What are NETS? (and a bit about surgery) · 2020. 8. 27. · e.g. ranitidine Somatostatin...
Transcript of What are NETS? (and a bit about surgery) · 2020. 8. 27. · e.g. ranitidine Somatostatin...
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What are Neuroendocrine Tumours ?(and a bit about surgery)
Tom Armstrong PhD FRCSEdHepatobiliary Surgeon
University Hospitals Southampton
PLANETS NET Conference, Southampton 2018
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What is the Wessex NET Group?
UHS• weekly MDT• joint clinic
QAH• joint clinic
RBH• monthly MDT• joint clinic
Poole
Dorchester
Salisbury
Winchester
Basingstoke
Chichester
IoW
Channel Islands
videolink
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What is the Wessex NET Group?
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What is the Wessex NET Group?
…. a partnership that has led to the recognition of the Wessex NET Group
European Centre of Excellence
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Nervism
1883 Ivan Pavlov• recognised that dogs salivate when given food• realised the dogs salivate when they think that they were going to be given food
First realisation that nervous system (brain) plays a dominant role in bodily functions
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More to it than just nervism:there is endocrinism too!
• What does endocrine mean?
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More to it than just nervism:there is endocrinism too!
• What does endocrine mean?
• Refers to a gland which secretes hormones directly into blood stream
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More to it than just nervism:there is endocrinism too!
• Hormone=chemical messenger sent from one cell to another in blood stream
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Endocrine system in humans
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How do nerves and endocrine system interact?
• 1867 Islands of cells in pancreas– Langerhans
• 1870 Glands within the intestines (EC cells)– Heidenhain
• 1902 Realisation that hormones regulated gut function– Bayliss and Starling
• 1938 EC cells made gut hormones and that these interacted with neurones– Feyter
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Neuroendocrine System in action
• Paradigm shift in understanding
Hormone: travels in blood stream
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Anatomy and Function of Gastrointestinal Tract
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Neuroendocrine Pancreatic Function
• Systemic Hormones – Insulin: drives sugars into cells
– Glucagon: releases sugars from liver
• Gut Hormones– Gastrin: production of acid in stomach
– VIP: encourages GI secretions
– Somatostatin: suppresses release of other hormones
– PPP: reduces apetite and slows release of digestive juices
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Neuroendocrine Pancreatic Function
Feedback Mechanisms
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Neuroendocrine Gut Function
• Gut Hormones– Serotonin: gut function
– (mood, sleep, healing)
– Bradykinin: gut contraction/motility
– (dilate blood vessels, causes low blood pressure)
– Histamine: immune function
– (too much causes wheezing and swelling)
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Why do tumours form?
• Environmental Factors
– Smoking, alcohol
• Chronic Inflammation
– Inflammatory bowel disease
• Genetic Factors
– MEN syndromes
Normal Feedback Mechanisms Fail
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Why do tumours cause disease?
• Block anatomical tracts (pipes)
– eg jaundice, vomiting, pain
• Stop normal function of organs
– eg liver
• Secrete excessive hormones
– eg insulin, thyroxin
– syndrome
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NETS
• 1890 Case report in Lancet
• Woman in 50’s
• Egg sized lumps in intestine
• Diarrhoea
• Flushing after eating
• 1907 Carcinoma like (Carcinoid)
• Oberndorfer
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NETS: anatomic distribution
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Functioning vs. Non-Functioning NETs
• Functioning
– Hormonally active, cause syndromes which lead to investigation
• Non-functioning
– Usually found incidentally or at a more advanced stage
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Presentation of Non-Functioning NETs
• Chance
• Jaundice
• Bowel Obstruction
• Cough
• Irritable bowel
• Anaemia
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Presentation of functioning NETs: Insulinoma
Low Blood Sugar• headache• lethargy• dizzyness• blurred vision
Stress Response• anxiety• tremor• nausea• sweating
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Insulinoma
Insulinoma: failure of negative feedback
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Insulinoma
Insulinoma: failure of negative feedback
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Insulinoma
Insulinoma: failure of negative feedback
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Insulinoma
Insulinoma: failure of negative feedback
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Insulinoma
• Comprise 75% of functioning pancreatic NET
• Still rare
• Usually present in 50s
• 90%<2cm
• 10% multiple
• 10% malignant: if metastasis
• 10% MEN-1
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Presentation of functioning NETs: Gastrinoma
• Excess stomach acid
• Ulceration
– Stomach
– Duodenum
• Pain, weight loss
• Doesn’t respond to treatment
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Gastrinoma
• Zollinger-Ellison Syndrome
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Gastrinoma
Proton PumpInhibitore.g. omeprazole
H2 Blockere.g. ranitidine
SomatostatinAnalogues
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Presentation of functioning NETs: Carcinoid (midgut NETs)
• Diarrhoea
• Abdominal pain
• Weight loss
• Flushing
• Heart failure
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Presentation of functioning NETs: Carcinoid (midgut NETs)
• Diarrhoea
• Abdominal pain
• Weight loss
• Flushing
• Heart failure
– serotonin
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Staging NETs
• TNM system
– Tumour= size/site of primary tumour
• +/- invasion of primary into adjacent organ
– Node= spread of primary tumour to lymph nodes
• via lymphatic channels
– Metastasis= spread of primary tumour to other organs
• via blood stream
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Staging NETs
• Scans– CT
– MRI
– Octrotide
– Gallium PET
• Endoscopy– Gastroscopy
– Colonoscopy
– Capsule
– Endoscopic ultrasound
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Grading NETs
• Need biopsy
– Primary
• Endoscopy
– Secondary/Metastasis
• Liver
Grade 1 NET
Grade 2NET
Grade 3NET
Grade 3 NEC
Proliferation index (Ki67)
<2% 3-19% 20-49% >50%
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Managing NETs
Localised
Metastatic
PI <2%
PI >20%
PI 2-20%
Curative Surgery
Systemic Therapy
Multimodal Treatment• ablation• embolisation• PRRT• surgical debulking• somatostatin analogues
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Understanding Treatment Terminology
• Systemic: – a treatment that treats any NET cell in the body
• Lanreotide/Octreotide• Chemotherapy• PRRT
• Locoregional: – a treatment aimed at one specific area of body or an organ
• Surgery• TACE or SIRT
• Cytoreductive/Debulking: – surgery to remove bulk of disease
• Multimodal:– A combination of treatments
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Evolution of NET Treatment
Oberg K Endocrinol Metab Clin N Am 2018; 47: 711-31
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Wessex NET GroupManagement Algorithm
CytoreductionSymptom Control
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Surgery for NETs
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Surgical Procedures: liver
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Surgical Procedures: liver
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Surgical Procedures: liver
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Surgical Procedures: liver
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Surgical Procedures: liver
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Surgical Procedures: pancreas
Enucleation of small PNETs
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Surgical Procedures: pancreas
Distal pancreatectomy +/- splenectomy
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Surgical Procedures: pancreas
Pancreaticoduodenectomy (Whipples)
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Whipple’s Procedure
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Surgical Procedures: bowel
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Surgical Procedures: bowel
LymphNodeStage
4
3
2
1
0
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Surgical Procedures: bowel
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Summary
• NETs are slow growing a slow growing type of cancer that form in the GI neuroendocrinesystem
• We do not know what causes them
• NETs can be described as functioning or non-functioning depending on whether they produce hormones
• There are many effective treatment modalities for NETs
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