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

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  • LARYNGEAL TRANSPLANTATIONDepartment of Otorhinolaryngologyand Head & Neck SurgerySestre milosrdnice hospitalZagreb

    mr.sc. Draen Shejbalmr.sc. Mirko Ivki

  • 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 1960s- Ogura, Takenouchi, and Silver- Vary vascular reanastomosis, reimplantation, and orthotopic canine transplants

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

  • Tehnical limitations, non selective immunosuppresion, ethical concerns

  • 1987; Marshall Strome and coll.RevascularisationReinnervationRejectionPreservationEthic consideration ( 100.000$)

  • REVASCULARISATION

    45 minsuperior thyroid a. provides > 80% of blood supply Larynx with thyroid gland3 phase study of revascularisation

  • SEPSIS-CANCERRECCURENCEREJECTIONIMMUNOSUPPRESSION

  • IMMUNOSUPPRESSIONLarynx and trachea- susceptible to rejection much like other tissuesMucosa is the major antigenic structureCartilage is only midly immunogenic

  • REJECTIONMUROMONAB CD 3CYCLOSPORINEMETHYLPREDNISOLONEMYCOPHELONATE 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.

    274cumulative 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 risk4.1% 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. 2000Division 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 performed11% non-lymphomatous malignancies51% head and neck96% 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 riskhommingLarynx transplantation: time is on our sideModern immunosuppression

  • REINNERVATIONLaryngeal 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 CARTILAGEBRANC. 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

  • PRESERVATION45 minutesHeparinized saline with cold: 3 6 hoursHypothermic perfusion techinques: 48 hours infinitely more complex, introducing the potential for mechanical failure, incrased incidence of infection

  • PRESERVATIOND urationU sefulR educes swellingE lectrolyte balanceX factor

  • ETHICAL CONSIDERATIONA question of acceptable risk versus potential benefit Transplanting a non-vital organWho is financially responsible- can the government or private insurers regualte?

  • 100.000 $

    If rejection occurred, transplant could be removed without great risk of deathSafety 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 TRANSPLANTATIONall expected complications were successfully overcome and the expected failures did not occur.

  • LARYNX IS A MISTERYThird postoperative day: HELLOAt one month both vocal fold was lateral, a voice was breathy , generatered by the aryepiglottic folds6 MONTHS A BOTH FOLDS WAS IN THE MIDLINE

  • HELLO !?LEFT RECCURENT NERVE OF THE TRANSPLANT WAS REINNERVATED BY THE PATIENTS SMALL REGIONAL MOTOR NERVES

    NORMAL RANGE- 36 MONTHS

  • RESPIRATION AND SWALLOWINGInitial plane: close tracheal stoma year after laser chordotomy of the left vocal foldAttempts to provide self closing valve were not succesfulRight side trachea- touch but not cughLeft no response3 months glottis and supraglotis were sensitive to touch, initiated a severe cughPurposeful swallowing and full oral alimentation returned soon thereafterTaste and smell returned

  • THYROID EFFECTS83 % was in the donors thyroid lobes17 % in the patientsDonors parathyroid glands were functional after a 10 hour period of ischemiaPatients 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

  • ETHICS CANCEROPHOBIAVital and non vital ESSENTIAL AND NOT ESSENTIAL SPEAK = HUMAN