Success of Endoscopic Pharyngoesophageal Dilation after Head and Neck Cancer Treatment

To assess clinical success and safety of endoscopic pharyngoesophageal dilation after chemoradiation or radiation for head and neck cancer and to identify variables associated with dilation failure

Low Complication Rates of Cranial and Craniofacial Approaches to Midline Anterior Skull Base Lesions

Objective: Surgery is a cornerstone of treatment for a wide variety of neoplastic, congenital, traumatic, and inflammatory lesions involving the midline anterior skull base and may result in a significant anterior skull base defect requiring reconstruction. This study is a retrospective analysis of the reconstruction techniques and complications seen in a series of 58 consecutive patients with midline anterior skull base pathology treated with craniotomy or a craniofacial approach. The complication rates in this series are compared with other retrospective series and specific techniques that may reduce complications are then discussed. Design: This is a retrospective analysis of 58 consecutive patients who had surgery for a midline anterior skull base lesion between January 1994 and July 2003. Data were collected regarding pathology, surgical approach, reconstruction technique, and complications. Results: Twenty-nine patients underwent surgery for a meningioma (50%). The remainder had frontoethmoidal cancer, mucoceles/invasive nasal polyps, encephalocele, esthesioneuroblastoma, anterior falx dermoid cyst with a nasal sinus tract, or invasive pituitary adenoma. In most patients, a low and narrow two-piece biorbitofrontal craniotomy was used. When possible, the dura was repaired before entering the nasal cavity. Thirteen patients experienced a complication (22%). There was one case of postoperative cerebrospinal fluid (CSF) leak (2%), one case of meningitis (2%), two cases of bone flap infection (3%), and two cases of symptomatic pneumocephalus (3%). There were no deaths, no reoperations for CSF leak, and no patient had a new permanent neurologic deficit other than anosmia. Conclusions: Transcranial approaches for midline anterior skull base lesions can be performed safely with a low incidence of postoperative CSF leak, meningitis, bone flap infection, and symptomatic pneumocephalus. Our results, particularly with regard to CSF leakage, compare favorably with other retrospective series

Commissioning of cryogenic preamplifiers for SAPHIRA detectors

SAPHIRA detectors, which are HgCdTe linear avalanche photodiode arrays manufactured by Leonardo, enable high frame rate, high sensitivity, low noise, and low dark current imaging at near-infrared wavelengths. During all University of Hawaii Institute for Astronomy lab testing and observatory deployments of SAPHIRA detectors, there was approximately one meter of cables between the arrays and the readout controllers. The output drivers of the detectors struggled to stably send signals over this length to the readout controllers. As a result, voltage oscillations caused excess noise that prevented us from clocking much faster than 1 MHz. Additionally, during some deployments, such as at the SCExAO instrument at Subaru Telescope, radio-frequency interference from the telescope environment produced noise many times greater than what we experienced in the lab. In order to address these problems, collaborators at the Australia National University developed a cryogenic preamplifier system that holds the detector and buffers the signals from its outputs. During lab testing at 1 MHz clocking speeds, the preamplifiers reduced the read noise by 45% relative to data collected using the previous JK Henriksen detector mount. Additionally, the preamplifiers enabled us to increase the clocking frequency to 2 MHz, effectively doubling the frame rate to 760 Hz for a full (320 × 256 pixel) frame or 3.3 kHz for a 128 × 128 pixel subarray. Finally, the preamplifiers reduced the noise observed in the SCExAO environment by 65% (to essentially the same value observed in the lab) and eliminated the 32-pixel raised bars characteristic of radio-frequency interference that we previous observed there.The authors acknowledge support from NSF award AST 1106391, NASA Roses APRA award NNX 13AC14G, and the JSPS (Grant-in-Aid for Research #23340051 and #26220704). Sean Goebel acknowledges funding support from Subaru Telescope and the Japanese Astrobiology Center

Comparative Analysis of MicroRNA Expression among Benign and Malignant Tongue Tissue and Plasma of Patients with Tongue Cancer

BackgroundIdentification of a microRNA (miRNA) pattern to be used as a biomarker for HNSCC is challenging given the heterogeneity of the disease and different methodologies used. To better define the field, we performed a prospective analysis of blood, tumor, and paired benign tissues in tongue squamous cell carcinoma (SCC) patients.MethodsPlasma samples were collected prior to surgery, and paired tumor and benign tissue blocks were collected from tongue cancer resections. Circulating free and exosomal miRNA, and paired tumor and benign tissues miRNA were analyzed. TaqMan-based miRNA arrays were used to quantitate the expression of 747 human miRNAs. The comparative Ct method assessed the miRNA profile results, and Student’s t-test determined statistical significance between tumor and benign samples.ResultsSixteen of 359 miRNAs detected were differentially expressed between paired tumor and benign tissue. Nine were upregulated, and seven downregulated in tumor tissue. All nine upregulated and six of seven downregulated tumor miRNAs were expressed in circulating exosomes. In contrast, eight of nine upregulated and four of seven downregulated tumor miRNAs were circulating free in the plasma.ConclusionAn aberrantly expressed pattern of miRNA was identified in both tumor and plasma of patients with tongue SCC, suggesting this may be a biomarker for SCC of the oral tongue. Circulating exosomes appear to be a more reliable method for evaluation of circulating tumor-miRNA expression. Further studies with a larger cohort of patients and serial blood samples are needed to validate our findings

Three Patients with Full Facial Transplantation

Unlike conventional reconstruction, facial transplantation seeks to correct severe deformities in a single operation. We report on three patients who received full-face transplants at our institution in 2011 in operations that aimed for functional restoration by coaptation of all main available motor and sensory nerves. We enumerate the technical challenges and postoperative complications and their management, including single episodes of acute rejection in two patients. At 6 months of follow-up, all facial allografts were surviving, facial appearance and function were improved, and glucocorticoids were successfully withdrawn in all patients

Nivolumab for Patients With High-Risk Oral Leukoplakia

ImportanceProliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy.ObjectiveTo determine the safety and clinical activity of anti-programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL.Design, setting, and participantsThis nonrandomized, open-label, phase 2 clinical trial was conducted from January 2019 to December 2021 at a single academic medical center; median (range) follow-up was 21.1 (5.4-43.6) months. Participants were a population-based sample of patients with PVL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of dysplasia).InterventionPatients underwent pretreatment biopsy (1-3 sites) and then received 4 doses of nivolumab (480 mg intravenously) every 28 days, followed by rebiopsy and intraoral photographs at each visit.Main outcomes and measuresThe primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: >80% decrease in score; partial response: 40%-80% decrease). Secondary analyses included immune-related adverse events, cancer-free survival (CFS), PD-1 ligand 1 (PD-L1) expression, 9p21.3 deletion, and other exploratory immunologic and genomic associations of response.ResultsA total of 33 patients were enrolled (median [range] age, 63 [32-80] years; 18 [55%] were female), including 8 (24%) with previously resected early-stage OSCC. Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score increase, or cancer). Nine patients (27%) developed OSCC during the trial, with a 2-year CFS of 73% (95% CI, 53%-86%). Two patients (6%) discontinued because of toxic effects; 7 (21%) experienced grade 3 to 4 immune-related adverse events. PD-L1 combined positive scores were not associated with response or CFS. Of 20 whole-exome sequenced patients, all 6 patients who had progression to OSCC after nivolumab treatment exhibited 9p21.3 somatic copy-number loss on pretreatment biopsy, while only 4 of the 14 patients (29%) who did not develop OSCC had 9p21.3 loss.Conclusions and relevanceThis immune checkpoint therapy precancer nonrandomized clinical trial met its prespecified response end point, suggesting potential clinical activity for nivolumab in high-risk PVL. Findings identified immunogenomic associations to inform future trials in this precancerous disease with unmet medical need that has been difficult to study.Trial registrationClinicalTrials.gov Identifier: NCT03692325