Search

Objective To compare the short-term efficacy indicators of laparoscopic technique and open surgery in patients with rectal cancer surgery, and to further evaluate the safety and efficacy of laparoscopic rectal cancer surgery. Methods This study adopted a prospective multicenter, open-label, non-randomized concurrent control method to analyze patients who received rectal cancer surgery from 10 colorectal tumor centers across the country from January 2017 to December 2018. The two groups of patients received laparoscopic-assisted surgery and conventional open surgery respectively. All surgeons were selected according to relevant standards and participated in the two groups of operations at the same time. Comprehensive evaluation and analysis of the operation and postoperative recovery, postoperative pathological results, survival information, postoperative related functional scores and other indicators. Results In the open surgery group, the proportion of tumors with a maximum diameter of more than 5 cm was higher (χ2 = 0.089, P = 0.018), and the proportion of T4 was higher (χ2 = 0.478, P P P P P = 0.105), but the incidence of incision infection was lower in the laparoscopy group (χ2 = 0.19, P P = 0.170). Multivariate analysis suggested that intraoperative blood loss, T stage, N stage, nerve invasion, and postoperative sepsis were independent prognostic factors for disease-free survival. Wexner score, IPSS score and LARS score were not statistically different between the two groups. Conclusion The pathological results and short-term outcomes of laparoscopic surgery for rectal cancer are comparable to those of conventional open surgery, and laparoscopic surgery is safe and feasible for rectal cancer patients.

Background Although surgical resection combined with neoadjuvant radiotherapy can reduce the local recurrence rate of rectal cancer, only some patients benefit from neoadjuvant radiotherapy. Therefore, how to screen out rectal cancer patients who are sensitive or resistant to radiotherapy has great clinical significance. Results We found that DSTN was highly expressed (P DSTNin neoadjuvant radiotherapy resistant tissues of rectal cancer had a shorter disease-free survival (P DSTNexpression increased after methyltransferase inhibitor inhibited DNA methylation in DNA promoter region of colorectal cancer cells (P DSTN could promote the sensitivity of colorectal cancer cells to radiotherapy, and overexpression of DSTNcould promote the resistance of colorectal cancer cells to radiation (P DSTN. The expression of β-catenin was highly expressed in radiotherapy resistant tissues, and there was a linear correlation between the expression of DSTN and β-catenin (P DSTNcould bind to β-catenin and increase the stability of β-catenin. Conclusion The degree of DNA methylation and the expression level of DSTN can be used as a biomarker to predict the sensitivity of neoadjuvant radiotherapy for rectal cancer, and DSTN and β-catenin are also expected to become a reference and a new target for the selection of neoadjuvant radiotherapy for rectal cancer.

Background Anastomotic leakage (AL) is one of the commonest and most serious complications after rectal cancer surgery. The previous analyses on predictors for AL included small-scale patients, and their prediction models performed unsatisfactorily. Methods Clinical data of 5,220 patients who underwent anterior resection for rectal cancer were scrutinized to create a prediction model via random forest classifier. Additionally, data of 836 patients served as the test dataset. Patients diagnosed with AL within 6 months' follow-up were recorded. A total of 20 candidate factors were included. Receiver operating characteristic (ROC) curve was conducted to determine the clinical efficacy of our model, and compare the predictive performance of different models. Results The incidence of AL was 6.2% (326/5,220). A multivariate logistic regression analysis and the random forest classifier indicated that sex, distance of tumor from the anal verge, bowel stenosis or obstruction, preoperative hemoglobin, surgeon volume, diabetes, neoadjuvant chemoradiotherapy, and surgical approach were significantly associated with AL. After propensity score matching, the temporary stoma was not identified as a protective factor for AL (P=0.58). Contrastingly, the first year of performing laparoscopic surgery was a predictor (P=0.009). We created a predictive random forest classifier based on the above predictors that demonstrated satisfactory prediction efficacy. The area under the curve (AUC) showed that the random forest had higher efficiency (AUC =0.87) than the nomogram (AUC =0.724). Conclusions Our findings suggest that eight factors may affect the incidence of AL. Our random forest classifier is an innovative and practical model to effectively predict AL, and could provide rational advice on whether to perform a temporary stoma, which might reduce the rate of stoma and avoid the ensuing complications.

Conventional proteomic approaches neglect tissue heterogeneity and spatial localization information. Laser capture microdissection (LCM) can isolate specific cell populations or histological areas from heterogeneous tissue specimens while preserving spatial localization information. Formalin-fixed paraffin-embedded (FFPE) is currently a standardized method for long-term stable preservation of clinical tissue specimens. However, spatially resolved proteomics (SRP) studies of FFPE tissues by combined LCM and mass spectrometry (MS)-based proteomics face challenges, such as formalin-induced protein crosslinking limits protein extraction and digestion, protein loss during sample preparation, and the detectability of MS for trace tissues. Therefore, it is necessary to specifically develop SRP sample preparation methods and MS methods suitable for trace FFPE tissues. Here, we provide an SRP method suitable for trace FFPE tissues produced by LCM, termed LCM-Magnetic Trace Analysis (LCM-MTA), which can significantly increase the sensitivity, recovery, and integrality of SRP. The starting material has been reduced to about 15 cells, which resolution is comparable to existing spatially resolved transcriptome (SRT). We also apply our LCM-MTA into SRP studies on clinical colorectal cancer (CRC) tissues and accurately distinguish the functional differences of different cell types. In conclusion, LCM-MTA is a convenient, universal, and scalable method for SRP of trace FFPE tissues, which can be widely used in clinical and non-clinical research fields.

Nicotinamide N-methyltransferase (NNMT), a major metabolic regulator, has been identified as a predictor of cancer prognosis in ovarian and colorectal cancers. The study aims to evaluate the significance of stromal NNMT in gastric cancer (GC). Expression of stromal NNMT in 612 GC and 92 non-malignant tissues specimens was investigated by immunohistochemistry (IHC). The association between NNMT expression and occurrence of cancer or patient outcome was further analyzed, and the factors contributing to disease prognosis were evaluated by multiple Cox models. Stromal NNMT expression was higher in the malignant tissue ( p

e15603 Background: Neoadjuvant chemoradiotherapy (nCRT) not only could bring tumor downsizing and downstaging but also could achieve clinical complete response (cCR) or pathological complete response (pCR). Although immunotherapy benefits MSI-H/dMMR rectal cancer patients, little response is observed in MSS/pMMR patients. Several clinical trials including VOLTAGE trial demonstrated that a combination of PD-1 inhibitor and nCRT could result in a promising pathological response even in MSS/pMMR patients. But the elucidation regarding organ preservation after treatment is lacking. Watch and Wait (W&W) is an effective strategy in rectal cancer patients showing cCR after nCRT to preserve organs. This study was designed to explore the efficacy, safety, and organ preservation rate of a combination of nCRT and PD-1 inhibitor(sintilimab) in MSS/pMMR patients with ultra-low rectal cancers. Methods: This was a single-arm, phase II trial. Patients with ultra-low rectal cancer that was confirmed as MSS/pMMR T1-3aN0-1M0 and received 50 Gy (25×2 Gy) chemoradiotherapy and 2 cycles of sintilimab, followed by 6 cycles of capecitabine or CAPOX regimen plus 2 cycles of sintilimab as consolidation therapy. Patients with cCR were managed using the W&W strategy, patients with ncCR were given local excision. The primary outcome was cCR rate and secondary outcomes were anal preservation rate, organ preservation rate, tumor regression grade (TRG), and safety profile. Results: From 2021 January to 2021 December, a total of 23 patients were enrolled. The median age was 55 y (range; 38 to 75). Male patients were 61%. cT2 was 56.5% (13/23), cT3 was 43.5% (10/23), cN0 was 69.6% (16/23), and cN1 was 30.4% (7/23). All patients completed 50Gy chemoradiotherapy. Nineteen patients received 4 cycles of sintilimab treatment, 3 patients received 3 cycles of sintilimab, and 1 patient received 1 cycle of sintilimab. cCR was 43.5% (10/23), ncCR was 26.1% (6/23), and cPR was 30.4% (7/23). The anal preservation rate was not assessed in 1 patient due to cerebral ischemic stroke. The anal preservation rate was 95.5% (21/22), rectal preservation rate was 59.1% (13/22). Ten patients underwent surgery. Among them, two patients achieved pCR, and the major pathologic response rate (TRG0-1) was 60.0% (6/10). The overall CR(cCR+pCR) rate was 52.2% (12/23). Grade 3/4 treatment-related adverse events occurred in 17.4% (4/23) of patients. No unexpected adverse events or deaths were observed. Conclusions: Given the favorable tolerability and encouraging cCR rate, nCRT plus sintilimab could be a feasible and safe option for patients with pMMR/MSS, ultra-low rectal cancer who have a strong desire to preserve the anus. Based on these results, a prospective, randomized, controlled, multicenter, phase III study is currently in progress (NCT05215379). Clinical trial information: ChiCTR2100042785.

Background Early detection of colorectal carcinoma (CRC) would help to identify tumors when curative treatments are available and beneficial. However, current screening methods for CRC, e.g., colonoscopy, may affect patients’ compliance due to the uncomfortable, invasive and time-consuming process. In recent decades, methylation profiles of blood-based circulating tumor DNA (ctDNA) have shown promising results in the early detection of multiple tumors. Here we conducted a study to investigate the performance of ctDNA methylation markers in early detection of CRC. Results In total, 742 participants were enrolled in the study including CRC (n = 332), healthy control (n = 333), benign colorectal disease (n = 65) and advanced adenoma (n = 12). After age-matched and randomization, 298 participants (149 cancer and 149 healthy control) were included in training set and 141 (67 cancer and 74 healthy control) were in test set. In the training set, the specificity was 89.3% (83.2–93.7%) and the sensitivity was 88.6% (82.4–93.2%). In terms of different stages, the sensitivities were 79.4% (62.1–91.2%) in patients with stage I, 88.9% (77.3–95.8%) in patients with stage II, 91.4% (76.9–98.2%) in patients with stage III and 96.2% (80.3–99.9%) in patients with stage IV. Similar results were validated in the test set with the specificity of 91.9% (83.1–97.0%) and sensitivity of 83.6% (72.5–91.6%). Sensitivities for stage I-III were 87.0% (79.7–92.4%) in the training set and 82.5% (70.2–91.3%) in the test set, respectively. In the unmatched total population, the positive ratios were 7.8% (5.2–11.2%) in healthy control, 30.8% (19.9–43.5%) in benign colorectal disease and 58.3% (27.5–84.7%) in advanced adenoma, while the sensitivities of stage I–IV were similar with training and test sets. Compared with methylated SEPT9 model, the present model had higher sensitivity (87.0% [81.8–91.2%] versus 41.2% [34.6–48.1%], P Conclusions Together our findings showed that ctDNA methylation markers were promising in the early detection of CRC. Further validation of this model is warranted in prospective studies.

Additional file 1: Supplemental Table 1. Two observers' agreement for objective parameters details.

Additional file 1. The performances of the early detection model in the subgroup analysis including total matched population, unmatched population, colorectal-related benign disease and stratification by age and the comparison between the early detection model and previously reported mSEPT9 model.

Background. The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. Method. Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. Results. X-tile plots identified 3 (P<0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P<0.001, P=0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P<0.001). Conclusion. More TD count (TD count≥4) was significantly associated with poor disease-specific survival in CRC patients.

Objectives Visceral arterial aneurysms may be treated using open surgery or endovascular repair, but the best approach remains controversial. This was a retrospective study aiming to compare open surgery and endovascular treatment strategies for visceral arterial aneurysms. Methods The study included all 93 patients who were admitted with visceral artery aneurysms between January 2001 and January 2011 at the Department of Vascular Surgery, Changhai Hospital, Shanghai, China. All cases underwent either open or endovascular procedures. Overall survival and adverse events were compared between the groups. Success rate, blood loss, length of surgery, and length of hospital stay were also compared. The patients were followed up at three, six, and 12 months then every year until April 2014. Results Open surgery was performed on 34 patients and endovascular procedures on 59. There were no differences in characteristics of the patients between the open surgery and endovascular groups. The perioperative complication rate was 52.9 and 13.6% in the open surgery and endovascular groups, respectively. Mean follow-up was 36.8 months (range: 11 months to 10 years). The one- and five-year survival rates were 100 and 60.6%, respectively, in the open surgery group, compared to 100 and 84.5% in the endovascular group. Multivariate analysis for factors related to overall survival showed that there was a significant relationship with the treatment approach (HR = 0.479, 95%CI: 0.278–0.825; P = 0.008) and the presence of false aneurysm (HR = 2.929, 95%CI: 1.388–6.180, P = 0.005). Conclusions Endovascular repair could be considered as an effective method for visceral artery aneurysm. Endovascular repair showed lower perioperative complication rates and better long-term survival.

The Denonvilliers’ fascia (DVF) plays an important role in rectal surgery because of its anatomic position and its relationship to the surrounding organs. It affects the surgical plane anterior to the rectum in the procedure of total mesorectal excision (TME). Anatomical and embryological studies have helped us to understand this structure to some extent, but many controversies remain. In terms of its embryonical origin, there are three mainstream hypotheses: peritoneal fusion of the embryonic cul-de-sac, condensation of embryonic mesenchyme, and mechanical pressure. Regarding its architecture, the DVF may be a single, two, or multiple layers, or a composite single-layer structure. In women, most authors deem that this structure does exist but they are willing to call it the rectovaginal septum rather than the DVF. Operating behind the DVF is supported by most surgeons. This article will review those mainstream studies and opinions on the DVF and combine them with what we have observed during surgery to discuss those controversies and consensuses mentioned above. We hope this review may help young colorectal surgeons to have a better understanding of the DVF and provide a platform from which to guide future scientific research.

A 23-year-old male patient was diagnosed as having a hypervascular pelvic mass by ultrasonography and magnetic resonance examination. A pathology puncture showed vitreous vascular Castleman’s disease. Because of concerns about tumor blood supply, embolization under digital subtraction angiography (DSA) was performed on the artery of the pelvic tumor before resection of the mass and surrounding rectum. Castleman’s disease of pelvic lymph node (mixed type, mainly hyaline vascular type) was confirmed pathologically from postoperative biopsy. Embolization of the blood-supply artery of a hypervascular mass should be considered before surgery is performed.

s Several studies have focused on umbilical cord-derived mesenchymal stem cells (UC-MSCs) due to their potential therapeutic effects in a cluster of diseases. However, there has been no bibliometric analysis evaluating the evolution in UC-MSC research. Therefore, this study aimed to assess scientific activity regarding UC-MSC research. Publications on UC-MSCs were retrieved from the Science Citation Index-Expanded (SCI-E) of the Web of Science (WoS) from 1975 to 2017. Statistical analyses were performed using Excel, GraphPad Prism 5, and VOSviewer software. Comparative analyses were employed to assess contributions between different countries, institutes, and researchers. With 21.26 citations per paper, 1206 papers cited 25,517 times were included. Mainland China contributed the most with 558 papers, with the most citations (6858 times) and the highest H-index (43). South Korea ranked first for number of papers per million people and per trillion gross domestic product (GDP). Keywords were stratified into two clusters by VOSviewer software: cluster 1, “treatments and effects”; and cluster 2, “characteristics”. The average appearing years (AAY) of keywords in cluster 1 was more recent than that in cluster 2. For promising hotspots, “TNF-α” showed the latest AAY at 2014.09, followed by “migration”, “angiogenesis”, and “apoptosis”. We conclude that the number of publications has been continuously growing dramatically since 2002 and that mainland China and South Korea are the most productive regions. The focus gradually shifts from “characteristics” to “treatments and effects”. Attention should be drawn to the latest hotspots, such as “TNF-α”, “migration”, “angiogenesis”, and “apoptosis”. Furthermore, funding agencies might increase investments in exploring the therapeutic potential of UC-MSCs. Electronic supplementary material The online version of this article (10.1186/s13287-018-0785-5) contains supplementary material, which is available to authorized users.

Details of group items by cluster in VOSviewer. (DOCX 21 kb)

To compare the clinicopathological features and prognosis between left-sided colon cancer (LC) and right-sided colon cancer (RC).Clinicopathological and follow-up data of 2 174 colon carcinoma cases undergoing resection at Shanghai Changhai Hospital of The Second Military Medical University from January 2000 to December 2010 were retrospectively analyzed. Patients with transverse colon cancer, overlapping position, unknown location, recurrent cancer, multiple primary cancer, concomitant malignant tumors, preoperative chemotherapy, local resection, incomplete clinical data and missed follow up were excluded. Finally, a total of 1 036 patients, whose primary tumors were radically removed, were enrolled, with 563 patients in LC group (including carcinoma in cecum, ascending colon and hepatic flexure) and 473 in RC group (including carcinoma in splenic flexure, descending colon and sigmoid colon). The clinicopathological features and survival, including median overall survival, 5-year overall survival rate, tumor specific median overall survival, cancer specific 5-year overall survival rate, were compared between LC and RC groups. Tumor specific overall survival was defined as the period between operation date to the date of death caused by cancer progression. Multivariate Cox regression analysis was used to analyze the influencing factors of survival. Propensity score matching was carried out to balance the clinicopathological factors between the two groups with the SAS 9.3, taking the following parameters into consideration (age, gender, gross appearance, tumor diameter, invasion depth, lymph node metastasis, distant metastasis, TNM stages, differentiation, CEA and CA199-9). Patients in RC group and LC group were matched according to the propensity scores and the clinicopathological characteristics and prognosis of two groups were compared again.No significant differences were identified between the two groups in age, distant metastasis and serum CEA level. Compared with RC group, LC group had more male patients [60.9%(343/563) vs. 51.0%(241/473), P=0.001], more ulcerative tumors [71.9% (405/563) vs. 65.3%(309/473), P=0.006], better differentiation [well/moderately differentiated: 87.5%(493/563) vs. 73.8%(349/473), P=0.000], lower infiltration depth [T1-2: 17.1%(96/563) vs. 10.1%(48/473), P=0.001], higher lymph node metastasis rate [N0: 53.3%(300/563) vs. 62.4%(295/473), P=0.013], lower TNM stage [stage I(: 13.3%(75/563) vs. 7.8%(37/473), P=0.000], lower serum CA199 level [37 kU/L: 68.4% (385/563) vs. 62.6% (296/473), P=0.022] and smaller tumor diameter [5.0 cm: 55.1%(310/563) vs. 38.3%(181/473), P=0.000]. The median overall survival was 82 months and 76 months in LC and RC groups, respectively, and the 5-year overall survival rate was 58.3% and 50.9%(P=0.038). The median tumor specific survival was 84 months and 78 months in LC and RC groups, respectively, and the 5-year tumor specific overall survival rate was 60.6% and 52.9% (P=0.031). Multivariate Cox regression analysis showed that tumor location (LC vs. RC) was not associated with overall survival (P=0.106) and tumor specific survival (P=0.091). After propensity score matching, no significant difference was found in clinicopathological factors and propensity score (0.458±0.129 vs. 0.459±0.129, P=0.622) between LC and RC group. After matching, there was no significant difference in overall survival rate (54.0% vs. 51.7%, P=0.982) and tumor specific overall survival rate(56.4% vs. 53.1%, P=0.819) between two groups.Significant difference exists between RC and LC in clinicopathological factors, but not in survival.

e15076 Background: Colorectal cancer (CRC) develops as a result of neoplastic progression, which often takes decades, providing a window for early detection. Unfortunately, there has been little success in developing blood-based screening method due to the low amount of ctDNA present in the circulation, especially in patients with early stage disease. The role of aberrant DNA methylation, occurring very early in tumorigenesis, has been well elucidated. In this prospective study, we evaluated the potentiality of DNA methylation status obtained from ctDNA as an early detection method. Methods: Panel Design: Methylation data of tumor samples (12 types, n = 4,772), adjacent normal (8 types, n = 411), and normal white blood cells (n = 656) from TCGA and GSE were compared. Differentially methylated sites were extracted using modified wald-test with an adjusted p-value < 0.05 and fold-change > 2. Our panel covers 80,672 CpG sites, spanning 1.05Mb of human genome. We performed targeted bisulfite sequencing on plasma samples of 67 (stage I: 13, II:29, III: 23, IV: 2) Chinese CRC patients and 144 healthy individuals to construct a model for deriving markers that are differentially methylated and their associated weight. The model was validated in 2 independent cohorts. Results: We constructed a model using a support vector machine (SVM)-based machine learning classifier based on top 4,000 differentially methylated regions (DMRs) selected by random forest between tumor and normal plasma samples. Subsequently, 5-fold cross-validation with 100-time repeats were performed to gain a robust estimation of model performance, achieving a sensitivity of 91%, specificity of 98% and area under curve (AUC) of 98.6%. The model was subsequently validated in 2 independent cohorts: one consisted of 57 stage I-III CRC patients and 74 healthy individuals and another one with 47 stage IV patients and the same 74 healthy individuals. The model yielded a sensitivity of 83% and 95% for the early and late stage cohorts, respectively. A specificity of 95% was obtained for both cohorts. Conclusions: Our findings demonstrated the potential of profiling DNA methylation, which can effectively distinguish cancerous from healthy, for the purpose of screening. This method has potential to serve as a supplementary or alternative approach in early detection.

The classical therapeutic indication for type B aortic dissection is based on either medication or open surgery; medication therapy is recommended for relatively stable uncomplicated type B aortic dissection. With improvements in endovascular repair and the potential risk of disease progression, it is now necessary to evaluate the requirement for revision of the therapeutic choice of uncomplicated type B aortic dissection based on morphological features and time window. Data from 252 patients diagnosed as uncomplicated type B aortic dissection from 1992 to 2015 were analyzed retrospectively. Among these cases, 117 patients received medication therapy and 135 patients underwent endovascular repair. The 60-month survival rate in the endovascular group was higher than that in the medication group (92.3% vs 67.6%). According to the morphological evaluation, visceral artery involvement and false/true lumen ratios over 0.7 were strong risk factors for medical treatment alone. Increased surgical time and blood loss were found in patients treated in the chronic phase, compared with those who underwent endovascular repair within 14 days of the onset of symptoms. With improvements in aortic remodeling techniques, endovascular repair has been shown to improve long-term survival rates of patients with uncomplicated aortic dissection. Considering the potential risk of death, we recommend that patients with visceral artery involvement and a false/true lumen ratio over 0.7 should receive endovascular repair aggressively. Furthermore, delayed endovascular repair in the chronic phase does not improve the long-term outcome of uncomplicated type B aortic dissection.

e15610Background: CRC is known to develop from the early precancerous lesion to full blown malignancy due to the accumulation of genetic and epigenetic aberrations. The role of aberrant DNA methyla...