Laryngeal transplantation

1. LARYNGEAL
TRANSPLANTATION
Department of Otorhinolaryngology
and Head & Neck Surgery
Sestre milosrdnice hospital
Zagreb
mr.sc. Dražen Shejbal
mr.sc. Mirko Ivkić

2. LIVER, LUNG, HEART….

3. LARYNX: QUALITY OF LIFE

4. POTENTIAL IMPACT
- 2,000 total laryngectomies
(majority of these patients probably not candidates
for laryngeal transplantation)
- Benign laryngeal neoplasms are uncommon
- Laryngeal trauma resulting in laryngectomy
or incompetent larynx even less common

5. Boles- 1960 applied objective criteria for
laryngeal transplantation
1. phonation dependent on pulmonary airflow
and vocal fold motion,
2. degluttion without aspiration
3. functional oral and nasal passages enabling
olfactory and gustatory sensation
• Late 1960’s- Ogura, Takenouchi, and Silver-
Vary vascular reanastomosis, reimplantation,
and orthotopic canine transplants

6. PIONEERS
• February 11, 1969-
Klyuskens and
Ringoir attempted
human laryngeal
transplant in
Belgium-

7. Tehnical limitations, non selective immunosuppresion, ethical concerns

8. 1987; Marshall Strome and coll.
• Revascularisation
• Reinnervation
• Rejection
• Preservation
• Ethic consideration ( 100.000$)

9. REVASCULARISATION
• 45 min
• superior thyroid a. provides > 80% of
blood supply
• Larynx with thyroid gland
• 3 phase study of revascularisation

12. IMMUNOSUPPRESSION
SEPSIS-CANCER
RECCURENCE
REJECTION

13. IMMUNOSUPPRESSION
• Larynx and trachea- susceptible to
rejection much like other tissues
• Mucosa is the major antigenic structure
• Cartilage is only midly immunogenic

14. REJECTION
• MUROMONAB CD 3
• CYCLOSPORINE
• METHYLPREDNISOLONE
• MYCOPHELONATE MOFETIL

15. Malignant disease in patients with long-term renal
transplants.
Gaya SB, Rees AJ, Lechler RI, Williams G, Mason PD.
Transplantation. 1995
Department of Medicine, Royal Postgraduate Medical School,
Hammersmith Hospital, L • 274 ondon, United Kingdom.
• cumulative risks of tumor development were
18% 10 years
50% 20 years.
• Skin tumors were the most common
• lymphoma, renal, bladder, and bronchial
carcinoma.

16. Malignant neoplasms following cardiac transplantation.
Curtil A, Robin J, Tronc F, Ninet J, Boissonnat P,
Champsaur G.
Eur J Cardiothorac Surg. 1997
Service de Chirurgie Thoracique et Cardiovasculaire C, Louis Pradel
Cardiovascular Hospital, Lyon, France
• 6.7% neoplasms developed in 18 of the 267 patients
at risk
• 4.1% lung neoplasms (especially adenocarcinoma)
11 of 268 patients,
• 78% significant smoking history (14)
• high incidence of lung neoplasms (especially
adenocarcinoma) which can be correlated with a
heavy cigarette use in the study population.

17. Head and neck cancer in cardiothoracic transplant
recipients.
Pollard JD, Hanasono MM, Mikulec AA, Le QT, Terris DJ
Laryngoscope. 2000
Division of Otolaryngology--Head and Neck Surgery, Stanford
University Medical Center, California
• 1069 heart (n = 855), heart/lung (n = 111), and lung (n = 103)
transplants were performed
• 11% non-lymphomatous malignancies
• 51% head and neck
• 96% cutaneous in origin
80% squamous cell carcinoma
16% were basal cell carcinoma
• 68% of cancer patients were smokers and
24% had significant alcohol use
• 55% of cancer patients died as a direct result of cancer

18. Liver transplantation for hepatocellular carcinoma: a
registry report of the impact of tumor characteristics on
outcome.
Klintmalm GB.
Ann Surg. 1998
Department of Surgery, Baylor University Medical Center, Dallas, Texas
• 422 patients
• 190 (46%) have died, 99 free of tumor and 91 with
tumor.
• overall patient survival was 44% at 5 years.
• 42% - recurrence in liver
28% lungs
• 26% hepatitis B
33% hepatitis C.
• Current policy in US: + HIV test does not exclude
transplantation

19. IMMUNOSUPPRESSION
DISCUSSION
• Immunosuppression increased cancer risk
• “homming”
• Larynx transplantation: time is on our side
• Modern immunosuppression

20. REINNERVATION
• Laryngeal synkinesis- generalized axon
regrowth: non-specific reinnervation of
both adductor and abductor intrinsic
musculature
• Sensory reinnervation for swallowing and
airway protection

21. Risk of synkinesis
is eliminated by
reinnervating the abductor
and adductor individually

23. •Average lenghts of the abductor and
adductor 5,4 – 5,6, min. diameter 0,5 mm
POST. CRICOARYTENOID M. AND
ARYTENOID CARTILAGE
BRANC. TO INTERARYTENOID M.
INFERIOR CRICOTHYROID LIG.
BRAN. TO POSTERIOR
CRICOARITENOID M.
RIGHT RECCURENS N.
SCALE 1 MM

24. REINNERVATION BANKING

26. Tucker, H.M. and Rusnov, M.
Laryngeal reinnervation for unilateral vocal cord paralysis:
Long term results. Ann Otolaryngol. 1981

27. PRESERVATION
• 45 minutes
• Heparinized saline with cold: 3 – 6 hours
• Hypothermic perfusion techinques: 48
hours – infinitely more complex,
introducing the potential for mechanical
failure, incrased incidence of infection

28. PRESERVATION
• D uration
• U seful
• R educes swelling
• E lectrolyte balance
• X factor

30. ETHICAL CONSIDERATION
• A question of acceptable risk versus
potential benefit
• Transplanting a ‘non-vital’ organ
• Who is financially responsible- can the
government or private insurers regualte?

31. 100.000 $
• If rejection occurred, transplant could be
removed without great risk of death
• Safety more attainable:
1. microvascular technics
2. fiberoptic endoscopy
3. follow for early rejection

32. Potter, et al., UK survey of 372 patients
after total laryngectomy:
1. 75% would like an laryngeal
transplantation if it were safe
2. Figure remained at 50% even if there
was little chance for normal speech
3. Only 20% would accept a graft if long
term immunosuppression were required

33. LARYNGEAL
TRANSPLANTATION
all expected complications were successfully
overcome
and the expected failures did not occur.

35. LARYNX IS A MISTERY
• Third postoperative day: “ HELLO”
• At one month both vocal fold was lateral, a
voice was breathy , generatered by the
aryepiglottic folds
• 6 MONTHS A BOTH FOLDS WAS IN
THE MIDLINE

36. “ HELLO !?”
• “LEFT RECCURENT NERVE OF THE
TRANSPLANT WAS REINNERVATED
BY THE PATIENT’S SMALL
REGIONAL MOTOR NERVES”
• NORMAL RANGE- 36 MONTHS

37. RESPIRATION AND
SWALLOWING
• Initial plane: close tracheal stoma year after laser
chordotomy of the left vocal fold
• Attempts to provide self closing valve were not
succesful
• Right side trachea- touch but not cugh
• Left no response
• 3 months glottis and supraglotis were sensitive to
touch, initiated a severe cugh
• Purposeful swallowing and full oral alimentation
returned soon thereafter
• Taste and smell returned

38. THYROID EFFECTS
• 83 % was in the donor’s thyroid lobes
• 17 % in the patient’s
• Donor’s parathyroid glands were functional
after a 10 hour period of ischemia
• Patient’s parathyroid functioning normally

39. COMPLICATION
-One episode of REJECTION after 15
months ( declined quality of voice, larynx
edema)
- returned to normal within three days
- INFECTION: three episodes of
tracheobronchitis ( amoxicillin clavulonate)
- pneumocistis carinii pneumonia

40. ETHIC´S CANCEROPHOBIA
• Vital and non vital
• ESSENTIAL AND NOT ESSENTIAL
• SPEAK = HUMAN