LARYNGEAL TRANSPLANTATION

Department of Otorhinolaryngologyand Head & Neck SurgerySestre milosrdnice hospitalZagreb

mr.sc. Dražen Shejbalmr.sc. Mirko Ivkić

LIVER, LUNG, HEART….

LARYNX: QUALITY OF LIFE

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

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

PIONEERS

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

Tehnical limitations, non selective immunosuppresion, ethical concerns

1987; Marshall Strome and coll.

• Revascularisation

• Reinnervation

• Rejection

• Preservation

• Ethic consideration ( 100.000$)

REVASCULARISATION

• 45 min

• superior thyroid a. provides > 80% of blood supply

• Larynx with thyroid gland

• 3 phase study of revascularisation

SEPSIS-CANCERRECCURENCE

REJECTION

IMMUNOSUPPRESSION

IMMUNOSUPPRESSION

• Larynx and trachea- susceptible to rejection much like other tissues

• Mucosa is the major antigenic structure

• Cartilage is only midly immunogenic

REJECTION

• MUROMONAB CD 3

• CYCLOSPORINE

• METHYLPREDNISOLONE

• MYCOPHELONATE MOFETIL

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, London, United Kingdom.• 274• cumulative risks of tumor development were

18% 10 years 50% 20 years.

• Skin tumors were the most common• lymphoma, renal, bladder, and bronchial

carcinoma.

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.

Head and neck cancer in cardiothoracic transplant recipients.

Pollard JD, Hanasono MM, Mikulec AA, Le QT, Terris DJLaryngoscope. 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

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

IMMUNOSUPPRESSION DISCUSSION

• Immunosuppression increased cancer risk

• “homming”

• Larynx transplantation: time is on our side

• Modern immunosuppression

REINNERVATION

• Laryngeal synkinesis- generalized axon regrowth: non-specific reinnervation of both adductor and abductor intrinsic musculature

• Sensory reinnervation for swallowing and airway protection

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

•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

REINNERVATION BANKING

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

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

PRESERVATION

• D uration

• U seful

• R educes swelling

• E lectrolyte balance

• X factor

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?

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

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

LARYNGEAL TRANSPLANTATION

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

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

“ HELLO !?”

• “LEFT RECCURENT NERVE OF THE TRANSPLANT WAS REINNERVATED BY THE PATIENT’S SMALL REGIONAL MOTOR NERVES”

• NORMAL RANGE- 36 MONTHS

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

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

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

ETHIC´S CANCEROPHOBIA

• Vital and non vital

• ESSENTIAL AND NOT ESSENTIAL

• SPEAK = HUMAN