RESUMO
Total neoadjuvant therapy (TNT) of rectal cancer improves rates of pathological complete remission and progression-free survival. With improved clinical response rates, interest grew in a non-operative approach/watch and wait (WaW) for this disease. In 2020, the working groups of ACO/AIO/ARO published a consensus statement on the use of TNT, including a non-operative approach. However, the best combination scheme remains unclear. Despite the increasing use of TNT, there is a lack of comprehensive data on its current implementation and practices. To address this knowledge gap, a multicenter survey was conducted to capture the use of TNT protocols in German-speaking radiotherapy departments. At the beginning of 2023, a GDPR-compliant online survey was conducted in Germany, Austria, and German-speaking Switzerland. The questionnaire comprised 43 questions covering various aspects of TNT, including chemotherapy and WaW concepts. Most respondents (98.4%) confirmed awareness of the consensus on TNT for rectal cancer. Institutions treated an average of 30.22 rectal cancer patients annually. Most respondents (76.2%) reported treating over 80% of patients neoadjuvantly. Regarding TNT, 33.3% treated 21-50% with such a protocol. No significant association was found between the institution type and TNT application. In 62/63 cases, tumor board discussion was standard before offering TNT. VMAT was the predominant technique (82.5%). For rectal cancer dosing, the 50/50.4Gy scheme was most common, followed by 45Gy with a boost and the 5 × 5Gy scheme. Dosing schemes for TNT varied slightly, with more participants reporting the use of 5 × 5Gy compared to radiation therapy for rectal cancer in general. CBCT was the primary IGRT method (88.9%). Larger hospitals typically administered chemotherapy themselves, while private practices collaborated with medical oncologists (p < 0.0001). The most common concurrent chemotherapy drugs were 5-fluorouracil/capecitabine (64.4%) and oxaliplatin (37.3%). A WaW strategy was reported to be institutional implemented by 63.8%. The timing of offering WaW was split, with 50% offering it after radiochemotherapy and 47% during the informed consent talk. For planned WaW, 62% prefer normofractionated TNT. TNT appears to be widely implemented in the German-speaking radio-oncological community, regardless of the type of institution. Image-guided therapy, multidisciplinary team decisions, and internal guidelines play an important role. TNT seems to have already altered treatment protocols for rectal cancer toward an organ-preserving approach in selected cases. In these WaW cases, normofractionation appears to be preferred over hypofractionation.
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Terapia Neoadjuvante , Neoplasias Retais , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/tratamento farmacológico , Humanos , Suíça , Alemanha , Áustria , Inquéritos e Questionários , Radioterapia (Especialidade) , Padrões de Prática MédicaRESUMO
Immuno-oncological cancer management is shifting to neoadjuvant treatments. In patients with gastrointestinal cancers, particularly locally advanced rectal cancer, neoadjuvant chemoimmunotherapy often induce complete responses, hence avoiding surgical intervention. Recent clinical trials indicate that combinations of oxaliplatin-based chemotherapy and PD-1/PD-L1-targeting immunotherapy can be safely administered before surgery with curative intent.
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Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Receptor de Morte Celular Programada 1 , Neoplasias Retais , Humanos , Neoplasias Retais/imunologia , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/tratamento farmacológico , Terapia Neoadjuvante/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Morte Celular Imunogênica/efeitos dos fármacos , Imunoterapia/métodos , Oxaliplatina/uso terapêutico , Oxaliplatina/farmacologia , Oxaliplatina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologiaRESUMO
PURPOSE: Transperineal minimally invasive surgery (TpMIS) during laparoscopic abdominoperineal resection (APR) is an emerging approach that allows for the precise treatment of lower rectal cancer. However, evidence regarding the efficacy of TpMIS is insufficient. This study evaluated the efficacy of TpMIS during laparoscopic APR for patients with lower rectal cancer. METHODS: Patients who underwent laparoscopic APR with TpMIS (TpMIS group; n = 12) and those who underwent conventional laparoscopic APR for low rectal cancer (conventional group; n = 13) were enrolled consecutively in this retrospective study. Standardized TpMIS was performed at our institution. Patient and tumor characteristics and intraoperative, postoperative, and pathological outcomes were compared between groups. The primary outcome was postoperative perineal wound infection. RESULTS: No patients in the TpMIS group experienced postoperative perineal wound infection; however, five (38.5%) patients in the conventional group experienced postoperative perineal wound infection (significant difference; p = 0.016). The estimated blood loss (median, 81 mL vs. 463 mL) and incidence of postoperative urinary dysfunction (8.3% vs. 46.1%) were significantly lower in the TpMIS group than in the conventional group. The postoperative hospital stay (median, 13 vs. 20 days) of the TpMIS group was significantly shorter than that of the conventional group. Pathological outcomes did not differ between groups. The positive circumferential resection margin rates of the TpMIS and conventional groups were 8.3% and 15.4%, respectively. CONCLUSION: TpMIS during laparoscopic APR was associated with significant improvements in the postoperative outcomes of patients with low rectal cancer.
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Laparoscopia , Períneo , Protectomia , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Masculino , Estudos Retrospectivos , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Feminino , Pessoa de Meia-Idade , Idoso , Protectomia/métodos , Protectomia/efeitos adversos , Períneo/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos de Coortes , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The current gold standard for extraperitoneal locally advanced rectal cancer is total neoadjuvant therapy (TNT) followed by total mesorectal excision. This research explored the number of lymph nodes in patients with locally advanced rectal cancer after TNT and its correlation with survival. MATERIALS AND METHODS: This is a post-hoc analysis based on the STELLAR trial, including patients with locally advanced rectal cancer from 16 tertiary centres who were randomized for short-term radiotherapy followed by chemotherapy (TNT group) or long-term concurrent chemotherapy group followed by total mesorectal excision between 2015 and 2018. This lymph node-related analysis is based on the TNT group. Subgroups were differentiated based on the lymph node harvest (below the median number: limited lymphadenectomy group, and greater than/equal to the median number: extended lymphadenectomy group). The primary outcomes were overall survival and disease-free survival (DFS). Correlations with clinical/pathological variables, lymphadenectomy categories and use of adjuvant chemotherapy were explored. RESULTS: Among the 451 patients enrolled in the STELLAR trial, 227 patients (50.3%) were assigned to the TNT group, including 29.5% females. The median number of lymph nodes retrieved in the TNT group was 11.0. Patients in the limited lymphadenectomy subgroup exhibited worse overall survival than those with extended lymphadenectomy (HR 2.95 (95% c.i. 1.47 to 5.92), P = 0.001). The overall survival was similar in the ypN0-limited and ypN1-extended subgroups (HR 0.38 (95% c.i. 0.11 to 1.30), P = 0.109). Adjuvant chemotherapy was associated with better overall survival and DFS than no adjuvant chemotherapy overall (P < 0.001) and in the limited lymphadenectomy subgroup (P < 0.001). However, there was no significant difference in overall survival or DFS with or without adjuvant chemotherapy in the extended lymphadenectomy subgroup (P = 0.887 and P = 0.192, respectively). CONCLUSION: In the STELLAR trial, the median number of lymph nodes harvested was 11. In patients with limited lymphadenectomy, the use of adjuvant therapy after TNT was beneficial and correlated with better prognosis compared with patients who did not receive adjuvant chemotherapy.
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Excisão de Linfonodo , Linfonodos , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Neoplasias Retais/mortalidade , Neoplasias Retais/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Linfonodos/patologia , Idoso , Intervalo Livre de Doença , Metástase Linfática , Adulto , Quimioterapia AdjuvanteRESUMO
INTRODUCTION: Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT-whether induction chemotherapy should precede or follow chemoradiotherapy-remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. METHODS: Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high-quality studies, specific inclusion and exclusion criteria were applied. RESULTS: The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO-12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. CONCLUSION: This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Resultado do Tratamento , Quimioterapia de Indução/métodos , Estadiamento de Neoplasias , Quimioterapia de Consolidação/métodos , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodosRESUMO
BACKGROUND: The hiatal ligament, as the anatomical landmark for the completion of total mesorectal excision (TME) for ultra-low rectal cancer, represents a continuation of the longitudinal muscle of the rectum. It receives vascular supply from the median sacral artery and contains lymphatic vessels. In cases where ultra-low rectal cancer is located in the posterior rectal wall, the hiatal ligament may theoretically serve as an anatomical region susceptible to direct tumor cell spread or distant metastasis. OBJECTIVE: To evaluate the effect of circumferential tumor location (CTL) on postoperative survival of low rectal cancer and to determine the effect of total hiatal ligament excision (THLE) on the prognosis of patients with posterior rectal cancer. METHODS: Patients with ultra-low rectal cancer who underwent laparoscopic surgery between March 2014 and October 2021 were enrolled in this study. Propensity score matching (PSM) analysis was used to compare the clinicopathological characteristics and prognosis of patients in the posterior group and the non-posterior group. Prognostic factors were identified using COX regression. PSM analysis was also used in the posterior tumor subgroup to compare the clinicopathological characteristics and prognosis of patients in the hiatal ligament traditional transection (HLTT) and THLE groups. RESULTS: After PSM, OS, and DFS were comparable between the posterior and non-posterior groups. Similarly, no difference was noted in the local recurrence rate between the two groups (p = 0.23). The prognosis of ultra-low rectal cancer was not affected by CTL. However, the local recurrence rate was significantly lower in the THLE group compared with the HLTT group (p = 0.023). Multivariate analysis of the posterior group identified CRM, TNM stage III, and HLTT as independent risk factors for local recurrence-free survival. CONCLUSIONS: CTL is not a prognostic risk factor for low rectal cancer. In posterior wall tumors, THLE significantly reduces the local recurrence rate for low rectal cancer.
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Recidiva Local de Neoplasia , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Ligamentos/cirurgia , Prognóstico , Laparoscopia/métodos , Estudos Retrospectivos , Reto/cirurgia , Reto/patologia , Protectomia/métodos , Pontuação de PropensãoRESUMO
INTRODUCTION: Inadequate treatment of enlarged lateral lymph nodes (LLNs) in rectal cancer patients is associated with an increased lateral local recurrence (LLR) risk, despite neoadjuvant treatment and total mesorectal excision (TME) surgery. There is a promising role for LLN dissection (LLND) to lower this risk, but this challenging procedure requires appropriate training. This study protocol describes a prospective evaluation of oncological outcomes after standardised treatment based on multidisciplinary training, thereby aiming for a 50% reduction in LLR rate. METHODS AND ANALYSIS: A prospective registration study will be opened in hospitals in which the involved multidisciplinary team members (radiologists, radiation oncologists, surgeons and pathologists) have received dedicated training to enhance knowledge and awareness of LLNs and in which standardised treatment including LLND has been implemented. Patients with rectal cancer and at least one enlarged LLN (short-axis ≥7.0 mm), or intermediate LLN (short-axis 5.0-6.9 mm) with at least one malignant feature on primary MRI, evaluated by a trained radiologist, are eligible. Patients will undergo neoadjuvant treatment by trained radiation oncologists, followed by TME surgery in combination with a minimally invasive, nerve-sparing LLND performed by trained surgeons. LLND specimens are evaluated by trained pathologists or grossing assistants. The primary outcome is LLR rate 3 years postoperatively. Secondary outcomes are morbidity, disease-free survival, overall survival and quality of life. To demonstrate a significant reduction in LLR rate from 13% (based on historical control data) to 6% after optimised treatment, 200 patients with enlarged LLNs are required. ETHICS AND DISSEMINATION: The medical ethics board of the Vrije Universiteit Medical Centre (VUMC), the Netherlands, approved the study on 23 November 2022 (reference: 2021.0524). Participating centres must obtain local approval and participants are required to provide written informed consent. Results obtained from this study will be communicated via peer-reviewed medical journals and presentations at conferences. TRAIL REGISTRATION NUMBER: NCT04486131, 24 July 2020, https://clinicaltrials.gov/ct2/show/NCT04486131.
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Excisão de Linfonodo , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Prospectivos , Terapia Neoadjuvante , Linfonodos/patologia , Recidiva Local de Neoplasia , Metástase Linfática , Estudos Multicêntricos como AssuntoRESUMO
INTRODUCTION: Robotic-assisted complete mesorectal excision (RATME) is increasingly being used by colorectal surgeons. Most surgeons consider RATME a safe method, and believe it can facilitate total mesorectal excision (TME) in rectal cancer, and may potentially have advantages over intersphincteric resection (ISR) and anus preservation. Therefore, this trial was designed to investigate whether RATME has technical advantages and can increase the ISR rate compared with laparoscopic-assisted TME (LATME) in patients with middle and low rectal cancer. METHODS AND ANALYSIS: This is a multicenter, superiority, randomized controlled trial designed to compare RATME and LATME in middle and low rectal cancer. The primary endpoint is the ISR rate. The secondary endpoints are coloanal anastomosis (CAA) rate, conversion to open surgery, conversion to transanal TME (TaTME), abdominoperineal resection (APR) rate, postoperative morbidity and mortality within 30 days, pathological outcomes, long-term survival outcomes, functional outcomes, and quality of life. In addition, certain measurements will be conducted to ensure quality and safety, including centralized photography review and semiannual assessment. DISCUSSION: This trial will clarify if RATME improves ISR and promotes anus preservation in patients with mid- and low-rectal cancer. Furthermore, this trial will provide evidence on the optimal treatment strategies for RATME and LATME in patients with mid- and low-rectal cancer regarding improved operational safety. TRIAL REGISTRATION: ClinicalTrials.gov NCT06105203. Registered on October 27, 2023.
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Canal Anal , Laparoscopia , Estudos Multicêntricos como Assunto , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Canal Anal/cirurgia , Resultado do Tratamento , Protectomia/métodos , Protectomia/efeitos adversos , Estudos de Equivalência como Asunto , Masculino , Fatores de Tempo , Feminino , Complicações Pós-Operatórias/etiologia , Adulto , Ensaios Clínicos Controlados Aleatórios como Assunto , Pessoa de Meia-Idade , Reto/cirurgia , Qualidade de VidaRESUMO
AIM: To describe the epidemiological and clinical data of impaired functional outcome secondary to anterior resection of the rectum and to identify the predictive factors of major low anterior resection syndrome (LARS) Methods: This retrospective study considered patients operated on for rectal tumors in surgical department in our hospital, between January 1st,2009 and December 31st, 2021. The primary outcome measure was the development of a major LARS immediately or after stoma closure. In order to identify independent predictors of major LARS, patients were divided into two groups: the "Major LARS" group and the "No Major LARS" group, and then we carried out a descriptive study, followed by an analytical study with logistic regression. RESULTS: We enrolled 42 patients operated for rectal tumor and had an anterior resection. Half of our patients developed LARS of which 14 developed major LARS. The median time to onset of LARS symptoms was 9 [2 -24] months. At the end of this study, 2 factors were retained: age (OR=2.48; CI95% [1.2- 5.10], p=0.012) and pT3T4 stage (OR=5.95; CI95% [1.07- 33.33], p=0.041) as independent predictive factors of a major LARS. Neoadjuvant therapy was also a risk factor for major LARS in our study with a statistically significant difference (p=0.025) between the two groups "Major LARS" and "No major LARS". CONCLUSION: LARS should be appropriately considered in the management of rectal cancer. Based on our results and data from the literature, age and mesorectal invasion were found to be independent predictors of major LARS.
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Complicações Pós-Operatórias , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Síndrome , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Adulto , Protectomia/efeitos adversos , Reto/cirurgia , Reto/patologia , Terapia Neoadjuvante/estatística & dados numéricos , Síndrome de Ressecção Anterior BaixaRESUMO
Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. 68Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI-04) PET/MRI, [18F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter's sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [68Ga]Ga-FAPI-04 PET/MRI and [18F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [68Ga]Ga-FAPI-04 change in SULpeak percentage, where SULpeak is SUVpeak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [68Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SULpeak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.
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Meios de Contraste , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Neoplasias Retais , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Meios de Contraste/química , Tomografia por Emissão de Pósitrons , Resultado do Tratamento , Terapia Neoadjuvante , Adulto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resposta Patológica Completa , QuinolinasRESUMO
BACKGROUND: With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma. METHODS: This retrospective study analyzed the clinicopathological data from 6,585 AJCC stage I-III rectal adenocarcinoma in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Kaplan-Meier survival analysis and multivariate Cox proportional were used to assess the impact of PR on survival. Propensity score matching (PSM) was employed to balance the baseline covariates between the PR and non-PR groups and to compare postoperative pathological differences. RESULTS: After PSM, PR did not improve overall survival (OS) in stages I (p = 0.33), II (p = 0.37), and III (p = 0.14) patients. Multivariate Cox analysis indicated that PR was not an independent prognostic factor for patients. Restricted cubic spline (RCS) analysis demonstrated a nonlinear negative correlation between OS hazard ratios and both circumferential resection margin (CRM) and lymph node evaluation (LNE). Compared to the non-PR group, patients in the PR group had lower tumor deposits (TD) (p < 0.001), positive CRM (p = 0.191), and perineural invasion (PNI) (p = 0.001). CONCLUSION: PR is not an independent prognostic factor for rectal adenocarcinoma patients. However, PR can reduce the likelihood of TD, CRM, and PNI, thereby potentially influencing the quality of surgery.
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Adenocarcinoma , Estadiamento de Neoplasias , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/radioterapia , Neoplasias Retais/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/radioterapia , Adenocarcinoma/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Programa de SEER , Terapia Neoadjuvante , Cuidados Pré-Operatórios/métodos , Pontuação de Propensão , Radioterapia Adjuvante , AdultoRESUMO
BACKGROUND: To prevent local recurrence caused by exfoliated cancer cells caught in the suture line, intraoperative rectal washout during surgery can be performed to eliminate exfoliated cancer cells. However, the impact of neoadjuvant chemoradiotherapy on exfoliated cancer cells is not well known. This study aimed to identify positive rate of malignant cells in rectal washout fluids of neoadjuvant chemoradiotherapy patients and to determine if neoadjuvant chemoradiotherapy could affect exfoliated cancer cells. METHODS: A total of 105 patients who underwent rectal washout intraoperatively for distal sigmoid colon and rectal cancer from April 2020 to September 2021 were analyzed. The primary outcome was positive rate of malignant cells in rectal washout fluids of patients who had received neoadjuvant chemoradiotherapy. RESULTS: The positive rate of malignant cells in washout fluids of patients who had received neoadjuvant chemoradiotherapy was 0.0% and those who had not was 32.1%. The overall positive rate was 23.8%. In the positive group, tumor sizes were bigger (4.64 ± 1.68 cm vs. 3.64 ± 2.00 cm, p = 0.026) and more patients had a fungating tumor shown in preoperative colonoscopy (96.0% vs. 71.3%, p = 0.012). Although these factors did not show statistical significance in multivariable logistic regression analysis, fungating tumor showed a trend towards significance (OR: 7.28, 95% CI: 0.90-58.77, p = 0.063). CONCLUSIONS: Our study suggests that neoadjuvant chemoradiotherapy could reduce exfoliated cancer cells, and rectal washout for the purpose of eliminating exfoliated cancer cells might be unnecessary in patients who have received neoadjuvant chemoradiotherapy.
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Terapia Neoadjuvante , Humanos , Masculino , Feminino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia/métodos , Irrigação Terapêutica/métodos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controleRESUMO
Objective: To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC). Methods: The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan-Meier method was used for survival analysis. Results: We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4-112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2-21.8) months. Conclusion: The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.
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Neoplasias Encefálicas , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias Encefálicas/secundário , Estudos Retrospectivos , Prognóstico , Idoso , Intervalo Livre de Doença , Adenocarcinoma/secundário , Estimativa de Kaplan-Meier , Taxa de SobrevidaRESUMO
The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The study aimed to identify the optimal model for predicting rectal cancer liver metastasis (RCLM). This involved constructing various prediction models to aid clinicians in early diagnosis and precise decision-making. METHODS: A retrospective analysis was conducted on 193 patients diagnosed with rectal adenocarcinoma were randomly divided into training set (n = 136) and validation set (n = 57) at a ratio of 7:3. The predictive performance of three models was internally validated by 10-fold cross-validation in the training set. Delineation of the tumor region of interest (ROI) was performed, followed by the extraction of radiomics features from the ROI. The least absolute shrinkage and selection operator (LASSO) regression algorithm and multivariate Cox analysis were employed to reduce the dimensionality of radiomics features and identify significant features. Logistic regression was employed to construct three prediction models: clinical, radiomics, and combined models (radiomics + clinical). The predictive performance of each model was assessed and compared. RESULTS: KRAS mutation emerged as an independent predictor of liver metastasis, yielding an odds ratio (OR) of 8.296 (95%CI: 3.471-19.830; p < 0.001). 5 radiomics features will be used to construct radiomics model. The combined model was built by integrating radiomics model with clinical model. In both the training set (AUC:0.842, 95%CI: 0.778-0.907) and the validation set (AUC: 0.805; 95%CI: 0.692-0.918), the AUCs for the combined model surpassed those of the radiomics and clinical models. CONCLUSIONS: Our study reveals that KRAS mutation stands as an independent predictor of RCLM. The radiomics features based on MR play a crucial role in the evaluation of RCLM. The combined model exhibits superior performance in the prediction of liver metastasis. CLINICAL TRIAL NUMBER: Not applicable.
Assuntos
Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Retais , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/genética , Neoplasias Retais/patologia , Feminino , Masculino , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Imageamento por Ressonância Magnética/métodos , Idoso , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adulto , Valor Preditivo dos Testes , RadiômicaRESUMO
PURPOSE: Local excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy. METHODS: This is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups. RESULTS: A total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93-1.00) and 95.5% (95% CI, 0.91-1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74-0.97) vs 4.2% (95% CI, 0.92-1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82-1.00) vs 12.6% (95% CI, 0.81-0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64-0.92) vs 84.7% (95% CI, 0.78-0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001). CONCLUSION: Patients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso , Quimiorradioterapia , Estudos Retrospectivos , Adulto , Intervalo Livre de DoençaRESUMO
PURPOSE: To develop and evaluate a nomogram that integrates clinical parameters with deep learning radiomics (DLR) extracted from Magnetic Resonance Imaging (MRI) data to enhance the predictive accuracy for preoperative lymph node (LN) metastasis in rectal cancer. METHODS: A retrospective analysis was conducted on 356 patients diagnosed with rectal cancer. Of these, 286 patients were allocated to the training set, and 70 patients comprised the external validation cohort. Preprocessed T2-weighted and diffusion-weighted imaging performed preoperatively facilitated the extraction of DLR features. Five machine learning algorithms-k-nearest neighbor, light gradient boosting machine, logistic regression, random forest, and support vector machine-were utilized to develop DLR models. The most effective algorithm was identified and used to establish a clinical DLR (CDLR) nomogram specifically designed to predict LN metastasis in rectal cancer. The performance of the nomogram was evaluated using receiver operating characteristic curve analysis. RESULTS: The logistic regression classifier demonstrated significant predictive accuracy using the DLR signature, achieving an Area Under the Curve (AUC) of 0.919 in the training cohort and 0.778 in the external validation cohort. The integrated CDLR nomogram exhibited robust predictive performance across both datasets, with AUC values of 0.921 in the training cohort and 0.818 in the external validation cohort. Notably, it outperformed both the clinical model, which had AUC values of 0.770 and 0.723 in the training and external validation cohorts, respectively, and the stand-alone DLR model. CONCLUSION: The nomogram derived from multiparametric MRI data, referred to as the CDLR model, demonstrates strong predictive efficacy in forecasting LN metastasis in rectal cancer.
Assuntos
Aprendizado Profundo , Metástase Linfática , Imageamento por Ressonância Magnética Multiparamétrica , Nomogramas , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Idoso , Adulto , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , RadiômicaRESUMO
The structural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy was studied on postoperative material using immunohistochemistry and electron microscopy. The differences in the expression of types I and III collagens, as well as in the ultrastructural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy were revealed. We observed high expression of collagen I and wide channels in the collagen matrix in the central areas of the well differentiated adenocarcinomas without neoadjuvant radiation therapy and in poorly differentiated adenocarcinomas after neoadjuvant radiation therapy, which can be associated with metastasis and poor prognosis for the patients.
Assuntos
Adenocarcinoma , Colágeno Tipo III , Colágeno Tipo I , Matriz Extracelular , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/ultraestrutura , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos da radiação , Matriz Extracelular/ultraestrutura , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Imuno-Histoquímica , IdosoRESUMO
PURPOSE: This study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN). MATERIALS AND METHODS: Patients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local-regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109). CONCLUSIONS: Our study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.