Small intestine, large surgery

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My own experience

At my diagnostic consultation, the Oncologist told me I had Stage 4 metastatic Small Intestine NET (SI NET). He also told me that surgery would almost definitely be on the cards and would be referring me to an experienced surgeon in a different hospital for assessment. I was assured this surgeon was one of the most experienced in the south of England for NETs. This was before the current multi-disciplinary team was set up, but it did all seem so very organised and I felt comfortable, albeit apprehensive. Worth pointing out that surgery is not normally offered in cancer at Stage 4 but the slow-growing nature of most NETs allows for some leeway here.  Statistics indicate that around 50% of SI NET present as metastatic cases, I’d like to think that number will reduce over time.  Some of the surgery issues also apply to non-metastatic cases.

It took a further 6 weeks before I met the surgeon and during this time, my oncologist continued with diagnostic tests such as Chromogranin A and 5HIAA. I also had a nuclear scan (Somatostatin Receptor Scintigraphy (SRS)) and an Echocardiogram to check my heart for the known risks of serotonin secreting midgut tumours. As a result of the positive SRS (octreotide scan), I was prescribed daily octreotide shots to reduce the effects of my carcinoid syndrome in order to de-risk the surgery. My surgery took place 2 months later and in between that I had a liver embolization and some more scans and tests. I took to my surgeon straight away, he had an engaging manner, he talked with some certainty about what he had in mind, he talked to me in terms I could understand, he was a straight talker, something I always appreciate.  So, in terms of where I lived, I felt lucky to have a great surgeon and one very familiar with Neuroendocrine Cancer. Like many SI NET patients, it wasn’t to be just surgery on the small intestine – due to the margins plus the complications which can often present with a small intestine primary, there was much work to be done.  If you wanted more detail about what he did, click the ‘surgery’ link in the next paragraph.

I went on to have that surgery, I then had another (liver), and then another (lymphadenectomy). In 14 months, I had 3 surgeries, half a dozen minor procedures and countless scans and tests. I continued to work throughout, and my employer was very generous and understanding.

Although many people have “upfront small intestine resection” (defined as a resection within 6 months of diagnosis), this isn’t an automatic event for all. Listening to many stories, I can see my experience isn’t the norm. My surgeon explained that I was considered “young and fit” and would be able to withstand the surgery. I didn’t really have any comorbidities that would present additional risk, other than signs of carcinoid syndrome which might precipitate a hormonal crisis under anaesthesia. He already had that covered by using an expert anaesthetist experienced in dealing with Neuroendocrine Cancer patients.

My surgeon was well known for his radical approaches to getting rid of disease. SI NETs are known to be linked to mesenteric fibrosis (desmoplasia) which can entangle the loops of the small intestine and loco-regional blood vessels. A less common area for this problem, and one which was afflicting me, is the retroperitoneal cavity which adds another dimension as this is behind the intestines and where you’ll find major blood vessels such as the aorta. Some cases which are deemed inoperable may be ‘operable’ in the “right hands”. Perhaps other surgeons might have shied away. But it’s not just surgical skill, it’s also about having experience of the vagaries of Neuroendocrine Cancer.  To quote US surgeon Niraj J. Gusani, this is not “regular” small bowel surgery and should be approached with great care and planning.  I would add that surgical margins are important with any cancer but as most SI NETs occur in the terminal ileum, these margins often mean that getting the right separation means other adjacent structures may be impacted, e.g. the ascending colon in the case of terminal ileum (right hemicolectomy).  Other things that must not be missed out in small bowel surgery in a NET patient include the technique of ‘running the bowel, SI NET primaries can often be multiples and operating in the mesentery and its complex structures is not for the inexperienced.

What is the small intestine?

Worth looking at the small intestine (small bowel) in more detail to get a feel for some of the issues with NET surgery in that area and its potential consequences. The small intestine, despite its name, is the longest part of the gastrointestinal tract. It works with other organs of the digestive system to further digest food after it leaves the stomach and to absorb nutrients. The entire digestive system works together to turn the food you eat into energy.  Once the digested food leaves the ileum, more than 95 percent of the nutrients (such as vitamins, minerals, proteins and carbohydrates) the body needs has been absorbed. What’s left moves on to the large intestine.

Anatomy. The small intestine is a long, winding tube connected to the stomach on one end and the large intestine on the other. It is only about as big around as an average middle finger and is from 20 to 25 feet (6 to 7.6 meters) long in an adult. It comprises 3 main parts or order of anatomy; the duodenum (connected to the stomach and semi circles around the pancreatic head) is around 20% of total length, the jejunum is another two fifths and finally the last section is the ileum. The primary function of both of these final two sections is to absorb nutrients into the bloodstream.  The ileum joins the cecum which is a joint/valve between the small and large intestines.  The area of the ileum where it connects to the cecum is known as the terminal ileum, worth mentioning because it’s a common location for primary SI NETs.  Also worth mentioned that the duodenum while technically part of the small intestine, has it’s own grouping of NETs known as Duodenal NETs or dNETs for short.  Furthermore, they can be closely related to Gastric NETs and Pancreatic NETs as some can be symptomatically similar (excess gastrin, gastrinoma) and some parts are technically inside the foregut region. Jejunum primaries are rare, the majority are found in the ileum.

other organs included for context

Peritoneum and Mesentery

This is very complex, but the entire small intestines are held together by the mesentery which is really part of a bigger abdominal structure called the peritoneum. The mesentery serves as a conduit for blood vessels, nerves and lymphatic vessels going to and from the organ in question. This is why the mesentery is frequently mentioned in relation to SI NETs Many cases of SI NETs frequently present as masses in the root of the mesentery (as mine was). It presents problems for lymph nodes, blood vessels and desmoplasia, the latter is thought to be caused by over-secretion of hormones with serotonin as the main culprit.  This adds complexity and risk to SI NET surgery.

Metastatic-carcinoid-tumor-to-the-root-of-the-mesentery-arrow-causing-typical
Metastatic Neuroendocrine Tumor to the root of the mesentery (arrow) causing typical circumferential desmoplastic reaction. Note the ‘hub and spoke’ look.

Surgery, watch and wait, non-operative management

There’s some controversy in certain scenarios.  In terms of treatment of different stages of disease, loco/locoregional/metastatic (Stage 1 through Stage 4), there can be different approaches.  At lower stages, surgeons may operate with curative intent but at the later cancer stages, debulking (reduce tumour bulk) or cytoreductive surgery (reduce numbers of tumour cells) is often warranted.  Clearly in cases deemed inoperable, watch and wait or non-operative management may be offered. Sometimes the decision to cut or not to cut is a very difficult one.

I also had liver metastasis, which was another factor to be considered by my team. With some cancers, particularly more aggressive ones, surgery at stage IV can be put aside in favour of non-invasive methods such as chemotherapy. But with well differentiated SI NETs, debulking surgery can be an option even in the presence of liver and other distant metastases.  It’s also possible to have inoperable primaries and operable secondaries and vice versa, which adds another dimension to treatment planning and approach.  Fortunately, surgery is only one mode of therapy and many multi-disciplinary teams (MDT) operate on a multi modal approach, e.g. surgery, somatostatin analogues, liver directed therapies, systemic targeted therapies (e.g. PRRT, EverolimusSunitinib (pNET)).  Surgery remains important though because it’s really the only potentially curative tool in the treatment arsenal for Neuroendocrine Cancer.

Recent papers 2020

I wanted to finish off by pointing out two recent papers published in 2020 (they may only be abstracts but sufficient for most.  The first paper looks at the benefits of upfront surgery for small bowel NETs. Journal of Clinical Oncology 38, no. 4_suppl (February 01, 2020) 620-620. Published online February 04, 2020. DOI: 10.1200/JCO.2020.38.4_suppl.620 

This was a ‘population-based analysis’ of 1000 patients with small bowel NET (SB-NET), metastatic at diagnosis between 2001-2017, and was conducted by linking administrative datasets. ‘Up front’ was defined as resection within 6 months of diagnosis. The paper concluded that up front small bowel resection (USBR) for metastatic SB-NETs was associated with clinical benefits over Non-Operative Management (NOM), in terms of decreased subsequent admissions and interventions, and improved survival. USBR should be considered for metastatic SB-NETs to improve patient outcomes. See diagram below. 

The second paper is authored by James Howe, a well-known experienced NET surgeon.  Entitled: Howe, J.R. It May Not Be Too Little or Too Late: Resecting Primary Small Bowel Neuroendocrine Tumors in the Presence of Metastatic Disease. Ann Surg Oncol 27, 2583–2585 (2020). https://doi.org/10.1245/s10434-020-08695-0

This paper acknowledges known best practices in debulking/cytoreductive surgery in Neuroendocrine Cancer. That is, for patients with metastatic disease, resection of the primary tumour and cytoreduction of liver metastases are the preferred approach where possible to improve long-term survival providing that a threshold of tumour reduction can be met.  In series requiring that 90% cytoreduction be achieved, only about 20% of all patients may undergo surgical treatment, whereas if the cytoreduction threshold is lowered to 70%, then up to three-fourths of patients may have cytoreduction attempted. Similar improvements in overall survival have been seen for patients, achieving 70–90% and more than 90% cytoreduction.  But this paper goes on to discuss the scenario where these thresholds cannot be met and there might in particular circumstances still be an option for surgical intervention to remove the primary without cytoreduction of liver metastases. Thus, asking the question posed in the title of the paper “is resecting the primary tumor after it has metastasized too little too late“.  The paper doesn’t really have a conclusion about that but the summary at the end is useful and hopefully discussions at the specialist level will lead to some studies leading to established guidelines. Although it was pointed out that such a contingency scenario does exist in North American NET (NANET) Guidelines.

I also wanted to include this analysis of some of the benefits of small intestine surgery from a very well-respected NET centre authored by some big NET names.

Aggressive Surgical Approach to the Management of Neuroendocrine Tumors: A Report of 1,000 Surgical Cytoreductions by a Single Institution by Woltering, Eugene & Voros, Brianne & Beyer, David & Wang, Yi-Zarn & Thiagarajan, Ramcharan & Ryan, Pamela & Wright, Anne & Ramirez, Robert & Ricks, M & Boudreaux, J.. (2017). Aggressive Surgical Approach to the Management of Neuroendocrine Tumors: A Report of 1,000 Surgical Cytoreductions by a Single Institution. Journal of the American College of Surgeons. 224. 10.1016/j.jamcollsurg.2016.12.032. 

Summary

It’s important to get an experienced surgeon for this sort of surgery. There are so many vagaries, such as surgical knowledge and techniques in this area of the anatomy, knowledge of the Neuroendocrine Cancer and epidemiology, e.g. how it normally spreads and recurs and a hundred other things.   As the slide above states, “patients with metastatic SB NETs can live many years” but the right diagnostics and the right treatment upfront, followed by the right surveillance, might all play a big part in that.

 

The most comprehensive small intestine surgical management guidelines on the ‘NET’ (James Howe et al). Small Intestine Neuroendocrine Tumours (SI NETs): To cut or not to cut?  

Small Intestine Neuroendocrine Tumours (SI NETs): To cut or not to cut? – Ronny Allan – Living with Neuroendocrine Cancer

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Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.   

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

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