中华胃肠外科杂志最新文献

Objective: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations (TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods: Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated. Results: (1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC. A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion: Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

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.

Neoadjuvant immunotherapy has achieved exciting efficacy with high clinical complete response (cCR) and pathologic complete response (pCR) rates and durable long-term effects. PD-1 checkpoint blockade-based immunotherapy has been highly successful in microsatellite instability high (MSI-H)/mismatch repair deficiency (dMMR) colorectal cancer and has been recommended as the first-line treatment for metastatic colorectal cancer by domestic and international guidelines. Several studies have shown that immunotherapy can be a potentially curable treatment for MSI-H rectal cancer and has even shown promise in organ preservation in colon cancer. In this study, we first clarified the feasibility of the watch-and-wait strategy after PD-1 checkpoint blockade treatment by indirect and direct evidence. Then from the assessment tools (including digital rectal examination, endoscopy, radiology, and lymph node assessment), the viable assessment methods of cCR for immunotherapy and related difficulties are proposed. Finally, the medication choices of immunotherapy, the treatment regimen, and the follow-up strategy are further discussed. We hope that neoadjuvant immunotherapy could be appropriately applied in MSI-H/dMMR colorectal cancer so that more patients can achieve organ preservation.

For patients with metastatic colorectal cancer (mCRC) who achieve disease control during first-line standard therapy, post-induction strategies should emphasize on quality of life improvement while maintaining disease control. Chemotherapy combined with anti-epidermal growth factor receptor (EGFR) monoclonal antibody is the standard first-line treatment for RAS wild-type mCRC patients. After anti-EGFR-based first-line induction therapy achieves at least stable disease, anti-EGFR-based maintenance treatment could maintain disease control while keeping a good safety profile. Based on research evidence and clinical practice, the Chinese expert consensus on anti-EGFR-based maintenance strategy for RAS wild-type mCRC aims to futher clarify the treatment timing, regimen options, adverse reaction management and follow-up strategy, providing standardized guidance to maximize the clinical benefit in RAS wild-type mCRC.

In recent years, domestic and foreign data have demonstrated that the watch and wait strategy has good safety and efficacy for patients who achieve clinical complete response (cCR) after neoadjuvant therapy. Watch and wait strategy and local resection in selective patients can achieve organ preservation and improve the quality of life. Since the release of the Expert Consensus on Watch and Wait Strategy Following Neoadjuvant Therapy for Rectal Cancer (2020 version), it has attracted widespread attention from medical professionals and patients in the field of rectal cancer treatment. In recent years, the proportion of cCR after neoadjuvant therapy has further increased, and the relevant data of observation strategy has gradually accumulated. However, there are still different opinions on issues such as outcome parameters, risks and benefits, eligible population, re-evaluation criteria and timing, follow-up and salvage methods, and strategies to improve efficacy. Though it can be explained by the various viewpoints, experiences, and evidences, it objectively hinders the development of watch and wait strategy. Therefore, the Chinese Watch and Wait Database Research Collaboration Group (CWWD), together with Chinese Society of Colorectal Surgery, Chinese Medical Association; Colorectal Cancer Physician Specialty Committee, Chinese Medical Doctor Association; Colorectal Cancer Committee, Chinese Anti-Cancer Association; Colorectal Surgeon Working Group, Medical Doctor Association and relevant experts has updated consensus into the 2024 version. This consensus lists the key issues in the practice of watch and wait for rectal cancer, marks the level of evidence and expert opinions through literature review and expert opinion, and exposes the unresolved problems to provide thoughts and solutions for future work in this area.

Objective: To investigate the safety and feasibility of endoscopic full-thickness resection (EFTR) in the treatment of near-clinical complete response (near-cCR) rectal cancer after neoadjuvant therapy. Methods: A 74-year-old female patient with cT3N0M0 stage rectal adenocarcinoma who refused radical surgery for rectal cancer underwent neoadjuvant chemoradiotherapy (5 cycles of CapeOx chemotherapy and concurrent radiotherapy for 25 sessions) after multidisciplinary team discussion. One month after completing neoadjuvant treatment, reassessment including digital rectal examination, colonoscopy, and pelvic enhanced magnetic resonance imaging suggested near-cCR. Despite this, the patient requested rectal-preserving therapy. Subsequently, EFTR was performed five weeks after completion of neoadjuvant treatment. Postoperatively, supportive care including fasting, antimicrobial therapy, and nutritional support was provided. The patient started a liquid diet on the 6th day postoperatively and was discharged on the 13th day. Results: Pathological analysis revealed tubular adenoma with low-grade epithelial dysplasia, with negative margins and negative involvement of the base. During one-year follow-up, there were no signs of local regrowth or distant metastasis, and satisfactory anal function was observed. Conclusion: EFTR is safe and feasible in patients with near-cCR rectal cancer after neoadjuvant therapy. This approach should be considered after thorough evaluation of the patient's condition.

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 organ

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

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 a

Neoadjuvant chemoradiotherapy has emerged as the standard treatment for locally advanced rectal cancer, esophageal cancer and gastroesophageal junction cancer which can not only improve the rate of local control but also induce pathological complete response in some patients. For patients who have achieved clinical complete response after neoadjuvant therapy, the watch & wait strategy and organ preservation could reduce unnecessary surgery and minimize the risk of postoperative complications, meanwhile greatly improve patients' quality of life without affecting the oncologic outcome. At present, a variety of methods, including white light endoscopy, endoscopic forceps biopsy, image enhanced endoscopy, endoscopic ultrasound, endoscopic ultrasound guided fine needle aspiration, endoscopic submucosal dissection, artificial intelligence assisted technology, etc., have become important assistance for the evaluation of tumor response after neoadjuvant chemoradiotherapy and have been widely used in clinical practice. This review will briefly introduce the application of the endoscopic approaches mentioned above and some novel endoscopic techniques and developing trends in response evaluation for patients with locally advanced rectal cancer, esophageal cancer and gastroesophageal junction cancer patients receiving neoadjuvant chemoradiotherapy.