Advances in three-dimensional tumor models for colorectal cancer / 中华肿瘤杂志

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 / 中华外科杂志

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 Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features / 中华外科杂志

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.

Quality of life of patients with locally advanced rectal cancer after neoadjuvant therapy and sphincter-preserving surgery / 中华胃肠外科杂志

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.

Risk factors of postoperative surgical site infection in colon cancer based on a single center database / 中华胃肠外科杂志

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.

Safety and prognosis analysis of transanal total mesorectal excision versus laparoscopic mesorectal excision for mid-low rectal cancer / 中华胃肠外科杂志

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.

Application of electric tube stapler in laparoscopic colorectal tumor surgery / 中华胃肠外科杂志

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.

Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder / 中华胃肠外科杂志

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.

Protective colostomy and protective ileostomy for the prevention of anastomotic leak in patients with rectal cancer after neoadjuvant chemoradiotherapy and radical surgery / 中华胃肠外科杂志

Objective: To investigate whether protective colostomy and protective ileostomy have different impact on anastomotic leak for rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT) and radical surgery. Methods: A retrospectively cohort study was conducted. Inclusion criteria: (1) Standard neoadjuvant therapy before operation; (2) Laparoscopic rectal cancer radical resection was performed; (3) During the operation, the protective enterostomy was performed including transverse colostomy and ileostomy; (4) The patients were followed up regularly; (5) Clinical data was complete. Exclusion criteria: (1) Colostomy and radical resection of rectal cancer were not performed at the same time; (2) Intestinal anastomosis is not included in the operation, such as abdominoperineal resection; (3) Rectal cancer had distant metastasis or multiple primary colorectal cancer. Finally 208 patients were included in this study. They suffered from rectal cancer and underwent protective stoma in radical surgery after nCRT at our hospital from January 2014 to December 2018. There were 148 males and 60 females with age of (60.5±11.1) years. They were divided into protective transverse colostomy group (n=148) and protective ileostomy group (n=60). The main follow up information included whether the patient has anastomotic leak and the type of leak according to ISREC Grading standard. Besides, stoma opening time, stoma flow, postoperative hospital stay, stoma related complications and postoperative intestinal flora were also collected. Results: A total of 28 cases(13.5%) suffered from anastomotic leak and 26 (92.9%) of them happened in the early stage after surgery (less than 30 days) . As for these early-stage leak, ISREC Grade A happened in 11 cases(42.3%), grade B in 15 cases(57.7%) and no grade C occurred. There was no significant difference in the incidence [12.8% (19/148) vs. 15.0% (9/60) , χ(2)=0.171, P=0.679] or type [Grade A: 5.4%(8/147) vs. 5.1%(3/59); Grade B: 6.8%(10/147) vs. 8.5%(5/59), Z=0.019, P=1.000] of anastomotic leak between the transverse colostomy group and ileostomy group (P>0.05), as well as operation time, postoperative hospital stay, drainage tube removal time or stoma reduction time (P>0.05). There were 10 cases (6.8%) and 24 cases (40.0%) suffering from intestinal flora imbalance in protective transverse colostomy and protective ileostomy group, respectively (χ(2)=34.503, P<0.001). Five cases (8.3%) suffered from renal function injury in the protective ileostomy group, while protective colostomy had no such concern (P=0.002). The incidence of peristomal dermatitis in the protective colostomy group was significantly lower than that in the protective ileostomy group [12.8% (9/148) vs. 33.3%(20/60), χ(2)=11.722, P=0.001]. Conclusions: It is equally feasible and effective for rectal cancer patients after nCRT to carry out protective transverse colostomy or ileostomy in radical surgery. However, we should pay more attention to protective ileostomy patients, as they are at high risk of intestinal flora imbalance, renal function injury and peristomal dermatitis.

Diagnosis and treatment of anastomotic leak after low anterior resection for rectal cancer: current status and future prospect / 中华胃肠外科杂志

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.

Prognosis and complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

Objective: To investigate the prognosis and postoperative complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A descriptive case series study was carried out. Patient inclusion criteria: (1) patients who underwent local excision by transanal endoscopic microsurgery (TEM) after nCRT; (2) magnetic resonance evaluated tumor regression grade (mrTRG) as 1, 2 after nCRT;(3) American Society of Anesthesiologists class I to III. Patient exclusion criteria: (1) with multiple primary colorectal cancers; (2) with other malignant tumors within five years; (3) with emergency surgicery indications like digestive tract obstruction, perforation or bleeding. Clinicopathological and follow-up data of rectal cancer patients with obvious tumor regression after nCRT who underwent local excision in Peking Union Medical College Hospital from January 2010 to August 2019 were retrospectively collected. Outcome measures included disease-free survival (DFS), short-term postoperative complications, and at postoperative 1-year during follow up, gas continence, fecal continence, and quality of life (using the EORTC QLQ-CR29 scale, higher score indicated worse quality of life) at postoperative 1-year. Results: A total of 40 patients were included in this study. There were 27 males and 13 females with an average age of (66.7±12.3) years. Preoperative rectal ultrasound and other imaging examinations indicated that the tumor was located in the anterior wall in 16 cases, the lateral wall in 12 cases, and the posterior wall in 12 cases. The distance between the lower margin of the tumor and the anal verge was (4.3±1.2) cm before nCRT and (5.1±0.9) cm after nCRT. According to mrTRG, 31 cases were assessed as mrTRG 1 and 9 cases as mrTRG 2. All the patients received local extended excision of rectal cancer using TEM platform. A total of 19 cases(47.5%) suffered from complications within one month postoperatively. Clavien-Dindo grade I complications happened in 14 cases, grade II in 3 patients, and grade III in 2 cases, who all were healed by conservative treatment. Except that 2 patient presented severe low anterior resection syndrome (LARS) at 1 year postoperatively, no severe anal dysfunction was found in this cohort patients. EORTC QLQ CR29 scale results for quality of life showed that at 1 year after TEM excision, except taste (Z=-1.968, P=0.049), anxiety (Z=-3.624, P<0.001) and skin irritation (Z=-2.420, P=0.023) were worse than the situation before neoadjuvant therapy, there were no statistically significant differences in other assessment results between pre-operation and post-operation (all P>0.05). Postoperative pathological results indicated complete tumor regression (pTRG0) in 17 cases, moderate remission (pTRG1) in 13, and mild remission (pTRG2) in 10. During the follow-up of (49.1±29.6) months, 3 patients had local recurrence and 4 had distant metastasis (3 patients with liver metastasis and 1 patient with lung metastasis followed by liver metastasis). No death was found and the 5-year disease-free survival (DFS) was 84.3%. Conclusions: Local excision through TEM following nCRT not only can be adopted as an important means to accurately determine complete clinical remission (cCR), but also has high therapeutic value for rectal cancer patients presenting cCR or near cCR, with little impact on defecatory function and quality of life. However, the morbidity of complication of TEM excision after nCRT is relatively high and there is a risk of recurrence and metastasis. Therefore, it is still necessary to strictly select the indications of local excision.

Surgical treatment strategies for left colon carcinoma with obstruction / 中国实用外科杂志

Left colon carcinoma with obstruction is a tough problem for the department of colorectal surgery to tackle with.It has specific clinical characters and various surgical patterns. Surgical strategies are still in great debate.Conventional three-staged operation and Hartmann operation still have a little value for clinical application. Colonic lavage during the operation combined with one-staged operation can be an important choice for emergency surgeries. As the popularization of colonic stent,selective operation after the insertion of colonic stent is considered to be safe and available. Selective laparoscopic surgery after colonic stent insertion accelerates the rehabilitation of patients and advances their quality of life,which correlates with the theories of minimally invasive surgery and accelerated rehabilitation. However,surgeons are supposed to pay more attention to perforation and relocation caused by colonic stent which may make tumor spread and increase the risk of recurrence. In order to reduce patients' trauma and increase their quality of life as well as long-term prognosis,surgeons need to pursue assistance from multi-disciplinary treatment(MDT) and accomplish an individualized treating project according to patients' condition.

Correlation between intestinal flora imbalance and anastomotic leakage after operation for middle to low rectal cancer / 中国实用外科杂志

OBJECTIVE: To analyze the risk factors and relationship between intestinal flora imbalance and anastomotic leakage after laparoscopic rectal cancer lower anterior resection(LAR)in patients with middle-low rectal cancer.METHODS: Clinical data of 155 patients with mid to low rectal cancer who underwent laparoscopic lower anterior resection at Peking Union Medical College Hospital from November 2016 to April 2019 were retrospectively analyzed.Postoperative intestinal flora imbalance and anastomotic leakage were evaluated,and statistical results were gained.RESULTS: Of the 155 patients,34(21.9%)patients had postoperative intestinal flora imbalance. Twenty patients of anastomotic leakage after operation(12.9%)were discovered,and 18 patients(11.6%)had both anastomotic leakage and intestinal flora imbalance. Univariate and multivariate logic regression analysis showed that intestinal flora imbalance(χ~2=25.674,OR=90.398,P0.05).CONCLUSION: The early diagnosis of postoperative intestinal floraimbalance in rectal cancer patients depends more on clinical experience. Intestinal floraimbalance,the enlargement of tumor diameterare risk factors for anastomotic leakage,and protective enterostomy would reduce the incidence of anastomotic leakage.

Three major problems and solutions in laparoscopic abdominoperineal resection for rectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the three major problems and solutions in laparoscopic abdominoperineal resection(APR) for rectal carcinoma.</p><p><b>METHODS</b>A retrospective study of 60 low rectal carcinoma cases undergoing selective laparoscopic APR from September 2010 to May 2013 in our hospital was undertaken. A laparoscopic sigmoid stoma was performed through the extraperitoneal route at the left lower abdomen puncture point after lymphadenectomy and tumor excision during operation. Using the unique intracorporeal suture technique of transanal endoscopic microsurgery(TEM), the pelvic peritoneum was closed by continuous suture with TEM needle-forceps and absorbable suture. Those patients with the successful pelvic peritoneum closure received continuous irrigation of presacral space from the third postoperative day to prevent perineal incision infection.</p><p><b>RESULTS</b>Only one patient (1.7%) was converted to laparotomy. Fifty-nine patients underwent laparoscopic APR and laparoscopic sigmoid stoma was successfully performed through the extraperitoneal route without abdominal incision, and the incidence of stoma complication was only 3.4%. Out of 59 patients undergoing laparoscopic APR, the pelvic peritoneum of 56 patients(94.9%) was closed successfully. The median time of closing the pelvic peritoneum was 15 min. Fifty-seven patients with pelvic peritoneum successfully closed by laparotomy or laparoscopic approach received continuous irrigation of presacral space and the median time of presacral drainage tube placement was 7.8 days. No patient developed postoperative intestinal obstruction. The rate of perineal wound healing in grade A, B and C was 87.7%, 8.8% and 3.5%, respectively. In the 3 patients whose pelvic peritoneum failed to be closed with simple drainage of presacral space, one developed postoperative intestinal obstruction and one had a grade C perineal wound healing.</p><p><b>CONCLUSIONS</b>Laparoscopic sigmoid stoma through the extraperitoneal route during laparoscopic APR for rectal carcinoma is feasible and safe. It is convenient and effective to close pelvic peritoneum by using TEM intracorporeal suture technique. It is worth discussing the role of continuous irrigation of presacral space postoperatively to prevent perineal incision infection.</p>

Clinical application of anterior perineal plane for ultra-low anterior resection of the rectum / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To summarize clinical experience in the treatment of low rectal cancer with anterior perineal plane for ultra-low anterior resection of the rectum(APPEAR).</p><p><b>METHODS</b>Clinical and follow-up data of 26 patients with low rectal cancer undergoing the APPEAR operation in Department of General Surgery at Peking Union Medical College from September 2009 to August 2011 were retrospectively analyzed.</p><p><b>RESULTS</b>The 26 cases consisted of 19 male and 7 female patients with an average age of (63.4 ± 9.5) years. The average tumor distance from the anal verge was (4.6 ± 0.7) cm according to preoperative examinations. Fourteen patients received neoadjuvant radiochemotherapy before the operation. All the 26 patients had successful sphincter-preserving operations. The average operative time was (170 ± 21) min and the average intra-operative blood loss (140 ± 69) ml. Complications included one case of intraoperative injury to the rectal wall and 4 cases of postoperative perineal wound infection. Postoperative pathological examination showed well to moderately differentiated adenocarcinomas(n=10), moderately differentiated adenocarcinomas with partial mucinous adenocarcinomas (n=7), poorly differentiated adenocarcinoma(n=1), villous adenoma with high-grade intraepithelial neoplasia (n=1), and rectal villous adenoma(n=1). In 6 cases no residual tumor cells were detected in the surgical specimens. All the patients were followed-up for an average period of(11.4 ± 5.6) months. No impaired urinary function or tumor recurrence was observed during the follow-up. Eighteen patients had the transverse colon stoma closure six months after the operation. The average Wexner continence score was 5.5 after colostomy reversal surgery. The anorectal manometry tests showed that maximum squeeze pressure of the anal sphincter was(224.0 ± 59.3) mm Hg. The maximum resting pressure was (42.5 ± 11.8) mm Hg, and the maximum tolerable volume of the rectum was (120.0 ± 27.4) ml. Anorectal reflexes were present in all these patients.</p><p><b>CONCLUSION</b>The APPEAR technique can be applied in the sphincter-preserving operations for low rectal cancer patients with satisfactory anal function.</p>

Safety and efficacy of prophylactic single antibiotics administration in selective open colorectal surgery / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of prophylactic single antibiotic administration in selective open colorectal surgery.</p><p><b>METHODS</b>Two hundred and seventy-five patients undergoing selective open colorectal surgery in the Peking Union Medical College Hospital from October 2009 to October 2011 were retrospectively reviewed. Prophylatic single antibiotic administration was used by intravenous infusion 30-60 min before incision. No antibiotics would be given after operation if there was no surgical site infection(SSI). According to the incidence of postoperative SSI, unexplained use of antibiotics, anastomotic leakage and distant-site infection, the clinical outcome was assessed to be prophylactic success, prophylactic failure or distant-site infection, respectively.</p><p><b>RESULTS</b>There was no intraoperative or postoperative antibiotics related drug anaphylaxis in all the 275 patients. By prophylactic single antibiotic administration, there were prophylactic success in 243 patients(88.4%,243/275), prophylactic failure in 23(8.4%,23/275), distant-site infection in 9(3.3%,9/275). In the 23 patients with failed prophylaxis, there were SSI in 13(4.7%,13/275) patients, postoperative use of broad-spectrum antibiotics for unexplained fever in 2(0.7%,2/275), postoperative anastomotic leakage in 8(3.6%,8/222).</p><p><b>CONCLUSION</b>Prophylactic single antibiotic administration in selective open colorectal surgery is safe and effective.</p>

Expression of hMLH1 in rectal intraepithelial neoplasm and early rectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore whether the abnormality of hMLH1 gene may be an early event of carcinogenesis in rectal carcinoma, and to evaluate the diagnostic value in differentiation between intraepithelial neoplasm and early stage of colorectal carcinoma.</p><p><b>METHODS</b>The expression of hMLH1 protein in 28 cases with early invasive rectal carcinoma(EIRC), 36 cases with rectal intraepithelial neoplasm(RIEN), and 30 cases with normal rectal mucosa(NRM) which were collected through surgical operations were detected by PV-9000 immunohistochemical method.</p><p><b>RESULTS</b>The positive expression rates of hMLH1 protein were 100%(30/30), 77.8%(28/36), and 39.3%(11/28) in NRM, RIEN, and EIRC respectively. The difference was statistically significant between RIEN and EIRC(P=0.002), and the difference was also statistically significant between RIEN and NRM(P=0.006). The positive expression of hMLH1 was not related to age, gender, tumor maximum diameter, dysplasia, tumor types, and distance from the anal verge in RIEV group(P>0.05). In EIRC group, hMLH1 was associated with tumor differentiation(P<0.05).</p><p><b>CONCLUSION</b>hMLH1 gene deletion may be an early event during carcinogenesis of rectal carcinoma, which may be useful in differentiation of intraepithelial neoplasm from early rectal carcinoma.</p>

Acquiring laparoscopic skill for colorectal surgery: based on the experience of a colorectal surgeon / 中华外科杂志

<p><b>OBJECTIVE</b>Laparoscopic colorectal surgery is a skill-dependent procedure. The present study aims to analyze the learning curve of a properly trained surgeon, with basic laparoscopic techniques, to become skillful in performing laparoscopic colorectal operations.</p><p><b>METHODS</b>A series of non-selective, consecutive 189 cases of laparoscopic colorectal surgery were accomplished, from December 2009 to February 2012, by one surgeon with years of skilled technique in laparoscopic cholecystectomy, rich experience in assisting laparoscopic colorectal surgery, and experience of approximately 180 procedures of gastric and colorectal surgery annually. 170 out of 189 procedures were radical operations for colorectal neoplasma, including right colectomies in 28 cases, left colectomies in 5 cases, sigmoidectomies in 28 cases, high Dixon procedures in 45 cases, low Dixon (total mesorectal excision, TME) procedures in 41 cases and Miles procedure in 23 cases. 19 other patients underwent combined procedures for multi-primary tumors or inflammatory enteritis. All these procedures were analyzed according to time span (the earlier half and later half) in respect to length of surgery, intraoperative blood loss, number of lymph nodes retrieved, intraoperative events and postoperative complications.</p><p><b>RESULTS</b>For radical right colectomy, the D2 dissection conducted in the earlier phase (n = 8) had the similar length of surgery, more blood loss and less LN retrieval, compared with the D3 dissection conducted in recent phase (n = 20). The earlier performed high Dixon procedures (n = 22) consumed longer time than the later procedures (n = 23) consumed, but with similar blood loss and LN retrieval. Low Dixon (TME) procedures showed significant differences in length of surgery and blood loss relative to time span. Recently performed simoidectomy and Miles procedures showed a trend of shorter time consumed compared with earlier performed procedures. Conversion ratio to open surgery was 1.05%. Adverse effects occurred in 8 cases of surgeries, including intestinal injury (3/189), insufficient distal margin (2/189), intraoperative bleeding (2/189) and vaginal injury (1/76). There was no operative death. Chief complications included urinary retention 5.82%, ileus 4.76%, anastomotic leak 4.24%, perineal infection 23.08% (6/26), wound dehiscence 2.65%, gastrointestinal bleeding 1.59%, peritoneal infection 1.06%. Surgery for distal rectum tended to have more complications, such as urinary retention, anastomotic leak and perineal infection. The later performed low Dixon procedures produced insignificantly fewer anastomotic leaks than those in the earlier phase.</p><p><b>CONCLUSIONS</b>For a trained surgeon with basic laparoscopic techniques, there are at least 15 - 25 cases of different procedures needed for him/her to become skilled to perform laparoscopic surgery. The learning curve should also depend on the annual number of colorectal surgeries.</p>

Hand-assisted laparoscopic versus laparoscopic-assisted right hemicolectomy: a clinical controlled study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the outcomes of right hemicolectomy performed either by the hand-assisted laparoscopic(HALS) or conventional laparoscopic surgery(LAS).</p><p><b>METHODS</b>Ninety-five patients undergoing HALS(n=47) from March 2002 to November 2006 or by LAS (n=48) from January 2007 to December 2009 were retrospectively studied. All the operations were performed by the same surgical team. Patient safety, postoperative recovery, complications, oncologic outcomes, medical expenses, and the follow-up results were compared between the two groups.</p><p><b>RESULTS</b>No severe complications or perioperative deaths were oberved. There were significant differences between the two groups in terms of intraoperative bleeding, operative time, and length of incision(all P<0.05). However, the conversion rate, intraoperative injuries, time to first bowel movement, postoperative bed-rest time, hospital stay, time to first oral intake, and the number of patients requiring postoperative analgesia were comparable between the two groups(P>0.05). Length of surgical specimen was (25.6±9.9) cm in the HALS group and was (26.8±7.9) cm in the LAS group, the diffenence was not statistically significant(P<0.05). The mean number of lymph nodes retrieved in HALS group was 18.2±12.1, which was significantly lower than that in LAS group(24.1±9.3, P<0.05). The medical expense of the LAS group was (28 049.8±7576.1) RMB, which was significantly higher than that of the HALS group(21 132.7±5323.4) RMB(P<0.05). A follow-up rate of 93.7% was achieved in the HALS group with 3 patients lost to follow-up. The follow-up duration ranged from 45.4 to 101.9 months with a median of 66.7 months. In LAS group, the follow-up rate was 96% with 2 patients lost to follow-up and the follow-up duration ranged from 12.4 to 45.7 months with a median of 21.6 months. There was no significant difference in 3-year disease-free survival(91.3% vs. 87.9%, P>0.05) between the two groups.</p><p><b>CONCLUSION</b>HALS and LAS can achieve similar minimal invasiveness efficacy and oncologic outcomes for right hemicolectomy.</p>

Impact of neoadjuvant chemoradiation on perineal wound healing after abdominoperineal resection for lower rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of neoadjuvant chemoradiation on perineal wound healing following abdominoperineal resection(APR) for lower rectal cancer.</p><p><b>METHODS</b>Data of 93 patients who underwent APR for low rectal cancer between January 2005 and January 2009 in Peking Union Medical College Hospital were reviewed, including patients who received neoadjuvant chemoradiation (n=29) and those undergoing surgery alone(n=64). Perineal wound healing was the primary outcome measurement. Condition of wound healing was classified as good, moderate, and poor and was compared between the two groups.</p><p><b>RESULTS</b>Twenty nine patients in the neoadjuvant group received preoperative regional radiation(50 Gy, 25 fractions/5 weeks) with synchronous FOLFOX4 chemotherapy(fluorouracil and oxaliplatin). In the neoadjuvant group, wound healing after APR was good in 18 patients(62.1%), moderate in 6(20.7%), and poor in 5(17.2%). In patients who had surgery alone, wound healing after APR was good in 41 patients(64.1%), moderate in 15(23.4%), and poor in 8(12.5%). There was no significant difference in the incidence of wound infection(poor wound healing)between the two groups(P=0.773).</p><p><b>CONCLUSION</b>Neoadjuvant chemoradiation therapy is not associated with increased perineal wound infection following abdominoperineal resection for low rectal cancer.</p>