Faculty Bibliography

OBJECTIVE:Endoscopic endonasal transsphenoidal surgery (EETS) is a widely accepted technique for sellar tumors. Common findings during preoperative assessment include septal deviations and turbinate hypertrophy. This study evaluated quality of life changes after concurrent septoplasty and/or inferior turbinoplasty during EETS. METHODS:A retrospective review was performed of a prospectively collected database including all patients undergoing EETS at our institution during a 10-month period between 2015 and 2016. Patients were divided into a septoplasty/inferior turbinoplasty group and a no septoplasty/inferior turbinoplasty group. The Sino-Nasal Outcome Test (SNOT-22) was used to evaluate quality of life. Mean preoperative scores were compared with 1- and 3-month postoperative scores within each cohort. The SNOT-22 was also reorganized into 5 distinct subdomains. Average subdomain scores were calculated, and preoperative and 1- and 3-month postoperative subdomain scores were compared within each cohort. A paired Student t test was used. P values < 0.05 were considered statistically significant. RESULTS:All 24 patients met inclusion criteria by completing preoperative and postoperative SNOT-22 surveys. In the septoplasty/inferior turbinoplasty group, preoperative and 3-month postoperative scores showed a clinically significant difference (P = 0.047). The septoplasty/inferior turbinoplasty group specifically showed a significant difference in the psychiatric and sleep SNOT-22 subdomains when comparing preoperative with 3-month postoperative scores (P = 0.03, P = 0.01). CONCLUSIONS:Patients who underwent concurrent septoplasty and/or turbinoplasty with EETS had a significantly improved quality of life compared with preoperative assessment, specifically regarding psychological and sleep symptoms.

Background: Although several studies have reported on actuarial survival outcomes following resection of hilar cholangiocarcinoma, the characteristics of patients who actually reached the 5-year milestone have not been adequately described. Methods: Patients who underwent resection for hilar cholangiocarcinoma from 2000-2015 in 10 US academic institutions participating in the Extrahepatic Biliary Malignancy Consortium were analyzed. Patients alive at last encounter with less than 5 years of follow-up were excluded. The clinicopathologic characteristics, perioperative, and long-term outcomes of actual 5-yr survivors and of patients who died within 5 years were compared. Results: Of 328 patients explored, 257 (78%) underwent curative resection and had an actuarial 5-year survival of 17%. After excluding 63 survivors with < 5 years follow-up, 194 patients were further classified as 5-year survivors (n = 23, 12%) and non-5-yr survivors. None of the 5-yr survivors had preoperative systemic biliary sepsis, portal vein embolization, T3 tumors with unilateral portal vein or hepatic artery invasion, or T4 tumors necessitating main portal vein or hepatic artery resection. However, actual 5-year survival was still achieved in the setting of bile duct resection only, R1 margins, poor differentiation, lymphovascular or perineural invasion, nodal metastasis, intraoperative blood transfusion, and serious postoperative complications. Fiveyear survival did not equal cure, as five 5-year survivors experienced disease recurrence, 2 before and 3 after the 5-year mark. There were ten actual 7-year survivors and four actual 10-year survivors. Conclusions: Although nodal metastasis, poor differentiation, and R1 margins are established predictors of poor outcome for hilar cholangiocarcinoma, the mere presence of these factors does not preclude patients from achieving a 5-year survival. In contrast, preoperative biliary sepsis, T3 or T4 stage, and the necessity for vascular resection and reconstruction appear to be prohibitive in reaching the 5-year milestone. This information can be utilized in the perioperative counseling of patients with this challenging malignancy

Cochlear implant (CI) recipients have difficulty understanding speech in noise even at moderate signal-to-noise ratios. Knowing the mechanisms they use to understand speech in noise may facilitate the search for better speech processing algorithms. In the present study, a computational model is used to assess whether CI users' vowel identification in noise can be explained by formant frequency cues (F1 and F2). Vowel identification was tested with 12 unilateral CI users in quiet and in noise. Formant cues were measured from vowels in each condition, specific to each subject's speech processor. Noise distorted the location of vowels in the F2 vs F1 plane in comparison to quiet. The best fit model to subjects' data in quiet produced model predictions in noise that were within 8% of actual scores on average. Predictions in noise were much better when assuming that subjects used a priori knowledge regarding how formant information is degraded in noise (experiment 1). However, the model's best fit to subjects' confusion matrices in noise was worse than in quiet, suggesting that CI users utilize formant cues to identify vowels in noise, but to a different extent than how they identify vowels in quiet (experiment 2).

Background: Beyond the most common adenocarcinoma type, several gallbladder cancer (GBC) histologies have been described as being associated with more favorable (papillary) or less favorable outcome (adenosquamous, mucinous, signet ring). We sought to examine the added value of histologic type and grade on the existing AJCC staging system for resected GBC. Methods: Patients who underwent resection of GBC from 1988-2013 were identified using the Surveillance Epidemiology End Results (SEER) registry. A prognostic score was created by assigning points for T stage, N stage, grade and histology based on the regression coefficient in multivariate analysis. The score was externally validated using the US Extrahepatic Biliary Malignancy Consortium (USEBMC) database (2000- 2015) and compared with the AJCC staging system. Results: Of 7,915 patients identified in SEER, 83% had adenocarcinoma, 7% papillary, 4% adenosquamous, 4% mucinous, and 2% signet ring. In the USEBMC database, the frequencies of the respective histologies were 86, 9, 2, 1 and 2%. Median survival per histologic type, for SEER and USEBMC respectively, were 45 and 110 mos for papillary, 16 and 24 mos for adenocarcinoma, 14 and 12mos for mucinous, 8 and 4mos for adenosquamous, and 9 and 15mos for signet ring (P between histologies < 0.001 for both cohorts). On multivariate analysis, T stage, N stage, grade and histology were independent predictors of survival. The developed prognostic score, based on points for each of these 4 variables, showed excellent discriminatory ability both in the SEER and USEBMC cohorts. The AUC for the prognostic score was significantly improved compared with the AJCC system (0.69 vs. 0.64, both P < 0.001 using SEER, and 0.76 vs. 0.66, both P < 0.001 using USEBMC). Conclusions: The incorporation of histology and grade into the TNM system allows for a simple and accurate tool to determine prognosis following resection of GBC. (Table Presented)

Objective Rhinoplasty, a surgical procedure that alters the shape or appearance of the nose while preserving or enhancing the nasal airway, ranks among the most commonly performed cosmetic procedures in the United States, with >200,000 procedures reported in 2014. While it is difficult to calculate the exact economic burden incurred by rhinoplasty patients following surgery with or without complications, the average rhinoplasty procedure typically exceeds $4000. The costs incurred due to complications, infections, or revision surgery may include the cost of long-term antibiotics, hospitalization, or lost revenue from hours/days of missed work. The resultant psychological impact of rhinoplasty can also be significant. Furthermore, the health care burden from psychological pressures of nasal deformities/aesthetic shortcomings, surgical infections, surgical pain, side effects from antibiotics, and nasal packing materials must also be considered for these patients. Prior to this guideline, limited literature existed on standard care considerations for pre- and postsurgical management and for standard surgical practice to ensure optimal outcomes for patients undergoing rhinoplasty. The impetus for this guideline is to utilize current evidence-based medicine practices and data to build unanimity regarding the peri- and postoperative strategies to maximize patient safety and to optimize surgical results for patients. Purpose The primary purpose of this guideline is to provide evidence-based recommendations for clinicians who either perform rhinoplasty or are involved in the care of a rhinoplasty candidate, as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The target audience is any clinician or individual, in any setting, involved in the management of these patients. The target patient population is all patients aged >/=15 years. The guideline is intended to focus on knowledge gaps, practice variations, and clinical concerns associated with this surgical procedure; it is not intended to be a comprehensive reference for improving nasal form and function after rhinoplasty. Recommendations in this guideline concerning education and counseling to the patient are also intended to include the caregiver if the patient is <18 years of age. Action Statements The Guideline Development Group made the following recommendations: (1) Clinicians should ask all patients seeking rhinoplasty about their motivations for surgery and their expectations for outcomes, should provide feedback on whether those expectations are a realistic goal of surgery, and should document this discussion in the medical record. (2) Clinicians should assess rhinoplasty candidates for comorbid conditions that could modify or contraindicate surgery, including obstructive sleep apnea, body dysmorphic disorder, bleeding disorders, or chronic use of topical vasoconstrictive intranasal drugs. (3) The surgeon, or the surgeon's designee, should evaluate the rhinoplasty candidate for nasal airway obstruction during the preoperative assessment. (4) The surgeon, or the surgeon's designee, should educate rhinoplasty candidates regarding what to expect after surgery, how surgery might affect the ability to breathe through the nose, potential complications of surgery, and the possible need for future nasal surgery. (5) The clinician, or the clinician's designee, should counsel rhinoplasty candidates with documented obstructive sleep apnea about the impact of surgery on nasal airway obstruction and how obstructive sleep apnea might affect perioperative management. (6) The surgeon, or the surgeon's designee, should educate rhinoplasty patients before surgery about strategies to manage discomfort after surgery. (7) Clinicians should document patients' satisfaction with their nasal appearance and with their nasal function at a minimum of 12 months after rhinoplasty. The Guideline Development Group made recommendations against certain actions: (1) When a surgeon, or the surgeon's designee, chooses to administer perioperative antibiotics for rhinoplasty, he or she should not routinely prescribe antibiotic therapy for a duration >24 hours after surgery. (2) Surgeons should not routinely place packing in the nasal cavity of rhinoplasty patients (with or without septoplasty) at the conclusion of surgery. The panel group made the following statement an option: (1) The surgeon, or the surgeon's designee, may administer perioperative systemic steroids to the rhinoplasty patient.

Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification. Panobinostat is a pan-histone deacetylase inhibitor that has demonstrated clinical activity as a single agent in early phase trials of myelofibrosis. We previously conducted a phase I trial of panobinostat monotherapy in patients with myelofibrosis and determined 25mg thrice weekly as the recommended phase II dose. We then completed an investigator initiated, Simon 2-stage, phase II trial of 22 myelofibrosis patients at our single institution. After 6 cycles of therapy, the overall response rate by IWG-MRT criteria was 36% (8/22; 95% CI: 16-56%). The median percent reduction in spleen volume was 34% (range, 1.6%-73%) in eight evaluable patients. The average reduction in JAK2V617F allele burden was 6.8% (Range; -4.0% to 20.2%) and one patient obtained a complete molecular response. Six patients remained on therapy in the extension phase for a median of 18 months (range, 7-44). Treatment discontinuation was frequent due to patient/physician perception of therapy ineffectiveness. The optimal dosing of panobinostat for the treatment of MF remains somewhat ill-defined but appears to be most effective and better tolerated when administered at lower doses over a prolonged duration of therapy.

Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 ( approximately 45-fold) relative to HGF-1 (human gingival fibroblasts) cells. We used the nonviral vector to transfect cancer with OPRM1, the mu-opioid receptor gene, as a novel method for treating cancer-induced pain. After HSC-3 cells were transfected with OPRM1, a cancer mouse model was created by inoculating the transfected HSC-3 cells into the hind paw or tongue of athymic mice to determine the analgesic potential of OPRM1 transfection. Mice with HSC-3 tumors expressing OPRM1 demonstrated significant antinociception compared with control mice. The effect was reversible with local naloxone administration. We quantified beta-endorphin secretion from HSC-3 cells and showed that HSC-3 cells transfected with OPRM1 secreted significantly more beta-endorphin than control HSC-3 cells. These findings indicate that nonviral delivery of the OPRM1 gene targeted to the cancer microenvironment has an analgesic effect in a preclinical cancer model, and nonviral gene delivery is a potential treatment for cancer pain.

Objective To determine the impact of unilateral vagal sacrifice for vagal schwannoma on postoperative swallowing function. Study Design Case series, chart review. Setting Academic medical institution. Subjects and Methods Ten patients underwent vagus nerve sacrifice for vagal schwannoma resection. Archived pathology records dating from 1985 through 2012 at our institution were retrospectively queried for cases of vagal schwannoma with vagus nerve sacrifice. Medical records were abstracted for demographic and disease information as well as cranial nerve and swallowing function. Preoperative and postoperative cranial nerve function, subjective and objective measures of swallowing function, Functional Oral Intake Scale (FOIS) level, and need for vocal fold medialization were variables collected. Data were analyzed with summary statistics. Results The patients who underwent vagal sacrifice for vagal schwannoma at our institution had a mean age of 42.3 years (median, 44 years; range, 15-63 years) and follow-up of 35.6 months (median, 9 months; range, 1-115 months). Most presented with no preoperative cranial nerve deficit or difficulty swallowing. Immediately postoperatively, 90% had a vagus nerve deficit, but 50% had no subjective difficulty swallowing, and 70% had a FOIS level of 7 at postoperative hospital discharge. Within 1 month after surgery, 70% had normal swallowing function according to a modified barium swallow study. A full diet was tolerated by mouth within an average of 2.7 days (median, 2 days; range, 1-6 days) after surgery in this cohort. Seventy percent required vocal fold medialization postoperatively for incomplete glottic closure. Conclusion Vagal nerve sacrifice during resection of vagal schwannoma can be performed with normal postoperative swallowing function.

OBJECTIVE:A significant proportion of children with congenital hearing loss who are candidates for cochlear implants (CIs) may have inner ear malformations (IEMs). Surgical and speech outcomes following CI in these children have not been widely reported. METHODS:The charts of children who were evaluated for a CI between 1/1/1986 and 12/31/2014 at a university-based tertiary level pediatric cochlear implant center were reviewed. Principal inclusion criteria included (i) age 1-18 years, (ii) history of bilateral severe to profound sensorineural hearing loss, and (iii) limited benefit from binaural amplification. Exclusion criteria included (i) underlying diagnosis of neurodevelopmental disorder and (ii) lack of follow up for speech assessment if a CI was performed. The following outcome measures were reviewed: (i) imaging findings with magnetic resonance imaging or high resolution computed tomography, (ii) intraoperative complications, and (iii) speech perception categorized as the ability to perceive closed set, open set, or none. RESULTS:The prevalence of IEMs was 27% (102 of 381), of which 79% were bilateral. Cochlear dysplasia accounted for 30% (40 of 136) of the anomalies. Seventy-eight of the 102 patients received a CI (78%). Surgery was noted to be challenging in 24% (19 of 78), with a perilymphatic gusher being the most common intraoperative finding. Cochlear dysplasia, vestibular dysplasia and cochlear nerve hypoplasia were associated with poor speech perception (open OR closed set speech recognition scores, 0-23%), although the outcomes in children with enlarged vestibular aqueduct were similar to those of children with normal inner ear anatomy (65%). CONCLUSIONS:Cochlear implantation is safe in children with IEMs. However, the speech perception outcomes are notably below those of patients with normal anatomy, with the exception of when an enlarged vestibular aqueduct is present.

Background: Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in several malignancies. Its effect on recurrence and survival in distal cholangiocarcinoma (DCC) is unknown. Methods: All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000-2015 were included. 30-day mortalities were excluded. Primary outcomes were recurrence-free (RFS) and overall survival (OS). Results: Of 314 pts with DCC, 206 (66%) underwent curative-intent pancreaticoduodenectomy. Median age was 67yrs, and 53 pts (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared to no-transfusion, patients who received a transfusion were more likely to have (+)margins (28vs14%; p < 0.03) and major complications (46vs16%; p < 0.001). Receipt of neoadjuvant or adjuvant therapy was similar between groups. Transfusion was associated with lower median RFS (19vs32mos; p = 0.006) and OS (15vs29mos; p = 0.003), which persisted on multivariable (MV) analysis for both RFS (HR 1.8; 95%CI 1.1-3.1; p = 0.03)and OS (HR 1.9; 95%CI 1.1-3.2; p = 0.03), after controlling for portal vein resection, EBL, margin status, grade, LVI, LN status, and major complications. Similarly, transfusion of >= 2 pRBC units was associated with lower RFS (17vs32mos; p < 0.001) and OS (14vs29mos; p < 0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95%CI 1.4-4.6; p = 0.002) and OS (HR 3.9; 95%CI 2.1-7.5; p < 0.001). The RFS and OS of patients transfused 1 unit was similar to those not transfused. Conclusions: Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit is not associated with the same adverse effects as >= 2units. This supports the judicious use of perioperative transfusion; protocols should be developed and followed