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Although off-midline incisions (unilateral low transverse or Pfannenstiel incision) have been reported to have a lower incidence of incisional hernia (IH) than periumbilical vertical incision for the purpose of specimen extraction, it is most commonly used in laparoscopic colon cancer surgery because off-midline incisions are associated with the limitation of colon exteriorization. This study aims to investigate the risk of IH after laparoscopic colectomy and compare midline vertical incision versus transverse incision focusing on the incidence of IH.Patients who underwent elective laparoscopic colectomy due to colon malignancy from June 2015 to May 2017 were included. All patients had either vertical (n = 429) or muscle splitting periumbilical transverse incisions (n = 125).Median duration of the follow-up period was 23.6 months, during which IHs occurred in 12.1% patients. The incidence of hernia was significantly lower in the transverse group (3 vs. 64, 2.4% vs. 14.9%, p 0.001). On multivariate analysis, BMI ≥ 23 [odds ratio (OR) 2.282, 95% confidence interval (CI) 1.245-4.182, p = 0.008], postoperative surgical site infection (OR 3.780, 95% CI 1.969-7.254, p 0.001) and vertical incision (OR 7.113, 95% CI 2.173-23.287, p 0.001) were independently related with increased incidence of IH.A muscle splitting periumbilical transverse incision could significantly reduce the rate of IH in minimally invasive colon cancer surgery.

Introduction: Proper handling and firing of the circular stapler are important for secure anastomosis in rectal cancer surgery. This study aimed to investigate the association between the first assistant and anastomotic leakage (AL) after rectal cancer surgery with double-stapling anastomosis. Methods: Patients with primary rectal cancer who underwent low anterior resection with double-stapling anastomosis between January 2015 and September 2019 were included. Data on clinicopathological characteristics, including the first assistant’s sex and experience level, were retrospectively reviewed, and the risk factors for AL were analyzed using propensity score matching analysis. Results: Among 758 rectal cancer surgeries, residents participated in 401 (52.9%) surgeries, and fellows participated in 357 (47.1%) surgeries as first assistants. After propensity score matching (n = 650), AL occurred in 5.4% (35/650). The first assistant’s experience level (resident: 5.5% vs. fellow: 5.2%, p = 0.862) and sex (male: 5.4% vs. female: 4.9%, p = 0.849) were not associated with the occurrence of AL. Male sex in patients was the only significant predictive factor for AL (odds ratio = 2.804, 95% confidence interval 1.070–7.351, p = 0.036). Discussion/Conclusion: The first assistant’s sex and experience level were not associated with AL after rectal cancer surgery with double-stapling anastomosis. These findings may justify resident participation in rectal cancer surgeries in which circular staplers are used.

There is a paucity of evidence on the value of intraperitoneal chemotherapy (IPC) following cytoreductive surgery (CRS) for colorectal peritoneal metastasis. This study aimed to evaluate the association between mitomycin C-IPC and survival outcomes following CRS.The institutional databases of two tertiary hospitals were reviewed to identify patients who underwent CRS for colorectal peritoneal metastasis. The outcomes of patients who underwent CRS without IPC were compared with those of patients who underwent CRS plus early postoperative intraperitoneal chemotherapy (EPIC) or CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC). The primary endpoints were cancer-specific survival (CSS), progression-free survival (PFS), and peritoneal PFS (P-PFS).In 149 patients with peritoneal metastasis alone, EPIC and HIPEC use was significantly associated with better CSS, PFS, and P-PFS in the multivariate analysis. CSS was also significantly associated with perioperative systemic chemotherapy. Among 42 patients with both peritoneal and extraperitoneal metastases, CSS was independently related to the completeness of cytoreduction score, location of extraperitoneal metastasis, and grade 3-4 complications.Mitomycin C-IPC after CRS was associated with better survival outcomes than CRS alone in patients with resectable peritoneal metastasis of colorectal cancer. This study found that IPC had beneficial effects regarding P-PFS in patients with both peritoneal and extraperitoneal metastases.

The relationship between microsatellite instability (MSI) and tumor response after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer remains unclear. The present study aimed to evaluate the association between MSI and tumor response to nCRT in rectal cancer treatment.Patients with rectal cancer from 2 tertiary hospitals who underwent nCRT, followed by radical surgery, were included. The microsatellite status was determined using a PCR-based Bethesda panel. Tumors with a Dworak's tumor regression grade of 3 or 4 were considered to have a good response. Predictive factors for a good response to nCRT were analyzed.Of the 1,401 patients included, 910 (65.0%) had MSI results and 1.5% (14 of 910) showed MSI-H. Among all the patients, 519 (37.0%) showed a good response to nCRT. A univariate analysis showed that MSI-H tended to be negatively associated with a good response to nCRT, but no statistical significance was observed (7.1%MSI-H was not associated with response to nCRT in patients with rectal cancer.

Purpose: This study aimed to evaluate the relationship between high-output stomas (HOSs), postoperative ileus (POI), and readmission after rectal cancer surgery with diverting ileostomy.Methods: We included 302 patients with rectal cancer who underwent restorative resection with diverting ileostomy between January 2011 and December 2015. HOSs were defined as stomas with ≥ 2,000 mL/day output. We analyzed predictive factors for readmission of these patients.Results: Forty-eight patients (15.9%) had HOSs during the hospital stay, and 41 patients (13.6%) experienced POI. HOSs were strongly associated with POI (45.8% vs. 7.5%, P < 0.001). The all-cause readmission rate was 16.9%, with 19 (6.3%) and 20 (6.6%) experiencing ileus and acute kidney injury, respectively. HOSs (27.1% vs. 15.0%, P = 0.040) and POI (34.1% vs. 14.2%, P = 0.002) were associated with all-cause readmission, and POI was associated with readmission with ileus (17.1% vs. 4.6%, P = 0.007). POI was an independent risk factor for all-cause readmission (adjusted odds ratio [OR], 2.640; 95% confidence interval [CI], 1.162 to 6.001; P = 0.020) and readmission with ileus (adjusted OR = 3.869; 95% CI 1.387 to 10.792; P = 0.010).Conclusion: POI was associated with readmission, particularly for subsequent ileus, in patients with diverting ileostomy. We should make efforts to reduce POI, such as strong control of HOSs, to prevent readmission.

Pre-operative evaluation identifying clinical-stage affects the decision regarding the extent of surgical resection in right colon cancer. This study was designed to predict a proper surgical resection through the prognosis of clinical Stage I right colon cancer.We included patients who were diagnosed with clinical and pathological Stage I right-sided colon cancer, including appendiceal, caecal, ascending, hepatic flexure and proximal transverse colon cancer, between August 2010 and December 2016 in two tertiary teaching hospitals. Patients who underwent open surgeries were excluded because laparoscopic surgery is the initial approach for colorectal cancer in our institutions.Eighty patients with clinical Stage I and 104 patients with pathological Stage I were included in the study. The biopsy reports showed that the tumour size was larger in the clinical Stage I group than in the pathological Stage I group (3.4 vs. 2.3 cm, P0.001). Further, the clinical Stage I group had some pathological Stage III cases (positive lymph nodes, P = 0.023). The clinical Stage I group had a higher rate of distant metastases (P = 0.046) and a lower rate of overall (P = 0.031) and cancer-specific survival (P = 0.021) than the pathological Stage I group. Compared to pathological Stage II included in the period, some of the survival curves were located below the pathological Stage II, but there was no statistical difference.The study results show that even clinical Stage I cases, radical resection should be considered in accordance with T3 and T4 tumours.

Background Current guidelines recommend the prescription of immune-enriched oral nutritional supplements for malnourished patients before major gastrointestinal surgery. However, the benefit of preoperative immunonutrition is still controversial. This randomized controlled trial aims to evaluate the effect of preoperative immunonutrition on the outcomes of surgery for colon cancer. Methods/design Patients with primary colon cancer will be included as study participants after screening. They will be randomly assigned (in a ratio of 1:1) to receive preoperative immunonutrition added to the normal diet (experimental arm) or consume normal diet alone (control arm). Patients in the experimental arm will receive oral supplementation (400 mL/day) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint is the rate of infectious complications, while the secondary endpoints are postoperative complication rate, change in body weight, length of hospital stay, and nature of fecal microbiome. The authors hypothesize that the rate of infectious complications would be 13% in the experimental arm and 30% in the control arm. With a two-sided alpha of 0.05 and a power of 0.8, the sample size is calculated as 176 patients (88 per arm). Discussion Although there have been many studies demonstrating significant benefits of preoperative immunonutrition, these were limited by a small sample size and potential publication bias. Despite the recommendation of immunonutrition before surgery in nutritional guidelines, its role in reduction of rate of infectious complications is still controversial. This trial is expected to provide evidence for the benefits of administration of preoperative immunonutrition in patients with colon cancer. Trial registration Clinical Research Information Service KCT0003770. Registered on 15 April 2019.

Fibroblast growth factor receptor 4 (FGFR4) is known to induce cancer cell proliferation, invasion, and antiapoptosis through activation of RAS/RAF/ERK and PI3K/AKT pathways, which are also known as major molecular bases of colon cancer carcinogenesis related with epidermal growth factor receptor (EGFR) signaling. However, the interaction between FGFR4 and EGFR signaling in regard to colon cancer progression is unclear. Here, we investigated a potential cross‐talk between FGFR4 and EGFR, and the effect of anti‐EGFR therapy in colon cancer treatment. To explore the biological roles of FGFR4 in cancer progression, RNA sequencing was carried out using FGFR4 transfected colon cell lines. Gene ontology data showed the upregulation of genes related to EGFR signaling, and we identified that FGFR4 overexpression secretes EGFR ligands such as amphiregulin (AREG) with consequent activation of EGFR and ErbB3. This result was also shown in in vivo study and the cooperative interaction between EGFR and FGFR4 promoted tumor growth. In addition, FGFR4 overexpression reduced cetuximab‐induced cytotoxicity and the combination of FGFR4 inhibitor (BLU9931) and cetuximab showed profound antitumor effect compared to cetuximab alone. Clinically, we found the positive correlation between FGFR4 and AREG expression in tumor tissue, but not in normal tissue, from colon cancer patients and these expressions were significantly correlated with poor overall survival in patients treated with cetuximab. Therefore, our results provide the novel mechanism of FGFR4 in connection with EGFR activation and the combination of FGFR4 inhibitor and cetuximab could be a promising therapeutic option to achieve the optimal response to anti‐EGFR therapy in colon cancer., Our study has characterized the cross‐talk between fibroblast growth factor receptor 4 (FGFR4) and epidermal growth factor receptor (EGFR)/ErbB3 signaling by the contribution of EGFR ligands secreted from FGFR4. These findings provide experimental evidence for combined treatment with FGFR4 inhibitor and anti‐EGFR therapy in colon cancer.

Aortoiliac calcification may be a surrogate marker of decreased visceral perfusion causing anastomotic leak (AL). The aim of this study was to evaluate the predictive role of aortoiliac calcification for AL after rectal cancer surgery. We enrolled patients with primary rectal cancer who had restorative resection at our institution between January 2013 and December 2015. An aortoiliac calcification score was calculated as the sum of calcification scores at the infrarenal aorta (0: no, 1: ≤ 3 cm, 2: > 3 cm) and the common iliac arteries (0: no, 1: unilateral, 2: bilateral). AL was classified into three grades: grade A, requiring no intervention; grade B, requiring therapeutic intervention without re-laparotomy; and grade C, requiring re-laparotomy. Clinicopathological characteristics were analyzed to identify risk factors for AL. There were 583 patients. Three-hundred forty-five (59.2%) had an aortoiliac calcification score ≥ 3, and 37 (6.3%) patients experienced AL, in 30 cases (5.1%) grade C AL. Patients with an aortoiliac calcification score ≥ 3 had a higher incidence of grade C AL (6.7% vs. 2.9%, p = 0.045). Multivariate logistic regression analysis revealed that an aortoiliac calcification score ≥ 3 was an independent risk factor for grade C AL (odds ratio = 2.669, 95% confidence interval 1.066–6.686, p = 0.036). Aortoiliac calcification may be considered a risk factor for grade C AL after rectal cancer surgery.

Objective This study aimed to assess the impact of preoperative immunonutrition on the outcomes of colon cancer surgery. Background Although current guidelines recommend that immunonutrition should be prescribed for malnourished patients before major gastrointestinal surgery, the benefit of preoperative immunonutrition remains debatable. Methods Between April 2019 and October 2020, 176 patients with primary colon cancer were enrolled and randomly assigned (1:1) to receive preoperative immunonutrition plus a normal diet (n = 88) or a normal diet alone (n = 88). Patients in the immunonutrition group received oral nutritional supplementation (400 mL/day) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint was the rate of infectious complications, and the secondary endpoints were the postoperative complication rate, change in body weight, and length of hospital stay. Results The rates of infectious (17.7% vs. 15.9%, P = 0.751) and total (31.6% vs. 29.3%, P = 0.743) complications were not different between the two groups. Old age was the only significant predictive factor for the occurrence of infectious complications (odds ratio = 2.990, 95% confidence interval 1.179-7.586, P = 0.021). The length of hospital stay (7.6 ± 2.5 vs. 7.4 ± 2.3 days, P = 0.635) and overall change in body weight (P = 0.379) were similar between the two groups. However, only the immunonutrition group showed weight recovery after discharge (+0.4 ± 2.1 vs. -0.7 ± 2.3 kg, P = 0.002). Conclusions Preoperative immunonutrition was not associated with infectious complications in patients undergoing colon cancer surgery. Routine administration of immunonutrition prior to colon cancer surgery cannot be justified.

Summary: Background: Among rectal cancer patients, some of good responders after neoadjuvant chemoradiotherapy (nCRT) are considered for non-operative treatments to avoid postoperative morbidities and permanent stoma. However, oncologic feasibility of non-operative treatment has not been fully understood. Methods: From 2008 to 2017, we retrospectively reviewed patient's records who had lower or mid rectal cancer and diagnosed to clinical complete response by magnetic resonance imaging after nCRT. Clinical differences and oncologic outcomes were compared among Radical surgery (RS), Local excision (LE) and Wait-and-see (WS) group. Results: Number of 129, 25, 15 patients included to RS, LE, WS groups. Local recurrence was frequent type of recurrence in both of LE and WS group (RS; 31.3%, LE; 80%, WS; 66.7%), and many patients in WS group omitted salvage treatment (RS; 75%, LE; 100%, WS; 33.3%). 5-years local-recurrence/disease-free survival rate (LRFS, DFS) between RS and LE were similar between each group, but WS showed significantly inferior outcomes than that of RS (LRFS; p = 0.001, DFS; p = 0.001). In multivariate analysis, WS protocol (OR; 7.163, 95% CI; 1.995–25.715) and cT4 stage (OR; 8.206, 95% CI; 1.596–42.198) were independent factors for LRFS. Conclusions: Wait-and-see group showed high rate of rejection of salvage treatments for recurrence, and poor oncologic outcomes. However, recent low-level evidences reported favorable outcome of WS protocol when salvage treatment was followed after recurrence. It seems that the application of WS protocol should be postponed until the results of randomized-controlled trials are available. Local excision seems to be good alternative option to radical surgery when salvage treatment is followed. Keywords: Rectal cancer, Complete response, Local excision, Wait-and-see

Purpose: The aim of this study was to assess oncological outcomes of postoperative radiotherapy plus chemotherapy (CRT) versus chemotherapy alone (CTx) in stage II or III upper rectal cancer patients who underwent curative surgery.Methods: We retrospectively reviewed 263 consecutive patients with pathologic stage II or III upper rectal cancer who underwent primary curative resection with postoperative CRT or CTx from January 2008 to December 2014 at Chonnam National University Hwasun Hospital. Multivariate and propensity score matching analyses were used to reduce selection bias.Results: Median follow-up was 48.1 months for the entire cohort and 53.5 months for the matched cohort. In subgroup analysis of the propensity score matched cohort, the 3-year local recurrence-free survival was 94.1% (95% confidence interval [CI], 87.8%–100%) in the CRT group and 90.1% (95% CI, 82.8%–97.9%) in the CTx group (P = 0.370). No significant difference in disease-free survival was observed according to treatment type. On multivariate analysis, circumferential resection margin involvement (hazard ratio [HR], 2.386; 95% CI, 1.190–7.599; P = 0.032), N stage (HR, 6.262; 95% CI, 1.843–21.278, P = 0.003), and T stage (HR, 5.896, 95% CI, 1.298–6.780, P = 0.021) were identified as independent risk factors for local recurrence of tumors of the upper rectum.Conclusion: Omission of radiotherapy in an adjuvant treatment setting may not jeopardize oncologic outcomes in stages II and III upper rectal cancer.

The colon originates from the midgut and hindgut, with subsequent differentiation into the right and left colon. The embryology, clinical symptoms, incidence, molecular pathways, and oncologic outcomes differ between right and left colorectal cancers. However, the differences have not been fully accepted.This study compared short- and long-term outcomes between right and left colon cancers.This study included 966 patients who underwent laparoscopic resection with radical lymph node dissection for stage I, II, and III colon cancers between 2009 and 2014 at a tertiary teaching hospital. We excluded cases with fewer than 12 retrieved lymph nodes, emergency operations, synchronous or multiple cancers, and those located in the transverse colon and rectum.ResultsAlthough the oncologic outcomes show no significant differences, colon cancer has characteristic, perioperative, and histopathologic differences according to its embryologic origin.

Purpose Treatment after failure of circumferential resection margin (CRM) conversion after preoperative chemoradiotherapy (pCRT) for locally advanced rectal cancer (LARC) has not been evaluated well. We conducted a single‐center, retrospective analysis to fill this information gap. Methods From 2008 to 2016, we included 112 patients who had predictive CRM involvement on baseline magnetic resonance imaging (MRI) and who underwent surgery following pCRT for LARC. Baseline and posttreatment radiologic and clinical factors were analyzed. Results Of 493 patients with LARC, 112 had CRM involvement by baseline MRI (mrCRM). In 40 patients (35.7%), mrCRM involvement was converted as negative posttreatment CRM (ymrCRM−). Multivariate analysis showed the risk factors for persistent CRM involvement (ymrCRM+) after pCRT were extramural venous invasion (mrEMVI+) (P = 0.030) and lower tumor location (P = 0.007). In addition, persistent CRM involvement after pCRT was an independent risk factor for predicting pathologic CRM involvement. The Cox proportional hazard model showed baseline positive mrEMVI remained significant for disease-free survival (DFS) (P < 0.001). On posttreatment MRI, abdominoperineal resection (P = 0.031), intersphincteric resection (P = 0.006), and persistent CRM involvement (P = 0.001) remained significant for local recurrence-free survival. With regard to DFS, persistent CRM involvement (P = 0.048) and positive EMVI on posttreatment MRI (ymrEMVI) (P = 0.014) were significant. In the patient subgroup with persistent CRM involvement, 5-year DFS in patients with mrEMVI and ymrEMVI was 29.8% and 21.2%, respectively. Conclusion Patients who fail to convert to negative CRM have extremely poor oncologic outcomes. Lower tumor height and negative mrEMVI status were good responders to ymrCRM conversion. Our results suggest that these patients require a more intensive treatment modality.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.

Aim The optimal surgical method for cancer of the mid-transverse colon has not been well established. The present study aimed to explore the distribution of lymph node metastasis and compare the outcomes of extended and transverse colectomies for cancer of the mid-transverse colon. Methods We retrospectively analysed the data of patients with cancer of the mid-transverse colon treated with either an extended hemicolectomy (right or left) or a transverse colectomy. A propensity score matching analysis was performed to rule out selection bias, and short-term and survival outcomes were compared. The distribution of lymph node metastasis was also investigated. Results A total of 107 patients were included, 70 of whom underwent an extended colectomy while 37 underwent a transverse colectomy. There were no significant differences in the operation time, postoperative complications, hospital stay, 3-year disease-free survival (86.5% vs. 90.9%, P = 0.675) and 5-year overall survival (87.4% vs. 93.0%, P = 0.349) between the two groups after propensity score matching. However, metastases were observed in the lymph nodes along the right colic artery (pericolic [#211], 14.0%; intermediate [#212], 8.2%; apical [#213], 9.8%) in the extended colectomy group. Conclusion Extended and transverse colectomies showed similar short-term and long-term outcomes for mid-transverse colon cancer. However, care should be taken to determine the extent of resection considering the possibility of metastatic lymph nodes along the right colic artery.

The prognosis of pathological T2N0 colon cancer has not been adequately investigated. This study aimed to determine the prognostic factors for pathological T2N0 colon cancer by comparing it with those for pathological T3N0 colon cancer. We retrospectively reviewed patients with primary colon cancer who underwent curative resection between January 2007 and December 2015 and included 889 patients with postoperative pathological T2-3N0M0 disease. The clinicopathological characteristics were analyzed to identify the independent prognostic factors. Pathological T2 (n = 185, 20.8%) and T3 (n = 704, 79.2%) tumors showed no difference in the 5-year disease-free survival (5Y DFS) rate (95.8% vs. 93.2%, p = 0.257) after a median follow-up of 55 months (range, 1–106 months). Multivariate Cox regression analysis showed that perineural invasion (hazard ratio [HR] = 2.041, 95% confidence interval [CI] 1.122–3.712, p = 0.019) and number of retrieved lymph nodes < 12 (HR = 2.994, 95% CI 1.327–6.753, p = 0.008) were independent prognostic factors for DFS. Pathological T2 tumors with poor prognostic factors showed similar 5Y DFS as that of T3 tumors with poor prognostic factors (88.9% vs. 88.6%, p = 0.916), but not with T3 tumors without poor prognostic factors (88.9% vs. 95.0%, p = 0.089). Pathological T2N0 colon cancer showed oncologic outcomes similar to that of T3N0 colon cancer. Therefore, more intensive surveillance is necessary for patients with high-risk T2N0 colon cancer.

Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03–1.13; OR: 3.33, 95% CI, 2.46–4.50; and OR: 1.15, 95% CI, 1.02–1.29, respectively). Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.

BACKGROUND AND AIMS: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (TCGA, n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10(−6), including genes in four novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In nine known GWAS-identified loci, we uncovered nine genes that have not been previously reported, whereas four genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < 0.01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSION: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

Background Very few studies have been conducted on the treatment strategy for enlarged paraaortic lymph nodes (PALNs) incidentally detected during surgery. The purpose of this study was to investigate the benefit of lymph node dissection in patients with incidentally detected enlarged PALNs. Methods We retrospectively reviewed patients with left colon and rectal cancer who underwent surgical resection with PALN dissection between January 2010 and December 2018. The predictive factors for pathologic PALN metastasis (PALNM) were analyzed, and survival analyses were conducted to identify prognostic factors. Results Among 263 patients included, 19 (7.2%) showed pathologic PALNM and 5 (26.33%) had enlarged PALNs incidentally detected during surgery. These 5 patients accounted for 2.2% of 227 patients who had no evidence of PALNM on preoperative radiologic examination. Radiologic PALNM (odds ratio [OR] 12.737, 95% confidence interval [CI] 3.472–46.723) and radiologic distant metastasis other than PALNM (OR = 4.090, 95% CI 1.011–16.539) were independent predictive factors for pathologic PALNM. Pathologic T4 stage (hazard ratio [HR] 2.196, 95% CI 1.063–4.538) and R2 resection (HR 4.643, 95% CI 2.046–10.534) were independent prognostic factors for overall survival (OS). In patients undergoing R0 resection, pathologic PALNM was not associated with 5-year OS (90% vs. 82.2%, p = 0.896). Conclusion Dissection of enlarged PALNs incidentally detected during colorectal surgery may benefit patients with favorable survival outcomes.

Some studies have suggested that circumferential tumor location (CTL) of rectal cancer may affect oncological outcomes. However, studies after preoperative chemoradiotherapy (CRT) are rare. This study aimed to evaluate the impact of CTL on oncologic outcomes of patients with mid to low rectal cancer who received preoperative CRT.Patients with mid to low rectal cancer who underwent total mesorectal excision after CRT from January 2013 to December 2018 were included in this retrospective study. The impact of CTL on the pathological circumferential resection margin (CRM) status, local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) was analyzed.Of the 381 patients, 98, 70, 127, and 86 patients were categorized into the anterior, posterior, lateral, and circumferential tumor groups, respectively. Tumor location was not significantly associated with the pathological CRM involvement (anterior, 12.2%CTL of rectal cancer after preoperative CRT was not significantly associated with the pathological CRM status, recurrence, and survival.

We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, n = 26, upfront chemotherapy, n = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%, p = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, p = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant.

Purpose A variety of clinical features of anastomotic leak occur during the surgical treatment of rectal cancer. However, little information regarding management of leakage is available and treatment guidelines have not been validated. The aim of this study was to evaluate the validity of currently proposed expert opinions on the management of anastomotic leak, after low anterior resection for rectal cancer. Methods A retrospective analysis was conducted for 1,786 patients who underwent sphincter-preserving surgery for rectal cancer between 2005 and 2015. Clinical outcomes including anastomotic leak-associated mortality and permanent stoma were analyzed. Results The overall incidence of anastomotic leak was 6.8% (122 of 1,786), including 6.1% (30 of 493 patients) with diverting stoma and 7.1% (92 of 1,293 patients) without diverting stoma (P = 0.505). A majority of patients without diversion were treated with diverting stoma (76 of 88 patients [86.4%]); 1 mortality (0.8%) was observed in this group. Treatments in the diversion group mainly included conservative treatment, local drainage, and/or transanal repair (26 of 30 patients [86.7%]). The anastomotic failure rates were 20.7% (19 of 92 patients) in the no diversion group and 53.3% (16 of 30 patients) in the diversion group. In the multivariate analysis, preoperative chemoradiotherapy (P < 0.001) and delayed diagnosis of anastomotic leak (P = 0.036) were independent risk factors for permanent stoma. Conclusion Management of anastomotic leak should be tailored to individual patients. When anastomotic leak occurred, preoperative chemoradiotherapy and delayed diagnosis seemed to be associated with permanent stoma.

Primary tumor resection (PTR) for unresectable metastatic colorectal cancer (mCRC) patients has been documented to be associated with postoperative hyper-neovascularization and enhanced growth of metastases, which may be prevented by bevacizumab. This study aimed to investigate the survival outcome of PTR in patients who received palliative bevacizumab-containing chemotherapy (BCT). From January 2006 to December 2018, medical records of 240 mCRC patients who received palliative BCT at a single tertiary colorectal cancer center were retrospectively reviewed. Patients were classified into three groups: PTR-a (PTR before BCT, n = 60), PTR-b (PTR during BCT, n = 17), and BCT-only group (n = 163). Resectable mCRCs or recurrent diseases were excluded, and the end-point was overall survival (OS) rate. Three groups had similar age, cell differentiation, location of the primary tumor, and the number of metastatic organs. More than two-thirds of patients who received PTR experienced disease-progressions (PD) during their postoperative chemotherapy-free time (PTR-a vs PTR-b; 66.7% vs 76.5%, P = .170), but OS was not inferior to the BCT-only group (PTR-a vs BCT-only; HR 0.477 [95% CI 0.302–0.754], P = .002/PTR-b vs BCT-only; HR 0.77 [95% CI 0.406–1.462], P = .425). The postoperative chemotherapy-free time was similar between PTR-a and PTR-b (median 32.0 [14–98] days vs 41.0 [18–71] days, P = .142), but non-obstructive indications (perforation, bleeding, pain) were the more frequent in the PTR-b than PTR-a. Young age, the number of BCT, and PTR-a were the independent factors for OS. The efficacy of the PTR for unresectable mCRC has been controversial, but this study demonstrated that PTR should be considered for the unresectable mCRC patients regardless before and during BCT.

Perineural invasion (PNI) has emerged as an important factor related to colorectal cancer spread; however, the impact of neoadjuvant chemoradiotherapy (nCRT) on PNI remains unclear. Herein, we investigated the prognostic value of PNI, along with lymphovascular invasion (LVI), in rectal cancer patients treated with nCRT. This single-center observational study of pathologic variables, including PNI and LVI, analyzed 1411 invasive rectal cancer patients (965 and 446 patients treated with primary resection and nCRT, respectively). The overall detection rates of LVI and PNI were 16.7 and 28.8%, respectively. The incidence of LVI was significantly lower in patients treated with nCRT (8.1 vs. 20.6%, P

This study aimed to evaluate the association between nutritional risk screening (NRS) score and administration of adjuvant chemotherapy for stage III colon cancer.A total of 404 patients with stage III colon cancer who underwent curative resection between January 2012 and December 2015 were included. Patients with a preoperative high nutritional risk score (NRS ≥4) were compared with those with an NRS4. Predictive factors for omission of adjuvant chemotherapy, and prognostic factors for overall survival (OS) were analyzed.Eighty (19.8%) patients had a high nutritional risk (NRS ≥4). An NRS score ≥4 was associated with higher risk of omission of adjuvant chemotherapy (26.3% vs. 13.6%, p = 0.006), which was significant after adjusting for covariables (odds ratio = 1.862, p = 0.047). Multivariable survival analysis showed that omission of adjuvant chemotherapy was an independent poor prognostic factor for OS (hazard ratio = 4.060, p 0.001).An NRS score ≥4 was associated with omission of adjuvant chemotherapy in stage III colon cancer, which resulted in poor OS.

Purpose The clinical importance of tissue CEA levels for predicting tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer has not been studied. Methods Serum CEA levels and tissue CEA expressions for 117 patients who underwent preoperative CRT for rectal cancer, were prospectively collected and analyzed at a tertiary university hospital Results The median follow-up time was 49 months (range, 3–61 months), and the 5-year disease-free survival (DFS) rate was 68.3 %. In multivariate analysis, serum CEA (log-transformed value) [odds ratio (OR) = 0.741, 95 % confidence interval (CI) 1.588–40.422, P = 0.021], tissue CEA/GAPDH ratio (OR = 3.673, 95 % CI 1.316–12.081, P = 0.019), and tumor circumferentiality (OR = 2.960, 955 CI, 1.101–8.999, P = 0.040) were the independent predictors for good tumor response to CRT. Serum CEA level was significant prognostic factor for DFS (P = 0.004) in multivariate analysis. However, tissue CEA was not associated with DFS. Conclusions Both serum and tissue CEA were significant factors for predicting good tumor response following preoperative CRT. However, tissue CEA was not associated with the oncologic outcome. The possibility of radiologic resistance of high CEA tumors is expected to be investigated through further studies.

Nutritional risk screening (NRS) score has been reported as a predictor of postoperative outcomes in patients undergoing abdominal surgery, although the correlation between NRS and anastomotic leakage (AL) after rectal cancer surgery is uncertain. This study aimed to evaluate the association between NRS score and AL following rectal cancer surgery. We retrospectively reviewed data of rectal cancer patients from a tertiary referral center in South Korea, and included 1063 patients with primary rectal cancer who underwent sphincter-preserving surgery between January 2011 and December 2015. We utilized the Chonnam National University Hwasun Hospital-Nutritional Risk Screening Tool (CNUHH-NRST), which was developed and cross-validated on the basis of the NRS 2002 and MST, as a screening tool of nutritional risk. Patients with NRS scores ≥4 were compared with those with NRS scores

Introduction Bile peritonitis is one of the rare complications that can occur after cholecystectomy or hepatectomy. It is associated with high mortality, prolonged hospital stay, and increased cost. We herein report 2 cases of bile leakage as a postoperative complication of right hemicolectomy. Patient concerns Two patients underwent a right hemicolectomy for colon cancer. Both patients had a history of cholecystectomy, and intrahepatic bile duct dilatation was observed in preoperative imaging study. During surgery, adhesiolysis was performed between the liver and the hepatic flexure of the colon due to adhesion in that area. Diagnosis Postoperatively, bile fluid was drained via an intraabdominal drainage tube. Both cases required surgical intervention to explore the origin of the leakage. In both cases, the anastomosis was intact, and the injury of the intrahepatic bile duct just beneath the liver surface was the origin of bile leakage. Interventions Suture ligation, irrigation, and drainage were performed in both patients. Outcomes There was no more bile leakage after reoperation, and both patients were discharged in good health after antibiotics treatment. Conclusion Although very rare, bile leakage due to intrahepatic duct injury can occur after right hemicolectomy in patients with a history of cholecystectomy and intrahepatic duct dilatation. It is necessary to consider the possibility of bile duct injury and anastomotic leakage if bile leakage is suspected after right hemicolectomy.

Background This study aimed to evaluate the prognostic significance of lymph node distribution (LND) in rectal cancer after neoadjuvant chemoradiation. Methods A total of 519 patients with primary rectal cancer who underwent curative resection after neoadjuvant chemoradiation were included. LND was classified into four groups: LND0, no lymph node metastasis (368/519, 70.9%); LNDp, lymph node metastasis along the inferior mesenteric artery (proximal) (15/519, 2.9%); LNDm, lymph node metastasis at the mesorectum (109/519, 21.0%); and LNDpm, lymph node metastasis at both the proximal and mesorectal areas (27/519, 5.2%). Clinicopathologic characteristics were analyzed to identify independent prognostic factors. Results In patients with positive lymph nodes, LND showed superior discrimination for 3-year DFS (LNDp 67.7%, LNDm 48.9%, and LNDpm 26.8%, P = 0.003) and 3-year LRFS (LNDp 93.3%, LNDm 81.4%, and LNDpm 60.5%, P = 0.009) compared to ypN stage (3-year DFS, N1 47.8%, N2 40.0%, P = 0.184; 3-year LRFS, N1 79.4%, N2 75.2%, P = 0.527). On multivariate survival analysis, LND was an independent prognostic factor for LRFS (P = 0.030) in patients with positive lymph nodes. Conclusions LND may improve the prognostic value of the ypTNM staging system for patients with node-positive rectal cancer after neoadjuvant chemoradiation, particularly in terms of local recurrence.

Background and Aims The CpG island methylator phenotype (CIMP) is found in approximately 30% of colorectal cancer (CRC) cases. However, the role of CIMP status in predicting oncologic outcomes in curatively resected CRC is still unclear. Study Between January 2006 and December 2006, we retrospectively reviewed 157 consecutive patients who underwent curative surgery for CRC. Prognostic significance of CIMP status was evaluated using reverse transcriptase-polymerase chain reaction. Results CIMP-high (H) and CIMP-none/low (N/L) tumors were found in 50 cases (31.8%) and 107 cases (68.2%), respectively. CIMP-H tumors were significantly associated with female sex, colonic location, poorly/mucinous histologic type, higher T category, perineural invasion, and MSI-high status (P = 0.001). During a median of 64.5 months, tumor recurrence developed in 47 (29.9%) patients. The 5-year disease-free survival for CIMP-H and CIMP-N/L was 61.4% and 76.3% (P = 0.018). In addition, multivariate analysis showed that CIMP-H was also a significant prognostic factor (P = 0.042). When analysis was performed according to anatomical location, more marked survival differences were observed in patients with colon cancer (P = 0.026) than in patients with rectal cancer (P = 0.210). Similarly, the role of CIMP status as a prognostic indicator was more prominent in patients with stage I/II (P = 0.006) than in patients with stage III/IV CRC (P = 0.65). Conclusions DNA methylation status can be considered as a useful predictor of survival after CRC surgery, particularly for patients with stage I/II disease or colon cancer.

Laparoscopic rectal cancer surgery with proper total mesorectal excision is a challenge for colorectal surgeons during trouble shooting. We used a beaded plastic urinary drainage bag hanger to encircle the rectum and clamp laparoscopic rectal transaction in this study. Sixty-three patients with rectal cancer underwent laparoscopic radical rectal resection with curative intent between February 2015 and December 2015. Plastic beaded form urinary Foley catheter bag hanger was inserted intracorporeally via right lower 12-mm trocar, encircling the rectal tube distal to the rectal lesion followed by fastening. Thirty patients in the rectal resection group (28 laparoscopic, 2 robotic-assisted) using the commercial beaded plastic hanger for Foley catheter drainage were compared to 33 patients who underwent conventional laparoscopic rectal resection. Low anterior resection was performed for both groups. The Foley bag hanger group had less operation time (162.6 min vs. 187.3 min, p = 0.006) and fewer numbers of stapler cartilage (1.6 vs. 2.1, p = 0.001). Intracorporeal ligation of the rectum with a beaded plastic Foley catheter bag hanger could be used as a valuable method for rectal handling and transaction in laparoscopic rectal cancer surgery.

PURPOSE The aim of this study was to compare the outcomes between patients under 60 years of age and older patients over 80 years of age who underwent laparoscopic colorectal surgery with colorectal cancer. METHODS A retrospective analysis of 519 colorectal patients who underwent laparoscopic colorectal surgery for colorectal adenocarcinoma between January 2007 and December 2012 was collected and categorized into 2 groups of patients, those under 60 years of age (n = 404) and those over 80 years of age (n = 115). RESULTS The group of patients over 80 years of age had a significantly higher ASA physical status classification (P < 0.001), more preoperative comorbidities (P < 0.001), had a tendency towards more tumors in a colonic location (P = 0.034), and more advanced American Joint Committee on Cancer TNM stage (P = 0.001). A higher proportion of right hemicolectomy and abdominoperineal resection was performed and more transfusions were required in the group of patients over 80 years of age (P = 0.002 and P = 0.001, respectively). There were no significant differences in operative time, conversion rate, resection margins, and numbers of harvested lymph nodes, hospital stay, and morbidity between the 2 groups. No postoperative mortality was found in the present study. The 3-year DFS for over 80 years age group and under 60 years age group were 73.5% and 73.9%, respectively (P = 0.770). CONCLUSION Laparoscopic colorectal surgery was effective and safe for elderly patients over 80 years of age and resulted in postoperative outcomes similar to those in younger patients. The postoperative morbidity after laparoscopic colorectal cancer surgery was not increased in over 80 years of age.

Purpose Radical lymph node dissection for right-sided colon cancer is technically challenging. No clear guideline is available for surgical resection of clinical stage I right-sided colon cancer. This study was designed to review the pathologic stage of clinical stage I right-sided colon cancer and determine the relevant extent of surgical resection. Methods Patients were treated for clinical stage I right-sided colon cancers (cecal, ascending, hepatic flexure, and proximal transverse colon) between July 2006 and December 2014 at a tertiary teaching hospital. Open surgery was not included because laparoscopic surgery is an initial major procedure in the institution. Results During the study period, 80 patients diagnosed with clinical stage I right-sided colon cancer were classified into 2 groups according to the pathology: stage 0/I and II/III. Tumor sizes were larger in the stage II/III group (P = 0.003). The stage II/III group had higher rates of vascular (P = 0.023) and lymphatic invasion (P = 0.023) and lower rates of well differentiation (P = 0.022). During follow-up, 1 case of local and 4 cases of systemic recurrences were found. Multivariate analysis to confirm odds ratios affecting change from clinical stage I to pathological stage II/III showed that tumor size (P = 0.010) and the number of retrieved lymph nodes (P = 0.046) were risk factors. Conclusion For right-sided colon cancer, even with clinical stage I included, radical lymph node dissection should be performed for exact staging with sufficient number of lymph nodes. This will help determine appropriate adjuvant treatment, especially in large tumor sizes.

Background The optimal extent of lymph node dissection in patients with descending colon cancer is still debatable. We designed this study to evaluate the distribution of lymph node metastasis and the appropriate extent of lymph node dissection in descending colon cancer patients. Methods We retrospectively reviewed the medical records of 118 descending colon cancer patients without distant metastasis, who underwent curative resection between January 2004 and December 2014. The distribution of lymph node metastasis was evaluated, and prognostic factors were analysed. Results The median follow-up period was 52 months (range 1-125 months). Twenty-six (22.0%) patients underwent high ligation of the inferior mesenteric artery (IMA), whereas 92 (78.0%) patients underwent ligation of the left colic artery, saving the IMA. Lymph nodes at the origin of the IMA showed no metastasis in any of the 26 patients who underwent high ligation of the IMA. After propensity score matching, 3-year disease-free survival (80.4% versus 92.9%, P = 0.471) and 5-year overall survival (81.8% versus 90.9%, P = 0.875) were not significantly different according to the type of IMA ligation. Conclusion In patients with descending colon cancer, there was no lymph node metastasis at the origin of the IMA, and ligation of the IMA showed no prognostic benefit.

Colon cancers are staged by assessing more than 12 lymph nodes, but there is still a controversy over the number of lymph nodes. Only a few studies of metastatic lymph node position in colon cancer have been published with its significance not completely understood. This study aimed to compare survival rates according to metastatic lymph node position following radical lymph node dissection for stage III colon cancers. This retrospective study evaluated data prospectively collected at a tertiary teaching hospital from 349 patients who underwent laparoscopic colectomy with radical node dissection between December 2009 and December 2014. Lymph nodes were numbered and classified into lymph node metastasis (LNM) groups LNM1, LNM2, and LNM3 and their short- and long-term outcomes were compared. The LNM1, LNM2, and LNM3 groups included 229, 94, and 26 patients, respectively. Patient characteristics differed by locations (p

Data on the incidence, risk factors, and oncologic impact of chylous ascites after colorectal cancer surgery are scarce. In this study, we aimed to assess the risk factors and the short-term and long-term impact of chylous ascites after colorectal cancer surgery. We retrospectively examined 2917 primary colorectal cancer patients who underwent surgical resection between January 2008 and December 2013. The short-term and long-term outcomes were compared between patients with and those without postoperative chylous ascites, and the risk factors for chylous ascites were analyzed. Chylous ascites developed in 138 (4.7 %) patients. A shorter operative time (odds ratio [OR] 0.992, 95 % confidence interval [CI] 0.988–0.996) and the number of retrieved lymph nodes (OR 1.015, 95 % CI 1.004–1.025) were independent risk factors for postoperative chylous ascites. All patients with chylous ascites were managed conservatively, without surgical intervention. The postoperative hospital stay was similar between the two groups (9.4 vs. 9.2 days, p = 0.467). After a median follow-up of 37 months (range 0–118 months), no significant difference was observed in the 3-year disease-free survival (85.0 vs. 83.9 %, p = 0.408) and 5-year overall survival (93.0 vs. 89.7 %, p = 0.662) between the two groups. A major drawback of this study was that the definition of chylous ascites was solely based on clinical signs. Nevertheless, we can conclude that chylous ascites after colorectal cancer surgery is associated with a shorter operative time and the number of retrieved lymph nodes, but is not associated with the short-term and long-term outcomes.