Prognostic Factor In Rectal Cancer Research Articles

Double Negativity of MRI-Detected and Pathologically-Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis. Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them. Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity (p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis. Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer.

ASO Visual Abstract: Double Negativity of MRI-Detected and Pathologically Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

ASO Visual Abstract: Double Negativity of MRI-Detected and Pathologically Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

Log odds of positive nodes as a prognostic factor for rectal cancer: a retrospective study.

Rectal cancer is an important cause of mortality and morbidity globally. The aim of this study was to investigate whether the log odds of positive nodes system is a better indicator than tumor node metastasis and lymph node ratio systems to determine rectum cancer prognosis, which is an important cause of mortality and morbidity globally. This was a single-center retrospective cross-sectional study. Data were obtained from the medical records of patients with rectum adenocarcinoma followed at Gazi University Hospital. The clinicopathological data of 128 patients with rectum adenocarcinoma who underwent low anterior resection or abdominoperineal resection between January 2010 and December 2018 was retrospectively reviewed. Patients with rectum adenocarcinoma as the first and only primary diagnosis, which was confirmed by histopathological examination, than those who had undergone complete curative resection via low anterior resection or abdominoperineal resection were included. Those with familial adenomatous polyposis or Lynch syndrome, those under 18 years of age, with a synchronous tumor, peritoneal spread, or metastatic disease at the time of diagnosis, and those with <12 lymph nodes dissected from the resection material were excluded from the study. In multivariate analysis, age, perineural invasion, tumor node metastasis stage, lymph node ratio stage, and log odds of positive nodes stage were found to be independent prognostic factors (p<0.05). LODDS2 patients' mortality rates were 9.495 times higher than LODDS0 patients [hazard ratio=9.495, (95%CI 4.155-21.694), p<0.001] while LNR2 stage patients' mortality rates were 7.016 times higher than LNR0 stage patients [hazard ratio=7.016, (95%CI 3.123-15.765), p<0.001] and N2 stage patients had a 5.135 times higher risk of mortality than those who were in N0 stage [hazard ratio=5.135 (95%CI 2.451-10.756), p<0.001]. Log odds of positive nodes is a more valuable prognostic factor for rectal cancer patients than tumor node metastasis and lymph node ratio systems to determine rectum cancer prognosis.

The application of quantitative perfusion analysis of golden-angle radial sparse parallel MRI and R2∗ value for predicting pathological prognostic factors in rectal cancer

To investigate the diagnostic value of golden-angle radial sparse parallel magnetic resonance imaging (MRI) (GRASP) and R2∗ in predicting the prognostic factors of resectable rectal cancer. A total of 108 patients with rectal adenocarcinoma were included in this retrospective study. The volume transfer constant (Ktrans), rate constant (Kep), plasma volume fraction (Ve), and R2∗ were obtained. Univariate and multivariate logistic regression were conducted. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the imaging parameters. The Ktrans was found to be significantly higher in rectal cancers with positive lymph node metastasis (LNM), higher tumour grade, positive lymphovascular invasion (LVI), and higher ki-67 (all p<0.05). The Kep was also significantly higher in the LNM-positive group (p<0.001), while the R2∗ was higher in rectal cancers with LNM-positive, higher tumour grade, LVI-positive, and higher ki-67 (all p<0.05). Combining the Ktrans and R2∗ provided the highest area under the ROC curve (AUC) for LNM-positive and higher ki-67 tumours differentiation (0.790 and 0.823, respectively). Combining quantitative parameters of the Ktrans and R2∗ could be used to non-invasively predict pathological prognostic factors preoperatively.

Exploration of Malignant Characteristics in Neoadjuvant Chemotherapy-Resistant Rectal Cancer, Focusing on Extramural Lesions

BackgroundExtramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD.MethodsFrom 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared.ResultsThe NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047).ConclusionsWe defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.

The Incidence and Prognosis Value of Perineural Invasion in Rectal Carcinoma: From Meta-Analyses and Real-World Clinical Pathological Features

AimsPerineural invasion (PNI) is a special type of metastasis of several cancers and has been reported as being a factor for poor prognosis in colorectal carcinoma. However, investigations of PNI in only rectal cancer and a comprehensive analysis combining meta-analyses with real-world case studies remain lacking. Materials and methodsFirst, articles from 2000 to 2020 concerning the relationship between PNI and rectal cancer prognoses and clinical features were meta-analysed. Subsequently, we carried out a retrospective analysis of 312 rectal cancer cases that underwent radical surgery in the real world. The incidence of PNI and the relationship between PNI and prognosis, as well as clinicopathological factors, were investigated. ResultsThe incidence of PNI was 23.09% and 33.01% in the meta-analysis and clinical cases, respectively. PNI occurred as early as stage I (2.94%). Moreover, neoadjuvant therapy significantly reduced the PNI-positive rate (20.34% versus 26.54%). Both meta-analysis and real-world clinical case studies suggested that PNI-positive patients had poorer prognoses than PNI-negative patients. We established an effective risk model consisting of T stage, differentiation and lymphovascular invasion to predict PNI in rectal cancer. ConclusionPNI is a poor prognostic factor for rectal cancer and could occur even in stage I. Additionally, neoadjuvant therapy could sufficiently reduce the PNI-positive rate. T stage, lymphovascular invasion and differentiation grade were independent risk factors for PNI and the risk model that included these factors could predict the probability of PNI.

The impact of mesorectal fat area on recurrence following total mesorectal excision for lower rectal cancer.

The mesorectal fat area (MFA) at the tip of the ischial spines on magnetic resonance imaging has been used to characterize mesorectal morphology. Recent studies reported that a larger MFA correlated with difficulties in rectal cancer surgery. However, the relationship between MFA and rectal cancer prognosis remains unclear. This study evaluated the impact of MFA on recurrence following robotic total mesorectal excision (TME) for rectal cancer. Patients who underwent robotic TME for lower rectal cancer from December 2011 to December 2016 were enrolled. Cox regression analysis was performed to determine variables associated with relapse-free survival (RFS). Patients were divided into groups based on MFA, and RFS was compared. Of 230 patients, 173 (75.3%) were male. The median age was 63years, and median MFA was 19.7 cm2. In multivariate analysis, smaller MFA (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.88-0.97; p < 0.01), p/yp stage II (HR, 3.81; 95% CI, 1.40-10.35; p < 0.01), and p/yp stage III (HR, 5.35; 95% CI, 1.88-15.27; p < 0.01) were independently associated with worse RFS. Sex, body mass index, and visceral fat area were not correlated with RFS. In the median follow-up period of 60.8months, patients with MFA < 19.7 cm2 had a significantly lower 5-year RFS rate (72.7%) than those with MFA ≥ 19.7 cm2 (85.0%). Smaller MFA was associated with worse RFS in patients undergoing robotic TME for lower rectal cancer. MFA is considered to be a prognostic factor in rectal cancer.

Distal Tumor Spread in Rectal Cancer-How Low Should We Go?

Distal tumor spread (DTS) is an adverse prognostic factor in rectal cancer correlating with advanced stage disease. We aimed to assess prevalence and location of distal tumor spread and impact of neoadjuvant chemoradiotherapy (NACRT) in patients who underwent proctectomy for rectal cancer. The pathology database at our institution was queried for all patients who underwent proctectomy with curative intent for rectal cancer from 1/2008 to 12/2016. Specimen slides were re-evaluated by a single expert rectal cancer pathologist to verify diagnosis and measure the distance to the distal resection margin. Main outcome measures were 3-year overall and disease-free survival. 275 consecutive patients were identified. 109/111 patients with clinical stage 3 disease received preoperative neoadjuvant chemoradiotherapy. DTS was found in 13 (4.7%) specimens, 6 with intra-mural and 7 with extra-mural distal tumor spread. DTS was found only in patients with clinical stage 3 disease. Length of DTS from the distal end of the tumor ranged from 0 to 30mm; in only 4 specimens DTS was >10mm. A positive distal resection margin was found in 5/275 (1.8%) specimens. A macroscopically tumor-free margin may suffice in patients with pre-treatment stage 1 or 2 disease. Furthermore, a 1cm margin is adequate in most patients with stage 3 disease.

Relevance of adjuvant chemotherapy in elderly patients with low rectal tumors.

37 Background: The balance between the benefits and toxicities of adjuvant systemic chemotherapy is crucial in the elderly, and often co-morbid patients who have undergone total mesorectal excision (TME) surgery for carcinomas of the lower rectum (1). Tumour distance from the anal verge is a known prognostic factor in rectal cancer (2, 3) and it may influence the effectiveness of adjuvant chemotherapy (AC) (4). This study evaluated the differences in the survival outcomes between patients on surveillance(S) and those who received AC in a multi-centre, real-world setting with a focus on the elderly cohort. Methods: Data was extracted from electronic patient records from 4 NHS trusts in Kent, UK. We retrospectively analysed records of patients between 1 Jan 2014 and 31 Dec 2019, who had neoadjuvant chemoradiotherapy, were down-staged and then offered either S or AC based on clinician’s judgement. The tumour distance from the anal verge was measured through high resolution MRI. The patients were downstaged following assessment as their pTNM staging was lower than their cTNM staging. Results: 589 patients treated for rectal cancer were identified. Of these, 168/589(28%) had non-metastatic disease, were later down-staged at TME and were offered S or AC. 95/168 (57%) of these patients received AC. Patients who received AC were younger (median age 63 vs 70 years, p&lt; 0.001) and with additional poor prognostic factors such as extramural venous invasion EMVI+ (74 vs 39%, p= 0.001), circumferential resection margin CRM+ (89 vs 70% p = 0.001) and pathological nodal involvement (AJCC stage III disease) ( p&lt; 0.001) (table) compared to those on S. Our findings did suggest that patients on surveillance with tumours &lt; 5cm from the anal verge had a longer disease-free survival(DFS) than those who received chemotherapy; this was especially the case in the elderly patient cohort (HR 0.13 95% CI 0.02-0.99, p= 0.049).Our findings also showed that the DFS benefit for patients under surveillance increased with age. Surveillance was most effective in patients over 60 years old compared to those under 60. However, age or distance from anal verge did not have an impact on overall survival (HR 1.01 95% Cl 0.95-1.08 p= 0.70). Conclusions: Although patients treated with AC were younger than patients on S, their tumours had additional poor prognostic factors. Patients on surveillance with tumours &lt;5cm from the anal verge enjoyed a longer DFS but no OS benefit. Elderly patients with tumours &lt; 5cm from the anal verge with no poor prognostic features could derive a benefit from surveillance and avoid chemotherapy-related toxicity. However, our findings will need to be corroborated in prospective studies. [Table: see text]

Preoperative MR radiomics based on high-resolution T2-weighted images and amide proton transfer-weighted imaging for predicting lymph node metastasis in rectal adenocarcinoma.

Lymph node (LN) metastasis is an important prognostic factor in rectal cancer (RC). However, accurate identification of LN metastasis can be challenged for radiologists. The aim of our study was to assess the utility of MRI radiomics based on T2-weighted images (T2WI) and amide proton transfer-weighted(APTw) images for predicting LN metastasis in RC preoperatively. A total of 125 patients with pathologically confirmed rectal adenocarcinoma (RA) from January 2019 to June 2021 who underwent preoperative MR were enrolled in this retrospective study. Radiomics features were extracted from high-resolutionT2WI and APTw images of primary tumor. The most relevant radiomics and clinical features were selected using correlation and multivariate logistic analysis. Radiomics models were built using five machine learning algorithms including support vector machine (SVM), logical regression (LR), k- nearest neighbor (KNN), naive bayes (NB), and random forest (RF). The best algorithm was selected for further establish the clinical- radiomics model. The receiver operating characteristic curve (ROC) analysis was used to assess the performance of radiomics and clinical-radiomics model for predicting LN metastasis. The LR classifier had the best prediction performance, with AUCs of 0.983 (95% CI 0.957-1.000), 0.864 (95% CI 0.729-0.972), 0.851 (95% CI 0.713-0.940) on the training set, validation, and test sets, respectively. In terms of prediction, the clinical-radiomics combined model outperformed the radiomics model. The AUCs of the clinical-radiomics combined model in the validation and test sets were 0.900 (95% CI 0.785-0.986), and 0.929 (95% CI 0.721-0.943), respectively. The radiomics model based on high-resolution T2WI and APTw images can predict LN metastasis accurately in patients with RA.

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

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

Diagnostic performance of synthetic magnetic resonance imaging in the prognostic evaluation of rectal cancer.

Numerous factors are related to the prognosis of rectal cancer, including T stage, N stage, metastasis, extramural venous invasion (EMVI), circumferential resection margin (CRM), and tumor differentiation. However, it is still a challenge to precisely evaluate them before therapy; therefore, we investigate whether synthetic magnetic resonance imaging and apparent diffusion coefficient (ADC) values could help predict the prognostic factors of rectal cancer. Eighty-seven patients (55 men and 32 women; mean age, 59±11 years) with pathologically confirmed rectal cancer were enrolled. Preoperative quantitative metrics, including T1, T2, proton density (PD), and ADC values, were measured with diffusion-weighted imaging (DWI) acquired by a single-shot echo-planar sequence and synthetic magnetic resonance imaging acquired by a multi-dynamic multi-echo sequence at 3.0 T, in patients with rectal cancer by two radiologists. We evaluated the diagnostic performance of synthetic magnetic resonance imaging using the independent sample t-test or Mann-Whitney U test and receiver operating characteristic (ROC) curve and multivariate logistic regression analyses and compared the area under the ROC curve of quantitative values using the DeLong test. The T2 and PD values showed a significant reduction among patients with poor differentiation and lymph node metastasis in rectal cancer. The area under the ROC curve values of T2 and PD values for predicting magnetic resonance imaging N stage and differentiation were 0.734, 0.682, and 0.673, 0.686, respectively. Moreover, combining T2 and PD values for magnetic resonance imaging N stage slightly improved the area under the ROC curve value of 0.774 (95% CI, 0.673-0.876). In the present study, the ADC and T1 values were not significant in the differentiation or clinical stage of rectal cancer (RC). Quantitative T2 and PD values obtained by synthetic magnetic resonance imaging might be used for evaluating prognostic factors of rectal cancer noninvasively. Furthermore, combining T2 and PD values further improved the diagnostic performance of magnetic resonance imaging N staging in rectal cancer. The ADC and T1 values were not significant in the differentiation or clinical stage of RC.

Analysis of Prognostic Factors of Rectal Cancer and Construction of a Prognostic Prediction Model Based on Bayesian Network.

BackgroundThe existing prognostic models of rectal cancer after radical resection ignored the relationships among prognostic factors and their mutual effects on prognosis. Thus, a new modeling method is required to remedy this defect. The present study aimed to construct a new prognostic prediction model based on the Bayesian network (BN), a machine learning tool for data mining, clinical decision-making, and prognostic prediction.MethodsFrom January 2015 to December 2017, the clinical data of 705 patients with rectal cancer who underwent radical resection were analyzed. The entire cohort was divided into training and testing datasets. A new prognostic prediction model based on BN was constructed and compared with a nomogram.ResultsA univariate analysis showed that age, Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), Carbohydrate antigen 125 (CA125), preoperative chemotherapy, macropathology type, tumor size, differentiation status, T stage, N stage, vascular invasion, KRAS mutation, and postoperative chemotherapy were associated with overall survival (OS) of the training dataset. Based on the above-mentioned variables, a 3-year OS prognostic prediction BN model of the training dataset was constructed using the Tree Augmented Naïve Bayes method. In addition, age, CEA, CA19-9, CA125, differentiation status, T stage, N stage, KRAS mutation, and postoperative chemotherapy were identified as independent prognostic factors of the training dataset through multivariate Cox regression and were used to construct a nomogram. Then, based on the testing dataset, the two models were evaluated using the receiver operating characteristic (ROC) curve. The results showed that the area under the curve (AUC) of ROC of the BN model and nomogram was 80.11 and 74.23%, respectively.ConclusionThe present study established a BN model for prognostic prediction of rectal cancer for the first time, which was demonstrated to be more accurate than a nomogram.

The application of apparent diffusion coefficients derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer.

To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer. One hundred forty-six patients with rectal cancer who underwent preoperative MRI were prospectively enrolled. Two radiologists independently placed free-hand regions of interest (ROIs) in the largest tumor cross section and three small ROIs on the peritumoral zone adjacent to the tumor contour. Maximum values of tumor ADC (ADCtmax), minimum values of tumor ADC (ADCtmin), mean values of tumor ADC (ADCtmean), mean values of peritumor ADC (ADCpmean), and ADCpmean/ADCtmean (ADC ratio) were obtained on ADC maps and correlated with prognostic factors using uni- and multivariate logistic regression, and receiver operating characteristic curve (ROC) analysis. Interobserver agreement was excellent for ADCtmax and ADCtmean (intraclass correlation coefficient [ICC], 0.915-0.958), and were good for ADCtmin, ADCpmean, and ADC ratio (ICC, 0.774-0.878). The ADC ratio was significantly higher in the poor differentiation, T3-4 stage, lymph node metastasis (LNM)-positive, extranodal extension (ENE)-positive, tumor deposit (TD)-positive, and lymphovascular invasion (LVI)-positive groups than that in the well-moderate differentiation, T1-2 stage, LNM-negative, ENE-negative, TD-negative, and LVI-negative groups (p = 0.008, < 0.001, < 0.001, 0.001, < 0.001, and < 0.001, respectively). The area under the ROC curve (AUC) of the ADC ratio was the highest for assessing poor differentiation (0.700), T3-4 stage (0.707), LNM-positive (0.776), TD-positive (0.848), and LVI-positive (0.778). Both the ADC ratio (AUC = 0.677) and ADCpmean (AUC = 0.686) showed higher diagnostic performance for assessing ENE. The ADC ratio could provide better predictive performance for assessing preoperative prognostic factors in resectable rectal cancer. • Both the peritumor/tumor ADC ratio and ADCpmean are correlated with important prognostic factors of resectable rectal cancer. • Both peritumor ADC and peritumor/tumor ADC ratio had higher diagnostic performance than tumor ADC for assessment of prognostic factors in resectable rectal cancer. • Peritumor/tumor ADC ratio showed the most capability for the assessment of prognostic factors in resectable rectal cancer.

Expression profile and prognostic significance of HOXB13 in rectal cancer.

This study aimed to investigate the expression pattern and prognostic significance of HOXB13 in rectal cancer. HOXB13 expression in rectal cancer and normal adjacent tissues was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, and its clinicopathological characteristics and prognosis were statistically tested. Furthermore, we evaluated the association between tumor immune infiltrating cells and HOXB13 using the tumor immune estimation resource (TIMER) database. The potential biological mechanism associated with HOXB13 overexpression was investigated by gene set enrichment analysis (GSEA). The expression of HOXB13 messenger RNA and protein in human rectal cancer tissues were significantly higher than those in the normal adjacent tissues (P < 0.05). HOXB13 expression was significantly correlated with depth of invasion, lymphatic invasion, lymph node metastasis, distant metastasis, and pathological tumor node metastasis stage (P < 0.05). Kaplan-Meier survival curves confirmed that HOXB13 overexpression was correlated negatively with overall survival and disease-free survival in rectal cancer (P < 0.05). Also, multivariate Cox regression analysis demonstrated that HOXB13 expression, age, and lymphatic invasion were independent prognostic factors in rectal cancer (P < 0.05). Plus, the results from the TIMER database indicated that HOXB13 expression has a significant association with several immune cell infiltrates. Finally, the GSEA results indicated that HOXB13 participated in the various immune-associated processes, including natural killer cell-mediated cytotoxicity and the T-cell receptor signaling pathway. Our study showed an essential role of HOXB13 in rectal cancer immunity and prognosis. Significantly, the overexpression of HOXB13 leads to the worse prognosis for patients with rectal cancer, which will contribute to understanding molecular mechanisms associated with tumor pathogenesis and prognosis in this disease.

T2*-weighted imaging and diffusion kurtosis imaging (DKI) of rectal cancer: correlation with clinical histopathologic prognostic factors.

Histopathologic prognostic factors of rectal cancer are closely associated with local recurrence and distant metastasis. We aim to investigate the feasibility of T2*WI in assessment of clinical prognostic factors of rectal cancer, and compare with DKI. This retrospective study enrolled 50 out of 205 patients with rectal cancer according to the inclusion criteria. The following parameters were obtained: R2* from T2*WI, mean diffusivity (MDk), mean kurtosis (MK), and mean diffusivity (MDt) from DKI using tensor method. Above parameters were compared by Mann-Whitney U-test or students' t test. Spearman correlations between different parameters and histopathological prognostic factors were determined. The diagnostic performances of R2* and DKI-derived parameters were analyzed by receiver operating characteristic curves (ROC), separately and jointly. There were positive correlations between R2* and multiple prognostic factors of rectal cancer such as T category, N category, tumor grade, CEA level, and LVI (P < 0.004). MDk and MDt showed negative correlations with almost all the histopathological prognostic factors except CRM and TIL involvement (P < 0.003). MK correlated positively with the prognostic factors except CA19-9 level and CRM involvement (P < 0.006). The AUC ranges were 0.724-0.950 for R2* and 0.755-0.913 for DKI-derived parameters for differentiation of prognostic factors. However, no significant differences of diagnostic performance were found between T2*WI, DKI, or the combined imaging methods in characterizing rectal cancer. R2* and DKI-derived parameters were associated with different histopathological prognostic factors, and might act as noninvasive biomarkers for histopathological characterization of rectal cancer.

Relationship between Lymph Node Ratio and Survival Rate in Preopertive Chemoradiation Rectal Cancer Patients

Background: Number of positive lymph nodes is one of the most-important prognostic factors in rectal cancer. Rectal cancer patients who undergo colorectal surgery following neoadjuvant chemoradiation therapy are sometimes unable to retrieve an adequate amount of lymph nodes. Objective: We proposed to confirm the new way to predict outcome of rectal cancer patients based on positive lymph node ratio. Materials and Methods: This is a retrospective, single-centered study, collecting data of patients from January 2011 to December 2017. Data from 149 patients with rectal cancer who underwent colorectal surgery following neoadjuvant chemoradiation were analyzed. Cox regression and Kaplan-Meier survival analysis were used to determine the prognostic values of lymph node ratio, total lymph nodes harvested, and TNM staging. Results: A higher positive lymph node ratio significantly related to poorer survival rate of patients with rectal cancer who received neoadjuvant chemoradiation. There was no statistically significant difference between total lymph nodes harvested and survival rate. There was no statistical difference in survival rate among pathological stages II, IIIA, IIIB, and IIIC. Five-year survival rates after neoadjuvant chemoradiation therapy were 86.18%, 75%, 86.50%, and 83.33% in rectal cancer patients stage II, IIIA, IIIB, and IIIC, respectively. Conclusion: The lymph node ratio can be used as predictor for survival in post-surgery rectal cancer patients who received neoadjuvant chemoradiation therapy. Future research is needed to find the optimum cut-off value. Keywords: Rectal cancer; Lymph node ratio; Survival rate

Prognostic Importance of MRI-Detected Extramural Venous Invasion in Rectal Cancer: A Literature Review and Systematic Meta-Analysis.

Extramural venous invasion (EMVI) is recognized as a poor prognostic factor in rectal cancer. There are well-documented limitations associated with pathology detection of EMVI, including variable reporting and the inability to use it preoperatively to guide neoadjuvant treatment. Magnetic resonance imaging (MRI)-detected EMVI (mrEMVI) has been proposed as an imaging biomarker. This review assesses the prognostic significance of mrEMVI on survival outcomes and whether regression of mrEMVI after neoadjuvant therapy is associated with improvements in survival. An electronic search was carried out using MEDLINE and EMBASE databases using the search terms "rectum," "cancer,", "MRI," and "outcomes." A systematic review and meta-analysis were carried out in accordance with Preferred Reporting for Systematic Reviews and Meta-Analyses guidelines using Review Manager software. A qualitative review was performed. A total of 7399 articles were identified, of which 33 were relevant to the review question. After a qualitative assessment, 20 articles were included in the meta-analysis. Baseline mrEMVI positivity is associated with significantly worsened overall survival (hazard ratio [HR] 1.84; 95% confidence interval [CI], 1.33-2.54; P=.0001) and significantly worsened disease-free survival (HR 2.41; 95% CI, 2.02-2.89; P < .00001). After neoadjuvant treatment, a positive mrEMVI status is associated with a significantly worsened overall and disease-free survival. Only 3 papers specifically looked at mrEMVI regression, but the results show that persistent mrEMVI-positive status after treatment is associated with significantly worsened disease-free survival compared with a change in mrEMVI from positive to negative (HR 1.93; 95% CI, 1.39-2.68; P < .0001). A subgroup analysis of MRI-detected lymph node metastases showed no significant association with survival, with a hazard ratio of 1.33 (95% CI, 0.98-1.80; P=.06). mrEMVI is significantly associated with worsened survival outcomes, both at baseline and after neoadjuvant treatment. Additionally, there is evidence that regression of mrEMVI after neoadjuvant treatment is associated with improved survival compared with mrEMVI persistence. The findings of this review emphasize the need for accurate and consistent reporting of mrEMVI status before and after neoadjuvant treatment and support the inclusion of mrEMVI into staging systems preferentially over lymph node metastases.

Prognostic Significance of EMVI in Rectal Cancer in a Tertiary Cancer Hospital in India.

Background Presence of extramural venous invasion (EMVI) is a poor prognostic factor for rectal cancer as per literature. However, India-specific data are lacking. Aim The aim of the study is to determine the prognostic significance of EMVI in locally advanced rectal cancer on baseline MRI. Materials and Methods We retrospectively reviewed 117 MRIs of operable non-metastatic locally advanced rectal cancers in a tertiary cancer institute. Three dedicated oncoradiologists determined presence or absence of EMVI, and its length and thickness, in consensus. These patients were treated as per standard institutional protocols and followed up for a median period of 37 months (range: 2–71 months). Kaplan-Meier curves (95% CI) were used to determine disease-free survival (DFS), distant-metastases free survival (DMFS), and overall survival (OS). Univariate analysis was performed by comparing groups with log-rank test. Results EMVI positive cases were 34/114 (29%). More EMVI-positive cases developed distant metastasis compared with EMVI-negative cases (14/34–41% vs. 22/83–26%). The difference, however, was not statistically significant ( p = 0.146). After excluding signet-ring cell cancers ( n = 14), EMVI showed significant correlation with DMFS ( p = 0.046), but not with DFS or OS. The median thickness and length of EMVI was 6 and 14 mm, respectively in patients who developed distant metastasis, as compared with 5 and 11 mm in those who did not, although this difference was not statistically significant. Conclusion EMVI is a predictor of distant metastasis in locally advanced non-metastatic, non-signet ring cell rectal cancers. EMVI can be considered another high-risk feature to predict distant metastasis.

M6A "Writer" Gene METTL14: A Favorable Prognostic Biomarker and Correlated With Immune Infiltrates in Rectal Cancer.

Rectal cancer (RC) is the leading cause of tumor-related death among both men and women. The efficacy of immunotherapy for rectal cancer is closely related to the immune infiltration level. The N6-methyladenosine (m6A) modification may play a pivotal role in tumor-immune interactions. However, the roles of m6A-related genes in tumor-immune interactions of rectal cancer remain largely unknown. After an evaluation on the expression levels of m6A-related genes and their correlations with the prognosis of rectal cancer patients, we found that METTL14 was the only gene to be significantly correlated with prognosis in rectal cancer patients. Therefore, we further observed the impact of METTL14 expression and m6A modification on the immune infiltration in rectal cancer. Our study indicates that low expression of the m6A “writer” gene METTL14 in rectal cancer may lead to the downregulation of m6A RNA modification, thus reducing the level of immune cell infiltration and resulting in poor prognosis. METTL14 expression level is an independent prognostic factor in rectal cancer and is positively correlated with the immune infiltration level. Our study identified METTL14 as a potential target for enhancing immunotherapy efficacy in rectal cancer.