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Head and neck squamous cell carcinoma (HNSCC) is a heterogenous disease where, in advanced stages, clinical and pathological stages do not correlate with outcome. Molecular and genomic biomarkers for HNSCC classification have shown promise for prognostic and therapeutic applications. In this study, we utilize automated image analysis techniques in whole slide images of HNSCC tumors to identify relationships between cytometric features and genomic phenotypes. Hematoxylin and eosin-stained slides of HNSCC tumors (N = 49) were obtained from the Cancer Imaging Archive (TCIA), along with accompanying clinical, pathological, genomic, and proteomic reports. Automated nuclear detection was performed across the entirety of slides, and cytometric feature maps were generated. Forty-one cytometric features were evaluated for associations with tumor grade, tumor stage, tumor subsite, and integrated genomic subtype (IGS). Thirty-two features demonstrated significant association with IGS when corrected for multiple comparisons. In particular, the basal subtype was visually distinguishable from the chromosomal instability and immune subtypes based on cytometric feature measurements. No features were significantly associated with tumor grade, stage, or subsite. This study provides preliminary evidence that features derived from tissue pathology slides could provide insights into genomic phenotypes of HNSCC.

ObjectivePharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide.Materials and MethodsFour healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration.ResultsThere were 3,076 human, 332 S. mitis, 102 G. haemolyans and 42 G. adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and ∼300 proteins that had a pConclusionThis pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotide’s effects on saliva and reports of improved PCF healing.

Additional file 1: Figure S1. CD45 + lymphocytes within the tumor microenvironment of OPSCC. A population of CD14 + lymphocytes are seen representing cells of hematopoietic lineage (A-C). The black box denotes areas visualized under higher power magnification. The above photomicrographs are serial sectios (4 μm thickness).

Results Discussion References Securing Feeding Tubes in Head and Neck Surgery: Septal Suture or Bridle Technique Samer Al-Khudari1 MD, Daniel Clayburgh2 MD PhD, Lisa Morris2 MD, Tammara Watts2 MD PhD, Mark K. Wax2 MD, Tamer A. Ghanem1 MD PhD 1Department of Otolaryngology-Head & Neck Surgery Henry Ford Health System, Detroit, Michigan 2Departmet of Otolaryngology –Head & Neck Surgery Oregon Health & Science University, Portland, Oregon Objectives: To compare use of the anterior septal suture (SS) technique versus the septal bridle technique (BT) in securing nasogastric feeding tubes in head and neck surgery patients. Study Design: A multicenter prospective nonrandomized controlled study was conducted on patients undergoing head and neck surgery with postoperative need for a nasogastric feeding tube. Methods: Patients underwent either a septal suture or a bridle technique to secure the feeding tube intraoperatively. They were assessed by a standard questionnaire and physical exam administered at three time points postoperatively: days 1-5 (time-1), 6-9 (time-2), and day 10 or greater (time-3). The following factors were assessed: subjective assessment of overall pain, pain due to securing mechanism, route of pain control, local complications, and tube dislodgement secondary to securing method. To analyze pain at each time point a nonparametric two sample Wilcoxon test was used. To analyze the change in pain from time 1 to time 2 a Wilcoxon matched pairs signed rank test was used. Results: 74 patients were enrolled in the study. 29 patients underwent a septal suture technique and 45 underwent the bridle technique. No local complications were reported secondary to either securing method. No tube dislodgments occurred directly as a result of either securing technique. Overall pain did not significantly differ in both cohorts at each time point (p=0.196, 0.808, 0.469). Pain due to the tube securing method was significantly less for the bridle technique at time points 1 and 2 but not at time 3 (p=0.037, 0.021, 0.722). Overall pain and pain due to securing method did not significantly differ in patients primarily controlled on PO or IV medication at time 1 (p=0.744, p=0.909). When analyzing the change in overall pain from time 1 to time 2 in both cohorts there was a significant decrease in pain (p=0.001, p=0.001). When analyzing the change in mean pain due to the securing mechanism from time 1 to time 2 it was found to be significant in the SS patients (p=0.036) and approaching significance in the BT patients (p=0.078). Conclusions: The septal suture and bridle technique are both effective methods in securing feeding tubes postoperatively in head and neck surgery patients. In both cohorts no local complications were directly attributed to securing method and no tube dislodgments were reported directly related to the securing method.

Additional file 2: Figure S2. IgG negative controls at 20Ă magnification. The above photomicrographs are serial sections (4Â Îźm thickness).

Additional file 6: Figure S7. Using the preliminary screening data, ELISA assays were conducted on SDF-1ι, VEGF, Gro-ι, IL-8, IL-6, and PDGF with the addition of CXCL7 to confirm the observations made in Additional file 1: Figure S6.

Additional file 3: Figure S4. The MSC markers gremlin-1 and CD105 are co-localized in the TM of patient with OCSCC (oral tongue). High power resolution confocal images from representative sections of human OCSCC specimens (A) demonstrate TM cells positive for the MSC markers anti-gremlin-1 (red) and anti-CD105 (green). An orange color on merged images indicates co-localization of gremlin-1 and CD105. In addition, TM MSCs were detected by anti-gremlin-1 (red) and anti-CD90 (blue). A magenta color on merged images indicates co-localization of gremlin and CD90 that did not co-localize with the hematopoietic marker, anti-CD45 (green) (B). The nuclei are depicted as grey.

Additional file 2: Figure S2. IgG negative controls at 20Ă magnification. The above photomicrographs are serial sections (4Â Îźm thickness).

Additional file 3: Figure S4. The MSC markers gremlin-1 and CD105 are co-localized in the TM of patient with OCSCC (oral tongue). High power resolution confocal images from representative sections of human OCSCC specimens (A) demonstrate TM cells positive for the MSC markers anti-gremlin-1 (red) and anti-CD105 (green). An orange color on merged images indicates co-localization of gremlin-1 and CD105. In addition, TM MSCs were detected by anti-gremlin-1 (red) and anti-CD90 (blue). A magenta color on merged images indicates co-localization of gremlin and CD90 that did not co-localize with the hematopoietic marker, anti-CD45 (green) (B). The nuclei are depicted as grey.

Additional file 6: Figure S7. Using the preliminary screening data, ELISA assays were conducted on SDF-1ι, VEGF, Gro-ι, IL-8, IL-6, and PDGF with the addition of CXCL7 to confirm the observations made in Additional file 1: Figure S6.