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Preoperative determination of lymph node (LN) status is crucial in treatment planning for rectal cancer. This study prospectively evaluated the risk factors for lymph node metastasis (LNM) at staging and restaging based on a node-by-node pairing between MRI imaging findings and histopathology and constructed nomograms to evaluate its diagnostic value.From July 2021 to July 2022, patients with histopathologically verified rectal cancer who underwent MRI before surgery were prospectively enrolled. Histological examination of each LN status in the surgical specimens and anatomical matching with preoperative imaging. Taking histopathological results as the gold standard, federating clinical features from patients and LN imaging features on MRI-T2WI. Risk factors for LN metastasis were identified by multivariate logistic regression analysis and used to create a nomogram. The performance of the nomograms was assessed with calibration plots and bootstrapped-concordance index and validated using validation cohorts.A total of 500 target LNs in 120 patients were successfully matched with node-by-node comparisons. A total of 353 LNs did not receive neoadjuvant therapy and 147 LNs received neoadjuvant chemoradiotherapy (neoCRT). Characterization of LNs not receiving neoadjuvant therapy and multivariate regression showed that the short diameter, preoperative CEA level, mrT-stage, border contour, and signal intensity were associated with a high risk of LN metastasis (P 0.05). The nomogram predicted that the area under the curve was 0.855 (95% CI, 0.794-0.916) and 0.854 (95% CI, 0.727-0.980) in the training and validation cohorts, respectively. In the neoadjuvant therapy group, short diameter, ymrT-stage, internal signal, and MRI-EMVI were associated with LN positivity (P 0.05), and the area under the curves using the nomogram was 0.912 (95% CI, 0.856-0.968) and 0.915 (95% CI, 0.817-1.000) in two cohorts. The calibration curves demonstrate good agreement between the predicted and actual probabilities for both the training and validation cohorts.Our nomograms combined with preoperative clinical and imaging biomarkers have the potential to improve the prediction of nodal involvement, which can be used as an essential reference for preoperative N staging and restaging of rectal cancer.

Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the potential to be novel biomarkers for cancer diagnosis. This study aims to summarize the role of exosomal circRNAs in cancer diagnosis by a meta-analysis.A comprehensive literature search was conducted up to July 2021 in PubMed, Web of Science, EMBASE, and Cochrane Database. To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance.Ten eligible studies with 514 controls and 557 patients were included in this diagnostic meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.75 (95% CI: 0.65-0.83), 0.84 (95% CI, 0.78-0.89), 5.87 (95% CI, 3.67-9.38), 0.28 (95% CI, 0.19-0.40), and 21.15 (95% CI, 10.25-43.68), respectively. The AUC was 0.89 (95% CI, 0.86-0.91). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability of 20%, the post probability positive, the post probability negative were 59% and 6%, respectively.Our results suggested that exosomal circRNAs might serve as powerful biomarkers in detecting cancers with high sensitivity and specificity. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

Background Total neoadjuvant therapy is a promising treatment for locally advanced rectal cancer, utilizing either short-course radiotherapy or long-course chemoradiotherapy, but their relative efficacy remains unclear. The aim of this Bayesian network meta-analysis was to investigate clinical outcomes amongst patients receiving total neoadjuvant therapy with short-course radiotherapy or long-course chemoradiotherapy, and those receiving long-course chemoradiotherapy alone. Methods A systematic literature search was performed. All studies that compared at least two of these three treatments for locally advanced rectal cancer were included. The primary endpoint was the pathological complete response rate, and survival outcomes were adopted as secondary outcomes. Results Thirty cohorts were included. Compared with long-course chemoradiotherapy, both total neoadjuvant therapy with long-course chemoradiotherapy (OR 1.78, 95 per cent c.i. 1.43 to 2.26) and total neoadjuvant therapy with short-course radiotherapy (OR 1.75, 95 per cent c.i. 1.23 to 2.50) improved the pathological complete response rate. Similar benefits were observed in the sensitivity and subgroup analyses, except for short-course radiotherapy with one to two cycles of chemotherapy. No significant differences in survival outcomes were found amongst the three treatments. Long-course chemoradiotherapy with consolidation chemotherapy (HR 0.44, 95 per cent c.i. 0.20 to 0.99) exhibited higher disease-free survival than long-course chemoradiotherapy alone. Conclusion Compared with long-course chemoradiotherapy, both short-course radiotherapy with greater than or equal to three cycles of chemotherapy and total neoadjuvant therapy with long-course chemoradiotherapy can improve the pathological complete response rate, and long-course chemoradiotherapy with consolidation chemotherapy may lead to a marginal benefit in disease-free survival. The pathological complete response rate and survival outcomes are similar for total neoadjuvant therapy with short-course radiotherapy or long-course chemoradiotherapy.

Antibody information.

CAFs promote peritoneal metastasis of ovarian cancer (S1); CSIOVDB analysis of CXCL14 expression in ovarian cancer (S2); CXCL14 inhibition attenuates ovarian cancer metastasis in vivo (S3); LINC00092 silencing induced increase of cleaved caspase-3 in specimens of ovarian cancer peritoneal metastasis model in nude mice (S4); Enhanced LINC00092 expression in ovarian cancer cells could offset the metastasis-attenuating effects of CXCL14 knockdown in CAFs (S5); RIP experiments were performed using an antibody against EZH2 on extracts from A2780s cell line (S6); Correlation between LINC00092 level and PFKFB2 expression in ovarian cancer (S7); PFKFB2 in the maintenance of metastatic phenotype of ovarian cancer (S8); Enhanced LINC00092 expression in ovarian cancer cells could offset the metastasis-attenuating effects of CXCL14 knockdown in CAFs (S9); The necessity and sufficiency of CAF-secreted CXCL14, LINC00092 in ovarian cancer cells and PFKFB2 in ovarian cancer cells in the process of metastasis formation in ovarian cancer (S10); A schematic model summarizing the proposed mechanistic model of the a positive feedback loop between CXCL14-positive CAFs and ovarian cancer cells favorable for cancer metastasis by manipulating Warburg effect (S11).

Description of additional methods and procedures used in the study. Also includes Supplemental References.

The majority of patients with epithelial ovarian cancer are diagnosed at a late stage when the peritoneal metastases exist; however, there is little knowledge of the metastatic process in this disease setting. In this study, we report the identification of the long noncoding RNA LINC00092 as a nodal driver of metastatic progression mediated by cancer-associated fibroblasts (CAF). Prometastatic properties of CAFs in vitro and in vivo were found to associate with elevated expression of the chemokine CXCL14. In clinical specimens, elevated levels of CXCL14 in CAFs also correlated with poor prognosis. Notably, CXCL14-high CAFs mediated upregulation of LINC00092 in ovarian cancer cells, the levels of which also correlated with poor prognosis in patients. Mechanistic studies showed that LINC00092 bound a glycolytic enzyme, the fructose-2,6-biphosphatase PFKFB2, thereby promoting metastasis by altering glycolysis and sustaining the local supportive function of CAFs. Overall, our study uncovered a positive feedback loop in the metabolism of CXCL14-positive CAFs and ovarian cancer cells that is critical for metastatic progression. Cancer Res; 77(6); 1369–82. ©2017 AACR.

Aim: The lymph node status plays an important role in rectal cancer, which depends on adequate lymph node harvest. Lymph node stain techniques increase the lymph node harvest. The aim of this prospective study is to investigate which subgroups of lymph nodes harvested were increased mostly. Methods: From May 2020 to May 2022, 172 stage II-III rectal cancer patients were randomized to methylene blue (MB) stained group or unstained group to retrieve the lymph nodes. Methylene blue solution was injected into the inferior mesenteric artery, we dissected lymph nodes by palpation and sight. The lymph nodes were divided into 3 groups depending on the anatomy (main lymph nodes, superior rectal and perirectal lymph nodes (SPLNs), and pericolic lymph nodes located beyond 10 cm proximal to the tumor), and 3 groups depending on the short diameter of the nodes (big: ≥5mm, small: 5mm~2mm, mini: ≤2mm). Results:The number of lymph nodes harvested with MB was significantly higher (22.0(14.8,32.0) vs 14.5 (11.0,22.0); p Conclusion:Intra-arterial injection of MB can significantly increase the number of lymph nodes harvested in rectal cancers, especially those mini lymph nodes. However, methylene blue staining did not significantly increase the number of positive lymph nodes and the proportion of patients with more than 12 lymph nodes, or affect lymph node staging accuracy after radical resection of rectal cancer

BACKGROUND This study aimed to evaluate the perioperative, pathological and oncological outcomes of open versus laparoscopic total mesorectal excision (TME) plus lateral lymph node dissection (LLND) for mid- and low- rectal cancer using propensity score matching. METHODS Between September 2009 and December 2018, consecutive patients who underwent open or laparoscopic TME plus LLND were collected. Based on the propensity score matching analysis, laparoscopic TME plus LLND was compared with open TME plus LLND for the perioperative, pathological, and oncological outcomes. RESULTS A total of 77 patients were collected. There were 13 patients who underwent open TME plus LLND (open group) and 64 patients who underwent laparoscopic TME plus LLND (laparoscopic group). After propensity score matching, 13 patients in the open group were matched to 39 patients in the laparoscopic group (1:3). The laparoscopic group had a significantly shorter length of incision (5 cm vs. 20 cm, p

The confinement of the pelvis and the complexity of pelvic fascial anatomy still pose difficulties in achieving good quality surgery for rectal cancer. We aimed to introduce small vessels on the mesorectal fascia and the parietal pelvic fascia as novel landmarks to aid in the identification of the inter-fascial dissection plane. Besides, the perioperative, survival, and functional outcomes of this surgical technique were reported. We first described that small vessels running on the mesorectal fascia and the parietal pelvic fascia showed distinctive features, which included (1) small vessels on the parietal fascia took the same orientation as the ureter or the sympathetic and parasympathetic nerve; (2) small vessels on the mesorectal fascia were coursing cranially and medially on the anterolateral aspect, and medially and caudally on the posterolateral aspect; (3) small vessels on the mesorectal fascia became invisible at the interface between the pelvic wall and the mesorectal fascia. These features could be applied in fascial identification and separation. Then, we reported the outcomes of low rectal cancer surgery with small vessels-guided technique. From 2013 to 2016, a consecutive series of 310 patients with low rectal cancer underwent laparoscopic total mesorectal excision with small vessels-guided technique. The positive rate of circumferential resection margin was 3.2%, and complete mesorectal excision was achieved in 97.8% (303/310) patients. The 3-year overall survival, disease-free survival, and local recurrence rates were 89.4%, 79.7%, and 2.6%, respectively. The urinary function was considered normal in 96.8% of patients, with a moderate dysfunction in 3.2% of patients. Besides, 29.5% of male patients occurred sexual function injury. Distinctive features of small vessels on the parietal pelvic fascia and the mesorectal fascia can serve as novel and additive landmarks in guiding precise inter-fascial dissection for low rectal cancer.

Lymph node status is critical for staging rectal cancer and determining neoadjuvant therapy regimens. Establishing a matching between imaging and histopathological lymph nodes is fundamental for predicting lymph node status. This study reports a technique to achieve node-by-node pairing of mesorectal lymph nodes between imaging findings and histopathology.Fifty-two patients with histopathologically verified rectal cancer underwent magnetic resonance imaging before surgery. The status of each lymph node in the surgical specimens was analyzed histopathologically and matched with preoperative imaging after the operation.A total of 346 mesorectal lymph nodes were located on imaging evaluation, of which 313 were confirmed histopathologically, and 33 were unmatched. The total success rate of the technique was 90.5%. Node-by-node analysis revealed 280 benign and 33 malignant nodal structures.The technique to match mesorectal lymph node imaging findings to histopathology was feasible and effective. It simplified the technical method and had a reasonable success matching rate, which could provide a standardized approach for obtaining a prospective correlation between imaging and histological findings, supporting all subsequent related studies at the level of mesorectal lymph nodes.

Purpose To develop a model for predicting response of Total Neoadjuvant Treatment (TNT) for patients with locally advanced rectal cancer (LARC) based on baseline MRI and clinical data using artificial intelligence method.Methods Patients with LARC who received TNT were enrolled retrospectively. We defined two groups of response to TNT as pCR vs non-pCR (Group 1), and high sensitivity vs moderate sensitivity vs low sensitivity (Group 2). We extracted and selected clinical and radiomic features on baseline T2WI. Then we built logistic regression (LR) models and deep learning (DL) models. Receiver operating characteristic (ROC) curves analysis was performed to assess predictive performance of models.Results Eighty-nine patients were assigned to the training cohort, and 29 patients were assigned to the testing cohort randomly. Four predictive models were built. The area under the ROC curve (AUC) of LR models, which were predictive of high sensitivity and pCR, were 0.853 and 0.866. While AUC of DL models were 0.829 and 0.838. The accuracy of the models with group 1 are higher than group 2. Conclusion There was no significant difference between LR model and DL model. The prediction model constructed by the grouping method of pCR vs non-pCR has a higher accuracy.

The aim of this study was to identify the indications and oncological outcomes of selective lateral lymph node dissection (sLLND) in rectal cancer patients. A retrospective study was conducted on consecutive patients with rectal cancer who had standard total mesorectal excision and sLLND at our institution. Clinicopathological characteristics and oncological outcomes were analyzed. We performed subgroup analysis and multivariate analysis based on patients with or without preoperative chemoradiotherapy to identify the related risk factors. A total of 77 consecutive patients with TME and sLLND were included. Twenty-two (28.6%) patients with pathological positive lateral lymph nodes metastasis (LLNM) were identified. Forty-seven (61%) patients accepted neoadjuvant chemoradiotherapy (nCRT). The pretreatment maximum short-axis diameters of LLN (≥ 8 mm) were the independent risk factors for LLNM among patients with LLN ≥ 5 mm. Lymph node metastasis were significantly higher in patients with pretreatment LLN ≥ 8 mm than in patients with LLN 5–8 mm (63% vs. 10%, p

Introduction Lateral pelvic recurrence can be a cause of local failure after surgery for low rectal cancer. Lateral lymph node dissection is often performed in East Asia for patients with enlarged lateral lymph nodes or because of the presence of risk factors. However, the outcomes of the conventional lateral lymph node dissection are unsatisfactory, with a considerably high local recurrence rate for patients with positive lateral nodes. Here, we introduce a modified technique to improve lateral nodes clearance. Technique This modified technique has 4 key steps: 1) separation of the ureterohypogastric nerve fascia medially, 2) identification of the visceral pelvic fascia and dissection along the inferior vesical or vaginal veins down to the pelvic floor, 3) division of the distal ends of visceral vessels according to the orientation of ureterohypogastric nerve fascia and visceral pelvic fascia for better nerve preservation, and 4) en bloc dissection through a lateral approach over the surfaces of the sacral plexus and piriformis muscle to reveal the course of distal internal iliac vessels before the division of visceral veins. Results Twenty-nine patients underwent laparoscopic lateral lymph node dissection successively with no conversion. The median blood loss for each lateral procedure was 37.5 mL (range, 0-300.0 mL). Eleven lateral nodes (median; range, 1-22 lateral nodes) were harvested for each lateral side. There was no perioperative mortality, and 4 patients developed major complications (Clavien-Dindo III-IV). Conclusion This modified technique characterized by the routine division of visceral vessels based on ureterohypogastric nerve fascia and visceral pelvic fascia is feasible and safe. It provides good lymph node harvest, autonomic nerve preservation, and improved bleeding control. Additional investigation is warranted to evaluate the safety, functional outcomes, and oncologic outcomes.

Hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) following cytoreductive surgery (CRS) has been applied for peritoneal metastasis (PM) from colorectal cancer (CRC). This study aimed to compare oxaliplatin (OX) with mitomycin C (MMC) in HIPEC for PM from CRC in surgical and survival outcomes. A systematic literature search was performed in PubMed and Ovid databases for studies comparing OX with MMC in HIPEC for PM from CRC. The last search was performed on June 21, 2020. Eleven articles published between 2006 and 2020 with 2091 patients were included. When compared with MMC group, the OX group showed significantly higher rate of major complications (P = 0.006, OR = 1.57, 95% CI [1.14, 2.16], I2 = 0%). Besides, no significant difference was observed between the two groups for survival outcomes, regardless of 3-year overall survival (P = 0.98, OR = 1.00, 95% CI [0.83, 1.22], I2 = 0%), 3-year disease-free survival (P = 0.98, OR = 1.00, 95% CI [0.83, 1.22], I2 = 0%), or 5-year overall survival (P = 0.91, OR = 1.01, 95% CI [0.81, 1.26], I2 = 0%). OX and MMC could achieve comparable survival in HIPEC for PM from CRC. However, in consideration of the high incidence of major complication in OX group, MMC might be the safer one in clinical routines.

Limited studies have been reported about the function of low level of microsatellite instability (MSI-L) in cancer. The aim of our study is to unveil the prognostic role of MSI-L in gastric cancer (GC). One hundred nine patients with locally advanced GC (T3-4a, N+, M0) who underwent neoadjuvant chemotherapy plus gastrectomy with extended (D2) lymph node dissection were collected. Clinicopathological characteristics, tumour regression score, disease-free survival (DFS), and overall survival (OS) were analysed and correlated with the MSI status. The MSI status of 96 patients was identified (7 (7.3%) with MSI-H, 12 (12.5%) with MSI-L, and 77 (80.2%) with MSS). MSI-L was significantly correlated with perineural invasion (P = 0.009) and decreased MUC5AC expression (P = 0.042). Poor response to neoadjuvant chemotherapy in MSI-L patients (83.3% assessed as poor response) was observed (P = 0.501). Compared with patients with MSS tumours, patients with MSI-L tumours showed poor DFS (P = 0.018) with a hazard ratio (HR) of 2.839 (95% CI 1.131-7.124, P = 0.026) from multivariable cox regression analysis. However, this was not associated with OS (P = 0.063). MSI-L is an independent poor prognostic biomarker for the locally advanced gastric cancer treated with neoadjuvant chemotherapy. Further studies with larger sample sizes are needed for validation.

Background This study aims to determine the real incidence of pericolic lymph nodes metastasis beyond 10 cm proximal to the tumor (pPCN) and its prognostic significance in rectal cancer patients. Methods Consecutive patients with rectal cancer underwent curative resection between 2015 and 2017 were included. Margin distance was marked and measured in vivo and lymph nodes were harvested on fresh specimens. Clinicopathological characteristics and oncological outcomes (3-year overall survival (OS) and disease-free survival (DFS)) were analyzed between patients with pPCN and patients without pPCN (nPCN). Results There were 298 patients in the nPCN group and 14 patients (4.5%) in pPCN group. Baseline characteristics were balanced except more patients received preoperative or postoperative chemoradiotherapy in pPCN group. Preoperative more advanced cTNM stage (log-rank p = 0.005) and intraoperative more pericolic lymph nodes beyond 10 cm proximal to the tumor (PCNs) (log-rank p = 0.002) were independent risk factors for pPCN. The maximum short-axis diameter of mesenteric lymph nodes ≥8 mm was also contributed to predicting the pPCN. pPCN was an independent prognostic indicator and associated with worse 3-year OS (66% vs 91%, Cox p = 0.033) and DFS (58% vs 92%, Cox p = 0.012). Conclusion The incidence of pPCN was higher than expected. Patients with high-risk factors (cTNM stage III or more PCNs) might get benefits from an extended proximal bowel resection to avoid residual positive PCNs.

Background: Ureteral injury is the most common urological complication of pelvic surgery. Lateral lymph node dissection (LLND) is a technically demanding procedure by laparoscopy after neoadjuvant chemoradiotherapy (nCRT), which may increase the risk of ureteral injury because the ureter and hypogastric fascia must be dissected from the vesicohypogastric fascia to preserve them. Case presentation: Here, we present a case of delayed ureteral leakage occurring in a 63-year-old male patient who underwent laparoscopic abdominoperineal resection (APR) with right LLND after nCRT. Ureteral reimplantation (vesicoureteric anastomosis) was performed in this patient due to the failure of the placement of the double J stent. Conclusions: Our case shows that ureteral leakage may occur in the pelvic segment of the ureter in the patient who underwent laparoscopic LLND, especially received preoperative radiotherapy or chemoradiotherapy.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. CRC recurrence and metastasis cause poor prognosis. ANGPTLs (angiopoietin-like proteins) are a family of proteins that are widely involved in metabolic disease and tumorigenesis. The roles of ANGPTLs in CRC are still controversial and deserve further research. In this study, several databases were employed to explore the expression profiles, prognostic values, genetic alterations, potential biological function, and immune infiltration correlation of ANGPTLs in CRC. The expression of ANGPTL4 was significantly positively correlated with the stage of CRC. Therefore, cell and molecular experiments were further performed to explore the roles of ANGPTL4. Our results showed that the transcriptions of ANGPTLs in colon cancer and rectal cancer tissues were lower than those in normal tissues, but the protein expression varied among different ANGPTLs. In addition, the high expression of ANGPTLs led to a relatively poor oncological outcome. Specifically, the expression of ANGPTL4 is significantly positively correlated with the stage of CRC. Further investigation revealed that ANGPTLs are mainly involved in signal transduction and the regulation of transcription, while KEGG pathway analyses demonstrated pathways in cancer. Additionally, we also observed that ANGPTL4 could promote the proliferation and migration of CRC cells, and four specific small molecule compounds had potential ANGPTL4-binding capabilities, suggesting the clinical application of these small molecule compounds on CRC treatment. Our findings imply the prognostic values and potential therapeutic targets of ANGPTLs in CRC.

Exosomes or other extracellular vesicles released from cells play an important role in cell-to-cell communication by transferring bio-information (DNA, coding/non-coding RNA, and proteins), which indicates parental cell status to recipient cells in the extracellular environment. Increasingly, evidence shows that tumor-derived exosomes mediate tumor pre-metastatic niche (PMN) remodeling to establish a supportive and receptive niche to promote tumor cell colonization and metastasis. Uptake of genetic information by target cells in the extracellular environment triggers epigenetic changes that contribute to PMN formation. Here, we provide a comprehensive overview of the current understanding of exosomes-mediated reprogramming of cells in PMN formation.

Background With local recurrence of rectal cancer continuing to decrease, distant recurrence is becoming a major concern, especially for patients with low- and intermediate-risk stage II/III rectal cancer. Therefore, a new treatment strategy is warranted for these patients. This single-arm phase II trial aimed to assess the effect of neoadjuvant chemotherapy (NCT) in low- and intermediate-risk stage II/III rectal cancer and explore candidate radiological and clinical parameters for early prediction of tumour response after two cycles of CAPOX. Methods Patients with mid–low stage II/III rectal cancer with low and intermediate risk were examined. The primary outcome was defined as a clinicopathological response by integrating tumour longitudinal length reduction (TLLR) on MRI into pathological tumour regression grade (TRG). After completing NCT, patients with TRG0–2 and TRG3 with a TLLR rate greater than 30 per cent were considered to be responders. Secondary outcomes included pathological complete response (pCR), adverse events and local and distant recurrence. Results This study enrolled 61 eligible patients. No patient was converted to neoadjuvant chemoradiotherapy owing to tumour progression. The clinicopathological response and pCR rates were 78.7 and 21.3 per cent respectively. After two cycles of CAPOX, TLLR, TRG on MRI, and mucosal lesion regression grade on endoscopy had potential discriminative ability (area under the curve greater than 0.7) for predicting both clinicopathological and pathological response. Conclusion NCT alone achieves good tumour response rates in patients with low- and intermediate-risk stage II/III rectal cancer, and predicting tumour response to NCT is feasible at an early treatment phase. Registration number NCT03666442 (http://www.clinicaltrials.gov).

OBJECTIVE The aim of this study was to compare stage II/III rectal cancers with or without high-risk factors, and evaluate the effect of neoadjuvant radiotherapy (NRT) in these 2 cohorts. BACKGROUND NRT is often used in stage II/III rectal cancers to improve local control, while not affecting overall survival. However, good-quality surgery without NRT may also achieve good local control in selected patients. METHODS According to risk-stratification criteria and clinical staging, consecutive eligible participants of stage II/III rectal cancer were preoperatively classified into patients with (high-risk) or without (low-risk) high-risk factors. Both groups were respectively randomized to receive either short-course radiotherapy (SCRT) + total mesorectal excision (TME) or TME alone, forming the following 4 groups: high-risk patients with (HiR) or without (HiS) radiation, and low-risk patients with (LoR) or without (LoS) radiation. The primary endpoint was local recurrence. The secondary endpoints included overall survival, disease-free survival, distant recurrence, quality of surgery, and safety (NCT01437514). RESULTS In total, 401 patients were analyzed. With a median 54 months' follow-up, low-risk patients obtained better 3-year cumulative incidence of local recurrence (2.2% vs 11.0%, P = 0.006), overall survival rate (86.9%vs 76.5%, P = 0.002), disease-free survival rate (87.0% vs 67.9%, P < 0.001), and cumulative incidence of distant recurrence (12.5% vs 29.4%, P < 0.001) than high-risk patients. With regard to 3-year cumulative incidence of local recurrence, no differences were observed between the LoR and LoS groups (1.2% vs 3.0%, P = 0.983) or the HiR and HiS groups (12.9% vs 8.9%, P = 0.483). CONCLUSIONS AND RELEVANCE Stratification of stage II/III rectal cancers according to risk factors to more precise subclassifications may result in noteworthy differences in survivals and local pelvic control. An extremely low cumulative incidence of local recurrence and survivals in low-risk patients can be achieved with upfront good quality of surgery alone. This trial, owing to the insufficient power, could not prove the noninferiority of surgery alone, but suggest a discriminative use of NRT according to clinical risk stratification in stage II/III rectal cancer.

A first-line biologic treatment for metastatic colorectal cancer (mCRC) is still controversial. We, therefore, performed a meta-analysis to determine the efficacy of first-line cetuximab versus bevacizumab for RAS and BRAF wild-type mCRC. In March 2018, an electronic search of the following biomedical databases was performed: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov and Web of Knowledge. Randomized controlled trials (RCTs) and prospective or observational cohort studies (OCSs) were included. Subgroup analyses of all RCTs were performed in all outcomes. All statistical analyses were performed using RevMan software 5.3. Two RCTs and three OCSs, involving a total 2576 patients, were included. The meta-analysis reported that cetuximab was associated with a longer overall survival (OS) [HR 0.89, 95% CI (0.81–0.98); p = 0.02], a higher ORR [RR 1.11, 95% CI (1.03–1.19); p = 0.006], higher complete response [RR 3.21, 95% CI (1.27–8.12); p = 0.01] and a greater median depth of response than bevacizumab. However, no significant difference was observed between cetuximab and bevacizumab groups for PFS, DCR, partial response, progressive disease, curative intent metastasectomy, EORR and incidence of grade 3 or higher adverse events. In the subgroup meta-analyses of the RCTs, inconsistent results compared to the main analysis, however, were found, in the ORR, DCR and curative intent metastasectomy. The current evidence indicates that compared to bevacizumab treatment, cetuximab provides a clinically relevant effect in first-line treatment against mCRC, at the cost of having lower stable disease.

Ganlu Ouyang,1 Xibiao Yang,2 Xiangbing Deng,3 Wenjian Meng,3 Yongyang Yu,3 Bing Wu,2 Dan Jiang,4 Pei Shu,1 Ziqiang Wang,3 Jin Yao,2 Xin Wang1 1Department of Radiation Oncology/Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Radiation Oncology/Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 of Wainan Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of ChinaTel +86 18980602291Email wangxin213@sina.comPurpose: To investigate the potential value of magnetic resonance imaging (MRI) in predicting response relevance to total neoadjuvant treatment (TNT) in locally advanced rectal cancer.Methods: We analyzed MRI of 71 patients underwent TNT from 2015 to 2017 retrospectively. We categorized the response of TNT as CR (complete response) vs non-CR, and high vs moderate vs low sensitivity. Logistic regression analysis was used to identify the best predictors of response. Diagnostic performance was assessed using receiver operating characteristic curve analysis.Results: Post-ICT (induction chemotherapy) ∆TL (tumor length), post-CRT (concurrent chemoradiotherapy) ∆LNN (the numbers of lymph node metastases), post-CCT (consolidation chemotherapy) ∆SDWI (maximum cross-sectional area of tumor on diffusion-weighted imaging), post-CCT ADCT (the mean apparent diffusion coefficient values of tumor) and post-CCT ∆LNV (volume of lymph node) were the best CR predictors. Post-ICT ∆TL, post-CRT EMVI (extramural vascular invasion) and post-CCT ∆ST2 (S on T2-weight) were the best significant factors for high sensitivity.Conclusion: Post-ICT ∆TL may be an early predictor of CR and high sensitivity to TNT. Dynamic analysis based on MRI between baseline and post-CCT could provide the most valuable prediction of CR. The grouping modality of CR vs non-CR may be more suitable for treatment response prediction than high vs moderate vs low sensitivity.Keywords: rectal cancer, total neoadjuvant treatment, MRI, response, TRG

Background This study aimed to explore the surgical outcomes of laparoscopic total mesorectal excision (TME) combined with en-bloc seminal vesicle resection (SVR) and partial prostate resection (PPR) for locally advanced rectal cancer (LARC) after chemoradiotherapy (CRT). Methods Patients receiving TME combined with en-bloc SVR and PPR for LARC after CRT from 2014 to 2019 were enrolled retrospectively. Patients' characteristics and surgical outcomes were collected and analysed. Results A total of six male patients were enrolled in this study. Among them, four patients proved to be T4b stage including three Denonvilliers fascia invasion and one seminal vesicle invasion. R0 resection was achieved in all patients. With a median follow-up time of 24 months, no local recurrence was observed. Conclusion It is safe and feasible to perform laparoscopic TME combined with en-bloc SVR and PPR in selected LARC patients after neoadjuvant CRT. It can provide a safe circumferential resection margin and R0 resection. More studies are warranted to improve the diagnostic accuracy for T4b stage after CRT and avoid unnecessary extended resection.

Additional file 3: Supplemental Table 3. Literature concerned the relationship between the length of proximal bowel resection and oncological outcomes in patients with colorectal cancer.

Additional file 1: Supplement Table 1. Cox regression analysis of prognostic factors for overall survival and disease-free survival in patients with IV stage rectal cancer.