Unique pattern of neutrophil migration and function during tumor progression.

Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant, uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancer exhibited much more spontaneous migration than that of control neutrophils from tumor-free mice. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and increased production of ATP, relative to that of control neutrophils. Their enhanced spontaneous migration was mediated by autocrine ATP signaling through purinergic receptors. In ectopic tumor models and late stages of cancer, bone marrow neutrophils demonstrated potent immunosuppressive activity. However, these cells had metabolic and migratory activity indistinguishable from that of control neutrophils. A similar pattern of migration was observed for neutrophils and polymorphonuclear myeloid-derived suppressor cells from patients with cancer. These results elucidate the dynamic changes that neutrophils undergo in cancer and demonstrate the mechanism of neutrophils' contribution to early tumor dissemination.

CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation.

Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.

Fatty acid transport protein 2 reprograms neutrophils in cancer.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are pathologically activated neutrophils that are crucial for the regulation of immune responses in cancer. These cells contribute to the failure of cancer therapies and are associated with poor clinical outcomes. Despite recent advances in the understanding of PMN-MDSC biology, the mechanisms responsible for the pathological activation of neutrophils are not well defined, and this limits the selective targeting of these cells. Here we report that mouse and human PMN-MDSCs exclusively upregulate fatty acid transport protein 2 (FATP2). Overexpression of FATP2 in PMN-MDSCs was controlled by granulocyte-macrophage colony-stimulating factor, through the activation of the STAT5 transcription factor. Deletion of FATP2 abrogated the suppressive activity of PMN-MDSCs. The main mechanism of FATP2-mediated suppressive activity involved the uptake of arachidonic acid and the synthesis of prostaglandin E2. The selective pharmacological inhibition of FATP2 abrogated the activity of PMN-MDSCs and substantially delayed tumour progression. In combination with checkpoint inhibitors, FATP2 inhibition blocked tumour progression in mice. Thus, FATP2 mediates the acquisition of immunosuppressive activity by PMN-MDSCs and represents a target to inhibit the functions of PMN-MDSCs selectively and to improve the efficiency of cancer therapy.

Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience.

Purpose: Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs. We hypothesized that TSRT beyond 6 weeks may not portend poorer outcomes for the former. Methods: We identified nonmetastatic, high-risk HPV+ OPSCCs treated with multimodal therapy at 2 institutions. Prolonged TSRT was defined as >6 weeks and was evaluated for association with recurrence-free survival (RFS). Radiation treatment time (RTT; time from the first to the last day of RT), total treatment package time (TTPT; time from surgery to the end of adjuvant treatments), de-escalated RT (dose ≤56 Gy), concurrent chemotherapy, smoking history, and treatment institution were evaluated as possible confounders. Results: In total, 96 patients were included. The median follow-up time was 62 months (4-123 months); 69 patients underwent transoral robotic surgeries, and 27 received open surgeries. The median postoperative RT dose was 60 Gy (50-70.8 Gy). The median TSRT, RTT, and TTPT were 38 days (11-208), 43 days (26-56 days), and 81 days (40-255 days), respectively. Ten patients failed treatment at a median of 8 months (4-64 months). Two locoregional and 4 distant failures occurred in the group without prolonged TSRT, whereas 2 locoregional and 2 distant failures were recorded in the prolonged TSRT group. Prolonged TTPT, de-escalated RT, chemotherapy, smoking history, and treatment institution were not associated with treatment failure. RTT was dropped from our analyses as no events appeared in the prolonged RTT group, and no reliable hazard ratio could be computed. Conclusions: TSRT > 6 weeks was not significantly associated with inferior outcomes in the postoperative management of HPV+ OPSCCs. Longer TSRT may facilitate better recovery from surgical toxicity, as needed, without compromising oncologic outcomes. The TSRT goal for these cancers should be investigated in future studies.

Assessment of a Multifaceted Approach, Including Frequent PCR Testing, to Mitigation of COVID-19 Transmission at a Residential Historically Black University.

Importance: COVID-19 posed an unprecedented threat to residential colleges in the fall of 2020. While there were mathematical models of COVID-19 transmission, there were no established or tested protocols of COVID-19 testing or mitigation for school administrators to follow. Objective: To investigate the association of a multifaceted COVID-19 mitigation strategy using social, behavioral, and educational interventions and a program of frequent testing with prevalence of disease spread. Design, Setting, and Participants: This cohort study was conducted as a retrospective review of COVID-19 positivity from August 16, 2020, to April 30, 2021, at Delaware State University, a publicly funded historically Black university. Participants included all students, faculty, and staff members with a campus presence. Positivity rates after use of mitigation strategies and testing on campus were compared with those of the surrounding community. Data were analyzed from July through September 2021. Exposures: Mitigation strategies included education and outreach about social distancing, masking, and handwashing, and a COVID-19 testing plan consisted of twice-weekly polymerase chain reaction (PCR) screening using anterior nasal samples (fall and early spring semester) and then saliva-based samples (middle to late spring semester). Main Outcomes and Measures: Cumulative tests, infections, daily quarantine, and isolation residence hall occupancy were measured, and comparisons were made with statewide COVID-19 positivity rates. Results: The campus cohort included 2320 individuals (1575 resident students, 415 nonresident students, and 330 faculty or staff members). There were 1488 (64.1%) women and 832 (35.9%) men; mean (SD) age was 27.5 (12.9) years. During the fall semester, 36 500 COVID-19 PCR tests were performed. Weekly positivity rates ranged from 0 of 372 tests to 16 of 869 tests (1.8%) (mean [SD] positivity rate, 0.5% [0.5%]; 168 positive results and 36 312 negative results). During the same period, statewide positivity ranged from 589 of 25 120 tests (2.3%) to 5405 of 54 596 tests (9.9%) (mean [SD] positivity rate, 4.8% [2.6%]). In the spring semester, 39 045 PCR tests were performed. Weekly positivity rates ranged from 4 of 2028 tests (0.2%) to 36 of 900 tests (4.0%) (mean [SD] positivity rate, 0.8% [0.9%]; 267 positive results and 38 767 negative results). During the same period, statewide positivity ranged from 1336 of 37 254 tests (3.6%) to 3630 of 42 458 tests (8.5%) (mean [SD] positivity rate, 5.1% [1.3%]). Compared with statewide rates, campus positivity rates were mean (SD) 4.4 (2.6) percentage points lower during the fall semester (P < .001) and mean (SD) 5.6 (1.6) percentage points lower during the spring semester (P < .001). Total daily quarantine and isolation residence hall occupancy ranged from 0 to 43 students in the fall and 1 to 47 students during the spring. Conclusions and Relevance: This study found that the combination of campuswide mitigation policies and twice-weekly COVID-19 PCR screening was associated with a significant decrease in COVID-19 positivity at a residential historically Black university campus compared with the surrounding community. Given the socioeconomic demographics of many students at historically Black colleges and universities, keeping these resident campuses open is critical not only to ensure access to educational resources, but also to provide housing and food security.

Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway.

Myeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity. These cells play an important role in accelerating tumor progression and undermining the efficacy of anti-cancer therapies. The natural mechanisms limiting MDSC activity are not well understood. Here, we present evidence that type I interferons (IFN1) receptor signaling serves as a universal mechanism that restricts acquisition of suppressive activity by these cells. Downregulation of the IFNAR1 chain of this receptor is found in MDSC from cancer patients and mouse tumor models. The decrease in IFNAR1 depends on the activation of the p38 protein kinase and is required for activation of the immune suppressive phenotype. Whereas deletion of IFNAR1 is not sufficient to convert neutrophils and monocytes to MDSC, genetic stabilization of IFNAR1 in tumor bearing mice undermines suppressive activity of MDSC and has potent antitumor effect. Stabilizing IFNAR1 using inhibitor of p38 combined with the interferon induction therapy elicits a robust anti-tumor effect. Thus, negative regulatory mechanisms of MDSC function can be exploited therapeutically.

Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer.

Here, we report that functional heterogeneity of macrophages in cancer could be determined by the nature of their precursors: monocytes (Mons) and monocytic myeloid-derived suppressor cells (M-MDSCs). Macrophages that are differentiated from M-MDSCs, but not from Mons, are immune suppressive, with a genomic profile matching that of M-MDSCs. Immune-suppressive activity of M-MDSC-derived macrophages is dependent on the persistent expression of S100A9 protein in these cells. S100A9 also promotes M2 polarization of macrophages. Tissue-resident- and Mon-derived macrophages lack expression of this protein. S100A9-dependent immune-suppressive activity of macrophages involves transcription factor C/EBPß. The presence of S100A9-positive macrophages in tumor tissues is associated with shorter survival in patients with head and neck cancer and poor response to PD-1 antibody treatment in patients with metastatic melanoma. Thus, this study reveals the pathway of the development of immune-suppressive macrophages and suggests an approach to their selective targeting.

Combination of post-operative radiotherapy and cetuximab for high-risk cutaneous squamous cell cancer of the head and neck: A propensity score analysis.

OBJECTIVES: The objective of this study was to investigate the safety, tolerability and preliminary efficacy of radiotherapy plus cetuximab in high risk CSCC patients. MATERIALS AND METHODS: Patients with high-risk CSCC diagnosed between 2006 and 2013 were analyzed. Patients were divided into two groups: radiotherapy alone versus radiotherapy plus cetuximab. Among 68 patients meeting study criteria, we identified 29 treated with cetuximab plus RT and 39 with RT alone. Primary analysis examined disease-free and overall survival, freedom from local and distant recurrence in the propensity score matched cohort. Propensity score analysis was performed with weighted factors including: Charlson Comorbidity Index score, age. KPS, primary location, T and N stage, recurrent status, margin status, LVSI, PNI and grade. Toxicity was assessed using the CTCAE v4.0. RESULTS: Median follow-up for living patients was 30 months. Patients in the cetuximab group were more likely to have advanced N stage, positive margins and recurrent disease. After propensity score matching the groups were well balanced. Six patients experienced ≥ grade 3 acute toxicity in the cetuximab group. The 1-year, 2-year and 5-year progression free survival (PFS) for patients in the cetuximab group were 86%, 72% and 66%, respectively. The 1-year, 2-year and 5-year overall survival (OS) for patients in the cetuximab group was 98%, 80% and 80%, respectively. CONCLUSIONS: Although limited by small numbers, the combination of cetuximab and radiotherapy in CSCC appears well tolerated there were more long-term survivors and less distant metastasis in the cetuximab group. These promising finding warrant further studies.

In vitro discrimination of tumor cell lines with an electronic nose.

OBJECTIVE: The electronic nose is a sensor of volatile molecules that is useful in the analysis of expired gases. Our hypothesis is that the electronic nose can distinguish between different types of upper aerodigestive tract tumor cells in vitro. STUDY DESIGN: Cells from both tumor and normal cell lines were suspended in saline, and a polymer composite electronic nose was used to evaluate the headspace gases. The data were subjected to principal components analysis, and Mahalanobis distances were calculated to demonstrate the ability of the electronic nose to distinguish among samples. RESULTS: The tumor cell lines, including adenocarcinoma, squamous cell carcinoma, and mesothelioma, were distinct from each other, and from the normal fibroblast and smooth muscle cells as seen on canonical discrimination plots. CONCLUSION: The electronic nose can distinguish between tumor cell lines in vitro and has the potential to be a useful screening test for cancer.

Transoral robotic surgery: supraglottic partial laryngectomy.

OBJECTIVES: We assessed the feasibility of performing transoral supraglottic partial laryngectomy with robotic instrumentation. METHODS: Transoral robotic surgery (TORS) was performed on 3 human patients with supraglottic carcinoma in a prospective human trial. The study was approved by our institutional review board and involved the da Vinci Surgical Robot (Intuitive Surgical, Inc, Sunnyvale, California). RESULTS: All procedures were completed robotically. The median overall operation time to perform the robotic procedure was 120 minutes (range, 1:32:48 to 2:58:18), including 18 minutes (range, 00:6:07 to 00:30:39) for exposure and robotic positioning. There were no intraoperative or postoperative complications or surgical mortality. CONCLUSIONS: The preliminary results of our series suggest that application of the da Vinci robotic surgical system for TORS to supraglottic partial laryngectomy is technically feasible and relatively safe. Furthermore, TORS provides excellent surgical exposure that allows complete tumor resection. Most importantly, TORS provides an alternative to open approaches and "conventional" transoral supraglottic partial laryngectomy.

Selective Targeting of Myeloid-Derived Suppressor Cells in Cancer Patients Using DS-8273a, an Agonistic TRAIL-R2 Antibody.

Purpose: Myeloid-derived suppressor cells (MDSC) are one of the major contributors to immune suppression in cancer. We recently have demonstrated in preclinical study that MDSCs are sensitive to TRAIL receptor 2 (TRAIL-R2) agonist. The goal of this study was to clinically test the hypothesis that targeting TRAIL-R2 can selectively eliminate MDSCs.Experimental Design: The TRAIL-R2 agonistic antibody (DS-8273a) has been tested in 16 patients with advanced cancers enrolled in a phase I trial. The antibody (24 mg/kg) was administered intravenously once every 3 weeks till disease progression, unacceptable toxicities, or withdrawal of consent. The safety and the presence of various populations of myeloid and lymphoid cells in peripheral blood and tumor tissues were evaluated.Results: The treatment was well tolerated with only mild to moderate adverse events attributable to the study drug. Treatment with DS-8273a resulted in reduction of the elevated numbers of MDSCs in the peripheral blood of most patients to the levels observed in healthy volunteers. However, in several patients, MDSCs rebounded back to the pretreatment level by day 42. In contrast, DS-8273a did not affect the number of neutrophils, monocytes, and other populations of myeloid and lymphoid cells. Decrease in MDSCs inversely correlated with the length of progression-free survival. In tumors, DS-8273a treatment resulted in a decrease of MDSCs in 50% of the patients who were able to provide pre- and on-treatment biopsies.Conclusions: Targeting TRAIL-R2 resulted in elimination of different populations of MDSCs without affecting mature myeloid or lymphoid cells. These data support the use of this antibody in combination immmunotherapy of cancer. Clin Cancer Res; 23(12); 2942-50. ©2016 AACR.

Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors.

Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with a CXCR2 antagonist blocked granulocyte infiltration of tumors and showed strong anti-tumor effects.

Transoral robotic surgery (TORS) for base of tongue neoplasms.

OBJECTIVE: To develop a minimally invasive surgical technique for the treatment of base of tongue neoplasms using the optical and technical advantages of robotic surgical instrumentation. STUDY DESIGN: Ten experimental procedures including tongue base exposure and dissections were performed on three cadavers and two mongrel dogs. Transoral robotic surgery (TORS) was then performed on three human patients with tongue base cancers in a prospective human trial. METHODS: Using the da Vinci Surgical Robot (Intuitive Surgical, Inc., Sunnyvale, CA), we performed a total of 10 base of tongue resections on edentulous and dentate cadavers as well as live mongrel dogs. In the cadaver models, exposure was evaluated using three different retractors, the Dingman, Crowe Davis, and FK retractors. The three human patients underwent TORS surgery of their tongue base cancers under an institutional review board approved prospective clinical trial. The ability to identify and preserve or resect key anatomic structures such as the glossopharyngeal, hypoglossal, and lingual nerves as well as techniques for identifying the lingual artery and achieving hemostasis were developed. RESULTS: The da Vinci Surgical Robot provided excellent visualization and enabled removal of the posterior one third to one half of the oral tongue in cadavers, dogs, and human patients. Among the three retractors evaluated, the FK retractor offered the greatest versatility and overall exposure for robotic instrument maneuverability. Complete resection to negative surgical margins with excellent hemostasis and no complications was achieved in the live patient surgeries. CONCLUSIONS: TORS provided excellent three-dimensional visualization and instrument access that allowed successful surgical resections from cadaver models to human patients. TORS is a novel and minimally invasive approach to tongue neoplasms that has significant advantages over classic open surgery or endoscopic transoral laser surgery.

Assessment of intraoperative safety in transoral robotic surgery.

INTRODUCTION: Robotic technology has been safely integrated into thoracic and abdominopelvic surgery, and the early experience has been very promising with very rare complications related to robotic device failure. Recently, several reports have documented the technical feasibility of transoral robotic surgery (TORS) with the daVinci Surgical System. Proposed pharyngeal and laryngeal applications include radical tonsillectomy, base-of-tongue resection, supraglottic laryngectomy, and phonomicrosurgery. The safety of transoral placement of the robotic endoscope and instruments has not been established. Potential risks specific to the transoral use of the surgical robot include facial skin laceration, tooth injury, mucosal laceration, mandible fracture, cervical spine fracture, and ocular injury. We hypothesize that these particular risks of transoral surgery are similar with robotic assistance compared with conventional transoral surgery. METHODS: To test this hypothesis, we attempted to intentionally injure a human cadaver with the daVinci Surgical System by impaling the facial skin and pharyngeal and laryngeal mucosa with the robotic instruments and endoscope. We also attempted to extract or fracture teeth and fracture the cadaver's mandible and cervical spine by applying maximal pressure and torque with the robotic arms. Experiments were documented with still and video photography. RESULTS: Impaling the cadaver's skin and mucosa resulted in only superficial lacerations. Tooth, mandible, and cervical spine fracture could not be achieved. CONCLUSIONS: Initial experiments performing TORS on a human cadaver with the daVinci Surgical System demonstrate a safety profile similar to conventional transoral surgery. Additionally, we discuss several strategies to increase patient safety in TORS.

Transoral robotic surgery (TORS): glottic microsurgery in a canine model.

OBJECTIVES/HYPOTHESIS: We hypothesize that bimanual, three-dimensional robotic surgery will prove valuable for glottic microsurgical procedures. STUDY DESIGN: To test this hypothesis, we developed and optimized a canine model for glottic microsurgery using a commercially available surgical robot. Methods Using a da Vinci Surgical Robot (Intuitive Surgical, Inc., Sunnyvale, CA), glottic microsurgery was performed with a hydrodissection technique in a canine model. The experiments were performed on two orotracheal intubated mongrel dogs under general anesthesia in the supine position on a standard operating room table. A videoscope and two, 360-degree rotating, 5- and 8-mm, wrested-end effector instruments were introduced transorally with three robotic arms. The surgeon performed the actual procedures while positioned at a robotic system console that was located across the operating room suite. The procedure was performed in duplicate and was documented with still and video photography. RESULTS: Glottic microsurgery was successfully performed using the da Vinci Surgical Robot, with both 5- and 8-mm instrumentation. The smaller, 5-mm instruments afforded greater visualization of the operative site and increased maneuverability, which resulted in reduced operative time. The robotic system provided excellent visualization as well as controlled and delicate microdissection at the vocal cord level. CONCLUSIONS: Robotic laryngeal microsurgery is technically feasible in the canine model and warrants consideration for evaluation in controlled human trials.

Transseptal suture to secure middle meatal spacers.

Middle meatal spacers are used by many sinus surgeons to aid postoperative care. Aspiration of a spacer is a concern. We demonstrate a novel method of securing spacers with a transseptal suture to prevent aspiration. We fashion each spacer from a powder-free, nonlatex glove finger that is packed with a Merocel sponge. The open end of the finger is closed with 2-0 Prolene sutures. For a bilateral procedure, the needle is left attached to one of the spacers. A spacer is placed in each ethmoid cavity, the attached needle is passed through the anterior cartilaginous septum, and the suture is tied to the suture on the opposite spacer. For unilateral procedures, the suture on the single spacer is passed to the contralateral side and tied on itself. One week later, the transseptal suture is cut and the spacers are removed. We performed this procedure on 78 patients who had undergone total ethmoidectomy. None of the spacers migrated during the 1 week they were in place. One patient complained of pain during removal of a spacer. During follow-up of 2 to 10 months, we found no evidence of injury to the septum at the site of the transseptal suture. We conclude that the transseptal suture is a safe and cosmetically superior method of securing middle meatal spacers.

Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important regulators of immune responses in cancer and have been directly implicated in promotion of tumor progression. However, the heterogeneity of these cells and lack of distinct markers hampers the progress in understanding of the biology and clinical importance of these cells. Using partial enrichment of PMN-MDSC with gradient centrifugation we determined that low density PMN-MDSC and high density neutrophils from the same cancer patients had a distinct gene profile. Most prominent changes were observed in the expression of genes associated with endoplasmic reticulum (ER) stress. Surprisingly, low-density lipoprotein (LDL) was one of the most increased regulators and its receptor oxidized LDL receptor 1 OLR1 was one of the most overexpressed genes in PMN-MDSC. Lectin-type oxidized LDL receptor 1 (LOX-1) encoded by OLR1 was practically undetectable in neutrophils in peripheral blood of healthy donors, whereas 5-15% of total neutrophils in cancer patients and 15-50% of neutrophils in tumor tissues were LOX-1+. In contrast to their LOX-1- counterparts, LOX-1+ neutrophils had gene signature, potent immune suppressive activity, up-regulation of ER stress, and other biochemical characteristics of PMN-MDSC. Moreover, induction of ER stress in neutrophils from healthy donors up-regulated LOX-1 expression and converted these cells to suppressive PMN-MDSC. Thus, we identified a specific marker of human PMN-MDSC associated with ER stress and lipid metabolism, which provides new insight to the biology and potential therapeutic targeting of these cells.

Transoral robotic surgery: supraglottic laryngectomy in a canine model.

OBJECTIVES/HYPOTHESIS: To develop a technique for computer enhanced robotic transoral supraglottic partial laryngectomy in the canine model. STUDY DESIGN: Surgical procedure on the larynx in a canine model with a commercially available surgical robot. METHODS: With use of the da Vinci Surgical Robot (Intuitive Surgical, Inc., Sunnyvale, CA), the supraglottic partial laryngectomy was performed on a mongrel dog that had been orotracheally intubated using general anesthesia. The videoscope and the 8 mm end-effectors of the robotic system were introduced through three ports, transorally. The surgical procedure was performed remotely from the robotic system console. The procedure was documented with still and video photography. RESULTS: Supraglottic partial laryngectomy was successfully performed using the da Vinci Surgical Robot, with 8 mm instrumentation. The robotic system allowed for celerity and accuracy secondary to findings specific to the surgical approach, including excellent hemostasis, superb visualization of the operative field with expeditious identification of laryngeal submucosal soft tissue and skeletal landmarks, and multiplanar transection of tissues. In addition, the use of the robotic system also was found to have technical advantages inherent in robotic surgery, including the use of "wristed" instrumentation, tremor abolition, motion scaling, and three-dimensional vision. CONCLUSIONS: The da Vinci Surgical Robot allowed for successful robotic transoral supraglottic partial laryngectomy in the canine model.

Robotic microlaryngeal surgery: a technical feasibility study using the daVinci surgical robot and an airway mannequin.

OBJECTIVES/HYPOTHESIS: The trend toward minimally invasive surgery has led to the development and mastery of endoscopic and laparoscopic surgical techniques. These minimally invasive approaches, which only two decades ago were either novel or experimental, are now mainstream. More recently, robot-assisted surgery has evolved as an adjunct to open and endoscopic techniques. Surgical robots are now approved by the United States Food and Drug Administration for a variety of thoracic and abdominal/pelvic surgical procedures. The purpose of this study is to demonstrate the technical feasibility of robot-assisted microlaryngeal surgery. STUDY DESIGN: Experimental surgical manipulation of the larynx in an airway mannequin with a surgical robot. METHODS: A variety of laryngoscopes and mouthgags, coupled with the daVinci Surgical Robot's (Intuitive Surgical, Sunnyvale, CA) 0-degree and 30-degree, two-dimensional and three-dimensional endoscopes, were utilized to optimize visualization of the larynx in an airway mannequin. Five millimeter and 8 mm microinstruments compatible with the daVinci robot were utilized to manipulate different elements of the larynx. Experiments were recorded with both still and video photography. RESULTS: The endoscope and robotic arms of the daVinci robot are well suited to airway surgery. CONCLUSIONS: Robot-assisted laryngeal surgery can be performed with currently available technology. The potential for fine manipulation of tissues, increased freedom of instrument movement, and endolaryngeal suturing may increase the precision of endoscopic laryngeal microsurgery and offers the potential to increase the variety of laryngeal procedures that can be performed endoscopically.

Robot-assisted pharyngeal and laryngeal microsurgery: results of robotic cadaver dissections.

OBJECTIVES/HYPOTHESIS: Robotic surgery has significant potential in pharyngeal and microlaryngeal surgery. We demonstrate the use of a surgical robot in pharyngeal and microlaryngeal surgery in a cadaver. STUDY DESIGN: Six experimental surgical dissections, modeled after commonly performed pharyngeal and microlaryngeal procedures, were performed in a cadaver with a commercially available surgical robot in an operating room suite to demonstrate proof of concept. METHODS: Using the daVinci Surgical Robot (Intuitive Surgical, Sunnyvale, CA), surgical procedures were performed on an edentulous, female cadaver. The procedures included 1) bilateral true vocal cord stripping, 2) rotation of a mucosal flap from the epiglottis to the anterior commissure, 3) partial vocal cordectomy, 4) arytenoidectomy, 5) partial epiglottectomy and thyrohyoid dissection and 6) partial resection of the base of tongue with primary closure. All procedures were timed and documented with still and video photography. RESULTS: The daVinci Surgical Robot, with currently available instruments, enabled performance of several laryngeal and pharyngeal surgical procedures on a cadaver. Laryngeal and pharyngeal exposure was excellent, instruments movement was unimpeded, tissue handling was delicate and precise, and endolaryngeal suturing was relatively easily performed. The duration of the different robotic cadaver dissections was comparable to procedure duration using conventional techniques. CONCLUSIONS: Using the daVinci Surgical Robot, six different pharyngeal and microlaryngeal dissections were successfully performed in a cadaver. The recent development of surgical robotics has a potential role in pharyngeal and microlaryngeal surgery. Surgical robots offer the ability to manipulate instruments at their distal ends with increased freedom of movement, scaled movement, tremor buffering, and under stereoscopic three-dimensional visualization. Surgical robots may increase the precision with which we perform currently described procedures; additionally, surgical robots may advance the field of endoscopic laryngeal and pharyngeal surgery.