Clinical efficacy of radical resection of rectal cancer with different surgical approaches and analysis of influencing factors of postoperative complications: a report of 3 418 cases / 中华消化外科杂志

Objective:To investigate the clinical efficacy of radical resection of rectal cancer with different surgical approaches and influencing factors of postoperative complications.Methods:The retrospective study was conducted. The clinicopathological data of 3 418 patients who underwent radical resection of rectal cancer in the Second Affiliated Hospital of Harbin Medical University from July 2011 to September 2020 were collected. There were 2 060 males and 1 358 females, aged (61±11)years. Patients meeting the requirements of radical resection and surgical indications underwent surgeries choosing from open radical colorectal cancer surgery, laparoscopic radical colorectal cancer surgery, and natural orifice specimen extraction surgery (NOSES). Observation indicators: (1) intraoperative and postoperative conditions of patients undergoing different surgical approaches; (2) comparison of preoperative clinical characteristics in patients undergoing different surgical approaches; (3) comparison of postoperative histopathological characteristics in patients undergoing different surgical approaches; (4) postoperative complications of patients undergoing different surgical approaches; (5) analysis of influencing factors of postoperative complications. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparisons between groups was analyzed using the Kruskal-Wallis rank test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Intraoperative and postoperative conditions of patients undergoing different surgical approaches. Of the 3 418 patients, 1 978 cases underwent open radical colorectal cancer sur-gery, 1 028 cases underwent laparoscopic radical colorectal cancer surgery and 412 cases underwent NOSES, respectively. The operation time, volume of intraoperative blood loss, cases with permanent stoma, preventive stoma or without fistula, time to postoperative first flatus, time to postoperative liquid food intake, cases transferred to intensive care unit after surgery, duration of postoperative hospital stay were 145(range, 55?460)minutes, 100(range, 30?1 000)mL, 435, 88, 1 455, 72(range, 10?220)hours, 96(range, 16?296)hours, 158, 10(range, 6?60)days, respectively, in patients undergoing open radical colorectal cancer surgery. The above indicators were 175(range, 80?450)minutes, 50(range, 10?800)mL, 172, 112, 744, 48(range, 14?120)hours, 72(range, 38?140)hours, 17, 9(range, 4?40)days, respectively, in patients undergoing laparoscopic radical colorectal cancer surgery and 180(range, 80?400)minutes, 30(range, 5?500)mL, 0, 45, 367, 48 (range, 14?144)hours, 72(range, 15?148)hours, 1, 6(range, 3?30)days, respectively, in patients undergoing NOSES. There were significant differences in the above indicators among the patients undergoing different surgical approaches ( H=291.38, 518.56, χ2=153.82, H=408.86, 282.97, χ2=78.66, H=332.30, P<0.05). (2) Com-parison of preoperative clinical characteristics in patients undergoing different surgical approaches. The gender, age, body mass index, cases with diabetes, cases with hypertension, cases with coronary heart disease, cases with anemia, cases with hypoproteinemia, cases with intestinal obstruction, tumor location, preoperative carcinoembryonic antigen, preoperative CA19-9 showed significant differences among patients undergoing open radical colorectal cancer surgery, laparoscopic radical colorectal cancer surgery and NOSES ( P<0.05). (3) Comparison of postoperative histopathological characteris-tics in patients undergoing different surgical approaches. Tumor histological type, tumor differentiation degree, tumor diameter, number of lymph node detected, nerve invasion, vascular invasion, lymph node invasion, tumor T staging, tumor N staging, tumor M staging, tumor TNM staging showed significant differences among patients undergoing open radical colorectal cancer surgery, laparos-copic radical colorectal cancer surgery and NOSES ( P<0.05). (4) Postoperative complications of patients undergoing different surgical approaches. Cases with postoperative complications as anastomotic leakage, abdominal infection, intestinal obstruction, anastomotic bleeding, incision complications, pulmonary infection, other complications were 52, 21, 309, 8, 130, 51, 59, respectively, in patients undergoing open radical colorectal cancer surgery. The above indicators were 33, 17, 75, 3, 45, 58, 9, respectively, in patients undergoing laparoscopic radical colorectal cancer surgery and 13, 4, 8, 0, 11, 10, 15, respectively, in patients undergoing NOSES. There were significant differences in the intes-tinal obstruction, incision complications, pulmonary infection, other complications among patients undergoing different surgical approaches ( χ2=122.56, 13.33, 20.44, 15.59, P<0.05) and there was no significant difference in the anastomotic leakage, abdominal infection, anastomotic bleeding among patients undergoing different surgical approaches ( χ2=0.96, 2.21, 3.08, P>0.05). (5) Analysis of influencing factors of postoperative complications. ① Analysis of influencing factors of intestinal obstruction in patients with radical resection of rectal cancer. Age as 20?39 years and 40?59 years, surgical approach as laparoscopic radical colorectal cancer surgery and NOSES were independent protective factors of intestinal obstruction in patients with radical resection of rectal cancer ( odds ratio=0.46, 0.59, 0.43, 0.13, 95% confidence interval as 0.21?1.00, 0.36?0.96, 0.33?0.56, 0.06?0.27, P<0.05). ② Analysis of influencing factors of incision complications in patients with radical resection of rectal cancer. Body mass index as 24.0?26.9 kg/m 2, surgical approach as laparoscopic radical colorectal cancer surgery and NOSES were independent protective factors of incision complications in patients with radical resection of rectal cancer ( odds ratio=0.24, 0.63, 0.46, 95% confidence interval as 0.11?0.51, 0.44?0.89, 0.24?0.87, P<0.05). ③ Analysis of influencing factors of pulmonary infection in patients with radical resection of rectal cancer. The surgical approach as laparoscopic radical colorectal cancer surgery was an independent risk factor of pulmonary infection in patients with radical resection of rectal cancer ( odds ratio=2.15, 95% confidence interval as 1.46?3.18, P<0.05), and tumor TNM staging as 0?Ⅰ stage was an independent protective factor ( odds ratio=0.10, 95% confidence interval as 0.01?0.88, P<0.05). ④ Analysis of influencing factors of other complica-tions in patients with radical resection of rectal cancer. Age as 20?39 years, 40?59 years, 60?79 years, body mass index as <18.5 kg/m 2, 18.5?23.9 kg/m 2, 24.0?26.9 kg/m 2, 27.0?29.9 kg/m 2, surgical approach as laparoscopic radical colorectal cancer surgery were independent protective factors of other complications in patients with radical resection of rectal cancer ( odds ratio=0.10, 0.29, 0.37, 0.08, 0.22, 0.35, 0.32, 0.29, 95% confidence interval as 0.01?0.81, 0.13?0.64, 0.17?0.78, 0.02?0.40, 0.09?0.52, 0.15?0.83, 0.12?0.89, 0.14?0.59, P<0.05). Conclusions:Compared to laparoscopic radical colorectal cancer surgery and NOSES, open radical colorectal cancer surgery has wide indication and short operation time, but less perioperative treatment effect. Laparoscopic radical colorectal cancer surgery and NOSES can achieve better surgical result and less postoperative complication when patients meeting surgical indications.

Influencing factors of refractory anastomotic stenosis after laparoscopic intersphincteric resec-tion for rectal cancer and construction of nomogram prediction model / 中华消化外科杂志

Objective:To investigate the influencing factors of refractory anastomotic stenosis after laparoscopic intersphincteric resection (Ls-ISR) for rectal cancer and construction of nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 495 patients who underwent Ls-ISR for rectal cancer in two medical centers, including 448 patients in Peking University First Hospital and 47 patients in Cancer Hospital Chinese Academy of Medical Sciences, from June 2012 to December 2021 were collected. There were 311 males and 184 females, aged 61 (range, 20-84)years. Observation indicators: (1) incidence of anastomotic stenosis; (2) influencing factors of refractory anastomotic stenosis after Ls-ISR; (3) construction and evaluation of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Follow-up was conducted using outpatient examination and telephone interview to detect the incidence of postoperative anastomotic leakage and anastomotic stenosis up to August 2022. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. Factors with P<0.10 in univariate analysis were included in multivariate analysis. The R software (3.6.3 version) was used to construct nomogram prediction model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the efficacy of nomogram prediction model. Results:(1) Incidence of anastomotic stenosis. All 495 patients underwent Ls-ISR successfully, without conversion to laparotomy, and all patients were followed up for 47(range, 8-116)months. During the follow-up period, there were 458 patients without anas-tomotic stenosis, and 37 patients with anastomotic stenosis. Of the 37 patients, there were 15 cases with grade A anastomotic stenosis, 3 cases with grade B anastomotic stenosis and 19 cases with grade C anastomotic stenosis, including 22 cases being identified as the refractory anastomotic stenosis. Fifteen patients with grade A anastomotic stenosis were relieved after anal dilation treat-ment. Three patients with grade B anastomotic stenosis were improved after balloon dilation and endoscopic treatment. Nineteen patients with grade C anastomotic stenosis underwent permanent stoma. During the follow-up period, there were 42 cases with anastomotic leakage including 17 cases combined with refractory anastomotic stenosis, and 453 cases without anastomotic leakage including 5 cases with refractory anastomotic stenosis. There was a significant difference in the refractory anastomotic stenosis between patients with and without anastomotic leakage ( χ2=131.181, P<0.05). (2) Influencing factors of refractory anastomotic stenosis after Ls-ISR. Results of multivariate analysis showed that neoadjuvant therapy, distance from tumor to anal margin ≤4 cm, clinic N+ stage were independent risk factors of refractory anastomotic stenosis after Ls-ISR ( hazard ratio=7.297, 3.898, 2.672, 95% confidence interval as 2.870-18.550, 1.050-14.465, 1.064-6.712, P<0.05). (3) Construction and evaluation of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Based on the results of multivariate analysis, neoadjuvant therapy, distance from tumor to anal margin and clinic N staging were included to constructed the nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Results of ROC curve showed the AUC of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR was 0.739 (95% confidence interval as 0.646-0.833). Conclusions:Neoadjuvant therapy, distance from tumor to anal margin ≤4 cm, clinic N+ stage are independent risk factors of refractory anastomotic stenosis after Ls-ISR. Nomogram prediction model based on these factors can predict the incidence of refractory anastomotic stenosis after Ls-ISR.

Evolution of Colorectal Surgery: from Classic to Innovation / 肿瘤防治研究

Colorectal surgery originated in early civilizations, since then, its evolution follows a certain pattern. Most surgical techniques have their historical basis and have never been separated from social, technological, and conceptual progress. Given that the development of colorectal surgery and the development of surgical platforms and surgical concepts have mutually reinforced each other, this article collects historical information related to colorectal surgery and provides its historical review from the ancient Egyptian culture to modern civilization, taking into account the development of surgical platforms and concepts. The evolution of colorectal surgery is described as "for an understanding of the future, look to the past". For colorectal surgeons, in particular, a proper understanding of the evolution of colorectal surgery is the best way to understand its direction.

Expression of glutathione peroxidases 4 in colon adenocarcinoma tissues and its relationship with clinicopathological features and prognosis of patients / 肿瘤研究与临床

Objective:To investigate the expression of glutathione peroxidases 4 (GPX4) in colon adenocarcinoma and its relationship with clinicopathological features and prognosis of patients.Methods:The data set of colon adenocarcinoma was obtained from The Cancer Genome Atlas (TCGA) database to analyze the expression of GPX4 in colon adenocarcinoma tissues and its predictive value for overall survival (OS). A total of 93 colon adenocarcinoma tissues and 87 adjacent mucosa tissues after operation from November 2009 to May 2010 provided by the National Human Genetic Resources Sharing Service Platform were selected. The expression of GPX4 protein was detected by using tissue chip immunohistochemistry. The relations between the expression of GPX4 protein and the clinicopathological features and OS of colon adenocarcinoma patients were analyzed. Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. The nomogram for predicting OS rate was established and drawn.Results:The analysis of data from TCGA database showed that in 380 cases of colon adenocarcinoma, the expression of GPX4 in colon adenocarcinoma tissues were higher than that in the normal colonic mucosa tissues [the value of fragments per kilobase of exon per million fragments mapped (FPKM): 85.654 (20.351-356.237) vs. 56.230 (48.783-63.931)], and the difference was statistically significant ( Z = -6.150, P<0.05). The OS in GPX4 high-expression group (FPKM ≥83.614) were poorer than that in GPX4 low-expression group (FPKM < 83.614) (median OS time: 84.40 months vs. 94.03 months, 5-year OS rate: 58.6% vs. 72.7%), and the difference was statistically significant ( P<0.05). Tissue chip immunohistochemical staining results show that the high-expression rate of GPX4 protein in colon adenocarcinoma tissues was higher than that in adjacent normal tissues [38.0% (35/92) vs. 7.3% (6/82)], and the difference was statistically significant ( χ2 = 22.727, P<0.01); the high-expression rate of GPX4 protein in left colon adenocarcinoma tissues was higher than that in right colon adenocarcinoma tissues [47.2% (25/53) vs. 25.6% (10/39), and the difference was statistically significant ( χ2 = 4.42, P = 0.036); the 5-year OS rate of patients in GPX4 high-expression group was lower than that in GPX4 low-expression group (25.7% vs. 57.9%), and the difference was statistically significant ( χ2 = 9.051, P<0.05). Multivariate Cox proportional hazards regression model analysis showed that lymph node metastasis (stage N 1-N 3) ( HR = 2.241, 95% CI 1.242-4.046, P = 0.007) and high expression of GPX4 ( HR = 2.783, 95% CI 1.598-4.848, P<0.01) were independent factors affecting the poor prognosis of colon adenocarcinoma patients. The above factors were used to establish a nomogram for predicting the prognosis of patients with colon adenocarcinoma, the C index was 0.739, indicating that the nomogram had good predictive performance. Conclusion:The expression of GPX4 is up-regulated in colon adenocarcinoma tissues, and its high expression is related to the malignant biological behavior of the tumor and poor prognosis.

Progress of clinicopathological features, diagnosis and treatment and screening of early-onset colorectal cancer / 肿瘤研究与临床

The incidence of early-onset colorectal cancer is increasing year by year, and it occupies an important position in colorectal cancer. Most of the characteristics of patients with early-onset colorectal cancer are different from those with late-onset colorectal cancer, the patients are diagnosed in a late stage, and their pathological manifestations show a type of poor prognosis. At present, there is a lack of consensus and guideline for the diagnosis, treatment and screening of early-onset colorectal cancer. A full understanding of the characteristics of early-onset colorectal cancer helps to understand its pathogenesis and guide screening and treatment to reduce the incidence and mortality of colorectal cancer. This article reviews the clinicopathological characteristics, molecular pathological mechanisms, diagnosis and treatment, and prognosis of early-onset colorectal cancer, in order to provide references for elucidating its etiology and formulating scientific and standardized screening strategies.

Current Status of “Watch-and-Wait” Rectal Cancer Treatment in Asia-Pacific Countries

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

Molecular mechanisms of cetuximab resistance in metastatic colorectal cancer / 国际肿瘤学杂志

Cetuximab has become an important molecular targeted drug for the treatment of metastatic colorectal cancer (mCRC), which increases the curative effect of chemotherapy and prolongs the survival time. However, some patients develop insensitiveness or resistance to cetuximab, while the complicated molecular mechanisms are not quite clear. With the deep research in epidermal growth factor receptor (EGFR) signaling pathway, the genetic alteration of KRAS, BRAF, PTEN and PIK3CA and polymorphism of microRNA (miRNA) have been proved to associated with cetuximab resistance. Wnt signaling pathway with its negative regulator RNF43 is also considered to be related with cetuximab resistance in recent studies. The review of the progress on molecular mechanisms of cetuximab resistance in mCRC can establish theoretical basis for finding out reasonable drugs to overcome the resistance.

Risk factor analysis for perineal incision complications after abdominoperineal resection in elderly patients with rectal cancer / 中华肿瘤杂志

Objective@#To evaluate the risk factors of perineal incision complications after abdominal abdominoperineal resection (APR) in elderly patients with rectal cancer.@*Methods@#From January 2007 to September 2018, the clinical data of 72 elderly rectal cancer patients (age≥80 years) underwent abdominoperineal resection at Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were collected and retrospectively analyzed. Univariate and multivariate analyses were performed to determine the risk factors of perineal incision complications in elderly patients with rectal cancer after APR.@*Results@#Of the 76 patients, 47 were male and 25 were female, with an average age of (81.8±1.8) years. The incidence of postoperative perineal incision complications was 23.6% (17/72), including 5 cases of wound infection, 4 cases of incision fat liquefaction, and 8 cases of delayed wound healing. All of the patients were well recovered and discharged without death. The result of univariate analysis showed that, the occurrence of perineal incision complications was associated with serum albumin level < 35g/L (χ2=4.860, P=0.027), intraperitoneal chemotherapy with fluorouracil sustained release/lobaplatin rinse (χ2=8.827, P=0.003), pelvic restoration (χ2=9.062, P=0.003), diabetes (χ2=6.387, P=0.011) and coronary heart disease (χ2=7.688, P=0.006). Multivariable logistic regression analysis showed that the intraoperative pelvic restoration (OR=0.17, 95% CI: 0.04~0.82, P=0.027) and diabetes (OR=4.32, 95% CI: 1.05~17.81, P=0.043) were independent risk factors for perineal incision complications.@*Conclusions@#Elderly patients with rectal cancer who undergo APR should preserve and restore the pelvic peritoneum as much as possible. Moreover, perioperative blood glucose monitoring is a powerful guarantee for preventing complications of perineal incision.

Short-term outcomes of patients treated with enhanced recovery after surgery combined with laparoscopic colorectal cancer surgery / 中华普通外科杂志

Objective To investigate the safety and efficacy of enhanced recovery after surgery (ERAS) used in laparoscopic colorectal cancer surgery.Methods We conducted a retrospective analysis of the medical records of 99 cases treated with ERAS programed laparoscopic colorectal cancer surgery (ERAS group) and 103 cases treated with traditional perioperative care and laparoscopic colorectal cancer surgery (controlled group) from Mar 2017 to Sep 2017 in our center.Results There was no significant difference in age,gender,BMI,ASA classification,tumor location,operation time,pathological stage and the incidence of postoperative complications between ERAS group and controlled group (all P ＞ 0.05).Compared to control group,ERAS had less blood loss,shorter time to pass first flatus,stool and start diet and shorter hospitalization day,with all the difference statistically significant [(60 ± 63)ml vs.(112 ± 245)ml,(3.0±0.8)dvs.(4.3 ±1.2)d,(3.5 ±1.0)dvs.(4.6±1.3)d,(4.1 ±1.2)dvs.(5.4± 2.0)d,(5.8±2.1)dvs.(7.8±2.5)d,t=-2.021、-9.216、-6.887、-5.252、-6.163,allP＜ 0.05].No patients in both groups suffered from readmission or death within 30 days after surgery.Conclusion Patients treated with ERAS programed laparoscopic colorectal cancer surgery is safe and effective,with rapid recovery and reduced hospital stay.

Treatment progress of colorectal cancer with lateral lymph node metastasis / 肿瘤研究与临床

About 15％-25％ of patients with locally advanced rectal cancer have lateral lymph node metastasis, lymph node metastasis is an important cause of postoperative recurrence and death. Currently, scholars hold different attitudes towards lateral pelvic lymph node dissection (LPLND), because LPLND has many problems such as difficult operation, long operation time and large amount of bleeding. Therefore, there is no optimal treatment strategy for colorectal cancer with enlarged lateral lymph nodes. This article reviews the treatment strategy of lateral lymph node metastasis, the selection factors of LPLND and the safety and feasibility of laparoscopic LPLND.