PREOPERATIVE ASSESSMENT OF RECTAL CANCER: AN ACCURATE MRI PROTOCOL A RADIOLOGICAL TEMPLATE

The aims of our poster are: -to review the MRI technique and protocol in preoperative local staging of rectal cancer (RC); -to identify radiological signs that are useful for both the clinician and the surgeon; -to provide some “tips & tricks” in the radiological evaluation of MR images in RC staging

Magnetic resonance imaging (MRI) in rectal cancer: a comprehensive review

Magnetic resonance imaging (MRI) has established itself as the primary method for local staging in patients with rectal cancer. This is due to several factors, most importantly because of the ability to assess the status of circumferential resection margin. There are several newer developments being introduced continuously, such as diffusion-weighted imaging and imaging with 3 T. Assessment of loco-regional lymph nodes has also been investigated extensively using different approaches, but more work needs to be done. Finally, evaluation of tumours during or after preoperative treatment is becoming an everyday reality. All these new aspects prompt a review of the most recent advances and opinions. In this review, a comprehensive overview of the current status of MRI in the loco-regional assessment and management of rectal cancer is presented. The findings on MRI and their accuracy are reviewed based on the most up-to-date evidence. Optimisation of MRI acquisition and relevant regional anatomy are also presented, based on published literature and our own experience

Role of diffusion Weighted Imaging (DWI) in determining response to neoadjuvant chemoradiation in locally advanced carcinoma rectum

OBJECTIVES: To assess the role of DWI in predicting response to neoadjuvant chemoradiotherapy in patients with locally advanced carcinoma rectum (LARC) compared with T2W imaging. Secondarily, to evaluate the accuracy of tumour regression grade (TRG) assessed using MRI (T2W and DWI) in comparison with histopathological TRG. METHODS: A prospective analysis of 70 patients with LARC, who underwent neoadjuvant CRT and subsequent surgery was done. All patients underwent pre- and post-CRT T2W MR and DWI. The tumour volumes on T2W and DW images, difference in tumour volumes, pre and post-CRT ADC, difference in tumour ADC were measured. The TRG on T2W MRI and DWI were independently assessed. Histopathologic tumour regression grade was the standard of reference. The diagnostic accuracy of the tests in predicting complete response was compared using ROC analysis. The agreement between the MR tumour regression grades and histopathology was assessed using kappa statistic. RESULTS: The range of volumetric and ADC values in each TRG category were derived. The groups were subdivided into complete response (CR, n=13) and non-CR groups. Tumour volume reduction rate (TVRR) calculated on DWI and T2W MR were both useful in assessing complete response, with the accuracy of DWI being superior (AUC 0.92 for DWI vs 0.72 for T2W). The tumour ADC increase rate (TAIR) and absolute increase (ΔADC) though statistically significant as a predictor of response was inferior to tumour volumetry on DWI (AUC 0.7). Using a cut-off value for the tumour volume reduction rate of more than 94% on DWI, the sensitivity and specificity for predicting CR was 83.3% with NPV of 95.7%. There was fair agreement between the TRG based on MRI (76.4%, kappa 0.25, p <0.01) /DWI (74.6%, kappa 0.24, p <0.01) and histopathological TRG Pre- and post-CRT volumetry, ADC values when viewed independently were not reliable. CONCLUSION: The parameters found to be of significance in assessing response to neoadjuvant CRT are tumour volume reduction rate - TVRR on DWI and T2W, tumour ADC increase rate – TAIR and ΔADC. Among these, volumetry based on DWI was superior with high diagnostic accuracy in predicting complete response. TVRR based on T2W and changes in ADC values had similar diagnostic accuracies. Tumour regression grade assessed using T2W MRI and DWI are also useful as prognostic markers for disease recurrence and overall survival

3D pelvimetry and biometric measurements: a surgical perspective for colorectal resections

Purpose: Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution. Methods: A 3D software was used for segmentation of DICOM data of consecutive patients aged 60&nbsp;years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx\u2019s tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses. Results: Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p &lt; 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape. Conclusion: Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum

Assessment of the Prognostic Factors for a Local Recurrence of Rectal Cancer: the Utility of Preoperative MR Imaging

OBJECTIVE: To determine the utility of MR imaging in evaluating the prognostic factors for a local recurrence of rectal cancer following a curative resection. MATERIALS AND METHODS: The preoperative MR images obtained from 17 patients with a local recurrence and 54 patients without a local recurrence, who had undergone a curative resection, were independently evaluated by three radiologists. The following findings were analyzed: the direct invasion of the perirectal fat by the primary rectal carcinoma, involvement of the perirectal lymph nodes, perirectal spiculate nodules, perivascular encasement, and an enlargement of the pelvic wall lymph nodes. The clinical and surgical profiles were obtained from the patients' medical records. The association of a local recurrence with the MR findings and the clinicosurgical variables was statistically evaluated. RESULTS: Of the MR findings, the presence of perivascular encasement (p = 0.001) and perirectal spiculate nodules (p = 0.001) were found to be significant prognostic factors for a local recurrence. Of the clinicosurgical profiles, the presence of a microscopic vascular invasion (p = 0.005) and the involvement of the regional lymph nodes (p = 0.006) were associated with a local recurrence. Logistic regression analysis showed that the presence of perirectal spiculate nodules was an independent predictor of a local recurrence (odds ratio, 7.382; 95% confidence interval, 1.438, 37.889; p = 0.017). CONCLUSION: The presence of perirectal spiculate nodules and perivascular encasement on the preoperative MR images are significant predictors of a local recurrence after curative surgery for a rectal carcinoma. This suggests that preoperative MR imaging can provide useful information to help in the planning of preoperative adjuvant therapy.ope

Factors predicting recurrence in rectal cancer

Background: Rectal cancer treatment has improved through important incremental surgical and oncological developments over the past decades. Localized disease is highly treatable with multimodal surgical and oncological therapy. Prognosis is dependent on several factors with tumour stage at diagnosis being the most important. Furthermore, curative treatment is highly dependent on radical surgical resection. Positive circumferential resection margin (CRM), lateral lymph node metastases and tumour deposits are examples of high-risk clinical situations associated with increased risk of recurrence and subsequently impaired long-term outcome and are investigated in this thesis.Aims: Paper I & II, to investigate CRM-positive resections in rectal cancer and effect on local recurrence and distant metastasis risk. Paper III, to describe MRI-positive lateral lymph nodes – investigating therapy and outcome in high-risk rectal cancer. Paper IV, to investigate the prognostic significance of tumour deposits as a risk factor and in comparison with lymph node involvement in rectal cancer.Method: Paper I-II & IV are retrospective national cohort studies. Paper III is a retrospective regional cohort study. Patient data was gathered from the Swedish ColoRectal Cancer Registry, medical records and the Swedish Cause of Death registry. Patients for paper I & II were between 2005 – 2013, for paper III between 2009 – 2014 and för paper IV between 2011 – 2014.Main outcome measures: Paper I, local recurrence. Paper II, distant metastasis. Paper III, descriptive tumour characteristics, overall survival, local recurrence and distant metastasis. Paper IV, local recurrence, distant metastasis, overall and relative survival.Results and conclusions: Exact CRM was associated with increased local recurrence risk. Neoadjuvant radiotherapy does not decrease risk of local recurrence in CRM-positive patients. Only a subset of patients with R1-resection (CRM 0.0 mm) suffered local recurrence during follow-up. Exact CRM equal to or less than 1.0 mm may be a risk factor for distant metastasis. However, several other factors likely contribute to increased risk of distant metastasis in CRM-positive patients. MRI-positive lateral lymph nodes were associated with synchrounous distant metastasis. Neoadjuvant (chemo)radiotherapy, abdominal rectal resection and selective lymph node dissection may be a useful approach in patients with MRI-positive lateral lymph nodes. Tumour deposits increased risk of both local recurrence and distant metastasis and decreased survival. The prognosis of patients with tumour deposits were comparable to pN1a-b stage mesorectal lymph node involvement

The Utility of Magnetic Resonance Imaging in the Multidisciplinary Treatment of Patients with Rectal Cancer

Rectal cancer is one of the most common types of cancer in both men and women. In recent years, the importance of magnetic resonance imaging (MRI) has greatly increased in the multidisciplinary treatment of patients with rectal cancer. MRI has a particularly important role in the most accurate preoperative staging of these patients, both in terms of assessing the local invasion of the tumor and in terms of assessing the status of pelvic lymph nodes. Many patients with rectal cancer, especially those in the advanced stage of the disease, in the preoperative period undergo neoadjuvant radio chemotherapy. The evaluation of the clinical response of these patients to neoadjuvant therapy is of crucial importance both in terms of personalized treatment and in terms of their prognosis. In this regard, MRI has its clearly defined role at present in evaluating the efficacy of neoadjuvant therapy, as well as in postoperative follow-up

직장암 병기 설정에서 직장 전용 고해상도 전산화단층촬영기법의 진단능 평가: 직장 자기공명영상 결과와의 비교

학위논문(석사) -- 서울대학교대학원 : 의과대학 의학과, 2022.2. 김세형.Objectives: To compare the diagnostic performance of high-resolution CT in preoperative rectal cancer staging to conventional CT, with high-resolution MRI results as gold standard. Methods: Fifty-one patients who underwent both CT and MRI with rectum distension for preoperative rectal cancer staging were enrolled. High-resolution CT images were obtained with a quadrupled matrix size and oblique multiplanar reconstruction. Two radiologists compared the diagnostic performance of T staging, extramural depth of invasion (EMD), ≤T2/≥T3, extramural venous invasion (EMVI), mesorectal LN metastasis between conventional and high-resolution CT, considering MRI results as gold standard. Results were compared using the Chi-square test, Fisher’s exact test, linear weighted kappa, ROC analysis, and Pearson’s correlation coefficients. Results: Compared to conventional CT, high-resolution rectal CT showed higher accuracy in T staging (reviewer 1, 82.4% vs. 76.5% [P=0.463]; reviewer 2, 82.4% vs. 62.7% [P=0.027]) and better correlation to MRI results (weighted kappa; reviewer 1, 0.89 vs. 0.83; reviewer 2, 0.82 vs. 0.64 [Ps<0.001]). In categorizing ≤T2/≥T3, high-resolution CT showed better correlation with MRI than conventional CT (weighted kappa; reviewer 1, 0.87 vs. 0.78; reviewer 2, 0.74 vs. 0.57). Reviewer 2 yielded better correlation to MRI in high-resolution CT than conventional CT in EMD (Pearson’s coefficient; 0.97 vs 0.91) and EMVI (weighted kappa; 0.78 vs 0.47), while the difference was minimal in reviewer 1. Accuracy of mesorectal LN metastasis did not significantly differ between both CT modalities. Conclusion: High-resolution rectal CT showed better performance in the T staging of rectal cancers than conventional CT, considering high-resolution MRI as gold standard.목적: 직장암의 수술 전 병기 설정에서 고식적 CT와 비교하여 고해상도 CT (high-resolution CT)가 보다 나은 진단능을 보이는지, 고해상도 MRI 결과를 기준으로 하여 비교하고자 한다. 대상과 방법: 대상 환자는 51명으로, 수술 전 직장암의 병기 설정을 목적으로 CT와 MRI를 모두 촬영하였으며 검사 전 초음파 젤을 이용하여 직장을 팽창시킨 상태로 촬영하였다. 고해상도 CT 영상은 고식적 CT와 비교하여 4배 크기의 매트릭스와 사위 삼차원 다평면재구성 (oblique multiplanar reconstruction) 방법을 적용하여 재구성하였다. 두 명의 영상의학과 전문의가 각 환자의 고해상도 CT 및 고식적 CT 영상에서 T 병기, 직장외 침윤깊이 (EMD), ≤T2/≥T3 여부, 직장외 정맥침범 (EMVI), 직장간막 림프절 침범 여부를 분석하여 MRI 분석 결과를 기준으로 하여 서로 비교하였다. 통계분석으로 카이제곱 검정, 피셔의 정확검정, 선형 가중카파 분석, 수신자조작특성곡선 분석, 피어슨의 상관계수 검정을 사용하였다. 결과: 직장암의 T 병기 설정에서 고식적 CT와 비교하여 고해상도 CT에서 보다 높은 정확도를 보였으며 (판독자 1, 82.4% 대 76.5% [P=0.463]; 판독자 2, 82.4% 대 62.7% [P=0.027]), 가중카파 분석에서도 MRI와 보다 일치하는 결과를 보였다 (판독자 1, 0.89 대 0.83; 판독자 2, 0.82 대 0.64 [각각 P<0.001]). ≤T2/≥T3 여부를 구분하는 데 있어 고해상도 CT가 고식적 CT에 비해서 MRI와 보다 일치하는 결과를 보였다 (가중카파 계수: 판독자 1, 0.87 대 0.78; 판독자 2, 0.74 대 0.57). 판독자 2에서는 고해상도 CT가 고식적 CT보다 직장외 침윤깊이 (EMD) (피어슨 상관계수 0.97 대 0.91) 및 직장외 정맥침범 (EMVI) (가중카파 0.78 대 0.47) 평가에서 MRI와 보다 유사한 결과를 보였으나, 판독자 1에서 이러한 차이는 거의 없었다. 직장간막 림프절 침범은 두 CT 사이에서 정확도에 차이가 없었다. 결론: 고해상도 MRI 결과를 기준으로 비교하였을 때 고해상도 CT는 고식적 CT에 비하여 직장암의 T 병기 설정에서 우수한 결과를 보였다.Chapter 1. Introduction 1 1.1. Study Background 1 1.2. Purpose of Research 2 Chapter 2. Materials and Methods 3 2.1. Patient Selection 3 2.2. CT Techniques 3 2.3. MRI Techniques 4 2.4. Image Analysis 5 2.5. Pathologic Analysis 5 2.6. Statistical Analysis 6 Chapter 3. Results 7 3.1. Patients 7 3.2. Results for all 51 patients with MRI as the gold standard 7 3.3. Results for 24 patients with pathology as gold standard 9 Chapter 4. Discussion 11 Tables (1-5) 15 Figures and Legends(1-4) 19 Bibliography 26 Supplementary Material 29 Abstract in Korean 30석

Application of intraoperative quality assurance to laparoscopic total mesorectal excision surgery

Introduction: The role of laparoscopy in the surgical management of rectal cancer is debated. Randomised trials have reported contrasting results with inadequate specimens obtained in a minority of patients. The reasons behind these findings are unclear. Complex surgical interventions and human performance are prone to variation, which may account for outcome differences, but neither are robustly measured. Application of quality assurance (QA) to the intraoperative period could explore surgical performance and any relationship with subsequent outcomes. The overarching aim of this thesis is the promotion of oncological and patient safety through application of QA to laparoscopic TME surgery. Methods: Evidence synthesis of QA tools was obtained through a systematic review to identify reported objective laparoscopic total mesorectal excision (TME) assessment tools. Development of novel QA tools for laparoscopic TME was performed and applied and validated using case video from two multicentre randomised trials with reliability and validity of the laparoscopic TME performance tool (L-TMEpt) assessed. A multicentre randomised trial comparing 3D vs. 2D laparoscopic TME was performed incorporating objective performance analyses. Scores divided surgeons into quartiles and compared with histopathological and clinical endpoints. A novel intraoperative adverse event classification was developed and piloted. Results: 176 cases from 48 credentialed surgeons were analysed. L-TMEpt inter-rater, test-retest and internal consistency reliabilities were established. Substantial variation in surgical performance were seen. Scores were strongly associated with the number of intraoperative errors, plane of mesorectal dissection and short-term patient morbidity. Upper quartile surgeons obtained excellent results compared with the lower quartile (mesorectal fascia 93% vs. 59%, NNT 2.9, p=0.002; 30-day morbidity 23% vs. 48%, NNT 4, p=0.043). Conclusions: Intraoperative QA using assessment tools can objectively and reliably measure complex cancer interventions. Laparoscopic TME surgical performance assessment showed substantial variation which is strongly associated with clinical outcomes holding implications for surgical trial design and interpretation.Open Acces

Biological and surgical determinants in the treatment of rectal cancer

RESUMO: O cancro do recto é uma doença muito complexa que tem vindo a aumentar nas idades mais jovens com um enorme impacto na qualidade de vida. Esta é uma patologia extremamente heterogénea no que concerne ao seu comportamento, dependente de vários factores que determinam não só o seu curso mas a resposta à terapêutica. Nas últimas décadas progressos significativos têm sido feitos na abordagem do cancro do recto devido a um melhor conhecimento da fisiopatologia da doença, conduzindo ao aparecimento de novas opções de tratamento. De forma síncrona com uma evolução técnica, o conceito terapêutico também se alterou, mudando de uma perspectiva exclusivamente focada nos outcomes oncológicos para um modelo com preocupações relacionadas com os resultados funcionais e a qualidade de vida. O ênfase passou também a residir na minimização dos efeitos deletérios do tratamento. Esta é a interrogação na base deste trabalho: é possível encontrar determinantes biológicos e cirúrgicos do tratamento do cancro do recto por forma a diminuir a morbilidade associada à terapêutica mas obtendo igualmente os resultados pretendidos? Existem vários factores biológicos que influenciam os resultados terapêuticos do cancro do recto mas verifica-se, igualmente, um inquestionável impacto da opção cirúrgica selecionada. Sendo a nossa meta a obtenção dos melhores resultados com a menor morbilidade, é necessário procurar estes determinantes biológicos e cirúrgicos do tratamento óptimo. O objectivo deste projeto é analisar possíveis determinantes da terapêutica do cancro do recto. São colocadas as seguintes questões: 1) poderemos optimizar a seleção dos doentes para quimioradioterapia neoadjuvante através da identificação de marcadores moleculares de resposta?, 2) poderemos melhor selecionar a técnica cirúrgica nomeadamente com a excisão total do mesorecto via transanal ou a excisão local em casos específicos? e 3) será possível uma melhor escolha dos doentes para ileostomia derivativa através da identificação de factores preditivos de morbilidade associada a este estoma? A terapêutica neoadjuvante é atualmente administrada aos doentes com adenocarcinoma localmente avançado do recto, maioritariamente com boa resposta tumoral. Contudo, cerca de um terço dos doentes submetidos a quimioradioterapia não beneficiam deste tratamento, têm risco acrescido de progressão de doença durante o mesmo bem como de toxicidade desnecessária. Até hoje, não foram ainda validados quaisquer marcadores preditivos de resposta à quimioradioterapia que possam ajudar na seleção dos doentes para esta terapêutica. Tendo em conta o seu papel na oncogénese do cancro do recto bem como o seu envolvimento na resposta ao tratamento médico, colocámos a hipótese de os microRNAs em particular microRNA-16, microRNA-21, microRNA-135b, microRNA-145 e o microRNA-335 poderem ser biomarcadores de resposta à quimioradioterapia, predizendo os bons e os maus respondedores. Foi encontrada uma associação estatisticamente significativa entre a sobre-expressão de microRNA-21 no tecido tumoral pré- quimioradioterapia e pior resposta à mesma. Os nossos resultados sugerem a possibilidade do microRNAs-21 ser um biomarcador de resposta patológica à quimioradioterapia no cancro do recto. A confirmação desta associação poderá ter uma translação para a prática clínica corrente, com a inclusão do miRNA nos algoritmos de decisão terapêutica, possibilitando uma melhor seleção dos candidatos a quimioradioterapia. Durante os últimos 30 anos, grandes progressos cirúrgicos foram introduzidos no cancro do recto com vista à melhoria dos outcomes e diminuição da morbilidade associada ao tratamento. O mais recente avanço neste âmbito é a excisão total do mesorecto via transanal introduzida em 2010, com resultados a curto prazo muito positivos. Contudo, os outcomes a longo prazo são ainda controversos. Analisámos os outcomes oncológicos dos primeiros 50 doentes submetidos a esta técnica na nossa instituição e procedemos à sua comparação com os obtidos por um grupo equiparado de doentes submetidos a excisão total do mesorecto laparoscópica. Mesmo refletindo a curva de aprendizagem da nova técnica, foram encontrados valores semelhantes entre os grupos no que concerne a sobrevivência global, sobrevivência livre de doença e recidiva local a curto e longo prazo. Estes resultados apontam para que a excisão total do mesorecto via transanal possa produzir outcomes oncológicos seguros, compatíveis com o que tem sido publicado para a abordagem laparoscópica. Contudo, este estudo também enfatiza a sua exigente curva de aprendizagem e o risco significativo de morbilidade que lhe está associado. Na realidade, qualquer que seja a opção cirúrgica utilizada no tratamento do cancro do recto distal, é necessária elevada proficiência, sendo que resultados óptimos só se atingem com treino adequado e auditoria contínua como garante da sua melhoria à medida que a experiência aumenta. Entendendo a excisão total do mesorecto como um dos grandes avanços no tratamento do cancro do recto, não podemos deixar de reconhecer o seu impacto negativo na qualidade de vida dos doentes com tumores distais. Neste contexto começaram a ser ponderadas estratégias terapêuticas menos agressivas com vista a uma menor morbilidade, nomeadamente quimioradioterapia seguida de excisão local. Através de uma revisão sistemática com metanálise que comparou, em contexto de neoadjuvância, os outcomes da excisão local com os da cirurgia radical, encontrámos valores de recidiva local, sobrevivência global e livre de doença semelhantes entre os grupos. Estes resultados podem ser explicados pelo facto de o mais importante determinante oncológico não ser o estadiamento inicial mas sim o pós quimioradioterapia, refletindo o comportamento biológico do tumor. No entanto, alguns estudos incluídos nesta metanálise apenas mostraram o estadiamento inicial. Na realidade, após a quimioradioterapia, a excisão local parece ser uma alternativa nos doentes com tumor restrito à submucosa e sem adenopatias objectiváveis (ycT1N0), nos doentes com co-morbilidades ou que recusam cirurgia radical. Na cirurgia de excisão total do mesorecto é frequentemente realizada ileostomia derivativa por forma a reduzir as consequências do leak anastomótico. Contudo, a maioria dos doentes não enfrenta esta complicação sendo desnecessariamente exposta à potencial morbilidade do estoma. De facto, o efeito protetor do estoma derivativo deve ser contrabalançado com a sua morbilidade, bastante relevante. Tendo investigado marcadores de complicações associadas à ileostomia, identificámos a Diabetes Mellitus e a morbilidade da cirurgia rectal índex como factores preditivos não só de maior morbilidade associada ao estoma e ao seu encerramento bem como de menor encerramento. Assim, quando ponderamos a realização de uma ileostomia derivativa na cirurgia do recto, há que ter em conta a influência destes fatores preditivos de morbilidade. É essencial individualizar as decisões terapêuticas e adoptar uma abordagem mais seletiva no uso do estoma derivativo, especialmente nos doentes em que o risco do mesmo pode superar as potenciais vantagens. Em suma, existem vários factores que influenciam a conduta terapêutica na abordagem do cancro do recto. Existem determinantes biológicos e cirúrgicos do tratamento desta doença que necessitam de ser estudados, com vista ao atingir dos melhores resultados com a menor morbilidade. O papel dos microRNAs na oncogénese é inquestionável como o é a influência de microRNAs específicos, nomeadamente o microRNA-21, na resposta à quimioradioterapia neoadjuvante. Igualmente, também é crítica a opção cirúrgica nos diferentes contextos clínicos. De facto, podemos individualizar as intervenções cirúrgicas através do uso seletivo da excisão total do mesorecto via transanal nos tumores distais ou da excisão local pós quimioradioterapia nos doentes de alto risco com boa resposta, confinada à submucosa. Igualmente, antes da realização de cirurgia de excisão radical, é imperativo optimizar o status geral do doente e controlar factores de risco modificáveis como a Diabetes Mellitus por forma a diminuir igualmente a morbilidade associada ao estoma de proteção.ABSTRACT:Rectal cancer (RC) is a very complex disease that has been increasing in younger patients, imposing a great impact in quality of life. It is an extremely heterogeneous pathology in what regards to behaviour, which is dependent of many factors that determine its course and response to treatment. In the past decades, significant progress has been made in the management of RC due to a better knowledge of disease pathophysiology and consequent development of new therapeutic options. Synchronously with the technical evolution, the concept of oncological treatment also changed, from a perspective exclusively focused on survival outcomes to a model involving concerns with functional results and quality of life. Emphasis changed to minimizing the deleterious effects of treatment. However, many rectal cancer patients are still submitted to medical therapies and surgical options without any benefit and that even add unjustified morbidity. This is the core question of this work: can we find biological and surgical determinants of RC treatment in order to decrease its related morbidity while achieving the intended outcomes? There are biological factors that influence clinical results and there is an undeniable impact of the surgical options we select. As our goal is obtaining the best possible outcomes minimizing morbidity, we must search for the biological and surgical determinants guidelining the optimal treatment. The aim of this project is to provide new insights to possible determinants of RC treatment. We ask the following questions: 1) can we better select patients for chemoradiotherapy through the identification of molecular predictors of response?, 2) can we individualize the surgical technique for each RC patient, using transanal total mesorectal excision or local excision in selected cases? and 3) can we improve assortment of patients for a derivative ileostomy identifying factors predictive of related morbidity? Neoadjuvant therapy is currently given to the majority of locally advanced rectal cancer with a majority of good tumour response. However, one third of patients that undergo chemoradiotherapy do not profit from this option, are at increased risk of disease progression and even unnecessary toxicity. So far, there are no validated predictors of response to chemoradiotherapy to aid in deciding whether the patient should or not undergo this therapy, avoiding related morbidity. Considering their role in rectal cancer oncogenesis and involvement in the response to medical therapies, we hypothesized that microRNAs (miRNAs or miRs), in particular microRNA-16, microRNA-21, microRNA-135b, microRNA-145 and microRNA-335 are biomarkers of response to neoadjuvant CRT, predicting good and bad responders. We found a statistically significant association of microRNA-21 overexpression in pre- chemoradiotherapy rectal cancer tissue and worse response. Our results suggest that microRNA-21 may, indeed, be a biomarker of pathological response in rectal cancer. Confirmation as such could translate into clinical application through the inclusion of the levels of microRNA-21 in algorithms of treatment decision, certainly allowing a better selection of candidates for chemoradiotherapy During the last 30 years, great surgical progress was introduced in RC treatment aiming to improve outcomes and diminishing the morbidity associated with treatment. The most recent of theses attempts is transanal total mesorectal excision, developed in 2010, which yielded very positive short-term results. However, long-term outcomes are still controversial and not clarified. We analysed the oncological outcomes of the learning curve of this technique at our institution and compared them to a matched cohort of patients submitted to the standard of care laparoscopic total mesorectal excision. Similar long-term results regarding local recurrence, overall survival and disease-free survival were found. These results point out to the fact that transanal total mesorectal excision can produce short and long-term oncological safe results, compatible to what has been published for the laparoscopic approach. However, this work also emphasized the demanding learning curve and significant risk for morbidity associated with this novel technique. The fact is that, whatever option is used to performed distal RC surgery, it requires advanced surgical skills and optimal results can only be achieved with adequate training and continuous evaluation of outcomes to ensure they improve as experience grows. Transanal total mesorectal excision does not intent to replace other established approaches to rectal surgery but to add new alternatives to address difficult cases. As we understand TME as one of the greatest revolutions of rectal cancer treatment we also acknowledge its negative impact on the quality of life of patients with distal tumours. In this setting, less aggressive therapeutic strategies started to be discussed in order to decrease therapeutic morbidity, namely neoadjuvant chemoradiotherapy combined with local excision. Through a systematic review and meta analysis that compared the outcomes of local excision and radical surgery in the post neoadjuvant setting, we found similar outcomes between groups in relation to local recurrence, overall survival and disease-free survival. These results are explained by the fact that the most relevant determinant of local recurrence and survival is not the baseline staging but the post chemoradiotherapy one, that reflects tumour biologic behaviour. However, some studies included in this metanalysis were based on initial staging. In sum, after CRT, patients with an incomplete response contained in the mucosa or submucosa with negative nodes (ycT1N0) may be an indication for LE. This strategy can also be considered in trial setting or as an option for patients refusing abdominoperineal resection or with significant comorbidity. Still in rectal cancer surgery, defunctioning ileostomy is frequently constructed to reduce the poor consequences of a leak. However, the majority of patients does not face anastomotic breakdown and is unnecessarily exposed to stoma potential complications. In fact, stoma protective effect needs to be balanced against its morbidity, which is actually quite high. We identified Diabetes Mellitus and complications of the index rectal surgery as predictive of higher ileostomy morbidity and of closure-related problems as well as lower ileostomy reversal. So, when deciding over diverting a colorectal or coloanal anastomosis, the influence of these predictive factors must be taken into account. It is essential to individualize treatment decisions and adopt a more selective approach concerning the use of a defunctioning ileostomy, especially for patients in which the risks of having a stoma may offset potential advantages. In summary, there are many factors influencing the proper therapeutic conduct to follow in the approach of rectal cancer. There are biological and surgical determinants of the treatment of this disease that need to be analysed, in order to achieve the best results with the lowest morbidity. The role of the microRNA in oncogenic pathways is undeniable as is the influence of specific microRNA, namely miR-21, in the response to chemoradiotherapy. Likewise, the choice of particular surgical interventions in different clinical settings can be critical to obtain the appropriate outcomes. We can individualize surgical options through the selective use of transanal total mesorectal excision in distal tumours or local excision in high risk patients with very good response, confined to the submucosa, in post neoadjuvant treatment. Likewise, prior to performing radical surgery, it is imperative to optimize patients and control modifiable risk factors as diabetes mellitus in order to decrease stoma-related morbidity