Rate of occult metastasis in lip squamous cell carcinoma: A systematic review and meta-analysis.

OBJECTIVES: The rate of occult metastasis in lip cancer is poorly studied. Management of the regional nodal basin in lip cancer is thus controversial. This study sought to understand the true rate of micrometastasis in lip cancer. MATERIALS AND METHODS: Systematic review and meta-analysis was conducted of English language studies reporting lip cancer sentinel node biopsy results. Studies were obtained from the PubMed database between the years 2000 and 2023 using the search terms "sentinel node biopsy" and "squamous cell carcinoma." Random effect and fixed effect meta-analyses were performed. RESULTS: Thirteen studies met inclusion criteria. Low heterogeneity was noted among the studies, as indicated by the I2 inconsistency test (I2 = 0%). The rate of occult metastasis ranged between 0 and 33% (mean 9%). A total of 189 lip sentinel node biopsies had been performed. Of these, 21 revealed occult nodal metastasis (11.1%, 95% CI 7.36%-16.44%). One step, generalized linear mixed modeling revealed the true rate of occult nodal metastasis to be 10% (95% CI (0.0504, 0.1746), p < 0.0001). CONCLUSION: The rate of occult metastasis in lip cancer approaches the threshold for elective management of the regional nodal basin. Sentinel node biopsy is optimally suited for management of high-risk early T stage lip cancer.

A prospective evaluation of neck and shoulder function following treatments of early-stage human papillomavirus-associated oropharynx cancer.

OBJECTIVES: To compare post-treatment neck and shoulder function between human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treatments. DESIGN: Prospective, repeated-measures study. SETTING: Tertiary care center. PARTICIPANTS: Treatment-naïve patients with American Joint Committee on Cancer eighth edition stage T0-3/N0-2 HPV+OPSCC. MAIN OUTCOME MEASURES: Patients completed the Neck Dissection Impairment Index (NDII) pre-treatment and 3-months and 1-year post-treatment. The NDII assesses 10 neck and shoulder functions scored 0-5 (total score 0-100), with higher scores suggesting better function. RESULTS: A total of 106 patients underwent: surgery alone (SA, n = 46, 43%), surgery with adjuvant radiation ± chemotherapy (S + a[C]XRT, n = 18, 17%), or definitive radiation ± chemotherapy (d[C]XRT, n = 42, 40%). cTN classification and pre-treatment NDII scores did not differ between groups. SA patients reported worsened 3-month post-treatment versus pre-treatment self-care (4.6 vs. 5.0), lifting light (4.6 vs. 5.0) and heavy (4.2 vs. 4.8) objects, overhead reach (4.5 vs. 4.9), activity (4.5 vs. 4.9), socialization (4.7 vs. 4.9), recreation (4.6 vs. 4.9), and overall score (86.8 vs. 95.3) (all p < 0.05). One-year post-treatment scores (n = 34) were no different than pre-treatment in all domains. S + a[C]XRT patients reported worsened 3-month versus pre-treatment stiffness (4.0 vs. 4.8), lifting heavy objects (3.8 vs. 4.9), overhead reach (4.2 vs. 4.9), socialization (4.6 vs. 5.0), recreation (4.4 vs. 4.9) and overall score (82.4 vs. 96.0) (all p < 0.05). One-year post-treatment scores (n = 13) were no different than pre-treatment in all domains. d[C]XRT patients reported worsened 3-month versus pre-treatment difficulty lifting heavy objects (4.3 vs. 4.7) and recreation (4.3 vs. 4.7). One-year posttreatment scores (n = 21) were no different than pre-treatment in all domains. CONCLUSION: HPV + OPSCC patients may experience mild shoulder/neck dysfunction 3 months after treatment that usually resolves by 1 year, independent of treatment modality.

Prospective quality of life outcomes for human papillomavirus associated oropharynx cancer patients after surgery alone.

PURPOSE: To evaluate changes in patient-reported quality of life (QOL) to inform treatment decisions for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC). MATERIALS AND METHODS: Patients with American Joint Committee on Cancer (AJCC) 8th edition cT0-T3 and cN0-N3 HPV + OPSCC treated with transoral robotic surgery to the primary site with neck dissection completed questionnaires prior to surgery and at three-months and one-year post-operatively. Questionnaires included four validated instruments: the University of Washington Quality of Life Questionnaire (UW-QOL), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Head and Neck Module (HN35), and the Neck Dissection Impairment Index (NDII). RESULTS: Forty-eight patients filled out pretreatment and three-month questionnaires. 37 patients filled out one-year questionnaires. With the UW-QOL, at three-months, patients reported a statistically significant and clinically meaningful decreased mean score for appearance that resolved at one-year (presurgery: 92.4, 3-month: 81.0, p < 0.001; one year: 86.5). At three months and one-year, significant and clinically meaningful decreased mean taste scores persisted (presurgery: 98.0; three-months: 76.3, one-year: 80.3; all p < 0.001). With the EORTC QLQ-C30 and HN35, at one-year, only mean scores for sense of taste or smell (one-year: 13.1; p < 0.001) did not return to baseline. With the NDII, patients returned to functions comparable to baseline in all domains. CONCLUSION: Post-treatment quality of life is high for HPV+ OPSCC patients treated with surgery alone. Mild taste and possibly smell dysfunction may continue in some patients. With careful selection, surgery alone for HPV + OPSCC offers favorable QOL outcomes. LAY SUMMARY: Patients with HPV+ associated oropharynx cancer treated with surgery alone completed quality of life questionnaires before and after surgery. Quality of life remained high for most patients, with a subset of patients experiencing mild taste dysfunction one-year after surgery.

Early detection of mandible osteoradionecrosis risk in a high comorbidity veteran population.

OBJECTIVE: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively. STUDY DESIGN: Retrospective analysis of prospective cohort. SETTING: Tertiary care Veterans Health Administration (VHA) medical center. METHODS: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively analyzed this patient cohort and extracted clinical and pathologic data for 164 patients with SCC of the oral cavity, oropharynx, larynx, and hypopharynx who received definitive or adjuvant EBRT (2016-2020). RESULTS: Most patients were dentate and 80 % underwent dental extractions prior to EBRT of which 16 (16 %) had complications. The rate of ORN was 3.7 % for oral cavity SCC patients and 8.1 % for oropharyngeal SCC patients. Median time to ORN development was 156 days and the earliest case was detected at 127 days post EBRT completion. All ORN patients were dentate and underwent extraction prior to EBRT start. CONCLUSION: ORN development can occur early following EBRT in a Veteran population with significant comorbid conditions but overall rates are in line with the general population. Prospective tracking of HNSCC patients throughout the post-treatment surveillance period is critical to early detection of this devastating EBRT complication.

Surgical management of non melanoma skin cancer of the head and neck.

Non-melanoma skin cancer (NMSC) is the most common malignancy in the world and is reaching epidemic proportions. The most common types of NMSC include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The head and neck is the most common site for NMSC, and surgery remains the mainstay of treatment. We review the etiology, risk factors, pathogenesis as well as the preoperative, operative, and postoperative considerations in the management of NMSC. Multidisciplinary evaluation and attention to each of these phases is imperative for favorable oncologic and functional patient outcomes.

Gastrostomy Utilization by Oropharyngeal Cancer Patients Is Partially Driven by Swallowing Function.

OBJECTIVE: Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rapidly increasing, as are survival rates, in large part due to the human papillomavirus (HPV). Treatment intensity, however, has remained unchanged, making treatment-related toxicity (i.e., dysphagia) a critical problem for an increasing number of patients. The primary objective of this study was to determine whether pretreatment objective swallowing measures can predict percutaneous fluoroscopic guided gastrostomy tube (PFG) utilization during OPSCC treatment. METHODS: Forty-one newly diagnosed OPSCC patients treated with radiation underwent evaluation of swallow function with modified barium swallow study (MBSS) prior to and at completion of radiation treatment using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST); a subset of patients were evaluated using the MD Anderson Dysphagia Inventory (MDADI). RESULTS: Patients were male (100%), primarily Caucasian (85.4%) and p16 positive (85.4%) with mean age of 65.7 years. PFG were placed in 70.7% patients (n = 29) and used by 63.4% (n = 26). Pre- and post-treatment DIGEST scores were associated with T-classification (t = -2.9, p = .001, t = -2.7, p = .01) and indicated deteriorating swallow function during treatment (mean change = 0.46 [t = -2.7, p = .01]). DIGEST and MDADI scores were generally not associated with patient PFG utilization. DIGEST and MDADI scores were significantly correlated prior to, but not following completion of treatment. CONCLUSION: Pre-treatment DIGEST and patient reported swallowing outcomes (MDADI) can be useful in identifying patients with unsafe and/or grossly inefficient swallowing function. However, objectively measured swallow function was not associated with PFG utilization. Development of PFG placement algorithms (reactive vs. prophylactic) therefore require additional inputs/metrics. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2153-2159, 2020.

Prognostic factors associated with achieving total oral diet following osteocutaneous microvascular free tissue transfer reconstruction of the oral cavity.

INTRODUCTION: Osteocutaneous microvascular free tissue transfer (OMFTT) is the current standard in reconstruction of large bony defects of the oral cavity. Although being able to swallow ranks as a top priority for patients undergoing OMFTT, factors associated with achieving an oral diet following surgery remain unclear. We sought to describe the rate of total oral diet achievement, and to identify possible pre-, intra-, and post-operative factors associated with achievement in patients undergoing OMFTT. METHODS: Retrospective review between January 1, 2010 and March 31, 2018 at two tertiary academic centers. RESULTS: 249 patients (67% male, mean age 58 years) met inclusion criteria, with a median follow up of 15 months. Overall, 142 (57%) of patients achieved a total PO diet post-operatively, with median time to achievement of 3.2 months. Multivariate analysis identified that lack of concurrent glossectomy (SHR 1.72 [1.09-2.70], p = 0.02), N0/1 disease (SHR 1.92 [1.16-3.13], p = 0.011), avoidance of post-operative fistula formation (SHR 1.96 [1.22-3.23], p = 0.005), pre-operative G-tube independence (SHR 3.33 [1.69-6.25], p < 0.001), and successful dental rehabilitation (SHR 2.08 [1.43-3.03], p < 0.001) are independently associated with total oral diet achievement. CONCLUSIONS: Bony resections not requiring glossectomy, limited nodal disease burden, pre-operative gastrostomy-independence, avoidance of post-operative fistula, and dental rehabilitation are independently associated with achievement of total oral diet following OMFTT reconstruction of the oral cavity. Counseling patients on associated risk factors is important in guiding post-treatment expectations. Minimization of post-operative fistula, and maximization of dental rehabilitation may significantly improve total oral diet achievement in this patient population.

Swallowing Function in Survivors of Oropharyngeal Cancer Is Associated With Advanced T Classification.

OBJECTIVES: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in the United States. The aim of this study was to characterize the functional status of OPSCC survivors to identify predictors of swallowing dysfunction in this patient population. METHODS: OPSCC survivors (n = 81) treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2005 and 2015 with at least 2 years of clinical follow-up were reviewed. Functional status was ascertained using (1) gastrostomy and tracheostomy placement and retention, (2) gastrostomy use at last follow-up, (3) patient-reported diet, and (4) modified barium swallow. RESULTS: Median follow-up duration was 5.6 years; 67% of patients had ≥10-pack-year tobacco exposure; 96% of tumors for which p16 data were available were p16 positive. At last follow-up, 82% of patients reported a regular diet, and only 9 patients required gastrostomy use. Gastrostomy use at last follow-up was higher in patients with T3 and T4 tumors compared with those with T1 and T2 tumors (P = .01). The relationship between T classification and gastrostomy use persisted even when the analysis was limited to p16+ tumors and p16+ tumors with ≥10-pack-year history of tobacco exposure. CONCLUSIONS: Advanced T classification at presentation is a critical predictor of gastrostomy use in long-term OPSCC survivors irrespective of p16 status or tobacco exposure history. LEVEL OF EVIDENCE: 2b.

Treatment Patterns in Veterans with Laryngeal and Oropharyngeal Cancer and Impact on Survival.

OBJECTIVES: Veterans with laryngeal and oropharyngeal cancer remain an understudied patient population despite a high incidence of disease and decreased survival compared to the general population. Our objective was to evaluate treatment patterns for laryngeal and oropharyngeal cancer in patients treated at one of the Veterans Health Administration's busiest cancer centers in order to generate some basic benchmarks for treatment delivery in the veteran population. METHODS: We reviewed 338 patients treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2012. RESULTS: Oropharyngeal site and advanced age were associated with worse overall and disease-free survival. Treatment periods (mean) were as follows: 1) referral-diagnosis, 26 days; 2) diagnosis-surgery, 29 days; and 3) diagnosis-radiation, 58 days. Adjuvant radiation was initiated within 6 weeks of surgery in 42% of patients and 68% of patients had a total treatment package time ≤100 days. Time from diagnosis to treatment initiation, surgery to adjuvant radiation interval and total treatment package time did not impact survival. CONCLUSIONS: This study establishes basic benchmarks for laryngeal and oropharyngeal cancer treatment delivery in veterans. Additional efforts are warranted to improve consistency and provide treatment in line with NCCN recommendations and literature consensus. LEVEL OF EVIDENCE: 2b.

Head and neck inflammatory pseudotumor: Case series and review of the literature.

Inflammatory pseudotumor (IP) is an uncommon idiopathic lesion that often imitates malignancy clinically and radiologically. Inflammatory pseudotumors have been found to occur in various sites but rarely in the head and neck. The histopathology, imaging, and treatment of three unique cases of head and neck inflammatory pseudotumors are described in this case series. Patients in Cases 1 and 2 presented with right level II neck mass and left parotid tail mass, respectively. The patient in Case 3 presented with otalgia, jaw pain and trismus, and a left parapharyngeal space mass. The tumors in Cases 1 and 3 significantly decreased in size with tapered courses of oral corticosteroids. The tumor in Case 2 was surgically excised without disease recurrence. Malignancy must be ruled out with incisional or excisional biopsy. Treatment includes surgical excision, oral corticosteroids, or both. The literature shows that radiotherapy and small-molecule inhibitors may be promising alternatives.

Prevalence of confirmed asthma varies in chronic rhinosinusitis subtypes.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma describe inflammation of the upper and lower airway, respectively. Not surprisingly, the prevalence of CRS and asthma has been linked, with up to 50% asthma prevalence in CRS with nasal polyposis (CRSwNP) patients. However, these prevalence rates do not address subtypes of CRSwNP including allergic fungal rhinosinusitis (AFRS). This study sets out to objectively determine asthma prevalence in CRS subtypes prospectively. METHODS: A prospective prevalence study of adult CRS patients was conducted over a 1-year period at a tertiary care center. Patients were grouped into CRSwNP, CRS without nasal polyposis (CRSsNP), or AFRS. Patients were administered the Asthma Screening Questionnaire (ASQ) and asthma was confirmed by pulmonary function testing (PFT) if positive on the ASQ. Chi square analysis was performed to compare the asthma prevalence among the CRS subtypes. RESULTS: A total of 410 patients (age 48.1 ± 16.4; 53.5% male) were included. Of these, 178 (43.4%) had CRSwNP, 166 (40.5%) had CRSsNP, and 66 (16.1%) met criteria for AFRS. Analysis revealed that 48.3% of CRSwNP patients, 16.5% of CRSsNP patients, and 23.6% of AFRS patients had asthma confirmed by PFTs. Chi square analysis showed a significant difference in asthma prevalence between CRSwNP and AFRS (p = 0.0016) and CRSwNP and CRSsNP (p = 0.0000), but no significant difference between CRSsNP and AFRS (p = 0.2380). CONCLUSION: There is a significant difference in the prevalence of asthma between CRSwNP and AFRS, suggesting a fundamental distinction in their etiologies despite similar immunologic profiles. Further efforts to delineate these biological disparities are underway.

Early diagnosis and therapy of Parkinson's disease: can disease progression be curbed?

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by the loss of dopamine (DA) neurons in the substantia nigra (SN). Currently, there are numerous therapeutic drugs for the treatment of PD; however, they are limited in efficacy and primarily target motor symptoms. Furthermore, these drugs have various adverse effects after long-term use. Usually, PD patients begin to take anti-parkinsonian drugs when they have developed obvious motor symptoms. At that time, a significant portion of the DA neurons in SN has been lost and the biology of the disease may have already been present for over a decade. This stage of PD diagnosis underscores the need for biomarkers that accurately indicate the onset of PD in order to apply disease-modifying therapies at an earlier stage of disease. However, development of disease modifying drugs has faced many setbacks, mostly due to the ways in which clinical trials are planned and executed. In this review paper, we summarize the recent findings of genetic biomarkers such as SNCA, LRRK2, parkin, PINK1, DJ1, etc., as well as evaluate the imaging techniques such as single proton emission computed tomography and positron emission tomography for their potential in diagnosing PD at earlier stages. Clinical trial designs, along with a comprehensive analysis of neuroprotective drugs for future treatment of PD, are also reviewed.

A mechanistic study of proteasome inhibition-induced iron misregulation in dopamine neuron degeneration.

Ubiquitin proteasome system (UPS) impairment and iron misregulation have been implicated in dopamine (DA) neuron degeneration in Parkinson's disease. As previously shown, proteasome inhibition in a rodent model can cause nigral neuron degeneration accompanied by iron accumulation. To investigate the involvement of iron in DA neuron degeneration, we generated an in vitro model by applying proteasome inhibitor lactacystin in DAergic cell line MES23.5 culture. We found that lactacystin caused marked increase in labile iron, reactive oxygen species and ubiquitin-conjugated protein aggregation prior to cell injury. These effects were attenuated by iron chelators or antioxidants. Furthermore, we demonstrated that the iron regulatory protein (IRP)/iron response element system contributed to UPS impairment-mediated DA neuron injury. We documented that IRP2 disruption resulted in an increase in transferrin receptor 1 (TfR1), a decrease in ferritin heavy chain (H-Frt), and eventually cell death. These findings provide insight into the mechanistic interplay between UPS impairment and iron misregulation and suggest that the disturbances in IRP2, TfR1 and H-Frt may contribute to DA neuron degeneration.