Alimentação saudável: dicas práticas para variedade e sabor: Reduzir o consumo de carnes vermelhas e evitar carnes processadas é uma das formas de se proteger do câncer de cólon e reto

Reduzir o consumo de carnes vermelhas e evitar carnes processadas é uma das formas de se proteger do câncer de cólon e reto

Preliminary comparative study of lower extremity pressure measurements under the conditions using former models and new lithotomy stirrups in rectal cancer surgery.

BACKGROUND: This study aimed to investigate the effect of the use of new lithotomy stirrups-2 on the pressure dispersal on lower limbs, which may lead to the prevention of well-leg compartment syndrome (WLCS) and deep venous thrombosis (DVT), which are the most commonly associated adverse events with laparoscopic and robot-assisted rectal surgery. METHODS: A total of 30 healthy participants were included in this study. The pressure (mmHg) applied on various lower limb muscles when using conventional lithotomy stirrups-1 and new type stirrups-2 was recorded in various lithotomy positions; 1) neutral position, 2) Trendelenburg position (15°) with a 0° right inferior tilt, and 3) Trendelenburg position (15°) with a 10° right inferior tilt. Using a special sensor pad named Palm Q®, and the average values were compared between two types of stirrups. RESULTS: The use of new lithotomy stirrups-2 significantly reduced the pressure applied on the lower limb muscles in various lithotomy positions compared with the use of lithotomy stirrups-1. The most pressured lower limb muscle when using both lithotomy stirrups was the central soleus muscle, which is the most common site for the development of WLCS and DVT. In addition, when using the conventional lithotomy stirrups-1, the pressure was predominantly applied to the proximal soleus muscle; however, when using lithotomy stirrups-2, the pressure was shifted to the more distal soleus muscle. CONCLUSION: These results suggest that the new lithotomy stirrups-2 is useful in reducing the pressure load on leg muscles, especially on the proximal to central soleus, and may reduce the incidence of WLCS and DVT after rectal surgery performed in the lithotomy position. Further clinical studies are needed to determine whether the use of lithotomy stirrups-2 prevents these complications in various clinical settings.

Effect of previous abdominal surgery on robotic-assisted rectal cancer surgery.

BACKGROUND: The effect of previous abdominal surgery (PAS) in laparoscopic surgery is well known and significantly adds to longer hospital length of stay (LOS), postoperative ileus, and inadvertent enterotomies. However, little evidence exists in patients with PAS undergoing robotic-assisted (RA) rectal surgery. METHODS: All patients undergoing RA surgery for rectal cancer were reviewed. Patients with PAS were divided into minor and major PAS groups, defined as surgery involving >1 quadrant. The primary outcome was the risk of conversion to open surgery. RESULTS: A total of 750 patients were included, 531 in the no-PAS (NPAS) group, 31 in the major PAS group, and 188 in the minor PAS group. Patients in the major PAS group had significantly longer hospital LOS (P < .001) and lower adherence to enhanced recovery pathways (ERPs; P = .004). The conversion rates to open surgery were similar: 3.4% in the NPAS group, 5.9% in the minor PAS group, and 9.7% in the major PAS group (P = .113). Estimated blood loss (EBL; P = .961), operative times (OTs; P = .062), complication rates (P = .162), 30-day readmission (P = .691), and 30-day mortality (P = .494) were similar. Of note, 53 patients underwent lysis of adhesions (LOA). On multivariate analysis, EBL >500 mL and LOA significantly influenced conversion to open surgery. EBL >500 mL, age >65 years, conversion to open surgery, and prolonged OT were risk factors for prolonged LOS, whereas adherence to ERPs was a protector. CONCLUSION: PAS did not seem to affect the outcomes in RA rectal surgery. Given this finding, the robotic approach may ultimately provide patients with PAS with similar risk to patients without PAS.

Management and staging of anal adenocarcinoma in the United States: a population-based analysis.

BACKGROUND: Anal adenocarcinoma is rare with no standardized treatment regimen or staging system. Therefore, different combinations of chemotherapy, radiation, and surgery are used in management. Within the staging system, tumor stage can be based on the depth of invasion, as for rectal adenocarcinoma, or size, as in anal squamous cell carcinoma. This study aimed to analyze patterns of care and clinically available staging systems for anal adenocarcinoma using a national database. METHODS: Adults diagnosed with anal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results database (2004-2019). In addition, 6 different treatment regimens were identified. Stages were categorized according to the American Joint Committee on Cancer classifications of rectal adenocarcinoma and anal squamous cell carcinoma. RESULTS: Of 1040 patients, 48% were female, the median age was 67 years, and 18% had distant metastases. Chemoradiotherapy + abdominoperineal resection was the most common treatment regimen (22%). Moreover, 5-year overall survival (OS) and disease-specific survival (DSS) were the highest for local excision only (67% and 85%) and the lowest in the alternative group (34% and 48%). After adjustment, the treatment groups that did not include surgery were associated with worse 5-year OS. In multivariable analysis, the T stage based on depth of invasion showed incrementally lower OS for T2 and T3 anal adenocarcinomas. CONCLUSION: Omission of surgical resection in combination with chemoradiotherapy was associated with worse OS and DSS, suggesting the relevance of surgery in anal adenocarcinoma management. Prognostically, rectal staging based on depth of invasion better discriminated between T stages, indicating that providers should consider using this system in practice.

Minor impact of anastomotic leakage in anterior resection for rectal cancer on long-term male urinary and sexual function.

PURPOSE: Anastomotic leakage after anterior resection for rectal cancer induces bowel dysfunction, but the influence on urinary and sexual function is largely unknown. This cross-sectional cohort study evaluated long-term effect of anastomotic leakage on urinary and sexual function in male patients. METHODS: Patients operated with anterior resection for rectal cancer in 15 Swedish hospitals 2007-2013 were identified. Anastomotic leakage and other clinical variables were retrieved from the Swedish Colorectal Cancer Registry and medical records. Urinary and sexual dysfunction were evaluated at 4 to 11 years after surgery using the International Prostate Symptom Score, International Index of Erectile Function, and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire CR29. The effect of anastomotic leakage on average scores of urinary and sexual dysfunction was evaluated as a primary outcome, and the single items permanent urinary catheter and sexual inactivity as secondary outcomes. The association of anastomotic leakage and functional outcomes was analyzed using regression models with adjustment for confounders. RESULTS: After a median follow-up of 84 months (interquartile range: 67-110), 379 out of 864 eligible men were included. Fifty-nine (16%) patients had anastomotic leakage. Urinary incontinence was more common in the leakage group, with an adjusted mean score difference measured by EORTC QLQ ColoRectal-29 of 8.69 (95% confidence interval: 0.72-16.67). The higher risks of urinary frequency, permanent urinary catheter, and sexual inactivity did not reach significance. CONCLUSION: Anastomotic leakage after anterior resection had a minor negative impact on urinary and sexual function in men.

Switching from FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab based on early tumor shrinkage in RAS wild-type metastatic colorectal cancer: A phase II trial (HYBRID).

BACKGROUND: Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC). METHODS: Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival. RESULTS: This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients. CONCLUSIONS: Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.

Clinical influence of prophylactic lateral lymph node dissection on oncologic outcomes of patients with mid-low rectal cancer undergoing mesorectal excision: a meta-analysis.

BACKGROUND: Although several recent meta-analyses have investigated the clinical influence of the addition of lateral lymph node dissection (LLND) on oncologic outcomes in patients with mid-low rectal cancer (RC) undergoing mesorectal excision (ME), most studies included in such meta-analyses were retrospectively designed. Therefore, this study aimed to explore the clinical influence of prophylactic LLND on oncologic outcomes in patients with mid-low RC undergoing ME. METHODS: A comprehensive electronic search of the literature up to July 2022 was performed to identify studies that compared oncologic outcomes between patients with mid-low RC undergoing ME who underwent LLND and patients with mid-low RC undergoing ME who did not undergo LLND. A meta-analysis was performed using fixed-effects models and the generic inverse variance method to calculate hazard ratios (HRs) and 95% CIs, and heterogeneity was analyzed using I2 statistics. RESULTS: A total of 6 studies, consisting of 3 randomized and 3 propensity score matching studies, were included in this meta-analysis. The results of the meta-analysis of 2 randomized studies demonstrated no significant effect of prophylactic LLND on improving oncologic outcomes concerning overall survival (OS) (HR, 1.22; 95% CI, 0.89-1.69; I2 = 0%; P = .22) and relapse-free survival (RFS) (HR, 1.03; 95% CI, 0.81-1.31; I2 = 28%; P = .83). CONCLUSION: The results of this meta-analysis revealed no significant influence of prophylactic LLND on oncologic outcomes-OS and RFS-in patients with mid-low RC who underwent ME.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Surgical management of rectal cancer with synchronous treatment of prostate cancer.

PURPOSE: To assess the safety and efficacy of synchronous treatments for rectal (RC) and prostate (PC) cancers. METHODS: Single-center retrospective study (2007-2021) of patients treated with neoadjuvant radiotherapy (RT) and total mesorectal excision (TME) for RC with synchronous PC treatment. The endpoints were 30-day postoperative severe complications, R0 resection rates, 3-year disease-free survival (DFS) and 3-year overall survival (OS). RESULTS: Among the 16 patients, 15 (93.7%) received neoadjuvant pelvic RT (40-50.4 Gray) followed by either transperineal high dose rate prostate brachytherapy (62.5%), prostate external RT boost (25.0%), or androgen deprivation therapy (ADT) alone (6.3%). One (6.3%) patient received neoadjuvant rectal brachytherapy and ADT. Pelvic RT was combined with chemotherapy in 87.5% of cases. TME was performed in all patients with low anterior resection (87.5%) or abdominoperineal resection (12.5%), primarily using minimally invasive surgery (87.5%). The R0 resection rate was 93.8%. Six (37.5%) patients experienced 30-day Clavien-Dindo grade IIIb complications, including one (7.1%) anastomotic leak. After a median follow-up of 39.0 months, 63.6% of diverting ileostomies were reversed. Three-year DFS from RC was 71.4% (CI 40.2-88.3) and 3-year OS was 84.4% (CI 95% 50.4-95.9). No PC recurrence or death occurred. CONCLUSIONS: Synchronous management of RC and PC with pelvic RT followed by curative prostate RT doses and TME showed acceptable morbidity and oncologic results. Prostate brachytherapy, the most commonly used treatment modality, allowed avoidance of prostatectomy and additional external RT to the rectum. PC should not limit the curative intent of RC, as all recurrences were from rectal origin.

Comparison of robotic versus laparoscopic surgery for visceral obesity in mid-low rectal cancer: a propensity-matched analysis.

Obesity is becoming more and more common, and measuring visceral fat area (VFA) is a useful diagnostic technique for visceral obesity (VO). The purpose of this research is to compare the surgical results of robotic versus laparoscopic rectal surgery, with a focus on assessing the benefits of the latter method for treating both VO and mid-low rectal cancer. Patients receiving laparoscopic or robotic anterior rectal excision at Northern Jiangsu People's Hospital's general surgery department were included in the retrospective analysis. 242 people in all took part in the study; 121 cases were assigned to the robotic surgery (RS) group and another 121 cases to the laparoscopic surgery (LS) group. In comparison to LS, our results show that RS led to a shorter period for the recovery of bowel function (p = 0.03), a shorter hospital stay (p < 0.001), a smaller intraoperative blood loss (p < 0.001), and a shorter time until the commencement of oral intake (p = 0.041). However, there were no statistically significant differences between the two groups in terms of the indices of histopathologic specimens, the proportion of temporary loop ileostomy, and the incidence of early postoperative problems (p > 0.05). When patients with VO undergo surgery for rectal cancer, RS has the added benefit of accelerating patient recovery while producing results that are similar to LS in the near run.

A comprehensive evaluation of 80 consecutive robotic low anterior resections: impact of not mobilizing the splenic flexure alongside low-tie vascular ligation as a standardized technique.

Rectal cancer surgery represents challenges due to its location. To overcome them and minimize the risk of anastomosis-related complications, some technical maneuvers or even a diverting ileostomy may be required. One of these technical steps is the mobilization of the splenic flexure (SFM), especially in medium/low rectal cancer. High-tie vascular ligation may be another one. However, the need of these maneuvers may be controversial, as especially SFM may be time-consuming and increase the risk of iatrogenic. The objective is to present the short- and long-term outcomes of a low-tie ligation combined with no SFM in robotic low anterior resection (LAR) for mid- and low rectal cancer as a standardized technique. A retrospective observational single-cohort study was carried out at Reina Sofia University Hospital, Cordoba, Spain. 221 robotic rectal resections between Jul-18th-2018 and Jan-12th-2023 were initially considered. After case selection, 80 consecutive robotic LAR performed by a single surgeon were included. STROBE checklist assessed the methodological quality. Histopathological, morbidity and oncological outcomes were assessed. Anastomotic stricture occurrence and distance to anal verge were evaluated after LAR by rectosigmoidoscopy. Variables related to the ileostomy closure such as time to closure, post-operative complications or hospital stay were also considered. The majority of patients (81.2%) presented a mid-rectal cancer and the rest, lower location (18.8%). All patients had adequate perfusion of the anastomotic stump assessed by indocyanine green. Complete total mesorectal excision was performed in 98.8% of the patients with a lymph node ratio < 0.2 in 91.3%. The anastomotic leakage rate was 5%. One patient (1.5%) presented local recurrence. Anastomosis stricture occurred in 7.5% of the patients. The limitations were small cohort and retrospective design. The non-mobilization of the splenic flexure with a low-tie ligation in robotic LAR is a feasible and safe procedure that does not affect oncological outcomes.

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer: A Nonrandomized Controlled Trial.

Importance: The available evidence regarding anti-epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies. Objective: To evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC. Design, Setting, and Participants: This nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months). Intervention: Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported. Results: Overall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects. Conclusions and Relevance: These findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.

Evaluation of the effect of prostate diameters on erectile dysfunction in patients who underwent low-anterior resection.

OBJECTIVE: Male erectile dysfunction is an important complication of rectal surgery. In this research, the effect of prostate dimensions on the development of postoperative erectile dysfunction in patients diagnosed with mid-rectum adenocarcinoma who underwent low anterior resection (LAR) is examined. PATIENTS AND METHODS: Thirty-one male patients diagnosed as mid-rectal adenocancer were included. The International Index of Erectile Function (IIEF) questionnaire was used to determine the patients' pre and postoperative erectile dysfunction levels, and the level of relationship between the change in these IIEF scores and prostate measurements determined by computed tomography were evaluated. RESULTS: There were statistically significant differences between IIEF index score and anterior posterior (AP) and transverse (TR) measurements (p≤0.001; p≤0.001), but no statistically significant difference was found between craniocaudal (CC) measurement values (p=0.169). CONCLUSIONS: The risk of nerve injury will be higher in those with a small prostate transverse diameter. Intraoperative nerve monitoring should be recommended primarily in younger patient groups.

Long-term outcomes of robot-assisted laparoscopic surgery versus conventional laparoscopic surgery for rectal cancer: single-center, retrospective, propensity score analyses.

Although the short-term outcomes of robot-assisted laparoscopic surgery (RALS) for rectal cancer are well known, the long-term oncologic outcomes of RALS compared with those of conventional laparoscopic surgery (CLS) are not clear. This study aimed to compare the long-term outcomes of RALS and CLS for rectal cancer using propensity score matching. This retrospective study included 185 patients with stage I-III rectal cancer who underwent radical surgery at our institute between 2010 and 2019. Propensity score analyses were performed with 3-year overall survival (OS) and relapse-free survival (RFS) as the primary endpoints. After case matching, the 3-year OS and 3-year RFS rates were 86.5% and 77.9% in the CLS group and 98.4% and 88.5% in the RALS group, respectively. Although there were no significant differences in OS (p = 0.195) or RFS (p = 0.518) between the groups, the RALS group had slightly better OS and RFS rates. 3-year cumulative (Cum) local recurrence (LR) and 3-year Cum distant metastasis (DM) were 9.7% and 8.7% in the CLS group and 4.5% and 10.8% in the RALS group, respectively. There were no significant differences in Cum-LR (p = 0.225) or Cum-DM (p = 0.318) between the groups. RALS is a reasonable surgical treatment option for patients with rectal cancer, with long-term outcomes similar to those of CLS in such patients.

Clinicopathological factors predict residual lymph node metastasis in locally advanced rectal cancer with ypT0-2 after neoadjuvant chemoradiotherapy.

PURPOSE: Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50-50.6 Gy for the planning gross tumor volume and 41.8-45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610-0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. CONCLUSION: The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.

Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. METHODS: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. RESULTS: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. CONCLUSIONS: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

Clinical application of the B-type sutured ileostomy in robotic-assisted low anterior resection for rectal cancer: a propensity score matching analysis.

Currently, there is no consensus on the position and method for temporary ileostomy in robotic-assisted low anterior resection for rectal cancer. Herein, this study introduced the B-type sutured ileostomy, a new temporary ileostomy technique, and compared it to the traditional one to assess its efficacy and safety. Between September 2020 and December 2022 in our centre, B-type sutured ileostomy was performed on 124 patients undergoing robotic-assisted low anterior resection for rectal cancer. A retrospective review of a prospectively collected database identified patients who underwent robotic-assisted low anterior resection for rectal cancer with a temporary ileostomy between January 2018 and December 2022. Patients who underwent B-type sutured ileostomy (B group) were matched in a 1:1 ratio with patients who underwent traditional ileostomy (Control group) using a propensity score based on age, sex, BMI, Comorbidity, American Society of Anesthesiologists (ASA) score, and Prior abdominal surgery history. Surgical and postoperative outcomes, health status, and stoma closure data were analyzed for both groups. ClinicalTrials.gov Identifier：NCT05915052.  The B group (n = 118) shows advantages compared to the Control group (n = 118) regarding total operation time (155.98 ± 21.63 min vs 168.92 ± 21.49 min, p = 0.001), postoperative body pain (81.92 ± 4.12 vs 78.41 ± 3.02, p = 0.001) and operation time of stoma closure (46.19 ± 11.30 min vs 57.88 ± 11.08 min, p = 0.025). The two groups had no other notable differences. The B-type sutured ileostomy is a safe and feasible option in robotic-assisted low anterior resection for rectal cancer. The B-type sutured ileostomy may offer advantages such as shorter overall surgical duration, lighter postoperative pain, and shorter second-stage ostomy incorporation surgery. However, attention should be directed towards the occurrence of stoma prolapse.

Tumor size impact on TNM staging which define post-operative complications in rectal cancer.

The purpose of this study was to see how accurate tumor size was at predicting T and N stages in rectal malignancies. Tumor sizes of 40 mm and greater than 40 mm were used to assess post-operative challenges in related to T1-T2 and T3-T4 stages, as well as between node N0 and node N1 and N2 patients. A total of 131 patients were treated for colorectal cancer, with 54 patients < 40 mm and 77 patients > 40 mm receiving Da Vinci colorectal surgery. Conferring to the Clavien-Dindo classification grade III, there's an increase in the percentage of tumors > 40 mm, which also impacts the percentage of intestinal obstruction, anastomotic leakage, GERD, and sepsis with a P < 0.05. A tumor size of more than 40 mm is strongly associated with advanced pT stages. Tumor size may serve in addition to clinical staging and improve the management of rectal cancer.

[Chinese expert consensus on the watch and wait strategy in rectal cancer patients after neoadjuvant treatment (2024 version)].

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.

[Endoscopic response evaluation in gastrointestinal cancers after neoadjuvant chemora- diotherapy].

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.