Long-term bowel functional outcomes following anal sphincter-preserving surgery for upper and middle rectal cancer: a single-center longitudinal study.

PURPOSE: Despite advances in neoadjuvant chemoradiotherapy and anal sphincter-preserving surgery for rectal cancer, bowel dysfunction is still unavoidable and negatively affects patients' quality of life. In this longitudinal study, we aimed to investigate the changes in bowel function with follow-up time and the effect of neoadjuvant chemoradiotherapy on bowel function following low anterior resection for rectal cancer. METHODS: In this study, 171 patients with upper or middle rectal cancer who underwent low anterior resection between 2012 and 2018 were included. Bowel function was assessed longitudinally with Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner scores every 6 months after restoration of bowel continuity. Patients with at least 2 follow-up visits were included. RESULTS: Overall, 100 patients received neoadjuvant chemoradiotherapy. Urgency, soilage, and fecal incontinence were noted within 24 months in the patients treated with neoadjuvant chemoradiotherapy. After 2 years of follow-up, significant bowel dysfunction and fecal incontinence were observed in the neoadjuvant chemoradiotherapy group. Low tumor level and neoadjuvant chemoradiotherapy were associated with delayed bowel dysfunction. CONCLUSION: Neoadjuvant chemoradiotherapy in combination with low tumor level was significantly associated with delayed bowel dysfunction even after 2 years of follow-up. Therefore, careful selection and discussion with patients are paramount.

Pretreatment MRI-detected extramural venous invasion as a prognostic and predictive biomarker for neoadjuvant chemoradiotherapy in non-metastatic rectal cancer: a propensity score matched analysis.

OBJECTIVES: This study evaluated pretreatment magnetic resonance imaging (MRI)-detected extramural venous invasion (pmrEMVI) as a predictor of survival after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Medical records of 1184 patients with rectal adenocarcinoma who underwent TME between January 2011 and December 2016 were reviewed. MRI data were collected from a computerized radiologic database. Cox proportional hazards analysis was used to assess local, systemic recurrence, and disease-free survival risk based on pretreatment MRI-assessed tumor characteristics. After propensity score matching (PSM) for pretreatment MRI features, nCRT therapeutic outcomes according to pmrEMVI status were evaluated. Cox proportional hazards analysis was used to identify risk factors for early recurrence in patients receiving nCRT. RESULTS: Median follow-up was 62.8 months. Among all patients, the presence of pmrEMVI was significantly associated with worse disease-free survival (DFS; HR 1.827, 95% CI 1.285-2.597, p = 0.001) and systemic recurrence (HR 2.080, 95% CI 1.400-3.090, p < 0.001) but not local recurrence. Among patients with pmrEMVI, nCRT provided no benefit for oncological outcomes before or after PSM. Furthermore, pmrEMVI( +) was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT. CONCLUSIONS: pmrEMVI is a poor prognostic factor for DFS and SR in patients with non-metastatic rectal cancer and also serves as a predictive biomarker of poor DFS and SR following nCRT in LARC. Therefore, for patients who are positive for pmrEMVI, consideration of alternative treatment strategies may be warranted. CLINICAL RELEVANCE STATEMENT: This study demonstrated the usefulness of pmrEMVI as a predictive biomarker for nCRT, which may assist in initial treatment decision-making in patients with non-metastatic rectal cancer. KEY POINTS: • Pretreatment MRI-detected extramural venous invasion (pmrEMVI) was significantly associated with worse disease-free survival and systemic recurrence in patients with non-metastatic rectal cancer. • pmrEMVI is a predictive biomarker of poor DFS following nCRT in patients with LARC. • The presence of pmrEMVI was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT.

Postchemoradiation magnetic resonance imaging circumferential resection margin predicts treatment failure after multidisciplinary directed sphincter preservation in low rectal cancer.

BACKGROUND: This study aimed to review the magnetic resonance imaging (MRI) features of patients with low rectal cancer (LRC) undergoing preoperative chemoradiotherapy (CRT) and investigate the risk factors for treatment failure after sphincter preserving surgery following preoperative CRT based on multidisciplinary approach. OBJECTIVES: Patients who underwent standard CRT and sphincter preserving radical surgery for LRC between January 2000 and December 2011 were retrospectively reviewed. Sphincter preservation failure (SPF) was defined as any one of the following: positive pathologic circumferential resection margin, local recurrence, failure to repair ileostomy, or permanent stoma formation due to anastomotic complications. RESULTS: Among the 191 patients, there were no overall significant differences between sphincter preservation success (n = 161) and SPF (n = 30) groups. SPF group showed a higher MRI circumferential resection margins (mrCRM) positive rate before and after CRT (before CRT: 33.3% vs. 16.1%, p = 0.027; after CRT: 23.3% vs. 6.2%, p = 0.002). Multivariate analysis showed that only mrCRM after CRT was associated with SPF (hazard ratio = 4.596, p = 0.005). SPF group showed worse 5-year cancer-specific survival (51% vs. 92.7%, p < 0.001). CONCLUSIONS: MRI-based assessment of the tumor after CRT plays a crucial role in predicting the success and feasibility of sphincter preservation as well as oncological outcomes in patients with LRC.

Machine-Learning Algorithms Using Systemic Inflammatory Markers to Predict the Oncologic Outcomes of Colorectal Cancer After Surgery.

BACKGROUND: This study aimed to investigate the clinical significance of machine-learning (ML) algorithms based on serum inflammatory markers to predict survival outcomes for patients with colorectal cancer (CRC). METHODS: The study included 941 patients with stages I to III CRC. Based on random forest algorithms using 15 compositions of inflammatory markers, four different prediction scores (DFS score-1, DFS score-2, DFS score-3, and DFS score-4) were developed for the Yonsei cohort (training set, n = 803) and tested in the Ulsan cohort (test set, n = 138). The Cox proportional hazards model was used to determine correlation between prediction scores and disease-free survival (DFS). Harrell's concordance index (C-index) was used to compare the predictive ability of prediction scores for each composition. RESULTS: The multivariable analysis showed the DFS score-4 to be an independent prognostic factor after adjustment for clinicopathologic factors in both the training and test sets (hazard ratio [HR], 8.98; 95% confidence interval [CI] 6.7-12.04; P < 0.001 for the training set and HR, 2.55; 95% CI 1.1-5.89; P = 0.028 for the test set]. With regard to DFS, the highest C-index among single compositions was observed in the lymphocyte-to-C-reactive protein ratio (LCR) (0.659; 95% CI 0.656-0.662), and the C-index of DFS score-4 (0.727; 95% CI 0.724-0.729) was significantly higher than that of LCR in the test set. The C-index of DFS score-3 (0.725; 95% CI 0.723-0.728) was similar to that of DFS score-4, but higher than that of DFS score-2 (0.680; 95% CI 0.676-0.683). CONCLUSIONS: The ML-based approaches showed prognostic utility in predicting DFS. They could enhance clinical use of inflammatory markers in patients with CRC.

Neoadjuvant chemotherapy versus upfront surgery as the initial treatment for patients with resectable, synchronous colorectal cancer liver metastases.

BACKGROUND: Although perioperative chemotherapy has been the standard treatment for colorectal cancer with resectable liver metastases (CRLM), studies that have compared neoadjuvant chemotherapy (NAC) and upfront surgery, especially in the setting of synchronous metastases are rare. METHODS: We compared perioperative outcomes, overall survival (OS) and overall survival after recurrence (rOS) in a retrospective study of 281 total and 104 propensity score-matched (PSM) patients who underwent curative resection, with or without NAC, for synchronous CRLM, from 2006 to 2017. A Cox regression model was developed for OS. RESULTS: After PSM, 52 NAC and 52 upfront surgery patients with similar baseline characteristics were compared. Postoperative morbidity, mortality, and 5-year OS rate (NAC: 78.9%, surgery: 64.0%; p = 0.102) were similar between groups; however, the NAC group had better rOS (NAC: 67.3%, surgery: 31.5%; p = 0.049). Initial cancer stage (T4, N1-2), poorly differentiated histology, and >1 hepatic metastases were independent predictors of worse OS. Based on these factors, patients were divided into low-risk (≤1 risk factor, n = 115) and high-risk (≥2 risk factors, n = 166) groups. For high-risk patients, NAC yielded better OS than upfront surgery (NAC: 74.5%, surgery: 53.2%; p = 0.024). CONCLUSIONS: Although NAC and upfront surgery-treated patients had similar perioperative outcomes and OS, better postrecurrence survival was shown in patients with NAC. In addition, NAC may benefit patients with worse prognoses; therefore, physicians should consider patient disease risk before initiating treatment to identify patients who are most likely to benefit from chemotherapy.

The Effect of Daytime Surgical Hospitalists on Reducing Night Shift Physicians' Workload.

BACKGROUND: The shortage of doctors at night makes it difficult to execute complex tasks and deliver accurate decisions. Therefore, reducing the night shift physician's workload is essential for patient safety. This study aimed to observe the effect of daytime surgical hospitalists on the reduction in night shift physicians' workload by analyzing the volume of electronic orders generated at night for postoperative patients. METHODS: A total of 9328 hospitalized patients who underwent colorectal or gastrointestinal surgery for more than 120 minutes were reviewed retrospectively. This study reviewed the nighttime volume difference of electronic orders between patients cared for by a daytime surgical hospitalist and patients cared for by a resident. Multiple logistic regression analysis was performed to analyze the risk factors of nighttime orders during hospitalization (dichotomous end point). Negative binomial regression analysis was also performed to analyze the volume of electronic orders as countable data, and the incident rate ratio was estimated (count end point). RESULTS: The risk of the occurrence of nighttime electronic order for patients treated by a surgical hospitalist was lower than that of patients cared for by a resident (adjusted odds ratio, 0.616; 95% confidence interval, 0.558-0.682; P < 0.001). In the negative binomial regression analysis, the total volume of electronic orders at night was lower in patients cared for by a surgical hospitalist than in patients cared for by a resident (adjusted incident rate ratio, 0.653; 95% confidence interval, 0.623-0.685; P < 0.001). CONCLUSIONS: The introduction of daytime surgical hospitalists is associated with the lower workload of night shift physicians.

Prediction of Microsatellite Instability in Colorectal Cancer Using a Machine Learning Model Based on PET/CT Radiomics.

PURPOSE: We investigated the feasibility of preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) radiomics with machine learning to predict microsatellite instability (MSI) status in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Altogether, 233 patients with CRC who underwent preoperative FDG PET/CT were enrolled and divided into training (n=139) and test (n=94) sets. A PET-based radiomics signature (rad_score) was established to predict the MSI status in patients with CRC. The predictive ability of the rad_score was evaluated using the area under the receiver operating characteristic curve (AUROC) in the test set. A logistic regression model was used to determine whether the rad_score was an independent predictor of MSI status in CRC. The predictive performance of rad_score was compared with conventional PET parameters. RESULTS: The incidence of MSI-high was 15 (10.8%) and 10 (10.6%) in the training and test sets, respectively. The rad_score was constructed based on the two radiomic features and showed similar AUROC values for predicting MSI status in the training and test sets (0.815 and 0.867, respectively; p=0.490). Logistic regression analysis revealed that the rad_score was an independent predictor of MSI status in the training set. The rad_score performed better than metabolic tumor volume when assessed using the AUROC (0.867 vs. 0.794, p=0.015). CONCLUSION: Our predictive model incorporating PET radiomic features successfully identified the MSI status of CRC, and it also showed better performance than the conventional PET image parameters.

Clinical Significance of Combining Preoperative and Postoperative Albumin-Bilirubin Score in Colorectal Cancer.

PURPOSE: Albumin-bilirubin (ALBI) score is a well-known prognostic factor for various diseases, including colorectal cancer (CRC). However, little is known about the significance of postoperative ALBI score changes in patients with CRC. MATERIALS AND METHODS: A total of 723 patients who underwent surgery were enrolled. Preoperative ALBI (ALBI-pre) and postoperative ALBI (ALBI-post) scores were divided into low and high score groups. ALBI-trend was defined as a combination of four groups comprising the low and high ALBI-pre and ALBI-post score groups. Kaplan-Meier survival curves were used to compare the overall survival (OS) between the different ALBI groups. The Cox proportional hazards model was used to examine the independent relevant factors of OS. Stratification performance was compared between the different ALBI groupings using Harrell's concordance index (C-index). RESULTS: ALBI-pre, ALBI-post, and ALBI-trend score groups were significant prognostic factors of OS in the univariable analysis. However, multivariable analysis showed that ALBI-trend was an independent prognostic factor while ALBI-pre and ALBI-post were not. The C-index of ALBI-trend (0.622; 95% confidence interval [CI], 0.587 to 0.655) was higher than that of ALBI-pre (0.589; 95% CI, 0.557 to 0.621; bootstrap mean difference, 0.033; 95% CI, 0.013 to 0.057) and ALBI-post (0.575; 95% CI, 0.545 to 0.605; bootstrap mean difference, 0.047; 95% CI, 0.024 to 0.074). CONCLUSION: Combining ALBI-pre and ALBI-post scores is an independent prognostic factor of OS and shows superior predictive power compared to ALBI-pre or ALBI-post alone in patients with CRC.

Combining prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score as a valuable prognostic factor for overall survival in patients with stage I-III colorectal cancer.

Background and aims: This study compared the prognostic significance of various nutritional and inflammatory indicators such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio, prognostic nutritional index, and controlling nutritional status score. In addition, we aimed to establish a more accurate prognostic indicator. Methods: We retrospectively evaluated 1112 patients with stage I-III colorectal cancer between January 2004 and April 2014. The controlling nutritional status scores were classified as low (0-1), intermediate (2-4), and high (5-12) scores. The cut-off values for prognostic nutritional index and inflammatory markers were calculated using the X-tile program. P-CONUT, a combination of prognostic nutritional index and the controlling nutritional status score, was suggested. The integrated areas under the curve were then compared. Results: The multivariable analysis showed that prognostic nutritional index was an independent prognostic factor for overall survival, whereas the controlling nutritional status score, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio were not. The patients were divided into three P-CONUT groups as follows: G1, controlling nutritional status (0-4) and high prognostic nutritional index; G2, controlling nutritional status (0-4) and low prognostic nutritional index; and G3, controlling nutritional status (5-12) and low prognostic nutritional index. There were significant survival differences between the P-CONUT groups (5-year overall survival of G1, G2, and G3 were 91.7%, 81.2%, and 64.1%, respectively; p < 0.0001). The integrated areas under the curve of P-CONUT (0.610, CI: 0.578-0.642) was superior to those of the controlling nutritional status score alone (bootstrap integrated areas under the curve mean difference=0.050; 95% CI=0.022-0.079) and prognostic nutritional index alone (bootstrap integrated areas under the curve mean difference=0.012; 95% CI=0.001-0.025). Conclusion: Prognostic effect of P-CONUT may be better than inflammatory markers such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio. Thus, it could be used as a reliable nutritional risk stratification tool in patients with colorectal cancer.

Comparison of Laparoscopic Versus Robot-Assisted Surgery for Rectal Cancers: The COLRAR Randomized Controlled Trial.

OBJECTIVE: To evaluate whether robotic for middle or low rectal cancer produces an improvement in surgical outcomes compared with laparoscopic surgery in a randomized controlled trial (RCT). BACKGROUND: There is a lack of proven clinical benefit of robotic total mesorectal excision (TME) compared with a laparoscopic approach in the setting of multicenter RCTs. METHODS: Between July 2011 and February 2016, patients diagnosed with an adenocarcinoma located <10 cm from the anal verge and clinically rated T1-4aNxM0 were enrolled. The primary outcome was the completeness of TME assessed by a surgeon and a pathologist. RESULTS: The RCT was terminated prematurely because of poor accrual of data. In all, 295 patients were assigned randomly to a robot-assisted TME group (151 in R-TME) or a laparoscopy-assisted TME group (144 in L-TME). The rates of complete TME were not different between groups (80.7% in R-TME, 77.1% in L-TME). Pathologic outcomes including the circumferential resection margin and the numbers of retrieved lymph nodes were not different between groups. In a subanalysis, the positive circumferential resection margin rate was lower in the R-TME group (0% vs 6.1% for L-TME; P =0.031). Among the recovery parameters, the length of opioid use was shorter in the R-TME group ( P =0.028). There was no difference in the postoperative complication rate between the groups (12.0% for R-TME vs 8.3% for L-TME). CONCLUSIONS: In patients with middle or low rectal cancer, robotic-assisted surgery did not significantly improve the TME quality compared with conventional laparoscopic surgery (ClinicalTrial.gov ID: NCT01042743).

Albumin-myosteatosis gauge as a novel prognostic risk factor in patients with non-metastatic colorectal cancer.

BACKGROUND: Myosteatosis and systemic inflammation are well-known prognostic factors in patients with colorectal cancer (CRC). The serum albumin level is a reflection of malnutrition and systemic inflammation, which in turn plays a key role in the development of myosteatosis. However, few studies have been conducted on these synergistic effects. This study aimed to examine the individual and synergistic effects of different prognostic markers related to skeletal muscle quality and serum albumin levels in patients with CRC. METHODS: This study enrolled patients with stage I-III CRC who underwent surgical resection between July 2006 and February 2014. Skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) were calculated using computed tomography at the L3 level obtained within 2 months prior to surgery. The albumin-myosteatosis gauge (AMG) was defined as SMD × albumin. Patients were divided into sex-specific quartiles (G1 to G4) according to the AMG, and analysis of variance for continuous variables and chi-square test for categorical variables were used to compare variables among quartiles. Cox proportional hazard models were constructed and integrated receiver operating characteristic curve (iAUC) analysis was used to compare the prognostic performance of SMD, albumin and AMG. RESULTS: Among the 906 participants, the median (interquartile) age was 64 (55-72) years, and 365 (40.3%) were female. AMG was significantly correlated with the occurrence of complications, albumin level, SMI and SMD (all P < 0.001). Overall survival (OS) differed significantly according to the AMG group, with 5-year OS for G1-G4 being 73.4%, 86.2%, 91.1% and 95.5%, respectively (P < 0.0001). Although SMI, SMD, albumin and AMG were all significant individual prognostic markers of OS in the univariable analysis, AMG remained the only independent prognostic factor in the multivariable analysis (G1 vs. G2, P = 0.045, G1 vs. G3, P = 0.005, G1 vs. G4, P < 0.001, respectively). The iAUC value of AMG [0.681, 95% confidence interval (CI) = 0.638-0.723] was superior to that of SMD (0.610, 95% CI = 0.566-0.654) (bootstrap iAUC mean difference = 0.071, 95% CI = 0.034-0.106), SMI (0.551, 95% CI = 0.511-0.594) (bootstrap iAUC mean difference = 0.129, 95% CI = 0.076-0.181) and albumin (0.627, 95% CI = 0.585-0.668) (bootstrap iAUC mean difference = 0.053, 95% CI = 0.010-0.098). CONCLUSIONS: In patients with stage I-III CRC, AMG is a meaningful predictor of survival, with superior prognostic value compared to SMI, SMD or albumin alone. Further studies are needed to determine their significance in different ethnic groups.

Single-incision versus conventional laparoscopic surgery for rectal cancer: a meta-analysis of clinical and pathological outcomes.

Introduction: Single-incision laparoscopic surgery (SILS) for rectal cancer is technically challenging. There is a lack of high-level evidence for the feasibility and safety of SILS for rectal cancer. Aim: To compare clinical and pathological outcomes of SILS versus conventional laparoscopic surgery (CLS) for rectal cancer. Material and methods: The PubMed, Embase, CENTRAL, and Web of Science databases were searched systematically up to November 2021. Eligibility criteria included randomized controlled trials and non-randomized clinical trials that compared the outcomes of SILS and CLS for rectal cancer. Outcomes of interest included operative, postoperative, and pathologic outcomes. Results: Meta-analysis was performed on 6 studies involving 417 patients. In total 181 patients underwent SILS and 236 underwent CLS. SILS had better outcomes for the incision length (MD = -49.58, 95% CI: -72.43 to -26.73), postoperative pain (visual analogue scale on postoperative day 1, MD = -0.96, 95% CI: -1.18 to -0.74; postoperative day 2, MD = -1.43, 95% CI: -2.29 to -0.57), and hospital stay (MD = -1.17, 95% CI: -1.84 to -0.50). Operative outcomes, including operation time, blood loss, conversion to laparotomy, and ileostomy rate, were similar. Perioperative mortality, overall complications, reoperation, and readmission were similar. Numbers of harvested lymph nodes, lengths of proximal and distal margin, circumferential resection margin involvements, incomplete mesorectal grade, and R0 resection rates were similar. Conclusions: SILS for rectal cancer presented superior outcomes for incision length, postoperative pain, and hospital stays. Perioperative mortality, morbidity, and pathologic outcomes of SILS were comparable to CLS. Future studies are required to determine the long-term oncologic outcomes of SILS for rectal cancer.

Impact of neoadjuvant treatment on rectal gastrointestinal stromal tumors.

Although gastrointestinal stromal tumors (GISTs) are rare disease and rectal GISTs is only 5% of total GISTs, they have the worst prognosis. Due to narrow pelvis, tumor rupture or positive resection margin are common in the management of rectal GISTs. The impact of neoadjuvant treatment on the clinical outcomes of rectal gastrointestinal stromal tumors (GISTs) remains unclear. Thus, we conducted a retrospective study to investigate the impact of neoadjuvant imatinib on rectal GIST. The cohort comprised 33 patients; of them, 10 and 23 belonged to the neoadjuvant (i.e., those who underwent neoadjuvant imatinib treatment) and the control group (i.e., those who underwent surgery without prior imatinib treatment), respectively. Neoadjuvant group was associated with more common levator ani muscle displacement (P = 0.002), and showed significantly larger radiologic tumor size (P = 0.036) than the control group. The mean tumor size was significantly decreased after imatinib treatment (6.8 cm to 4.7cm, P = 0.006). There was no significant difference in resection margin involvement (P >0.999), and sphincter preservation rates (P = 0.627) between the two groups. No difference was observed with respect to morbidities, hospital stay, local recurrence and disease-free survival. Neoadjuvant imatinib treated group had similar propensity with control group after treatment. We thought reduced tumor sized could enhance resectability and provide more chance to preserve sphincter for rectal GIST patients. Considering large tumor size and higher rate of sphincter invasion in the neoadjuvant group, imatinib treatment could be helpful as a conversion strategy to make huge and low-lying rectal GIST operable and achieve better surgical outcomes.

AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis.

Recent development of the chemical inhibitors specific to oncogenic KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog) mutants revives much interest to control KRAS-driven cancers. Here, we report that AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis. AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation. Then, AIMP2-DX2 competitively blocks the access of Smurf2 (SMAD Ubiquitination Regulatory Factor 2) to KRAS, thus preventing ubiquitin-mediated degradation. Moreover, AIMP2-DX2 levels are positively correlated with KRAS levels in colon and lung cancer cell lines and tissues. We also identified a small molecule that specifically bound to the KRAS-binding region of AIMP2-DX2 and inhibited the interaction between these two factors. Treatment with this compound reduces the cellular levels of KRAS, leading to the suppression of KRAS-dependent cancer cell growth in vitro and in vivo. These results suggest the interface of AIMP2-DX2 and KRAS as a route to control KRAS-driven cancers.

Clinical Significance of Early Carcinoembryonic Antigen Change in Patients With Nonmetastatic Colorectal Cancer.

Background: This study aimed to evaluate the prognostic significance of preoperative, postoperative, and trajectory changes in carcinoembryonic antigen (CEA) levels in patients with colorectal cancer (CRC). Methods: This retrospective study included patients who underwent surgical resection for nonmetastatic CRC. The optimal cutoff values of preoperative CEA (CEA-pre), early postoperative CEA (CEA-post), and CEA level change (CEA-delta) were determined to maximize the differences in overall survival (OS) among groups. The patients were divided into three groups according to CEA-trend: normal, low CEA-pre; normalized, high CEA-pre/low CEA-post; elevated, high CEA-pre/high CEA-post. The integrated area under the curve (iAUC) was used to compare the discriminatory power of all variables. Results: A total of 1019 patients diagnosed with stage I-III CRC were enrolled. The optimal cutoff values of CEA level were determined as 2.3 ng/mL for CEA-pre, 2.3 ng/mL for CEA-post, and -0.93 ng/mL for CEA-delta. Although subgroup dichotomization showed that CEA-pre, CEA-post, CEA-delta, and CEA-trend were all associated with OS in univariate analysis, CEA-trend was the only independent prognostic factor in multivariate analysis. The iAUC of CEA-trend was superior to that of CEA-pre, CEA-post, and CEA-delta. Compared with the normal group, the normalized group showed worse OS (p=.0007) in stage II patients but similar OS (p=.067) in stage III patients. Conclusion: The optimal cutoff value of CEA level in the preoperative and postoperative periods was determined to be 2.3 ng/mL, and the combination of CEA-pre and CEA-post showed better prognostic stratification. However, its prognostic significance may differ depending on the CRC stage.

Risk factors and economic burden of postoperative anastomotic leakage related events in patients who underwent surgeries for colorectal cancer.

BACKGROUND: Nationwide research about the clinical and economic burden caused by anastomotic leakage (AL) has not been published yet in Korea. This study assessed the AL rate and quantified the economic burden using the nationwide database. METHODS: This real world evidence study used health claims data provided by the Korean Health Insurance Review and Assessment Service (HIRA, which showed that 156,545 patients underwent anterior resection (AR), low anterior resection (LAR), or ultra-low anterior resection (uLAR) for colorectal cancer (CRC) between January 1, 2007 and January 31, 2020. The incidence of AL was identified using a composite operational definition, a composite of imaging study, antibacterial drug use, reoperation, or image-guided percutaneous drainage. Total hospital costs and length of stay (LOS) were evaluated in patients with AL versus those without AL during index hospitalization and within 30 days after the surgery. RESULTS: Among 120,245 patients who met the eligibility criteria, 7,194 (5.98%) patients had AL within 30 days after surgery. Male gender, comorbidities (diabetes, metastatic disease, ischemic heart disease, ischemic stroke), protective ostomy, and multiple linear stapler use, blood transfusion, and urinary tract injury were associated with the higher odds of AL. Older age, rectosigmoid junction cancer, AR, LAR, and laparoscopic approach were related with the reduced odds of AL. Patients with AL incurred higher costs for index hospitalization compared to those without AL (8,991 vs. 7,153 USD; p<0.0001). Patients with AL also required longer LOS (16.78 vs. 14.22 days; p<0.0001) and readmissions (20.83 vs. 13.93 days; p<0.0001). CONCLUSION: Among patients requiring resection for CRC, the occurrence of AL was associated with significantly increased costs and LOS. Preventing AL could not only produce superior clinical outcomes, but also reduce the economic burden for patients and payers.

A new juvenile Yamaceratops (Dinosauria, Ceratopsia) from the Javkhlant Formation (Upper Cretaceous) of Mongolia.

Here we report a new articulated skeleton of Yamaceratops dorngobiensis (MPC-D 100/553) from the Khugenetjavkhlant locality at the Shine Us Khudag (Javkhlant Formation, ?Santonian-Campanian) of the eastern Gobi Desert, Mongolia, which represents the first substantially complete skeleton and the first juvenile individual of this taxon. The specimen includes a nearly complete cranium and large portions of the vertebral column and appendicular skeleton. Its skull is about 2/3 the size of the holotype specimen, based on mandibular length. Its juvenile ontogenetic stage is confirmed by multiple indicators of skeletal and morphological immaturity known in ceratopsians, such as the long-grained surface texture on the long bones, the smooth external surface on the postorbital, open neurocentral sutures of all caudal vertebrae, a large orbit relative to the postorbital and jugal, the low angle of the lacrimal ventral ramus relative to the maxillary teeth row, narrow frontal, and straight ventral edge of the dentary. Osteohistological analysis of MPC-D 100/553 recovered three lines of arrested growth, implying around 3 years of age when it died, and verified this specimen's immature ontogenetic stage. The specimen adds a new autapomorphy of Yamaceratops, the anteroventral margin of the fungiform dorsal end of the lacrimal being excluded from the antorbital fossa. Furthermore, it shows a unique combination of diagnostic features of some other basal neoceratopsians: the ventrally hooked rostral bone as in Aquilops americanus and very tall middle caudal neural spines about or more than four times as high as the centrum as in Koreaceratops hwaseongensis, Montanoceratops cerorhynchus, and Protoceratops andrewsi. The jugal with the subtemporal ramus deeper than the suborbital ramus as in the holotype specimen is also shared with A. americanus, Liaoceratops yanzigouensis, and juvenile P. andrewsi. Adding 38 new scorings into the recent comprehensive data matrix of basal Neoceratopsia and taking into account the ontogenetically variable characters recovered Y. dorngobiensis as the sister taxon to Euceratopsia (Leptoceratopsidae plus Coronosauria). A second phylogenetic analysis with another matrix for Ceratopsia also supported this position. The new phylogenetic position of Y. dorngobiensis is important in ceratopsian evolution, as this taxon represents one of the basalmost neoceratopsians with a broad, thin frill and hyper-elongated middle caudal neural spines while still being bipedal.

Association of Albumin-Bilirubin Grade and Myosteatosis with its Prognostic Significance for Patients with Colorectal Cancer.

BACKGROUND: The albumin-bilirubin (ALBI) grade is a useful prognostic and predictive marker for patients with liver disease. Its clinical significance has been limited to patients with colorectal cancer (CRC). Furthermore, the association between the ALBI grade and skeletal muscle-related indices is unclear. METHODS: This study enrolled 1015 patients who underwent computed tomography (CT) scans within 31 days before surgery. The prognostic value of the ALBI grade in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between the ALBI grade and the skeletal muscle index or radiodensity (myosteatosis) was evaluated. The predictive accuracy of ALBI alone and in combination with myosteatosis was compared using Harrell's concordance index (C-index). RESULTS: The significant prognostic factors for OS identified in the multivariable analysis were the ALBI group (low vs high: hazard ratio [HR], 1.566; 95 % confidence interval [CI], 1.174-2.089; p = 0.002) and myosteatosis (low vs. high: HR, 0.648; 95 % CI, 0.486-0.865; p = 0.003). The rate of low-grade myosteatosis increased as the ALBI grade increased. The C-index of combined ALBI and myosteatosis (0.650; 95 % CI, 0.618-0.683) was superior to that of ALBI alone (0.603; 95 % CI, 0.575-0.631; bootstrap incremental area under the curve [iAUC] mean difference, 0.047; 95 % CI, 0.012-0.070) and myosteatosis alone (0.608; 95 % CI, 0.577-0.640; bootstrap iAUC mean difference, 0.042; 95 % CI, 0.023-0.064). CONCLUSION: The ALBI grade is significantly associated with myosteatosis. The ALBI grade is a significant prognostic factor, and the combination of ALBI and myosteatosis show an additive value in discriminating survival of patients with CRC.

The Clinical Impact of Combining Neutrophil-to-Lymphocyte Ratio with Sarcopenia for Improved Discrimination of Progression-Free Survival in Patients with Colorectal Cancer.

This study aimed to evaluate the clinical impact of combined sarcopenia and inflammation classification (CSIC) in patients with colorectal cancer (CRC). The skeletal muscle index (SMI) and neutrophil-to-lymphocyte ratio (NLR) were measured in 1270 patients who underwent surgery between January 2005 and April 2014. A Cox proportional hazards model was used to evaluate the correlation of sarcopenia, NLR, and CSIC, with progression-free survival (PFS). The integrated area under the curve (iAUC) was used to compare the discriminatory performance of each model. Using the cut-off values for SMI suggested by Martin et al. and for an NLR of 2.26, the CSIC was defined as follows: nonsarcopenia with low NLR (group 1), nonsarcopenia with high NLR (group 2), sarcopenia with low NLR (group 3), and sarcopenia with high NLR (group 4). Sarcopenia alone was not statistically significant. Multivariate analysis identified that CSIC (group 4 vs. group 1; hazard ratio (HR), 1.726; 95% CI, 1.130-2.634; p = 0.011) and NLR (HR, 1.600; 95% CI, 1.203-2.128; p = 0.001) were independently associated with PFS. The CSIC improved the prediction accuracy of PFS compared with NLR (iAUC mean difference = 0.011; 95% CI, 0.0018-0.028). In conclusion, the combination of sarcopenia and NLR could improve prognostic accuracy, and thus compensate for the limitation of sarcopenia.