A Mendelian randomization study between chronic periodontitis and non-alcoholic fatty liver disease.

BACKGROUND AND OBJECTIVE: Observational studies have suggested a potential association between non-alcoholic fatty liver disease (NAFLD) and chronic periodontitis (CP). However, these studies are prone to confounding factors. The aim of this study was to assess the causal relationship between NAFLD and CP using a two-sample bidirectional Mendelian randomization (MR) analysis method. METHODS: Datasets of CP and NAFLD were retrieved from the European database, and instrumental variables (IVs) related to exposure were selected for the MR analysis. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the consistency of the selected IVs, following which the analysis results were visualized. RESULTS: Genetic variants associated with CP and NAFLD were identified as IVs, and the MR assessment was performed using the summary data (CP: 3046 cases and 195 395 controls; NAFLD: 894 cases and 217 898 controls). CP increased the risk of NAFLD (inverse variance weighted [IVW], b = 0.132 > 0, p = .006 < .05), whereas the reverse was not observed (IVW, b = -0.024 < 0, p = .081 > .05). The sensitivity analysis indicated no heterogeneity or horizontal pleiotropy. CONCLUSION: The MR analysis suggested that CP could increase the risk of NAFLD among European populations.

Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial.

INTRODUCTION: Neoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little possibility for organ preservation. Immunotherapy has been shown to have significant survival benefits in microsatellite instability-high patients but poor response in microsatellite stable (MSS) patients. Studies have demonstrated that radiotherapy and immunotherapy have synergistic effects in cancer treatment. There is no existing evidence about the clinical efficacy of immunotherapy combined with nCRT for patients with MSS ultra-low rectal cancer. METHOD AND ANALYSIS: This trial is an open-labelled multicentre prospective randomised controlled trial (NCT05215379) with two parallel groups and allocation ratio 1:1 (nCRT+immunotherapy vs nCRT group). Eligible participants will be aged 18-75 years, with a desire for anus preservation, confirmed cT1-3aN0-1M0 rectal adenocarcinoma, confirmed MSS type, inferior margin of ≤5 cm from the anal verge. The primary endpoint of this trial is complete clinical response (cCR) rate. Immunotherapy is added after 1 week of chemoradiotherapy for two cycles, and then the patients will be administered two cycles of immunotherapy and CAPOX. The evaluations will be carried out after the completion of the whole neoadjuvant therapy. We expect the programme to improve the cCR rate and the quality of life for patients with ultra-low rectal cancer. ETHICS AND DISSEMINATION: This trial was approved by the Ethics committee of Changhai Hospital and other medical centres (Grant number:CHEC2022-118). The results of this study will provide further insight into the clinical efficacy of immunotherapy in combination with nCRT in patients with MSS ultra-low rectal cancer. TRIAL REGISTRATION NUMBER: NCT05215379.

Clinicopathological features and prognosis of synchronous and metachronous colorectal cancer: a retrospective cohort study.

BACKGROUND: To investigate the clinicopathological features and prognosis of synchronous and metachronous multiple primary colorectal cancer. MATERIALS AND METHODS: Patients who underwent operation for synchronous and metachronous colorectal cancer at the colorectal surgery department of Shanghai Changhai Hospital between January 2000 and December 2021 were included. Perioperative indicators were comprehensively compared and included in the survival analyses. RESULTS: In total, 563 patients with synchronous ( n =372) and metachronous ( n =191) colorectal cancer were included. Patients with synchronous colorectal cancer were more likely to have a long onset time, positive carcinoembryonic antigen, advanced TNM stage, large tumor, perineural invasion, p53 high expression, and mismatch repair proficient. Compared with metachronous colorectal cancer, patients with synchronous colorectal cancer showed worse 5-year overall survival (68.6±3.0% vs 81.9±3.5%, P =0.018) and 5-year disease-free survival (61.2±3.1% vs 71.0±3.9%, P =0.022). In the subgroup analysis, segmental resection was an independent risk factor for the long-term outcomes of bilateral synchronous colorectal cancer. CONCLUSIONS: Clinicopathological and molecular features were different between synchronous and metachronous colorectal cancer. Patients with synchronous colorectal cancer showed a worse prognosis than those with metachronous colorectal cancer. Bilateral synchronous colorectal cancer requires extended resection to achieve improved long-term outcomes.

Co-occurrence of fecal incontinence with constipation or irritable bowel syndrome indicates the need for personalized treatment.

BACKGROUND: This study aimed to compare the prevalence and symptoms of fecal incontinence (FI) in relation to irritable bowel syndrome (IBS-associated FI), constipation (constipation-associated FI), and isolation (isolated FI). METHODS: Data were analyzed from 3145 respondents without organic comorbidities known to influence defecation function from the general Chinese population who filled in the online Groningen Defecation and Fecal Continence questionnaire. FI, IBS, and constipation were evaluated with the Rome IV criteria. KEY RESULTS: The prevalence of FI was 10.5% (n = 329) in the non-comorbidity group. After multivariable logistic regression analysis, IBS (odds ratio [OR]: 12.55, 95% confidence interval [CI]: 9.06-17.36) and constipation (OR: 4.38, 95% CI: 3.27-5.85) were the most significant factors contributing to FI. Based on this finding, 106/329 (32.2%) had IBS-associated FI, 119/329 (36.2%) had constipation-associated FI, and 104/329 (31.6%) had isolated FI. Among the 329 FI respondents, there was a high prevalence of IBS and constipation-related symptoms, including abdominal pain (81.5%) and abdominal bloating (77.8%) for IBS and straining during defecation (75.4%), incomplete defecation (72.3%), defecation blockage (63.2%), anal pain during defecation (59.3%), and hard stools (24%) for constipation. The patients with IBS-associated FI asked for specialists' help less frequently than those with isolated FI. Interestingly, among the patients with constipation-associated FI, 56.3% used anti-diarrhea medicine. CONCLUSIONS AND INFERENCES: The prevalence of IBS-associated FI, constipation-associated FI, and isolated FI is comparably high. It is important to diagnose and target the cause of FI to provide personalized and cause-targeting care instead of treating only the FI symptoms.

Comparison of functional and oncological outcome of conformal sphincter preservation operation, low anterior resection, and abdominoperineal resection in very low rectal cancer: a retrospective comparative cohort study with propensity score matching.

PURPOSE: Conformal sphincter preservation operation (CSPO) procedure is a sphincter preservation procedure for preserving the anal canal function for very low rectal cancers. This study investigated the functional and oncological outcome of conformal sphincter preservation operation by comparing with low anterior resection (LAR) and abdominoperineal resection (APR). METHODS: This is a retrospective comparative study. Patients who received conformal sphincter preservation operation (n = 52), low anterior resection (n = 54), or abdominoperineal resection (n = 69) were included between 2011 and 2016 in a tertiary referral hospital. Propensity score matching was applied to adjust the baseline characteristics which may influence the choice of the surgical procedure. RESULTS: Twenty-one pairs of conformal sphincter preservation operation vs. low anterior resection and 29 pairs of conformal sphincter preservation operation vs. abdominoperineal resection were selected. The first group had a higher tumor location than the second group. Compared with the low anterior resection group, the conformal sphincter preservation operation group had shorter distal resection margins; however, no significant differences were identified in daily stool frequency, Wexner incontinence score, local recurrence, distant metastasis, overall survival, and disease-free survival between both groups. Compared with the abdominoperineal resection group, the conformal sphincter preservation operation group had shorter operative time and shorter postoperative hospital stay. No significant differences were identified in local recurrence, distant metastasis, overall survival, and disease-free survival. CONCLUSION: Conformal sphincter preservation operation is oncologically safe compared to APR and LAR, and has similar functional findings to LAR. Studies comparing CSPO with intersphincteric resection should be performed.

Single-cell sequencing technology in colorectal cancer: a new technology to disclose the tumor heterogeneity and target precise treatment.

Colorectal Cancer (CRC) is one of the most common gastrointestinal tumors, and its high tumor heterogeneity makes traditional sequencing methods incapable of obtaining information about the heterogeneity of individual cancer cells in CRC. Therefore, single-cell sequencing technology can be applied to better analyze the differences in genetic and protein information between cells, to obtain genomic sequence information of single cells, and to more thoroughly analyze the cellular characteristics and interactions in the CRC microenvironment. This will provide a more comprehensive understanding of colorectal cancer development and metastasis and indicate the treatment plan and prognosis. In this study, we review the application of single-cell sequencing to analyze the tumor microenvironment of CRC, explore the mechanisms involved in CRC metastasis and progression, and provide a reference for potential treatment options.

Validation of the Chinese DeFeC questionnaire: a comprehensive screening tool for symptoms and causes of constipation and incontinence.

BACKGROUND: Currently, the diagnosis of defecation disorders in China is usually based on varied and ambiguous criteria. We aimed to translate the Groningen Defecation and Fecal Continence (DeFeC) questionnaire to Chinese and test its reproducibility and feasibility in the general Chinese population. METHODS: The Groningen Defecation Questionnaire was translated into Chinese according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). The feasibility and reproducibility were evaluated by performing a test-retest online survey and calculating the Cohen's kappa (κ) coefficient [or intraclass correlation coefficient (ICC)], with 0.01-0.20 considered slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement; and 0.81-1.00, almost perfect agreement. RESULTS: In total, 130 respondents completed the questionnaire twice, with a mean age of 47.08±12.46 years. No remarks were made that indicted that the questions were difficult to understand. The median time to complete the questionnaire was 20.78 min [interquartile range (IQR), 14.83-29.20 min] for the first time. The κ coefficient of all defecation function-related domains ranged between 0.25 and 0.71, with an average value of 0.53. The constipation and fecal incontinence-related domains showed a substantial and moderate agreement level, as indicated by κ of 0.65 and 0.52, respectively. The Agachan constipation score and Wexner incontinence score showed perfect and substantial agreement, as indicated by an ICC of 0.88 and 0.74, respectively. CONCLUSIONS: The Chinese version of the Groningen DeFeC questionnaire is highly feasible and reproducible and can be applied in clinical and research activities for the Chinese population.

DSTN Hypomethylation Promotes Radiotherapy Resistance of Rectal Cancer by Activating the Wnt/ß-Catenin Signaling Pathway.

PURPOSE: Although surgical resection combined with neoadjuvant radiation therapy can reduce the local recurrence rate of rectal cancer, not all patients benefit from neoadjuvant radiation therapy. Therefore, screening for patients with rectal cancer who are sensitive or resistant to radiation therapy has great clinical significance. METHODS AND MATERIALS: Patients with rectal cancer were selected according to postoperative tumor regression grade, and tumor samples were taken for detection. Differential genes between radiation-resistant and radiation-sensitive tissues were screened and validated by Illumina Infinium MethylationEPIC BeadChip, proteomics, Agena MassARRAY methylation, reverse transcription quantitative real-time polymerase chain reaction, and immunohistochemistry. In vitro and in vivo functional experiments verified the role of DSTN. Protein coimmunoprecipitation, western blot, and immunofluorescence were used to investigate the mechanisms of DSTN-related radiation resistance. RESULTS: DSTN was found to be highly expressed (P < .05) and hypomethylated (P < .01) in rectal cancer tissues resistant to neoadjuvant radiation therapy. Follow-up data confirmed that patients with high expression of DSTN in neoadjuvant radiation therapy-resistant rectal cancer tissues had shorter disease-free survival (P < .05). DSTN expression increased after methyltransferase inhibitor inhibition of DNA methylation in colorectal cancer cells (P < .05). In vitro and in vivo experiments showed that knockdown of DSTN promoted the sensitivity of colorectal cancer cells to radiation therapy, and overexpression of DSTN promoted the resistance of colorectal cancer cells to radiation (P < .05). The Wnt/ß-catenin signaling pathway was activated in colorectal cancer cells overexpressing DSTN. ß-catenin was highly expressed in radiation therapy-resistant tissues, and there was a linear correlation between the expression of DSTN and ß-catenin (P < .0001). Further studies showed that DSTN can bind to ß-catenin and increase its stability. CONCLUSIONS: The degree of DNA methylation and the expression level of DSTN can be used as biomarkers to predict the sensitivity of neoadjuvant radiation therapy for rectal cancer. DSTN and ß-catenin are also expected to become a reference for the selection of neoadjuvant radiation therapy.

An easy-to-use artificial intelligence preoperative lymph node metastasis predictor (LN-MASTER) in rectal cancer based on a privacy-preserving computing platform: multicenter retrospective cohort study.

BACKGROUND: Although the surgical treatment strategy for rectal cancer (RC) is usually based on the preoperative diagnosis of lymph node metastasis (LNM), the accurate diagnosis of LNM has been a clinical challenge. In this study, we developed machine learning (ML) models to predict the LNM status before surgery based on a privacy-preserving computing platform (PPCP) and created a web tool to help clinicians with treatment-based decision-making in RC patients. PATIENTS AND METHODS: A total of 6578 RC patients were enrolled in this study. ML models, including logistic regression, support vector machine, extreme gradient boosting (XGB), and random forest, were used to establish the prediction models. The areas under the receiver operating characteristic curves (AUCs) were calculated to compare the accuracy of the ML models with the US guidelines and clinical diagnosis of LNM. Last, model establishment and validation were performed in the PPCP without the exchange of raw data among different institutions. RESULTS: LNM was detected in 1006 (35.3%), 252 (35.3%), 581 (32.9%), and 342 (27.4%) RC patients in the training, test, and external validation sets 1 and 2, respectively. The XGB model identified the optimal model with an AUC of 0.84 [95% confidence interval (CI), 0.83-0.86] compared with the logistic regression model (AUC, 0.76; 95% CI, 0.74-0.78), random forest model (AUC, 0.82; 95% CI, 0.81-0.84), and support vector machine model (AUC, 0.79; 95% CI, 0.78-0.81). Furthermore, the XGB model showed higher accuracy than the predictive factors of the US guidelines and clinical diagnosis. The predictive XGB model was embedded in a web tool (named LN-MASTER) to predict the LNM status for RC. CONCLUSION: The proposed easy-to-use model showed good performance for LNM prediction, and the web tool can help clinicians make treatment-based decisions for patients with RC. Furthermore, PPCP enables state-of-the-art model development despite the limited local data availability.

Erratum: miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells: Erratum.

[This corrects the article DOI: 10.7150/jca.42731.].

Predictive value of modified MRI-based split scar sign (mrSSS) score for pathological complete response after neoadjuvant chemoradiotherapy for patients with rectal cancer.

PURPOSE: To measure the diagnostic performance of modified MRI-based split scar sign (mrSSS) score for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for patients with rectal cancer. METHODS: The modified MRI-based split scar sign (mrSSS) score, which consists of T2-weighted images (T2WI)-based score and diffusion-weighted images (DWI)-based score. The sensitivity, specificity, and accuracy of modified mrSSS score, endoscopic gross type, and MRI-based tumor regression grading (mrTRG) score, in the prediction of pCR, were compared. The prognostic value of the modified mrSSS score was also studied. RESULTS: A total of 189 patients were included in the study. The Kendall's coefficient of interobserver concordance of modified mrSSS score, T2WI -based score, and DWI-based score were 0.899, 0.890, and 0.789 respectively. And the maximum and minimum k value of the modified mrSSS score was 0.797 (0.742-0.853) and 0.562 (0.490-0.634). The sensitivity, specificity, and accuracy of prediction of pCR were 0.66, 0.97, and 0.90 for modified mrSSS score; 0.37, 0.89, and 0.78 for endoscopic gross type (scar); and 0.24, 0.92, and 0.77 for mrTRG score (mrTRG = 1). The modified mrSSS score had significantly higher sensitivity than the endoscopic gross type and the mrTRG score in predicting pCR. Patients with lower modified mrSSS scores had significantly longer disease-free survival (P < 0.05). CONCLUSION: The modified mrSSS score showed satisfactory interobserver agreement and higher sensitivity in predicting pCR after nCRT in patients with rectal cancer. The modified mrSSS score is also a predictor of disease-free survival.

Re-recognition of BMPR1A-related polyposis: beyond juvenile polyposis and hereditary mixed polyposis syndrome.

Background: Bone morphogenetic protein receptor type 1A (BMPR1A) is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2, which have overlapping phenotypes. This study aimed to elucidate whether these two syndromes are just two subtypes of a single syndrome rather than two isolated syndromes. Methods: We sequenced the BMPR1A gene in 186 patients with polyposis and colorectal cancer, and evaluated the clinicopathological features and phenotypes of the probands and their available relatives with BMPR1A mutations. Results: BMPR1A germline mutations were found in six probands and their three available relatives. The numbers of frameshift, nonsense, splice-site, and missense mutations were one, one, two, and two, respectively; two of the six mutations were novel. Typical juvenile polyps were found in only three patients. Two patients had colorectal cancer rather than any polyps. Conclusions: Diseases in BMPR1A germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers. The variety of phenotypes reflected the features of BMPR1A-mutation carriers, which should be recognized as a spectrum of one syndrome. Genetic testing may be a good approach to identifying BMPR1A-related syndromes.

N6-methyladenosine-modified circular RNA QSOX1 promotes colorectal cancer resistance to anti-CTLA-4 therapy through induction of intratumoral regulatory T cells.

BACKGROUND: Colorectal cancer (CRC) is the 3rd most common cancer worldwide. CircRNAs are promising novel biomarkers for CRC. T regulatory (Treg) cells express the immune checkpoint receptor of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and promote tumor immunological tolerance. We therefore investigate the biological functions and mechanisms of circQSOX1 in CRC tumorigenesis; involvement of circQSOX1 in promoting Treg cell-mediated CRC immune escape in anti-CTLA-4 therapy. METHODS: Bioinformatics analyses were performed for circQSOX1expressions, specific binding sites, and N6-methyladenosine (m6A) motifs of circQSOX1, thatwere further validated with a series of experiments. Functions of circQSOX1 in promoting CRC development, Treg cells-based immune escape, and anti-CTLA-4 therapy response were investigated both in vitro and in vivo. RESULTS: High circQSOX1 expression was associated with carcinogenesis and poor clinical outcome of CRC patients. METTL3-mediated RNA m6A modification on circQSOX1 could be read by IGF2BP2 in CRC cells. CircQSOX1 promoted CRC development by regulating miR-326/miR-330-5p/PGAM1 axis. CircQSOX1 regulated glycolysis and promoted immune escape of CRC cells, and inhibits anti-CTLA-4 therapy response in CRC patients. CONCLUSION: m6A-modified circQSOX1 facilitated CRC tumorigenesis by sponging miR-326 and miR-330-5p to promotes PGAM1 expression, which further promoted CRC immune escape by activating glycolysis and inactivating the anti-CTLA-4 therapy response of CRC. Combined treatment with sh-circQSOX1 and anti-CTLA-4 could be a strategy to overcome Treg cell-mediated CRC immune therapy resistance.

Effects of Hypovitaminosis D on Preoperative Pain Threshold and Perioperative Opioid Use in Colorectal Cancer Surgery: A Cohort Study.

BACKGROUND: Postoperative pain after colorectal cancer surgery has a significant impact on postoperative physical and mental health. Vitamin D deficiency has been correlated with both acute pain states, including postoperative and post-traumatic pain, and several chronic pain diseases. The effects of hypovitaminosis D on preoperative pain threshold and perioperative opioid use in colorectal cancer surgery still need to be studied. OBJECTIVES: To find the relationship between hypovitaminosis D on pain threshold, perioperative opioid use, and postoperative complications in colorectal cancer surgery. STUDY DESIGN: A total of 112 patients, who were enrolled in this prospective, observational trial, were divided into 2 groups based on their preoperative serum 25-hydroxyvitamin D (25 [OH] D3) levels: (1) group D: vitamin D-deficient group (< 20 ng/mL); and (2) group S: vitamin D-sufficient group (>= 20 ng/mL). METHODS: Primary outcomes were pain threshold indexes, perioperative dosages of opioid use, and postoperative pain. Secondary outcomes were other postoperative complications. RESULTS: Preoperative serum level of vitamin D was 14.94 ± 3.10 ng/mL in group D and 24.20 ± 4.80 ng/mL in group S. Significant differences were showed in the 3 indexes of pain threshold and analgesic consumption between the 2 groups (P < 0.05). A low 25 (OH) D3 level was associated with a higher opioid dose of sufentanil. There was an association between 25 (OH) D3 and pain enduring threshold (PET), beta coefficient beta = 0.532, 95% confidential interval  (0.440, 0.623), P < 0.001. The history of diabetes mellitus (DM) and vitamin C and vitamin D levels may be risk factors of surgical site infections (SSI), and the binary logistics regression model is statistically significant, chi-squared = 35.028, P < 0.001. LIMITATIONS: There is room for further expansion in the sample size. Our study lacked objective indicators to measure pain threshold. Intestinal recovery time and total hospital stay were not included in the final analysis. In the follow-up study, the vitamin D supplementation group should be set and the specific site of colorectal cancer surgery also needs to be divided more carefully. CONCLUSIONS: On the basis of the study results, hypovitaminosis D is associated with increased perioperative opioid consumption in colorectal cancer surgery. Sensory perception and pain threshold of patients with insufficient 25 (OH) D3 concentration were more sensitive, and PET was lower. History of DM, vitamin D, and vitamin C may be factors related with SSI. Future studies are needed to investigate their relationship further and discover if postoperative pain and pain threshold can benefit from vitamin D supplementation in these patients.

Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers.

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was - 0.3 (95%CI - 4.0 ~ 3.4) mm, - 0.9 (95%CI - 3.4 ~ 1.7) mm, and - 0.4 (95%CI - 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.

Evaluation of the learning curve for conformal sphincter preservation operation in the treatment of ultralow rectal cancer.

BACKGROUND: To investigate the learning curve of conformal sphincter preservation operation (CSPO) in the treatment of ultralow rectal cancer and to further explore the influencing factors of operation time. METHODS: From August 2011 to April 2020, 108 consecutive patients with ultralow rectal cancer underwent CSPO by the same surgeon in the Department of Colorectal Surgery of Changhai Hospital. The moving average and cumulative sum control chart (CUSUM) curve were used to analyze the learning curve. The preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data were compared before and after the completion of learning curve. The influencing factors of CSPO operation time were analyzed by univariate and multivariate analysis. RESULTS: According to the results of moving average and CUSUM method, CSPO learning curve was divided into learning period (1-45 cases) and learning completion period (46-108 cases). There was no significant difference in preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data between the two stages. Compared with the learning period, the operation time (P < 0.05), blood loss (P < 0.05), postoperative flatus and defecation time (P < 0.05), liquid diet time (P < 0.05), and postoperative hospital stay (P < 0.05) in the learning completion period were significantly reduced, and the difference was statistically significant. Univariate and multivariate analysis showed that distance of tumor from anal verge (≥ 4cm vs. < 4cm, P = 0.039) and T stage (T3 vs. T1-2, P = 0.022) was independent risk factors for prolonging the operation time of CSPO. CONCLUSIONS: For surgeons with laparoscopic surgery experience, about 45 cases of CSPO are needed to cross the learning curve. At the initial stage of CSPO, beginners are recommended to select patients with ultralow rectal cancer whose distance of tumor from anal verge is less than 4 cm and tumor stage is less than T3 for practice, which can enable beginners to reduce the operation time, accumulate experience, build self-confidence, and shorten the learning curve on the premise of safety.

Machine learning-based random forest predicts anastomotic leakage after anterior resection 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.

MRI-based nomogram analysis: recognition of anterior peritoneal reflection and its relationship to rectal cancers.

BACKGROUND: This study is aimed to explore the factors influencing the visualization of the anterior peritoneal reflection (APR) and evaluated the feasibility of measuring the distance from the anal verge to APR (AV-APR), the tumor height on MRI and the accuracy of determining the tumor location with regard to APR. METHODS: We retrospectively analyzed 110 patients with rectal cancer. A univariate and multivariate logistic regression was performed to identify the independent factors (age, sex, T stage, the degree of bladder filling, pelvic effusion, intraoperative tumor location, BMI, uterine orientation, the distance from seminal vesicle/uterus to rectum) associated with the visualization of the APR on MRI. The nomogram diagram and receiver operating characteristic curve (ROC curve) were established. Intraclass correlation coefficient (ICC) was used to evaluate the consistency of the distance of AV-APR. The Pearson correlation coefficient was used to characterize the agreement between measurements of the tumor height by colonoscopy and MRI. The Kappa statistics was used to evaluate the value of MRI in the diagnosis of the tumor location with regard to the APR. RESULTS: Multivariate logistic regression showed that BMI (P = 0.031, odds ratio, OR = 1.197), pelvic effusion (P = 0.020, OR = 7.107) and the distance from seminal vesicle/uterus to the rectum (P = 0.001, OR = 3.622) were correlated with the visualization of APR. The cut-off point of BMI and the distance from seminal vesicle/uterus to the rectum is 25.845 kg/m2 and 1.15 cm. The area under curve (AUC) (95% Confidence Interval, 95% CI) of the combined model is 0.840 (0.750-0.930). The favorable calibration of the nomogram showed a non-significant Hosmer-Lemeshow test statistic (P = 0.195). The ICC value (95% CI) of the distance of AV-APR measured by two radiologists was 0.981 (0.969-0.989). The height measured by MRI and colonoscopy were correlated with each other (r = 0.699, P < 0.001). The Kappa value was 0.854. CONCLUSIONS: BMI, pelvic effusion, and the distance from seminal vesicle/uterus to rectum could affect the visualization of APR on MRI. Also, it's feasible to measure the distance of AV-APR, the tumor height, and to evaluate the tumor location with regard to APR using MRI.

Rectal cancer patients with downstaging after neoadjuvant chemoradiotherapy and radical resection do not benefit from adjuvant chemotherapy.

BACKGROUND: Whether adjuvant chemotherapy is beneficial for rectal cancer patients who respond well to neoadjuvant chemoradiotherapy (NCRT) and undergo radical resection is controversial. This study aimed to assess the effect of adjuvant chemotherapy on the oncological outcomes of ypT0-2N0 rectal cancer patients after NCRT and radical resection, and identify the prognostic factors. METHODS: The clinical and pathological data of rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection between January, 2010 and June, 2018 were collected and retrospectively analyzed. The oncological outcomes of the chemotherapy (chemo) group and the non-chemotherapy (non-chemo) group were compared. Multivariate analysis, using a Cox proportional hazard model, was performed to identify independent predictors of oncological outcome. RESULTS: Of the 121 rectal cancer patients enrolled, 90 patients received postoperative adjuvant chemotherapy with no fewer than 3 cycles (the chemo group), and the other 31 patients with fewer than 3 cycles (the non-chemo group). There was no significant difference in the 5-year disease-free survival (DFS) or overall survival (OS) rates between the two groups (DFS: 79.1% vs. 82.9%, P=0.442; OS: 87.5% vs. 78.2%, P=0.667). cT4 is an independent risk factor for OS (HR =4.227, 95% CI: 1.128-15.838, P=0.02) and DFS (HR =4.878, 95% CI: 1.752-13.578). Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT significantly improved the DFS rate (HR =0.212, 95% CI: 0.058-0.776, P=0.019). CONCLUSIONS: Rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection did not benefit significantly from postoperative adjuvant chemotherapy. For these patients, cT4 was an independent risk factor for OS and DFS. Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT can significantly improve DFS.

Greater Peripouch Fat Area on CT Image Is Associated with Chronic Pouchitis and Pouch Failure in Inflammatory Bowel Diseases Patients.

BACKGROUND: The causes of chronic antibiotic refractory pouchitis (CARP) and pouch failure in inflammatory bowel disease (IBD) patients remain unknown. Our previous small study showed peripouch fat area measured by MRI was associated with pouchitis. AIMS: To explore the relationship between peripouch fat area on CT imaging and pouch outcomes. METHODS: This is a historical cohort study. Demographic, clinical, and radiographic data of IBD patients with abdominal CT scans after pouch surgery between 2002 and 2017 were collected. Peripouch fat areas and mesenteric peripouch fat areas were measured on CT images at the middle pouch level. RESULTS: A total of 435 IBD patients were included. Patients with higher peripouch fat areas had a higher prevalence of CARP. Univariate analyses demonstrated that long duration of the pouch, high weight or body mass index, the presence of primary sclerosing cholangitis or other autoimmune disorders, and greater peripouch fat area or mesenteric peripouch fat area were risk factors for CARP. Multivariable analyses demonstrated that the presence of primary sclerosing cholangitis or autoimmuned disorders, and greater peripouch fat area (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.016-1.047, P < 0.001) or mesenteric peripouch fat area were independent risk factors for CARP. Of the 435 patients, 139 (32.0%) had two or more CT scans. Multivariable Cox proportional hazard analyses showed that "peripouch fat area increase ≥ 15%" (OR 3.808, 95%CI 1.703-8.517, P = 0.001) was an independent predictor of pouch failure. CONCLUSIONS: A great peripouch fat area measured on CT image is associated with a higher prevalence of CARP, and the accumulation of peripouch fat is a risk factor for pouch failure. The assessment of peripouch fat may be used to monitor the disease course of the ileal pouch.