[Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database].

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

[Reassessment of practice of Chinese surgeons since introduction of the watch and wait strategy after neoadjuvant therapy for rectal cancer].

Objective: To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer. Methods: A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ2 or Fisher's exact probability tests. Results: The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ2=12.83, P<0.001; χ2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion: Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.

[Regarding the selection of individualized therapy after neoadjuvant therapy for gastrointestinal tumors].

Gastrointestinal tumors have been widely concerned because of increasing morbidity and mortality. In the process of exploring the therapeutic patterns of gastrointestinal tumors, patients treated with neoadjuvant therapies have good effect of tumor regression and favorable prognosis. Thus, neoadjuvant therapy strategies are recommended by major guidelines of gastrointestinal tumors in the world. Meanwhile, they have a great impact on the traditional methods of surgery, the influence mainly involves the reduction of the surgical margin and the scope of lymph node dissection in gastric cancer, while involves performing organ preservation and watch & wait in selective patients with colorectal cancer. These effects and changes were based on effective control of local recurrence by neoadjuvant therapies, and the advantages of neoadjuvant therapy in terms of tumor regression and survival supported by many studies. It is also based on the patient's desire for organ preservation and non-surgical treatment. Meanwhile, application of neoadjuvant therapy strategies increase surgical difficulty and postoperative complications, but the overall impact on patient prognosis is weak. Therefore, the selection of an appropriate treatment model after neoadjuvant therapy requires an effective overall post-treatment evaluation. In particular, it is necessary to pay attention to the evaluation of imaging, endoscopy, etc., while effectively performing monitoring and follow-up, and finally establishing an appropriate salvage treatment. This article will review the status and problems of individualized treatment after neoadjuvant therapy of gastrointestinal tumor.

Workplace violence in radiology: results of a systematic review.

BACKGROUND: Workplace violence (WPV) is a growing issue in health care with far-reaching consequences for health workers' physical and psychological well-being. While some medical specialities like emergency medicine have always been considered at higher risk for WPV, several studies have also reported its occurrence in radiology. AIMS: This systematic review aimed to comprehensively synthesize the types of WPV in radiology, its psychological impact, and the underlying risk and protective factors. METHODS: We searched five electronic databases (PubMed, Web of Science Core Collection, Scopus, PsycINFO and CINAHL) and additional literature, including grey literature, and established weekly search alerts. Two reviewers independently conducted all methodological steps, involving a third reviewer in case of disagreement. RESULTS: Of the 12 205 retrieved records, 103 full-text articles were evaluated, and 15 studies were included. Across studies, verbal aggression, sexual harassment (mostly against women) and physical violence were experienced by up to 100%, 85% and 46% of health workers, respectively. Perpetrators were patients and patients' caregivers, followed by co-workers. Victims suffered from various psychological symptoms, such as anxiety (22%-54%), fear (6%-39%), depression (32%) and repeated disturbing memories (21%). Risk factors included female gender, understaffing, worker inexperience, poor communication and lengthy waiting times. Social support and security personnel presence were among the identified protective factors. CONCLUSIONS: Health workers are at high risk of experiencing WPV in the radiological setting, with a strong psychological impact. Radiological departments should create a safe healthcare environment that actively manages the identified risk factors and offers psychological support to affected workers.

[Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study].

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

[Recognition of empty pelvic syndrome and its prevention and treatment].

With the development of existing surgical techniques, equipment and treatment concepts, more and more medical centers begin to carry out extensive resection for recurrent pelvic malignant tumors or those with multivisceral invasion. Exenteration may facilitate curative resection and improve the outcome of the patients. Therefore, pelvic exenteration has gradually become the standard of care for locally advanced pelvic malignancies. At present, pelvic exenteration leads to high intraoperative and postoperative complications and mortality, and therefore compromise the safety and long-term quality of life. Cumulating evidences suggest remnant cavity after exenteration might trigger the pathophysiological process and cause downstream complications which can be defined as empty pelvis syndrome. The literature related to empty pelvic syndrome was summarized, the possible cause of empty pelvic syndrome was analyzed. After the pelvic exenteration, the closed pelvic residual cavity formed continuous negative pressure with the gradual absorption of air in the cavity, bacterial propagation, and accumulation of fluid, which had an impact on the distribution of organs in the abdominal and pelvic cavity. At the same time, whether physical processes also play a role in the occurrence of empty pelvic syndrome remains to be explored. It is concluded that the diagnosis is mainly based on the patient's medical history, clinical manifestations and radiological findings, and the history of pelvic exenteration is the most important indicator in the diagnosis. In terms of prevention measures, we should identify the high-risk groups of the occurrence of empty pelvic syndrome, and then take accurate and individualized preventive measures. Various new biomaterials have more advantages in preventive pelvic cavity filling than traditional human tissue filling. Mesentery plays an important role in the morphology, peristalsis and arrangement of the small intestine. More attention should be paid to reducing the ectopic placement of the small intestine into the pelvic cavity by protecting the mesentery structure and restoring or rebuilding the mesentery morphology. In terms of treatment measures, there is still a lack of standard treatment pathway for empty pelvic syndrome.

[Neoadjuvant immunotherapy for colorectal cancer].

Immunotherapy has been one of the hot topics in the field of colorectal cancer research in recent years. Patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) are the main beneficiaries of immunotherapy. The response rate of patients with dMMR/MSI-H colorectal cancer receiving neoadjuvant immunotherapy is nearly 100%, of which the pathological complete response rate approximately accounts for 60%-67%. The prospect of neoadjuvant immunotherapy in dMMR or MSI-H colorectal cancer patients, especially in the rectal cancer patients, lies in achieving sustainable clinical complete response so as to achieve organ preservation and avoid adverse effects on reproductive, sexual, bowel and bladder function after surgery and radiotherapy. Studies have shown that part of the colorectal cancer patients of microsatellite stability (MSS) or mismatch repair proficient (pMMR) can respond to neoadjuvant immunotherapy in combination with other treatment methods such as radiotherapy and chemotherapy. In pMMR or MSS colorectal cancer, optimizing neoadjuvant immunotherapy regimens and finding effective efficacy prediction biomarkers are important research directions. In neoadjuvant immunotherapy, overcoming primary and secondary resistance and identifying the pseudoprogression and hyperprogression of neoadjuvant immunotherapy are clinical challenges that require attention. This paper comprehensively reviews the research progress, controversies,challenges and future research directions of neoadjuvant immunotherapy (mainly immune checkpoint inhibitors) in colorectal cancer.

[Perpetuation of defunctioning stoma: risk factors and countermeasures].

Defunctioning stoma is an effective method to reduce symptomatic anastomotic leakage after rectal cancer surgery. It is of concern that about 1 in 5 defunctioning stomas will not be restored, that is, becoming permanent. And that is usually beyond expectation by physicians and patients, which deserves enough attention. The causes are complex, including anastomotic complications, tumor progression, perioperative death, poor anal function and patient willingness. Possible risk factors include symptomatic anastomotic leakage, age, tumor location, neoadjuvant therapy, anal function, TNM stage, ASA score, hospital factors, etc. Those factors may occur in various stages of patient referral such as before neoadjuvant therapy, prior to surgery, intra or post-operative period, and follow-up. Adequate physician-patient communication and shared decision-making, comprehensive tumor and patient function assessment, rational treatment strategy, careful manipulation during operation and good quality control, and meticulous perioperative management are important steps to reduce the permanent stoma. When shared decision-making, patients' needs should be fully considered while unnecessary expectations of anal preservation should be avoided. The risk of perpetuation of defunctioning stoma should be fully informed. Safe operation, especially anastomosis, is the key to avoid permanent stoma. And attention should be paid to the early detection and intervention of postoperative anastomotic stenosis.

[Current status and the necessity for enterostomy training: Results of a national survey in China].

Objective: To investigate the perceptions, attitudes, and surgical strategies of Chinese surgeons, toward stoma management. Methods: We conducted a nationwide, cross-sectional, questionnaire-based survey among individuals working at relevant departments in any tier of hospitals, including general surgery, gastrointestinal surgery, surgical oncology, emergency, and others, that was involved in managing enterostomies. We required that participants be senior surgeons who had participated in performing enterostomy surgery. The questionnaire consisted of five dimensions: personnel qualification and training, attitude toward ostomy complications, preoperative siting, the process of acquiring ostomy-related surgical skills, and awareness and adoption of relevant techniques. Descriptive statistical analysis was performed. Results: From July 2021 to July 2022, we sent 488 questionnaires through a WeChat link or two-dimensional barcode. We received 467 (95.7%) responses from 196 hospitals in 26 provinces. Among the respondents, 426 (91.2%) were from tertiary hospitals, the departments of which comprised general surgery (130, 27.8%), gastrointestinal surgery (210, 45.0%), surgical oncology (116, 24.8%), and other departments (11, 2.4%). Senior surgeons accounted for 311(66.6%) of the participants. We found that: (1) mentorship by senior surgeons was the primary source of knowledge about ostomies (83.3%, 389/467), followed by mentorship by others and surgical atlases (44.8%, 209/467), and self-education (42.0%, 196/467). (2) Concerns about correlations between complications and surgical procedures that were believed to be "closely" or "probably" related to complications (79.0%, 369/467) were expressed by 99.4% (464/467) of the surgeons. Stenosis and intestinal obstruction requiring unplanned surgery were not uncommon (61.0%, 285/467). Of the listed complications, 46.7% (218/467) were believed to be related to surgical procedures and 79.0% (369/467) avoidable. Only 58.7% (274/467) of surgeons had participated in training and discussion of stoma complications whereas 99.1% (463/467) believed that joint training and discussions between surgeons and enterostomal therapists were necessary. (3) The main reasons for creation of stomas that were not consistent with prior siting included: stoma site marked preoperatively not a suitable trocar site (56.1%, 262/467), defunctioning stoma marking according to standards for permanent stomas (50.7%, 237/467), and inappropriate marking (43.3%, 202/467). (4) The rate of awareness of relevant procedures was generally high; however, it was less than 75% for stoma creation by circular stapler (64.1%, 257/401) and parastomal drainage (44.1%, 177/401). Eversion suture of mucosa and supporting rods were utilized in 65.6% (263/401) and 56.4% (226/401), respectively. Peritoneum (or posterior rectus abdominis sheath) (68.3%, 274/401), anterior rectus abdominis sheath (54.4%, 218/401), and skin (80.6%, 323/401) were the most commonly used tissues for fixation and suture layers of defunctioning and permanent stomas. However, closure of subcutaneous tissue was controversial, suturing being advocated by 26.7% (107/401) and 32.7% (131/401) of surgeons, respectively. Complications were considered to depend mainly on technical skills rather than the amount of suturing by 81.5% (327/401) of the participating surgeons. Conclusions: The complications of stoma surgery are related to the awareness and technical skills of surgeons, indicating there are insufficient training, education, management, and research. Standardization of enterostomy technical strategies and stoma management are therefore imperative.

[Current status, controversy and challenge in the neoadjuvant immunotherapy of colorectal cancer].

Neoadjuvant therapy for colorectal cancer is widely used in rectal cancer, locally advanced colon cancer, and resectable metastatic and recurrent colorectal cancer. Mismatch repair deficient(dMMR) and microsatellite instablity-high (MSI-H) colorectal cancer patients who benefit from the efficacy of immune checkpoint inhibitors are expected to further improve the efficacy of traditional neoadjuvant therapy based on radiotherapy and chemotherapy. In this paper, the current status of immunotherapy (with emphasis on immune checkpoint inhibitors) is elucidated, and the opportunities of its application in neoadjuvant therapy are analyzed, including poor sensitivity of dMMR tumors to traditional therapy, good immune response of early tumors, predictable, manageable and controllable toxicity of immune checkpoint inhibitors. Colorectal cancer patients have growing and diverse needs to be met. Current controversies and challenges are analyzed, and the future directions are pointed out, including active screening of benefit groups, exploration of efficacy prediction markers, optimization of neoadjuvant immunotherapy models, attention to efficacy evaluation and new therapeutic endpoints. Neoadjuvant therapy should be effective, moderate and accurate based on the treatment target. It is the prerequisite and basis to guarantee medical safety and improve therapeutic effect to attach importance to the standardization and safety of clinical research and to pay attention to patients' interests and legal and ethical demands.

[Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer].

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.

[A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics].

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

[Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder].

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.

[Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors].

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

[Role of multidisciplinary cooperation in the diagnosis and treatment of pelvic floor disorder disease].

The pelvic floor disorder disease (PFDD) typically originates from supportive tissue defects or injuries in the pelvic floor with a wide spectrum of symptoms such as urinary incontinence, pelvic organ prolapse, sexual dysfunction, fecal incontinence and chronic pelvic pain. But its etiology is complex, involving multiple systems and organs. So the best management of PFDD requires the implementation of multidisciplinary team (MDT). Pelvic floor centers have been developed abroad to provide pelvic floor services. In the setting of PFDD, the concept of MDT starts lately and develops slowly in China. The MDT approach was demonstrated to improve general rehabilitation, psychological state and quality of life. However, there is no unified standardization for MDT diagnosis and treatment of PFDD at home and abroad. Meanwhile, the personnel composition, responsibilities, training, and operation mode of the MDT need to be further developed. Perfecting the management mode of MDT team members, establishing standardized training programs and assessment criteria play crucial role in the future development of MDT in PFDD.

[Gunsight closure versus purse-string closure techniques in loop stoma reversal: a multicenter prospective randomized controlled trial].

Objective: To compare the wound healing time, Surgical site infection (SSI) rate and other postoperative outcomes between the gunsight closure and purse-string closure technique in loop stoma closure. Methods: Between November 2013 and December 2017, a total of 143 patients who underwent gunsight stoma reversal were included in this multicenter prospective randomized controlled trial. The patients were randomized to undergo gunsight (gunsight group, n=72) or purse-string closure technique (purse-string group, n=71). The primary endpoint was wound healing time. The second endpoints were the incidence of SSI, morbidity, and patient satisfaction. Statistical analysis between groups was performed using the t-test, repeated measures analysis of variance, Mann-Whitney U test, χ(2) test or Fisher's exact test. Results: There were 45 males and 27 females with age of 67 (11) (M(Q(R))) years in gunsight group, 42 males and 29 females with age of 65 (20) years in purse-string group. The body mass index, American Society of Anesthesiologist classification, comorbidities, primary diagnosis, the type of ostomy, intraoperative blood loss, perioperative complications, postoperative hospital stay, hospitalization cost, SSI rate and incisional hernia (stoma site) between the 2 groups were not significantly different (P>0.05). Although had a statistically longer operating time (80(10) minutes vs. 70(10) minutes, Z=-2.381, P=0.017), patients who underwent gunsight procedure and a significantly shorter wound healing time (17(2) days vs. 25(4) days, Z=-10.199, P<0.01), higher patient satisfaction score with regards to wound healing time (3(1) vs. 3(1), Z=-4.526, P<0.01), and higher total patient satisfaction score (25(3) vs. 25(3), Z=-2.529, P=0.011) compared with those who underwent purse-string procedure. Conclusions: The gunsight and purse-string techniques are effective procedures for stoma reversal and both have low SSI rate. The gunsight technique is associated with shorter wound healing time, higher levels of patient satisfaction compared with purse-string technique, and is recommended as the closure technique of choice.

[Necessity of studies on intentional watch and wait strategy in rectal cancer from the perspective of history of surgical oncology].

The comprehensive treatment of solid tumor has become a mature treatment model. Under this model, many tumors, such as breast cancer, anal squamous cell carcinoma, rectal gastrointestinal stromal tumor and rectal cancer, are undergoing the evolutionary process of reducing the extent of surgery and witnessing an increasing demand for organ preservation. Watch and wait (W&W) after neoadjuvant chemoradiation therapy (nCRT) for rectal cancer is a hot topic in recent years. Available data suggest that patients with clinical or expected pathologic complete remission who adopt a W&W strategy are more likely to achieve an outcome similar to surgery, but with a significant improvement in quality of life. From the perspective of the evolution of surgical oncology, it is necessary to conduct further researches on patient screening, strategy improvement, evaluation optimization, and risk control during implementation. Encouraging doctor-patient shared decision-making, adequate patient communication and informed consent, careful design and practice of clinical research, and accumulation of high-level evidence are crucial to this effort. The concept of "intentional W&W" will help to promote the researches, and we should also be alert to the challenges and risks in the implementation process.

[Total neoadjuvant therapy followed by watch and wait approach or organ preservation for MRI stratified low-risk rectal cancer: early result from a prospective, single arm trial].

Objective: To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer. Methods: A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR). Results: Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE. Conclusion: Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

[Short-term outcomes and prognosis of palliative surgery for malignant bowel obstruction caused by peritoneal metastasis of colorectal cancer].

Objective: To explore the short-term efficacy and prognosis of palliative surgical treatment for malignant bowel obstruction (MBO) caused by peritoneal metastasis of colorectal cancer (mCRC). Methods: A retrospective cohort study was conducted. The inclusion criteria for patients were as follows: (1) primary colorectal cancer; (2) massive peritoneal metastasis; (3)obstructive site located below Treitz ligament by imaging; (4) obstruction refractory to conservative treatment; (5) estimated rese survival time more than 2 months; (6) patients and their families had strong willingness for operation; (7) surgical treatment included stoma/bypass and debulking surgery. In accordance with the above criteria, clinicopathological data of 46 patients undergoing palliative surgery at Peking University Gastrointestinal Cancer Center, Unit III from January 2016 to October 2018 were retrospectively collected. Postoperative symptomatic relief rate, morbidity of complication within 30 days, complication classification (Clavien-Dindo classification), mortality and survival after operation were analyzed. Kaplan-Meier method was used to evaluate survival and Cox regression analysis was used to identify prognostic factors. Results: Among 46 patients, 30 were male and 16 were female with median age of 63 (19-87) years; 23 patients received stoma/bypass surgery (stoma/bypass group), and 23 cases received tumor debulking surgery (debulking group). The overall symptom relief rate was 76.1% (35/46), while symptom relief rate in the debulking group was 91.3% (21/23), which was significantly higher than 60.9% (14/23) in the stoma/bypass group (χ(2)=4.301, P=0.038). Postoperative complications occurred in 25 patients. The complication rate was 52.2% (12/23) in the debulking group and 56.5% (13/23) in the stoma/bypass group, without statistically significant difference (χ(2)=0.088, P=0.767). Morbidity of complication beyond grade III was 8.7% (2/23) and 13.0% (3/23) in the debulking group and stoma/bypass group respectively, without statistically significant difference (χ(2)=0.224, P=0.636). Four patients died within 30 days after operation, 2 (8.7%) in each group. Twenty-four patients underwent 1-8 cycles of chemotherapy ± targeting therapy (regimens: CapeOX ± Bevacizumab, FOLFOX/FOLFIRI ± Bevacizumab/Cetuximab), including 10 cases in the stoma/bypass group and 14 cases in the debulking group. Two patients of debulking group received postoperative radiotherapy and chemotherapy (50.6 Gy/22 f, with concurrent oral capecitabine). Till the last follow up of April 2019, 34 patients died (34/46, 73.9%) with a median overall survival time of 6.4 months, and the 6-month and 1-year survival rate was 54.5% and 29.2% respectively. The median survival time in the debulking group was significantly longer than that in the stoma/bypass group (11.5 months vs. 5.2 months, χ(2)=5.117, P=0.024). The median survival time of the 35 patients with symptomatic relief after operation was significant longer than that of 11 patients without relief (7.1 months vs 5.1 months, χ(2)=3.844, P=0.050). Multivariate analysis showed stoma/bypass surgery (HR=2.917, 95%CI:1.357-6.269, P=0.006) and greater omental metastasis (HR=4.060, 95%CI:1.419-11.617, P=0.009) were independent risk factors associated with prognosis of patients with MBO caused by peritoneal mCRC. Conclusions: For patients of MBO caused by peritoneal mCRC, tumor debulking surgery may achieve higher symptom relief rate and prolong survival. Greater omental metastasis indicates poor prognosis.