Management of the Salivary Glands and Facial Nerve in Face Transplantation.

BACKGROUND: Since the first face transplant in 2005, 35 cases have been performed worldwide with acceptable graft survival and satisfactory return of function and appearance. With increasing experience, it is emerging that the salivary glands can contribute to the challenges encountered in the perioperative period. METHODS: A comprehensive review of the literature regarding management of the salivary glands and facial nerve in facial transplantation was performed. Data gathered included inclusion or exclusion of submandibular and parotid glands in the recipient and allograft, extent of mucosal inclusion in the allograft, salivary complications and treatment, level and method of facial nerve repair, and motor nerve outcomes. RESULTS: Information on salivary gland management was available for 25 cases. Undesirable salivary events were documented in 12 cases (48 percent). The source of complications was the parotid in five cases (42 percent), a combination of the parotid and submandibular glands in three cases (25 percent), and minor salivary glands in four cases (33 percent). Postoperative botulinum toxin injections resolved salivary collections in four cases. Facial nerve continuity was restored at the level of the trunk/primary divisions (66 percent) or the terminal branches (34 percent), with inclusion of the whole parotid dictating a trunk repair and exclusion of the parotid dictating a terminal branch repair. CONCLUSIONS: The salivary glands warrant increased attention in surgical planning and postoperative care. Exclusion of the salivary glands from the facial allograft with repair of the terminal branches of the facial nerve appears to be preferable. Botulinum toxin should be considered for prophylaxis and treatment of salivary collections. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Treatment of severe keratoconjunctivitis sicca by parotid duct transposition after tympanic neurectomy in rabbits.

PURPOSE: To investigate the feasibility of parotid duct transposition after tympanic neurectomy to treat severe keratoconjunctivitis sicca (KCS) in rabbits. METHODS: Thirty rabbits were divided into three groups in experiment 1. One eye was operated on, and the contralateral eye served as the control. In the KCS group, the lacrimal gland, harderian gland, and nictitating membrane were removed. In the group with parotid duct transposition (DT), the parotid duct was transposed into the lower conjunctival fornix. In the group with parotid duct transposition after tympanic neurectomy (DTTN), the tympanic nerve was resected in addition to parotid duct transposition. Schirmer test was performed and density of corneal staining was determined monthly after surgery, and goblet cell density was measured at postoperative month 3. In experiment 2, the tympanic nerve was resected on one side in 12 rabbits. Both sides of the parotid gland were resected for histopathology at intervals of 2 months to 1 year after surgery. RESULTS: Tear secretion from operated eyes at rest increased significantly after surgery in the treatment groups compared with the KCS group. Tear secretion from operated eyes after chewing was significantly lower in the DTTN than in the DT group. The corneal staining scores were higher in the operated than in the control eyes of the three groups, without significant difference among the operated eyes. Parotid gland atrophy on the operated side occurred at postoperative month 4 and recovered to normal 1 year after surgery. CONCLUSIONS: Parotid duct transposition after tympanic neurectomy could effectively reduce gustatory epiphora but may be insufficient to promote ocular surface health.

Face transplant graft procurement: a preclinical and clinical study.

BACKGROUND: Most articles on face composite tissue allotransplantation have considered ethical and immunologic aspects. Few have dealt with the technical aspects of graft procurement. The authors report the technical difficulties involved in procuring a lower face graft for allotransplantation. METHODS: After a preclinical study of 20 fresh cadavers, the authors carried out an allotransplantation of the lower two-thirds of the face on a patient in January of 2007. The graft included all the perioral muscles, the facial nerves (VII, V2, and V3) and, for the first time, the parotid glands. RESULTS: The preclinical study and clinical results confirm that complete revascularization of a graft consisting of the lower two-thirds of the face is possible from a single facial pedicle. All dissections were completed within 3 hours. Graft procurement for the clinical study took 4 hours. The authors harvested the soft tissues of the face en bloc to save time and to prevent tissue injury. They restored the donor's face within approximately 4 hours, using a resin mask colored to resemble the donor's skin tone. All nerves were easily reattached. Voluntary activity was detected on clinical examination 5 months postoperatively, and electromyography confirmed nerve regrowth, with activity predominantly on the left side. The patient requested local anesthesia for biopsies performed in month 4. CONCLUSIONS: Partial facial composite tissue allotransplantation of the lower two-thirds of the face is technically feasible, with a good cosmetic and functional outcome in selected clinical cases. Flaps of this type establish vascular and neurologic connections in a reliable manner and can be procured with a rapid, standardized procedure.

Transplantation of the major salivary glands.

BACKGROUND: In absolute aqueous-deficient dry eye, severe signs and symptoms may persist despite punctal occlusion and frequent application of artificial tear substitutes. In this group of patients the three major salivary glands, the parotid, the submandibular and the sublingual gland, have been used to lubricate the ocular surface. MATERIAL AND METHODS: A PubMed search was performed using the keywords 'dry eye, major salivary glands, parotid gland, parotid duct, sublingual gland, submandibular gland (SMG), transposition, transplantation' to identify the current literature on major salivary gland transplantation. The surgical procedures are described, their principle advantages and disadvantages and the published results are analyzed. RESULTS: To use the parotid gland as a source of substitute lubrication its secretory duct is transposed to the lower conjunctival fornix. The procedure results in a purely serous secretion and severe gustatory reflex epiphora. Parts of the sublingual gland, which produces a mucoserous secretion, have been transplanted into the subconjunctival space. Since the graft is left without a direct vascularisation, it frequently becomes non-functional. The SMG finally produces a more tear-like, seromucinous secretion. It is transferred as a free, denervated graft to the temporal fossa, where a microvascular anastomosis with the temporal artery and vein is established. Graft survival in the long term is 72%. Graft viability is associated with a significant improvement of Schirmer's test, break-up time, rose bengal staining and symptoms. In 38% of eyes with a viable graft, salivary epiphora results, which is independent of gustatory stimuli. Since the salivary tear film is substantially hypoosmolar, microcystic epithelial oedema can result and subsequent corneal transplantation remains unsuccessful. CONCLUSION: Of the three major salivary glands, the parotid and the SMG have been used successfully to provide substitute lubrication in severely dry eyes. The surgical technique varies significantly in terms of complexity and reversibility. While the procedures are capable of improving comfort, due to the salivary character of the new tear film subsequent ocular surface reconstruction remains unsuccessful.

Surgical algorithm for management of HIV lipodystrophy.

BACKGROUND: The accepted standard for treatment of human immunodeficiency virus disease, highly active antiviral therapy, may cause significant side effects, such as facial lipoatrophy and lipodystrophy. Facial wasting or a buffalo hump deformity may be pathognomonic for treated human immunodeficiency virus disease. In addition to facial wasting, cystic parotid degeneration may further distort the face. The authors outline the defects as a series of triangles defined by anatomical boundaries. METHODS: In a group of 27 patients, 17 were treated for buffalo hump (three isolated and 14 with associated facial wasting). Another 10 patients were treated for isolated facial wasting. RESULTS: The 14 patients who underwent liposuction of the buffalo hump with subsequent injection of the aspirate into the face had approximately 40 to 50 percent of the grafts survive. Recurrent or severely fibrous humps were treated with ultrasound-assisted liposuction. In six patients, autografts to the lypoatrophic face were utilized. Two patients undergoing gynecomastia reduction had successful grafting with the resected breast. Three patients with cystic degeneration of the parotid underwent superficial parotidectomy with rotation or grafting of the parotid into the defect, for a total of six individual procedures. CONCLUSION: The authors present an algorithm for treatment of buffalo hump and facial wasting deformities associated with human immunodeficiency virus lipodystrophy syndrome, with an emphasis on long-term results with autogenous tissue.

Parotid gland tissue is able partially to assume pituitary functions under the influence of hypothalamic factors: in vivo and in vitro studies.

To test whether salivary tissue can secrete pituitary hormones, female Sprague-Dawley rats were hypophysectomized (hypox) and the following were transplanted to the sella turcica: parotid gland (group 3, n=33), adrenal gland (group 4, n=30), muscle (group 5, n=24). Group 2 (n=21) had the sella turcica filled with dentist's cement. In addition a group of rats (group 1, n=22) remained intact as controls. All groups were followed for 8 months. Daily vaginal smears showed normal cyclicity in controls and constant dioestrus in all hypox groups. Blood samples, taken once every 30 days before and after LHRH stimulation, showed significantly lower (P<0.001) plasma LH values in all hypox groups compared with controls. In group 3, a gradual and significant increase (P<0.05) was observed in the LH response to LHRH in parallel with a partial recovery of oestrous smears. No LH modification was observed in the other hypox groups. Plasma prolactin (PRL) levels were also very low in all hypox groups and were unaltered throughout the study. At the end of the experiments, half the animals were killed by decapitation and the hypothalamic-pituitary areas carefully dissected, homogenized and analysed for LH and PRL content. The remaining animals were perfused with 4% paraformaldehyde to obtain fixing of the whole body tissues. Hypothalamic and transplant areas were carefully dissected, frozen, cut and submitted to immunochemical procedures. LH content in the graft of group 3 animals was markedly (P<0.001) lower than in the control pituitary, but significantly higher (P<0.05) than in the other hypox groups. Immunochemistry showed LH and PRL positive cells in the graft of group 3 animals, whereas neither positive cells, nor LH content were observed in the parotid gland in situ. Experiments were completed with in vitro cultures of parotid glands in the presence or absence (controls) of synthetic hypothalamic hormones or rat hypothalamic extracts. After 1.5 weeks of culture, a significantly higher LH concentration (P<0.05) was observed in the wells treated with synthetic hypothalamic hormones (216+/-46 pg/ml vs 41+/-6 pg/ml in controls). When hypothalamic extracts were used, the LH levels increased more markedly (1834+/-190 pg/ml vs 36+/-6 pg/ml in controls) and those values were maintained during 3 weeks of culture. Immunostaining of these cultures showed a positive LH reaction in the epithelial cells found in the hypothalamic extract-treated wells. Both in vivo and in vitro studies confirm the transdifferentiation of parotid gland tissue to pituitary hormone-producing cells under hypothalamic influence.

Acquisition of cholinergic and peptidergic properties by sympathetic innervation of rat sweat glands requires interaction with normal target.

The sweat glands, a target of cholinergic sympathetic neurons, were replaced with parotid gland, a target of noradrenergic sympathetic neurons, in neonatal rats. This transplantation paradigm allowed sympathetic neurons that would normally innervate the sweat glands and develop a cholinergic phenotype to innervate the parotid gland instead. The innervation of the transplanted parotid gland did not develop a cholinergic phenotype, as assessed by choline acetyltransferase activity and acetylcholinesterase immunoreactivity, but continued to express intense catecholamine fluorescence. In addition, immunoreactivity for vasoactive intestinal peptide, normally expressed by the sympathetic innervation of the sweat glands but not the parotid, was observed in only a small percentage of the parotid-associated fibers. These results suggest that cellular interactions between neurons and their targets play an important role in the differentiation of mature neurotransmitter and neuropeptide phenotypes in vivo.

Adrenocortical function in hypophysectomized dogs with parotid gland transplants in direct contact with the basal hypothalamus.

Adrenocortical activity was studied in three groups of dogs: control-normal, hypophysectomized (hypox), and dogs with a piece of parotid gland grafted into the sella turcica immediately after removal of the whole hypophysis (hypox + graft). Cortisol plasma level (Fk) was estimated by the competitive protein binding method. The mean base-line Fk for 21 normal dogs was 0.8 +/- 0.1 microgram/dl; for 12 hypox dogs 0.03 +/- 0.01 microgram/dl, and for hypox + graft dogs 0.5 +/- 0.2 microgram/dl. After mild or severe stresses the normal and hypox + graft dogs showed an increment in Fk; hypox dogs showed no change. Adrenal glands of hypox dogs revealed striking diminution in fasciculata and reticularis layers, whereas hypox + graft dogs approached normal. Light microscopy studies of the parotid gland graft showed signs of cellular differentiation. Groups of proliferating cells forming follicular structures were present mainly in the part of the parotid tissue closely associated to third ventricle presenting different staining affinities.

A follow-up investigation of patients who have had parotid duct transplantation surgery to control drooling.

Reports concerning surgical techniques to help combat the problem of drooling not only are new and limited, but few contain postsurgical follow-up information. In this study, the parents of parotid duct transplant patients rated or described particular aspects of their child's drooling or conditions associated with the drooling before and after surgery. Specific presurgical lingual patterns of these patients, as noted from cinefluorography analysis, are also reviewed.

Results of the Wilke operation to stop drooling in cerebral palsy.

Bilateral submaxillary gland excision and posterior transplantation of the elongated parotid ducts (as advocated by Wilkie) has proved to be an excellent procedure in the surgical treatment of drooling. I report a series of 20 patients who had excellent results from this, with amelioration of the drooling and minimal postoperative complications.

Histo-physiological study of hypophysectomized dogs in which the hypophysis was replaced by parotid gland.

This work is an attempt to repeat and confirm the results published by Alvarez-Buylla et al., concerning to hypophysectomy and transplant in salivary gland in dogs. It was found that the survival time was longer in the hypophysectomized-transplanted animals than in those merely hypophysectomized. The 131I uptake by the thyroid of transplanted dogs was lower than by normal dogs, but higher than by the hypophysectomized ones. The histological examination of the hypothalamic-hypophyseal region in both groups of operated animals showed remnants of pars tuberalis cells. The graft of the parotid gland became vascularized exhibiting dilated tubules containing PAS positive granules. An atrophy of thyroid and adrenal glands was also observed. Primordial follicles, follicles in development and cell cords could be found in the ovary of all transplanted animals; in some dogs corpus luteum could also be observed. These results suggest that the transplanted gland in some way provides conditions for the remnant of the hypophyseal cells to perform their function.

Histological study of the operative zone in dogs with parotid gland grafts in the sella turcica.

No remnants of adenohypophyseal tissue were found in 83% of the 70 dogs studied; in 17% of the animals remnants amounting to from 1 to 3% of normal hypophyseal tissue were found. These traces showed significant histological and cytological changes, and were most frequently found located on the floor of the sella turcica at some distance from their usual site. It is doubtful whether these residua have any functional significance, since the hypophysectomized dogs with such remnants had a survival time that corresponded to that of dogs with total hypophysectomy (6 months). The microscopic structure of the fragment of transplanted parotid (salivary gland) presents rich vascularization, changes in cellular distribution and a loss of the excretory duct. A better histological aspect was observed in the transplanted cells of the dogs with longer survival time. An important correlation exists between functional behavior of the operated animals and the histological state of the transplanted parotid tissue.