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Abstract Background Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies. Methods In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5’ end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls. Results This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965–0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV. Conclusion Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.

Abstract Objective This study investigates the impact of Titin (TTN) gene mutations on radiotherapy sensitivity in rectum adenocarcinoma (READ) by examining changes in the tumour immune microenvironment. Methods Data on gene expression and mutations in READ were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics analysis explored the correlation between TTN mutations and immune cell infiltration. In vitro, lentiviral vectors were used to assess TTN mutations' effects on ANKRD1 expression in two READ cell lines. ANKRD1 was overexpressed, and clonogenic assays evaluated radiotherapy sensitivity. Flow cytometry, immunofluorescence, and comet assays examined mutations' impact on cell cycle, apoptosis, and DNA damage response (DDR). An in vivo mouse model and formalin‐fixed paraffin‐embedded samples from locally advanced rectal cancer (LARC) patients before and after radiotherapy were analyzed, followed by prognostic evaluation. Results Bioinformatics revealed that TTN mutations increase radiation sensitivity in LARC by slowing cell proliferation, promoting apoptosis, and reducing DDR. TTN mutations also inhibit ANKRD1 expression via JUN disruption and enhance CD4/CD8 T‐cell infiltration, improving anti‐tumour immunity and outcomes. Observations from the clinical study showed a substantial decline in ANKRD1 expression levels alongside a notable surge in the counts of CD4+ and CD8+ T cells after undergoing radiotherapy. Patients with TTN mutations, low ANKRD1 expression, and high densities of CD4+ and CD8+ T cells had longer 3‐year disease‐free survival in READ. Conclusion Our findings reveal that TTN mutations can serve as biomarkers for enhanced radiotherapy sensitivity in READ. By altering the tumour's immune microenvironment, these mutations may provide a novel target for personalized radiotherapy strategies, potentially improving therapeutic outcomes in patients with READ. Highlights The association between TTN mutations and tumour mutation burden, as well as immune cell infiltration in READ, is examined. TTN mutations enhance the radiation sensitivity of READ cells and weaken DNA damage repair in response to radiation. TTN mutations increase the radiation sensitivity of READ cells by inhibiting ANKRD1. The infiltration of CD8+ and CD4+ T cells induced by TTN mutations is essential for anti‐tumour immunity. TTN mutations serve as a biomarker for the pathological response to preoperative radiotherapy in READ.

Abstract Background In this study, we aimed to identify the risk factors in patients with rectal anastomotic re-leakage and develop a prediction model to predict the probability of rectal anastomotic re-leakage after stoma closure. Methods This study was a single-center retrospective analysis of patients with rectal cancer who underwent surgery between January 2010 and December 2020. Among 3225 patients who underwent Total or Partial Mesorectal Excision (TME/PME) surgery for rectal cancer, 129 who experienced anastomotic leakage following stoma closure were enrolled. Risk factors for rectal anastomotic re-leakage were analyzed, and a prediction model was established for rectal anastomotic re-leakage. Results Anastomotic re-leakage after stoma closure developed in 13.2% (17/129) of patients. Multivariable analysis revealed that neoadjuvant chemoradiotherapy (odds ratio, 4.07; 95% confidence interval, 1.17–14.21; p = 0.03), blood loss > 50 ml (odds ratio, 4.52; 95% confidence interval, 1.31–15.63; p = 0.02), and intersphincteric resection (intersphincteric resection vs. low anterior resection: odds ratio, 6.85; 95% confidence interval, 2.01–23.36; p = 0.002) were independent risk factors for anastomotic re-leakage. A nomogram was constructed to predict the probability of anastomotic re-leakage, with an area under the receiver operating characteristic curve of 0.828 in the cohort. Predictive results correlated with the actual results according to the calibration curve. Conclusions Neoadjuvant chemoradiotherapy, blood loss > 50 ml, and intersphincteric resection are independent risk factors for anastomotic re-leakage following stoma closure. The nomogram can help surgeons identify patients at a higher risk of rectal anastomotic re-leakage.

Pelvic exenteration is often required for primary rectal cancer beyond total mesorectal excision (PRC-bTME) and locally recurrent rectal cancer (LRRC). Some patients with radical resection can achieve long-term survival, but they need to face risks, such as huge surgical trauma, serious perioperative complications, permanent loss of organ function and decline in quality of life. Preoperative evaluation of PRC-bTME and LRRC should emphasize multidisciplinary collaboration and develop individualized diagnosis and treatment strategies. The principles of function preservation and risk-benefit balance in surgery oncology should be followed, and R0 resection should be emphasized. Perioperative complications, surgical trauma and organ function loss should be minimized to achieve the best quality control and balance point. This consensus was formulated by the Colorectal Cancer Committee of the Chinese Medical Doctor Association and the Gastrointestinal Surgery Committee of China International Exchange and Promotive Association for Medical and Health Care. The draft was formed based on the summary of domestic and foreign research progress and expert experience. After discussion, review and modification by experts, an anonymous voting was conducted for each major opinion, and in-depth verification was carried out according to the principles of evidence-based medicine. Finally, the Chinese expert consensus on the pelvic exenteration with primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) was formed. This consensus mainly summarizes the indications and contraindications of pelvic exenteration (PE) for PRC-bTME and LRRC, preoperative diagnosis and evaluation, perioperative treatment, as well as the resection scope, surgical methods, reconstruction of related organs, safety and complications of PE, postoperative follow-up and other issues, in order to provide guidance for PE in patients with PRC-bTME and LRRC.

Colorectal cancer (CRC) is a global health concern, ranking among the leading causes of cancer-related mortality. This review critically evaluates the role of liquid biopsy in detecting minimal residual disease (MRD) in CRC. The increasing incidence, particularly in China, highlights the urgency of innovative approaches for early prediction of recurrence and metastasis. The importance of MRD should be underscored as residual tumor cells post-treatment significantly impact patient prognosis. Liquid biopsy methods, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and circulating tumor RNA, are dissected for their potential in identifying molecular markers associated with CRC. The focus on ctDNA highlights its non-invasive nature, real-time monitoring capabilities, and superiority over traditional detection methods in terms of sensitivity and timeliness. The review also delves into the limitations, such as clonal hematopoiesis and the critical consideration of optimal timing for postoperative ctDNA detection. In conclusion, the review highlights the significant potential of liquid biopsy, particularly ctDNA, as a dynamic and non-invasive tool for MRD detection in CRC. By complementing traditional methods, liquid biopsy contributes to precision in tumor research and personalized treatment. These advancements offer promising avenues for improving CRC patient prognosis and tailoring individualized treatment strategies.

IntroductionThe aim of research was to study the feasibility and safety of surgery providing specimen extraction through natural orifices in patients with colorectal cancer.Materials and methodsThis study is a comparative retrospective analysis of findings obtained from 265 patients who underwent surgical treatment using NOSES technique and 275 patients who underwent laparoscopic-assisted (LA) resection. Data included preoperative patients’ information, intraoperative findings, results of postoperative pathological examination of surgical specimens, early postoperative period analysis, and follow-up.ResultsBoth groups were comparable in terms of gender, age and BMI. The duration of surgery was similar in both groups (p = 0.94). Intraoperative blood loss under NOSES interventions was slightly lower than in laparoscopic-assisted surgeries (p 0.05). It was revealed that in the NOSES group, the function of the gastrointestinal tract normalized at an earlier time, slightly the time to start liquid food intake and the duration of postoperative hospital stay were reduced (p 0.05).ConclusionThe results of this study demonstrate that NOSES technique is a relatively safe and effective surgical option in patients with colorectal cancer. It has high surgical efficiency providing no increased risk of surgical intervention, reducing total number of postoperative complications, reducing duration of postoperative hospital stay, reducing the time for gastrointestinal function recovery and the start of food intake. This study supports that NOSES has clear advantages over conventional laparoscopic-assisted surgery.

Abstract Background More accurate prediction of distant metastases (DM) in patients with colorectal cancer (CRC) would optimize individualized treatment and follow‐up strategies. Multiple prediction models based on machine learning have been developed to assess the likelihood of developing DM. Methods Clinicopathological features of patients with CRC were obtained from the National Cancer Center (NCC, China) and the Surveillance, Epidemiology, and End Results (SEER) database. The algorithms used to create the prediction models included random forest (RF), logistic regression, extreme gradient boosting, deep neural networks, and the K‐Nearest Neighbor machine. The prediction models' performances were evaluated using receiver operating characteristic (ROC) curves. Results In total, 200,958 patients, 3241 from NCC and 197,717 CRC from SEER were identified, of whom 21,736 (10.8%) developed DM. The machine‐learning‐based prediction models for DM were constructed with 12 features remaining after iterative filtering. The RF model performed the best, with areas under the ROC curve of 0.843, 0.793, and 0.806, respectively, on the training, test, and external validation sets. For the risk stratification analysis, the patients were separated into high‐, middle‐, and low‐risk groups according to their risk scores. Patients in the high‐risk group had the highest incidence of DM and the worst prognosis. Surgery, chemotherapy, and radiotherapy could significantly improve the prognosis of the high‐risk and middle‐risk groups, whereas the low‐risk group only benefited from surgery and chemotherapy. Conclusion The RF‐based model accurately predicted the likelihood of DM and identified patients with CRC in the high‐risk group, providing guidance for personalized clinical decision‐making.

Abstract Background The diagnostic criteria and effect of persistent descending mesocolon (PDM) on sigmoid and rectal cancers (SRCs) remain controversial. This study aims to clarify PDM patients' radiological features and short-term surgical results. Method From January 2020 to December 2021, radiological imaging data from 845 consecutive patients were retrospectively analyzed using multiplanar reconstruction (MRP) and maximum intensity projection (MIP). PDM is defined as the condition wherein the right margin of the descending colon is located medially to the left renal hilum. Propensity score matching (PSM) was used to minimize database bias. The anatomical features and surgical results of PDM patients were compared with those of non-PDM patients. Results Thirty-two patients with PDM and 813 patients with non-PDM were enrolled into the study who underwent laparoscopic resection. After 1:4 matching, patients were stratified into PDM (n = 27) and non-PDM (n = 105) groups. The lengths from the inferior mesenteric artery (IMA) to the inferior mesenteric vein (1.6 cm vs. 2.5 cm, p = 0.001), IMA to marginal artery arch (2.7 cm vs. 8.4 cm, p = 0.001), and IMA to the colon (3.3 cm vs. 10.2 cm, p = 0.001) were significantly shorter in the PDM group than those in the non-PDM group. The conversion to open surgery (11.1% vs. 0.9%, p = 0.008), operative time (210 min vs. 163 min, p = 0.001), intraoperative blood loss (50 ml vs. 30 ml, p = 0.002), marginal arch injury (14.8% vs. 0.9%, p = 0.006), splenic flexure free (22.2% vs. 3.8%, p = 0.005), Hartmann procedure (18.5% vs. 0.0%, p

Abstract Background Colorectal polyp is known a precursor of colorectal cancer (CRC) that holds an increased risk for progression to CRC. Circulating cell-free DNA (cfDNA) methylation has shown favorable performance in the detection and monitoring the malignant progression in a variety of cancers. Results To discover cfDNA methylation markers for the diagnosis of CRC, we first performed a genome-wide analysis between eight CRC and eight polyp tissues using the Infinium HumanMethylationEPIC BeadChip. We identified 7008 DMCs, and after filtering, we validated 39 DMCs by MethylTarget sequencing in 62 CRC and 56 polyp tissues. A panel of four CpGs (cg04486886, cg06712559, cg13539460, and cg27541454) was selected as the methylation marker in tissue by LASSO and random forest models. A diagnosis prediction model was built based on the four CpGs, and the methylation diagnosis score (md-score) can effectively discriminate tissues with CRC from polyp patients (AUROC > 0.9). Finally, the cg27541454 was confirmed hypermethylated in CRC (AUC = 0.85) in the plasma validation cohort. Conclusions Our findings suggest that the md-score could robustly detect CRC from polyp tissues, and cg27541454 may be a promising candidate noninvasive biomarker for CRC early diagnosis.

Abstract Introduction This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. Materials and methods A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. Results In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P

Abstract Background There are different surgical strategies that can treat synchronous colorectal cancer (SCRC) involving separate segments, namely extensive resection (EXT) and left hemicolon-sparing resection (LHS). We aim to comparatively analyze short-term surgical results, bowel function, and long-term oncological outcomes between SCRC patients treated with the two different surgical strategies. Methods One hundred thirty-eight patients with SCRC lesions located in the right hemicolon and rectum or sigmoid colon were collected at the Cancer Hospital, Chinese Academy of Medical Sciences, and the Peking University First Hospital from January 2010 to August 2021 and divided into EXT group (n = 35) and LHS group (n = 103), depending on their surgical strategies. These two groups of patients were compared for postoperative complications, bowel function, the incidence of metachronous cancers, and prognosis. Results The operative time for the LHS group was markedly shorter compared with the EXT group (268.6 vs. 316.9 min, P = 0.015). The post-surgery incidences of total Clavien-Dindo grade ≥ II complications and anastomotic leakage (AL) were 8.7 vs. 11.4% (P = 0.892) and 4.9 vs. 5.7% (P = 1.000) for the LHS and EXT groups, respectively. The mean number of daily bowel movements was significantly lower for the LHS group than for the EXT group (1.3 vs. 3.8, P

Purpose Numerous indicators can be used to predict tumor patients’ prognosis and tumor regression grade (TRG). The role of the neutrophil-lymphocyte ratio (NLR) among individuals with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) hasn't been studied, nevertheless. This study aims to explore the predictive value of the NLR before nCRT (pre-NLR) in TRG and prognosis of LARC patients undergoing nCRT.. Methods In this retrospective investigation, 326 LARC patients receiving nCRT in total were included. The link between the pre-NLR and TRG was examined using a logistic regression analysis. A Cox-based nomogram was created in the meanwhile to forecast overall survival (OS). With the use of calibration plots and receiver operating characteristic (ROC) curves, we evaluated the nomogram's predictive capabilities. Results The median pre-NLR across 326 patients was 2.2 (interquartile range, IQR: 1.7-2.7). In the logistic regression analysis, only the pre-NLR for TRG in LARC patients receiving nCRT was statistically significant (odds ratio, OR = 0.62, 95% CI: 0.47-0.80, P

Abstract Liver metastasis is the main cause of death in patients with colorectal cancer (CRC); thus, necessitating effective biomarkers and therapeutic targets for colorectal cancer liver metastasis (CRLM). Fibroblast growth factor 19 (FGF19) is a protumorigenic gene in numerous human malignancies. In this study, it is shown that FGF19 plays an indispensable role in CRLM. FGF19 expression and secretion are markedly correlated with liver metastasis and lower overall survival rates of patients with CRC. An in vivo metastasis model shows that FGF19 overexpression confers stronger liver‐metastatic potential in CRC cells. Mechanistically, FGF19 exerts an immunomodulatory function that creates an environment conducive for metastasis in CRLM. FGF19 mediates the polarization of hepatic stellate cells to inflammatory cancer‐associated fibroblasts (iCAFs) by activating the autocrine effect of IL‐1α via the FGFR4‐JAK2‐STAT3 pathway. FGF19‐induced iCAFs promote neutrophil infiltration and mediate neutrophil extracellular trap (NET) formation in liver metastatic niches via the production of complement C5a and IL‐1β, which in turn accelerates the liver colonization of CRC cells. Importantly, targeting FGF19 signaling with fisogatinib efficiently suppresses FGF19‐induced liver metastasis in a mouse model. In summary, this study describes the mechanism by which FGF19 regulates CRLM, thereby providing a novel target for CRLM intervention.

As science and technology have advanced, surgical techniques have become increasingly sophisticated. A revolution was triggered by the appearance of new electrical and optical instruments, shifting the field of surgery in the direction of “minimally invasive” and “noninvasive” procedures. Natural orifice specimen extraction surgery has emerged as a rising star in the field of minimally invasive surgery. It has increased rapidly, and it has become a hot topic in recent years. Natural orifice specimen extraction surgery has shown advantages in alleviating postoperative pain, improving bowel movements, providing a cosmetic effect, and improving psychological state without adversely affecting cancer outcomes. Different approaches have been classified and summarized for natural orifice specimen extraction surgery based on the procedure for specimen extraction and the location of the tumor, and natural orifice specimen extraction surgery can be used in resection all parts of the colorectum. The international natural orifice specimen extraction surgery consensus and monograph have also been published to improve the standardization of the application of this technique. Additional steps need to be taken to standardize natural orifice specimen extraction surgery, such as conducting large-scale randomized controlled trials, establishing a training system, and developing specific tools. Still, the natural orifice specimen extraction surgery procedure continues to follow the development of minimally invasive surgery and may be one of the future treatment options.

Abstract Background Recent data based on large databases show that bowel preparation (BP) is associated with improved outcomes in patients undergoing elective colorectal surgery. However, it remains unclear whether BP in elective colectomies would lead to similar results in patients with diverticulitis. The purpose of this study was to investigate whether bowel preparation affected the surgical site infections (SSI) and anastomotic leakage (AL) in patients with diverticulitis undergoing elective colectomies. Study design We identified 16,380 diverticulitis patients who underwent elective colectomies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) colectomy targeted database (2012–2017). Multivariate logistic regression models were employed to investigate the impact of different bowel preparation strategies on postoperative complications, including SSI and AL. Results In the identified population, a total of 2524 patients (15.4%) received no preparation (NP), 4715 (28.8%) mechanical bowel preparation (MBP) alone, 739 (4.5%) antibiotic bowel preparation (ABP) alone, and 8402 (51.3%) MBP + ABP. Compared to NP, patients who received any type of bowel preparations showed a significantly decreased risk of SSI and AL after adjustment for potential confounders (SSI: MBP [OR = 0.82, 95%CI: 0.70–0.96], ABP [0.69, 95%CI: 0.52–0.92]; AL: MBP [OR = 0.66, 95%CI: 0.51–0.86], ABP [0.56, 95%CI: 0.34–0.93]), where the combination type of MBP + ABP had the strongest effect (SSI:OR = 0.58, 95%CI:0.50–0.67; AL:OR = 0.46, 95%CI:0.36–0.59). The significantly decreased risk of 30-day mortality was observed in the bowel preparation of MBP + ABP only (OR = 0.32, 95%CI: 0.13–0.79). After the further stratification by surgery procedures, patients who received MBP + ABP showed consistently lower risk for both SSI and AL when undergoing open and laparoscopic surgeries (Open: SSI [OR = 0.51, 95%CI: 0.37–0.69], AL [OR = 0.47, 95%CI: 0.25–0.91]; Laparoscopic: SSI [OR = 0.58, 95%CI: 0.47–0.72, AL [OR = 0.49, 95%CI: 0.35–0.68]). Conclusions MBP + ABP for diverticulitis patients undergoing elective open or laparoscopic colectomies was associated with decreased risk of SSI, AL, and 30-day mortality. Benefits of MBP + ABP for diverticulitis patients underwent robotic surgeries warrant further investigation.

The liver is the main target organ for hematogenous metastases of colorectal cancer, and colorectal liver metastasis is one of the most difficult and challenging situations in the treatment of colorectal cancer. In order to improve the diagnosis and comprehensive treatment in China, the Guidelines have been edited and revised for several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, increase the local damage rate of liver metastases, prolong long-term survival, and improve quality of life. The revised Guideline version 2023 includes the diagnosis and followup, prevention, multidisciplinary team (MDT), surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, with stateoftheart experience and findings, detailed content, and strong operability.

Because of its significant advantage of fast postoperative recovery, natural orifice specimen extraction surgery (NOSES) has attracted increasing attention worldwide. However, the NOSES in gastric cancer (GC) treatment still needs more clinical practice, especially for the rare anatomical anomaly. Situs inversus totalis (SIT) is a rare autosomal recessive anatomical anomaly with an incidence ranging between 1/8,000 and 1/25,000 births. We present a video of transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy performed in a 59-year-old woman known to have SIT. Preoperative investigations revealed that the patient had early GC at the antrum. A gastroscopy report from the local hospital showed signet-ring cell carcinoma. The preoperative computed tomography scan revealed irregular thickening of the gastric wall at the junction of the greater curvature and antrum without metastasis to the lymph nodes. In total, laparoscopic D2 distal gastrectomy was performed with transvaginal specimen extraction. Billroth II with Braun anastomosis was performed for reconstruction. The length of the operation was 240 min without intraoperative complications and with minimal blood loss of 50 ml. The patient was uneventfully discharged on postoperative Day 7. The final pathology confirmed signet-ring cell carcinoma confined to the mucosal muscle without metastasis in 16 lymph nodes. Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy can be safely performed in patients with SIT and has similar surgical outcomes to usual laparoscopic gastrectomy.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

Background: Totally laparoscopic right colectomy has been demonstrated to be safe and feasible. Two manners of anastomosis, namely, antiperistaltic and isoperistaltic stapled side-to-side anastomosis, have been described before. However, research concerning the influence of different peristaltic orientations on anastomosis is rare and, if there is, included relatively small cases without long-term outcomes. The aim of this study was to compare the short- and long-term outcomes of intracorporeal isoperistaltic side-to-side anastomosis and antiperistaltic side-to-side anastomosis for right colectomy. Methods: We retrospectively reviewed 214 consecutive patients who underwent totally laparoscopic right colectomy from January 2017 to December 2020 at our medical center. Two modalities of anastomosis were used: isoperistaltic totally side-to-side anastomosis and antiperistaltic totally side-to-side anastomosis. Data on demographics, disease features, pathological characteristics, operative details, and short-term outcomes were collected and analyzed. Results: We found that operative features such as operating time, intraoperative bleeding, length of resected intestine, number of harvested lymph nodes, and length of incision, as well as measures of postoperative recovery such as time to first flatus, time to first defecation, and length of stay, were statistically comparable between the 2 groups. The postoperative complication rate was also similar between the 2 groups. The median follow-up time was 35.6 months, and no differences were observed in the long-term outcomes. Conclusion: Intracorporeal isoperistaltic side-to-side anastomosis can achieve short- and long-term outcomes similar to those of antiperistaltic side-to-side anastomosis. Both techniques are safe and feasible.

Abstract Background Natural orifice specimen extraction surgery (NOSES) has been increasingly applied in radical surgery of abdominal and pelvic organs, but it is still in the exploratory stage. There is insufficient evidence to prove its efficacy. Methods From January 2013 to June 2017, a total of 351 patients diagnosed with rectal cancer were eventually included in this study. Patients who underwent NOSES were assigned to the NOSES group, while patients undergoing conventional laparoscopic assisted resection were assigned as to the LAP group. Propensity score matching was used to align clinicopathological features between the two groups. Results From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (47.0 ± 60.4 ml vs 87.1 ± 101.2 ml, P = 0.011), shorter postoperative gastrointestinal recovery (50.7 ± 27.3 h vs 58.6 ± 28.5 h, P = 0.040), less postoperative analgesic use (36.8% vs 52.8%, P = 0.019), lower postoperative pain scores (P

Colorectal cancer (CRC) is the second most common cause of cancer-related death among both men and women worldwide and the third most common cancer overall. About 20% of patients diagnosed with CRC were discovered to have distant metastatic lesions, the majority of which were located in the liver. For the optimum treatment of CRC patients with hepatic metastases, interventional radiologists, medical oncologists, and surgeons must all collaborate. The surgical excision of the primary tumor is an important part of CRC treatment since it has been found to be curative in cases of CRC with minimal metastases. However, given the evidence to date was gathered from retrospective data, there is still controversy over the effectiveness of primary tumor resection (PTR) in improving the median overall survival (OS) and quality of life. Patients who have hepatic metastases make up a very tiny fraction of those who are candidates for resection. With a focus on the PTR, this minireview attempted to review the current advancements in the treatment options for hepatic colorectal metastatic illness. This evaluation also included information on PTR’s risks when performed on individuals with stage IV CRC.

PurposeTotal laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR.MethodsRC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score.ResultsA total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set.ConclusionThis preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.

BackgroundProgrammed cell death protein 1 (PD-1) receptor has two ligands,programmed death-ligand 1 (PD-L1) and PD-L2. When compared with PD-L1, PD-L2 has not received much attention, and its role remains unclear.MethodsThe expression profiles of pdcd1lg2 (PD-L2-encoding gene) mRNA and PD-L2 protein were analyzed using TCGA, ICGC, and HPA databases. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of PD-L2. We used GSEA, Spearman’s correlation analysis and PPI network to explore the biological functions of PD-L2. PD-L2-associated immune cell infiltration was evaluated using the ESTIMATE algorithm and TIMER 2.0. The expressions of PD-L2 in tumor-associated macrophages (TAMs) in human colon cancer samples, and in mice in an immunocompetent syngeneic setting were verified using scRNA-seq datasets, multiplex immunofluorescence staining, and flow cytometry. After fluorescence-activated cell sorting, flow cytometry and qRT-PCR and transwell and colony formation assays were used to evaluate the phenotype and functions of PD-L2+TAMs. Immune checkpoint inhibitors (ICIs) therapy prediction analysis was performed using TIDE and TISMO. Last, a series of targeted small-molecule drugs with promising therapeutic effects were predicted using the GSCA platform.ResultsPD-L2 was expressed in all the common human cancer types and deteriorated outcomes in multiple cancers. PPI network and Spearman’s correlation analysis revealed that PD-L2 was closely associated with many immune molecules. Moreover, both GSEA results of KEGG pathways and GSEA results for Reactome analysis indicated that PD-L2 expression played an important role in cancer immune response. Further analysis showed that PD-L2 expression was strongly associated with the infiltration of immune cells in tumor tissue in almost all cancer types, among which macrophages were the most positively associated with PD-L2 in colon cancer. According to the results mentioned above, we verified the expression of PD-L2 in TAMs in colon cancer and found that PD-L2+TAMs population was not static. Additionally, PD-L2+TAMs exhibited protumor M2 phenotype and increased the migration, invasion, and proliferative capacity of colon cancer cells. Furthermore, PD-L2 had a substantial predictive value for ICIs therapy cohorts.ConclusionPD-L2 in the TME, especially expressed on TAMs, could be applied as a potential therapeutic target.

PurposeRecently, totally laparoscopic ileostomy reversal (TLAP) has received increasing attention and exhibited promising short-term outcomes. The aim of this study was to detail the learning process of the TLAP technique.MethodsBased on our initial experience with TLAP from 2018, a total of 65 TLAP cases were enrolled. Demographics and perioperative parameters were assessed using cumulative sum (CUSUM), moving average, and risk-adjusted CUSUM (RA-CUSUM) analyses.ResultsThe overall mean operative time (OT) was 94 min and the median postoperative hospitalization period was 4 days, and there was an estimated 10.77% incidence rate of perioperative complications. Three unique phases of the learning curve were derived from CUSUM analysis, and the mean OT of phase I (1–24 cases) was 108.5 min, that of phase II (25–39 cases) was 92 min, and that of phase III (40–65 cases) was 80 min, respectively. There was no significant difference in perioperative complications between these 3 phases. Similarly, moving average analysis indicated that the operation time was reduced significantly after the 20th case and reached a steady state after the 36th case. Furthermore, complication-based CUSUM and RA-CUSUM analyses indicated an acceptable range of complication rates during the whole learning period.ConclusionOur data demonstrated 3 distinct phases of the learning curve of TLAP. For an experienced surgeon, surgical competence in TLAP can be grasped at around 25 cases with satisfactory short-term outcomes.

BackgroundRecently, totally laparoscopic (TLAP) surgery has suggested its potential on ileostomy reversal. This study aimed to compare the short-term outcomes between TLAP and traditional open ileostomy reversal.Patients and methodsFrom September 2016 to September 2021, 107 eligible patients underwent TLAP (n = 48) or open (n = 59) loop ileostomy reversal were retrospectively enrolled. Surgical parameters, postoperative recovery and complications were identified and compared between TLAP technique vs. open surgery.ResultsThe operation time and estimated blood loss showed no obvious difference between TLAP and open group. However, TLAP reversal significantly decreased the incision length (4.5cm vs. 6cm, P

Objective To evaluate the feasibility, safety, and short-term outcomes of middle rectal resection followed by transanal specimen extraction. Methods Forty-four patients with small mid-rectal tumors underwent laparoscopic rectal resection followed by transanal specimen extraction. Results The procedure was successful in all patients without intraoperative conversion or additional access. The mean operation time was 182.7 minutes (range, 130–255 minutes), the mean blood loss was 26.5 mL (range, 5–120 mL), the mean postoperative exhaust time was 31.3 hours (range, 16–60 hours), and the mean length of hospital stay was 9.5 days (range, 8–19 days). One patient developed anastomotic leakage, which was treated by intravenous antibiotics and daily pelvic cavity flushes through the abdominal drainage tube. No infection-related complications or anal incontinence were observed. The mean tumor size was 2.1 cm (range, 1.6–3.2 cm), the mean number of harvested lymph nodes was 16.5 (range, 6–31), and the mean follow-up time was 8.5 months (range, 2–16 months). By the last follow-up, no signs of recurrence had been found in any patient. Conclusion The combination of standard laparoscopic proctectomy and transanal specimen extraction could become a well-established strategy for selected patients.

Abstract Background The impact of primary tumour location on the prognosis of patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rarely discussed, and the evidence is still limited. Methods Patients with PM arising from CRC treated with CRS and HIPEC at the China National Cancer Center and Huanxing Cancer Hospital between June 2017 and June 2019 were systematically reviewed. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analysed. Results A total of 70 patients were divided into two groups according to either colonic or rectal origin (18 patients in the rectum group and 52 patients in the colon group). Patients with PM of a colonic origin were more likely to develop grade 3–4 postoperative complications after CRS+HIPEC (38.9% vs 19.2%, P = 0.094), but this difference was not statistically significant. Patients with colon cancer had a longer median overall survival (OS) than patients with rectal cancer (27.0 vs 15.0 months, P = 0.011). In the multivariate analysis, the independent prognostic factors of reduced OS were a rectal origin (HR 2.15, 95% CI 1.15–4.93, P = 0.035) and incomplete cytoreduction (HR 1.99, 95% CI 1.06–4.17, P = 0.047). Conclusion CRS is a complex and potentially life-threatening procedure, and we suggest that the indications for CRS+HIPEC in patients with PM of rectal origin be more restrictive and that clinicians approach these cases with caution.

BackgroundLymphangiomatosis is an extremely rare disease with potential soft tissue, bone, and spleen involvement, which can be characterized by lymphangioma. Only a few cases of colon and mesenteric lymphangiomatosis have been reported. We report a case presenting with fatigue, periumbilical pain, and intermittent bloody stools. This patient underwent a series of examinations. Exploratory laparoscopy, in particular, yielded very valuable images and videos for this disease, which can provide evidence for the diagnosis of this disease.Case summaryThe current patient had fatigue, periumbilical pain, and intermittent bloody stools. Colonoscopy indicated numerous variable-sized hyaline cysts in the colon. Submucosal puncture was performed during colonoscopy. The patient was readmitted to the hospital due to periumbilical pain. B-ultrasound and abdominal CT showed multiple hypoechoic nodules in the mesenteric area. Exploratory laparoscopy was performed, and histopathology revealed that D2-40 was positive. Based on auxiliary examination and laparoscopic biopsy, surgeons and pathologists reached the diagnosis of mesenteric lymphangiomatosis.ConclusionClinicians need to comprehensively improve their knowledge of lymphangiomatosis, and the combination of clinical symptoms, histological characteristics, and colonoscopy biopsy findings should be considered to improve lymphangiomatosis diagnosis, thereby reducing misdiagnosis.Core tipColon and mesenteric lymphangiomatosis is an extremely uncommon benign condition of unknown etiology and pathogenesis in adult patients. We report a case of mesenteric lymphangiomatosis in a 37-year-old woman who presented with fatigue, periumbilical pain, and intermittent bloody stools, as well as lesions in the kidney, spleen, and bones. This case provides new insights into the diagnosis and treatment of this disease.

BackgroundRadiation therapy (RT) is a standard treatment for the local control of primary pelvic cancers (PPC), yet the risk of second corpus uteri cancer (SCUC) in PPC patients undergoing RT is still controversial. This study investigated the impact of RT on the risk of SCUC and assessed the survival outcome.MethodsWe queried nine cancer registries for PPC cases in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of SCUC was analyzed using Cox regression and Fine–Gray competing risk regression analysis. The Poisson regression analysis was employed to assess the standardized incidence ratios (SIRs) and radiation-attributed risk (RR) for SCUC. We evaluated the overall survival of patients with SCUC using the Kaplan–Meier method.ResultsReceiving radiotherapy was strongly associated with a higher risk of developing SCUC for PPC patients in Fine–Gray competing risk regression (No-RT vs. RT: adjusted HR = 1.77; 95% CI, 1.40–2.28; p < 0.001). The incidence of SCUC in PPC patients who received RT was higher than in the US general population (SIR, 1.66; 95% CI, 1.41–1.93; p < 0.05), but the incidence of SCUC in patients who did not receive RT was lower than with the US general population (SIR, 0.68; 95% CI, 0.61–0.75; p < 0.05). The dynamic SIR and RR for SCUC decreased with decreasing age at PPC diagnosis and decreased with time progress. In terms of overall survival, 10-year survival rates with SCUC after No-RT (NRT) and SCUC after RT were 45.9% and 25.9% (HR = 1.82; 95% CI, 1.46–2.29; p < 0.001), respectively.ConclusionRadiotherapy for primary pelvic cancers is associated with a higher risk of developing SCUC than patients unexposed to radiotherapy. We suggest that patients with pelvic RT, especially young patients, should receive long-term monitoring for the risk of developing SCUC.

Background: The type 2 mannose receptor C (MRC2) is involved in tumor biological processes and plays a new role in the remodeling of the extracellular matrix turnover. Previous studies have demonstrated MRC2 expression profiling and prognostic relevance in some tumor types. However, the clinical and immunotherapeutic value of MRC2 in pan-cancers remains controversial. Our study aimed to evaluate MRC2 expression pattern, clinical characteristics and prognostic significance in 33 cancers, explore the relationship between MRC2 and immune-related characteristics, and assess the prediction of MRC2 for the immunotherapeutic response.Methods: Transcriptional and clinical data of 33 cancers were downloaded from The Cancer Genome Atlas database (TCGA) database and two independent immunotherapeutic cohorts were obtained from GSE67501 and the IMvigor210 study. Next, patients stratified by MRC2 expression levels were displayed by Kaplan-Meier plot to compare prognosis-related indexes. Meanwhile, immune infiltrates of different cancers were estimated by tumor immune estimation resources (TIMER) and CIBERSORT. The ESTIMATE algorithm was used to estimate the immune and stromal scores in tumor tissues. MRC2 expression and immunological modulators, including immune inhibitors, immune stimulators, and MHC molecules, were screened through the TISIDB portal. Gene-set enrichment analysis analyses were performed to explore the underlying biological process of MRC2 across different cancers. The immunotherapeutic response prediction was performed in two independent cohorts (GSE78220: metastatic melanoma with pembrolizumab treatment and IMvigor210: advanced urothelial cancer with atezolizumab intervention).Results: MRC2 is expressed differently in many cancers and has been shown to have potential prognostic predicting significance. MRC2 was significantly associated with immune cell infiltration, immune modulators, and immunotherapeutic markers. Notably, the immunotherapeutic response group was associated with lower MRC2 expression in metastatic melanoma and advanced urothelial carcinoma cohort.Conclusion: This study demonstrated that MRC2 could be a prognostic indicator for certain cancer and is critical for tumor immune microenvironments. MRC2 expression level may influence and predict immune checkpoint blockade response as a potential indicator.

BackgroundRadiation therapy (RT) is a crucial modality for the local control of pelvic cancer (PC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. This study aimed to identify the relationship between radiation therapy received for the treatment of primary PC and subsequent secondary bladder cancer (SBC).MethodsThe Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for PC. Fine-gray competing risk regression and Cox regression analyses were employed to assess the cumulative incidence of SBC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since PC diagnosis, calendar year of PC diagnosis stage, and age at PC diagnosis were also performed. Overall survival (OS) was compared among different treatment groups with SBC by Kaplan–Meier analysis.ResultsA total of 318,165 observations showed that the primary cancers were located in pelvic cavity, 256,313 patients did not receive radiation therapy (NRT), 51,347 patients who underwent external beam radiation therapy (EBRT), and 10,505 patients receiving a combination of EBRT and brachytherapy (EBRT–BRT) who developed SBC. Receiving two types of radiotherapy was strongly consistent with a higher risk of developing SBC for PC patients in Fine-Gray competing risk regression (NRT vs. EBRT, adjusted HR= 1.71, 95% CI: 1.54-1.90, P

Background Although endoscopic submucosal dissection (ESD) is considered to be a curative treatment for early colorectal cancer, additional surgery with lymph node dissection is routinely recommended for patients treated in non-curative ESD, owing to the risk of residual cancer and lymph node metastasis (LNM). However, in clinical practice, few patients are found to have either residual cancer or LNM after additional surgery. Therefore, we conducted this study to determine the risk factors associated with residual cancer and LNM. Methods Patients with early colorectal cancer after non-curative ESD and additional surgery from January 2015 to May 2019 were retrospectively identified. Clinicopathological characteristics were collected to determine the predictors of residual cancer and LNM. Results A total of 62 patients were enrolled for analysis in this study. After additional surgery, residual cancer and LNM was detected in 12 patients (19.35%). Clinicopathological comparison of patients with the presence or absence of residual cancer and LNM demonstrated that piecemeal resection (80% vs. 14.04%, P

Abstract Fibroblast activation protein alpha (FAP) is a marker of cancer-associated fibroblast, which is also expressed in cancer epithelial cells. However, the role of FAP in colorectal cancer (CRC) cells remains to be elucidated. Here we investigate the expression pattern of FAP in CRC tissues and cells to prove that FAP is upregulated in CRC cells. Loss- of and gain-of-function assays identified FAP promotes migration and invasion instead of an effect on cell proliferation. Microarray assays are adopted to identify the different expressed genes after FAP knockdown and gene set enrichment analysis (GSEA) is used to exploit the involved signaling pathway. Our works reveal FAP exerts a function dependent on NF-κB signaling pathway and FAP expression is associated with NF-κB signaling pathway in clinical samples. Our work shows FAP is secreted by CRC cells and soluble FAP could promote metastasis. To investigate the mechanism of FAP influencing the NF-κB signaling pathway, LC/MS is performed to identify the proteins interacting with FAP. We find that FAP binds to ENO1 and activates NF-κB signaling pathway dependent on ENO1. Blocking ENO1 could partially reverse the pro-metastatic effect mediated by FAP. We also provide evidences that both FAP and ENO1 are associated with CRC stages, and high levels of FAP and ENO1 predict a poor survival in CRC patients. In summary, our work could provide a novel mechanism of FAP in CRC cells and a potential strategy for treatment of metastatic CRC.

Abstract Natural orifice specimen extraction surgery (NOSES) is an intra-abdominal procedure that does not require an auxiliary incision to take a surgical sample from the abdominal wall through the natural orifice, but there are few systematic clinical studies on it. The aim of this study was to demonstrate the safety and feasibility of NOSES. We retrospectively analyzed the clinical data and follow-up of 165 patients with low rectal cancer who underwent NOSES or conventional laparoscopic surgery at our center from January 2013 to June 2015. From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (49.3 ± 55.8 ml vs. 75.1 ± 57.3 ml, p = 0.02), shorter postoperative gastrointestinal recovery (42.3 ± 15.5 h vs. 50.1 ± 17.0 h, p = 0.01), less postoperative analgesic use (35.6% vs. 57.6%, p = 0.02), lower postoperative pain scores, lower rate of postoperative complications (6.8% vs. 25.4%, p = 0.01), better satisfaction of the image and cosmesis of the abdominal wall postoperatively, and higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups. Overall, NOSES is a safe and reliable minimally invasive surgical technique for patients with low rectal cancer.

Abstract Background This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses. Results In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01–1.14; P=0.015) and grade 3–4 postoperative complications (HR, 1.86, 95% CI, 1.22–3.51; P=0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01–1.02; P

Abstract Background To evaluate the feasibility and safety of a new surgical method, complete laparoscopic extended right hemicolectomy with preservation of the ileocecal junction in right-transverse colon cancer. Methods We retrospectively analyzed and compared the data of consecutive patients with right-transverse colon cancer who underwent complete laparoscopic extended right hemicolectomy with preservation of the ileocecal junction (n = 23) and conventional complete laparoscopic extended right hemicolectomy (n = 34) in our hospital between October 2017 to May 2019, respectively. Results The overall operation time of the ileocecal junction-preserved group was significantly shorter than that of the control group (p = 0.048). There was no difference in the number of harvested lymph nodes, metastatic lymph nodes, and rate of metastatic lymph nodes (p > 0.05). The ileocecal junction-preserved group showed shorter time of first flatus, lower frequency of postoperative diarrhea, and shorter duration of postoperative hospitalization. Furthermore, it also showed that the defecation frequency was lower in the ileocecal junction-preserved group than the control group on the 1st, 3rd, and 6th month (p < 0.05), and the number of patients who defecated at night or defecated four times or more a day was less in the ileocecal junction-preserved group than control group on the 1st month (p < 0.05). Conclusion The complete laparoscopic extended right hemicolectomy with preservation of the ileocecal junction promises as a safe and feasible surgical procedure for right-transverse colon cancer, associated with earlier recovery of bowel function, shorter operation time, and similar pathological outcomes when compared to the conventional laparoscopic procedure.

Abstract Background To retrospectively evaluate the feasibility and safety of intraoperative assessment of bowel perfusion in totally laparoscopic surgery for colon cancer using indocyanine green fluorescence imaging (IGFI). Methods From October 2017 to June 2019, consecutive patients with colon cancer who underwent totally laparoscopic surgery were enrolled retrospectively and grouped into the IGFI group (n = 84) and control group (n = 105). In the IGFI group, indocyanine green (ICG) was injected intravenously, and the bowel perfusion was observed using a fluorescence camera system prior to and after completion of the anastomosis. Results The two groups were demographically comparable. The IGFI group exhibited a significantly shorter operative time (p = 0.0374) while intraoperative blood loss did not significantly differ among the groups (p = 0.062). In the IGFI group, average time to perfusion fluorescence was 48.4 ± 14.0 s after ICG injection, and four patients (4.8%) were required to choose a more proximal point of resection due to the lack of adequate fluorescence at the point previously selected. There were no differences in terms of pathological outcomes, postoperative recovery and the postoperative complication rates between the groups (p>0.05). Conclusion IGFI shows promise as a safe and feasible tool to assess bowel perfusion during a totally laparoscopic surgery for colon cancer and may reduce the operative time.

Purpose Current acceptance of the watch-and-wait (W&W) approach by surgeons in Asia-Pacific countries is unknown. An international survey was performed to determine status of the W&W approach on behalf of the Asia-Pacific Federation of Coloproctology (APFCP). Methods Surgeons in the APFCP completed an Institutional Review Board-approved anonymous e-survey and/or printed letters (for China) containing 19 questions regarding nonsurgical close observation in patients who achieved clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT). Results Of the 417 responses, 80.8% (n = 337) supported the W&W approach and 65.5% (n = 273) treated patients who achieved cCR after nCRT. Importantly, 78% of participants (n = 326) preferred a selective W&W approach in patients with old age and medical comorbidities who achieved cCR. In regard to restaging methods after nCRT, the majority of respondents based their decision to use W&W on a combination of magnetic resonance imaging results (94.5%, n = 394) with other test results. For interval between nCRT completion and tumor response assessment, most participants used 8 weeks (n = 154, 36.9%), followed by 6 weeks (n = 127, 30.5%) and 4 weeks (n = 102, 24.5%). In response to the question of how often responders followed-up after W&W, the predominant period was every 3 months (209 participants, 50.1%) followed by every 2 months (75 participants, 18.0%). If local regrowth was found during follow-up, most participants (79.9%, n = 333) recommended radical surgery as an initial management. Conclusion The W&W approach is supported by 80% of Asia-Pacific surgeons and is practiced at 65%, although heterogeneous hospital or society protocols are also observed. These results inform oncologists of future clinical study participation.

Background This study aimed to investigate the association between radiotherapy for cancer and cardiovascular disease (CVD) deaths and evaluate the relative risk for CVD deaths in the general population and among patients with cancer treated with radiotherapy. Methods and Results The statistics of cancers from 16 sites were extracted from the Surveillance, Epidemiology, and End Results database and evaluated. Multivariable Cox proportional hazards regression analysis was used to analyze the association between radiotherapy and cardiovascular‐specific survival. The standardized mortality ratio for CVD deaths was estimated by comparing the observed deaths of patients with cancer treated with radiotherapy to the expected deaths of the general population. Of the 2 214 944 patients identified from the database, 292 102 (13.19%) died from CVD. Multivariable Cox proportional hazards regression analyses demonstrated that radiotherapy was an independent risk factor for cardiovascular‐specific survival among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. The long‐term cardiovascular‐specific survival of patients with cancer who underwent radiotherapy was significantly lower than that of patients who did not undergo radiotherapy. The incidence of CVD deaths among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers who underwent radiotherapy was higher than that among the general population. Standardized mortality ratio significantly decreased with increasing age at cancer diagnosis, gradually decreased within 10 years of diagnosis and increased after 10 years of diagnosis. Conclusions Radiotherapy is associated with worse cardiovascular‐specific survival in patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. Long‐term surveillance of cardiovascular conditions should be performed after radiotherapy.

Background: Colon cancer (CC) remains one of the most common malignancies with a poor prognosis. Pyroptosis, referred to as cellular inflammatory necrosis, is thought to influence tumor development. However, the potential effects of pyroptosis-related regulators (PRRs) on the CC immune microenvironment remain unknown.Methods: In this study, 27 PRRs reported in the previous study were used to cluster the 1,334 CC samples into three pyroptosis-related molecular patterns. Through subtype pattern differential analysis and structure network mining using Weighted Gene Co-expression Network Analysis (WGCNA), 854 signature genes associated with the PRRs were discovered. Further LASSO-penalized Cox regression of these genes established an eight-gene assessment model for predicting prognosis.Results: The CC patients were subtyped based on three distinct pyroptosis-related molecular patterns. These pyroptosis-related patterns were correlated with different clinical outcomes and immune cell infiltration characteristics in the tumor microenvironment. The pyroptosis-related eight-signature model was established and used to assess the prognosis of CC patients with medium-to-high accuracy by employing the risk scores, which was named “PRM-scores.” Greater inflammatory cell infiltration was observed in tumors with low PRM-scores, indicating a potential benefit of immunotherapy in these patients.Conclusions: This study suggests that PRRs have a significant effect on the tumor immune microenvironment and tumor development. Evaluating the pyroptosis-related patterns and related models will promote our understanding of immune cell infiltration characteristics in the tumor microenvironment and provide a theoretical basis for future research targeting pyroptosis in cancer.

Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB), and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using the Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high-mRNAsi scores are associated with poor overall survival in stage IV CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low-mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 34 key genes as candidate prognosis biomarkers. Finally, a three-gene prognostic signature (PARPBP, KNSTRN, and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort.Conclusion: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

Abstract Background Colorectal cancer is common in elderly patients. Laparoscopy is widely used to approach this kind of disease. This study was to examine short-term outcomes and long-term survival for laparoscopic and open surgery in elderly patients with colorectal cancer. Methods From January 2007 to December 2018, patients with colorectal cancer older than 80 operated at China National Cancer Center were included in the study. Propensity score matching (PSM) was used to minimize the adverse effects. The clinical data between open and laparoscopic surgery was compared, and the effect of factors on overall survival (OS) and disease-free survival (DFS) was analyzed by Cox proportional hazard model. Results Ninety-three pairs were selected after PSM. Patients in laparoscopic group had less intraoperative blood loss, postoperative complications, time to first flatus, time to oral feeding, postoperative hospital stay, and higher retrieved lymph node (P 0.05), besides the CEA level, III/IV stage, and perineural invasion were independent predictors of survival (P

Abstract Background Anastomotic leakage (AL) is a common complication after anterior resection of rectal cancer. Few studies have been conducted to determine whether the traditional predictors of AL can be applied to elderly patients (age ≥ 80) undergoing anterior resection (AR) or low anterior resection (LAR) of rectal cancer. This study was designed to explore the predictive factors for AL after anterior resection of rectal cancer in patients over 80 years old. Methods From January 2007 to May 2019, consecutive elderly (age ≥ 80) rectal cancer patients undergoing AR or LAR at our institution were systematically reviewed. The general information, perioperative outcomes, and comorbidities were collected. Results A total of 288 consecutive patients were included in this study. The average age was 82.8 ± 2.4 years, and 30 (10.4%) patients developed AL. The univariate analyses showed that neoadjuvant therapy (50.0% vs. 27.9%, P = 0.013), the number of stapler firings ≥ 3 (60.0% vs. 36.0%, P = 0.011), and coronary heart disease (CHD) (46.7% vs. 17.8%, P < 0.001) were associated with an increased incidence of AL. The multivariate analysis showed that the number of stapler firings ≥ 3 (OR = 4.77, 95% CI = 1.33–15.21, P = 0.035) and CHD (OR = 8.33, 95% CI = 1.94–13.05, P = 0.003) were independent risk factors for AL. Conclusion The number of stapler firings ≥ 3 and CHD were independent risk factors for AL in elderly patients (age ≥ 80) with rectal cancer. A temporary ileostomy or the Hartmann procedure is recommended for patients with CHD, male patients, patients considered to be obese, and patients with a lower tumor location, which may increase the number of stapler firings. Certainly, we recommend that the number of stapler firings should be minimized to alleviate the economic and physical burden of patients.

Background: The low expression of miR93/25 (members of miR-106b~25 cluster) promoted the invasion and metastasis of colon cancer cells, which predicted poor survival. However, the role of miR-106b-5p, the member of miR-106b~25 cluster, in colorectal cancer (CRC) remains unclear. Methods: Bioinformatics methods were used to predict the potential pairs of lncRNA-miRNA-mRNA. In situ hybridization and qPCR were used to evaluate the expression of MALAT1 and miR-106b-5p in the paraffin-embedded normal and CRC tissues. Kaplan–Meier analysis with the log-rank test was used for survival analyses. Immunohistochemistry staining was applied to investigate the expression of SLAIN2. Fluorescence recovery after photobleaching assay was applied to observe the microtubule (MT) mobility. In vitro and in vivo invasion and metastasis assays were used to explore the function of MALAT1/miR-106b-5p/SLAIN2 in the progression of CRC. Findings: miR-106b-5p was identified as a suppressor in CRC. Functionally, ectopic or silencing the expression of miR-106b-5p inhibited or promoted the invasion and metastasis of CRC cells in vitro and in vivo. The long non-coding RNA MALAT1 regulated the miR-106b-5p expression and further mediated the mobility of SLAIN2-related MTs by functioning as a competing endogenous RNA in vitro and in vivo, which resulted in the progression of CRC. Clinically, low miR-106b-5p expression predicted poor survival of CRC patients, especially in combination with high MALAT1/ SLAIN2 expression. Interpretation: miR-106b-5p served as a suppressor in combination with MALAT1/miR-106b-5p/SLAIN2, which might be a group of potential prognostic biomarkers in the prognosis of CRC. Fund: This work was supported by National Program Project for Precision Medicine in National Research and Development Plan of China (2016YFC0905300), National Natural Science Foundation of China (81572930), National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC0905303, 2016YFC1303200), Beijing Science and Technology Program (D17110002617004), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32012), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001), Incentive Fund for Academic Leaders of Oncology Hospital, Chinese Academy of Medical Sciences (RC2016003), and Beijing Hope Run Special Fund from Cancer Foundation of China (LC2017A19). The project of Shanghai Jiaotong Univversity (YG2017QN30). Keywords: miR-106ba-5p, MALAT1, Microtubules mobility, Colorectal cancer progression

Abstract The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

BackgroundAlthough radiation therapy (RT) improves local control for rectal cancer (RC), the long-term risks from RT, including development of a secondary malignancy, are controversial. The risk and prognosis of secondary bladder cancer (SBC) in RC patients undergoing RT have not been adequately studied. Our goal is to investigate the impact of RT on the risk of developing SBC and assess their survival outcomes.MethodsThis large population-based study included RC patients as their initial primary cancer from nine registries of the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015. The cumulative incidence of SBC was assessed by using Fine and Gray’s competing risk regression. The standardized incidence ratio (SIR) was used to compare the incidence of SBC in RC survivors to the US general population. The Kaplan-Meier method was used to evaluate the 10-year overall survival (OS) and 10-year cancer specific survival (CSS) for patients with SBC.ResultsOf 74,646 RC patients, 24,522 patients were treated with surgery and RT and 50,124 patients were treated with surgery alone. The incidence of SBC was 1.85% among patients who received RT and 1.24% among patients who did not. The incidence of SBC in RC patients who received RT was higher than the US general population (SIR, 1.35; 95% CI, 1.19-1.53, P

Introduction: Neoadjuvant chemoradiotherapy (nCRT) followed by operation has become the standard treatment for locally advanced rectal cancer (LARC). However, considering the possible toxicity and complications of radiochemotherapy, nCRT is seldom used for the elderly. The purpose of this study was to assess the safety and long-term effect of nCRT combined with TME in elderly patients with LARC. Method: Four-hundred-fourteen LARC patients were divided into 2 groups: 108 patients were in the elderly group (≥ 65 years old) and 306 patients were in the non-elderly group (