Widespread innervation of motoneurons by spinal V3 neurons globally amplifies locomotor output in mice.

While considerable progress has been made in understanding the neuronal circuits that underlie the patterning of locomotor behaviours such as walking, less is known about the circuits that amplify motoneuron output to enable adaptable increases in muscle force across different locomotor intensities. Here, we demonstrate that an excitatory propriospinal neuron population (V3 neurons, Sim1 + ) forms a large part of the total excitatory interneuron input to motoneurons (∼20%) across all hindlimb muscles. Additionally, V3 neurons make extensive connections among themselves and with other excitatory premotor neurons (such as V2a neurons). These circuits allow local activation of V3 neurons at just one segment (via optogenetics) to rapidly depolarize and amplify locomotor-related motoneuron output at all lumbar segments in both the in vitro spinal cord and the awake adult mouse. Interestingly, despite similar innervation from V3 neurons to flexor and extensor motoneuron pools, functionally, V3 neurons exhibit a pronounced bias towards activating extensor muscles. Furthermore, the V3 neurons appear essential to extensor activity during locomotion because genetically silencing them leads to slower and weaker mice with a poor ability to increase force with locomotor intensity, without much change in the timing of locomotion. Overall, V3 neurons increase the excitability of motoneurons and premotor neurons, thereby serving as global command neurons that amplify the locomotion intensity.

Embryonic temporal-spatial delineation of excitatory spinal V3 interneuron diversity.

Spinal neural circuits that execute movement are composed of cardinal classes of neurons that emerged from distinct progenitor lineages. Each cardinal class contains multiple neuronal subtypes characterized by distinct molecular, anatomical, and physiological characteristics. Through a focus on the excitatory V3 interneuron class, here we demonstrate that interneuron subtype diversity is delineated through a combination of neurogenesis timing and final laminar settling position. We have revealed that early-born and late-born embryonic V3 temporal classes further diversify into subclasses with spatially and molecularly discrete identities. While neurogenesis timing accounts for V3 morphological diversification, laminar settling position accounts for electrophysiological profiles distinguishing V3 subtypes within the same temporal classes. Furthermore, V3 interneuron subtypes display independent behavioral recruitment patterns demonstrating a functional modularity underlying V3 interneuron diversity. These studies provide a framework for how early embryonic temporal and spatial mechanisms combine to delineate spinal interneuron classes into molecularly, anatomically, and functionally relevant subtypes in adults.

Management of positive resection margins following transoral laser microsurgery for glottic cancer.

Objectives: The current literature provides limited guidance on the management of positive margins (PMs) following transoral laser microsurgery (TLM) for glottic squamous cell carcinoma (SCC). Long-term data exploring the treatment of PMs with both initial observation and re-resection are limited. Our objective was to determine the optimal treatment for PM patients following TLM for glottic SCC. Methods: Clinical information on glottic SCC patients with PMs following treatment with TLM was prospectively collected at our institution from 2007 to 2018. We use a laryngeal template during the initial TLM where the area of resection is outlined for future reference. Data were compared with univariate analysis and survival plots were generated using the Kaplan-Meier method. Results: A total of 29 patients with PMs were treated with either re-resection (19 patients), close observation (6 patients), or adjuvant radiation alone (4 patients). Re-resection patients had SCC or severe dysplasia on initial margin pathology and 23% with early-stage disease had recurrence (T1-T2). Five (83%) patients who underwent close observation required re-resection based on clinical suspicion of recurrence (confirmed on final pathology), which was significantly different from the re-resection patients (p < .05). Close observation was therefore discontinued as a management of PMs. Four patients (21%) had no residual malignancy on re-resection specimens. Deep margins only accounted for 17% of all PMs. Disease-specific survival for all PM patients at 5 years was 82.4% (SE 9.6%, CI 53.4%-91.6%). Conclusions: Our long-term experience with treating early-stage glottic SCC with TLM supports re-resection as an appropriate management for cases of PMs. Level of Evidence: 4.

Five-year survival outcomes in oropharyngeal squamous cell carcinoma following transoral laser microsurgery.

Objective: To determine the 5-year survival outcomes of patients with oropharyngeal cancer treated with transoral laser microsurgery at our institution. Methods: A prospective longitudinal cohort study of all cases of oropharyngeal squamous cell cancer or clinically unknown primaries diagnosed at our institution between September 1, 2014, to December 31, 2019, treated with primary transoral laser microsurgery were analyzed. Patients with a previous history of head and neck radiation were excluded from analysis. Kaplan-Meier survival curves were used to estimate 5-year overall survival, disease-specific survival, local control, and recurrence free survival rates in oropharyngeal squamous cell carcinoma. Results: Of 142 patients identified, 135 met criteria and were included in the survival analysis. Five-year local control rates in p16 positive and negative disease were 99.2% and 100%, respectively, with one locoregional failure in the p16 positive cohort. Five-year overall survival, disease-specific survival, and recurrence free survival in p16 positive disease were 91%, 95.2%, and 87% respectively (n = 124). Five-year overall survival, disease-specific survival, and recurrence free survival in p16 negative disease were 39.8%, 58.3%, and 60%, respectively (n = 11). The permanent gastrostomy tube rate was 1.5% and zero patients received a tracheostomy at the time of surgery. One patient (0.74%) required a return to the OR for a post-operative pharyngeal bleed. Conclusion: Transoral laser microsurgery is a safe primary treatment option for oropharyngeal squamous cell carcinoma with high 5-year survival outcomes, notably in p16 positive disease. More randomized trials are needed to compare survival outcomes and associated morbidity in transoral laser microsurgery compared to treatment with primary chemoradiation. Level of Evidence: 3.

Frequency and accuracy of intraoperative bone margin sampling for T4a cancers of the head and neck at the QEII Health Sciences Centre: a retrospective chart review.

BACKGROUND: Stage T4a cancers are associated with a 5-year survival of 21.6-59.0%. Adequate resection of these tumors is a critical factor in maximizing survival. Tumors invading bone pose a unique challenge to intraoperative bone margin assessment. Due to processing limitations, there had been no formal standardized protocol for intraoperative bone sampling at the QEII Health Sciences Centre. These resections often involve extensive reconstruction, making salvage surgery difficult if positive margins are detected post-surgically. The purpose of this study was to assess the accuracy and frequency of intraoperative bone margin assessment during the study period and to determine survival and recurrence rates associated with positive final bone margins. METHODS: A retrospective chart review was conducted including patients with stage T4a head and neck cancer involving bone that underwent primary surgical resection in Nova Scotia between 2009 and 2019. Eligible patients were identified through the Cancer Care Nova Scotia registry. Exclusion criteria included patients with stage T4a tumors involving bone that did not receive primary surgical treatment with curative intent and patients with stage T4a tumors that did not invade bone. RESULTS: Of 67 patients included, 50 were amenable to intraoperative bone margin sampling while 18 had intraoperative sampling. Four patients had positive intraoperative margins and one had final positive bone margins. The incidence of final bone margin positivity was 7.5%. Median survival following surgery was 4.56 years for patients with final negative bone margins (n = 62) and 3.98 years for patients with positive final bone margins (n = 5). All patients with final positive bone margins received adjuvant radiation therapy. Of patients with negative final bone margins, 16.1% received no adjuvant therapy, 61.3% received adjuvant radiation therapy and 21.0% received adjuvant chemoradiation therapy. CONCLUSION: Intraoperative bone margin sampling occurred in 26.8% of all cases and 36.0% of amenable cases. Median survival of patients with positive final bone margins was 0.58 years lower than those with negative final bone margins, although this difference did not reach statistical significance. This will provide baseline data for comparison of the standardized intraoperative bone margin sampling protocol implemented at the QEII Health Sciences Centre.

Margin Sampling and Survival Outcomes in Oral Cavity and p16-Positive Oropharyngeal Squamous Cell Carcinoma.

Objective: To compare the association of margin sampling technique on survival outcomes in surgically treated cT1-2 oral cavity and oropharyngeal squamous cell carcinoma. Study Design: A prospective longitudinal cohort study. Setting: Tertiary care academic teaching hospital in Halifax, Nova Scotia. Methods: All cases of surgically treated cT1-2 oral cavity and oropharyngeal cancer undergoing specimen-oriented margin analysis between January 1, 2017, and December 31, 2018 were analyzed. The specimen-oriented cohort was compared with a cohort of patients from January 1, 2009, to December 31, 2014, where a defect-oriented margin sampling protocol was used. Kaplan-Meier survival curves were used to estimate 2-year overall survival, disease-specific survival, local control, and recurrence-free survival rates in oral cavity and p16-positive oropharyngeal squamous cell carcinoma. Cox proportional hazards models were used to assess the effect of margin sampling method on disease-specific survival and local control. Results: There was no significant association between margin sampling technique and 2-year survival outcomes for surgically treated cT1-2 oral cavity and oropharyngeal squamous cell carcinoma. In the multivariate Cox proportional hazard model, the hazard ratio (HR) of specimen-oriented sampling was not significantly different for disease-specific survival (HR, 1.32; 95% CI, 0.3032-5.727; P = .713) or local control (HR, 0.4087; 95% CI, 0.0795-2.099; P = .284). Conclusion: Intraoperative margin sampling method was not associated with a significant change in 2-year survival outcomes. Despite no effect on survival outcomes, implementation of a specimen-oriented sampling method has potential for cost avoidance by decreasing the number of re-resections for positive or close margins.

The role of V3 neurons in speed-dependent interlimb coordination during locomotion in mice.

Speed-dependent interlimb coordination allows animals to maintain stable locomotion under different circumstances. The V3 neurons are known to be involved in interlimb coordination. We previously modeled the locomotor spinal circuitry controlling interlimb coordination (Danner et al., 2017). This model included the local V3 neurons that mediate mutual excitation between left and right rhythm generators (RGs). Here, our focus was on V3 neurons involved in ascending long propriospinal interactions (aLPNs). Using retrograde tracing, we revealed a subpopulation of lumbar V3 aLPNs with contralateral cervical projections. V3OFF mice, in which all V3 neurons were silenced, had a significantly reduced maximal locomotor speed, were unable to move using stable trot, gallop, or bound, and predominantly used a lateral-sequence walk. To reproduce this data and understand the functional roles of V3 aLPNs, we extended our previous model by incorporating diagonal V3 aLPNs mediating inputs from each lumbar RG to the contralateral cervical RG. The extended model reproduces our experimental results and suggests that locally projecting V3 neurons, mediating left-right interactions within lumbar and cervical cords, promote left-right synchronization necessary for gallop and bound, whereas the V3 aLPNs promote synchronization between diagonal fore and hind RGs necessary for trot. The model proposes the organization of spinal circuits available for future experimental testing.

Injection laryngoplasty during transoral laser microsurgery for early glottic cancer: a randomized controlled trial.

BACKGROUND: Transoral laser microsurgery is widely used for treating T1/T2 glottic cancers. Hyaluronic acid (HA) is commonly used in vocal cord augmentation. We investigated the impact of intra-operative injection laryngoplasty on voice outcomes in early glottic cancer. METHODS: Twenty patients were randomized to the treatment group receiving HA injection to the vocal cord contralateral to the lesion; or the control group, receiving no injection. Patients had a Voice Handicap Index-10 (VHI-10) questionnaire and a Maximum Phonation Time (MPT) measurement preoperatively and at 3, 12 and 24 months post-operatively. Mean change in VHI-10 and MPT, compared to baseline and between time points, were compared. Survival estimates were calculated. RESULTS: Mean VHI-10 scores improved over time amongst all patients. There were no changes in mean VHI-10 from pre-operative values to 3, 12 or 24 months post-operatively. There were no significant differences when comparing various timepoints between groups. There were no significant changes in MPT amongst the groups, or the time-points compared. Two-year overall survival was 91.7%; disease free survival was 80.9%; no difference in recurrence free survival was seen between the groups. CONCLUSION: Subjective voice scores improved over time in both groups; there were no improvements in VHI-10 or MPT scores in the injection group, over control, at any time points. We saw no significant impact for intra-operative HA injection laryngoplasty on subjective or objective voice outcomes following surgery for early glottic cancers.

Functional and Oncologic Outcomes of Octogenarians Undergoing Transoral Laser Microsurgery for Laryngeal Cancer.

OBJECTIVE: To evaluate the oncologic and functional outcomes of transoral laser microsurgery (TLM) for glottic cancers in patients ≥80 years. STUDY DESIGN: Prospectively collected case series. SETTING: QEII Health Sciences Centre, Halifax, Canada. METHODS: This case series used a prospectively collected glottic cancer database to examine consecutive elderly patients (≥80 years old) undergoing TLM. Kaplan-Meier analysis was used to evaluate rates of disease-free, disease-specific, and overall survival as the primary end points of oncologic control. Secondary functional outcomes included voice function, length of hospital stay, and time to readmission. RESULTS: From 2005 to 2017, 17 octogenarian patients underwent TLM for glottic cancer. Median follow-up was 4.19 years (interquartile range, 0.71-6.95). Kaplan-Meier estimates of 5-year survival were 78.4% (disease free), 92.9% (disease specific), and 81.9% (overall). The median length of hospital stay was 1 day (range, 0-8). There was only 1 readmission within 30 days of surgery. No patients in this study developed significant surgical or postoperative complications requiring unplanned readmissions. Patient-perceived voice function improved to normal after treatment in 62.5% of patients. CONCLUSION: The results of this study suggest that TLM is a safe and effective treatment modality for glottic cancer in patients aged ≥80 years, providing good oncologic control and satisfactory functional outcomes.

Patient and tumor factors contributing to distant metastasis in well-differentiated thyroid cancer: a retrospective cohort study.

BACKGROUND: Distant metastasis in thyroid cancer significantly reduces survival in patients with well-differentiated thyroid carcinoma (WDTC). There is limited information available to clinicians regarding pathological features that confer a higher risk of distant metastasis (DM). This study aimed to identify patient and tumor factors that were associated with the development of DM over time in patients with WDTC. METHODS: A retrospective cohort analysis of patients with WDTC (n = 584) at our institution was performed between 2007 and 2017. A total of 39 patients with DM and 529 patients with no DM (NDM) were included. Patient demographics, tumor characteristics and patient survival were compared between the DM and NDM groups using a univariate analysis. Multivariate Cox-proportional hazards model was used to evaluate the risk of developing distant metastasis over time. Kaplan-Meier analysis was used to compare survival between the DM and NDM groups. RESULTS: Distant metastasis had a substantial impact on disease-specific survival (DSS) at 5 and 10-years in the DM group; 71.0% (SE 8.4%) and 46.9% (SE 11.6%) respectively, compared to 100% survival in the NDM group (p < 0.001). The DM group had significantly higher proportions of males, lymphovascular invasion (LVI), nodal metastasis (NM), large tumor size (TS), extrathyroidal extension (ETE), positive resection margins, multifocality, follicular thyroid cancer (FTC), tall cell variant of papillary thyroid cancer (PTC), and Hurthle cell carcinoma (HCC), when compared to the NDM group (p < 0.05). A TS ≥ 2 cm (Hazard Ratio (HR) 1.370), NM (HR 3.806) and FTC (HR 7.068) were associated with a significantly increased hazard of developing distant metastasis in patients with WDTC. CONCLUSIONS: TS ≥ 2 cm, NM and FTC are associated with a significantly increased propensity for developing DM in our cohort of WDTC patients.

Medical Intervention Alone vs Surgical Drainage for Treatment of Peritonsillar Abscess: A Systematic Review and Meta-analysis.

OBJECTIVE: Peritonsillar abscesses (PTAs) are common emergency consultations for otolaryngologists. Medical management alone may offer satisfactory treatment without the risk associated with surgical drainage. Therefore, we performed a systematic review of medical treatment alone compared to surgical drainage for the treatment of PTA. DATA SOURCES: MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov. REVIEW METHODS: Studies comparing the outcomes of medically treated to surgically treated patients were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. All screening and data extraction were completed by 2 independent reviewers. Meta-analysis was performed using a random-effects model. Subgroup and sensitivity analyses were performed. RESULTS: Ten cohort studies and 2 randomized studies were included (ntotal = 33,468). Study quality was low, with only 1 study providing multivariable analysis. The combined rate of treatment failure in patients initially treated with medical management alone was 5.7% compared to 5.5% in the surgical group. There was no statistically significant difference in the odds of treatment failure between interventions through random-effects meta-analysis (odds ratio [OR], 1.10; 95% CI, 0.53-2.26; I 2 = 41%; P = .13). Subgroup analysis excluding pediatric-specific studies revealed similar odds of treatment failure when initially managed with medical intervention (OR, 0.92; 95% CI, 0.56-1.50; P = .39; I 2 = 0%). CONCLUSION: Meta-analysis of available studies demonstrated no difference in odds of treatment failure for patients with PTA managed through medical intervention alone compared to surgical intervention. These findings should be interpreted with caution due to high probability of bias and overall low quality of studies.

Intraoperative Primary Tumor Identification and Margin Assessment in Head and Neck Unknown Primary Tumors.

OBJECTIVE: Surgical management of the unknown primary head and neck squamous cell carcinoma (UP HNSCC) remains controversial due to challenging clinical diagnosis. This study compares positron emission tomography-computed tomography (PET-CT) findings with intraoperative identification of primary tumors and compares intraoperative frozen-section margins to final histopathology. In addition, adjuvant therapy indications are provided. STUDY DESIGN: Prospective cohort study. SETTING: Academic university hospital. SUBJECTS AND METHODS: Sixty-one patients with UP HNSCC were included. Patients received PET-CT, followed by oropharyngeal transoral laser microsurgery (TLM). Margins were assessed intraoperatively using frozen sections and afterward by final histopathology. Adjuvant treatment was based on final histopathology. RESULTS: The sensitivity of localizing the primary tumor with PET-CT was 50.9% with a specificity of 82.5%. The primary tumor was found intraoperatively on frozen sections in 82% (n = 50) of patients. Five more tumors were identified on final histopathology, leading to a total of 90% (n = 55). Of the 50 intraoperatively found tumors, 98% (n = 49) had negative margins on frozen sections, and 90% (n = 45) were truly negative on final histopathology. Eighteen patients (29.5%) avoided adjuvant treatment. CONCLUSION: PET-CT localized the primary tumor in fewer than half the cases. This protocol identified 90% of primary tumors. Intraoperative frozen-section margin assessment has shown potential with a specificity of 92% compared to final histopathology. As a result, adjuvant therapy was avoided in almost one-third of our patients.

Systematic review and meta-analysis of T1 glottic cancer outcomes comparing CO2 transoral laser microsurgery and radiotherapy.

BACKGROUND: The objective of this study is to compare the oncologic outcomes of CO2 transoral laser microsurgery (TLM) and radiotherapy (RT) for treatment of T1 glottic carcinoma. METHODS: A literature search was conducted in the following databases: Medline/PubMed, Web of Science, EMBASE, and the Cochrane Library. Search results were screened, and publications comparing oncologic outcomes of T1N0M0 glottic carcinoma treated with TLM or RT were included. Data was extracted independently by two authors, and publication quality was graded according to the Oxford Centre for Evidence-based Medicine. Meta-analysis was performed for overall survival, disease specific survival, laryngeal preservation, and local control. RESULTS: Sixteen studies were included in the meta-analysis, the majority being retrospective cohort studies with two prospective cohort studies. Included studies were rated as either Level II or III evidence. Meta-analysis favoured treatment with TLM for T1 glottic carcinoma patients for the following outcomes: overall survival (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.07-2.14; P = 0.02), disease specific survival (OR, 2.70; CI, 1.32-5.54; P = 0.007), and laryngeal preservation (OR, 6.31; CI, 3.77-10.56; P < 0.00001). There was no difference in local control between TLM and RT in T1 glottic cancer (OR, 1.19; CI, 0.79-1.81; P = 0.40). DISCUSSION: Our study provides a current and thorough comparison of TLM and RT outcomes in T1 glottic carcinoma. Limitations of our study include lack of randomized control trials, and non-randomized allocation of patients to treatment groups. Our meta-analysis suggests that TLM is the superior modality in terms of overall survival, disease specific survival, and laryngeal preservation. Future prospective randomized controlled studies are required for confirming these findings and developing appropriate clinical practice guidelines. LEVEL OF EVIDENCE: 2A; as per the Centre of Evidence Based Medicine.

The downstaging approach to irresectable oesophageal and gastric cancer: a single centre experience.

BACKGROUND: There is uncertainty over optimal management of locally advanced non-metastatic oesophageal and gastric (OG) adenocarcinomas which are deemed irresectable at time of diagnosis due to local tumour or nodal burden. Current practice in our regional centre is to administer chemotherapy in a "downstaging" strategy in the hope of achieving tumour shrinkage to allow radical treatment. Patients without sufficient response to downstaging are treated palliatively. The aim of this study was to review our single unit outcomes of this treatment strategy. METHODS: Data was collected retrospectively from electronic patient records on all cases discussed at regional MDT over a 32-month period (January 2015-August 2017). RESULTS: A total of 44 patients [70.5% male, median age 70 years, 13 (29.5%) oesophageal, 12 (27.3%) junctional and 19 (43.2%) gastric] were included in the study. Thirty-six (81.8%) of patients received the full number of planned cycles of chemotherapy; toxicity and disease progression (both 6.8% of cases) were the most common reasons for early cessation of treatment. Seventeen (38.6%) patients underwent resection and an R0 resection was achieved in 13 (76.5%) of these patients. After median follow up of 16.8 months, the median overall survival (OS) in the resection vs. palliative cohorts was 42.6 vs. 16.4 months (P<0.05). CONCLUSIONS: Our data show that a downstaging approach can be successfully implemented (R0 resection achieved) in up to a third of patients with good survival results. Further prospective data identifying patient and pathological characteristics predicting response to treatment are needed to optimise selection into a downstaging programme.

Submental liposuction for the management of lymphedema following head and neck cancer treatment: a randomized controlled trial.

BACKGROUND: Patients who have undergone treatment for head and neck cancer are at risk for neck lymphedema, which can severely affect quality of life. Liposuction has been used successfully in cancer patients who suffer from post-treatment limb lymphedema. The purpose of our study was to review the outcomes of head and neck cancer patients at our center who have undergone submental liposuction for post-treatment lymphedema and compare their subsequent results with a control group. METHODS: All head and neck cancer patients at an oncology center in tertiary hospital setting who complained to their attending surgeon or radiation oncologist regarding cervical lymphedema secondary to head and neck cancer treatment, and had been disease-free for a minimum of one year, with no previous facial plastic surgical procedures were eligible for inclusion into the study. Study design was a non-blinded randomized controlled trial. Twenty patients were randomized into a treatment arm (underwent submental liposuction n = 10) and control arm (n = 10). Both groups of patients completed two surveys (Modified Blepharoplasty Outcome Evaluation and the validated Derriford Appearance Scale) on initial office visit after consenting for the trial. The treatment group then completed the surveys 6 months post-operatively while the control group filled the surveys 6 months after the initial assessment but had no intervention. Mann-Whitney U tests were performed to compare the responses of those that did and did not receive liposuction. RESULTS: Our study demonstrated a statistically significant improvement in patients' self-perception of appearance and statistically significant subjective scoring of appearance following submental liposuction. CONCLUSIONS: Submental liposuction is an effective and safe procedure to improves the quality of life for head and neck cancer patients suffering from post-treatment lymphedema.

Spatial patterns of pollutants in water of metropolitan drain in Lahore, Pakistan, using multivariate statistical techniques.

The present study was conducted to investigate the pollutant load in surface water of the Sattukatla drain in Lahore, Pakistan. This drain is receiving high volumes of pollutants from industries and municipal sewage. To study the pollution status of this urban drain, different parameters such as pH, EC, TDS, BOD, NO3, PO4, COD, K, Mg, Ca, Ni, Fe, Co, Pb, Cu, Cd, and Zn were analyzed. These 17 parameters were monitored along the longitudinal gradient of drain consisting of 15 key sampling sites. The studied parameters were subjected to hierarchical cluster analysis (HCA) and factor analysis (FA). The HCA divided 15 sampling sites into three zones, i.e., low pollution, medium pollution, and high pollution. The PCA identified three major contributors, industrial followed by municipal sewage and agricultural sources. The trend of heavy metal levels was observed as Cu > Zn > Fe > Pb > Co > Ni > Cd. The results indicate levels of pollutants above the permissible limits described by NEQS, Pakistan for wastewater. There is an urgent need to address the issue and install treatment plants to reduce the pollution load on this urban drain in Lahore city.

Management of head and neck primary unknown squamous cell carcinoma using combined positron emission tomography-computed tomography and transoral laser microsurgery.

OBJECTIVES/HYPOTHESIS: The unknown primary of the neck is commonly encountered by the head and neck surgeon. Despite the exhaustive diagnostic tools employed in traditional detection protocols, many unknown primaries are not found, and the patient is subjected to wide-field radiation and chemotherapy during treatment. Localizing the primary tumor has demonstrated therapeutic benefits, improved quality of life, and overall survival. The authors' objective was to determine the efficacy of a new management protocol for unknown primaries of the head and neck. STUDY DESIGN: Prospective cohort study. METHODS: Our technique involved a preoperative positron emission tomography-computed tomography (PET-CT) followed by a planned transoral laser microsurgery (TLM) approach. Efficacy was assessed based on survival statistics, disease control, detection rates, the proportion of patients not receiving adjuvant therapy, and the proportion of PET-CT scans helpful for detection of the primary cancer. RESULTS: The occult primary was located in 25 of the 27 patients (93%), with the majority found in the palatine tonsil (52%). Both overall survival and disease-specific survival was 80% at 36 months. Local control was achieved in 100% of patients. After surgery, 37.0% (n = 10) received adjuvant radiation alone and 33.3% (n = 9) of patients went on to receive adjuvant chemoradiation. On imaging, 72% (n = 18) of PET-CT scans correctly localized the primary tumor. CONCLUSIONS: Occult head and neck primaries present a diagnostic challenge that is not adequately overcome using traditional detection protocols. The current study presents our unique protocol at Dalhousie University, which demonstrates the efficacy of the PET-CT TLM protocol from both a detection and therapeutic perspective. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2307-2311, 2018.

Source and Biological Response of Biochar Organic Compounds Released into Water; Relationships with Bio-Oil Composition and Carbonization Degree.

Water-soluble organic compounds (WSOCs) were extracted from corn stalk biochar produced at increasing pyrolysis temperatures (350-650 °C) and from the corresponding vapors, collected as bio-oil. WSOCs were characterized by gas chromatography (semivolatile fraction), negative electron spray ionization high resolution mass spectrometry (hydrophilic fraction) and fluorescence spectroscopy. The pattern of semivolatile WSOCs in bio-oil was dominated by aromatic products from lignocellulose, while in biochar was featured by saturated carboxylic acids from hemi/cellulose and lipids with concentrations decreasing with decreasing H/C ratios. Hydrophilic species in poorly carbonized biochar resembled those in bio-oil, but the increasing charring intensity caused a marked reduction in the molecular complexity and degree of aromaticity. Differences in the fluorescence spectra were attributed to the predominance of fulvic acid-like structures in biochar and lignin-like moieties in bio-oil. The divergence between pyrolysis vapors and biochar in the distribution of WSOCs with increasing carbonization was explained by the hydrophobic carbonaceous matrix acting like a filter favoring the release into water of carboxylic and fulvic acid-like components. The formation of these structures was confirmed in biochar produced by pilot plant pyrolysis units. Biochar affected differently shoot and root length of cress seedlings in germination tests highlighting its complex role on plant growth.

Combination of electrospray ionization, atmospheric pressure photoionization and laser desorption ionization Fourier transform ion cyclotronic resonance mass spectrometry for the investigation of complex mixtures - Application to the petroleomic analysis of bio-oils.

The comprehensive description of complex mixtures such as bio-oils is required to understand and improve the different processes involved during biological, environmental or industrial operation. In this context, we have to consider how different ionization sources can improve a non-targeted approach. Thus, the Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been coupled to electrospray ionization (ESI), laser desorption ionization (LDI) and atmospheric pressure photoionization (APPI) to characterize an oak pyrolysis bio-oil. Close to 90% of the all 4500 compound formulae has been attributed to CxHyOz with similar oxygen class compound distribution. Nevertheless, their relative abundance in respect with their double bound equivalent (DBE) value has evidenced significant differences depending on the ion source used. ESI has allowed compounds with low DBE but more oxygen atoms to be ionized. APPI has demonstrated the efficient ionization of less polar compounds (high DBE values and less oxygen atoms). The LDI behavior of bio-oils has been considered intermediate in terms of DBE and oxygen amounts but it has also been demonstrated that a significant part of the features are specifically detected by this ionization method. Thus, the complementarity of three different ionization sources has been successfully demonstrated for the exhaustive characterization by petroleomic approach of a complex mixture.