Background and Purpose:Neoadjuvant immunotherapy currently significantly enhances treatment efficacy for locally advanced rectal cancer(LARC);However,clinical management of immune-related adverse events(irAEs)lacks robust evidence.This study aimed to investigate the characteristics,clinical management strategies,and outcomes of irAEs during neoadjuvant immunotherapy for rectal cancer,providing a basis for optimizing irAEs monitoring and intervention.Methods:We retrospectively analyzed clinical data from LARC patients who developed irAEs after receiving neoadjuvant immunotherapy at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,between July 2022 and June 2024.Types of irAEs,severity,time of onset,management strategies,and outcomes were recorded.All patients underwent regular follow-up for at least 6 months.This study has been approved by Peking Union Medical College Hospital,Chinese Academy of Medical Sciences(ethical approval number:I-24PJ0024).Descriptive statistics were used to summarize irAEs patterns and management approaches.Results:A total of 41 irAE episodes occurred among the 30 patients.Mild irAEs(Grade 1-2)accounted for 78.0%(32/41),while severe irAEs(Grade 3-4)constituted 22.0%(9/41).Five patients(16.7%)permanently discontinued treatment due to severe toxicity.Endocrine toxicities were most frequent(36.6%,15/41),primarily characterized by progression from hyperthyroidism to hypothyroidism;75.0%required thyroid hormone replacement therapy.One case of delayed-onset adrenal insufficiency was alleviated with glucocorticoid(GC)therapy.Among hepatotoxicities(19.5%,8/41),62.5%were Grade 3 injury,and 37.5%required GC intervention;two patients experienced recurrence during adjuvant chemotherapy.Three cases of severe myositis occurred,accompanied by asymptomatic myocardial injury(evidenced by markedly elevated creatine kinase and concurrent changes in cardiac biomarkers),all requiring high-dose GC pulse therapy combined with intravenous immunoglobulin or immunosuppressants(recovery period:2-4 months).Nine dermatological reactions were managed with topical therapy.Two gastrointestinal events occurred,including one Grade 3 diarrhea treated with GCs.The overall GC usage rate was 31.7%(13/41),with 76.9%administered for Grade≥3 irAEs.Conclusion:irAEs during neoadjuvant immunotherapy for LARC are predominantly mild-to-moderate and manageable with supportive care.However,some patients develop severe(Grade 3-4)irAEs requiring multidisciplinary management.GC usage is concentrated in higher-grade irAEs,with severe myositis and cardiac involvement necessitating intensive immunosuppressive therapy despite their rarity.Recurrence of irAEs during adjuvant chemotherapy in a minority of patients underscores the necessity for early recognition,graded intervention,and comprehensive management throughout the entire treatment cycle.

Background and Aims:For patients with mid-to-low rectal cancer who achieve clinical complete response(cCR)or near-cCR after neoadjuvant chemoradiotherapy(nCRT),the key concern for both clinicians and patients is how to preserve anal function as much as possible without significantly compromising oncological outcomes.This study was performed to evaluate the safety and feasibility of local excision as an anus-preserving approach in rectal cancer patients with cCR or near-cCR.Methods:A retrospective analysis was conducted on 51 patients with mid-to-low rectal cancer who underwent local resection after achieving cCR or near-cCR following nCRT at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,between March 2014 and July 2023.The clinical characteristics,imaging and pathological findings,surgical outcomes,as well as oncological and functional results were reviewed.Results:Among the 51 patients,34 were male and 17 were female,with a mean age of 61±14 years.Pre-nCRT imaging staging showed:cT1-2N0 in 12 cases(23.5％),cT3N0 in 13 cases(25.5％),cT1-3N0-1 in 19 cases(37.4％),and cT1-3N2 in 7 cases(13.7％).The average tumor distance from the anal verge was(4.5±1.1)cm.After achieving cCR or near-cCR following nCRT,all patients underwent local resection:40 cases(78.4％)underwent transanal endoscopic microsurgery(TEM),7 cases(13.7％)underwent transanal minimally invasive surgery(TAMIS),and 4 cases(7.8％)underwent conventional transanal local excision.The postoperative complication rate was 27.5％(14/51),with 71.4％classified as Clavien-Dindo grade Ⅰ.Postoperative histopathology showed ypT0 in 26 cases(51.0％),ypT1 in 8 cases(15.7％),ypT2 in 16 cases(31.4％),and ypT3 in 1 case(2.0％).The concordance rate between pathological results and preoperative imaging was 54.9％.Over a median follow-up of 60 months(range:34-79),there were 4 cases(7.8％)of local recurrence,12 cases(23.5％)of distant metastasis,and 5 cancer-related deaths(9.8％).Six months postoperatively,both the Wexner score and the low anterior resection syndrome(LARS)score significantly improved compared to post-nCRT values[Wexner:1(0-2)vs.2(1-5);LARS:3.3±5.75 vs.4.3±6.86;both P＜0.01].Conclusion:For patients with mid-to-low rectal cancer who achieve cCR or near-cCR after nCRT,local en bloc resection of the bowel wall lesions enables accurate assessment of residual tumor status and facilitates personalized subsequent treatment,potentially sparing some patients from radical surgery.Local resection can be a viable anus-preserving option for patients who are unfit for or strongly averse to radical resection.However,local excision cannot replace radical surgery,and its precise indications warrant further investigation.

The integration of immunotherapy into neoadjuvant treatment for locally advanced rectal cancer has markedly increased complete response rates, offering greater potential for organ preservation. However, the reduced restaging accuracy after immunotherapy has limited the applicability of the watch-and-wait strategy. As an organ-preserving approach that enables residual lesion removal and pathological assessment, local excision not only reduces the risk of local regrowth associated with watch-and-wait, but also enables full-thickness tumor bed sampling to determine pathological stage, regression pattern, and molecular characteristics, thereby supporting risk stratification and individualized decision-making. Moving forward, local excision is expected to achieve precise, risk-adapted organ preservation by optimizing surgical timing and techniques, and integrating multimodal parameters including imaging, pathology, and the tumor microenvironment, ultimately attaining the dual aim of maximizing both oncologic efficacy and functional preservation.

Objective:To investigate the complications, along with their diagnosis and management, that follow local excision for rectal cancer after neoadjuvant therapy.Methods:The clinical data of 53 patients with rectal cancer who underwent local resection after neoadjuvant treatment in Peking Union Medical College Hospital from January, 2010 to December, 2024 were retrospectively collected for this descriptive case series study. Indications for local resection were: (1) age ≥ 18 years; (2) American Society of Anesthesiologists (ASA) classification I-III; (3) pathologically confirmed rectal adenocarcinoma; (4) distance from the lower edge of the tumor to the anal edge of less than 8 cm; and (5) use of preoperative neoadjuvant therapy. Contraindications of local resection were: (1) multiple primary colorectal cancer and (2) intestinal obstruction, intestinal perforation, or and gastrointestinal bleeding that required emergency surgery. There were 36 males and 17 females, and the median age was 62 (26-85) years. After neoadjuvant therapy, the median distance from the tumor to the anal margin was 4.5 (range, 2.2-6.9) cm. The main outcome measures included: surgical details, pathological findings, postoperative complications, anorectal function, and oncological outcomes (recurrence and survival).Results:Surgical methods included transanal endoscopic microsurgery (TEM) in 47 cases, transanal minimally invasive surgery (TAMIS) in 3 cases, and traditional transanal local resection in 3 cases. Of the 53 patients, 29 (54.7%) had pathological complete response (pCR), namely pT0 stage; 8 cases were pT1, 15 cases were pT2, and 1 case was pT3. Twenty-four cases (45.3%) had 33 complications. Clavien-Dindo grade I-II accounted for 97.0% (32/33), including 14 cases (26.4%) of wound dehiscence. Low anterior resection syndrome (LARS) occurred in 7 cases (13.2%), including 5 minor cases and 2 major cases. Postoperative fever occurred in 7 cases (13.2%); urinary retention occurred in 3 cases (5.7%); and diarrhea occurred in 1 case (1.9%). Clavien Dindo grade III was observed in only 3.0% (1/33) of patients, which was a rectovaginal fistula. Among the 14 patients with wound dehiscence, 7 cases only suffered anal pain and were cured after symptomatic analgesic treatment. Five cases suffered anal pain with hematochezia but improved after treatment with essential diet, hemostasis, intravenous antibiotics, pain relief, and sitz bath. Two cases of secondary perianal infection were treated with intravenous antibiotics, local drainage, parenteral nutrition support, and symptomatic treatment, and the wounds healed within 2 months. One patient with rectovaginal fistula underwent transverse colostomy. After six months, the fistula healed and stoma reversal was performed. Seven patients with LARS received anal lifting exercise and defecation reflex training, and anal function recovered to the preoperative level after 1 year. Other complications improved after symptomatic treatment, pain relief, or catheter replacement. The median follow-up time was 60 months. Local recurrence occurred in 4 patients (7.5%) and distant metastasis occurred in 12 patients (22.6%). Seven patients (13.2%) died. The 5-year disease-free survival rate was 75.5%, and the 5-year overall survival rate was 86.8%.Conclusions:Local excision for rectal cancer following neoadjuvant therapy has a high incidence of complications, mainly wound-related, due to the decline of rectal wound healing ability after radiotherapy. However, most of the complications were relieved after symptomatic treatment, and the risk was controllable.

Background and Purpose:Neoadjuvant immunotherapy currently significantly enhances treatment efficacy for locally advanced rectal cancer(LARC);However,clinical management of immune-related adverse events(irAEs)lacks robust evidence.This study aimed to investigate the characteristics,clinical management strategies,and outcomes of irAEs during neoadjuvant immunotherapy for rectal cancer,providing a basis for optimizing irAEs monitoring and intervention.Methods:We retrospectively analyzed clinical data from LARC patients who developed irAEs after receiving neoadjuvant immunotherapy at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,between July 2022 and June 2024.Types of irAEs,severity,time of onset,management strategies,and outcomes were recorded.All patients underwent regular follow-up for at least 6 months.This study has been approved by Peking Union Medical College Hospital,Chinese Academy of Medical Sciences(ethical approval number:I-24PJ0024).Descriptive statistics were used to summarize irAEs patterns and management approaches.Results:A total of 41 irAE episodes occurred among the 30 patients.Mild irAEs(Grade 1-2)accounted for 78.0%(32/41),while severe irAEs(Grade 3-4)constituted 22.0%(9/41).Five patients(16.7%)permanently discontinued treatment due to severe toxicity.Endocrine toxicities were most frequent(36.6%,15/41),primarily characterized by progression from hyperthyroidism to hypothyroidism;75.0%required thyroid hormone replacement therapy.One case of delayed-onset adrenal insufficiency was alleviated with glucocorticoid(GC)therapy.Among hepatotoxicities(19.5%,8/41),62.5%were Grade 3 injury,and 37.5%required GC intervention;two patients experienced recurrence during adjuvant chemotherapy.Three cases of severe myositis occurred,accompanied by asymptomatic myocardial injury(evidenced by markedly elevated creatine kinase and concurrent changes in cardiac biomarkers),all requiring high-dose GC pulse therapy combined with intravenous immunoglobulin or immunosuppressants(recovery period:2-4 months).Nine dermatological reactions were managed with topical therapy.Two gastrointestinal events occurred,including one Grade 3 diarrhea treated with GCs.The overall GC usage rate was 31.7%(13/41),with 76.9%administered for Grade≥3 irAEs.Conclusion:irAEs during neoadjuvant immunotherapy for LARC are predominantly mild-to-moderate and manageable with supportive care.However,some patients develop severe(Grade 3-4)irAEs requiring multidisciplinary management.GC usage is concentrated in higher-grade irAEs,with severe myositis and cardiac involvement necessitating intensive immunosuppressive therapy despite their rarity.Recurrence of irAEs during adjuvant chemotherapy in a minority of patients underscores the necessity for early recognition,graded intervention,and comprehensive management throughout the entire treatment cycle.

The integration of immunotherapy into neoadjuvant treatment for locally advanced rectal cancer has markedly increased complete response rates, offering greater potential for organ preservation. However, the reduced restaging accuracy after immunotherapy has limited the applicability of the watch-and-wait strategy. As an organ-preserving approach that enables residual lesion removal and pathological assessment, local excision not only reduces the risk of local regrowth associated with watch-and-wait, but also enables full-thickness tumor bed sampling to determine pathological stage, regression pattern, and molecular characteristics, thereby supporting risk stratification and individualized decision-making. Moving forward, local excision is expected to achieve precise, risk-adapted organ preservation by optimizing surgical timing and techniques, and integrating multimodal parameters including imaging, pathology, and the tumor microenvironment, ultimately attaining the dual aim of maximizing both oncologic efficacy and functional preservation.

Background and Aims:For patients with mid-to-low rectal cancer who achieve clinical complete response(cCR)or near-cCR after neoadjuvant chemoradiotherapy(nCRT),the key concern for both clinicians and patients is how to preserve anal function as much as possible without significantly compromising oncological outcomes.This study was performed to evaluate the safety and feasibility of local excision as an anus-preserving approach in rectal cancer patients with cCR or near-cCR.Methods:A retrospective analysis was conducted on 51 patients with mid-to-low rectal cancer who underwent local resection after achieving cCR or near-cCR following nCRT at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,between March 2014 and July 2023.The clinical characteristics,imaging and pathological findings,surgical outcomes,as well as oncological and functional results were reviewed.Results:Among the 51 patients,34 were male and 17 were female,with a mean age of 61±14 years.Pre-nCRT imaging staging showed:cT1-2N0 in 12 cases(23.5％),cT3N0 in 13 cases(25.5％),cT1-3N0-1 in 19 cases(37.4％),and cT1-3N2 in 7 cases(13.7％).The average tumor distance from the anal verge was(4.5±1.1)cm.After achieving cCR or near-cCR following nCRT,all patients underwent local resection:40 cases(78.4％)underwent transanal endoscopic microsurgery(TEM),7 cases(13.7％)underwent transanal minimally invasive surgery(TAMIS),and 4 cases(7.8％)underwent conventional transanal local excision.The postoperative complication rate was 27.5％(14/51),with 71.4％classified as Clavien-Dindo grade Ⅰ.Postoperative histopathology showed ypT0 in 26 cases(51.0％),ypT1 in 8 cases(15.7％),ypT2 in 16 cases(31.4％),and ypT3 in 1 case(2.0％).The concordance rate between pathological results and preoperative imaging was 54.9％.Over a median follow-up of 60 months(range:34-79),there were 4 cases(7.8％)of local recurrence,12 cases(23.5％)of distant metastasis,and 5 cancer-related deaths(9.8％).Six months postoperatively,both the Wexner score and the low anterior resection syndrome(LARS)score significantly improved compared to post-nCRT values[Wexner:1(0-2)vs.2(1-5);LARS:3.3±5.75 vs.4.3±6.86;both P＜0.01].Conclusion:For patients with mid-to-low rectal cancer who achieve cCR or near-cCR after nCRT,local en bloc resection of the bowel wall lesions enables accurate assessment of residual tumor status and facilitates personalized subsequent treatment,potentially sparing some patients from radical surgery.Local resection can be a viable anus-preserving option for patients who are unfit for or strongly averse to radical resection.However,local excision cannot replace radical surgery,and its precise indications warrant further investigation.

Objective:To investigate the complications, along with their diagnosis and management, that follow local excision for rectal cancer after neoadjuvant therapy.Methods:The clinical data of 53 patients with rectal cancer who underwent local resection after neoadjuvant treatment in Peking Union Medical College Hospital from January, 2010 to December, 2024 were retrospectively collected for this descriptive case series study. Indications for local resection were: (1) age ≥ 18 years; (2) American Society of Anesthesiologists (ASA) classification I-III; (3) pathologically confirmed rectal adenocarcinoma; (4) distance from the lower edge of the tumor to the anal edge of less than 8 cm; and (5) use of preoperative neoadjuvant therapy. Contraindications of local resection were: (1) multiple primary colorectal cancer and (2) intestinal obstruction, intestinal perforation, or and gastrointestinal bleeding that required emergency surgery. There were 36 males and 17 females, and the median age was 62 (26-85) years. After neoadjuvant therapy, the median distance from the tumor to the anal margin was 4.5 (range, 2.2-6.9) cm. The main outcome measures included: surgical details, pathological findings, postoperative complications, anorectal function, and oncological outcomes (recurrence and survival).Results:Surgical methods included transanal endoscopic microsurgery (TEM) in 47 cases, transanal minimally invasive surgery (TAMIS) in 3 cases, and traditional transanal local resection in 3 cases. Of the 53 patients, 29 (54.7%) had pathological complete response (pCR), namely pT0 stage; 8 cases were pT1, 15 cases were pT2, and 1 case was pT3. Twenty-four cases (45.3%) had 33 complications. Clavien-Dindo grade I-II accounted for 97.0% (32/33), including 14 cases (26.4%) of wound dehiscence. Low anterior resection syndrome (LARS) occurred in 7 cases (13.2%), including 5 minor cases and 2 major cases. Postoperative fever occurred in 7 cases (13.2%); urinary retention occurred in 3 cases (5.7%); and diarrhea occurred in 1 case (1.9%). Clavien Dindo grade III was observed in only 3.0% (1/33) of patients, which was a rectovaginal fistula. Among the 14 patients with wound dehiscence, 7 cases only suffered anal pain and were cured after symptomatic analgesic treatment. Five cases suffered anal pain with hematochezia but improved after treatment with essential diet, hemostasis, intravenous antibiotics, pain relief, and sitz bath. Two cases of secondary perianal infection were treated with intravenous antibiotics, local drainage, parenteral nutrition support, and symptomatic treatment, and the wounds healed within 2 months. One patient with rectovaginal fistula underwent transverse colostomy. After six months, the fistula healed and stoma reversal was performed. Seven patients with LARS received anal lifting exercise and defecation reflex training, and anal function recovered to the preoperative level after 1 year. Other complications improved after symptomatic treatment, pain relief, or catheter replacement. The median follow-up time was 60 months. Local recurrence occurred in 4 patients (7.5%) and distant metastasis occurred in 12 patients (22.6%). Seven patients (13.2%) died. The 5-year disease-free survival rate was 75.5%, and the 5-year overall survival rate was 86.8%.Conclusions:Local excision for rectal cancer following neoadjuvant therapy has a high incidence of complications, mainly wound-related, due to the decline of rectal wound healing ability after radiotherapy. However, most of the complications were relieved after symptomatic treatment, and the risk was controllable.

Objective To explore the relationship between body composition and aerobic exercise ca-pacity of individuals entering the plateau.Methods The body composition of forty-five subjects was as-sessed by using the bioelectrical impedance.All subjects underwent step movement with the step height of 40 cm,at a speed of 25 b/min for 5 minutes on the plain and the simulated low-pressure oxygen chamber at an altitude of 4000 m.Blood oxygen saturation and heart rate before and immediate-ly after exercise were recorded,and the VO2max(mL/kg·min)was calculated.Then,Multiple Linear Re-gression and Pearson correlation analysis were employed to explore the correlation between body compo-sition and VO2max.Moreover,subjects were divided into two groups according to the average value of each body component,and the effect of a single component on the decrease of VO2max in the plateau environment(ΔVO2max,plain-VO2max-plateau-VO2max)was investigated.Results Compared with on the plain,VO2max decreased significantly in the simulated plateau environment.The body composition of all subjects was within the normal range.However,the body mass index(BMI)of 6 subjects(accounting for 13％)exceeded 24 kg/m2.Their muscles of the upper limb and trunk were approximately 95％and required strengthening.Correlation analysis indicated that there was no significant correlation between body composition and VO2max.Compared with the low body water group,the ΔVO2max of the high body water group was significantly lower.Conclusion In the early stage of entering the plateau environment,the aerobic exercise capacity of the human body is reduced,and sufficient water within the normal range helps to improve the aerobic exercise capacity in such environment.

Objective:To investigate the influencing factors for permanent protective stoma in locally advanced rectal cancer (LARC) patients after neoadjuvant chemoradiotherapy (nCRT) and radical resection.Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 216 patients with LARC who were admitted to Peking Union Medical College Hospital from June 2019 to May 2022 were collected. There were 144 males and 72 females, aged 60(53,68)years. All patients underwent nCRT followed by radical resection and protective stoma. Observation indicators: (1) permanent protective stoma and anastomotic complications after nCRT and radical resection; (2) influencing factors for permanent protective stoma after nCRT and radical resection; (3) influencing factors for anastomotic complications after nCRT and radical resection. Comparison of measurement data with normal distribution between groups was performed using the independent sample t test. Comparison of measurement data with skewed distribution between groups was performed using the Mann-Whitney U rank sum test. Comparison of count data between groups was performed using the chi-square test or Fisher exact probability. Univariate analysis was conducted using appropriate statistical methods based on the data type. Factors with P<0.15 in univariate analysis were included in binary Logistic regression for multivariate analysis using a forward stepwise method based on maximum likelihood estimation. Results:(1) Permanent protective stoma and anastomotic complications after nCRT and radical resection. All the 216 patients were followed up of 40(23,51)months. Of the 216 patients, 36 cases developed permanent protective stoma, of which 24 cases could not have stoma reversal based on preoperative evaluation, while 12 cases required re-colostomy with transverse colostomy after complications from reversal surgery. Of the 216 patients, 25 cases deve-loped anastomotic-related complications. (2) Influencing factors for permanent protective stoma after nCRT and radical resection. Results of multivariate analysis showed that anastomotic-related complication was an independent risk factor for permanent protective stoma in LARC patients after nCRT and radical resection ( odd ratio=17.503, 95% confidence interval as 6.097-50.244, P<0.05). (3) Influencing factors for anastomotic complications after nCRT and radical resection. Results of multivariate analysis showed that age ≤50 years, low body mass index, prolonged operation time were all independent risk factors for anastomotic-related complications in LARC patients after nCRT and radical resection( odd ratio=0.385, 0.770, 1.105, 95% confidence interval as 0.151-0.979, 0.654-0.907, 1.007-1.023, P<0.05). Conclusions:Anastomotic-related complication is an independent risk factor for permanent protective stoma in LARC patients after nCRT and radical resection. Age ≤50 years, low body mass index, prolonged operation time are independent risk factors for anastomotic-related complications in LARC after nCRT and radical resection.