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PURPOSE: Improvements in neoadjuvant therapy for locally advanced cT4 rectal cancer have led to improved tumour response and thus a variety of suitable management strategies. The aim of this study was to report management and outcomes of patients with cT4 rectal cancer undergoing a spectrum of treatment strategies from organ preservation (OP) to pelvic exenteration (PE). METHODS: Patients who underwent elective treatment for cT4 rectal cancer between 2016 and 2021 were included. All patients were treated with curative intent. Surgical management was adapted to tumour response. Kaplan-Meier curves were generated to compare 3-year overall survival (3y-OS), local recurrence (3y-LR) and distant metastases (3y-DM) between different strategies. RESULTS: Among 152 patients included, 13 (8%) underwent OP, 71 (47%) TME and 68 (45%) APR/PE. The median follow-up was 31.3 months. Patients undergoing OP had a lower tumour pretreatment (p < 0.001). Compared to patients with TME, those with APR/PE had a higher rate of ypT4 (p = 0.001) with a lower R0 rate (p = 0.044). The 3y-OS and 3y-DM were 78% and 15.1%, respectively, without significant differences. The 3y-LR was 6.6%, and patients with OP had a significantly worse 3y-local regrowth compared to 3y-LR in patients with TME and APR/PE (30.2% vs. 5.4% vs. 2%, p = 0.008). CONCLUSION: cT4 tumours may be suitable for the full spectrum of rectal cancer management from organ preservation to pelvic exenteration depending on tumour response to neoadjuvant therapy. However, careful attention is required in OP as local regrowth in up to 30% of cases reinforces the need for sustained active surveillance in Watch&Wait programmes.
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Estudos de Viabilidade , Terapia Neoadjuvante , Exenteração Pélvica , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Resultado do Tratamento , Recidiva Local de Neoplasia/patologia , AdultoRESUMO
AIMS: This review aims to evaluate the feasibility of robot-assisted laparoscopic surgery (RALS) as an alternative to standard laparoscopic surgery (SLS) for the treatment of bowel deep-infiltrative endometriosis. Additionally, it aims to provide guidance for future study design, by gaining insight into the current state of research, in accordance with the IDEAL framework. METHOD: A systematic review was conducted to identify relevant studies on RALS for bowel deep infiltrating endometriosis in Medline, Embase, Cochrane Library and PubMed databases up to August 2023 and reported in keeping with PRISMA guidelines. The study was registered with PROSPERO Registration: CRD42022308611 RESULTS: Eleven primary studies were identified, encompassing 364 RALS patients and 83 SLS patients, from which surgical details, operative and postoperative outcomes were extracted. In the RALS group, mean operating time was longer (235 ± 112 min) than in the standard laparoscopy group (171 ± 76 min) (p < 0.01). Patients in the RALS group experienced a shorter hospital stay (5.3 ± 3.5 days vs. 7.3 ± 4.1 days) (p < 0.01), and appeared to have fewer postoperative complications compared to standard laparoscopy. Research evidence for RALS in bowel DE is at an IDEAL Stage 2B of development. CONCLUSION: RALS is a safe and feasible alternative to standard laparoscopy for bowel endometriosis treatment, with a shorter overall length of stay despite longer operating times. Further robust randomized trials recommended to delineate other potential advantages of RALS.
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Endometriose , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Endometriose/cirurgia , Endometriose/patologia , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Tempo de Internação , Duração da Cirurgia , Enteropatias/cirurgiaRESUMO
BACKGROUND: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS: One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION: These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.
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Adenocarcinoma , Polipose Adenomatosa do Colo , DNA Glicosilases , Neoplasias Gástricas , Humanos , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/terapia , Polipose Adenomatosa do Colo/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/terapia , Adenocarcinoma/diagnóstico , DNA Glicosilases/genética , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Síndromes Neoplásicas Hereditárias/diagnóstico , Europa (Continente) , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/terapia , PóliposAssuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Robóticos/educação , Procedimentos Cirúrgicos Robóticos/normas , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Cirurgia Colorretal/educação , Cirurgia Colorretal/normas , Europa (Continente) , Sociedades MédicasRESUMO
INTRODUCTION: Over the past 2 decades, physicians' wellbeing has become a topic of interest. It is currently unclear what the current needs are of early career academic surgeons (ECAS). METHODS: Consensus statements on academic needs were developed during a Delphi process, including all presenters from the previous European Surgical Association (ESA) meetings (2018-2022). The Delphi involved (1) a literature review, (2) Delphi form generation, and (3) an accelerated Delphi process. The Delphi form was generated by a steering group that discussed findings identified within the literature. The modified accelerated e-consensus approach included 3 rounds over a 4-week period. Consensus was defined as >80% agreement in any round. RESULTS: Forty respondents completed all 3 rounds of the Delphi. Median age was 37 years (interquartile range 5), and 53% were female. Majority were consultant/attending (52.5%), followed by PhD (22.5%), fellowship (15%), and residency (10%). ECAS was defined as a surgeon in 'development' years of clinical and academic practice relative to their career goals (87.9% agreement). Access to split academic and clinical contracts is desirable (87.5%). Consensus on the factors contributing to ECAS underperformance included: burnout (94.6%), lack of funding (80%), lack of mentorship (80%), and excessive clinical commitments (80%). Desirable factors to support ECAS development included: access to e-learning (90.9%), face-to-face networking opportunities (95%), support for research team development (100%), and specific formal mentorship (93.9%). CONCLUSION: The evolving role and responsibilities of ECAS require increasing strategic support, mentorship, and guidance on structured career planning. This will facilitate workforce sustainability in academic surgery in the future.
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Internato e Residência , Cirurgiões , Humanos , Feminino , Adulto , Masculino , Avaliação das Necessidades , Consenso , Técnica DelphiRESUMO
BACKGROUND: Obesity can pose perioperative challenges related to obesity-associated co-morbidities and technical factors. However, the true impact of obesity on postoperative outcomes is not well established and reports are conflicting. The aim was to perform a systematic review and meta-analysis to explore the effect of obesity on perioperative outcomes for general surgery procedures in distinct obesity subtypes. METHODS: A systematic review was performed for studies reporting postoperative outcomes in relation to BMI in upper gastrointestinal, hepatobiliary and colorectal based on an electronic search using the Cochrane Library, Science Direct, PubMed and Embase up to January 2022. The primary outcome was the incidence of 30-day postoperative mortality among patients with obesity undergoing general surgical procedures in comparison to patients with normal range BMI. RESULTS: Sixty-two studies, including 1 886 326 patients, were eligible for inclusion. Overall, patients with obesity (including class I/II/II) had lower 30-day mortality rates in comparison to patients with a normal BMI (odds ratio (OR) 0.75, 95 per cent c.i. 0.66 to 0.86, P < 0.0001, I2 = 71 per cent); this was also observed specifically in emergency general surgery (OR 0.83, 95 per cent c.i. 0.79 to 0.87, P < 0.0000001, I2 = 7 per cent). Compared with normal BMI, obesity was positively associated with an increased risk of 30-day postoperative morbidity (OR 1.11, 95 per cent c.i. 1.04 to 1.19, P = 0.002, I2 = 85 per cent). However, there was no significant difference in postoperative morbidity rates between the cohorts of patients with a normal BMI and class I/II obesity (OR 0.98, 95 per cent c.i. 0.92 to 1.04, P = 0.542, I2 = 92 per cent). Overall, the cohort with obesity had a higher rate of postoperative wound infections compared with the non-obese group (OR 1.40, 95 per cent c.i. 1.24 to 1.59, P < 0.0001, I2 = 82 per cent). CONCLUSION: These data suggest a possible 'obesity paradox' and challenge the assumption that patients with obesity have higher postoperative mortality compared with patients with normal range BMI. Increased BMI alone is not associated with increased perioperative mortality in general surgery, highlighting the importance of more accurate body composition assessment, such as computed tomography anthropometrics, to support perioperative risk stratification and decision-making. REGISTRATION NUMBER: CRD42022337442 (PROSPERO https://www.crd.york.ac.uk/prospero/).
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Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Fatores de Risco , Obesidade/complicações , Comorbidade , Índice de Massa CorporalRESUMO
Importance: Postoperative urinary retention (POUR) is a well-recognized complication of inguinal hernia repair (IHR). A variable incidence of POUR has previously been reported in this context, and contradictory evidence surrounds potential risk factors. Objective: To ascertain the incidence of, explore risk factors for, and determine the health service outcomes of POUR following elective IHR. Design, Setting, and Participants: The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) study, an international, prospective cohort study, recruited participants between March 1 and October 31, 2021. This study was conducted across 209 centers in 32 countries in a consecutive sample of adult patients undergoing elective IHR. Exposure: Open or minimally invasive IHR by any surgical technique, under local, neuraxial regional, or general anesthesia. Main Outcomes and Measures: The primary outcome was the incidence of POUR following elective IHR. Secondary outcomes were perioperative risk factors, management, clinical consequences, and health service outcomes of POUR. A preoperative International Prostate Symptom Score was measured in male patients. Results: In total, 4151 patients (3882 male and 269 female; median [IQR] age, 56 [43-68] years) were studied. Inguinal hernia repair was commenced via an open surgical approach in 82.2% of patients (n = 3414) and minimally invasive surgery in 17.8% (n = 737). The primary form of anesthesia was general in 40.9% of patients (n = 1696), neuraxial regional in 45.8% (n = 1902), and local in 10.7% (n = 446). Postoperative urinary retention occurred in 5.8% of male patients (n = 224), 2.97% of female patients (n = 8), and 9.5% (119 of 1252) of male patients aged 65 years or older. Risk factors for POUR after adjusted analyses included increasing age, anticholinergic medication, history of urinary retention, constipation, out-of-hours surgery, involvement of urinary bladder within the hernia, temporary intraoperative urethral catheterization, and increasing operative duration. Postoperative urinary retention was the primary reason for 27.8% of unplanned day-case surgery admissions (n = 74) and 51.8% of 30-day readmissions (n = 72). Conclusions: The findings of this cohort study suggest that 1 in 17 male patients, 1 in 11 male patients aged 65 years or older, and 1 in 34 female patients may develop POUR following IHR. These findings could inform preoperative patient counseling. In addition, awareness of modifiable risk factors may help to identify patients at increased risk of POUR who may benefit from perioperative risk mitigation strategies.
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Hérnia Inguinal , Laparoscopia , Retenção Urinária , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Retenção Urinária/cirurgia , Hérnia Inguinal/cirurgia , Hérnia Inguinal/complicações , Estudos de Coortes , Incidência , Estudos Prospectivos , Estudos Retrospectivos , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de Risco , Anestesia GeralRESUMO
Total mesorectal excision (TME) is accepted as the gold standard for oncological resection in rectal cancer. The best approach to TME is debated and often surgeons will select a preferred approach. In this study, we aimed to describe how both robotic (R-TME) and transanal (TaTME) TME can be integrated into high-volume rectal cancer surgeon practice with a comparison of clinical and oncological outcomes and cost analysis. A prospective comparative cohort study was performed in a high-volume rectal cancer centre comparing the previous 50 R-TME and 50 TaTME performed by the same surgeon. A comparison of tumour characteristics was performed to highlight a specific role for each technique. Clinical outcomes (operative duration, length of stay (LOS) and perioperative morbidity), cancer quality indicators (resection margin and completeness of TME) and cost analysis were compared. Statistical analysis was performed using IBM SPSS, version 20. R-TME was preferred in mid-rectal cancer, compared to TaTME preferred in low rectal cancer (9 cm vs. 5 cm, p < 0.001). Operative duration was longer in R-TME compared to TaTME (265 vs. 179 min, p < 0.001). Major complications (CD III-IV complications) were experienced in 10% of R-TME and 14% of TaTME (p = 0.476). A 98% (n = 49) clear R0 resection margin was achieved with both R-TME and TaTME and mesorectum quality defined as 'complete' in 86% (n = 43) in R-TME and 82% (n = 41) in TaTME. Length of hospital stay was shorter in R-TME (5 vs. 7 days, p = 0.624). An overall difference of 131 was observed favouring TaTME. In high-volume rectal cancer surgery practice, both R-TME and TaTME can be practised and tailored according to patients and tumour characteristics, with comparable clinical and cancer outcomes and is cost-effective.
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Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Cirurgia Endoscópica Transanal , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Margens de Excisão , Estudos Prospectivos , Estudos de Coortes , Análise Custo-Benefício , Complicações Pós-Operatórias/etiologia , Laparoscopia/métodos , Cirurgia Endoscópica Transanal/métodos , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
Robot-assisted surgery (RAS) continues to grow globally. Despite this, in the UK and Ireland, it is estimated that over 70% of surgical trainees across all specialities have no access to robot-assisted surgical training (RAST). This study aimed to provide educational stakeholders guidance on a pre-procedural core robotic surgery curriculum (PPCRC) from the perspective of the end user; the surgical trainee. The study was conducted in four Phases: P1: a steering group was formed to review current literature and summarise the evidence, P2: Pan-Specialty Trainee Panel Virtual Classroom Discussion, P3: Accelerated Delphi Process and P4: Formulation of Recommendations. Forty-three surgeons in training representing all surgical specialties and training levels contributed to the three round Delphi process. Additions to the second- and third-round surveys were formulated based on the answers and comments from previous rounds. Consensus opinion was defined as ≥ 80% agreement. There was 100% response from all three rounds. The resulting formulated guidance showed good internal consistency, with a Cronbach alpha of > 0.8. There was 97.7% agreement that a standardised PPCRC would be advantageous to training and that, independent of speciality, there should be a common approach (95.5% agreement). Consensus was reached in multiple areas: 1. Experience and Exposure, 2. Access and context, 3. Curriculum Components, 4 Target Groups and Delivery, 5. Objective Metrics, Benchmarking and Assessment. Using the Delphi methodology, we achieved multispecialty consensus among trainees to develop and reach content validation for the requirements and components of a PPCRC. This guidance will benefit from further validation following implementation.
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Procedimentos Cirúrgicos Robóticos , Especialidades Cirúrgicas , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Consenso , Técnica Delphi , Currículo , Especialidades Cirúrgicas/educação , Competência ClínicaRESUMO
BACKGROUND: Orthognathic surgery is a reliable and safe method to improve maxillo-mandibular malformations. However, it is a complex procedure that can affect deeper structures and the terminal blood supply of specific areas, thereby affecting the results. Occasionally, despite careful digital planning and diagnosis, esthetic complications may occur, such as scarring or mucogingival alterations, including localized aseptic necrosis with associated recessions. In more severe cases, larger fragments of necrosis may be involved. METHODS AND RESULTS: The aim of this case report was to present a case, including diagnosis, treatment plan, periodontal plastic surgical technique, and follow-up for a recession type 3 (RT3) defect. This RT3 gingival defect was associated with necrotic crestal bone exposure in the anterior esthetic area resulting from a complication after orthognathic surgery. CONCLUSIONS: Partial reconstruction of the interdental papilla can be possible through consideration of the defect characteristics, use of microsurgical principles, and utilization of a suitable connective tissue grafting technique. KEY POINTS: Why is this case new information? To the authors' knowledge, there is very limited clinical and scientific evidence regarding the management of esthetic complications associated with ischemic necrosis resulting from orthognathic surgeries. This case study identified the management of papillary reconstructions of these mucogingival defects. What are the keys to the successful management of this case? For an ideal case management, adequate plaque and infection control and timely notice of the defect appearance are critical. Additionally, proper surgical soft tissue management of the affected papillae and surrounding area is required. Finally, the type of connective tissue graft to be used, its management and fixation, and proper postoperative protocols are needed for case success. What are the primary limitations to success in this case? Despite the limitations of this study, the authors consider that the treatment of mucogingival complications related to orthognathic surgeries is possible, using microsurgical concepts and connective tissue grafts to reconstruct papillae.
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Retração Gengival , Osteonecrose , Humanos , Gengiva/transplante , Retração Gengival/etiologia , Retração Gengival/cirurgia , Estética Dentária , Tecido Conjuntivo/transplante , Doença IatrogênicaRESUMO
AIM: The systematic use of a defunctioning ileostomy for 2-3 months postoperatively to protect low colorectal anastomosis (<7 cm from the anal verge) has been the standard practice after total mesorectal excision (TME). However, stoma-related complications can occur in 20%-60% of cases, which may lead to prolonged inpatient care, urgent reoperation and long-term definitive stoma. A negative impact on quality of life (QoL) and increased healthcare expenses are also observed. Conversely, it has been reported that patients without a defunctioning stoma or following early stoma closure (days 8-12 after TME) have a better functional outcome than patients with systematic defunctioning stoma in situ for 2-3 months. METHOD: The main objective of this trial is to compare the QoL impact of a tailored versus systematic use of a defunctioning stoma after TME for rectal cancer. The primary outcome is QoL at 12 months postoperatively using the European Organization for. Research and Treatment of Cancer QoL questionnaire QLQ-C30. Among 29 centres of the French GRECCAR network, 200 patients will be recruited over 18 months, with follow-up at 1, 4, 8 and 12 months postoperatively, in an open-label, randomized, two-parallel arm, phase III superiority clinical trial. The experimental arm (arm A) will undergo a tailored use of defunctioning stoma after TME based on a two-step process: (i) to perform or not a defunctioning stoma according to the personalized risk of anastomotic leak (defunctioning stoma only if modified anastomotic failure observed risk score ≥2) and (ii) if a stoma is fashioned, whether to perform an early stoma closure at days 8-12, according to clinical (fever), biochemical (C-reactive protein level on days 2 and 4 postoperatively) and radiological postoperative assessment (CT scan with retrograde contrast enema at days 7-8 postoperatively). The control arm (arm B) will undergo systematic use of a defunctioning stoma for 2-3 months after TME for all patients, in keeping with French national and international guidelines. Secondary outcomes will include comprehensive analysis of functional outcomes (including bowel, urinary and sexual function) again up to 12 months postoperatively and a cost analysis. Regular assessments of anastomotic leak rates in both arms (every 50 randomized patients) will be performed and an independent data monitoring committee will recommend trial cessation if this rate is excessive in arm A compared to arm B. CONCLUSION: The GRECCAR 17 trial is the first randomized trial to assess a tailored, patient-specific approach to decisions regarding defunctioning stoma use and closure after TME according to personalized risk of anastomotic leak. The results of this trial will describe, for the first time, the QoL and morbidity impact of selective use of a defunctioning ileostomy and the potential health economic effect of such an approach.
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Neoplasias Retais , Estomas Cirúrgicos , Humanos , Ileostomia/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Qualidade de Vida , Neoplasias Retais/terapia , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
With global expansion of robotic surgery, there is increasing interest in its application in colonic surgery. This study aimed to report the feasibility of robotic assisted colonic resection as a post hoc analysis of a randomised controlled trial (RCT) by comparing outcomes following laparoscopic and robotic colectomy. The PAROS trial was a phase III RCT that compared outcomes in low pressure (LP, 7 mmHg) and standard pressure (SP, 12 mmHg) pneumoperitoneum in elective colectomy. A post hoc analysis was performed to compare clinical and operative outcomes in laparoscopic and robotic colonic resection in a high volume colorectal surgery practice. A health economic comparison was also performed. Data were analysed using IBM SPSS StatisticsTM, version 20. 127 patients were compared [34% (n = 43) robotic, 66% (n = 84) laparoscopic]. LP pneumoperitoneum was practiced in 47% (n = 20) robotic and 50% (n = 42) laparoscopic cases. Cancer procedures were more commonly performed in the robotic group (p = 0.009). Clinical outcomes were comparable including post-operative surgical complications (p = 0.493). Operative times were longer (p = 0.005) but length of hospital stay (LOS) was one day shorter in the robotic group (p = 0.05). Conversion to SP pneumoperitoneum was required in 9.5% (n = 8) of the LP laparoscopic group compared to 2.3% (n = 1) of the LP robotic group. Surgeons reported good operative visibility in all robotic cases and 94% (n = 80) laparoscopic cases. Considering, capital investment and maintenance, instrumentation and LOS, robotic cases were 651 more expensive per case. Robotic-assisted surgery is feasible in colonic resection and may facilitate shorter LOS and the possibility to complete MIS using low pressure pneumoperitoneum.
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Laparoscopia , Pneumoperitônio , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos de Viabilidade , Pneumoperitônio/complicações , Colectomia/métodos , Colo , Laparoscopia/métodos , Duração da Cirurgia , Tempo de Internação , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
PURPOSE: Metabolomic analysis in colorectal cancer (CRC) is an emerging research area with both prognostic and therapeutic targeting potential. We aimed to identify metabolomic pathway activity prognostic for CRC recurrence and overall survival and cross-reference such metabolomic data with prognostic genomic single-nucleotide polymorphisms (SNPs). METHODS: A systematic search of PubMed, Embase and Cochrane Library was performed for studies reporting prognostic metabolomic pathway activity in CRC in keeping with PRISMA guidelines. The QUADOMICS tool was used to assess study quality. MetaboAnalyst software (version4.0) was used to map metabolites that were associated with recurrence and survival in CRC to recognise metabolic pathways and identify genomic SNPs associated with CRC prognosis, referencing the following databases: Human Metabolome Database (HMDB), the Small Molecule Pathway Database (SMPDB), PubChem and Kyoto Encyclopaedia of Genes and Genomes (KEGG) Pathway Database. RESULTS: Nine studies met the inclusion criteria, reporting on 1117 patients. Increased metabolic activity in the urea cycle (p = 0.002, FDR = 0.198), ammonia recycling (p = 0.004, FDR = 0.359) and glycine and serine metabolism (p = 0.004, FDR = 0.374) was prognostic of CRC recurrence. Increased activity in aspartate metabolism (p < 0.001, FDR = 0.079) and ammonia recycling (p = 0.004, FDR = 0.345) was prognostic of survival. Eight resulting SNPs were prognostic for CRC recurrence (rs2194980, rs1392880, rs2567397, rs715, rs169712, rs2300701, rs313408, rs7018169) and three for survival (rs2194980, rs169712, rs12106698) of which two overlapped with recurrence (rs2194980, rs169712). CONCLUSIONS: With a caveat on study heterogeneity, specific metabolites and metabolic pathway activity appear evident in the setting of poor prognostic colorectal cancers and such metabolic signatures are associated with specific genomic SNPs.
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Neoplasias Colorretais , Polimorfismo de Nucleotídeo Único , Humanos , Amônia , Neoplasias Colorretais/tratamento farmacológico , Genômica , Metabolômica/métodos , PrognósticoRESUMO
BACKGROUND: Assessment of tumor response in rectal cancer after neoadjuvant treatment by MRI (Tumour Regression Grade, TRG 1-5) is well standardized. The overall timing and method of defining complete response (cCR) remain controversial. The aim of this work was to evaluate the feasibility of a defined Response Surveillance Program (RSP) to increase organ preservation for locally advanced rectal cancer after neoadjuvant treatment. METHODS: A standardized program of clinical (CR), radiological (RR) and metabolic (MR) assessment of tumor response is defined over a 6 month period from completion of NACRT with formal assessment performed every 2 months (M). Patients with TRG1-3 at M2 and TRG1-2 at M4 continue in the program up to M6 assessment. Patients managed with this protocol from 2016 to 2020 were analyzed. The primary endpoint was rectal preservation rate. Secondary endpoints included disease-free survival and overall survival at 3 years. RESULT: 314 potentially suitable patients were enrolled in the RSP and 50 patients completed the six month program and were successfully enrolled into watch and wait. Fourteen (28%) were T2 tumor stage, 27 (54%) T3 and nine (18%) were T4. During watch and wait, patients with locoregional recurrence (n = 11) were treated with local excision (n = 3), endocavitary radiotherapy (n = 1), TME (n = 5) and APR (n = 2). With a median follow-up of 32 months, the rectal preservation rate was 88%, with a 3-year disease-free survival of 67% and an overall survival of 98%. CONCLUSION: This study validates the feasibility of the practical implementation of a Response Surveillance Program to increase organ preservation rates without compromising oncological outcomes in rectal cancer.
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Preservação de Órgãos , Neoplasias Retais , Humanos , Resultado do Tratamento , Estudos de Viabilidade , Quimiorradioterapia/métodos , Recidiva Local de Neoplasia , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Conduta Expectante/métodosRESUMO
OBJECTIVE: To assess the oncological benefit of adjuvant chemotherapy (AC) in node positive (ypN+) rectal cancer after neoadjuvant chemoradiotherapy and radical surgery. BACKGROUND: The evidence for AC after total mesorectal excision for locally advanced rectal cancer is conflicting and the net survival benefit is debated. METHODS: An international multicenter comparative cohort study was performed comparing oncological outcomes in tertiary rectal cancer centers from the Netherlands and France. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision surgery and with positive lymph nodes on histologic examination (ypN+) were included for analysis. Kaplan-Meier curves were generated to compare disease-free (DFS) and overall survival in AC and non-AC groups. RESULTS: Of 1265 patients screened, a total of 239 rectal cancer patients with ypN+ disease were included. Demographic and clinical characteristics were similar in both groups. Higher systemic recurrence rates were observed in the non-AC group compared with those who received AC [32.0% (n=40) vs 17.5% (n=11), respectively, P =0.034]. DFS at 1 and 5 years postoperatively were significantly better in the AC group (92% vs 80% at 1 year; 72% vs 51% at 5 years, P =0.024), whereas no difference in overall survival was observed. CONCLUSIONS: In this multicenter comparative cohort study, we identified an oncological benefit of AC in both systemic recurrence and DFS in ypN+ rectal cancer patients. From this data, systemic chemotherapy continues to confer oncological benefit in locally advanced ypN+ rectal cancer.