PME and TME groups. Local (5.3% vs. 4.3%, P>0.999) and systemic (8.5% vs. 16.0%, P=0.181) recurrence rates also did not differ between the 2 groups, respectively, in patients with middle and upper rectal cancer. The 5-year disease-free survival (81.4% vs. 74.0%, P=0.537) and overall survival (88.0% vs. 81.1%, P=0.847) rates also did not differ between the PME and TME groups, confined to middle rectal cancer. Moreover, 5-year recurrence and survival rates were not affected by distal resection margins of 2 cm (P=0.112) to 4 cm (P>0.999), regardless of pathological stages. Postoperative complication rate was higher in the TME than in the PME group (21.4% vs. 14.5%, P=0.027). Incontinence was independently associated with TME (odds ratio [OR], 2.009; 95% confidence interval, 1.015-3.975; P=0.045), along with older age (OR, 4.366, P<0.001) and prolonged operation time (OR, 2.196; P=0.500). Conclusion: PME can be primarily recommended for patients with middle rectal cancer with lower margin of >5 cm from the anal verge.

Robot-assisted lateral pelvic lymph node dissection in patients with advanced rectal cancer: a single-center experience of 65 cases.

The treatment of lateral pelvic lymph node (LPLN) metastasis of rectal cancer has evolved because of technical difficulties from open surgery to laparoscopy and, recently, robot-assisted surgery. This study aimed to evaluate the technical feasibility and short- and long-term outcomes of robot-assisted LPLN dissection (LPND) following total mesorectal excision (TME) in advanced rectal cancer. Clinical data of 65 patients who underwent robotic-assisted TME with LPND from April 2014 to July 2022 were reviewed. Data regarding operative details, postoperative morbidity (within 90 postoperative days) for short-term outcomes and lateral recurrence as long-term outcomes were analyzed. Among the 65 patients with LPND, preoperative chemoradiotherapy was performed in 49 (75.4%). The mean operative time was 306.8 (range 191-477) min, and the mean time of unilateral LPND was 38.6 (range 16-66) min. LPND was bilaterally performed in 19 (29.2%) patients. The mean number of each side of harvested LPLNs was 6.8. Lymph node metastasis was observed in 15 (23.0%) patients, and 10 (15.4%) patients had postoperative complications. Lymphocele (n = 3) and pelvic abscess (n = 3) were the most common, followed by voiding difficulty, erectile dysfunction, obturator neuropathy, and sciatic neuropathy (all n = 1). During the 25 months of median follow-up, no lateral recurrence of the LPND site was noted. Robot-assisted LPND following TME is safe and feasible and showed acceptable short- and long-term outcomes. Despite some study limitations, we may be able to apply this strategy more widely through subsequent prospective controlled studies.

Reduced expression of alanyl aminopeptidase is a robust biomarker of non-familial adenomatous polyposis and non-hereditary nonpolyposis colorectal cancer syndrome early-onset colorectal cancer.

BACKGROUND: Early-onset colorectal cancer (EOCRC) has been increasing in incidence worldwide but its genomic pathogenesis is mostly undetermined. This study aimed to identify robust EOCRC-specific gene expression patterns in non-familial adenomatous polyposis (FAP) and non-hereditary nonpolyposis colorectal cancer syndrome (HNPCC) EOCRC. METHOD: We first performed gene expression profiling analysis using RNA sequencing of discovery cohort comprised of 49 EOCRC (age <50) and 50 late-onset colorectal cancer (LOCRC) (age >70) specimens. To obtain robust gene expression data from this analysis, we validated differentially expressed genes (DEGs) through TCGA cohort (EOCRC:59 samples, LOCRC:229 samples) and our validation cohort (EOCRC:72 samples, LOCRC:43 samples) using real-time RT-PCR. After the validation of DEGs, we validated the selected gene at protein levels using Western blotting. To identify whether genomic methylation regulates the expression of a particular gene, we selected methylation sites using The Cancer Genome Atlas (TCGA) datasets and validated them by pyrosequencing in our validation cohort. RESULTS: The EOCRC patients included in this study had significantly more prominent family history of cancer than the LOCRC patients (23 [46.9%] vs. 13 [26%], p = 0.050). Alanyl aminopeptidase (ANPEP) was significantly downregulated in the EOCRC tissues (FC = 1.78, p = 0.0007) and was also commonly downregulated in the TCGA cohort (FC = -1.08, p = 0.0021). Moreover, the ANPEP mRNA and protein expression levels were significantly downregulated in the EOCRC tissues of our validation cohort (p = 0.037 and 0.027). In comparisons of the normal and tumor tissues in public datasets, the ANPEP level was significantly lower in the tumor tissue in the TCGA dataset (p < 2.2 × 10-16 ) and GSE196006 dataset (p = 0.0005). Furthermore, the ANPEP expression level did not show a decreasing tendency at a young age in the normal colon tissue of the GTEx dataset. Lastly, the hypermethylation of cg26222247 in ANPEP was identified to be weakly associated with reduced ANPEP expression in our EOCRC cohort. CONCLUSION: The reduced expression of ANPEP was identified as a novel biomarker of non-FAP and non-HNPCC EOCRC.

Pathologic Implications of Magnetic Resonance Imaging-detected Extramural Venous Invasion of Rectal Cancer.

BACKGROUND: Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer. MATERIALS AND METHODS: This study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT. RESULTS: Of the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT. CONCLUSION: MR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT.

Technical, functional, and oncological validity of robot-assisted total-intersphincteric resection (T-ISR) for lower rectal cancer.

BACKGROUND: Few studies fairly compared anorectal function and prognostic outcomes between patients undergoing abdominoperineal resection (APR) and anorectal-function-saving operations (ASO) under the equivalent conditions. By contrast, surgeons used to be somewhat hesitant to conduct total intersphincteric resection (T-ISR) as maximal ASO, due to its technical complexity and potential anorectal dysfunction. METHODS: Propensity-score matched cohorts undergoing robot-assisted R0 surgery [T-ISR vs APR vs partial-subtotal ISR (PS-ISR)/lower anterior resection (LAR)] for rectal cancer (n = 1361) were included. Operative outcomes, recurrence, and disease-free/overall survival (DFS/OS) were analyzed. Anorectal function was evaluated based on fecal incontinence score and high-resolution manometry between the T-ISR and other ASO groups. RESULTS: Few differences were detected between the T-ISR and APR groups. More patients undergoing APR had T4 stage disease, while the lowest tumor margin was the same in both groups (mean, 1.5 cm from anal verge). Prognostic outcomes did not differ between the T-ISR and APR groups, including local (5.1% vs 7.7%, p = 1) or systemic (15.4% vs 25.6%, p = 0.401) recurrence, and 5-year DFS (78.7% vs 61.5%, p = 0.1) and OS (89% vs 82.1%, p = 0.434) rates, nor were there differences between the T-ISR and PS-ISR/LAR groups. The PS-ISR group generally showed less anorectal dysfunction than the T-ISR group, but maximal tolerance volume did not differ between these two groups and was within the range for the healthy population. CONCLUSIONS: T-ISR can replace most traditional APR, except for advanced T4 disease with aggressive infiltration into the levator-sphincters, and can provide tolerable anorectal dysfunction.

Efficacy of preoperative chemoradiotherapy in patients with cT2N0 distal rectal cancer.

PURPOSE: This study was designed to determine the feasibility of preoperative chemoradiotherapy (PCRT) in patients with clinical T2N0 distal rectal cancer. METHODS: Patients who underwent surgery for clinical T2N0 distal rectal cancer between January 2008 and December 2016 were included. Patients were divided into PCRT and non-PCRT groups. Non-PCRT patients underwent radical resection or local excision (LE) according to the surgeon's decision, and PCRT patients underwent surgery according to the response to PCRT. Patients received 50.0 to 50.4 gray of preoperative radiotherapy with concurrent chemotherapy. RESULTS: Of 127 patients enrolled, 46 underwent PCRT and 81 did not. The mean distance of lesions from the anal verge was lower in the PCRT group (P=0.004). The most frequent operation was transanal excision and ultralow anterior resection in the PCRT and non-PCRT groups, respectively. Of the 46 patients who underwent PCRT, 21 (45.7%) achieved pathologic complete response, including 15 of the 24 (62.5%) who underwent LE. Rectal sparing rate was significantly higher in the PCRT group (11.1% vs. 52.2%, P<0.001). There were no significant differences in 3- and 5-year overall survival and recurrence-free survival regardless of PCRT or surgical procedures. CONCLUSION: PCRT in clinical T2N0 distal rectal cancer patients increased the rectal sparing rate via LE and showed acceptable oncologic outcomes. PCRT may be a feasible therapeutic option to avoid abdominoperineal resection in clinical T2N0 distal rectal cancer.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Prognostic significance of lymph node yield on oncologic outcomes according to tumor response after preoperative chemoradiotherapy in rectal cancer patients.

PURPOSE: This study aimed to evaluate the predictive value of lymph node yield (LNY) for survival outcomes according to tumor response after preoperative chemoradiotherapy (PCRT) in patients with rectal cancer. METHODS: This study was a retrospective study conducted in a tertiary center. A total of 1,240 patients with clinical stage II or III rectal cancer who underwent curative resection after PCRT between 2007 and 2016 were included. Patients were categorized into the good response group (tumor regression grade [TRG], 0-1) or poor response group (TRG, 2-3). Propensity score matching was performed for age, sex, and pathologic stage between LNY of ≥12 and LNY of <12 within tumor response group. The primary outcome was 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: LNY and positive lymph nodes were inversely correlated with TRG. In good responders, 5-year DFS and 5-year OS of patients with LNY of <12 were better than those with LNY of ≥12, but there was no statistical significance. In poor responders, the LNY of <12 group had worse survival outcomes than the LNY of ≥12 group, but there was also no statistical significance. LNY of ≥12 was not associated with DFS and OS in multivariate analysis. CONCLUSION: LNY of <12 showed contrasting outcomes between the good and poor responders in 5-year DFS and OS. LNY of 12 may not imply adequate oncologic surgery or proper staging in rectal cancer patients treated by PCRT. Furthermore, a decrease in LNY should be comprehended differently according to tumor response.

Lifestyle interventions after colorectal cancer surgery using a mobile digital device: A study protocol for a randomized controlled trial.

BACKGROUND: In treating colorectal cancer, surgical techniques and adjuvant treatments have advanced over the past century, but relatively less attention has been given to improve health-related quality of life (HRQOL). Recent studies report a significant association between cancer recurrence and patient lifestyle after surgery, hence emphasizing the need to assist patients to reduce this risk through appropriate lifestyle choices. The proposed study will evaluate the effects of digital interventions on lifestyle after surgery for colorectal cancer using mobile applications. METHODS: A randomized controlled trial design was proposed. A total of 320 patients diagnosed with colorectal cancer aged between 20 and 70 years were to be enrolled and randomized in equal numbers into 4 groups (3 groups assigned to different mobile applications and a control group). Surveys that evaluate HRQOL, physical measurements, and metabolic parameters (fasting glucose, hemoglobin A1C, triglyceride, high-density lipoprotein cholesterol), and fat/muscle mass measurements by abdominal computed tomography (CT), will be conducted prior to surgery and every 6 months post-surgery for 18 months. Statistical analysis will be used to compare the outcomes between groups. DISCUSSION: Results from this study could provide evidence that easily accessible mobile applications can influence patient lifestyles. Results showing minimal effects of such applications could also be constructive for improving healthcare-related applications.

Preoperative albumin-bilirubin score as a prognostic indicator in patients with stage III colon cancer.

The albumin-bilirubin (ALBI) score was created to assess the severity of liver dysfunction and to predict prognosis of hepatocellular carcinoma. Purpose of this study was to investigate the prognostic value of the ALBI score in patients with stage III colon cancer using propensity score matching (PSM) analysis. This study analyzed 510 patients with stage III colon cancer who had surgery between 2014 and 2015. The ALBI score was calculated as follows: (log10 bilirubin (µmol/L) [Formula: see text] 0.66) + (albumin (g/L) [Formula: see text] -0.0852), and the optimal cut-off value was determined using a receiver operating characteristic analysis and the Youden Index. According to the calculated cut-off value, patients were divided into two groups: Group A (ALBI ≤ - 2.54) and Group B (ALBI > - 2.54). The average ALBI score was - 2.68 (from - 3.39 to - 0.69). Group A had a significantly higher 5-year disease-free survival rate (85.5% vs 75.7%, p = 0.02), 5-year cancer-specific survival rate (93.7% vs 84.4%, p = 0.02), and 5-year overall survival rate (90.6% vs 77.4%, p = 0.01) than Group B. High ALBI scores were found to be an independent risk factor for both disease-free survival (HR 1.68, p = 0.048) and cancer-specific survival (HR 2.24, p = 0.028). The preoperative ALBI score was found to be a promising prognostic indicator for predicting recurrence and survival in patients with stage III colon cancer in this study. Because the ALBI score is simple and inexpensive to obtain, it has the potential to be a useful clinical marker for colon cancer patients.

Cumulative incidence and risk factors for pouch adenomas associated with familial adenomatous polyposis following restorative proctocolectomy.

BACKGROUND: The emergence of restorative total proctocolectomy has significantly reduced the lifetime colorectal cancer risk associated with familial adenomatous polyposis (FAP). However, adenomas may develop in the ileal pouch over time and may even progress to carcinoma. We evaluated the cumulative incidence, time to development, and risk factors associated with ileal pouch adenoma. AIM: To evaluate the cumulative incidence, time to development, and risk factors associated with pouch adenoma. METHODS: In this retrospective, observational study conducted at a tertiary center, 95 patients with FAP who underwent restorative proctocolectomy at our center between 1989 and 2018 were consecutively included. The mean follow-up period was 88 mo. RESULTS: Pouch adenomas were found in 24 (25.3%) patients, with a median time of 52 mo to their first formation. Tubular adenomas were detected in most patients (95.9%). There were no high-grade dysplasia or malignancies. Of the 24 patients with pouch adenomas, 13 had all detected adenomas removed. Among the 13 patients who underwent complete adenoma removal, four (38.5%) developed recurrence. Among 11 (45.8%) patients with numerous polyps within the pouch, seven (63.6%) exhibited progression of pouch adenoma. The cumulative risks of pouch adenoma development at 5, 10, and 15 years after pouch surgery were 15.2%, 29.6%, and 44.1%, respectively. Severe colorectal polyposis (with more than 1000 polyps) was a significant risk factor for pouch adenoma development (hazard ratio, 2.49; 95% confidence interval: 1.04-5.96; P = 0.041). CONCLUSION: Pouch adenomas occur at a fairly high rate in association with FAP after restorative proctocolectomy, and a high colorectal polyp count is associated with pouch adenoma development.

The Prognostic Reliability of Lymphovascular Invasion for Patients with T3N0 Colorectal Cancer in Adjuvant Chemotherapy Decision Making.

Lymphovascular invasion (LVI) is a high-risk feature guiding decision making for adjuvant chemotherapy. We evaluated the prognostic importance and reliability of LVI as an adjuvant chemotherapy indicator in 1634 patients with pT3N0 colorectal cancer treated with curative radical resection between 2012 and 2016. LVI and perineural invasion (PNI) were identified in 382 (23.5%) and 269 (16.5%) patients, respectively. In total, 772 patients received adjuvant chemotherapy. The five-year recurrence-free survival (RFS) and OS rates were 92% and 94.8%, respectively. Preoperative obstruction, PNI, and positive margins were significantly associated with RFS and OS; however, adjuvant chemotherapy and LVI were not. Pathologic slide central reviews of 242 patients using dual D2-40 and CD31 immunohistochemical staining was performed. In the review cohort, the diagnosis of LVI and PNI was changed in 82 (33.9%) and 61 (25.2%) patients, respectively. Reviewed LVI, encompassing small vessel invasion, lymphatic invasion, and large vessel invasion, was not an independent risk factor associated with OS but was related to RFS. The prognostic importance of LVI and adjuvant chemotherapy was not defined because LVI may be underrecognized in pathologic diagnoses using hematoxylin and eosin staining slides only, leading to low recurrence rate predictions. Using LVI as a guiding factor for adjuvant chemotherapy requires further consideration.

Genomic and transcriptomic analysis of Korean colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is the third most common type of diagnosed cancer in the world and has the second-highest mortality rate. Meanwhile, South Korea has the second-highest incidence rate for CRC in the world. OBJECTIVE: To assess the possible influence of ethnicity on the molecular profile of colorectal cancer, we compared genomic and transcriptomic features of South Korean CRCs with European CRCs. METHODS: We assembled a genomic and transcriptomic dataset of South Korean CRC patients (KOCRC; n = 126) from previous studies and European cases (EUCRC; n = 245) selected from The Cancer Genome Atlas (TCGA). Then, we compared the two datasets in terms of clinical data, driver genes, mutational signature, gene sets, consensus molecular subtype, and fusion genes. RESULTS: These two cohorts showed similar profiles in driver mutations but differences in the mutation frequencies of some driver genes (including APC, TP53, PABPC1, FAT4, MUC7, HSPG2, GNAS, DENND5B, and BRAF). Analysis of hallmark pathways using genomic data sets revealed further differences between these populations in the WNT, TP53, and NOTCH signaling pathways. In consensus molecular subtype (CMS) analyses of the study cases, no BRAF mutations were found in the CMS1 subtype of KOCRC, which contrasts with previous findings. Fusion gene analysis identified oncogenic fusion of PTPRK-RSPO3 in a subset of KOCRC patients without APC mutations. CONCLUSIONS: This study presents insights into the genomic landscape of KOCRCs and reveals some similarities and differences with EUCRCs at the molecular level.

Involvement of tissue changes induced by neoadjuvant treatment in total mesorectal excision (TME): novel suggestions for determining TME quality.

BACKGROUND: Few studies to date have investigated morphological changes after neoadjuvant treatment (NAT) and their implications in total mesorectal excision (TME). This study was primarily designed to evaluate whether tissue changes associated with NAT affected the quality of TME and additionally to suggest a more objective method evaluating TME quality. METHODS: This study enrolled 1322 consecutive patients who underwent curative robot-assisted surgery for rectal cancer. Patients who did and did not receive NAT were subjected to propensity-score matching, yielding 402 patients in each group. RESULTS: NAT independently reduced complete achievement of TME [odds ratio (OR) = 2.056, p = 0.017]. Intraoperative evaluation identified seven tissue changes significantly associated with NAT, including tumor perforation, mucin pool, necrosis, fibrosis, fat degeneration, and rectal or perirectal edema NAT (p < 0.001-0.05). Tumor perforation (OR = 5.299, p = 0.001) and mucin pool (OR = 14.053, p = 0.002) were independently associated with inappropriate (near-complete + incomplete) TME. Complete TME resulted in significantly reduced local recurrence (4.3% vs 15.3%, p = 0.003) and increased 5-year DFS rate (80.6% vs 67.6%, p = 0.047) compared with inappropriate one. By contrast, two tiers of complete and near-complete TMEs vs incomplete TME did not. Notably, among patients with complete TME, those who received NAT had a lower 5-year DFS than those who did not (77.8% vs 83.3%, p = 0.048). CONCLUSIONS: NAT-associated tissue changes, somewhat interrupting complete TME, may provide unsolved clue to the relative inability of NAT to improve overall survival. The conventional three-tier grading of TME seems to be simplified into two tiers as complete and inappropriate.

Comparative survival risks in patients undergoing abdominoperineal resection and sphincter-saving operation for rectal cancer: a 10-year cohort analysis using propensity score matching.

PURPOSE: Abdominoperineal resection (APR) has been considered to have a higher risk of local recurrence and poorer survival outcome than sphincter-saving operation (SSO) in patients with rectal cancer. This study compared long-term oncologic outcomes and prognostic parameters in propensity score-matched patients who underwent APR and SSO. METHODS: This study analyzed 958 consecutive patients with lower rectal cancer who underwent preoperative chemoradiotherapy followed by APR or SSO between 2005 and 2015. Propensity score matching analysis was performed to adjust baseline characteristics, including clinical stage, tumor distance from the anal verge, and tumor size. RESULTS: In the entire cohort, the APR group had larger and lower tumors and showed significantly shorter 5-year disease-free survival (DFS) than the SSO group (64.5% vs. 75.8%, p = 0.01). After propensity score matching, there were no significant between-group differences in local (9.5% vs. 8.0%, p = 0.59) and systemic (27.9% vs. 23.4%, p = 0.3) recurrence rates, and 5-year DFS (67.5% vs. 69.9%, p = 0.49) and overall survival (80.8% vs. 82.9%, p = 0.65) rates. A lower number of lymph nodes retrieved was independently associated with recurrence and survival outcomes in the APR group, whereas poorly differentiated histology was an independent associated parameter in the SSO group. Advanced stage and perineural invasion were identified as independent prognostic parameters in both groups. CONCLUSIONS: This study indicated that the long-term oncologic outcomes of APR were comparable to those of SSO. Because prognostic parameters associated with oncologic outcomes differed between the respective procedures, correctable parameters could be ameliorated through complete total mesorectal excision and personalized systemic treatment.

Clostridium difficile infection after ileostomy closure and anastomotic failure in rectal cancer surgery patients.

BACKGROUND: Diverting ileostomy during resection of rectal cancer is frequently performed in patients at risk of anastomotic failure. Clostridium difficile infection (CDI) is reported to be frequent in patients who receive ileostomy closure with a questionable association to postoperative anastomosis leak. The primary aim of this study was to determine the incidence of CDI following ileostomy closure in patients who underwent rectal cancer surgery; the secondary aim was to assess the rate of postileostomy closure CDI in patients who presented with leakage at the original colorectal anastomosis site. METHODS: Medical records of patients with rectal cancer who underwent ileostomy closure between January 2015 and December 2019 were retrospectively reviewed. All patients had previously received resection and anastomosis for primary rectal cancer with diverting ileostomy. Data regarding CDI incidence, preoperative status, perioperative management, and clinical outcomes were collected. CDI positivity was determined by direct real-time PCR and enzyme-linked fluorescent assays for detecting toxin A and B.Statistical analyses were computed for CDI risk factors. RESULTS: A total of 1270 patients were included and 208 patients were tested for CDI owing to colitis-related symptoms. The incidence of CDI was 3.6 per cent (46 patients). Multivariable analysis for CDI risk factors identified adjuvant chemotherapy (hazard ratio (HR) 2.28; P = 0.034) and colorectal anastomosis leakage prior to CDI (HR 3.75; P = 0.008). Finally, patients with CDI showed higher colorectal anastomosis leakage risk in multivariable analysis after ileostomy closure (HR 6.922; P = 0.001). CONCLUSION: Patients with CDI presented with a significantly higher rate of colorectal anastomosis leakage prior to ileostomy closure.

Correlative Significance of Tumor Regression Grade and ypT Category in Patients Undergoing Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: In patients with locally advanced rectal cancer, the treatment response to preoperative chemoradiotherapy (PRCRT) varies, and the ypT stage may change as a result of tumor shrinkage. The purpose of this study was to evaluate the correlative significance and determine the prognostic value of tumor regression grade and ypT category staging systems. MATERIALS AND METHODS: This retrospective observational study was conducted in a tertiary center. A total of 1240 patients with rectal cancer who underwent curative resection after PRCRT between January 2007 and December 2016 were consecutively included. RESULTS: A significant association was found between the American Joint Committee on Cancer/College of American Pathology tumor regression grading system and ypT category, indicating a potential correlation between worse tumor regression grade and more advanced T stage (Cramer's V = 0.255, P < .001). The ypT stage and tumor regression grade were independent predictors of each other (P < .001). The good response group (tumor regression grades 0-1) had significantly higher 5-year disease-free survival (85.5% vs. 68.2%, P < .001) and overall survival (92.1% vs. 81.0%, P < .001) rates than the poor response group (tumor regression grades 2-3). However, the ypT and ypN categories were the most important independent prognostic factors for disease-free and overall survival. CONCLUSIONS: Tumor regression grade and ypT category were significantly correlated. Although tumor regression grade alone is not definitive, it is closely related to the ypT stage and impacts oncologic outcomes. These findings should be taken into consideration when stratifying the prognosis of patients undergoing PRCRT.