pituitary adenoma surgery: complication avoidance while ... · •selective tumor removal...

Pituitary Adenoma Surgery: Complication Avoidance

While Pushing the Remission Envelope

Daniel Kelly, MD

Colleagues: Garni Barkhoudarian, Chester Griffiths, Pejman Cohan,

Sarah Rettinger, Felipe Sfeir, Walavan Sivakumar, Amy Eisenberg

Sheri Palejwala, Felipe Sfeir, Xiang Fabio Huang

Disclosures

• Mizuho, Inc. - royalties

Common Brain & Skull Base TumorsStandardized Incidence Rates

(new cases/100,000 persons/year)

Tumor Type SIR In USA/yr

• Meningioma 7.7 26,000

• Glioma 7.1 20,000

• Pituitary adenoma 3.2 11,000

• Schwannoma 1.9 6000

• Total Primary Brain Tumors 71,000

• Brain Metastases 250,000

Goals of Surgery• Selective tumor removal

– Eliminate hyper-secretion syndromes

(Acromegaly, Cushing’s, Prolactinoma, TSH-oma)

– Reduce mass effect – visual loss & headaches

– Avoid additional therapies – radiosurgery, medical therapy

• Preserve pituitary gland function

• Complication Avoidance

• Rapid mobilization and discharge home on POD#1 or 2

Pituitary Adenoma Surgery Outcomes

Remission & Outcome Rate

Acromegaly

Cushing’s diseaseProlactinoma

Endocrine-Inactive total removal

Resolution of: - Visual Deficit- Hypopituitarism- Headache

65-85%

65-90%

60-85%

60-90%

75-85%

25-50%

75-80%

* Lower success

rates with larger,

more invasive

tumors and non-

visible adenomas

in CD

Author Series nAnterior

Hypopit

Perm

DI

CSF

LeakMeningitis Epistaxis

Carotid

Injury

Sellar

Hematoma

Visual

WorseningDeath

Dehdashti 2008 200 3.0 1.0 3.5 1.0 1 0 0.5 0 0

Gondim 2011 301 11.6 6.3 2.6 0.6 1.9 0.9 0.6 0.3 1

Berker 2012 570 2.1 0.5 1.3 0.8 0.6 0.2 0 0 0

Halvorsen 2014 238 N/A N/A 4.7 2 N/A 0.4 1.3 2 1.3

Paluzzi 2014 555 3.1 2.5 5.0 0.9 1 0.3 1.1 0 0.2

Dallapiazza 2015 80 7.5-10 5.0 2.5 1.3 1.3 1.3 1.3 0 0

Magro 2016 300 13.7 6.2 2.7 3.3 2.3 0.3 2.0 2.4 0.7

OVERALL 2244 2-14% 1-6% 1-5% 1-3% 1-2% 0-1% 0-2% 0-2% 0-1%

Surgical Complication Rates from Recent

Endoscopic Pituitary Adenoma Series

Koutourousiou

2013

Giant Adenoma54 16.7 9.6 16.7 5.5 0 0 3.7 3.7 5.5

Complication rates are higher

for more challenging tumors…

Canada

Brazil

Turkey

Norway

USA

USA

France

55 of 150 pts (37%) with CS invasion- 74% direct observation- 71% histologically confirmed

• Overall remission rate – 85%

• Remission rate with CS invasion – 69%

• No new permanent cranial neuropathy

September 2017

Pushing the Envelope

144 of 384 pts (37%) with CS invasion

Complications:

- 1 ICA injury

- 1 perm CN6 palsy

- 1 perm visual worsening- 3 hematomas requiring re-op

*

Microscope Endoscope

36%

McLaughlin et al 2012 JNS

Perioperative Timeline

• Surgery time: 3 - 4 hours

• Blood loss: 100 – 200 cc

• Nasal packing: in 20-25%

• MRI on POD#1

• Discharge home on POD#1 or 2

• Follow-up sodium, cortisol check ~POD #5

• 1st Neurosurgical & ENT clinic visit 7-10 post-op

• 1st Endocrine clinic visit 2-3 weeks

• Activity:

– Up and walking on POD 1 but no strenuous activity for a week

– flying OK after 7-10 days, driving OK after 2 weeks

– Anything goes after 3 weeks

Road to Success…or Failure

Complication TimelinePatient

selection

& workup

CSF leak repair &

skull base closure

Tumor removal & gland preservation

Carotid artery localization

Nasal phase

Experience & instrumentation

Sphenoidotomy

Sellar exposure

Success

Post-op

Surveillance

Point of no-return

Tumor, Gland & Carotid Identification

Endonasal Endoscopic Room Setup

• Navigation – almost every case• Aline & Foley – not in simple adenomas • Cranial Nerve Monitoring – for adenomas extending into cav sinus

• Head position - mildly flexed, not fixed• Prep for fat graft

Endonasal Endoscopic Room Setup

ACTA Neurochir 2014

Avoiding Sino-nasal Complications: Mucosal & Vessel Sparing Approach, Wide Sphenoidotomy and Sellar Openings

Avoiding Carotid Artery Injury

• Study the anatomy…know the anatomy

Avoiding Carotid Artery Injury

• Navigate

• Doppler ultrasound

Lack of knowledge of the course of the carotids can result

in overly conservative and suboptimal exposure

0%

2%

4%

6%

8%

10%

12%

14%

16%

< 20 mm 20 - 30 mm > 30 mm > 40 mm

New Pituitary Failure by Tumor Size

Percent

Giant

Adenoma

Overall risk: 5%

Fatemi et al Neurosurgery October 2008 Paiva et al Clin Endocriniology 2009

• N = 372 operations

• Gland incision/resection in 21%

• New hypopituitarism in 3 pts (4%)

• No difference compared to pts without gland incision/resection

Case Examples

Endocrine-Inactive Macroadenoma

Acromegaly29 yr old man: 5 yr h/o increasing shoe & ring size, snoring, excessive sweating

IGF-1>1200 ngml; GH 14.5 ng/ml; total testosterone 171

Acromegaly

Acromegaly

Post-op day 2 GH 0.9Residual

Cavernous

Sinus Tumor

Post-op day 2 GH 0.9

4 months Post-op

IGF-1 GH 1

1 month: 271 0.8

2 month: 409; OGTT 0.4

3 month: 475 … Somatuline

13 month: 263

(normal 53-331 ng/ml)

Acromegaly

Giant Adenoma with Acromegaly50 yr old man with headaches, low libido, low energy

Elevated prolactin - 49, IGF-1 520ng/ml (norm 121-237 ng/ml); low testosterone and T4

Walsh, M ichael, Benedic tWalsh, M ichael, Benedic t

P age: 11 of 20Page: 11 of 20 IM:11 SE:1001IM:11 SE:1001















April 2015Stopped cabergoline

Sept 2014Post-op

Sept 2014 Feb 2017

On no therapy but

in biochemical

remission & normal

hormonal function

Path: Atypical adenoma,

GH & prolactin staining

Cabergoline started

Therapeutic Options in Cushing’s Disease

• Transsphenoidal Adenomectomy

• Medical Therapy – pasireotide &

mifepristone

• Radiosurgery & Radiotherapy

• Bilateral Adrenalectomy

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.korlym.com/&ei=FX2hVO-1OcrXoATduYKoAQ&bvm=bv.82001339,d.cGU&psig=AFQjCNG-uH42P-kI4jRslUrqXO0wJb6TAA&ust=1419955853875817

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.multivu.com/mnr/59517-novartis-signifor-fda-approval&ei=b32hVPnDAYnUoAS60IGYAw&bvm=bv.82001339,d.cGU&psig=AFQjCNGRNgpek-Z6s1v7VvS95jUWeZMDfA&ust=1419955931372828

Pseudo-capsule DissectionOldfield J Neurosurgery 2006 Jagannathan J Neurosurgery 2009

• Encapsulated adenoma found in 261 pts (48% MRI neg)

• Immediate post-op hypocortisolism 256 (98%)

61-year-old woman: 4-year history progressive weight gain,

fatigue, skin thinning, and osteoporosis.

Elevated 24 hr UFC, midnight salivary cortisol & serum ACTH

9 years in

remission

Cushing’s Disease – Microscopic Approach

PRE-OP MRI

• 32 year old woman with 3 yrs of progressive weight gain, fatigue, insomnia,

poor concentration and memory, mood swings, irregular periods, easy bruising

• 24-hour urinary free cortisol↑: 237 mcg/24hr (normal 4-50)

• Morning ACTH↑: 85 pg/ml (norm 6-50); cortisol↑: 30.1 mcg/dl (norm 4-22)

Cushing’s Disease – Endoscopic Approach

PRE-OP MRI Cushing’s Disease POST-OP Day 1

Pre-op Early Post-op

ACTH Ref Range: 6-58 pg/mL 85 <5 (L)

Cortisol Units: ug/dL 30.1 0.7

1 year in

remission

Cushing’s disease with Cavernous Sinus Invasion Re-exploration after 2 prior surgeries in 2015 & 2016

POD#1 AM Cortisol 0.7; In remission for 2 months

Beltran, C onsueloBeltran, C onsuelo

2001018487320010184873

9/13/19759/13/1975

41 YEA R41 YEA R

FF

Page: 30 of 60Page: 30 of 60

A cq no: ---A cq no: ---

KV p: 120KV p: 120

mA : 227mA : 227

T ilt: 0T ilt: 0

RD: 237RD: 237

P rovidence St Jhons P rovidence St Jhons

C T HEA D W WO C O NTRA STC T HEA D W WO C O NTRA ST

MPR 3X3 SA G L TO RMPR 3X3 SA G L TO R

2/24/2017 11:30:03 A M

11063009PRV11063009PRV

C O NTRA STC O NTRA ST

LO C : 87 LO C : 87

THK: 3THK: 3

HFSHFS

IM: 30 SE: 80445IM: 30 SE: 80445

DFO V :23.7x23.7cmDFO V :23.7x23.7cm

W: 150W: 150

C : 50C : 50

Z: 1Z: 1

AA PP

HH

FF

Beltran, C onsueloBeltran, C onsuelo

2001018487320010184873

9/13/19759/13/1975

41 YEA R41 YEA R

FF

Page: 46 of 79Page: 46 of 79

A cq no: ---A cq no: ---

KV p: 120KV p: 120

mA : 227mA : 227

T ilt: 0T ilt: 0

RD: 237RD: 237

P rovidence St Jhons P rovidence St Jhons

C T HEA D W WO C O NTRA STC T HEA D W WO C O NTRA ST

MPR 3X3 C O RO NA LMPR 3X3 C O RO NA L

2/24/2017 11:30:03 A M

11063009PRV11063009PRV

C O NTRA STC O NTRA ST

LO C : 135 LO C : 135

THK: 3THK: 3

HFSHFS

IM: 46 SE: 80444IM: 46 SE: 80444

DFO V :23.7x23.7cmDFO V :23.7x23.7cm

W: 450W: 450

C : 40C : 40

Z: 1Z: 1

RR LL

HH

FF

- 85% female, Age 30-58 years

- Macro 23%, Micro 49%, Nonvisible Micro 28%

- Prior surgery 25%

Cushing’s Series – 72 patientsHistology as Predictor of Remission

Histopathology Results Immediate remission* Remission Sustained remission

Histology and + ACTH immune staining 44/49 (90%) 47/49 (96%) 41/49 (83%)

Histology alone w/o immune staining 4/8 (50%) 5/8 (63%) 4/8 (50%)

Inadequate tissue for histopathology 8/15 (53%) 9/15 (60%) 8/15 (53%)

Total 56/72 (78%) 61/72 (85%) 54/72 (75%)

*Cortisol level below 5ng/dl first 48hrs

Cushing’s Series – 72 patientsOdds Ratios of Factors for Sustained Remission

OR* Sustained remission P value

First-time surgery 0.9 0.87

No cavernous sinus Invasion 2.8 0.08

Visible microadenoma 2.9 0.07

No cyclical Cushing's 2.9 0.1

Histology and immunostaining for ACTH 5.5 <0.01

Selective adenomectomy 6.1 <0.01

Selective adenomectomy, histology & ACTH staining 13 <0.01

Post op cortisol ≤2ug 72hrs 19 <0.01

Post-operative CSF Leaks

▪ Most common complication after transsphenoidal surgery with potential serious sequelae:

▪ Meningitis

▪ Tension pneumocephalus

▪ Re-operation

▪ Prolonged hospitalization

The Achilles’ Heel of an Otherwise “Perfect” Operation

Birch, A lan, LynnBirch, A lan, Lynn

Page: 8 of 17Page: 8 of 17 IM:8 SE:12IM:8 SE:12











Endocrine-inactive Adenoma; Grade 1 CSF Leak

Pre-Op

Post-op MRI

Post-op CT

*

**

**

Post-op MRI

Post-op MRI

Preventing CSF LeaksOperative Neurosurgery, April 2007

• A solid or semi-solid buttress essential to hold repair in position

• Size of leak should dictate extent of repair

Overall Repair Failure Rate (N=668):

decreased from 4% to 1% (p=0.02)

Grade 3 Leak Repair Failure Rate

(N=58): decreased from 18% to 7%

Overall Repair Failure Rate (N=551):

decreased from 2% to 1%

Grade 3 Leak Repair Failure Rate

(N=83): decreased from 9% to 2%

Endoscopic series

2010 - 2017Microscopic series

1998 - 2006

The Learning Curve Continues

Team Approach for Pituitary Adenomas

DiagnosisPost-op follow-up Surgery

Radio-surgery

BLAMedical Therapy

Disease Recurrence

Primary careEndocrinologyNeurosurgeryDxic NeuroRadNeuro IRNeuro-ophthalmology

NeurosurgeryOtolaryngologyEndocrinologyNeuropathology

NeurosurgeryOtolaryngologyEndocrinologyPrimary careNeuropsych

EndocrinologyNeurosurgeryDxic NeuroRadNeuro IRNeuropsychMedical oncology

EndocrinologyMedical oncology

Radiation OncologyNeurosurgeryDxic NeuroRad

EndocrinologyEndocrine SurgPathology

Long-term follow-up

EndocrinologyPrimary careNeurosurgeryDxic NeuroRadNeuropsych

Conclusions

• With growing experience using the endoscopic technique, there has

been incremental increase in aggressiveness of tumor resection at

many centers

• With improved understanding of complex cavernous sinus anatomy,

surgical remission rates of invasive tumors will likely improve further

• Careful balance of striving for remission and complication

avoidance is needed

• Multi-disciplinary approach essential for optimal decision making and

multimodality care including hormonal therapies and radiotherapy

pituitary adenoma surgery: complication avoidance while ... · •selective tumor removal...

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