Dr. Sirjani graduated from the University of Arizona with Honors in Biochemistry and was awarded the most outstanding senior award for the college of sciences and the Centennial Achievement Award. He matriculated to the University of Arizona School of Medicine on the Dean’s Scholarship.
He completed a residency in Otolaryngology at Washington University in St. Louis and a fellowship in Head and Neck Cancer and Microvascular reconstruction at the University of Washington in Seattle in 2009.
He joined the Division of Head and Neck Surgery in 2009 and, since 2012, has also served as Chief of Otolaryngology at the VA in Palo Alto. Dr. Sirjani has pioneered the use of telemedicine to provide complicated head and neck cancer care to remote VA satellite across the Pacific and Mountwaint West.
Under his leadership, the Stanford VA has become a premier hub for head and neck cancer care in the West Coast.
As the director of the salivary program at Stanford since 2013, Dr. Sirjani’s practice is focused on minimally invasive parotidectomy.
He was the first surgeon at Stanford to offer patients sialendoscopy. His research interests include innovations in minimizing morbidity from parotid cancer treatment.
Dr. Sirjani’s research interests focus on surgical simulation and surgical innovation. He invented the only partoidectomy surgical simulator in the country, which is funded by CIMIT and used to teach other surgeons about the tension placed on the facial nerve during Parotidectomy. Stanford is now a primary center for the treatment of salivary related cancers.
Dr. Sirjani incorporates new innovations, basic science research, and his high volume of operative experience to tailor operations to best suite the patient.
- Cancer > Head and Neck Cancer
- Parotid Neoplasms
- Salivary Gland Neoplasms
- Skull Base Neoplasms
- Surgical Flaps
- Neck Dissection
- Carcinoma, Skin Appendage
Clinical Associate Professor, Otolaryngology (Head and Neck Surgery)
Chief of Otolaryngology, VA Palo Alto (2012 - Present)
Director, Stanford Salivary Gland Program (2013 - Present)
Honors & Awards
Who's Who in America, Marquis Who's Who Publications Board (2017-2018)
Faculty Teaching Award, Stanford Department of Otolaryngology (2017)
Faculty Teaching Award, Stanford Department of Otolaryngology (2013)
"Surgery at the End of Life", American College of Surgeons, Issues Committee of Resident and Associate Society (2012)
"Reconstructive Dilemma of a Rare Mandibular Tumor", Saint Louis ENT Club (2006)
Resident Award, Association for Research in Otolaryngology (2004)
Michael Paparella Award for Outstanding Research, Washington University (2003)
Young Investigator Award, Academy of Clinical Laboratory Physicians and Scientists (2000)
Caldwell Research Award, University of Arizona College of Medicine (1999)
Excellence in Teaching Histology, University of Arizona College of Medicine (1999)
Dean's Scholar, University of Arizona College of Medicine (1996-2001)
Centennial Achievement Award, University of Arizona (1996)
Most Outstanding Senior Award in Biochemistry, University of Arizona (1996)
Most Outstanding Senior Award in the College of Science, University of Arizona (1996)
Silver Bowl Award (4.0 GPA excluding last semester), University of Arizona (1996)
Phi Kappa Phi, University of Arizona (1992-96)
Boards, Advisory Committees, Professional Organizations
Active Candidate for Fellowship, Triological Society (2016 - Present)
Member, American Academy of Otolaryngology, Medical Devices and Drugs Committee (2013 - Present)
Member, North American Skull Base Society (2012 - Present)
Member, Association of Northern California Oncologist (2011 - Present)
Member, American Telemedicine Association (2011 - Present)
Residency:Washington University School Of Medicine Registrar (2008) MO
Internship:Washington University School Of Medicine Registrar (2002) MO
Medical Education:University of Arizona College of Medicine Office of the Registrar (2001) AZ
Fellowship, Stanford Biodesign Faculty Fellowship, Innovation (2017)
F.A.C.S, American College of Surgeons (2013)
Board Certification: Otolaryngology, American Board of Otolaryngology (2010)
Fellowship:University of Washington Medical Center (2009) WA
Post-Sophomore Fellow, University of Arizona College of Medicine, Pathology (1999)
Bachelor of Science, University of Arizona, Biochemistry (1996)
Current Research and Scholarly Interests
Innovation of devices to improve the quality of life of patients with advanced head and neck cancers, minimal invasive parotid surgery, surgical simulation, flap reconstruction of large head and neck defects to restore cosmesis and function (speech, swallowing), stem cell recovery of radiation induced salivary damage, and salivary gland cancer biology
Phase I Panitumumab IRDye800 Optical Imaging Study
Phase I trial to evaluate the safety of escalating dose levels of conjugated panitumumab-IRDye800 in subjects with head and neck squamous cell carcinoma (HNSCC) that undergo surgery with curative intent.
Cetuximab IRDye800 Study as an Optical Imaging Agent to Detect Cancer During Surgical Procedures
This study is an open label, single institution, Phase 1 dose-escalation study to determine the safety profile of cetuximab-IRDye800 used in subjects with head and neck squamous cell carcinoma (HNSCC) that undergo surgery with curative intent. Participants will be given a dose of an approved head and neck cancer drug (Cetuximab) along with an investigational study drug called Cetuximab-IRDye800. Cetuximab-IRDye800 is a drug that is given prior to surgery that attaches to cancer cells and appears to make them visible to the doctor when he uses a special camera during the operation. The investigators are evaluating whether or not the use of the study drug along with the special camera will better identify the cancer while patients are in the operating room.
Stanford is currently not accepting patients for this trial. For more information, please contact Alifia Hasan, 650-721-4088.
Multispectral Imaging to Characterize Patterns of Vascular Supply Within Lymphoepithelial Mucosa in Oropharyngeal Cancer
The purpose of this study is to characterize the blood supply at the base of the tongue and within the tonsil region. We hypothesize that high-resolution Narrow Band Imaging (NBI) will improve the diagnosis of oropharyngeal carcinoma (OPC). The goal is to provide the better assessment of tumor and thus providing better preoperative expectations to patients with OPC or tumor extent prior to radiation therapy.
Stanford is currently not accepting patients for this trial. For more information, please contact Nikta Bedi, 650-723-5957.
Retrograde parotidectomy under local anesthesia for benign, malignant, and inflammatory lesions.
American journal of otolaryngology
OBJECTIVE: To report the patient selection, surgical technique, and outcomes of parotidectomy using local anesthesia under monitored anesthesia care (MAC).METHODS: A retrospective chart review was performed for patients undergoing parotidectomy under local anesthesia at an academic head and neck surgery center.RESULTS: Six patients deemed high risk for general anesthesia (GA) due to medical comorbidities or with a strong preference to avoid GA underwent parotidectomy using local anesthesia and MAC. Parotidectomy was performed for several indications, including benign tumors, malignant tumors, and chronic sialadenitis. Mean age of patients was 78.0 ± 7.9 years, and all had an American Society of Anesthesia score ≥ 2 and Charlson comorbidity index ≥4. Mean operative time was 102.8 ± 38.3 min, comparable to that of parotidectomy under general anesthesia. No major complications occurred. Minor complications included three cases of temporary postoperative facial nerve weakness limited to 1-2 lower division branches. At most recent follow up (10 to 48 months), all patients were medically stable and disease free.CONCLUSION: In carefully selected patients, parotidectomy under local anesthesia is a viable treatment alternative that can be offered to patients. Successful outcomes require preoperative counseling, meticulous technique, and close collaboration with anesthesia colleagues.
View details for DOI 10.1016/j.amjoto.2019.01.002
View details for PubMedID 30691973
Regionalization of Head and Neck Cancer Surgery May Fragment Care and Impact Overall Survival.
OBJECTIVE: While surgical treatment concentrates in tertiary care centers, an increasing number of patients request postoperative radiation therapy (PORT) at a separate center closer to home. Our goal was to determine whether fragmentation of surgery and PORT were associated with poorer oncologic outcomes.METHODS: We conducted a retrospective cohort study of 32,813 head and neck cancer patients treated with surgery and PORT in the National Cancer Data Base. Our main outcome was overall survival (OS). Statistical analysis included chi2 , t tests, Kaplan-Meier, and Cox regression analysis.RESULTS: Fragmented care was independently associated with increased risk of mortality (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03-1.13), whereas distance to surgical center>30 miles (HR, 0.92; 95% CI, 0.87-0.97) was associated with improved OS. On subgroup analysis, fragmented care was associated with decreased OS only among patients who had surgery at an academic center (HR, 1.10; 95% CI, 1.04-1.17). Within academic centers, greater distance from the surgical center was associated with improved survival only in patients who received PORT at the same facility (HR, 0.85; 95% CI, 0.78-0.93), but this effect was negated among patients who had fragmented care (HR, 0.97; 95% CI, 0.85-1.11).CONCLUSION: When cancer care is fragmented, there is no longer a survival benefit for patients to travel for surgical care at academic medical centers. Fragmented care is independently associated with worse survival, and further research is needed to evaluate the causes of this difference in survival to determine if improving care coordination can mitigate this survival difference.LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.
View details for DOI 10.1002/lary.27440
View details for PubMedID 30152007
Association of Time between Surgery and Adjuvant Therapy with Survival in Oral Cavity Cancer.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
2018; 158 (6): 1051–56
Objective The National Cancer Center Network recommends starting radiation therapy within 6 weeks after surgery for oral cavity squamous cell carcinoma (OCSCC), but there is limited evidence of the importance of the total time from surgery to completion of radiation therapy (package time). We set out to determine if there was an association between package time and survival in OCSCC and to evaluate the impact of treatment location on outcomes. Study Design Retrospective cohort study. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of patients with OCSCC who completed postoperative radiation therapy at an academic medical center from 2008 to 2016. The primary endpoints were overall survival and recurrence-free survival. Statistical analysis included chi2 tests and Cox proportional hazards regressions. Results We identified 132 patients with an average package time of 12.6 weeks. On multivariate analysis, package time >11 weeks was independently associated with decreased overall survival (hazard ratio, 6.68; 95% CI, 1.42-31.44) and recurrence-free survival (hazard ratio, 2.94; 95% CI, 1.20-7.18). Patients who received radiation therapy at outside facilities were more likely to have treatment delays (90.2% vs 62.9%, P = .001). Conclusions Prolonged package times are associated with decreased overall and recurrence-free survival among patients with OCSCC. Patients who received radiation therapy at outside facilities are more likely to have prolonged package times.
View details for DOI 10.1177/0194599817751679
View details for PubMedID 29313448
Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes.
Proceedings of the National Academy of Sciences of the United States of America
Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated Aldh3a1-/- adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d-limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy.
View details for DOI 10.1073/pnas.1802184115
View details for PubMedID 29794221
Association of Survival With Shorter Time to Radiation Therapy After Surgery for US Patients With Head and Neck Cancer
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
2018; 144 (4): 349–59
Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial.To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry.In this observational cohort study, 25 216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB).Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT.Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation.We identified 25 216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18 968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25 216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation.Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.
View details for DOI 10.1001/jamaoto.2017.3406
View details for Web of Science ID 000430575900012
View details for PubMedID 29522072
View details for PubMedCentralID PMC5876822
Jaw Opening Decreases Window to the Deep Parotid Lobe.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
To describe the relationship between jaw opening and access to the deep parotid window, we identified the following distances in 10 human skulls: symphysis to angle of mandible, mastoid tip to angle of mandible, angle of mandible to condylar process, and mastoid tip to condylar process. With the jaw closed and open, these distances were measured with 1 to 3 wooden blocks, each measuring 1 cm, between the upper and lower incisors. The triangular deep parotid area formed by the last 3 distances was calculated. A repeated measures analysis of variance showed a significant decrease in the deep parotid area with increasing interincisal distance ( P < .01). A generalized estimating equation model demonstrated a statistically significant decreasing area of the deep parotid window with increasing interincisal distance. These results suggest that nasal intubation may improve access to the parotid window.
View details for DOI 10.1177/0194599818766317
View details for PubMedID 29609515
Outcomes in Head and Neck Resections That Require Multiple-Flap Reconstructions: A Systematic Review.
JAMA otolaryngology-- head & neck surgery
Complex head and neck cancer defects that require multiflap reconstructions are technically feasible, but the morbidity and patient outcomes of such large-scale head and neck operations have yet to be systematically reviewed.To systematically review existing literature to characterize the outcomes of large-scale head and neck resections that require multiple-flap reconstructions (defined as defects that require >1 flap [free, pedicled, or combinations thereof]).Two authors independently searched PubMed, Embase, and the Cochrane Review databases for English-only texts published on any date. Included studies examined patients who underwent complex head and neck surgical resections that required multiple simultaneous flaps for reconstruction. Included studies reported results on at least one of the following outcomes: functional and aesthetic, patient survival, or cost (estimated by operating room time, length of stay, and/or complications). Methodological Index for Non-Randomized Studies (MINORS) criteria for bias and modified Oxford Centre for Evidence-Based Medicine recommendations were used to assess study quality.Twenty-four studies published from November 1, 1992, through September 1, 2016, met the final inclusion criteria, with a total of 487 patients (370 male [79.4%]; mean [SD] weighted age, 55.1 [4.1] years). Sixty-two of 250 patients (24.8%) were partially or fully dependent on feeding tubes at follow-up. Twenty-two of 75 patients (29.3%) had poor postoperative oral competence, causing moderate to severe drooling. Nineteen of 108 patients (17.6%) had unintelligible speech. Nine of 64 patients (14.1%) were unsatisfied with their aesthetic outcome. The mean (SD) reported survival was 2.36 (1.39) years. The mean (SD) length of stay was 24.5 (12.2) days in 219 patients. Eighty-eight minor complications (eg, partial flap necrosis, donor site complications) and 185 major complications (eg, surgical reexplorations, flap loss, or cardiopulmonary complications) were reported in 380 patients. Mean (SD) MINORS scores were 16.0 (3.2) for comparison studies and 11.4 (1.8) for noncomparison studies.Because of limited patient life expectancies, modest functional and aesthetic outcomes, and significant associated costs, surgeons should weigh the curative potential and palliative benefits for individual patients with a comprehensive view of the overall outcomes of extensive head and neck resections and reconstructions. Realistic expectations should be emphasized during preoperative discussions with patients.
View details for DOI 10.1001/jamaoto.2018.0835
View details for PubMedID 29978196
Oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States, 1973-2013.
OBJECTIVE: To analyze oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States for the years 1973 through 2013.STUDY DESIGN: Cross-sectional study using a large population-based cancer database.METHODS: Data on incidence and mortality rates were extracted from the Surveillance, Epidemiology, and End Results (SEER) 9 Database. Annual percentage change in rates was calculated using Joinpoint regression analysis (National Cancer Institute, Bethesda, MD).RESULTS: Incidence rates increased (annual percent change [APC]; 1.52, 95% confidence interval [CI] 0.17 to 2.88) from 1973 to 1983, remained stable (APC -0.52, 95% CI -1.30 to 0.26) from 1983 to 1997, and increased (APC 1.32, 95% CI 0.83 to 1.81) from 1997 to 2013. Overall, incidence rates increased for males (APC 0.73, 95% CI 0.22 to 1.25) but not females (APC -0.77, 95% CI -0.68 to 0.82). Incidence rates increased in the white population (APC 0.79, 95% CI 0.33 to 1.25) but decreased in the black population (APC -0.72, 95% CI -1.41 to -0.02). The incidence rates increased for tongue-base tumors (APC 1.17, 95% CI 0.42 to 1.92) and tonsil tumors (APC 0.47, 95% CI 1.10 to 4.96) but decreased for other sites. Incidence-based mortality decreased (APC -0.78, 95% CI -1.13 to -0.42) from 1993 to 2013.CONCLUSION: Oropharyngeal squamous cell carcinoma incidence rates increased in a nonlinear fashion from 1973 to 2013, whereas mortality rates declined. This, along with variation in trends by demographic and tumor factors, suggest that human papilloma virus is the main driver of the recent rise in incidence.LEVEL OF EVIDENCE: 2b. Laryngoscope, 2017.
View details for DOI 10.1002/lary.26972
View details for PubMedID 29086431
Retrograde Parotidectomy and facial nerve outcomes: A case series of 44 patients
AMERICAN JOURNAL OF OTOLARYNGOLOGY
2017; 38 (5): 533–36
The most common surgical method to remove benign parotid tumors remains the prograde approach. We examined if a retrograde surgical technique offers better outcomes than historical prograde controls.A retrospective chart review at Stanford Hospital was conducted to identify retrograde parotidectomies between February 2012 and October 2014 that were staffed by the senior author (DS) with resident involvement. Facial nerve (FN) outcomes and other post-surgical parameters were recorded.We identified 44 consecutive cases and found that 18.2% (n=8) of patients experienced temporary paresis and 2.3% (n=1) experienced minor (HB 2) permanent paresis limited to one branch. The average hospital length of stay was 0.64 days and complication rate was 6.8%.The retrograde technique has complication rates comparable to historical rates for the prograde technique and is amenable to minimally invasive outpatient superficial parotidectomy.
View details for DOI 10.1016/j.amjoto2017.05.003
View details for Web of Science ID 000411304900006
View details for PubMedID 28647300
Node-positive cutaneous squamous cell carcinoma of the head and neck: Survival, high-risk features, and adjuvant chemoradiotherapy outcomes.
Head & neck
Data lacks to guide treatment of regionally metastatic cutaneous head and neck squamous cell carcinoma (HNSCC).We conducted a retrospective review of 80 patients treated for regionally metastatic cutaneous HNSCC. The effect of various clinicopathologic variables on overall survival (OS) was investigated, in addition to outcomes by treatment modality.On multivariate regression, cutaneous primary >2 cm (p = .03) and extracapsular spread (ECS; p = .01) were significantly associated with decreased OS. Location of regional metastasis (neck vs parotid vs both) had no effect on OS (p = .2), nor did the presence of a cutaneous primary at the time of presentation (p = .9). The 3-year survival was 43%, 52%, and 49% for surgery alone, adjuvant radiation, and adjuvant chemoradiation, respectively. Fifty-one percent of patients had a recurrence of their disease.Regionally metastatic cutaneous HNSCC is an aggressive disease associated with high recurrence rates. Patients with tumors >2 cm and ECS have poorer OS despite adjuvant therapy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 881-885, 2017.
View details for DOI 10.1002/hed.24692
View details for PubMedID 28252823
Risk of Nodal Metastasis in Major Salivary Gland Adenoid Cystic Carcinoma.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
Objective To determine the risk of nodal metastasis, examine risk factors for nodal metastasis, and evaluate the impact of nodal metastasis on survival in patients with major salivary gland adenoid cystic carcinoma. Study Design Retrospective cohort study from a large population- based cancer database. Methods Data were extracted from the SEER 18 database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute. The study cohort included 720 patients diagnosed with major salivary gland adenoid cystic carcinoma between 1988 and 2013. Results The overall rate of lymph node metastasis was 17%. T3 disease (odds ratio, 4.74) and T4 disease (odds ratio, 9.24) were associated with increased risk of nodal metastasis. Age, sex, and site were not associated with nodal metastasis. Nodal metastasis was associated with worse overall survival (hazard ratio, 2.56) and disease-specific survival (hazard ratio, 3.27), after adjusting for T stage, presence of distant metastasis, site, surgical resection, radiotherapy, neck dissection, age, sex, race, marital status, and year of diagnosis. Conclusion Major salivary gland adenoid cystic carcinoma carries significant risk of nodal metastasis. Advanced T stage is associated with increased risk of nodal metastasis. Nodal metastasis is associated with worse survival.
View details for DOI 10.1177/0194599817690138
View details for PubMedID 28168897
Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
2016; 142 (12): 1224-1230
The guidelines for head and neck cancer recommend consideration of adjuvant postoperative radiotherapy (PORT) for patients with pT1N1 or pT2N1 disease in the absence of other adverse features. This recommendation was recently changed for oropharyngeal (OP) squamous cell carcinoma (SCC).To examine the use and outcomes of PORT for N1 OP SCC and oral cavity (OC) SCC.This retrospective cohort study identified 1467 adult patients with OC SCC and 790 patients with OP SCC with pT1N1 or pT2N1 disease in the absence of other adverse features from the National Cancer Database from January 1, 2004, to December 31, 2013. Patients who received adjuvant chemotherapy or palliative radiotherapy or who had adverse pathologic features were excluded. Statistical analysis included χ2 tests and Cox proportional hazards regression analysis. Data were analyzed from November 10, 2015, to June 30, 2016.Overall survival.Of the 1467 patients with OC SCC (842 men [57.4%]; 625 women [42.6%]; mean [SD] age, 61.3 [13.8] years), 740 (50.4%) received PORT. Of the 790 patients with OP SCC (584 men [73.9%]; 206 women [26.1%]; mean [SD] age, 58.2 [10.3] years), 449 (56.8%) received PORT. After controlling for patient demographics, pathologic characteristics, and hospital-level variables, PORT was associated with improved overall survival for patients with OC SCC (hazard ratio [HR], 0.76; 95% CI, 0.63-0.92) and OP SCC (HR, 0.62; 95% CI, 0.41-0.92) with pN1 disease without adverse features. On stratified analysis, this association persisted for patients younger than 70 years (OC SCC HR, 0.77; 95% CI, 0.61-0.97; OP SCC HR, 0.48; 95% CI, 0.31-0.75) and those with pT2 disease (OC SCC HR, 0.64; 95% CI, 0.43-0.96; OP SCC HR, 0.56; 95% CI, 0.32-0.95), but there was no association with overall survival among patients 70 years or older (OC SCC HR, 0.78; 95% CI, 0.58-1.06; OP SCC HR, 1.55; 95% CI, 0.63-3.82) and those with pT1 disease (OC SCC HR, 0.80; 95% CI, 0.60-1.07; OP SCC HR, 0.66; 95% CI, 0.35-1.24).PORT may be associated with improved survival in patients with pN1 OC and OP SCC, especially in those younger than 70 years or those with pT2 disease.
View details for DOI 10.1001/jamaoto.2016.3519
View details for Web of Science ID 000391467800014
View details for PubMedID 27832255
Lymph Node Count From Neck Dissection Predicts Mortality in Head and Neck Cancer
JOURNAL OF CLINICAL ONCOLOGY
2016; 34 (32): 3892-?
Multiple smaller studies have demonstrated an association between overall survival and lymph node (LN) count from neck dissection in patients with head and neck cancer. This is a large cohort study to examine these associations by using a national cancer database.The National Cancer Database was used to identify patients who underwent upfront nodal dissection for mucosal head and neck squamous cell carcinoma between 2004 and 2013. Patients were stratified by LN count into those with < 18 nodes and those with ≥ 18 nodes on the basis of prior work. A multivariable Cox proportional hazards regression model was constructed to predict hazard of mortality. Stratified models predicted hazard of mortality both for patients who were both node negative and node positive.There were 45,113 patients with ≥ 18 LNs and 18,865 patients with < 18 LNs examined. The < 18 LN group, compared with the ≥ 18 LN group, had more favorable tumor characteristics, with a lower proportion of T3 and T4 lesions (27.9% v 39.8%), fewer patients with positive nodes (46.6% v 60.5%), and lower rates of extracapsular extension (9.3% v 15.1%). Risk-adjusted Cox models predicting hazard of mortality by LN count showed an 18% increased hazard of death for patients with < 18 nodes examined (hazard ratio [HR] 1.18; 95% CI, 1.13 to 1.22). When stratified by clinical nodal stage, there was an increased hazard of death in both groups (node negative: HR, 1.24; 95% CI, 1.17 to 1.32; node positive: HR, 1.12; 95% CI, 1.05 to 1.19).The results of our study demonstrate a significant overall survival advantage in both patients who are clinically node negative and node positive when ≥ 18 LNs are examined after neck dissection, which suggests that LN count is a potential quality metric for neck dissection.
View details for DOI 10.1200/JCO.2016.67.3863
View details for Web of Science ID 000388926900012
View details for PubMedID 27480149
Contemporary mandibular reconstruction.
Current opinion in otolaryngology & head and neck surgery
2016; 24 (5): 433-439
Multiple disease processes, including neoplasia, trauma, and medication side-effects, necessitate segmental resection and subsequent reconstruction of the mandible. As surgical techniques have advanced, several technologies have been developed with the potential to significantly transform a surgeon's approach to the restoration of mandibular continuity. The purpose of this review is to highlight many of these relatively newer tools and discuss their evolving role in mandibular reconstruction.Several contemporary studies have documented the application of different approaches and modifications to mandibular reconstruction - including computer-aided design or computer-aided modeling, contemporary plating systems, osseointegrated implants, and various modifications to existing osseocutaneous free tissue transfer options - and have reported relatively high success rates.In discussing these reports, we present a survey of current and developing technologies in the field of mandibular reconstruction and aim to provide sufficient context for the gradual integration of these techniques into practice.
View details for DOI 10.1097/MOO.0000000000000284
View details for PubMedID 27348352
Faster Triage of Veterans With Head and Neck Cancer.
Federal practitioner : for the health care professionals of the VA, DoD, and PHS
2016; 33 (Suppl 5): 24S–29S
High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.
View details for PubMedID 30766220
Ameloblastoma: a clinical review and trends in management
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
2016; 273 (7): 1649-1661
Ameloblastoma is a rare odontogenic neoplasm of the mandible and maxilla, with multiple histologic variants, and high recurrence rates if improperly treated. The current mainstay of treatment is wide local excision with appropriate margins and immediate reconstruction. Here we review the ameloblastoma literature, using the available evidence to highlight the change in management over the past several decades. In addition, we explore the recent molecular characterization of these tumors which may point towards new potential avenues of personalized treatment.
View details for DOI 10.1007/s00405-015-3631-8
View details for Web of Science ID 000377413500003
View details for PubMedID 25926124
Consultation via telemedicine and access to operative care for patients with head and neck cancer in a Veterans Health Administration population
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
2016; 38 (6): 925-929
The purpose of this study was to evaluate a telemedicine model that utilizes an audiovisual teleconference as a preoperative visit.Veterans Health Administration (VHA) patients with head and neck cancer at 2 remote locations were provided access to the Palo Alto Veterans Affairs (PAVA) Health Care System otolaryngology department via the telemedicine protocol: tissue diagnosis and imaging at the patient site; data review at PAVA; and a preoperative teleconference connecting the patient to PAVA. Operative care occurred at PAVA. Follow-up care was provided remotely via teleconference.Fifteen patients were evaluated. Eleven underwent surgery, 4 with high-grade neoplasms (carcinoma). Average time from referral to operation was 28 days (range, 17-36 days) and 72 (range, 31-108 days), respectively, for high-grade and low-grade groups. The average patient was spared 28 hours traveling time and $900/patient was saved on travel-related costs.A telemedicine model enables timely access to surgical care and permits considerable savings among select VHA patients with head and neck cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: 925-929, 2016.
View details for DOI 10.1002/hed.24386
View details for Web of Science ID 000379939900021
View details for PubMedID 26899939
- Oral Squamous Cell Carcinoma Mimicking Peri-Implantitis CLINICAL ADVANCES IN PERIODONTICS 2016; 6 (2): 83–88
Botulinum Toxin Confers Radioprotection in Murine Salivary Glands
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2016; 94 (5): 1190-1197
Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage.We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment.Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation.These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of xerostomia in patients with head and neck cancer.
View details for DOI 10.1016/j.ijrobp.2015.12.371
View details for Web of Science ID 000372564800026
View details for PubMedCentralID PMC4839970
Anterolateral approach to the upper cervical spine: Case report and operative technique
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
2015; 37 (9): E115-E119
Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. © 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.
View details for DOI 10.1002/hed.23951
View details for Web of Science ID 000359605700004
View details for PubMedID 25522016
CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma.
2014; 5 (16): 6854-6866
Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.
View details for PubMedID 25149537
Neurotrophic factor GDNF promotes survival of salivary stem cells.
journal of clinical investigation
2014; 124 (8): 3364-3377
Stem cell-based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin-CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland of irradiated mice successfully restored saliva secretion and increased the number of functional acini. Gene-expression analysis revealed that glial cell line-derived neurotrophic factor (Gdnf) is highly expressed in Lin-CD24+c-Kit+Sca1+ stem cells. Furthermore, GDNF expression was upregulated upon radiation therapy in submandibular glands of both mice and humans. Administration of GDNF improved saliva production and enriched the number of functional acini in submandibular glands of irradiated animals and enhanced salisphere formation in cultured salivary stem cells, but did not accelerate growth of head and neck cancer cells. These data indicate that modulation of the GDNF pathway may have potential therapeutic benefit for management of radiation-induced xerostomia.
View details for DOI 10.1172/JCI74096
View details for PubMedID 25036711
View details for PubMedCentralID PMC4109543
A Novel Aldehyde Dehydrogenase-3 Activator (Alda-89) Protects Submandibular Gland Function from Irradiation without Accelerating Tumor Growth.
Clinical cancer research
2013; 19 (16): 4455-4464
To determine the effect of Alda-89 (an ALDH3 activitor) on (i) the function of irradiated (radiotherapy) submandibular gland (SMG) in mice, (ii) its toxicity profile, and (iii) its effect on the growth of head and neck cancer (HNC) in vitro and in vivo.Adult mice were infused with Alda-89 or vehicle before, during, and after radiotherapy. Saliva secretion was monitored weekly. Hematology, metabolic profile, and postmortem evaluation for toxicity were examined at the time of sacrifice. Alda-89 or vehicle was applied to HNC cell lines in vitro, and severe combined immunodeficient (SCID) mice transplanted with HNC in vivo with or without radiation; HNC growth was monitored. The ALDH3A1 and ALDH3A2 protein expression was evaluated in 89 patients with HNC and correlated to freedom from relapse (FFR) and overall survival (OS).Alda-89 infusion significantly resulted in more whole saliva production and a higher percentage of preserved acini after radiotherapy compared with vehicle control. There was no difference in the complete blood count, metabolic profile, and major organ morphology between the Alda-89 and vehicle groups. Compared with vehicle control, Alda-89 treatment neither accelerated HNC cell proliferation in vitro, nor did it affect tumor growth in vivo with or without radiotherapy. Higher expression of ALDH3A1 or ALDH3A2 was not significantly associated with worse FFR or OS in either human papillomavirus (HPV)-positive or HPV-negative group.Alda-89 preserves salivary function after radiotherapy without affecting HNC growth or causing measurable toxicity in mice. It is a promising candidate to mitigate radiotherapy-related xerostomia.
View details for DOI 10.1158/1078-0432.CCR-13-0127
View details for PubMedID 23812668
View details for PubMedCentralID PMC3745542
Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy.
Oral surgery, oral medicine, oral pathology and oral radiology
2013; 116 (1): e37-51
Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%-85% of the patients. Not only does xerostomia significantly impair patients' quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape.
View details for DOI 10.1016/j.oooo.2013.02.017
View details for PubMedID 23643579
Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence
2013; 119 (7): 1349-1356
In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months.A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans.PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive.HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.
View details for DOI 10.1002/cncr.27892
View details for Web of Science ID 000316811900010
A Novel Aldehyde Dehydrogenase-3 Activator Leads to Adult Salivary Stem Cell Enrichment In Vivo
CLINICAL CANCER RESEARCH
2011; 17 (23): 7265-7272
To assess aldehyde dehydrogenase (ALDH) expression in adult human and murine submandibular gland (SMG) stem cells and to determine the effect of ALDH3 activation in SMG stem cell enrichment.Adult human and murine SMG stem cells were selected by cell surface markers (CD34 for human and c-Kit for mouse) and characterized for various other stem cell surface markers by flow cytometry and ALDH isozymes expression by quantitative reverse transcriptase PCR. Sphere formation and bromodeoxyuridine (BrdUrd) incorporation assays were used on selected cells to confirm their renewal capacity and three-dimensional (3D) collagen matrix culture was applied to observe differentiation. To determine whether ALDH3 activation would increase stem cell yield, adult mice were infused with a novel ALDH3 activator (Alda-89) or with vehicle followed by quantification of c-Kit(+)/CD90(+) SMG stem cells and BrdUrd(+) salispheres.More than 99% of CD34(+) huSMG stem cells stained positive for c-Kit, CD90 and 70% colocalized with CD44, Nestin. Similarly, 73.8% c-Kit(+) mSMG stem cells colocalized with Sca-1, whereas 80.7% with CD90. Functionally, these cells formed BrdUrd(+) salispheres, which differentiated into acinar- and ductal-like structures when cultured in 3D collagen. Both adult human and murine SMG stem cells showed higher expression of ALDH3 than in their non-stem cells and 84% of these cells have measurable ALDH1 activity. Alda-89 infusion in adult mice significantly increased c-Kit(+)/CD90(+) SMG population and BrdUrd(+) sphere formation compared with control.This is the first study to characterize expression of different ALDH isozymes in SMG stem cells. In vivo activation of ALDH3 can increase SMG stem cell yield, thus providing a novel means for SMG stem cell enrichment for future stem cell therapy.
View details for DOI 10.1158/1078-0432.CCR-11-0179
View details for Web of Science ID 000298133600009
View details for PubMedID 21998334
View details for PubMedCentralID PMC3544360
- Lefort I Osteotomy access to the Anterior Skull Base Operative Techniques in Otolaryngology 2010; 21 (1): 22-25