MUC1 and Polarity Markers INADL and SCRIB Identify Salivary Ductal Cells.

Current treatments for xerostomia/dry mouth are palliative and largely ineffective. A permanent clinical resolution is being developed to correct hyposalivation using implanted hydrogel-encapsulated salivary human stem/progenitor cells (hS/PCs) to restore functional salivary components and increase salivary flow. Pluripotent epithelial cell populations derived from hS/PCs, representing a basal stem cell population in tissue, can differentiate along either secretory acinar or fluid-transporting ductal lineages. To develop tissue-engineered salivary gland replacement tissues, it is critical to reliably identify cells in tissue and as they enter these alternative lineages. The secreted protein α-amylase, the transcription factor MIST1, and aquaporin-5 are typical markers for acinar cells, and K19 is the classical ductal marker in salivary tissue. We found that early ductal progenitors derived from hS/PCs do not express K19, and thus earlier markers were needed to distinguish these cells from acinar progenitors. Salivary ductal cells express distinct polarity complex proteins that we hypothesized could serve as lineage biomarkers to distinguish ductal cells from acinar cells in differentiating hS/PC populations. Based on our studies of primary salivary tissue, both parotid and submandibular glands, and differentiating hS/PCs, we conclude that the apical marker MUC1 along with the polarity markers INADL/PATJ and SCRIB reliably can identify ductal cells in salivary glands and in ductal progenitor populations of hS/PCs being used for salivary tissue engineering. Other markers of epithelial maturation, including E-cadherin, ZO-1, and partition complex component PAR3, are present in both ductal and acinar cells, where they can serve as general markers of differentiation but not lineage markers.

Neurturin-containing laminin matrices support innervated branching epithelium from adult epithelial salispheres.

Cell transplantation of autologous adult biopsies, grown ex vivo as epithelial organoids or expanded as spheroids, are proposed treatments to regenerate damaged branching organs. However, it is not clear whether transplantation of adult organoids or spheroids alone is sufficient to initiate a fetal-like program of branching morphogenesis in which coordinated branching of multiple cell types including nerves, mesenchyme and blood vessels occurs. Yet this is an essential concept for the regeneration of branching organs such as lung, pancreas, and lacrimal and salivary glands. Here, we used factors identified from fetal organogenesis to maintain and expand adult murine and human epithelial salivary gland progenitors in non-adherent spheroid cultures, called salispheres. These factors stimulated critical developmental pathways, and increased expression of epithelial progenitor markers such as Keratin5, Keratin14, FGFR2b and KIT. Moreover, physical recombination of adult salispheres in a laminin-111 extracellular matrix with fetal salivary mesenchyme, containing endothelial and neuronal cells, only induced branching morphogenesis when neurturin, a neurotrophic factor, was added to the matrix. Neurturin was essential to improve neuronal survival, axon outgrowth, innervation of the salispheres, and resulted in the formation of branching structures with a proximal-distal axis that mimicked fetal branching morphogenesis, thus recapitulating organogenesis. Epithelial progenitors were also maintained, and developmental differentiation programs were initiated, showing that the fetal microenvironment provides a template for adult epithelial progenitors to initiate branching and differentiation. Further delineation of secreted and physical cues from the fetal niche will be useful to develop novel regenerative therapies that instruct adult salispheres to resume a developmental-like program in vitro and to regenerate branching organs in vivo.

Facial nerve function after partial superficial parotidectomy: An 11-year review (1987-1997).

Permanent facial nerve dysfunction is a potential complication of every parotid surgery. Partial superficial parotidectomy, a conservative resectioning that requires neither dissection of the full facial nerve nor excision of the superficial lobe, produces lower rates of facial nerve dysfunction and soft tissue deformity than the traditional method. This report describes a single surgeon's experience with partial superficial parotidectomy from 1987 to 1997. Fifty-nine patients with mobile, benign, and low-grade malignant tumors, limited to the superficial lobe, underwent partial superficial parotidectomy with selective nerve dissection. Adequate margins were obtained, based on the premise that the tumor-to-nerve margin is often the true one. No patients had permanent nerve paralysis or paresis, and only 10 incurred transient facial nerve paresis. Age, histology, and sex were not significant factors in postoperative facial nerve function. No patients had recurrences.

Facial nerve monitoring in parotid surgery: the standard of care?

Recent reports have suggested that the incidence of permanent facial nerve paralysis or paresis after surgery for benign parotid tumors is between 3% and 5%. The intraoperative use of nerve-integrity monitors has been advocated to reduce the incidence of facial nerve paralysis. The purpose of this study was to compare postoperative facial nerve function after monitored and unmonitored parotid surgical procedures. The charts of 69 consecutive patients with parotid lesions who underwent surgery from 1987 to 1996 were retrospectively surveyed. Sixteen high-risk patients were excluded from the study. The study group consisted of 53 patients (33 unmonitored and 20 monitored) who underwent lateral parotidectomy for mobile tumors of the superficial lobe of the parotid gland. No patient demonstrated permanent facial paralysis. In 9 patients (17%), transient nerve paralysis developed: 5 (15%) of the 33 patients who underwent lateral parotidectomy without the use of a nerve-integrity monitor and 4 (20%) of the 20 patients who underwent lateral parotidectomy with the use of a nerve-integrity monitor. Nerve-integrity monitoring is optional for mobile parotid tumors of the superficial lobe.

Failure of radiation therapy in stage I and II glottic squamous cell carcinoma.

Radiation therapy is frequently employed for Stage I and II lesions of the glottis. This study of the clinical course of patients with such cancers of the glottis was undertaken in an attempt to determine the period of greatest risk for recurrence and the most common location of recurrence, which can have treatment implications.

Adenoid cystic carcinoma of the minor salivary glands.

Management of minor salivary gland adenoid cystic carcinoma is a controversial problem. Few clinicians obtain adequate experience in the treatment of this disease, which is often frustrated by early and late distant metastases. Fourteen cases of minor salivary gland adenoid cystic carcinoma recorded in the Delaware Registry over a 20-year period (1968 to 1988) were reviewed retrospectively. These cases were evaluated for their duration of symptoms; size, location, and histologic subtype of the lesion; perineural invasion; lymph node metastases; and treatment to determine the relationship of these factors to survival. Location and histologic subtype of the lesion and duration of symptoms were found to have a more significant impact on survival than size of the lesion, perineural invasion, or lymph node metastases. Surgery is the mainstay of therapy for minor salivary gland adenoid cystic carcinoma, with resection that includes disease-free margins but spares function being advocated. Although adjunctive radiation therapy has not been shown to increase survival, it is reasonable in lesions with perineural invasion and/or lymph node metastases.

The tonsil and adenoid controversy.

This paper will review the anatomy, histology, immunology, bacteriology, indications, complications, and trends in modern tonsil and adenoid surgery. Information on tonsils and adenoids, both in their normal and abnormal states, has proliferated over the last two decades. A considerable variation in opinion remains on the subject. Historical fluctuations in the indications for tonsil and adenoid surgery have resulted in swings in the quantity of surgery performed. This paper will attempt to bring contemporary information together to provide reasonable guidelines for management of disease tonsils and adenoids.

Suppressed sneezing as a cause of hearing loss and vertigo.

Two cases of inner ear injury caused by suppressed sneezing are described. One patient experienced vestibular symptoms in the form of reflexogenic vertigo that was relieved by surgical section of the tensor tympani tendon. The other patient had a sudden severe permanent sensorineural hearing loss. It is proposed that the aerodynamic pressure increase associated with suppressed sneezing is transmitted via the eustachian tube to cause an implosive fistula of either the round or oval window with injury to the membranous labyrinth.

Acute bilateral sequential vestibular neuritis.

Two cases of bilateral sequential vestibular neuritis demonstrate the significant persistent disequilibrium that follows involvement of the second ear. The etiology for the loss of vestibular function is postulated to be a viral neuritis. Vestibular suppressant drugs are helpful in relieving nausea and vomiting in the acute phase of the disease; however, they are of no therapeutic value for the protracted disequilibrium following involvement of the second ear. An awareness of this disorder as a disease entity will minimize diagnostic and therapeutic frustration on the part of the physician and provide a realistic prognosis for the patient. Unfortunately, the prognosis is for permanent but somewhat lessening disequilibrium with the passage of time and depends in great part on the subject's age.