pancreatic neuroendocrine neoplasm (pnen) case
DESCRIPTION
Pancreatic Neuroendocrine Neoplasm (pNEN) case. Case Presentation : Dr. Chatzellis Eleftherios MD Intern in Endocrinology. Endocrinology Unit Pathophysiology Department Laikon General Hospital. Case History - 2001. 58 year old male patient 2001 : abdominal pain - PowerPoint PPT PresentationTRANSCRIPT
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Pancreatic Neuroendocrine Neoplasm (pNEN) case
Endocrinology UnitPathophysiology DepartmentLaikon General Hospital
Case Presentation:Dr. Chatzellis Eleftherios MD
Intern in Endocrinology
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58 year old male patient 2001: abdominal pain CT scan: 5cm tumor pancreatic tail
Multiple focal lesions in the liver FNAB (liver lesion) Well Differentiated NEN
grade 2 (ki67 = 4%) CgA = 5,2 nmol/l (<4), other markers negative No secretory symptoms (non-functioning pNEN) SRS (Octreoscan): avid uptake (Krenning score = 3) in both
primary pNEN and liver metastases
Case History - 2001
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Case History
Chromogranin A
ki67
H&E stain
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Case History 2001-2005 Sweden (Uppsala) Suggested surgery to reduce tumor
burden and local complications Patient refused Chemotherapy (Streptozotocin + 5-FU)
+ Somatostatin analogues (SSA’s) 1 year later (2002): DISEASE PROGRESSION (PD) Addition of pegylated INF-a Chemotherapy was discontinued after 2,5 years (mild
renal impairment) 2002-2005 : STABLE DISEASE (SD) CgA = 10,5 nmol/l (<4)
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Case History 2006-2008 2006: Hypercalcemia occurred for the first time
Ca = 11,8 mg/dl (8,5 - 10,1)P = 1,98 mg/dl (2,5 - 4,5)PTH = 2,54 pg/ml (10 - 65)PTHrP = 84 pmol/l (<2)CgA = 45 nmol/l (<4)
Imaging: DISEASE PROGRESSION (PD) Increased SSA’s dosage [+peg-INFa] Normalization Ca 2006-2008: STABLE DISEASE (SD) - Biochemical control
Humoral Malignancy-associated Hypercalcemia(PTHrP- related)
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Case History 2008-2009 2008: peg-INFa discontinued (depression) 2008: Hypercalcemia (12,9 mg/dl)
+ DISEASE PROGRESSION (PD) 2008-2009: 177Lu-DOTATATE x5 cycles (25.6 GBq) Increased SSA’s dosage Addition of pasireotide 1200μg bid Ca = 10,7 mg/dl, CgA=115 nmol/l, PTHrP=140 pmol/l 2009: DISEASE PROGRESSION (PD)
+ biochemical relapse (Ca = 11,8 mg/dl)
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Case History 2009-2010 + Temozolomide + Capecitabine (CAP-TEM) 2009-2010: STABLE DISEASE (SD) Biochemical control of Ca required additional
treatment:SOM230 and SSA’sForced DiuresisPrednisolone 40mg/dBiphosphonates (i.v. zolendronate 4mg monthly)Cinacalcet 90mg/d]
SIDE-EFFECTS: Proximal myopathy - muscle atrophy, patient immobilization (wheel chair), severe Diabetes Mellitus (~100 IU insulin/d)
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Case History 2010 Tumor burden reduction (cytoreduction) necessary
Biochemical control (Ca)Reduce treatment side-effects
OPTIONS:Surgery Patient still deniedPRRT Already performed (GFR, marrow toxicity)RF Ablation Not applicable due to large liver
lesionsEmbolization (TAE/TACE)
Pre-embolization evaluation : Portal vein thrombosis
Selective approach (embolization of small branches of hepatic artery)
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Case History - TAE
Pre-embolization Post-embolization
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Post-embolization status TMZ + Capecitabine SSA’s Pasireotide 1200mcg/d Prednisolone 40 mg/d Zolendronate 4mg/m Insulin treatment
Ca = 10,2 mg/dlCgA = 50 nmol/l
PTHrP = 38 pmol/l
Case History - TAE
TMZ + Capecitabine SSA’s at ½ dosage X Prednisolone 8 mg/d X X
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Case History 2010 6 months after TAE Ca = 13,2 mg/dl DISEASE PROGRESSION (PD) Painful lump on left thigh
T1 T2
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Case History 2010
Bone scintigraphy Tc 99m
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Case History 2010 BONE METASTASES vs BENIGN LESION Bone Biopsy Brown tumor (in the context of
prolonged PTHrP action on bone) New liver lesion biopsy ki67 = 4%, IHC (+) for PTHrP
PTHrP Immunohistochemistry H&E stain
Bone biopsyLiver metastases biopsy
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Case History 2010-2012 Temozolomide (200mg/m2 Days 1-5 q4w) +
Bevacizumab (10 mg/kg q2w) + Everolimus (10mg/d) [+SSA’s] Ca = 8,8 mg/dl Temozolomide and Bevacizumab D/C after 6 months
due to thrombocytopenia 2010-2012: STABLE DISEASE (SD)
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Case History 2012-2014 2012: DISEASE PROGRESSION (PD) Ca=9,34 mg/dl, PTHrP = 50 pmol/l Sunitinib 37,5 mg/d [+SSA’s] 6 months later: Ca = 6,5 mg/dl !!! 2012-2014: STABLE DISEASE (SD)
April 2014: Patient deceased †(hepatic encephalopathy - malnutrition)
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20052001 2006 2006 2008 2009 2009 2009 2010 2010 2010 2012 2012 2014
SSA’s
STZ+5FU
Pegylated INFa
PRRT
Pasireotide
Everolimus Sunitinib
Embolization
PDPD PD PD
CAP-TEM
PD PD
BEV-TEM
PTHrP
Ca
CgA
†
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Case synopsis WD pNEN grade 2 Stage IV (liver metastases) Change of functional status during disease course Rare PTHrP secretion (paraneoplastic syndrome) Even more rare: brown tumor due to PTHrP Employment of several treatment agents/modalities to
achieve both tumoral and biochemical control Importance of cytoreductive interventions and novel
molecular targeted therapies in controlling secretory symptoms/syndrome
Long survival despite metastatic disease at presentation (application of different therapeutic modalities)
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Improving Survival of NET patients
James Yao, ENETS 2014
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