Dysbiosis of gut microbiota during fecal stream diversion in patients with colorectal cancer.

BACKGROUND: The effect of fecal stream diversion on the gut microbiota is still uncertain. The present study was designed to assess the effect of fecal stream diversion on the composition of the gut microbiota in patients with colorectal cancer. We included patients undergoing left-sided colorectal cancer surgery with (ileostomy group) or without (control group) diverting ileostomy. Fecal samples were collected from 10 patients in each group before surgery (t1) and after ileostomy repair in the ileostomy group and 6-12 months after the initial surgery in the control group (t2). The fecal microbiota was assessed using 16S rRNA sequencing, and changes in the composition of the fecal microbiota were compared between the two groups. RESULTS: Alpha diversity analysis revealed that the complexity of fecal microbiota decreased between t1 and t2 only in the ileostomy group. Beta diversity analysis also showed dissimilarity between t1 and t2 only in the ileostomy group. The composition of the microbiota was similar between the two groups at t1. However, at t2, the ileostomy group had lower proportion of beneficial bacteria (Lachnospiraceae, 3.8% vs. 29.9%, p < 0.001; Ruminococcaceae, 0.6% vs. 18.4%, p < 0.001; Blautia, 0.1% vs. 9.1%, p < 0.001; Faecalibacterium, 0.2% vs. 7.5%, p < 0.001) and a higher proportion of harmful bacteria (Proteobacteria, 17.9% vs. 5.1%, p = 0.006; Clostridium, 16.2% vs. 1.1%, p = 0.013; Streptococcus, 17.7% vs. 1.6%, p = 0.002) than the control group. CONCLUSIONS: Fecal stream diversion was closely associated with less diversity and dysbiosis of the gut microbiota.

Effect of preoperative immunonutrition on fecal microbiota in colon cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND/OBJECTIVES: This study aimed to evaluate the effect of preoperative immunonutrition on the composition of fecal microbiota following a colon cancer surgery. MATERIALS/METHODS: This study was a secondary analysis of a randomized controlled trial assessing the impact of preoperative immunonutrition on the postoperative outcomes of colon cancer surgery. Patients with primary colon cancer were enrolled and randomly assigned to receive additional preoperative immunonutrition or a normal diet alone. Oral nutritional supplementation (400 mL/day) with arginine and ω-3 fatty acids were administered to patients in the immunonutrition group for 7 days prior to surgery. Thirty-two fecal samples were collected from 16 patients in each group, and the composition of fecal microbiota was compared between the 2 groups. RESULTS: At the phylum level, no significant difference was observed in the composition of microbiota between the 2 groups (Firmicutes, 69.1% vs. 67.5%, P = 0.624; Bacteroidetes, 19.3% vs. 18.1%, P = 0.663; Actinobacteria, 6.7% vs. 10.6%, P = 0.080). The Firmicutes/Bacteroidetes ratio (4.43 ± 2.32 vs. 4.55 ± 2.51, P = 0.897) was also similar between the 2 groups. At the genus level, the proportions of beneficial bacteria such as Faecalibacterium spp. (8.1% vs. 6.4%, P = 0.328) and Prevotella spp. (6.9% vs. 4.8%, P = 0.331) were higher, while that of Clostridium spp. was lower (0.5% vs. 1.2%, P = 0.121) in the immunonutrition group, but the difference was not significant. CONCLUSIONS: Immunonutrition showed no significant association with the composition of fecal microbiota. The relationship between immunonutrition and the fecal microbiota should be investigated further in large-scale studies.

Impact of Preoperative Immunonutrition on the Outcomes of Colon Cancer Surgery: Results from a Randomized Controlled Trial.

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/d) 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 before colon cancer surgery cannot be justified.

Oncological impact of intraperitoneal chemotherapy after cytoreductive surgery for patients with colorectal peritoneal metastasis: A bi-institutional retrospective analysis.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Association between microsatellite instability and tumor response to neoadjuvant chemoradiotherapy for rectal cancer.

Purpose: 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. Methods: 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. Results: 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% vs. 24.1%, P = 0.208). Multivariate analysis showed that well-differentiated tumors were the only predictive factor for good response to nCRT (odds ratio [OR], 2.241; 95% confidence interval [CI], 1.492-3.364; P < 0.001). MSI status tended to be associated with the response to nCRT (OR, 0.215; 95% CI, 0.027-1.681; P = 0.143). Conclusion: MSI-H was not associated with response to nCRT in patients with rectal cancer.

Impact of circumferential tumor location of mid to low rectal cancer on oncologic outcomes after preoperative chemoradiotherapy.

Purpose: 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. Methods: 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. Results: 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% vs. posterior, 14.3% vs. lateral, 11.0% vs. circumferential, 17.4%; P = 0.232). Univariate analyses revealed no correlation between CTL and 3-year LRFS (93.0% vs. 89.1% vs. 91.5% vs. 88%, P = 0.513), 3-year DFS (70.3% vs. 70.2% vs. 75.3% vs. 75.7%, P = 0.832), and 5-year OS (74.7% vs. 78.0% vs. 83.9% vs. 78.2%, P = 0.204). Multivariate analysis identified low rectal cancer and pathological CRM involvement as independent risk factors for all survival outcomes (all P < 0.05). Conclusion: CTL of rectal cancer after preoperative CRT was not significantly associated with the pathological CRM status, recurrence, and survival.

Effect of the First Assistant on Anastomotic Leakage after Rectal Cancer Surgery with Double-Stapling Anastomosis: A Propensity Score Matching Analysis.

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.

Proper surgical extent for clinical Stage I right colon cancer.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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, P < 0.001). 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. CONCLUSION: The study results show that even clinical Stage I cases, radical resection should be considered in accordance with T3 and T4 tumours.

Periumbilical Transverse Incision for Reducing Incisional Hernia in Laparoscopic Colon Cancer Surgery.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: A muscle splitting periumbilical transverse incision could significantly reduce the rate of IH in minimally invasive colon cancer surgery.

Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.

Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.

Postoperative bile leakage caused by intrahepatic duct injury during right hemicolectomy: A case report.

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.

Perineural invasion and number of retrieved lymph nodes are prognostic factors for T2N0 colon cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Distribution of lymph node metastasis and oncological outcomes of mid-transverse colon cancer: extended versus transverse colectomy.

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.

Prognostic significance of enlarged paraaortic lymph nodes detected during left-sided colorectal cancer surgery: a single-center retrospective cohort study.

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.

A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal 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.

The Relationship Between High-Output Stomas, Postoperative Ileus, and Readmission After Rectal Cancer Surgery With Diverting Ileostomy.

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.

Comparison of Right-side and Left-side Colon Cancers Following Laparoscopic Radical Lymphadenectomy.

PURPOSE: 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. AIM OF THE STUDY: This study compared short- and long-term outcomes between right and left colon cancers. MATERIALS AND METHODS: 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.Results: The right colon group included 343 (35.5%) patients and the left colon group 623. Female patients had a high incidence of right colon cancer (p < 0.001). Right colon cancer had longer operative times (p = 0.012), and more bleeding during the operation (p = 0.001). The size of the tumor was larger (p < 0.001) and more lymph nodes were harvested (p < 0.001) on the right side. Vascular (p = 0.006) and lymphatic (p = 0.004) invasion was greater in the right colon, but left colon cancer showed greater neural invasion (p = 0.008). Cancers on the right side also had a tendency to be poorly differentiated (p < 0.001). The groups did not differ in disease-free, overall, and cancer-specific survival rates for stage. CONCLUSION: Although the oncologic outcomes show no significant differences, colon cancer has characteristic, perioperative, and histopathologic differences according to its embryologic origin.

Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.

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 (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 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 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 < .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. CONCLUSIONS: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

Tailored treatment of anastomotic leak after rectal cancer surgery according to the presence of a diverting stoma.

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.