Nasogastric tube feeding after transoral robotic surgery for oropharynx carcinoma.

PURPOSE: To determine the need for and predictors of nasogastric tube feeding (NGTF) use and duration after transoral robotic surgery (TORS) for oropharynx squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: This is a retrospective cohort study. For 95 OPSCC patients undergoing TORS with or without concurrent unilateral or bilateral neck dissections (ND), we evaluated NGTF use and duration, along with demographic, clinical, histopathologic, and treatment risk factors. RESULTS: 23.2% (22/95) of patients received NGTF. Univariate analysis found that NGTF was significantly more likely in larger tumor specimens (mean: 2.32 cm vs. 1.84 cm; p = 0.043) and after concurrent bilateral (46.7%) compared to unilateral (17.4%) ND (p = 0.043). Multivariable analysis also found increased tumor size (p = 0.035) and concurrent bilateral ND (p = 0.04) to be significant risk factors for NGTF. The following were not statistically significantly associated with NGTF use: sex, age, smoking history, HPV status, base of tongue (BOT) resection (20%) vs. radical tonsillectomy (25.9%), pT2 (27.0%) vs. pT1 (20.4%) vs pT0 (16.7%), BOT with (28.6%) vs. without epiglottis resection (22.2%), and surgery for additional margins the same day (27.3%) (all p > 0.1). Patients who underwent NGTF had a mean duration of 18 days (2-96, SD: 20.7 days) with 12 (55.6%) having over 2 weeks of use. No significant predictors of longer duration of NGTF were identified. CONCLUSIONS: A majority of patients undergoing TORS do not need NGTF. When NGTF is needed, the duration of use is usually longer than 14 days. Larger tumor size and concurrent bilateral ND are risk factors for NGTF.

Sialendoscopy in Chronic Obstructive Sialadenitis Without Sialolithiasis: A Prospective Cohort Study.

OBJECTIVES: To evaluate long-term chronic sialadenitis symptoms in patients without sialolithiasis following sialendoscopy-assisted salivary duct surgery (SASDS) compared to a control group managed conservatively. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary care center. METHODS: Thirty-six patients (52 glands) with chronic sialadenitis without sialolithiasis completed the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire at presentation and at 3-month time intervals thereafter for 1 year. Lower COSS scores represent lower symptom severity. We compared 27 patients who underwent SASDS to 9 control patients who elected conservative management. RESULTS: COSS gland-specific scores from 38 SASDS-treated glands (cases) and 14 control glands were similar at baseline. At 6 to 12 months (mean, 8.4 months), the surgically treated group had significantly lower scores and a greater score reduction from baseline compared to controls (mean score change [95% confidence interval] cases: 20.7 points [15.7-25.8]; controls: 11.7 points [4.9-18.4]; P = .04). There was a significant difference in scores between the 2 groups over time (P < .001). A greater proportion (72%) of cases reported partial or complete resolution of overall sialadenitis symptoms at 6 to 12 months compared to the controls (22%, P < .05). CONCLUSION: Compared to patients electing for conservative management, patients with sialadenitis without sialolithasis treated with SASDS had improved symptom scores and a greater reduction of symptom severity after 6 months. With SASDS, patients had higher rates of significant overall symptom improvement. In evaluating chronic sialadenitis, assessment at multiple time points is necessary to capture the intermittent and cyclical pattern of obstructive symptoms.

Vasodilation by Verapamil-Nitroglycerin Solution in Microvascular Surgery.

OBJECTIVE: Papaverine is a topical vasodilator commonly used during microvascular surgery to inhibit undesired vasoconstriction. A previous national shortage of papaverine prompted evaluation of an alternative, effective vasodilator. This study aims to assess the experience of a solution of verapamil and nitroglycerin (VG) as a potential alternative pharmacologic vasodilator. STUDY DESIGN: Retrospective case series. SETTING: Two tertiary academic medical centers. SUBJECTS AND METHODS: Among 298 patients, 306 consecutive free tissue transfers performed between 2014 and 2017 for head and neck defect reconstruction utilized a VG solution. Patient and flap characteristics, intraoperative patient and flap complications, and postoperative complications were reviewed. Diameter of the cervical recipient artery was measured intraoperatively before and after topical application of the VG solution in a subset of 43 patients (44 flaps). RESULTS: Flaps included fibula, radial forearm, subscapular system, and anterolateral thigh. In total, 3 (0.98%) flaps failed with varied etiology unrelated to the VG solution (venous thrombosis, arterial anastomosis thrombosis, physical damage to the perforator). Specific to topical application of the VG solution, the mean recipient artery diameter increased from 2.1 to 3.1 mm, a 48% increase (P < .01). There were no intraoperative cardiac events or complications attributable to the VG solution. CONCLUSION: We describe the use of a VG solution for pharmacologic vasodilation during microvascular free tissue transfer. Its use was associated with an acceptable incidence of adverse events, none of which were directly attributable to the VG solution. Apparent and sustained vasodilation was demonstrated. The VG solution represents a safe and efficacious alternative to papaverine in microvascular surgery.

Machine Learning for Predicting Complications in Head and Neck Microvascular Free Tissue Transfer.

OBJECTIVES/HYPOTHESIS: Machine learning (ML) is a type of artificial intelligence wherein a computer learns patterns and associations between variables to correctly predict outcomes. The objectives of this study were to 1) use a ML platform to identify factors important in predicting surgical complications in patients undergoing head and neck free tissue transfer, and 2) compare ML outputs to traditionally employed logistic regression models. STUDY DESIGN: Retrospective cohort study. METHODS: Using a dataset of 364 consecutive patients who underwent head and neck microvascular free tissue transfer at a single institution, 14 clinicopathologic characteristics were analyzed using a supervised ML algorithm of ensemble decision trees to predict surgical complications. The relative importance values of each variable in the ML analysis were then compared to logistic regression models. RESULTS: There were 166 surgical complications, which included bleeding or hematoma in 30 patients (8.2%), fistulae in 25 patients (6.9%), and infection or dehiscence in 52 patients (14.4%). There were 59 take-backs (16.2%), and six total (1.6%) and five partial (1.4%) flap failures. ML models were able to correctly classify outcomes with an accuracy of 65% to 75%. Factors that were identified in ML analyses as most important for predicting complications included institutional experience, flap ischemia time, age, and smoking pack-years. In contrast, the significant factors most frequently identified in traditional logistic regression analyses were patient age (P = .03), flap type (P = .03), and primary site of reconstruction (P = .06). CONCLUSIONS: In this single-institution dataset, ML algorithms identified factors for predicting complications after free tissue transfer that were distinct from traditional regression models. LEVEL OF EVIDENCE: 2c Laryngoscope, 2020.

Treatment modality impact on quality of life for human papillomavirus-associated oropharynx cancer.

OBJECTIVES/HYPOTHESIS: Compare treatment-related quality of life (QOL) impact for early-stage human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC) patients. STUDY DESIGN: Retrospective cohort at a tertiary center. METHODS: Stage I (T0-2/N0-1) HPV+ OPSCC patients (n = 76) with pretreatment Karnofsky scores ≥80 reported QOL after surgery alone (n = 17, 22%), surgery with adjuvant radiation ± chemotherapy (S-a[C]XRT) (n = 23, 30%), or definitive radiation ± chemotherapy (d[C]XRT) (n = 36, 47%) with the University of Washington QOL version 4 (UW-QOL); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (EORTC QLQ-C30) and Head and Neck Module (EORTC QLQ-HN35); University of Michigan Xerostomia, and Neck Dissection Impairment Index questionnaires (median follow-up = 2.2 years, interquartile range = 1.0-4.2 years). Treatment adverse events and gastrostomy tube rates were assessed. RESULTS: Over 87% of each treatment group reported good or better overall QOL. Each group had low gastrostomy tube and treatment-specific complication rates. S-a(C)XRT and d(C)XRT patients had similar mean scores with wide ranges for most individual and all composite categories. S-a(C)XRT compared to d(C)XRT patients reported significantly fewer dental problems (EORTC QLQ-C30/HN35 means = 10.1 vs. 34.3, P = .007), worse appearance (UW-QOL means = 72.8 vs. 82.6, P = .02), and worse coughing (EORTC QLQ-C30/HN35 means = 31.9 vs. 15.7, P = .007). Surgery alone compared to d(C)XRT and S-a(C)XRT patients reported significantly better salivary/taste/oral functions and less pain, financial, oral/dental, and sexual problems. CONCLUSIONS: For early-stage HPV+ OPSCC, patients usually achieve acceptable QOL regardless of treatment. S-a(C)XRT and d(C)XRT patients report generally similar QOL including neck/shoulder pain/function, but with a wide range in a limited patient sample. Surgery alone should be considered, when oncologically and functionally safe, given the better associated QOL. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E48-E56, 2020.

Human Papillomavirus-Associated Oropharyngeal Cancer: Patterns of Nodal Disease.

OBJECTIVE: To characterize patterns of neck lymph node (LN) metastases in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, represented by p16 positivity (p16+OPSCC). STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: Neck dissection (ND) specimens of nonirradiated p16+OPSCC patients were analyzed for frequencies of clinically evident and occult LNs by neck level. Local, regional, and distant recurrences were reviewed. RESULTS: Seventy p16+OPSCC patients underwent primary site transoral robotic surgery and 82 NDs of varying levels. Metastatic pathologic LNs were found at the following frequencies: 0% (0/28) in level I, 75.6% (62/82) in level II with 57.4% (35/61) in level IIA and 13.1% (8/61) in level IIB, 22.0% (18/82) in level III, 7.0% (5/71) in level IV, and 6.3% (1/16) in level V. The level V LN was clinically evident preoperatively. Five of 21 (23.8%) elective NDs contained occult LNs, all of which were in level II and without extranodal extension. Twenty-seven (38.6%) patients underwent adjuvant radiation; 19 (27.1%) patients underwent adjuvant chemoradiation. With a mean follow-up of 29 months, 3 patients had developed recurrences, with all but 1 patient still alive. All patients who recurred had refused at least a component of indicated adjuvant treatment. CONCLUSIONS: For p16+OPSCC, therapeutic NDs should encompass any levels bearing suspicious LNs and levels IIA-B, III, and IV, while elective NDs should be performed and encompass at least levels IIA-B and III. These selective ND plans, followed by indicated adjuvant treatment, are associated with a low nodal recurrence rate.

One-Year symptom outcomes after sialolithiasis treatment with sialendoscopy-assisted salivary duct surgery.

OBJECTIVES: For chronic obstructive sialadenitis, there is a paucity of long-term prospective evidence of disease-specific symptom outcomes after sialendoscopy-assisted salivary duct surgery (SASDS). We prospectively assessed patients with sialolithiasis before and at 3 months and 1 year after SASDS using the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire. METHODS: A prospective cohort study of adult patients with sialolithiasis who underwent SASDS and completed the COSS questionnaire over a 1-year follow-up period. The COSS questionnaire consists of 20 disease-specific symptom questions. COSS score outcomes were classified by complete, partial, and nonresolution, as well as by clinically significant improvement. RESULTS: Ninety-six patients underwent SASDS in 110 glands, of which 69 glands (63%) had findings of sialolithiasis. The following median COSS scores were reported for sialolithiasis glands: preoperative, 27.5 (interquartile range [IQR]: 12.5-44); 3 months, 1 (IQR: 0-5); and 1 year, 1 (IQR: 0-5.5). Patients with sialolithiasis reported statistically significant improvements in COSS scores from preoperative to 3 months post-SASDS (P > 0.05). A vast majority of patients maintained this improvement from 3 months to 1 year, indicating durability. Complete resolution of symptoms was attained in 95% and 85% of glands at 3 months and 1 year, respectively. Open/hybrid compared to endoscopic-only sialolithiasis extraction achieved similar 3-month and 1-year COSS outcomes. Potential risk factors for symptom persistence after SASDS included nonreachable parenchymal sialoliths and concurrent inflammatory disease and/or stenosis. CONCLUSION: SASDS for sialolithiasis extraction is associated with durable, long-term benefit regardless of endoscopic or open technique or sialolith location, suggesting that subsequent ductal stenosis from iatrogenic or sialolithiasis-related inflammation fibrosis is unlikely. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:396-402, 2019.

One-year outcomes of sialendoscopic-assisted salivary duct surgery for sialadenitis without sialolithiasis.

OBJECTIVES: To prospectively examine durability of long-term outcomes in sialendoscopy-assisted salivary duct surgery (SASDS) in chronic obstructive sialadenitis without sialolithiasis (COSWS). METHODS: A prospective cohort study of adult patients with COSWS who completed Chronic Obstructive Sialadenitis Symptoms (COSS) Questionnaire prior to and at 3 months and 1 year following SASDS. COSS scores scaled to 0 to 100 were analyzed by statistically significant improvements and previously published ranges corresponding to complete, partial, and nonresolution of symptoms. RESULTS: Twenty-nine patients with COSWS affecting 41 glands had statistically significant improvements in COSS scores at 3 months following SASDS. These improvements usually were sustained at 1 year, supporting durability of treatment effect over time. A majority of cases (30 of 41, 73%) achieved at least a partial resolution of sialadenitis symptoms (COSS score ≤ 25) at 1-year follow-up. Symptom improvement after SASDS was noted in 14 of 18 (78%) glands with radioiodine-induced sialadenitis (RAI-IS). The highest proportion of persistent or recurrent disease at 1-year post-SASDS was found in autoimmune sialadenitis (2 of 4, 50%) and glands with proximal or multifocal stenoses (6 of 12, 50%). At 1 year, distal duct stenoses achieved a significantly higher proportion of partial or complete symptom resolution (18 of 21, 86%) than cases with proximal or multifocal stenoses (6 of 12, 50%; P = 0.044). CONCLUSIONS: SASDS is effective in reducing symptoms in duct stenosis and RAI-IS, usually with durable treatment benefits at long-term follow-up. Distal stenoses appear to be more amenable to sialendoscopic treatment, achieving greater symptom reduction than proximal/multifocal stenoses. Additional larger multi-center studies are needed to further characterize risk factors for COSWS refractory to SASDS. LEVEL OF EVIDENCE: 2 Laryngoscope, 129:890-896, 2019.

Advanced head and neck surgical techniques: A survey of US otolaryngology resident perspectives.

OBJECTIVES: To assess the perspectives of OHNS residents with regards to their training in the following advanced head and neck surgery techniques: transoral robotic surgery (TORS), transoral laser microsurgery (TLM), sialendoscopy, and surgeon-performed ultrasound (SP-US) for possible curricula development. METHODS: Cross-sectional survey. A 20-item questionnaire was electronically distributed to OHNS residency programs assessing volume of cases, training barriers, satisfaction, additional training preferences, and pertinence to future practice. RESULTS: One hundred thirty-one residents completed the questionnaire. Trainee satisfaction with advanced techniques did not vary significantly with level of training (PGY) or intent to pursue fellowship. Residents who participated in more TLM, sialendoscopy, and SP-US cases were significantly more likely to be satisfied with their training (all p<0.05). The most frequently reported limitation to training was low home institution procedure volume. Seventy-eight of 123 respondents (63.4%) indicated insufficient opportunity to participate in TORS, with most residents reporting that TORS was preferentially performed by attendings (59/78, 75.6%). Forty-five of 126 (35.7%) reported having adequate access to skills training in TORS, compared to 43.6%, 48.4%, and 54.8% for sialendoscopy, TLM, and SP-US, respectively. A vast majority expressed interest in home institution-sponsored training courses in SP-US (120/127, 94.5%) and sialendoscopy (105/129, 81.4%). Many anticipated using SP-US (63.3%) and sialendoscopy (49.6%) in their future practices. CONCLUSION: Greater resident participation in advanced head and neck surgical procedures is associated with higher trainee satisfaction. There is a possible need for additional home institution-sponsored training courses, especially in sialendoscopy and SP-US. LEVEL OF EVIDENCE: N/A.

Surgeon-performed ultrasound for the assessment of parotid masses.

BACKGROUND: Studies on parotid gland ultrasound assessments performed specifically by surgeons are seldom reported. METHODS: Retrospective series of a single academic surgeon experience, analyzing 70 new parotid masses with evaluable preoperative SP-US characteristics, location measurements, and perioperative events. RESULTS: 31/70 masses were malignant. SP-US characteristics significantly associated with both malignancy and positive margins included extraparenchymal extension, irregular borders, hypervascularity, infiltration, and the lack of deep enhancement. The larger the skin-to-deep-aspect-of-tumor distance, the more likely the tumor was deep to FN. For the 39 cytologically benign tumors, neither CT nor MRI provided additional information to change management except for full delineation of parapharyngeal space extension in 2 cases. CONCLUSION: SP-US can help predict parotid mass benignity/malignancy, positive margin risk, and tumor relation to FN. SP-US may be used as the sole imaging in cytologically benign tumors unless the deep tumor extent cannot be identified.

Fetal Mammalian Heart Generates a Robust Compensatory Response to Cell Loss.

BACKGROUND: Heart development is tightly regulated by signaling events acting on a defined number of progenitor and differentiated cardiac cells. Although loss of function of these signaling pathways leads to congenital malformation, the consequences of cardiac progenitor cell or embryonic cardiomyocyte loss are less clear. In this study, we tested the hypothesis that embryonic mouse hearts exhibit a robust mechanism for regeneration after extensive cell loss. METHODS AND RESULTS: By combining a conditional cell ablation approach with a novel blastocyst complementation strategy, we generated murine embryos that exhibit a full spectrum of cardiac progenitor cell or cardiomyocyte ablation. Remarkably, ablation of up to 60% of cardiac progenitor cells at embryonic day 7.5 was well tolerated and permitted embryo survival. Ablation of embryonic cardiomyocytes to a similar degree (50% to 60%) at embryonic day 9.0 could be fully rescued by residual myocytes with no obvious adult cardiac functional deficit. In both ablation models, an increase in cardiomyocyte proliferation rate was detected and accounted for at least some of the rapid recovery of myocardial cellularity and heart size. CONCLUSION: Our study defines the threshold for cell loss in the embryonic mammalian heart and reveals a robust cardiomyocyte compensatory response that sustains normal fetal development.

Molecular regulation of cardiomyocyte differentiation.

The heart is the first organ to form during embryonic development. Given the complex nature of cardiac differentiation and morphogenesis, it is not surprising that some form of congenital heart disease is present in ≈1 percent of newborns. The molecular determinants of heart development have received much attention over the past several decades. This has been driven in large part by an interest in understanding the causes of congenital heart disease coupled with the potential of using knowledge from developmental biology to generate functional cells and tissues that could be used for regenerative medicine purposes. In this review, we highlight the critical signaling pathways and transcription factor networks that regulate cardiomyocyte lineage specification in both in vivo and in vitro models. Special focus will be given to epigenetic regulators that drive the commitment of cardiomyogenic cells from nascent mesoderm and their differentiation into chamber-specific myocytes, as well as regulation of myocardial trabeculation.

Identification of cardiovascular lineage descendants at single-cell resolution.

The transcriptional profiles of cardiac cells derived from murine embryos and from mouse embryonic stem cells (mESCs) have primarily been studied within a cell population. However, the characterization of gene expression in these cells at a single-cell level might demonstrate unique variations that cannot be appreciated within a cell pool. In this study, we aimed to establish a single-cell quantitative PCR platform and perform side-by-side comparison between cardiac progenitor cells (CPCs) and cardiomyocytes (CMs) derived from mESCs and mouse embryos. We first generated a reference map for cardiovascular single cells through quantifying lineage-defining genes for CPCs, CMs, smooth muscle cells (SMCs), endothelial cells (EDCs), fibroblasts and mESCs. This panel was then applied against single embryonic day 10.5 heart cells to demonstrate its ability to identify each endocardial cell and chamber-specific CM. In addition, we compared the gene expression profile of embryo- and mESC-derived CPCs and CMs at different developmental stages and showed that mESC-derived CMs are phenotypically similar to embryo-derived CMs up to the neonatal stage. Furthermore, we showed that single-cell expression assays coupled with time-lapse microscopy can resolve the identity and the lineage relationships between progenies of single cultured CPCs. With this approach, we found that mESC-derived Nkx2-5(+) CPCs preferentially become SMCs or CMs, whereas single embryo-derived Nkx2-5(+) CPCs represent two phenotypically distinct subpopulations that can become either EDCs or CMs. These results demonstrate that multiplex gene expression analysis in single cells is a powerful tool for examining the unique behaviors of individual embryo- or mESC-derived cardiac cells.

Somatic Cell Reprogramming into Cardiovascular Lineages.

Ischemic cardiac disease is the leading cause of death in the developed world. The inability of the adult mammalian heart to adequately repair itself has motivated stem cell researchers to explore various strategies to regenerate cardiomyocytes after myocardial infarction. Over the past century, progressive gains in our knowledge about the cellular mechanisms governing fate determination have led to recent advances in cellular reprogramming. The identification of specific factors capable of inducing pluripotent phenotype in somatic cells as well as factors that can directly reprogram somatic cells into cardiomyocytes suggests the potential for these approaches to translate into clinical therapies in the future. Although conceptually appealing, the field of cell lineage reprogramming is in its infancy, and further research will be needed to improve the efficiency of the reprogramming process and the fidelity of the reprogrammed cells to their in vivo counterpart.