30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Non-opioid analgesics and post-operative pain following transoral robotic surgery for oropharyngeal cancer.

OBJECTIVE: To investigate associations between multimodal analgesia and post-operative pain among patients undergoing transoral robotic surgery for oropharyngeal squamous cell carcinoma. METHODS: Records of patients who underwent surgery from 5 September 2012 to 30 November 2016 were abstracted. Associations were assessed using multivariable analysis. RESULTS: A total of 216 patients (mean age of 59.1 years, 89.4 per cent male) underwent transoral robotic surgery (92.6 per cent were human papilloma virus positive, 87.5 per cent had stage T1-T2 tumours, and 82.9 per cent had stage N0-N1 nodes). Gabapentin (n = 86) was not associated with a reduction in severe pain. Ibuprofen (n = 72) was administered less often in patients with severe pain. Gabapentin was not associated with increased post-operative sedation (p = 0.624) and ibuprofen was not associated with increased bleeding (p = 0.221). Post-operative opioid usage was not associated with surgical duration, pharyngotomy, bilateral neck dissections, tumour stage, tumour size, subsite or gabapentin. CONCLUSION: Scheduled low-dose gabapentin was not associated with improved pain control or increased respiratory depression. Ibuprofen was not associated with an increased risk of bleeding and may be under-utilised.

Characterization of a spontaneously arising murine squamous cell carcinoma (SCC VII) as a prerequisite for head and neck cancer immunotherapy.

BACKGROUND: To develop novel therapeutic approaches for patients with head and neck malignancies, poorly immunogenic murine models of squamous cell carcinoma (SCC) need to be defined. METHODS: The phenotype, growth characteristics, and responsiveness to tumor-specific T-cell transfer of a spontaneously arising murine SCC (SCC VII) were characterized. RESULTS: SCC VII expresses major histocompatibility complex (MHC) class I molecules yet is resistant to tumor-specific T-cell killing and relatively insensitive to killing mediated by lymphokine-activated killer (LAK) cells. Intradermal tumors are reproducibly established after vaccination of 5 x 10(4) cells, and systemic micrometastases are apparent after intravenous administration of 2.5 x 10(4) cells. Immunotherapy of 3-day lung metastases using tumor-specific T cells and systemic interleukin-2 (IL-2) was ineffective in reducing the number of metastases in vivo. CONCLUSIONS: SCC VII is a poorly immunogenic murine squamous cell cancer, which represents an ideal model for preclinical testing of immunotherapeutic approaches for patients with SCC of the upper aerodigestive tract.

Endoscopic transnasal pituitary surgery: report on 180 cases.

The endoscopic transnasal approach is an evolving technique for treating lesions in the sella turcica. Since this method was introduced at our institution 4 years ago, the majority of transsphenoidal procedures are performed with it. The records of all patients having endoscopic transnasal hypophysectomy at the Mayo Clinic during the last 4 years were reviewed retrospectively. The criteria analyzed were safety, functional and cosmetic outcome, and complications. During the 4-year period, the operative procedure was modified to improve operative exposure and safety. The results of our review showed a significant decrease in length of hospital stay, reduced operative time, reduced need for nasal packing, and elimination of a sublabial incision. The complication rate was equivalent to that reported for the traditional transseptal transsphenoidal approach. As the neurosurgeons at our institution gained experience with this approach, an increasing number of pituitary microadenomas were resected safely and successfully. In addition, because of the limited septal dissection, this approach is particularly helpful for revision operations. This approach also can be used for the full range of pituitary lesions and in conjunction with adjunctive techniques, including frontal craniotomy and gamma-knife irradiation. Currently, the endoscopic transsphenoidal approach is the method preferred for surgically treating pituitary lesions in adults at our institution.

Epstein-Barr virus DNA is not increased in tonsillar carcinoma.

Epstein-Barr virus (EBV) is a known oncogenic virus associated with a wide variety of cancers, including nasopharyngeal carcinoma. Waldeyer's ring, a collection of lymphoid tissues, includes the nasopharynx, pharyngeal, and lingual tonsils. To determine if EBV plays a causative role in carcinomas arising from other tissues in Waldeyer's ring, we examined pharyngeal tonsillar carcinomas for evidence of EBV infection. As previously reported, DNA was extracted from 53 consecutive tonsil cancers, as well as from age- and gender-matched non-cancerous tonsillectomy specimens. Three different sets of primers for discrete exons of EBV were then used to determine if active or latent EBV infection was expressed in the extracted DNA using the polymerase chain reaction (PCR). All positive bands were then sequenced to confirm the presence of amplified EBV fragments. None of the samples showed evidence for active EBV infection. In primers demonstrating latent infection, 1 of 53 (1.9%) of tumors were positive, versus 6 of 53 (11.3%) of the controls. These results indicate that EBV expression is not increased in DNA from tonsil cancers and that EBV infection does not have a causal relationship with tonsil cancer.

The anatomical basis of the Abbé flap.

OBJECTIVES: Objective of the study were 1) to determine the course, including specific relationship to the vermilion border, free margin of the lip, and orbicularis oris and number of the superior and inferior labial arteries, and 2) to discuss the relevance of this anatomy to design of the Abbé flap. STUDY DESIGN: Detailed anatomical dissections of the mid and lower face of injected cadaver heads. METHODS: Sixteen superior labial arteries and 15 inferior labial arteries in 9 adult cadaver heads ranging in age from 41 to 90 years were studied. RESULTS: The superior labial artery was a single vessel in all cases. At the oral commissure the vessel was superior to the vermilion border in 94% of the dissections. At the midline the vessel was within the vermilion border in 75% of dissections. The vessel was found within the orbicularis oris in 19% of dissections and between the mucosa and the orbicularis oris in 81% of dissections. The inferior labial artery was a single vessel in all dissections. Its course was variable in position relative to the vermilion border and to its take-off from the facial artery. In the central portion of the lip the vessel was found within the orbicularis oris in 13% of dissections and between the mucosa and the orbicularis oris in 87% of dissections. CONCLUSIONS: The superior labial artery is found within 10 mm of the free margin of the upper lip. The inferior labial artery is variable in its course, varying up to 15 mm from the free margin of the lower lip.

Norian craniofacial repair system bone cement for the repair of craniofacial skeletal defects.

PURPOSE: To describe the use of the Norian Craniofacial Repair System (CRS) calcium phosphate bone cement in the restoration of craniofacial skeletal defects. METHODS: Consecutive case series. RESULTS: Calcium phosphate bone cement was used to repair craniofacial skeletal defects in three patients. Indications included repair of a posttraumatic orbital floor defect causing hypo-ophthalmos, reconstruction of frontal craniotomy and temporalis muscle donor sites in a patient who had undergone resection of an invasive squamous cell carcinoma, and augmentation of a post-traumatic anterior maxillary skeletal defect. The primary outcome measure was the restoration of bony volume and support. The use of calcium phosphate bone cement in these patients was effective and without complications. CONCLUSIONS: Norian CRS calcium phosphate bone cement is useful in the repair of craniofacial skeletal defects.

Pediatric transseptal transsphenoidal pituitary surgery.

The use of the transseptal transsphenoidal approach to the pituitary gland has gained acceptance as a safe, relatively atraumatic means of removing pituitary tumors. The outcome in adult patients has been successful; however, the outcome in pediatric patients whose noses may still be developing is not well described. We reviewed the outcomes in 41 patients younger than age 18 years who underwent transseptal transsphenoidal pituitary surgery at our institution between 1986 and 1997 (20 boys and 21 girls; age, 3 to 17 years; mean age, 13.4 years). The most common diagnosis was prolactin-secreting adenoma (14 patients), followed by craniopharyngioma (7 patients). Presenting symptoms included headache (20 patients), galactorrhea (13 patients), and menstrual irregularities (11 patients). The most common early complication was transient diabetes insipidus (20 patients). No patient experienced serious bleeding at pack removal and no patient developed a cerebrospinal fluid leak postoperatively. Follow-up ranged from 3 months to 12.7 years, with 7 patients experiencing recurrent or residual disease between 6 days and 2 years after their original transseptal procedure. The most common long-term surgical complication was nasal obstruction in 5 patients, 3 of whom also complained of seasonal allergies. Four patients complained of recurrent sinus infections, and 4 patients noted an external nasal deformity as a result of the surgery.

Use of methotrexate for autoimmune hearing loss.

To assess the efficacy of low-dose methotrexate (MTX) given long-term for the treatment of autoimmune hearing loss, we performed a prospective open-label study of 11 patients with treatment-refractory autoimmune hearing loss. All patients had ongoing episodic worsening of hearing in 1 or both ears before enrollment despite traditional medical therapy. The MTX dose was 7.5 to 17.5 mg/wk. Hearing loss and vertigo were evaluated at baseline and at completion of the study. Hearing improvement was defined as an improvement in the pure tone threshold (PT) average of >10 dB or an increase in speech discrimination (SD) of >15%, whereas worsening was defined as a worsening of >10 dB in PT or a decrease of >15% in SD in at least 1 ear. The MTX was well tolerated. Among the 6 patients with Meniere's disease. 4 had improvement or resolution of vertigo, while 2 had no improvement. Disequilibrium improved in all 3 patients with Cogan's syndrome. According to the parameters defined above, hearing improved in 9 patients (82%), was unchanged in 1 patient (9%), and worsened in 1 patient (9%). Long-term low-dose MTX therapy may be a useful therapy for some patients who have hearing loss with a presumptively autoimmune-mediated component that is refractory to traditional therapies.

Exaggerated hemodynamic responses to nasal injection and awakening from anesthesia in a Cushingoid patient having transsphenoidal hypophysectomy.

A 51-year-old female patient, with an adrenocorticotrophic hormone-secreting pituitary tumor, was scheduled for transphenoidal hypophysectomy. She had a history of recent onset diabetes mellitus and a 2-year history of arterial hypertension. Despite ongoing medical therapy, preoperative blood pressure was 150-160/90-120 mm Hg. During general anesthesia, in response to perinasal infiltration with 10 ml of a solution containing lidocaine 200 mg and epinephrine 100 microg, blood pressure increased from 144/80 mm Hg to 317/175 over 3 minutes, as assessed by direct blood pressure monitoring. At the completion of the anesthetic, as the patient awakened and coughed and moved, blood pressure again increased dramatically, this time from 154/87 mm Hg to 285/170 over 3 minutes. Five months postoperatively, the patient's serum cortisol concentrations had normalized and her cuff blood pressure was 126/82, despite a reduction in her antihypertensive medications. The dramatic intraoperative blood pressure changes in this patient were attributed to the effects of hypercortisolemia on the normal physiologic responses to epinephrine and patient movement.

Transcranial-transdural real-time ultrasonography during transsphenoidal resection of a large pituitary tumor. Case report.

Ultrasonography has been used in neurosurgical operative procedures for several decades. The authors report the case of a large pituitary tumor that was subtotally resected using endoscopy via the transnasal-transsphenoidal approach, with the aid of transcranial real-time ultrasound. To our knowledge, this is the first reported case in which intraoperative transcranial-transdural real-time ultrasound was used to facilitate the resection of a skull base tumor.

Round window membrane permeability to transforming growth factor-alpha: an in vitro study.

OBJECTIVE: Recent studies have identified the capacity of transforming growth factor-alpha (TGF-alpha) to stimulate mammalian labyrinthine hair cell regeneration after acute ototoxic damage. Augmenting hair cell regeneration with such growth factors may have a role in potentiation of recovery of cochlear function after hair cell injury. Transtympanic application of aqueous solutions to the round window membrane (RWM) has proved successful as a drug delivery route. The purpose of this study was to test the permeability of the mammalian RWM to TGF-alpha in an inexpensive and reliable in vitro model. METHODS: Guinea pig RWM niches were harvested and transferred to a 2-chamber apparatus, and TGF-alpha was applied to the middle-ear side of the chamber. ELISAs of TGF-alpha were measured at intervals during a 96-hour period. RESULTS: Aliquots taken during a 96-hour interval demonstrated passage of TGF-alpha in concentrations sufficient to stimulate hair cell regrowth. CONCLUSIONS: The apparatus allows study of RWM permeability to other substances and provides a basic model for study of RWM physiology. TGF-alpha is able to pass through a mammalian RWM.

Pediatric lymphangiomas of the head and neck.

To better define the cause, presentation, diagnosis, and staging of lymphangiomas, we reviewed all cases of lymphangiomas of the head and neck region in children seen at our institution between 1986 and 1996. Sixty-seven children were identified (31 male and 36 female). Age at presentation ranged from birth to 18 years. All but 8 patients presented with an obvious mass, and 5 required tracheotomy because of airway obstruction. The most common location was the submandibular region (37%), followed by the parotid gland (31%). Treatment ranged from observation to extensive and multiple resections. Thirty-one patients underwent only 1 resection, and 2 patients received interferon as part of their treatment. Lesions involving the lip, hypopharynx and/or larynx, the tongue, and the floor of the mouth had high rates of recurrent or persistent disease. We review our experience with these difficult lesions and propose a staging system based on functional deficit, cosmetic changes, sites of involvement, and age at diagnosis.

Traumatic carotid artery dissection causing blindness.

A case of delayed postoperative visual loss due to bilateral traumatic carotid artery dissection is presented. In patients with a major craniofacial injury due to a high-speed motor vehicle accident, we suggest that carotid artery duplex ultrasonography be used in the initial evaluation for possible carotid artery dissection. Magnetic resonance imaging of the head and neck with magnetic resonance angiography should be performed subsequently if indicated. Early diagnosis and initiation of therapy can minimize complications.

Pediatric parotid masses.

OBJECTIVE: To evaluate the incidence, types, and treatment outcomes of pediatric parotid lesions. DESIGN: Retrospective case review, histological tissue review, and literature review. SETTING: Tertiary care center. PATIENTS: All patients aged 18 years and younger with parotid masses evaluated and treated at the Mayo Clinic, Rochester, Minn, from January 1, 1970, to December 31, 1997. RESULTS: Parotid masses were identified in 118 children (60 boys and 58 girls). At diagnosis, the ages of patients were from birth through 18 years, and 72 (61.0%) were aged 10 years and older. An asymptomatic mass was the most common presentation. Forty-three patients (36.4%) had infectious or inflammatory lesions, 56 (47.5%) had benign lesions, and 19 (16.1%) had malignant lesions. The most common benign lesions were pleomorphic adenoma (22.9%) and hemangioma (10.2%). The most common malignant lesions were mucoepidermoid carcinoma (6.8%) and acinic cell carcinoma (3.4%). The most common treatment was total parotidectomy (40.7%). Surgical complications included temporary facial nerve weakness in 22 (18.6%) patients, permanent facial weakness in 11 (9.3%), and permanent paralysis in 2 (1.7%). Pleomorphic adenoma recurred in 4 (14.8%) of 28 patients and mucoepidermoid carcinoma in 3 (37.5%) of 8 patients. One patient with adenoid cystic carcinoma died of the tumor. CONCLUSIONS: Although pediatric parotid masses are unusual, they can represent a variety of pathological diagnoses, including malignancy. We advocate prompt evaluation and treatment of these masses, and suggest guidelines for their management, based on diagnosis.

Preliminary comparison of the endoscopic transnasal vs the sublabial transseptal approach for clinically nonfunctioning pituitary macroadenomas.

OBJECTIVE: To assess the advantages and disadvantages of an endoscopic transnasal approach to pituitary surgery for a select group of clinically nonfunctioning macroadenomas and to compare results of this approach with the sublabial transseptal approach at a single institution. PATIENTS AND METHODS: We retrospectively reviewed the records of 26 patients with clinically nonfunctioning pituitary macroadenomas approached endoscopically and 44 matched control patients with the same tumors approached sublabially between January 1, 1995, and October 31, 1997. RESULTS: At baseline, the groups were not significantly different for age, sex distribution, number of comorbid conditions, visual field defects, degree of anterior pituitary insufficiency, or preoperative assessment of tumor volume or invasiveness. Mean (SD) operative times were significantly reduced in the endoscopic group vs the sublabial group: 2.7 (0.7) hours vs 3.4 (0.9) hours (P < .001). Postoperative assessment of surgical resection and postoperative alterations of anterior pituitary function or visual fields were not significantly different between groups, and complication rates were similar in both groups. CONCLUSION: This endoscopic transnasal approach to pituitary resection results in significantly shorter operative time without compromising the extent of tumor resection. The distinct disadvantage of this approach is an off-center view of the sella and a diminished working channel to the sella turcica. For these reasons, the endoscopic approach or its variation is an alternative to the sublabial approach but should be considered only by experienced pituitary neurosurgeons.

Relationship of human papillomavirus to Schneiderian papillomas.

OBJECTIVES/HYPOTHESIS: To classify a large group of Schneiderian papillomas (SPs) into their histologic subtypes and to determine the incidence of human papillomavirus (HPV) in each subtype. STUDY DESIGN: Pathologic review and polymerase chain reaction-based (PCR-based) examination of archived tissue. METHODS: Slides of 114 tumors diagnosed as Schneiderian, inverting, fungiform, or cylindric cell papillomas, or any associated carcinomas, were examined by a head and neck pathologist. Using PCR, consensus primers for the L1 region of HPV were used to determine the presence of HPV in the tumors. This was also performed on normal turbinate control specimens. RESULTS: Eighty-two (78%) were the inverting subtype, 21 (20%) the fungiform subtype, and 2 (2%) the cylindric cell type. Nine tumors were diagnosed as either verrucous or squamous cell carcinoma. Eighty-eight percent of the tumors had DNA of sufficient quality to be amplified using PCR. Of these, 5 of 69 (6.8%) inverting, 17 of 17 (100%) fungiform, and 0 of 2 cylindric cell papillomas were positive for HPV. One of nine (11.1%) cancers was positive for HPV. No normal turbinate tissue contained HPV. HPV types 6b and 11 accounted for all cases of fungiform papillomas. Of the five HPV-positive inverting papillomas, three had HPV type 11 and two had HPV type 16. The single carcinoma containing HPV contained HPV type 18. CONCLUSIONS: The histologic subtype of SPs is important, as their etiologies appear to be different. HPV 6b and 11 appear to be involved in all cases of fungiform papillomas but are only rarely involved in cases of inverting or cylindric cell papillomas. HPV 16 may rarely play a role in cases of inverting papillomas, and HPV 16 and 18 may be involved in a subset of cases of carcinomas originating in an inverting papilloma.

Safety of paranasal sinus surgery in patients with cystic fibrosis.

OBJECTIVE: Document the safety of paranasal sinus surgery in cystic fibrosis patients and review the changing trends in paranasal sinus surgery in the cystic fibrosis population. STUDY DESIGN: Retrospective review. MATERIALS AND METHODS: Chart review of cystic fibrosis patients who underwent paranasal sinus surgery from 1955 to 1997. RESULTS: Indications for surgery included chronic sinusitis, nasal obstruction, purulent rhinorrhea, head pain, and pyocele. Average duration of anesthesia was 2.1 hours. The complication rate from general anesthesia was zero. Excessive bleeding and significant hypoxia did not occur. CONCLUSIONS: Paranasal sinus surgery and general anesthesia can be safely performed in cystic fibrosis patients. The indications for paranasal sinus surgery are changing from symptomatic nasal obstruction to pre-lung transplantation care. Today, treatment has evolved to include placement of sinus catheters for direct topical instillation of antibiotics and consideration of maxillary and frontal sinus obliteration.

A biomechanical study of the human cricoarytenoid joint.

OBJECTIVES/HYPOTHESIS: To develop a model to investigate the biomechanics of the cricoarytenoid joint and establish stiffness, laxity, and range of motion of the cricoarytenoid joint in adult human larynges. STUDY DESIGN: Laboratory investigation of freshly frozen larynges from adult humans, measuring the stiffness, laxity, and range of motion in intact and injured cricoarytenoid joints. METHODS: Eight normal-appearing frozen cadaver larynges from adult humans were studied. The cricoid cartilage was fixed to a load cell sensitive to forces in three dimensions. A probe was rigidly fixed to the arytenoid cartilage and attached to a frame to allow active rotation, rocking, and gliding of the arytenoid. A computer program simultaneously recorded forces generated by these motions and tracked the motion of the arytenoid in three dimensions. The joint was studied before and after injury to the posterior cricoarytenoid ligament, and the joint surfaces were digitized after completion of these studies. RESULTS: A successful method of evaluating the biomechanical properties of the cricoarytenoid joint was developed. Comparing intact and injured joints confirmed that laxity and range of motion increased during rocking, gliding, and rotational motion when the cricoarytenoid ligament had been divided. Stiffness measurements for rocking, rotation, and gliding also were documented. CONCLUSIONS: The model of study introduced in this report provides a significant and unique method of investigating the biomechanics of the cricoarytenoid joint, allowing insight into the basic joint characteristics and alteration in joint biomechanics related to injuries and surgical procedures. Dividing the cricoarytenoid ligament increases laxity and range of motion in sagittal rocking, gliding, and axial rotation. Secondary constraints on the joint provide significant stiffness of greater degrees of displacement. Further studies should provide insight into the significant secondary elements supporting the joint and into the mechanisms of cricoarytenoid injuries, as well as the effect of surgical procedures on the cricoarytenoid joint.