SUMMARY Here we describe a multiplexed immunohistochemical platform, with computational image processing workflows including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas, and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination, and revealed that response to therapy correlated with degree of mono-myelocytic cell density, and percentages of CD8+ T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification, and provide digital image processing pipelines (https://github.com/multiplexIHC/cppipe) to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to thus improve biomarker discovery and assessment.

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This paper presents the clinical motivation, design specifications, kinematics, statics, and actuation compensation for a newly constructed telerobotic system for Minimally Invasive Surgery (MIS) of the throat. A hybrid dual-arm telesurgical slave, with twenty joint-space Degrees of Freedom (DoF), is used in this telerobotic system to provide the necessary dexterity in deep surgical fields such as the throat. The telerobotic slave uses novel continuum robots that use multiple super-elastic backbones for actuation and structural integrity. The paper presents the kinematics of the telesurgical slave and methods for actuation compensation to cancel the effects of backlash, friction, and flexibility of the actuation lines. A method for actuation compensation is presented in order to overcome uncertainties of modeling, friction, and backlash. This method uses a tiered hierarchy of two novel approaches of actuation compensation for remotely actuated snake-like robots. The tiered approach for actuation compensation uses compensation in both joint space and configuration space of the continuum robots. These actuation hybrid compensation schemes use intrinsic model information and external data through a recursive linear estimation algorithm and involve compensation using configuration space and joint space variables. Experimental results validate the ability of our integrated telemanipulation system through experiments of suturing and knot tying in confined spaces.

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The functional organization of laryngeal motoneurons in the nucleus ambiguous (NA) was evaluated in adult male rats before and after recurrent laryngeal nerve section and reinnervation. Using retrograde double labeling techniques with fluorescent probes, we obtained the number and position of labeled neurons by using the Bioquant 3-D imaging system. Reinnervation was documented by electromyography. In nine control animals vector analysis revealed significant (p less than .05) separation of the posterior cricoarytenoid (PCA) muscle motoneurons and the thyroarytenoid and lateral cricoarytenoid (TA/LCA) muscle motoneurons. The PCA motoneurons were positioned ventromedially in the NA, and TA/LCA motoneurons were found dorsolaterally in the NA. Rostral-caudal separation was not significant. Electromyography revealed phasic electrical activity synchronous with respiration in the PCA, and activity synchronous with deglutition in the TA/LCA. In four animals surviving 15 weeks following recurrent laryngeal nerve section and primary neurorrhaphy, functional organization within the NA was lost and phasic motor unit activity synchronous with respiration was seen in the TA/LCA muscle as well as the PCA. Vector analysis revealed the reinnervating motoneurons for both the PCA and TA/LCA to be positioned dorsolaterally, similar to the control group TA/LCA motoneurons. These findings demonstrate a shift in the topographic organization of laryngeal motoneurons within the NA following reinnervation, with random organization occurring at the neurorrhaphy site.

Laryngeal implantation for medialization has improved our ability to manage the patient with vocal fold motion impairment. We present preliminary data evaluating the use of preformed hydroxylapatite laryngeal implants and instrumentation for rapid determination of implant size and position. A window in the thyroid ala is created by means of a standard fenestra template. One of 5 prosthesis templates is inserted through the window for determination of correct size and position. The corresponding implant is then inserted and secured with a hydroxylapatite shim. Thirty-five patients have been implanted for vocal fold paralysis, and 4 patients were implanted for soft tissue deficits or bowing. Thirty-one of 35 patients have reported subjective improvement (89%). Improvement was demonstrated in 13 of 15 (87%) patients with complete preoperative and postoperative objective voice function measurements. Complications include 1 implant extrusion and 1 case of airway obstruction secondary to edema. Preliminary results indicate that prefabricated hydroxylapatite implants are effective for medialization thyroplasty. Advantages include a readily available implant selection, rapid determination of correct size and position, and improved implant stabilization with a hydroxylapatite shim.

This interim analysis of the first prospective study of the incidence of VTE in patients with head and neck cancer showed a VTE rate slightly higher than previously estimated in retrospective studies. There have been no unexpected serious adverse events and no rationale for early termination of the study.

Medialization thyroplasty is generally considered a phonosurgical procedure for voice augmentation in patients with glottic insufficiency. This article addresses specifically the issue of dysphagia and aspiration in patients with laryngeal paralysis. A retrospective review of patients undergoing medialization thyroplasty is performed. From 1991 to 1995, 84 patients at The Johns Hopkins Medical Institutions underwent medialization thyroplasty for unilateral vocal fold motion impairment. At presentation 48 patients had isolated recurrent laryngeal nerve injury, 26 with combined superior laryngeal nerve/recurrent laryngeal nerve injury and 10 with idiopathic nerve injury. Sixty-one percent of patients had swallowing difficulties. The severity of symptoms is greater in the superior laryngeal nerve/recurrent laryngeal nerve group. Before surgery 13 patients were dependent on feeding tubes. Nine patients improved to the point at which all alimentation was taken by mouth and tube feedings were discontinued after medialization thyroplasty. One patient was subsequently converted to a full oral diet after cricopharyngeal myotomy. Three patients remained dependent on feeding tubes. The pathophysiology of dysphagia including clinical and experimental observations is reviewed. In addition, the nonsurgical and surgical approaches to treatment of patients with laryngeal paralysis are reviewed.