Pancreatic Neuroendocrine Tumours – to cut or not to cut

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Background 

I’ve written before about pancreatic NETs (pNETs), much of which has been on the awareness side of my advocacy work, particularly emphasising the differences with core Pancreatic Cancer (adenocarcinoma).

Pancreatic NETs are quite difficult to diagnose and treat, some of that difficulty is due to the location of the pancreas and accessibility for surgeons and radiographers. It’s not helped by the fact that most pNETs are non-functional, making diagnosis more difficult as there is little clinical suspicion to scan, but also results in more late diagnoses.

Although biopsies are possible, mainly via endoscopic ultrasound or laparoscopy, they can still be difficult to reach.  In some cases, biopsies are not done until after the surgical removal of tumours. The latter scenario plus surgery after a positive biopsy result does present an increased risk of morbidity and mortality.  Consequently, physicians (and patients) often have difficult decisions to make.   I discussed some of these issues in my article To cut or not to cut which covers all types of NETs, but it’s particularly relevant to pNETs.

Many medical publications and many NET specialists will talk about the need to find and resect the primary tumour but with pancreatic primaries, there’s always some caution and this is reflected in NET Guidelines in most regions.  The topic of removing or watching remains controversial in pancreatic NETs.  

Types of Pancreatic neuroendocrine tumour surgery

In addition to classic debulking/cytoreductive surgery including for liver metastases, surgery on the pancreas is complicated and needs expert skills., Types include:

  • Distal pancreatectomy: Surgery to remove the body and tail of the pancreas. The spleen may also be removed if cancer has spread to the spleen.
  • Enucleation: Surgery to remove the tumour only. This may be done when cancer occurs in one place in the pancreas. However, it is for selective cases only, but low-grade/indolent pancreatic NETs may fall into this category.  Some hospitals offer this procedure online – here is one example Enucleation of Pancreatic Tumors Procedure | Stanford Health Care
  • Pancreatoduodenectomy (Whipple Surgery): A surgical procedure in which the head of the pancreas, the gallbladder, nearby lymph nodes, and part of the stomach, part of the small intestine, and bile duct are removed. Enough of the pancreas is left to make digestive juices. The organs removed during this procedure depend on the patient’s condition.  There can be variations of this (plus or minus) depending on circumstances.
  • Total pancreatectomy. This operation removes the entire pancreas, as well as the gallbladder, part of the stomach and small intestine, and the spleen. This surgery might be an option if cancer has spread throughout the pancreas but can still be removed. But this type of surgery is used less often than the other operations because there doesn’t seem to be a major advantage in removing the whole pancreas, and it can have major side effects.

Pancreatic NETs – To cut or not to cut

There are guidelines for the treatment of pNETs and most seem to have tumour size thresholds to aid decision making but that is just one factor.   I’ve listened to many presentations by NET specialists talking about the dilemma of cutting or not cutting and the ‘debate’ is still happening 3 years since I took an interest in the subject.  Most guidelines seem to use 2cm as a threshold for surgical removal (>2cm) or watch and wait (<2cm) but there are other factors that could also indicate surgical removals such as a functioning tumour producing one of the pNET syndromes (i.e. palliative surgery) or the tumour threatening important vessels (i.e. pre-emptive surgery).  These guidelines include ENETS, NANETS and NCCN.  Currently, it’s difficult for physicians to know how aggressive a pNET could become over time and this hinders decision-making.

As indicated above, often the decision to cut or not to cut is made easier when a patient is symptomatic, exhibiting signs of one of the pancreatic NET syndromes, this helps in decision-making regardless of tumour size as the surgery becomes palliative in approach.  However, most pancreatic NETs are non-functional.  This 2020 paper here is therefore very interesting and also touches on the subject of whether the primary tumour is resected in the setting of unresectable metastatic disease.  Pancreatic surgery is a big deal so always consult your specialists for further advice.  Read more here. 

For those interested in this debate, you may like a recent article from the 2019 Society of Surgical Oncology Annual Cancer Symposium where Cristina R. Ferrone, MD, the surgical director of the liver program in the Division of General Surgery at Massachusetts General Hospital, in Boston, and Peter J. Allen, MD, the chief of surgical oncology at Duke Cancer Institute, in Durham, N.C., describe the benefits of resection versus observation in small neuroendocrine tumors of the pancreas and outlined the risks of under- and over-treatment, respectively.  Click here.  It’s two sides of the coin and you may find the discussion interesting.

You may also find this NET Research Foundation-sponsored video interesting from very well-known and respected NET surgeon Dr James Howe.  The link will take you directly to the part about pancreatic surgery (10.30).  Click here to watch.

And this 2021 article also features NET Surgeon Dr James Howe – click here to read. 

Analysis of Prospective Evaluation of the Management of Sporadic Nonfunctioning Asymptomatic Pancreatic Neuroendocrine Neoplasms (PNEN) ≤ 2 cm (ASPEN Study)

We could benefit from studies into longevity and quality of life in those who had small non-functional pancreatic NETs (NF-PNET) less than 2cm.  There’s an interesting trial taking place coordinated by a senior surgeon in Italy with up to 1000 participants collecting data from 40 institutions.  This is based on a dramatic increase in the diagnosis of small, incidentally discovered, NF-PNET (many incidental and found via modern imaging techniques checking for something else). Various studies indicate the safety of conservative management for these lesions and The European Neuroendocrine Tumor Society (ENETS) (….and others) propose a “wait and see” approach for small NF-PNET.  “The aim of the study is to evaluate the most appropriate management of sporadic asymptomatic non-functioning pancreatic neuroendocrine neoplasms (NF-PNEN) ≤ 2 cm. NF-PNEN management will be decided at the hospital and all therapeutics decisions will be decided/coordinated by the treating physician. Patients will be either submitted to surgical resection or to active surveillance”.  The wording indicates Neuroendocrine Neoplasm (NEN) indicating Neuroendocrine Carcinoma patients are included.  However, the exclusion and inclusion criteria in the clinical trial document need to be taken into account. 

Click here to read more

Summary and further reading

Of course, what we really need is better prognostic testing which will help to guide therapy decisions, in particular surgery.  Read my article on molecular research for Neuroendocrine Neoplasms (to follow, currently in draft but will be drawn from some of the references below).

1. Subtypes of Pancreatic Neuroendocrine Tumors and Effect on Disease Recurrence – By The ASCO Post, posted: 15 Jul 2019.

2. Robust molecular stratification provides insights into cell lineage correlates –  By ESMO posted 09 Jul 2019.

3. NET Research Blog – NETRF-Funded Finding May Help Predict Pancreatic NET (pNET) Recurrence posted 1 Jul 2019.

4. Daxx Mutations – click here

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 as they are not members of the private group or followers of my sites in any official capacity.  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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5 thoughts on “Pancreatic Neuroendocrine Tumours – to cut or not to cut

  • Mike Day

    Very interesting article. My wife had a pNET removed 3 years ago and the 2 NETs from her liver the following June. Recent scans, including gallium dotate and MRI, show about 8 small tumours present in her liver. She started hormone injections 3 months ago, thankfully with minimum side effects, and following a scan in 2 weeks is due to see consultant early October to determine if the injections are inhibiting growth/spread of tumours. We will keep you informed!

  • Sandra Mullinns

    Ronny I had ablation done on 2places on liver mets from pancreas it worked very well for me still waiting for first mri after mine were functioning I still dont know all I need to but learning much from you forever gratefull to you

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