A Robotic System for Transanal Endoscopic Microsurgery: Design, Dexterity Optimization, and Prototyping

This article proposes a master–slave operated robotic system that features the novel slave manipulator with a modular distal continuum section to address the shortcomings of traditional transanal endoscopic microsurgery (TEM). The slave manipulator consists of two seven degrees-of-freedom (7-DoF) surgical instruments and a 5-DoF endoscopic arm that are designed with distal continuum structures and unfolded with a Y configuration after inserting through a transanal port to enhance hand–eye coordination and instrument triangulation. The proposed robot is designed for adaptation in narrow and shallow rectal spaces, facilitating intuitive hand–eye coordination and enhanced operational dexterity with reduced obstruction of the field of view

Educational models for training in minimally invasive colorectal surgery

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth most deadly cancer in the world for which surgery is the main treatment. Colorectal surgery can be performed through a wide incision in the abdomen or using minimally invasive surgical (MIS) techniques. Some of these techniques include transanal endoscopic microsurgery (TEM ), transanal minimally invasive surgery (TAMIS), transanal total mesorectal excision (TaTME ), and robot-assisted surgery. Studies increasingly confirm that resections using MIS techniques are safe, oncologically equivalent to open surgery and have better short-term results. These surgical approaches are, however, technically demanding and result in a steep learning curve. The main objective of this study is to review the different MIS techniques for colorectal surgery, as well as the training tools and programs designed to achieve the necessary surgical skills. Different training programs in colorectal surgery have been reported for the different surgical techniques analyzed. Most of these programs are based on training tools in the form of surgical simulators, physical and virtual, as well as the use of experimental and cadaveric models. However, structured training programs in minimally invasive colorectal surgery remain scarce, and there should be a consensus on the fundamental training aspects for the various surgical techniques presented. These training programs should ensure that surgeons acquire sufficient surgical skills to be competent in the development of these surgical techniques, improving the quality of the patient’s surgical outcomes.Rak jelita grubego (RJG) jest trzecim co do częstotliwości rozpoznawania nowotworem złośliwym na świecie, a także czwartą przyczyną zgonów na nowotwory złośliwe. Głównym elementem leczenia RJG jest operacja, którą można wykonać przez rozległe nacięcie powłok lub za pomocą technik minimalnie inwazyjnych. Do tych drugich należą: endoskopowa chirurgia transanalna (TEM ), przezodbytowa chirurgia minimalnie inwazyjna (TAMIS), przezodbytowe całkowite wycięcie mezorektum (TaTME ) oraz chirurgia wspomagana robotowo. Analizy danych potwierdzają, że techniki minimalnie inwazyjne są bezpieczne, równie skuteczne onkologicznie co techniki tradycyjne, a także wiążą się z szybszym powrotem chorych do pełnej sprawności. Ich wspólną cechą są niestety wysokie wymagania techniczne oraz długa krzywa uczenia. W artykule omówione zostały różne techniki minimalnie inwazyjne stosowane w leczeniu RJG oraz metody nauczania tych technik. Jak dotąd opracowano wiele sposobów szkolenia dla różnych technik operacyjnych. Większość opiera się na symulatorach chirurgicznych zarówno rzeczywistych, jak i wirtualnych oraz na wykorzystaniu modeli eksperymentalnych i preparatów z ludzkich zwłok. Niestety usystematyzowane modele szkolenia w minimalnie inwazyjnej chirurgii RJG są nadal rzadkością. Widać wyraźnie potrzebę opracowania konsensusu dotyczącego szkolenia w poszczególnych metodach operacyjnych. Tego rodzaju programy powinny zapewnić uczestniczącym w nich chirurgom zdobycie wiedzy pozwalającej na skuteczne wykonywanie zabiegów w celu zapewnienia pacjentom jak najlepszych efektów leczenia

Robotic manipulators for single access surgery

This thesis explores the development of cooperative robotic manipulators for enhancing surgical precision and patient outcomes in single-access surgery and, specifically, Transanal Endoscopic Microsurgery (TEM). During these procedures, surgeons manipulate a heavy set of instruments via a mechanical clamp inserted in the patient’s body through a surgical port, resulting in imprecise movements, increased patient risks, and increased operating time. Therefore, an articulated robotic manipulator with passive joints is initially introduced, featuring built-in position and force sensors in each joint and electronic joint brakes for instant lock/release capability. The articulated manipulator concept is further improved with motorised joints, evolving into an active tool holder. The joints allow the incorporation of advanced robotic capabilities such as ultra-lightweight gravity compensation and hands-on kinematic reconfiguration, which can optimise the placement of the tool holder in the operating theatre. Due to the enhanced sensing capabilities, the application of the active robotic manipulator was further explored in conjunction with advanced image guidance approaches such as endomicroscopy. Recent advances in probe-based optical imaging such as confocal endomicroscopy is making inroads in clinical uses. However, the challenging manipulation of imaging probes hinders their practical adoption. Therefore, a combination of the fully cooperative robotic manipulator with a high-speed scanning endomicroscopy instrument is presented, simplifying the incorporation of optical biopsy techniques in routine surgical workflows. Finally, another embodiment of a cooperative robotic manipulator is presented as an input interface to control a highly-articulated robotic instrument for TEM. This master-slave interface alleviates the drawbacks of traditional master-slave devices, e.g., using clutching mechanics to compensate for the mismatch between slave and master workspaces, and the lack of intuitive manipulation feedback, e.g. joint limits, to the user. To address those drawbacks a joint-space robotic manipulator is proposed emulating the kinematic structure of the flexible robotic instrument under control.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