[Advances in three-dimensional tumor models for colorectal cancer].

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.

[Analysis of influencing factors and clinical value of anterior peritoneal reflection for patients with rectal cancer].

Objectives: To investigate the factors influencing the height of anterior peritoneal reflection (APR) for patients with rectal cancer, and to analyze the relationship between the APR and the lateral lymph node metastasis. Methods: Clinical data of 432 patients with tumor located within and below APR were retrospectively collected from the rectal cancer database at the Department of General Surgery, Peking Union Medical College Hospital from August 2020 to September 2022. Ninty-eight non-rectal cancer patients were also enrolled as a control group. There were 308 males and 124 females in the tumor group, aged (M(IQR)) 62 (16) years (range: 24 to 85 years) and 53 males and 45 females in the control group, aged 60 (22) years (range: 27 to 87 years). The APR height, pelvis, and tumor-related parameters were measured by MRI. A multifactor linear regression model was established to analyze the dependent correlation factors of APR height. These factors of the two groups were matched by propensity score matching and their APR heights were compared after matching. An ordinal Logistic regression model was established to explore the relationship between APR-related parameters and radiographic lateral lymph node metastasis. Results: The APR height of the tumor group was (98.7±14.4) mm (range: 43.3 to 154.0 mm) and the control group was (95.1±12.7) mm (range: 68.0 to 137.9 mm). Multivariable linear regression revealed that the greater the weight (B=0.519, 95%CI: 0.399 to 0.640, P<0.01), the anterior pelvic depth (B=0.109, 95%CI: 0.005 to 0.213, P=0.039) and the smaller the bi-ischial diameter (B=-0.172, 95%CI:-0.294 to -0.049, P=0.006), the higher the APR height. The tumor group had a higher APR height than the control group after propensity score matching ((98.3±14.2) mm vs. (95.1±12.7) mm, t=-1.992, P=0.047). Ordinal Logistic regression indicated that the longer segment of the tumor invade the nonperitoneal rectum was an independent influencing factor of radiographic lateral lymph node metastasis (OR=1.016, 95%CI: 1.002 to 1.030, P=0.021), while the distance between the anal verge and the tumor was not (OR=0.986, 95%CI: 0.972 to 1.000, P=0.058). Conclusions: The higher the weight, the deeper and narrower the pelvis, the higher the APR height. There is a certain relationship between APR and lateral lymph node metastasis on imaging.

[Development and validation of a prognostic prediction model for patients with stage â to â ¢ colon cancer incorporating high-risk pathological features].

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

[Analysis of prognosis factors of postoperative cardiac complications in colorectal cancer patients with comorbid coronary artery disease].

Objective: To examine the prognosis factors of postoperative cardiac complications in colorectal cancer patients co-morbidated with coronary artery disease. Methods: Clinical data of 449 patients colorectal cancer patients co-morbidated with coronary artery disease accepted redical surgery from April 2013 to April 2020 at Department of General Surgery, Peking Union Medical College Hospital were analyzed retrospectively. There were 306 males and 143 females, aging (68.7±8.9) years (range: 44 to 89 years). Postoperative acute coronary syndrome, new-onset arrhythmia and heart failure that causes clinical symptoms were recorded as cardiac complications. t test, χ2 test and Fisher exact test were used for univariate analysis of prognosis factors of postoperative cardiac events. The variables with P<0.05 were included in the multivariate Logistic regression was used to determine the independent prognosis factors. Results: After surgery, 44 patients (9.8%) suffered from at least one cardiac event, including 30 patients with acute coronary syndrome, 19 patients with new-onset arrhythmia and 9 patients with heart failure. There were 3 deaths in the cohort within 30 days after surgery. Two patients died from cardiac-related complications, and one from septic shock due to postoperative anastomotic leaks. On Univariate analysis showed that cardiac complications were associated with age ≥80 years, co-morbidated diabetes, emergency surgery, re-operation, anastomotic leakage, intestinal flora disorder and elevation of preoperative neutrophil-lymphocyte ratio (χ2: 4.308 to 12.219, all P<0.05). Multivariate Logistic regression analysis identified age ≥80 years(OR=3.195, 95%CI: 1.379 to 7.407, P=0.007), co-morbidated diabetes (OR=2.551, 95%CI: 1.294 to 5.025, P=0.007), emergency surgery (OR=4.717, 95%CI: 1.052 to 20.833, P=0.043), and elevated preoperative neutrophil-lymphocyte ratio (OR=1.114, 95%CI: 1.018 to 1.218, P=0.018) as independent prognosis factors for cardiac complications. Conclusions: Emergency surgery, advanced age, co-morbidated type 2 diabetes and elevated preoperative neutrophil-lymphocyte ratio may increase the risk of postoperative cardiac complications in colorectal cancer patients with coronary artery disease. Surgeons should strictly master surgical indications, pay attention to preoperative assessment, perioperative monitoring, and diagnosis and treatment of postoperative complications in order to reduce the risk of complications.

[Clinicopathological characteristics, diagnosis, and treatment of 29 cases of signet ring cell carcinoma of the rectum and sigmoid colon].

Objective: To investigate the clinicopathological characteristics and the therapeutic effects of signet ring cell carcinoma (SRCC) of rectum and sigmoid colon. Methods: Clinical data and the follow-up information of 29 SRCC patients treated in our tertiary care center from 2008 to 2018 were retrospectively reviewed. The clinicopathological features, diagnostic and therapeutic effects, and the prognostic outcomes were analyzed. Results: Among the 29 patients, 17 were male, 12 were female. The average age was (48.7±14.3) years. Colonoscopy revealed the features of diffuse circumferential thickening of the bowel wall in 20/29 cases (69.0%), while in 9/29 cases (31.0%), endoscopic biopsies showed false negative results. Twenty-five% (4/16) and 17.6% (3/17) lesions were misdiagnosed as the inflammatory changes by endoscopic rectal ultrasonography exam and rectal MRI scan, respectively. Thirteen of the 29 patients received the neoadjuvant chemoradiotherapy (NCRT), 27 patients underwent the radical resection surgeries, and 8 underwent the postoperative radiotherapy. With a median follow-up of 38.5 (3.5-87.0) months, the cumulative 3-years overall survival (OS) rate was 54.0%, and the cumulative 3-years disease-free survival (DFS) rate was 43.0%. The OS rates of patients treated with or without NCRT (non-NCRT) were 46.2% and 69.2%, respectively, without significant difference (P>0.05). The DFS rates of patients treated with or without NCRT were 45.8% and 39.2%, respectively, without significant difference (P>0.05). Parameters including age younger than 40 years and tumor size larger than 5 cm were independent potential risk factors for shortened OS (P<0.05). Conclusions: SRCC of the rectum and sigmoid colon is a rare malignant tumor with special clinical manifestations. It is younger-onset, highly malignant and with very poor prognosis. Therefore, in-depth researches with focus upon the progress of molecular oncology are urgently needed to substantially improve the therapeutic effect of this disease.

[The 479th case: cognitive impairment, respiratory failure, colon mass].

A 78-year-old man was admitted to Peking Union Medical College Hospital with fever, weakness of lower extremities, less speech, loss of memory. Fever was relieved after antibiotic treatment, while cognitive impairment and disorder of consciousness progressed rapidly, followed by critical pulmonary infections, respiratory failure, and septic shock. Lab tests showed negative occult blood, normal serum CEA level and positive Anti-nuclear-antibody. PET-CT suggested that strong FDG uptake signals were seen at sigmoid, while bilateral frontal lobe, temporal lobe, parietal lobe, posterior cingulate gyrus showed lower metabolic activity. Colonoscopy biopsy revealed differentiated adenocarcinoma of sigmoid colon. Therefore, paraneoplastic syndrome of nervous system secondary to colon cancer was considered. Rapid and proper diagnosis and treatment were completed by multidisciplinary team including departments of neurology, gastroenterology, general surgery, ICU, rheumatology, clinical nutrition. The laparoscopic sigmoid colectomy was performed under general anesthesia. The patient finally presented with significant improvement of cognition and consciousness. Respiratory function was totally recovered.

[Analysis of Clavien-Dindo classification and its prognosis factors of complications after laparoscopic right hemicolectomy].

Objective: To analyze the Clavien-Dindo classification of complications after right hemicolectomy and to explore the prognosis factors for postoperative complications. Methods: The retrospective case-control study was adopted. The clinical data of 176 patients who underwent right hemicolectomy at Department of General Surgery, Peking Union Medical College Hospital from October 2016 to February 2018 were collected. There were 95 male and 81 female patients with age of (62.4±12.7) years. The Clavien-Dindo classification was used for postoperative complications. Univariate and multivariate analysis were used to analyze the independent prognosis factors of complications after right colon resection. Results: Of the 176 patients, 2 patients had intraoperative complications (1.1%) and 39 patients had postoperative complications (22.2%), of which 10 cases had more than two complications, with a total of 53 complications. The proportions of Clavien-Dindo grade Ⅰ, Ⅱ, Ⅲ and Ⅳ complications were 41.5% (22/53), 49.1% (26/53), 7.5% (4/53), and 1.9%(1/53). Postoperative complications were associated with age, smoking history of the last 1 year, combined organ resection, lymph node dissection, intracorporeal anastomosis, and preoperative blood AST and Ca levels (all P<0.05). The results of multivariate analysis showed that intracorporeal anastomosis (OR=5.62, 95% CI: 2.46 to 12.85, P=0.00), preoperative blood AST (OR=-0.009, 95% CI: -0.018 to 0.000, P=0.04) and Ca (OR=0.51, 95% CI: 0.08 to 0.95, P=0.02) levels were independent prognosis factors affecting complications after right hemicolectomy. Conclusions: Complications of right hemicolectomy were mainly Clavien-Dindo grade Ⅰ and Ⅱ. Laparoscopic intracorporeal anastomosis should be carefully chosen, which may increase postoperative complications.

[Oncological outcomes analysis of colorectal cancer with unfavorable histological features].

Objective: To explore the effect of unfavorable histological features on the clinical outcomes of patients receiving radical resection of colorectal cancer. Methods: A retrospective analysis of patients with colorectal cancer who received radical surgery between January 2013 and December 2015 at Department of General Surgery, Peking Union Medical College Hospital was performed. The impact of unfavorable histological features on the oncological outcomes of patients with lymph node-negative colorectal cancer were analyzed.A total of 167 patients were enrolled, including 98 males and 69 females with age of (63.6±11.6) years. Observation indicators included age, T stage, lymphovascular invasion, perineural invasion, tumor deposits, number of lymph node dissection, degree of differentiation, tissue type, and circumferential margin. Univariate analysis was performed with χ(2) test and multivariate analysis was performed with Cox regression model. Results: Univariate analysis showed that positive circumferential margins (CRM), tumor deposits and age were associated with disease free survival (DFS) rate; positive CRM, age, tumor deposits, and lymph nodes dissection less than 12 were significantly associated with overall survival (OS) rate (all P<0.05). Multivariate analysis showed that over 70 years of age (HR=1.053, 95% CI: 1.013 to 1.095, P=0.009), poorly differentiated adenocarcinoma (HR=7.572, 95%CI: 1.815 to 31.587, P=0.005), tumor deposits (HR=4.711, 95% CI: 1.809 to 12.264, P=0.002), mucinous adenocarcinoma (HR=3.063, 95% CI: 1.003 to 9.354, P=0.049), lymphovascular invasion (HR=2.885, 95% CI: 1.062 to 7.832, P=0.038), and nerve infiltration (HR=6.610, 95% CI: 1.037 to 42.122, P=0.046) were adverse prognostic factors of DFS rate; poorly differentiated adenocarcinoma (HR=12.200, 95% CI: 1.985 to 74.972, P=0.007), tumor nodules (HR=5.379, 95% CI: 1.636 to 17.685, P=0.006), over 70 years of age (HR=1.062, 95% CI: 1.013 to 1.114, P=0.013), and perineural invasion (HR=8.043, 95% CI: 1.026 to 63.055, P=0.047) were adverse prognostic factors of OS rate. There was no significant difference in the 3-year DFS rate and 3-year OS rate between T1-2 group and T3-4 group (P>0.05). Conclusion: Over 70 years of age, poorly differentiated adenocarcinoma, mucinous adenocarcinoma, tumor nodules, lymphovascular invasion, and perineural invasion are independent adverse prognostic factors of lymph node-negative colorectal cancer.

MicroRNA-219-5p functions as a tumor suppressor partially by targeting platelet-derived growth factor receptor alpha in colorectal cancer.

Platelet-derived growth factor receptor (PDGFR) signaling pathway was involved in the progress of colorectal cancer (CRC). By using the bioinformatic system online, we found that PDGFRα is a potential target of miR-219-5p. However, the expression pattern and underlying mechanisms of miR-219-5p had not been elucidated in CRC. Herein, we first evaluated the expression of miR-219-5p in tumor tissues by real-time polymerase chain reaction. Next, we confirmed that PDGFRα is the target of miR-219-5p by using luciferase report. And then, we investigated the biological functions of miR-219-5p in vitro in cell proliferation and apoptosis as well as cell cycle by gain and loss of function strategies. Data shown that miR-219-5p is down-regulated in CRC tissues compared with the corresponding matched normal tissues. PDGFRα was a direct target of miR-219-5p. Overexpression of miR-219-5p could inhibit cell proliferation, promote cell apoptosis and induce cell cycle arrest at the G1 phase. Furthermore, miR-219-5p suppressed the activation of the phosphatidylinositol 3-kinase/Akt signaling pathway and downregulated G1 cell-cycle-related protein cyclin D1, cyclin-dependent kinase (CDK) 4, and CDK6. Taken together, our results demonstrate that miR-219-5p functions as a tumor suppressor partially by targeting PDGFRα in colorectal cancer.

Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4.

Here we report the case of a 69-year-old Chinese Han woman who presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia and high transferrin saturation. Subsequent genetic analyses identified a novel heterozygous mutation (p.Cys326Phe) in the SLC40A1 gene. This is the first report regarding a SLC40A1 mutation in the Chinese Han population and provides novel clinical evidence for the importance of p.Cys326 in SLC40A1 gene function.

A laparoscopic approach to benign retrorectal tumors.

BACKGROUND: Retrorectal tumors (RTs) are rare in adults. Their surgical excision is often difficult because of their anatomic location. The aim of this study was to evaluate the results of straight laparoscopic resection of RTs in our institution. METHODS: Eight patients (six women and two men) with benign RTs were treated by laparoscopic resection in our tertiary care center between September 2012 and June 2013. Exclusion criteria included malignant tumors, lesions with fistula formation, and anterior sacral meningoceles. Clinical data, imaging features, operative details, pathological results, and treatment outcomes were reviewed and analyzed. RESULTS: Eight cases of benign RT with an average diameter of 8.9 ± 1.7 cm were treated by a straight laparoscopic procedure. The mean operative time was 122 ± 36 min, and the average intraoperative blood loss was 46 ± 33 ml. The median postoperative stay was 5 days (range 3-8 days), and all patients were discharged without serious complications. During a median follow-up of 11 months, no tumor recurrence was observed. CONCLUSIONS: In our experience, a laparoscopic approach is safe for removing benign tumors in the retrorectal space. This approach may provide access to this difficult-to-reach space and has the advantages of allowing excellent visualization, meticulous dissection, less morbidities, and fast recuperation.

[Effects of tumor location and mismatch repair on clinicopathological features and survival for non-metastatic colon cancer: A retrospective, single center, cohort study].

Objective: To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers. Methods: This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two-thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left-sided colon cancers (LCCs). Clinicopathological features were compared using the χ2 test or Mann-Whitney U test. Survival was estimated by Kaplan-Meier curves and the log-rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results: The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m2 vs. 23.2 [21.3, 25.5] kg/m2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow-up time for all patients was 48 (range 33, 59) months. The log-rank test revealed no significant differences in disease-free survival (DFS) (P=0.668) or overall survival (OS) (P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204‒0.862, P=0.018), whereas a higher proportion of T3-4 (HR=2.178, 95%CI: 1.089‒4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443‒3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115‒3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146‒0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103‒1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log-rank test revealed no significant differences in DFS (P=0.343) or OS (P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS (P=0.047) and OS (P=0.040) than did patients with pMMR. Conclusions: Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

[Risk factor and early diagnosis of anastomotic leakage after rectal cancer surgery].

Anastomotic leakage (AL) is one of the most serious complications after sphincter- preserving surgery for rectal cancer, which can significantly prolong the length of stay of patients, increase perioperative mortality, cause dysfunction, shorten overall survival and recurrence-free survival of patients. In order to reduce the serious consequences caused by AL, prediction of AL through preoperative and intraoperative risk factors are of great importance. However, the influences of neoadjuvant chemoradiotherapy, protective stoma, laparoscopic surgery and some intraoperative manipulations on AL are still controversial. Through the auxiliary judgment of anastomotic blood supply during operation, such as indocyanine green imaging, hemodynamic ultrasound, etc., it is expected to achieve the source control of AL. Early diagnosis of AL can be achieved by attention to clinical manifestations and drainage, examination of peripheral blood, drainage and intestinal flora, identification of high risk factors such as fever, diarrhea and increased infectious indicators, and timely administration of CT with contrast enema.

[Quality of life of patients with locally advanced rectal cancer after neoadjuvant therapy and sphincter-preserving surgery].

Objective: To investigate quality of life (QoL) of patients with locally advanced rectal cancer (LARC) who underwent low anterior resection with protective stoma under neoadjuvant therapy mode, and to explore the changes of QoL of patients from before neoadjuvant therapy to 12 months after stoma reversal. Methods: A descriptive case series study was carried out. A retrospective study was performed on patients with mid and low LARC who received complete neoadjuvant long course radiotherapy and chemotherapy, followed by radical low anterior resection (LAR) combined with protective stoma at Peking Union Medical College Hospital from December 2017 to January 2020. Inclusion criteria: (1) patients with rectal MRI assessment of mT3-4b or mN1-2 without distant metastasis (M0) before neoadjuvant therapy; (2) distance from tumor lower margin to the anal verge <12 cm; (3) rectal adenocarcinoma confirmed by biopsy before neoadjuvant therapy; (4) complete cycle of neoadjuvant therapy; (5) patients undergoing radical LAR with sphincter preservation and protective ostomy; (6) patients receiving follow-up for more than 12 months after stoma reversal. Exclusion criteria: (1) patients as grade Ⅳ to Ⅴclassified by the American Society of Anesthesiologists (ASA); (2) patients with multiple primary colorectal cancer; (3) patients with history of other malignant tumors in the past 5 years; (4) patients of emergency surgery; (5) pregnant or lactating women; (6) patients with history of severe mental illness; (7) patients with contraindication of MRI, radiotherapy, chemotherapy, or surgical treatment. A total of 83 patients were enrolled, including 51 males and 28 females with median age of 59 years and mean BMI of (24.4±3.1) kg/m(2). EORTC QLQ-CR29, international erectile function index (IIEF), Wexner constipation score and low anterior resection syndrome (LARS) score were applied to investigate the QoL of the patients before neoadjuvant therapy, 3 and 12 months after ostomy reversal, including rectal anal function and sexual function. M (P25, P75) was used for the scores of the scale. Results: (1) EORTC QLQ-CR29 score showed that before neoadjuvant therapy, before surgery, 3 months and 12 months after ostomy reversal, anxiety [64.4 (52, 0, 82.5), 75.3 (66.0, 89.5), 82.6 (78.5, 90.0), 83.6 (78.0, 91.0)] and concern about body image [76.8 (66.0, 92.0), 81.1 (76.5, 91.5), 85.5 (82.5, 94.0), 86.1 (82.0, 92.0)] were improved (all P<0.01); pelvic pain [5.4 (2.0, 8.0), 5, 0 (2.0, 7.8), 3.9 (1.0, 5.0), 3.0 (1.0, 5.0)], urinary incontinence [15.7 (7.0, 22.0), 11.1 (0, 17.5), 10.0 (0, 17.0), 9.9 (0, 16.0)], impotence [14.3 (4.2, 19.0), 12.2 (0, 16.8), 5.6 (0, 10.0), 5.2 (0.2, 8.0)], urinate [26.4 (13.0, 38.5), 13.9 (0, 20.0), 13.4 (2.5, 21.5), 13.2 (2.0, 20.0)] and mucous bloody stool [4.7 (3.0, 6.0), 2.6 (0, 5.0), 2.2 (0, 5.0), 1.9 (0, 4.0)] were improved as well (all P<0.01). The scores fluctuated in the improvement of male sexual function, abdominal pain, dry mouth, worry about body mass change, skin pain and dyspareunia, but the symptoms were significantly improved after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). There were no significant changes in female sexual function, dysuria, dysgeusia and fecal incontinence after ostomy reversal compared with before neoadjuvant therapy (all P>0.05). (2) IIEF scale showed that all scores were similar before and after neoadjuvant therapy (all P>0.05). (3) Rectal and anal function scale revealed that before neoadjuvant therapy, before operation, 3 months and 12 months after stoma reversal, gas incontinence [3.1 (0, 4.0), 2.3 (0, 4.0), 1.8 (0, 4.0), 1.2 (0, 3.0)] and urgent defecation [7.2 (0, 11.0), 5.2 (0, 11.0), 2.9 (0, 9.0), 1.7 (0, 0)] were improved (all P<0.001). In terms of improving incomplete emptying sensation, the symptoms fluctuated, but the symptoms improved significantly after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). While the symptoms of assistance with defecation [0 (0, 0), 0.7 (0, 1.0), 0.6 (0, 1.0), 0.7 (0, 1.0)] and defecation failure [0.2 (0, 0), 1.0 (0, 2.0), 0.8 (0, 1.5), 0.8 (0, 1.0)] showed a worsening trend (all P<0.001). Stratified analysis was performed on patients with different efficacy of neoadjuvant therapy to compare the changes in QoL before and after neoadjuvant therapy. Patients with less sensitive and more sensitive neoadjuvant therapy showed similar changes in function and symptoms. Patients with less sensitive therapy showed significant improvement in dysuria, urinary incontinence, skin pain and dyspareunia (all P<0.05), and the symptom of defecation frequency in more sensitive patients was significantly improved (P<0.05). Conclusions: For patients with LARC, neoadjuvant radiochemotherapy combined with radical LAR and protective stoma can improve QoL in many aspects. It is noted that patients show a worsening trend in the need for assistance with defecation and in defecation failure.

[Safety and prognosis analysis of transanal total mesorectal excision versus laparoscopic mesorectal excision for mid-low rectal cancer].

Objective: To compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.

[Predictive value of MRI pelvic measurements for "difficult pelvis" during total mesorectal excision].

Objective: Total mesorectal resection (TME) is difficult to perform for rectal cancer patients with anatomical confines of the pelvis or thick mesorectal fat. This study aimed to evaluate the ability of pelvic dimensions to predict the difficulty of TME, and establish a nomogram for predicting its difficulty. Methods: The inclusion criteria for this retrospective study were as follows: (1) tumor within 15 cm of the anal verge; (2) rectal cancer confirmed by preoperative pathological examination; (3) adequate preoperative MRI data; (4) depth of tumor invasion T1-4a; and (5) grade of surgical difficulty available. Patients who had undergone non-TME surgery were excluded. A total of 88 patients with rectal cancer who underwent TME between March 2019 and November 2021 were eligible for this study. The system for scaling difficulty was as follows: Grade I, easy procedure, no difficulties; Grade II, difficult procedure, but no impact on specimen quality (complete TME); Grade III, difficult procedure, with a slight impact on specimen quality (near-complete TME); Grade IV: very difficult procedure, with remarkable impact on specimen quality (incomplete TME). We classified Grades I-II as no surgical difficulty and grades III-IV as surgical difficulty. Pelvic parameters included pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with the difficulty of TME, and a nomogram predicting the difficulty of the procedure was established. Results: The study cohort comprised 88 patients, 30 (34.1%) of whom were classified as having undergone difficult procedures and 58 (65.9%) non-difficult procedures. The median age was 64 years (56-70), 51 patients were male and 64 received neoadjuvant therapy. The median pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance were 12.0 cm, 11.0 cm, 8.6 cm, 4.9 cm, 12.6 cm, 3.7 cm, 3.0 cm, 13.3 cm, 10.2 cm, and 12.2 cm, respectively. Multivariable analyses showed that preoperative chemoradiotherapy (OR=4.97,95% CI: 1.25-19.71, P=0.023), distance between the tumor and the anal verge (OR=1.31, 95% CI: 1.02-1.67, P=0.035) and pubic tubercle height (OR=3.36, 95% CI: 1.56-7.25, P=0.002) were associated with surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC = 0.795, 95%CI: 0.696-0.895). Conclusion: Our research demonstrated that our system for scaling surgical difficulty of TME is useful and practical. Preoperative chemoradiotherapy, distance between tumor and anal verge, and pubic tubercle height are risk factors for surgical difficulty. These data may aid surgeons in planning appropriate surgical procedures.

[Risk factors of postoperative surgical site infection in colon cancer based on a single center database].

Objective: To explore the incidence and risk factors of postoperative surgical site infection (SSI) after colon cancer surgery. Methods: A retrospective case-control study was performed. Patients diagnosed with colon cancer who underwent radical surgery between January 2016 and May 2021 were included, and demographic characteristics, comorbidities, laboratory tests, surgical data and postoperative complications were extracted from the specialized prospective database at Department of General Surgery, Peking Union Medical College Hospital. Case exclusion criteria: (1) simultaneously multiple primary colon cancer; (2) segmental resection, subtotal colectomy, or total colectomy; (3) patients undergoing colostomy/ileostomy during the operation or in the state of colostomy/ileostomy before the operation; (4) patients receiving natural orifice specimen extraction surgery or transvaginal colon surgery; (5) patients with the history of colectomy; (6) emergency operation due to intestinal obstruction, perforation and acute bleeding; (7) intestinal diversion operation; (8) benign lesions confirmed by postoperative pathology; (9) patients not following the colorectal clinical pathway of our department for intestinal preparation and antibiotic application. Univariate analysis and multivariate analysis were used to determine the risk factors of SSI after colon cancer surgery. Results: A total of 1291 patients were enrolled in the study. 94.3% (1217/1291) of cases received laparoscopic surgery. The incidence of overall SSI was 5.3% (69/1291). According to tumor location, the incidence of SSI in the right colon, transverse colon, left colon and sigmoid colon was 8.6% (40/465), 5.2% (11/213), 7.1% (7/98) and 2.1% (11/515) respectively. According to resection range, the incidence of SSI after right hemicolectomy, transverse colectomy, left hemicolectomy and sigmoid colectomy was 8.2% (48/588), 4.5% (2/44), 4.8% (8 /167) and 2.2% (11/492) respectively. Univariate analysis showed that preoperative BUN≥7.14 mmol/L, tumor site, resection range, intestinal anastomotic approach, postoperative diarrhea, anastomotic leakage, postoperative pneumonia, and anastomotic technique were related to SSI (all P<0.05). Multivariate analysis revealed that anastomotic leakage (OR=22.074, 95%CI: 6.172-78.953, P<0.001), pneumonia (OR=4.100, 95%CI: 1.546-10.869, P=0.005), intracorporeal anastomosis (OR=5.288, 95%CI: 2.919-9.577,P<0.001) were independent risk factors of SSI. Subgroup analysis showed that in right hemicolectomy, the incidence of SSI in intracorporeal anastomosis was 19.8% (32/162), which was significantly higher than that in extracorporeal anastomosis (3.8%, 16/426, χ(2)=40.064, P<0.001). In transverse colectomy [5.0% (2/40) vs. 0, χ(2)=0.210, P=1.000], left hemicolectomy [5.4% (8/148) vs. 0, χ(2)=1.079, P=0.599] and sigmoid colectomy [2.1% (10/482) vs. 10.0% (1/10), χ(2)=2.815, P=0.204], no significant differences of SSI incidence were found between intracorporeal anastomosis and extracorporeal anastomosis (all P>0.05). Conclusions: The incidence of SSI increases with the resection range from sigmoid colectomy to right hemicolectomy. Intracorporeal anastomosis and postoperative anastomotic leakage are independent risk factors of SSI. Attentions should be paid to the possibility of postoperative pneumonia and actively effective treatment measures should be carried out.

Combination of differentiation and T stage can predict unresponsiveness to neoadjuvant therapy for rectal cancer.

AIM: The study aimed to identify the factors predictive for extreme unresponsiveness to neoadjuvant therapy for rectal cancer. METHOD: Ninety-six patients with rectal cancer received neoadjuvant therapy (41 were treated with radiotherapy and 55 with chemoradiotherapy) before surgery. Tumour response, downstaging, pathological complete response (pCR) and disease-free survival were evaluated. RESULTS: Tumour response, downstaging and pCR occurred in 70 (72.9%), 47 (49.0%) and 14 (14.6%) patients, respectively. Univariate analyses showed that a large tumour size, T4 stage, elevated serum tumour markers, poor differentiation, radiotherapy alone and mucinous tumour were indicators of poor tumour response and/or downstaging. On multivariate analysis, chemoradiotherapy was found to be predictive for tumour response and downstaging, whereas mucinous type and T4 stage negatively affected tumour response. No variable was found to be associated with pCR, but poor differentiation and T4 stage together predicted extreme unresponsiveness with a high specificity and a high positive predictive value. Very poor disease-free survival was also observed in patients simultaneously carrying these phenotypes. CONCLUSION: Neoadjuvant chemoradiotherapy is superior to radiotherapy alone in producing a response of rectal cancer. Unresponsiveness was most likely to occur in patients with poor differentiation and T4 disease.

[Diagnosis and treatment of anastomotic leak after low anterior resection for rectal cancer: current status and future prospect].

Anastomotic leak is one of inevitable postoperative complications of rectal cancer. With the improvement of surgical techniques, the enhancement of the cognization of rectal cancer, and the development of surgical instruments, surgical procedures of rectal cancer are getting more sophisticated. The anastomosis is performed lower and lower, however the incidence of anastomotic leak is not significantly decreased. In addition, different from intraperitoneal anastomotic leak, the low rectal anastomotic leak after low anterior resection has many special issues in the diagnosis and treatment in clinic. The incidence of peritonitis caused by low anastomotic leak is low, the onset time is late, and symptoms of peritonitis are mild. So most low anastomotic leak is treated conservatively, second surgical repair or resection of anastomotic site is rarely performed, and proximal intestinal diversion is commonly performed. In the prevention of low anastomotic leak, some techniques and precautions during the perioperative period and identification of high risk factors might play important roles. Combined our clinical experiences, we introduced the diagnosis, treatment, prevention and research progression of low anastomotic leak after anterior resection of low rectal cancer, we hope it would be helpful.

[Application of electric tube stapler in laparoscopic colorectal tumor surgery].

Objective: To investigate the application of electric tube stapler in laparoscopic colorectal tumor surgery. Methods: A descriptive case series study was conducted. Clinical data of patients who underwent laparoscopic colorectal surgery in Peking Union Medical College Hospital in August 2021 using domestic electric tube stapler were collected to analyze the occurrence of postoperative anastomotic leakage, anastomotic bleeding and other complications as well as postoperative intestinal function recovery. Results: A total of 11 patients with colorectal tumor were enrolled in this study, including 8 males and 3 females. Eight patients underwent laparoscopic low anterior resection (1 patient underwent protective ileostomy), and three patients underwent laparoscopic sigmoid carcinoma radical resection. During operation, power system failure of stapler occurred in 1 patient, and the replacement manual device was used to complete the anastomosis. No anastomotic leakage or bleeding occurred in the cohort of patients. There was no conversion to laparotomy or conventional anastomosis. One patient developed acute myocardial infarction 2 days after surgery. The average time to the first flatus after surgery was (2.4±0.8) days and the average length of hospital stay was (10.0±6.1) days. Conclusions: The application of electric tube stapler in laparoscopic colorectal tumor surgery has many advantages, such as safe and effective anastomosis, low morbidity of postoperative complications, and rapid recovery of intestinal function. Domestic electric tube stapler can be applied in minimally invasive surgery for colorectal tumor.