the role of gastroenterologist in the management of gep -neΝs...puli et al, world j gastroenterol...
TRANSCRIPT
Dr. Christos G. Toumpanakis MD PhD FRCP AGAF
Consultant in Gastroenterology/Neuroendocrine Tumours
Honorary Associate Professor, University College of London
Neuroendocrine Tumour Unit - ENETS Centre of Excellence
ROYAL FREE HOSPITAL, London,UK
The role of Gastroenterologist
in the management of GEP - NEΝs
DISCLOSURE OF INTEREST
NOVARTIS: advisory board, research grants, educational grants, honoraria for lectures
IPSEN: advisory board, research grants, educational grants, honoraria for lectures
AAA: research grants, educational grants, honoraria for lectures
Lexicon: advisory board
PFIZER: advisory board, educational grants
DIAGNOSTIC APPROACH
• History and clinical examination
• Biochemical tests (“Biomarkers”)
• Imaging studies
( for localization of primary and metastatic lesions)
• Histology - “ gold standard”
DIFFERENTIAL DIAGNOSIS –Diarrhoea + Abdominal pain
“Small bowel NENs” associated
diarrhoea + abdominal pain
• Diarrhoea always secretory
(persists with fasting)
• Abdominal pain
- Even during the night
- Usually periumbilical
- Occurring > 2 h after meals
- Not settling after defecation
- Features of sub-acute bowel obstruction
Diarrhoea and abdominalpain due to IBS
• Usually young females• Non-secretory diarrhoea
• Alternating with constipation•Abdominal pain settling with defecation,
not occurring during the night
GEP – NETs
• Small bowel NETs (Carcinoid syndrome & other causes)
• VIPomas (chronic diarrhoea, dehydration and hypokalemia)
• Gastrinomas (chronic diarrhoea that responds to PPIs)
• Glucagonomas (+ other features of those tumours e.g migratory necrolytic erythema)
• Somatostatinomas (steatorrhoea)
Non-GEP NETs
• Bronchial NETs (carcinoid syndrome)
• Medullary Thyroid Carcinomas
NETS THAT CAN CAUSE CHRONIC DIARRHOEA
DIFFERENTIAL DIAGNOSIS OF
PERSISTENT DIARRHOEA IN SMALL BOWEL NETS
Refractory Carcinoid Syndrome
SteatorrhoeaBile acid malabsorption
Small bowel bacterial overgrowthMesenteric ischemia
DIAGNOSTIC APPROACH
• History and clinical examination
• Biochemical tests (“Biomarkers”)
• Imaging studies
( for localization of primary and metastatic lesions)
• Histology - “ gold standard”
The role of upper GI endoscopy for diagnosis of gastric NEΝs
Type 1 gNEN
Type 2 gNEN
Type 4 gNEC
The surrounding mucosa should be ALWAYS biopsiedespecially in gastric NENs
Type 3 gNEN
Types of G-NENs
Type I Type ΙΙ Type ΙΙΙ
Relative frequency 70 – 80% 5 – 6% 14 – 25%
Features Usually multiple (<10mm) Usually multiple (<10mm) Usually solitary(> 20mm)
Ass. diseases Atrophic gastritis ΜΕΝ-1/ Gastrinoma No
Histology G1 G1 G2 / G3
Serum Gastrin Raised Raised Normal
Gastric p H Alkaline Hyperacid Normal
Metastases < 5 % 10 – 30% 50 – 100%
Tumour relateddeaths
- < 10% 25 – 30%
MiNEN
(? type 4)
6 – 8%
Very aggressive
Mixed histological
characteristics
Metastases > 80%
The role of lower GI endoscopy for diagnosis of rectal NEΝs
Role of wireless small bowel capsule endoscopy
� Indications :
- To detect the primary (-ies) in suspected small
intestinal NENs
- To identify source of small bowel bleeding in NENs
Sensitivity : 75 – 83%
(CT : 62.5 %, Push enteroscopy : 44%, colonoscopy :
22%)
Specificity : 37.5%
Positive Predictive Value : 55%
Negative Predictive Value : 60%
Nujaim et al, Gastroenterology Res 2017
Furnari et al, J Gastrointersin Liver Dis 2017
Role of double balloon enteroscopy (DBE)
� Rarely, small bowel NENs can be
diagnosed only with DBE
* * *# ++ *
� Indications :
- To precisely localize the primary (-ies) in suspected
small intestinal NENs
- To identify +/- treat the cause of small bowel bleeding
in NENs
DBE vs Capsule endoscopyDBE identified additional lesions in 62% of patients in a recent surgical series(82% of them confirmed in histology)
Gangi et al, J Gastointerstinal Surg 2018
Rossi et al, United European Gastroenterology J 2017
Telese et al, UKI NETS 2017
The role of Endoscopic Ultrasound in G-I NENs
� Type 1 and 2 gastric NENs: to evaluate the depth of invasion and indication to endoscopic treatment that is reserved to lesions not infiltrating beyond the muscularis propria.
� Type 3 gastric NENs: to stage the disease by assessing the presence of regional lymph-node involvement.
� To stage duodenal NENs with diameter >2 cm. To exclude loco-regional lymph node metastases and thus indication for endoscopic mucosal resection.
� To determine the indication of endoscopic removal in Rectal NENS versus transanal excision or radical surgery, in particular for those with diameter >2 cm, by assessing depth of invasion and the presence of lymph node metastases. To follow up patients after resection.
Zilli at al, Dig Liver Dis 2018
The role of Endoscopic Ultrasound in pancreatic NENs
� To differentiate pancreatic NENs from
adenocarcinoma
� To localize small pancreatic NENs, mainly
insulinomas or gastrinoma, before surgery,
especially if other non-invasive imaging studies are
negative
� To stage the NEN by evaluating the presence of
vascular invasion or loco-regional lymph node
� To evaluate the distance between pancreatic lesion
and the main pancreatic duct in a pre-operative
setting, thus predicting the risk of developing
pancreatic fistula
Zilli at al, Dig Liver Dis 2018
Diagnostic accuracy of EUS
• Pooled sensitivity: 87%• Pooled specificity: 98%
• Mean detection rate: 90% in suspected p NENs (mean detection rate of CT/MRI : 73%)
• Increased pre-op p NEN detection by 25%
Puli et al, World J Gastroenterol 2013
James et al, Gastrointest Endosc 2015Manta et al, J Gastrointest Liv Dis 2016
Endoscopic resection in Gastric -NENs
Snare polypectomy, Endoscopic Mucosal Resection (EMR) or Endoscopic Submucosal Dissection
(ESD) ?
� 33 pts, (polyps 2 – 20 mm), 45% polypectomy with snare.
� 63.6% had recurrence (within 8 months).
Merola et al, Neuroendocrinology 2011
• 62 pts had either EMR or ESD. • The overall ESD complete resection rate was
higher than that of the EMR rate (94.9% versus 83.3%, P value = 0.174).
• A statistically lower vertical margin involvement
rate was achieved when ESD was performed compared to when EMR was performed (2.6% versus 16.7%, P value = 0.038).
• The complication rate was not significantly different between the two groups.
Kim et al, Gastroenterol Res Pract 2014
EUS-guided RFA for pancreatic NENs
� Two devices are currently used:
- HabibTM EUS-RFA catheter; EMcision Ltd., London, UK)
- EUSRA from STARmed, Korea or HybridTherm Probe [HTP], from
ERBE) that resembles the conventional EUS FNA needle.
� The controlled heating of the target lesion can be visualized real-time
with EUS as the appearance of echogenic bubbles around the
needle tip.
� More than one zone in the lesion can be ablated depending on its
size .
Lakhtakia, Clin Endoscopy 2017
Results of EUS-RFA in p NENs
No of
ptsTumour Mean size
in mm
RF sessions Outcome Recurrence Complications
Armellini et al 1 P NET 20 1 Complete - None
Rossi et al 1 P NET 9 1 Complete None at 34 mo None
Pai et al 2 P NET 27 1,2 Necrosis None in 1 mo None
Lakhtakia et al 3 INSULINOMAS 18 2 Size reduction None in 12 mo None
Lakhtakia, Clin Endoscopy 2017
Take Home messages
� Many NETs can cause chronic diarrhoea
� Consider also other causes of diarrhoea, than refractory carcinoid syndrome, in small bowel
NETs
� Upper and lower GI endoscopy provide the diagnosis of gastric, duodenal and rectal NENs
� Wireless capsule endoscopy can identify the primary (-ies) and cause of obscure GI bleeding in
small bowel NENs
� Double balloon enteroscopy can localize precisely the primary (-ies) in small bowel NENs
� EUS can assess the depth of invasion of G-I wall, from a G-I NEN prior to endoscopic treatment
� EUS can be very important in diagnosis, localization, staging and pre-op assessment of p NENs
� EMR & ESD are the methods of choice in endoscopic treatment of gastric and rectal NENs,
when indicated, with ESD being associated with higher R0 resection rates
� EUS RFA seems promising for endoscopic treatment of localized /functional p NENs
Thank you
very much