Cristián Gallardo interviews Calvin Coffey and Christina Fleming on the subject of mesenteric principles and mesenteric-based colorectal surgery, in the third episode of our Cutting Edge series.
J. Calvin Coffey (PhD FRCSI) is Head of Department of Surgery, University Hospitals Group Limerick, Foundation Chair of Surgery, School of Medicine, University of Limerick, Editor-in-Chief Mesentery and Peritoneum (MAP), and author of Mesenteric Principles of Gastrointestinal Surgery, 1st Edition.
Christina Fleming (FRCSI) is a Surgical Specialist Registrar at Royal College of Surgeons in Ireland, a member of the Association of Surgeons in Training Council (@ASiTofficial), and Chair of the Irish Surgical Research Collaborative (@ISRCtweets).
Cristián Gallardo: Firstly, let me say it is a pleasure to interview both of you about mesenteric principles and mesenteric-based colorectal surgery. Let me start the interview telling you that it is a privilege to have the opportunity to interview an author who has made important contributions to both surgery and the study of human anatomy.
One of the earliest depictions of the mesentery associated with the small bowel and colon was generated by Leonardo Da Vinci. The Da Vinci mesentery was continuous and it remained that way for centuries until 1885 when Treves' findings were presented. Since then and over the following centuries the depiction in most anatomical, embryological, surgical and radiological literature has been a fragmented mesentery, associated only with the small intestine and transverse and sigmoid colon.
To introduce this topic to our readers and according to your research, can you briefly tell us what do you think about these statements?
Calvin Coffey: Thank you for the invitation and I am delighted to be doing this interview with Christina.
Italian Renaissance anatomists and artists had a far better understanding of abdominal anatomy than that which we have had up to recently. For example, for a long time, it was erroneously stated that Da Vinci's depiction of the intestine was incorrect - that statement was wrong - it is remarkably accurate. If you look at Vesalius' depiction of the portal venous system, again, this was described as incorrect - now we know Vesalius was right. If you take the illustrations of Asseli, Eustachi, all the greats of classical anatomy (interestingly, all Italian) their depictions of abdominal anatomy was cast aside as inaccurate representations of human form. Now we know they were correct. It is time to go back to the Italian texts of the 1500s and take a serious look at all of them again.
CG: I've read with great interest your investigation on The Mesentery in The Lancet. According to the review in the journal 'The Lancet Gastroenterology and Hepatology', you mentioned the proposed reclassification of the mesentery as an organ. Would you like to explain this further?
CC: Thank you. The best way to consider the mesenteric organ is to think about the liver, spleen or intestine. These have a parenchyma, and if you peel back their capsule (or serosa), you see a parenchyma. The same applies to the mesentery. If you peel back the surface lining of the mesentery, you expose the underlying adipose parenchyma. Another term for this is the mesenteric mesoderm. As it develops and acquires the same shape in every single human, the mesenteric mesoderm builds up around blood vessels.
In the adult, some regions of the mesentery are covered on either surface by peritoneum. Others are only covered on one surface, by peritoneum. The same applies for the liver, spleen and intestine – they all have peritonealised and non-peritonealised surfaces. So, next time you are handling the mesentery intraoperatively, think in terms of the mesenteric mesoderm.
As it develops in the foetus or embryo, the mesenteric mesoderm disconnects from the posterior abdominal wall except at sites of vascular inflow. It then develops beneath the surface mesothelium, displacing this laterally, towards the periphery of the abdomen, and acquiring the shape it has in the adult. By the end of development, all its conjugate organs (abdominal digestive organs) are positioned in the position that we are all familiar with (liver in the right upper quadrant with the gallbladder beneath, spleen in the left upper quadrant and so on).
Throughout development and in the adult, abdominal digestive organs and mesentery comprise one distinct anatomical domain. All genitourinary organs are positioned on the musculoskeletal frame and comprise the second distinct anatomical domain of the abdomen. Vesalius, Asseli, Eustachi (possibly even Da Vinci), also knew this. In this model, the mesenteric model, the peritoneum is simply the surface lining of the mesenteric domain (i.e. visceral peritoneum), the surface lining of the non-mesenteric domain (the parietal peritoneum) and the junction between both (i.e. the reflection).
This is the mesenteric modal of abdominal anatomy, it provides us with the anatomical basis of all that we do as abdominal surgeons. As surgeons, we divide the peritoneal reflection. Doing that provides access to the plane formed between the mesenteric mesoderm (the mesenteric domain) and the posterior abdominal wall (the non-mesenteric domain). Separating both of these (mesofascial separation) disconnects the two domains.
This principle applies at all levels from the OG junction to the anorectal junction. I have yet to read a question on abdominal anatomy, that this model cannot answer or explain.
CG: What are the implications of reclassifying the mesentery as an organ?
CC: Doing so forces us to change our understanding of how the body is organised, and how it functions. If you think about all abdominal digestive organs directly connected to a single mesentery, and that this connects them back to the rest of the body, then of course this is a very important and perhaps even essential organ. The mesentery must coordinate the functions of the individual organs, as part of functions of the body in general.
Thinking about it as an organ also forces us to ask the questions as to whether there are diseases of it, and how these can be diagnosed and treated. When you approach it in that light, you begin to see very clearly, that there are primary diseases of the mesentery (mesenteropathies) and that these can now be better diagnosed and treated, because they are better understood. A good example is malrotation. This was previously considered an abnormality of the intestine and the standard technical approach to its correction was a Ladd’s procedure. We now know that malrotation is simply failure of the mid-region switch of the mesentery to occur, and that by recapitulating that switch, we can correct the underlying abnormality.
CG: Why do you think the mesentery has been misunderstood?
CC: I think the fundamental error was in our understanding of the anatomy of the mesentery. It is remarkable to think that Italian Renaissance anatomists and artists had it right – they recognised the shape of the mesentery. The erroneous idea that there are multiple separate mesenteries, and that parts of the digestive system lack mesentery, came to prominence because of a limited set of surgeons (Amussat/Gray/Treves) who exerted a considerable influence over anatomy and whose statements went accepted and unchallenged from the 1850s up to 2012.
CG: Taking into account the multiple functions the mesentery has during development, what are the direct contributions it has in the adult human setting?
CC: I would strongly recommend looking at our article published at the invitation of the Royal Society of Biology, for a summary of the direct contributions of the mesentery in the adult setting. The book Mesenteric Principles of Gastrointestinal Surgery also explains function in detail.
CG: Thanks to this research we have now a new understanding of the mesentery. Firstly, we know every digestive organ develops within the mesentery embryologically and secondly, we know that by dividing the peritoneum and fascia it allows surgeons to take out every organ en bloc as a single unit. How is this relevant to surgical oncology?
Christina Fleming: Thank you for this question. This is such an important point as mesenteric principles are a fundamental concept underpinning modern surgical oncology practice particularly relating to the gastrointestinal tract. We know that tumors usually arise and then spread in a domain specific manner. It is extremely rare for a colon cancer, for example, to metastasise to the kidney, or uterus, or bladder, because they are in different anatomical domains. This important principle is the basis behind the success of total mesorectal excision (TME) and complete mesocolic excision (CME) and the increased use of mesenteric based principles in the treatment of gastric, oesophageal and pancreatic cancers. Seminal work by Professor Heald and colleagues recognized the substantial role of mesorectal excision in containing local spread of rectal cancer and this has radically enhanced rectal cancer treatment. It is unlikely that there will be any further surgical advancement that will rival the impact of performing a mesentery-including resection for cancer on rectal cancer outcomes. Along similar concepts, Professor Hohenberger’s description of the three principles of a CME to include complete inclusion of the mesenteric package has resulted in more favourable cancer outcomes.
CG: How is it relevant to IBD surgery?
CC: It is highly likely the mesentery has a pathobiological role in Crohn’s disease. Therefore, we need to think about targeting it. Emerging evidence from our group and others indicates that if you target it by resecting it, you alter the natural history or progression of the disease. Some may say this is a big statement that is not supported by data. Yes, the data is at an early stage, but the finding that if you exclude the mesentery from an anastomosis, then you also alter the natural history of Crohn’s disease, also supports the statement. So, it appears we can target the mesentery from a therapeutic perspective. Of course, the ideal would be to generate non-surgical means of achieving the same goal. The current armamentarium of medical modalities does not appear to target the mesentery.
CG. Some suggest that a mesentery-including resection in Crohn's disease may be associated with increased morbidity, do you agree with this?
CF: That is correct there is a school of thought that including the mesentery may be associated with increased surgical morbidity however there is a paucity of published data to support this. We have recently drafted a manuscript reporting on 30-day morbidity with particular emphasis on bleeding related complications and perioperative transfusion requirement. Based on our institutional practice at University Hospital Limerick we have not identified any increased morbidity, in particular no increase in major vascular injuries, bleeding complications or perioperative blood transfusion requirements. As is described in Professor Coffey’s 2018 paper, mesentery-including resection is performed when the mesentery can be fully mobilised back to the level of the mesenteric root but the root region itself is not dissected through. This is an important technical point. If there is significant inflammation at the time of surgery precluding this then we perform a defunctioning loop ileostomy and return at a later interval when inflammation has improved to reassess for suitability of mesentery-including resection. In our experience, subsequent mesentery-including resection can be achieved in over 90% of patients. Perhaps diversion exerts a modification to the diversity of the microbiome that contributes to inflammatory improvement along with conventional therapies in this setting, we are keen to explore this further. Adopting this operative approach we conclude that mesentery-including surgery is safe in Crohn's disease in correctly selected patients.
CG: Could you give some examples of mesenteric-based surgery and how these have changed some practices in colon and rectal surgery?
CF: I think Professor Coffey has already outlined some excellent examples including his work in mesentery-including ileocolic resection for Crohn’s disease resulting in reduced surgical recurrence rates. Supporting the concept of the pathobiological role of the mesentery in inflammatory bowel disease is work on proctectomy for Crohn’s published by Buskens et al from the Academic Medical Centre in Amsterdam. In this work the authors identify an increase in perineal complications when a ‘close to rectum’ resection is performed compared to a total mesorectal excision and an augmented pro-inflammatory immune status of the associated mesorectal tissue identified. In colorectal cancer surgery, total mesorectal excision pioneered by Professor Heald offers a further example which has resulted in radical reduction in local recurrence rates in rectal cancer. In similar fashion CME has shown survival benefit in Professor Hohenberger’s series and from the Danish Colorectal Cancer Group.
CG: What impact do you think the new understanding of the mesentery and mesenteric anatomy may have on training in colorectal surgery?
CF: Thank you for this question. As a trainee nearing the end of training, I think this is really important to reflect on and think about. I think training in colorectal surgery is rapidly evolving and in the current era of advancing innovation it is important to reflect on and not neglect the fundamentals of anatomy and pathophysiology. Having a clear and in dept understanding of anatomy and disease process involved both in benign and malignant colorectal disorders, as has been highlighted, is key to providing high quality surgical care. I think standardising nomenclature that we use in colorectal surgery is important in training, particularly when moving through different surgical units to optimise the ability to progress and achieve competencies. Finally, I think the COVID-19 pandemic has forced a step change in the way we work, train and communicate in surgery and has advanced the digitalisation of surgical training. The digital and data driven future of surgical training will be fast paced and will highlight more than ever the importance of standardisation in terminology and core fundamentals and understanding of anatomical structure and disease process.
CG: Thank you so much for sharing your knowledge with us.
References
- Coffey JC, O'Leary DP. The mesentery: structure, function, and role in disease. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):238-247.
- Coffey CJ, Kiernan MG, Sahebally SM, Jarrar A, Burke JP, Kiely PA, Shen B, Waldron D, Peirce C, Moloney M, Skelly M, Tibbitts P, Hidayat H, Faul PN, Healy V, O'Leary PD, Walsh LG, Dockery P, O'Connell RP, Martin ST, Shanahan F, Fiocchi C, Dunne CP. Inclusion of the Mesentery in Ileocolic Resection for Crohn's Disease is Associated With Reduced Surgical Recurrence. J Crohns Colitis. 2018 Nov 9;12(10):1139-1150.
