Preoperative CEA Research Articles

Risk Factors of Colorectal Cancer Recurrence After Curative Resection Surgery: A Systematic Review and Meta-analysis

Context: According to the World Health Organization, colorectal cancer (CRC) is the third most prevalent cancer globally, with the highest mortality rate after lung cancer. Some studies predicted risk factors provoking CRC recurrence. However, no single study discussed CRC recurrence. Objectives: This study aimed to quantitatively estimate the influence of several risk factors toward early recurrence of CRC. Methods: We utilized four medical databases, including Pubmed, Cochrane, Wiley library, and ScienceDirect, and a range of literature searches between July to October 2020 with output study, odds ratio (OR), and some risk factors. We used PRISMA protocol along with several relevant keywords with NOS method was utilized to assess the quality of the study. Fixed- and randomized effect model were utilized to control each numerical analysis’ bias. Results: We found six studies that compared the risk factor of CRC recurrence after curative resection with curative-intention encompassing a total of 15.457 patients. We found seven risk factors of colorectal cancer recurrence, including vascular invasion (OR 2.3; IK95%: 01.56 - 3.4; P < 0.0001), depth of invasion (T stage) (OR 2.27; IK95%: 1.14 - 4.51; P = 0.02), pre-operative CEA serum (OR 2.24 IK95%: 1.57 - 3.2; P < 0.0001), post-operative CEA serum (OR 5.97 IK95%: 3.04 - 11.74; P < 0,0001), pre-operative CA19-9 serum (OR 3.03; IK95%: 1.74 - 5.25; P < 0.0001), and regional nodal metastasis (N stage) (OR 2.56; IK95% 1.41 - 4.62; P = 0.002). Conclusions: Risk factors of earlier CRC recurrence were diversely reviewed. The elevation of post-operative CEA serum was assumed as the main factor in this study; however, most of the studied parameters were statistically significant.

ASO Visual Abstract: Impact of Preoperative CEA Uptrend on Survival Outcomes in Patients with Colorectal Liver Metastasis after Hepatectomy

ASO Visual Abstract: Impact of Preoperative CEA Uptrend on Survival Outcomes in Patients with Colorectal Liver Metastasis after Hepatectomy

Abstract 6178: COVID-19 pandemic and clinicopathologic characteristics of colorectal cancer in Korea: A multicenter, retrospective study

Abstract Background: The coronavirus disease 2019 (COVID-19) pandemic has affected not only the control and management of infectious diseases, but also those of other diseases by deteriorating the general healthcare systems worldwide. In accordance with the suggestion by the WHO for postponement of non-urgent procedures, diagnosis and treatment strategies for the patients with malignancy have been changed. The aim of this study was to investigate the impact of COVID-19 pandemic on primary colorectal cancer (CRC) from multi-institutions in Korea. Methods: Medical records of consecutive patients with CRC between March 2019 and February 2021 in six university hospitals were reviewed. Recurrent diseases, admission for management of complications or enterostomy repair, and other pathologies than adenocarcinoma were excluded. Baseline characteristics and perioperative outcomes were compared after a cohort was divided into the two groups: before and after around March 2020, when the COVID-19 test has been mandatory for all admitted patients in most institutions. Treatment characteristics and pathologic outcomes were also compared between the two groups. Results: A total of 3895 patients with CRC admitted during the study period. After 454 patients were excluded, 1820 and 1621 patients were assigned to the pre-pandemic and pandemic groups. The proportion of patients who could not receive curative or palliative surgery for stage IV diseases was not different (88 vs. 91, P>0.999), and 3262 patients underwent surgery for primary CRC. Among them, the pandemic group showed more previous abdominal surgery (21.2% vs. 15.4%, P<0.001), higher preoperative CEA level (46.7 vs. 16.0 ng/mL, P=0.021), and less stent insertion for obstructive lesion (33% vs. 46.4%, P=0.043). There was no difference in sex, age, the ASA grade, and tumor location between the groups. Perioperative outcomes including operation time, operation method, operation type, and postoperative complication rates were not different, whereas more stoma formation was performed in the pandemic group (15.3% vs. 12.4%, P=0.024). Pathologic outcomes including TNM stage, tumor diameter, harvested lymph nodes, and lymphovascular invasion were not different. However, the pandemic group showed higher tendency of lymph node metastasis (44% vs. 40.6%, P=0.070) and more adjuvant chemotherapy (26.4% vs. 20.1%, P<0.001). Conclusions: Although a few factors indicated more advanced CRC, clinical features and perioperative outcomes of the patients in COVID-19 pandemic seemed not to be aggravated in Korea. The national healthcare system which was not shut down in the pandemic, and relatively small number of COVID-19 prevalence might influence these results, although patients’ access and medical checkup seemed to decrease slightly. The cause and effect of decreased medical access would be clarified by long-term follow up data. Citation Format: Yoon Dae Han, Jun Sang Shin, Sung Uk Bae, Woo Ram Kim, Dae Ro Lim, Chang Woo Kim. COVID-19 pandemic and clinicopathologic characteristics of colorectal cancer in Korea: A multicenter, retrospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6178.

Elevated Carcinoembryonic Antigen at the Time of Recurrence as a Poor Prognostic Factor in Colorectal Cancer: A Propensity Score Matching Analysis

There are few studies on the prognostic impact of CEA level at the time of recurrence in recurrent colorectal cancer. The objective of this study was to evaluate the prognostic value of serum CEA levels at the time of recurrence in patients with recurrent colorectal cancer. Between 2007 and 2014, 962 consecutive recurrent patients for colorectal cancer were analyzed. These patients were divided into two groups according to CEA level at the time of recurrence (r-CEA): high r-CEA (≥5 ng/ml) (n = 428) and normal r-CEA (<5 ng/ml) (n = 534). The prognostic effects of r-CEA were evaluated by one-to-one propensity score matching (PSM) to adjust factors between groups. After matching, a total of 778 patients, 389 per group, were analyzed. After matching, the 5-year disease-free survival rate for the high r-CEA group was significantly lower than that for the normal r-CEA group. The 5-year overall survival rate was 56.5% in the high r-CEA group and 66.0% in the normal r-CEA group (p = 0.008). The 5-year cancer-specific survival rate was 61.7% in the high group and 67.5% in the normal group (p = 0.035). In a multivariate analysis of prognostic factors, high preoperative CEA level at the time of recurrence, poor histologic grade, and lymphatic invasion were associated with poorer overall survival. The high r-CEA level group showed significantly poorer prognosis than the normal r-CEA group. Therefore, the r-CEA level can be used as a prognostic factor in recurrent colorectal cancer. Aggressive adjuvant treatment needs to be considered for patients with an initially high CEA level and lymph node positivity who are prone to recurrence.

Recurrence risk stratification model for patients with stage I-III colorectal cancer based on clinicopathological and postoperative ctDNA predictors.

e15511 Background: The aim of this study was to propose a new kind of recurrence risk classification and further establish a prognostic model for resected stage I-III colorectal cancer (CRC). Methods: From 2017 to 2020, 142 patients diagnosed with stage I-III CRC at Peking University Shougang Hospital were recruited for this study. Tissues and paired white blood cells were analyzed with a 733-gene NGS panel, and peripheral plasma obtained 7-10 days after surgery was analyzed with a 127-gene ultra-deep target panel in a CLIA-certified laboratory. The relationship between the postoperative ctDNA status, clinicopathological features and recurrence-free survival (RFS) was identified by log-rank test and Cox regression analysis. Results: In total, 108 patients successfully completed both tissue and postoperative plasma NGS tests, of which 17 patients were postoperatively positive for ctDNA (tumor-informed, ≥1 somatic mutation). Postoperative ctDNA positivity was independently associated with poorer RFS (HR = 8.4, P &lt; 0.0001). Postoperative recurrence rates were significantly higher in ctDNA-positive patients than ctDNA-negative patients (76.5% vs 16.5%, P &lt; 0.0001). Univariate analysis showed that, in addition to ctDNA status, stage, vascular invasion, neural invasion, and preoperative CEA were all significantly associated with worse RFS (P &lt; 0.05). Furthermore, in a COX regression model, the contribution of these clinicopathological factors to RFS has been adjusted. The model showed good discrimination [the concordance index (c-index): 0.811] of recurrence. Clinically high-risk groups according to clinicopathological risk model had significantly poorer RFS than low-risk groups (HR = 10.6, P &lt; 0.001). In the clinicopathological high-risk group, ctDNA-positive patients can still further differentiate the higher risk of recurrence (HR = 3.7, P = 0.0012). There were similar trends in the clinicopathological low-risk group (HR = 6.1, P = 0.066). Combining the clinicopathological model and ctDNA, patients with either clinicopathological high-risk or ctDNA-positive had a significantly poorer RFS, compared with both clinicopathological low-risk and ctDNA-negative (HR = 12.9, P &lt; 0.0001). Conclusions: Postoperative ctDNA can independently predict the risk of recurrence in stage I-III CRC. Combining clinicopathological factors and ctDNA showed superiority for recurrence risk stratification over either alone. This recurrence risk stratification model may serve as a useful clinical tool to help clinicians determine individualized treatment plans for stage I-III CRC patients. However, the model still needs further external cohort validation.

Preoperative risk factors of lymph node metastasis in clinical N0 lung adenocarcinoma of 3\xa0cm or less in diameter

BackgroundLung adenocarcinoma is the most common subtype of non-small cell lung cancer. The surgical strategy of lymph node dissection is controversial because many more patients are diagnosed at an early stage in clinical practice.MethodsWe retrospectively reviewed 622 clinical N0 lung adenocarcinoma patients with 3 cm or less in tumor size who underwent lobectomy or segmentectomy combined with lymph node dissection in our hospital from January 2017 to December 2019. We performed univariate and multivariate analyses to identify preoperative risk factors of lymph node metastasis.ResultsLymph node metastasis was found in 60 out of 622 patients. On univariate analysis, lymph node metastasis was linked to smoking history, preoperative CEA level, tumor size, tumor location (peripheral or central), consolidation/tumor ratio, pleural invasion, and pathologic type. However, only the preoperative CEA level, tumor size, and consolidation/tumor ratio were independent risk factors in multivariate analysis. The ROC curve showed that the cutoff value of tumor size was 1.7 cm. There was no lymph node metastasis in patients without risk factors.ConclusionsThe preoperative CEA level, tumor size, and consolidation/tumor ratio were independent risk factors of lymph node metastasis in clinical N0 lung adenocarcinoma with tumor size ≤ 3 cm. The lymph node metastasis rate was extremely low in clinical N0 lung adenocarcinoma patients without risk factors and lymph node dissection should be avoided in these patients to reduce surgical trauma.

Preoperative risk stratification of permanent stoma in patients with non-metastatic mid and low rectal cancer undergoing curative resection and a temporary stoma.

Although a temporary stoma can mitigate the severity of anastomotic leakage, some rectal cancer patients retain a permanent stoma after sphincter-preserving surgery. Therefore, this study aimed to identify independent preoperative risk factors for permanent stoma and establish a prediction model for mid-and low-rectal cancer patients who underwent sphincter-preserving surgery and temporary stoma. We retrospectively reviewed consecutive patients with non-metastatic rectal cancer between 2000 and 2015. The risk factors for permanent stomas were collected and analyzed. A total of 1020 rectal cancer patients with temporary stoma were included. The overall rate of permanent stoma was 17.5% (n = 179). Cancer progression and anastomotic complications are major causes of permanent stomas. Multivariate analysis showed that preoperative risk factors such as advanced age, male sex, preoperative CEA ≥ 10ng/ml, T4 stage, N stage, low rectal tumor, and ASA ≥ III were independent preoperative risk factors after adjustment. The ROC curve of the risk factors and permanent stoma showed an AUC of 0.689, a cut-off value of 2.5, a sensitivity of 0.689, and a specificity of 0.622. The permanent stoma rates were significantly higher between risk scores ≤ 2 and > 2 (29.9% vs. 11.3%, p < 0.001). Preoperative CEA ≥ 10ng/ml, T4 stage, N stage, low rectal tumor, advanced age, ASA ≥ III, and male sex were independent preoperative prognostic factors for a permanent stoma. The risk was higher with a score greater than two. Therefore, the risk of subsequent permanent stoma should be evaluated and informed to the patient prior to the primary surgery.

Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment

BackgroundThe aim of this study was to develop a prediction model for 10-year overall survival (OS) after resection of colorectal liver metastasis (CRLM) based on patient, tumour and treatment characteristics. MethodsConsecutive patients after complete resection of CRLM were included from two centres (1992–2019). A prediction model providing 10-year OS probabilities was developed using Cox regression analysis, including KRAS, BRAF and histopathological growth patterns. Discrimination and calibration were assessed using cross-validation. A web-based calculator was built to predict individual 10-year OS probabilities. ResultsA total of 4112 patients were included. The estimated 10-year OS was 30% (95% CI 29–32). Fifteen patient, tumour and treatment characteristics were independent prognostic factors for 10-year OS; age, gender, location and nodal status of the primary tumour, disease-free interval, number and diameter of CRLM, preoperative CEA, resection margin, extrahepatic disease, KRAS and BRAF mutation status, histopathological growth patterns, perioperative systemic chemotherapy and hepatic arterial infusion pump chemotherapy. The discrimination at 10-years was 0.73 for both centres. A simplified risk score identified four risk groups with a 10-year OS of 57%, 38%, 24%, and 12%. ConclusionsTen-year OS after resection of CRLM is best predicted with a model including 15 patient, tumour, and treatment characteristics. The web-based calculator can be used to inform patients. This model serves as a benchmark to determine the prognostic value of novel biomarkers.

Construction and Validation of Convenient Clinicopathologic Signatures for Predicting the Prognosis of Stage I-III Gastric Cancer.

BackgroundPatients with stage I-III gastric cancer (GC) undergoing R0 radical resection display extremely different prognoses. How to discriminate high-risk patients with poor survival conveniently is a clinical conundrum to be solved urgently.MethodsPatients with stage I-III GC from 2010 to 2016 were included in our study. The associations of clinicopathological features with disease-free survival (DFS) and overall survival (OS) were examined via Cox proportional hazard model. Nomograms were developed which systematically integrated prognosis-related features. Kaplan–Meier survival analysis was performed to compare DFS and OS among groups. The results were then externally validated by The Sixth Affiliated Hospital, Sun Yat-sen University.ResultsA total of 585 and 410 patients were included in the discovery cohort and the validation cohort, respectively. T stage, N stage, lymphatic/vascular/nerve infiltration, preoperative CEA, and CA19-9 were independent prognostic factors (P < 0.05). Two prognostic signatures with a concordance index (C-index) of 0.7502 for DFS and 0.7341 for OS were developed based on the nomograms. The 3-year and 5-year calibration curves showed a perfect correlation between predicted and observed outcomes. Patients were divided into three risk groups (low, intermediate, high), and distinct differences were noticed (p < 0.001). Similar results were achieved in the validation cohort. Notably, a free website was constructed based on our signatures to predict the recurrence risk and survival time of patients with stage I-III GC.ConclusionsThe signatures demonstrate the powerful ability to conveniently identify distinct subpopulations, which may provide significant suggestions for individual follow-up and adjuvant therapy.

Machine Learning Approach to Stratifying Prognosis Relative to Tumor Burden after Resection of Colorectal Liver Metastases: An International Cohort Analysis.

Assessing overall tumor burden on the basis of tumor number and size may assist in prognostic stratification of patients after resection of colorectal liver metastases (CRLM). We sought to define the prognostic accuracy of tumor burden by using machine learning (ML) algorithms compared with other commonly used prognostic scoring systems. Patients who underwent hepatectomy for CRLM between 2001 and 2018 were identified from a multi-institutional database and split into training and validation cohorts. ML was used to define tumor burden (ML-TB) based on CRLM tumor number and size thresholds associated with 5-year overall survival. Prognostic ability of ML-TB was compared with the Fong and Genetic and Morphological Evaluation scores using Cohen's d. Among 1,344 patients who underwent resection of CRLM, median tumor number (2, interquartile range 1 to 3) and size (3 cm, interquartile range 2.0 to 5.0) were comparable in the training (n = 672) vs validation (n = 672) cohorts; patient age (training 60.8 vs validation 61.0) and preoperative CEA (training 10.2 ng/mL vs validation 8.3 ng/mL) was also similar (p > 0.05). ML empirically derived optimal cutoff thresholds for number of lesions (3) and size of the largest lesion (1.3 cm) in the training cohort, which were then used to categorize patients in the validation cohort into 3 prognostic groups. Patients with low, average, or high ML-TB had markedly different 5-year overall survival (51.6%, 40.9%, and 23.1%, respectively; p < 0.001). ML-TB was more effective at stratifying patients relative to 5-year overall survival (low vs high ML-TB, d = 2.73) vs the Fong clinical (d = 1.61) or Genetic and Morphological Evaluation (d = 0.84) scores. Using a large international cohort, ML was able to stratify patients into 3 distinct prognostic categories based on overall tumor burden. ML-TB was noted to be superior to other CRLM prognostic scoring systems.

Predicting Distant Metastasis in Young-Onset Colorectal Cancer After Surgery: A Retrospective Study.

BackgroundAlthough overall colorectal cancer (CRC) cases have been declining worldwide, there has been an increase in the incidence of the CRC among individuals younger than 50 years old, which is associated with distant metastasis (DM) and poor prognosis.MethodsYoung-onset CRC patients’ postoperative data were collected from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Data from the SEER database were divided into early stage and advanced stage according to whether chemoradiotherapy was recommended in the guidelines. Independent risk factors for DM were explored by using univariate and multivariate logistic regression separately. A predictive model was established and presented as nomogram in the training set of advanced stage. The model was internally verified in testing set and externally validated in a cohort of 145 patients from Zhongnan Hospital of Wuhan University. The accuracy, reliability, and clinical application value were assessed using the receiver operating characteristic curve (ROC), the area under the curve (AUC), calibration curve, and decision curve analysis (DCA), respectively. Different risk subgroups of DM were classified according to the scores of the nomogram in the training set of advanced stage.ResultsA total of 5,584 patients were eligible and enrolled in our study in which 1,277 were in early stage and 4,307 in advanced stage. Preoperative CEA positive was found to be an independent predictor of DM in early stage. Multivariate logistic regression analysis showed that tumor size, degree of differentiation, T stage, N stage, preoperative CEA, and whether radiation or chemotherapy performed were independent risk factors for DM (all, p < 0.05) in advanced stage. Great accuracies were achieved in our nomogram with AUC of 0.801 in training set, 0.811 in testing set, and 0.791 in the validation cohort, respectively. Calibration curves and DCA in internal validation and external validation both showed good stability and clinical utility values.ConclusionsPreoperative CEA positive was a significant predictor of DM for young-onset CRC patients. A novel nomogram containing clinical and pathological features was established for predicting DM of advanced CRC in patients younger than 50 years old. This tool may serve as an early alert for clinicians to DM and make better clinical treatment regimens.

Nomogram for predicting occurrence of synchronous liver metastasis in colorectal cancer: a single-center retrospective study based on pathological factors

PurposeThe purpose of this study was to explore the risk factors for synchronous liver metastasis (LM) of colorectal cancer (CRC) and to construct a nomogram for predicting the occurrence of synchronous LM based on baseline and pathological information.MethodsThe baseline and pathological information of 3190 CRC patients were enrolled in the study from the Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University between 2012 and 2020. All patients were divided into development and validation cohorts with the 1:1 ratio. The characters of LM and none-LM patients in newly diagnosed colorectal cancer were utilized to explore the risk factors for synchronous LM with the univariate and multivariate logistic regression analyses. A predictive nomogram was constructed by using an R tool. In addition, receiver operating characteristic (ROC) curves was calculated to describe the discriminability of the nomogram. A calibration curve was plotted to compare the predicted and observed results of the nomogram. Decision-making curve analysis (DCA) was used to evaluate the clinical effect of nomogram.ResultsThe nomogram consisted of six features including tumor site, vascular invasion (VI), T stage, N stage, preoperative CEA, and CA-199 level. ROC curves for the LM nomogram indicated good discrimination in the development (AUC = 0.885, 95% CI 0.854–0.916) and validation cohort (AUC = 0.857, 95% CI 0.821–0.893). The calibration curve showed that the prediction results of the nomogram were in good agreement with the actual observation results. Moreover, the DCA curves determined the clinical application value of predictive nomogram.ConclusionsThe pathologic-based nomogram could help clinicians to predict the occurrence of synchronous LM in postoperative CRC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.

The prognostic significance of apical lymph node metastasis in patients with high-risk stage III colon cancer

The effect of apical lymph node (APN) metastasis on the prognosis of colon cancer is unknown. The present study investigated the impact of APN metastasis on the prognosis of the patients with high-risk stage III colon cancer. This retrospective multi-institutional study included patients with pathological high-risk stage III colon cancer who underwent surgery between April 2009 and December 2014. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors for overall survival (OS) and relapse-free survival (RFS). A total of 185 patients were collected. The 5-year OS rates of patients with and without APN metastasis were 35.0% and 72.1%, respectively (p = 0.0014). The 5-year RFS rates of patients with and without APN metastasis was 16.2% and 57.2%, respectively (p = 0.0002). The rate of distant metastasis in patients with APN metastasis was significantly higher than that in patients without APN metastasis (68.8% vs. 36.7%, p = 0.012). The univariate analysis revealed that the differentiation, lymph node ratio, and APN metastasis were significantly associated with 5-year OS, and the preoperative CEA and CA19-9 levels and APN metastasis were significantly associated with 5-year RFS. The multivariate analysis showed that APN metastasis was an independent risk factor for 5-year OS and RFS. APN metastasis may be independently associated with the prognosis of patients with high-risk Stage III colon cancer.

Prognostic Impact of Total Lesion Glycolysis (TLG) from Preoperative 18F-FDG PET/CT in Stage II/III Colorectal Adenocarcinoma: Extending the Value of PET/CT for Resectable Disease

Simple SummaryPET/CT is rarely performed initially in resectable colorectal cancer and is usually considered for detection of distant metastasis. However, we perceived another potential role of PET/CT in addition to diagnosis and staging, which is providing prognostication of the oncologic outcome by PET parameters extracted from initial PET/CT before surgery. This study evaluated the prognostic role of preoperative 18F-FDG PET/CT in 327 stage II/III colorectal cancer patients and comprehensively investigated the PET parameters with multiple threshold levels to select optimal parameters most robustly related to DFS. Several PET parameters including SUVmax, MTV2.5, MTV3, TLG2.5, TLG3, and TLG30% were significantly related to DFS, with TLG2.5 retaining statistical significance in multivariate analysis with other clinicopathologic prognostic factors. Prognostication with PET/CT at the time of initial diagnosis has substantial benefits over pathologic prognostic factors available only after surgery by giving oncologists an opportunity to consider treatment intensification or de-intensification before initiation of treatment.We investigated the prognostic role of metabolic parameters from preoperative 18F-FDG PET/CT in stage II/III colorectal adenocarcinoma. A total of 327 stage II/III colorectal adenocarcinoma patients who underwent curative resection were included. The maximal standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed for optimal cut-offs and their effect on DFS. Differences in DFS rates and hazard ratios for DFS between cut-offs were statistically significant in SUVmax, MTV2.5, MTV3, TLG 2.5, TLG3, and TLG30%. Factors significantly related to DFS in univariate Cox regression were age, sex, stage, preoperative CEA, SUVmax, MTV2.5, MTV3, TLG2.5, TLG3, and TLG30%. Age, sex, preoperative CEA, and TLG2.5 (p = 0.009) sustained statistically significant difference in multivariate analysis. The 1-, 3-, and 5-year DFS rates for TLG2.5 ≤ 448.5 were 98.1%, 79.6%, and 74.8%, significantly higher than 78.4%, 68.5%, and 61.1% of TLG2.5 > 448.5, respectively (p = 0.012). TLG, a parameter indicating both the metabolic activity and metabolic volume, was the strongest predictor independently associated with DFS, among several PET parameters with statistical significance. These results suggest the potential prognostic value of preoperative 18F-FDG PET/CT in stage II/III resectable colorectal cancer.

Upfront Surgery or Neoadjuvant Chemotherapy for Colorectal Liver Metastases? A Machine-Learning Decision-Tree to Identify the Best Potential Policy

Background: How to select patients for neoadjuvant chemotherapy rather than upfront surgery is still controversial in case of colorectal-liver-metastases(CLM). A model to assess the best potential candidates to upfront or neoadjuvant strategies was developed by machine-learning. Methods: Consecutive CLM patients at first hepatectomy were enrolled and grouped whether they had upfront surgery (UFS) or neoadjuvant therapy then surgery (NEOS). Baseline differences were weighted by Inverse-Probability-Weighting(IPW); survival analyses and risk predictions were estimated. A mortality risk model was built by Random-Forest(RF) to assess the best-potential-treatment(BPT) for each patient. A classification-and-regression-tree(CART) was developed to automatically identify the characteristics of BPT-upfront and BPT-neoadjuvant candidates. Results: Between 2005 and 2019, 448 patients were enrolled: 95 UFS and 353 NEOS. Baseline differences were weighted by IPW, obtaining two balanced pseudopopulation: UFS=432 and NEOS=440. Mortality risk was not impacted by neoadjuvant therapy (HR 1.44, 95%CI: 0.95-2.17, p=0.07). A mortality prediction model was fit by RF, showing an AUROC of 75.2%. NEOS was the BPT for 245 patients, while UFS for 203. At CART, planning a R1vasc surgery was the main factor determining who were best candidates for NEOS and UFS, followed by primitive tumor localization, number of metastases, age, sex, RAS status and pre-operative CEA. In case of R1vasc, patients with CEA=>10, or those with lower CEA but being female or being male with a tumor located in the right colon, were the best candidate to UFS. Conclusion: Upfront resection should be carefully reconsidered resulting the BPT in several complex conditions compared to NEOS.

M2-Type Macrophages Induce Tregs Generation by Activating the TGF-β/Smad Signalling Pathway to Promote Colorectal Cancer Development.

PurposeThe increase of both M2-type macrophages and Tregs is closely associated with the development of colorectal cancer. However, the mechanism of their interaction is still unclear. In this study, we investigated the correlation of M2-type macrophages with Tregs and the possible mechanisms between them.MethodsUsing immunohistochemistry, we analysed Smad3 (a key protein in the TGF-β/Smad signalling pathway) expression in colorectal cells, as well as infiltrating numbers of CD163 (a marker for M2-type macrophages), Foxp3 (a marker for Tregs) in 250 surgically resected colorectal cancer tissues, matched normal and paracancerous tissues. The relation of CD163 and Foxp3 was investigated in CRC with clinicopathological characteristics and preoperative tumour markers.ResultsCD163, Foxp3 and Smad3 were upregulated in CRC tissues compared to matched normal and paracancerous tissues. Interestingly, CD163 and Foxp3 were significantly positively correlated in CRC, and both were significantly positively correlated with Smad3. Both CD163 and Foxp3 were upregulated with increasing tumour TNM staging, increasing number of lymph node metastases and increasing vascular invasion. Additionally, CD163 was upregulated with increasing depth of infiltration. The number of M2-type macrophages and the expression levels of preoperative CEA, CA19-9 and CA72-4 were significantly positively correlated. The number of Tregs was significantly positively correlated with the expression levels of preoperative CEA and CA19-9.ConclusionM2-type macrophages may induce Tregs generation through activation of the TGF-β/Smad signalling pathway, which can promote the development of colorectal cancer.

Clinical Significance of and Predictive Risk Factors for the Postoperative Elevation of Carcinoembryonic Antigen in Patients With Non-Metastatic Colorectal Cancer.

BackgroundRecently, a few researches focus on the correlation between postoperative carcinoembryonic antigen (post-CEA) and the outcome of colorectal cancer (CRC), but none investigates the predictive value of post-CEA in a prognostic model. Besides, current recommendations on the frequency of post-CEA surveillance are not individualized and well followed. There is an absence of identification of patients who are more likely to have abnormal post-CEA levels and need more frequent CEA measurements.MethodsConsecutive CRC patients who underwent curative surgery were enrolled and randomly divided into the discovery (n=352) and testing cohort (n=233). Impacts of preoperative CEA (pre-CEA) and post-CEA on prognosis were assessed. Cox regression model was applied to develop prognostic nomograms, which were validated by the concordance index (C-index), calibration curve, and receiver operating characteristic curve (ROC) analysis. And prediction improvement of the nomograms was assessed with net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Logistic regression was used to identify predictive risk factors and construct the prediction model for post-CEA elevation.ResultsPost-CEA independently predicted overall survival (OS) and disease-free survival (DFS), while pre-CEA did not. Post-CEA elevation represented higher risks in patients with normal pre-CEA, compared to those with persistent elevated CEA. The nomograms for OS and DFS were established with body mass index, tumor differentiation, N stage, lymphocyte-to-monocyte ratio, and post-CEA. The nomograms showed good calibration and superior discrimination than pTNM stage, with the C-index of 0.783 and 0.759 in the discovery set and 0.712 and 0.774 in the testing set for OS and DFS, respectively. Comparisons between models using IDI and NRI implied that the nomograms performed better than pTNM stage and the predictive power could be improved with the addition of post-CEA. The prediction model for post-CEA elevation was established with age, platelet-to-lymphocyte ratio, preoperative CA19-9, and pre-CEA. The AUC of the model in the two cohorts was 0.802 and 0.764, respectively.ConclusionsElevated post-CEA was a strong indicator of poor prognosis. The addition of post-CEA significantly enhanced the performance of prognostic nomograms. And the prediction model for post-CEA elevation may help identify patients who ought to reasonably receive more intensive postoperative surveillance of CEA levels.

Acetabular remodeling after graft extrusion, rotation or impaction in Dega and Pemberton acetabuloplasties for developmental dysplasia of the hip.

Traditionally graft displacement following Pemberton and Dega acetabuloplasties involves internal fixation for treatment of developmental dysplasia of hip (DDH). This study was performed to assess the acetabular remodeling by conservative management of graft displacement among patients with DDH. This was a retrospective study of 20 patients 17 (85%) women and 3 (15%) men; mean age 22.90 ± 6.96 months with DDH who underwent Pemberton and Dega acetabuloplasties at King Khalid University Hospital, Riyadh between January 2013 and January 2018. All patients after losing acetabular correction during immediate postoperative period were treated by conservative management. The management involved application of Spica cast for 6 weeks that was trimmed to broomstick cast for an extended period of time and finally replaced by nocturnal abduction brace until normal acetabular index (AI) was achieved. The patients were followed up for a mean period of 44.60 ± 12.36 months. Out of the total, 18 (90%) patients with DDH were successfully treated by conservative management. The mean preoperative AI of 43.70° ± 5.91° improved to 21.35o ± 6.32o at the final follow-up (P < 0.001) which was no different when compared to the mean of unaffected hips (19.70o ± 2.96o; P < 0.44). The mean preoperative CEA of all the patients was negative that improved during the conservative treatment to 29.20° ± 10.0° which was no different when compared with the mean of unaffected (31.70° ± 4.64o; P = 0.32) hips at the final follow-up. doption of less aggressive approach for management of displaced, rotated or impacted autograft following acetabuloplasties among children with DDH was not only a useful conservative approach for remodeling of hips but also obviated the need for additional surgical intervention.

Nomogram to Predict Distant Metastasis Probability for Pathological Complete Response Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

PurposeThis study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes.Methods and MaterialsA total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan–Meier survival curve.ResultsAge, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, P = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively (P = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT3-4, with cN+ or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all P > 0.05). Active treatment after DM was more beneficial than palliative treatment (P < 0.001).ConclusionThe nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.

Prognostic Impact of Carcinoembryonic Antigen Levels in Rectal Cancer Patients Who Had Received Neoadjuvant Chemoradiotherapy.

PurposeCarcinoembryonic antigen (CEA) is a useful marker for rectal cancer. The aim of this study was to investigate the prognostic impact of CEA level according to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients who underwent radical surgery.MethodsA total of 245 patients with rectal cancer who underwent radical surgery were retrospectively evaluated. Serum CEA level was measured preoperatively and postoperatively. We compared survival outcomes based on CEA level before and after surgery according to nCRT.ResultsOf the 245 patients, elevation of CEA level was observed preoperatively in 79 and postoperatively in 30, respectively. Eighty-seven (35.5%) patients received nCRT, and elevated CEA level was a significant prognostic factor both before and after surgery. In patients who had not received nCRT, an elevated CEA level was a significant prognostic factor before surgery but was not significant after surgery. In a multivariate analysis for prognostic factors, elevation of preoperative CEA level was an independent prognostic factor of disease-free survival (DFS) regardless of nCRT. Postoperative CEA level was an independent prognostic factor of DFS in patients who had received nCRT but was not a factor in patients who had not received nCRT.ConclusionSerum CEA level was an independent prognostic factor both preoperatively and postoperatively in rectal cancer patients who had received nCRT.