Citations

Abstract Background and study aims The US FDA recently approved a cancer treatment with pembrolizumab based upon the tumor biomarker status of deficient mismatch repair (dMMR) rather than a specific disease-based approach. We sought to determine if endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) could determine dMMR and quantification of PD-L1 expression to potentially guide the delivery of tumor agnostic immunotherapy. Patients and methods Immunohistochemistry was performed on archived pancreas core biopsy specimens. Tumors with absent nuclear staining of DNA mismatch repair proteins represented dMMR. Tumors were considered to have any or high PD-L1 expression, if expressed in ≥ 1 % or ≥ 50 % of tumor cells. Results Histologic specimen adequacy for MMR status assessment was satisfactory in 97.2 % of tumors. dMMR and high PD-L1 expression was identified in 3 % and 8.1 % of the cohort. Conclusion In the setting of tumor type agnostic immunotherapy, it is projected that at least 3 % of malignant pancreas lesions will be sensitive to pembrolizumab and up to 8 % sensitive to the family of immune checkpoint inhibitors. This highlights the expanding role of EUS-FNB in the field of precision immuno-oncology.

Implantable devices to measure neurochemical or electrical activity from the brain are mainstays of neuroscience research and have become increasingly utilized as enabling components of clinical therapies. In order to increase the number of recording channels on these devices while minimizing the immune response, flexible electrodes under 10 µm in diameter have been proposed as ideal next-generation neural interfaces. However, the representation of motion artifact during neurochemical or electrophysiological recordings using ultra-small, flexible electrodes remains unexplored. In this short communication, we characterize motion artifact generated by the movement of 7 µm diameter carbon fiber electrodes during electrophysiological recordings and fast-scan cyclic voltammetry (FSCV) measurements of electroactive neurochemicals. Through in vitro and in vivo experiments, we demonstrate that artifact induced by motion can be problematic to distinguish from the characteristic signals associated with recorded action potentials or neurochemical measurements. These results underscore that new electrode materials and recording paradigms can alter the representation of common sources of artifact in vivo and therefore must be carefully characterized.

Abstract Background Pneumatosis intestinalis has long been a marker of advanced bowel ischemia and prompts urgent laparotomy. In post-operative settings, the presence of pneumatosis represents a significant management dilemma. We share a case-series of post-esophagectomy patients with pneumatosis intestinalis and no corollary intra-abdominal pathologic findings on re-exploration. Methods January 2000 to December 2017, 1760 patients underwent Ivor-Lewis esophagectomy or gastrectomy with jejunostomy-tube placement. Charts were reviewed retrospectively to identify patients with pneumatosis intestinalis discovered in the post-operative period. Demographic data, operative details and postoperative course were reviewed including incidence and details of re-exploration. Results Eleven patients met inclusion criteria. Nine were male (81.8%) and mean age was 69 years. All patients had radiographic confirmation of pneumatosis intestinalis and in many cases portal venous gas (Figure 1). Clinical course was variable without discernable trends in vitals or laboratory values. Development of significant postoperative ileus along with delivery of enteral tube feeds through a jejunostomy tube preceded development of the pneumatosis in all patients. Nine patients were re-explored and none had evidence of bowel ischemia. Conclusion The finding of pneumatosis intestinalis in the post-operative setting can be alarming and pose a management dilemma. With the advent of improved and readily available imaging, there has been an increase in findings that have no corollary physical symptomatology. In this series of patients, despite dramatic radiographic findings, none had ischemic bowel. Pneumatosis intestinalis alone in patients who have undergone esophagectomy should not be considered an indication for emergency re-exploration. Disclosure All authors have declared no conflicts of interest.

Abstract Background Endoscopic mucosal resection (EMR) can be performed en-bloc in Barrett's esophagus (BE) lesions that are ≤2 cm in size. The true size of a BE lesion may be underestimated under white light endoscopy, limiting the rate of en-bloc resection. Volumetric laser endomicroscopy (VLE) provides high-resolution cross-sectional imaging of BE. A greater number of VLE glands are associated with BE dysplasia and may help predict lesion size. The aim of this study was to determine the association between VLE gland count and outcome of resection. Methods EMR specimens from patients with a history of dysplastic BE were imaged with VLE. EMRs performed on BE lesions ≤2cm in size with intent at en-bloc resection were included. Manual quantification of epithelial glands was performed in blinded fashion. Image visualization enhancement software was used to quantify the surface area occupied by epithelial glands on en-face VLE. Histologic en-bloc (R0) and incomplete (R1) resection of the targeted lesion was defined by the absence and presence of dysplasia and/or cancer at the specimen margins respectively. Results The study sample consisted of 37 EMRs from 31 patients. The mean (SD) size of EMRs was 1.04 (0.37) cm. Pathology showed low-grade dysplasia (N = 12), high-grade dysplasia (N = 19), and intramucosal cancer (N = 6). The en-bloc resection rate was 37.8% (R0: N = 14; R1: N = 23). The mean (SD) number of epithelial glands was 13.0 (6.7) and 28.8 (23.9) for R0 and R1 specimens, respectively, with a statistically significant mean difference of 15.8 glands (95% CI: 2–29, P = 0.02) between the two groups. A gland count of 28 or higher per EMR specimen predicted R1 with 100% sensitivity and 39% specificity (ROC: 0.69). The mean (SD) surface area occupied by epithelial glands in R0 and R1 specimens was 0.98 (1.1) mm2 and 2.3 (2.4) mm2, respectively. There was strong correlation between manual gland counts and epithelial gland surface area (R2: 0.81, P < 0.001). Conclusion A higher number of VLE glands in EMR specimens is associated with a lower en-bloc resection rate suggesting that white-light endoscopy underestimates lesion size and that VLE may have a potential role in lesion margin assessment. Disclosure All authors have declared no conflicts of interest.

Objective: Vocal cord dysfunction (VCD) is characterized by paradoxical vocal fold movement (PVFM) during inspiration. The aim of this study was to determine whether ultrasound could accurately differentiate between normal and PVFM during respirations in a resting state. Design: Prospective, single-subject design. Setting: Academic medical center. Patients: A speech-language pathologist who was able to volitionally alternate between normal and PVFM when breathing at rest was recruited to participate in the study. Interventions: The subject was instructed to randomly alternate between normal and PVFM 20 times (10 times each). A single investigator imaged the vocal folds using ultrasound and reported when the subject alternated between the 2 respiratory states. Main Outcome Measures: The subject recorded when they changed between the 2 respiratory states, whether the investigator identified with the change occurred, and if the correct respiratory state was identified. Results: The investigator recognized when the subject changed respiratory states and correctly identified the new respiratory state 100% of the time. Conclusions: The findings of the current study were promising and suggest that ultrasound may have utility in the diagnosis of VCD. However, because of the preliminary nature of these results, further research is required before recommending its clinical implementation.

Purpose To determine the feasibility of shear wave elastography (SWE) with B‐mode ultrasound in predicting the stiffness of the rotator cuff muscle before arthroscopic rotator cuff repair to evaluate the difficulty of the surgical procedure, as well as to compare SWE with the Goutallier stage on magnetic resonance imaging (MRI). Methods Thirty‐eight patients with a full‐thickness supraspinatus tear requiring arthroscopic rotator cuff repair participated. The Goutallier stage of fatty infiltration on MRI was measured before surgery, as was the SWE modulus of the anterior superficial, anterior deep, posterior superficial, and posterior deep (PD) regions of the supraspinatus muscle. To measure the stiffness of the supraspinatus musculotendinous unit during surgery, the supraspinatus tendon was axially stretched until the anatomic insertion site was reached, and force per deformation was recorded. The correlation between stiffness of the supraspinatus and SWE value in each region of the supraspinatus muscle or Goutallier stage was determined. In addition, patients were divided into 2 groups: (1) In the complete footprint coverage group, greater than 50% of the footprint was covered during the stiffness measurement, and (2) in the incomplete footprint coverage group, less than 50% of the footprint was covered during the stiffness measurement. Differences in SWE value and Goutallier stage were measured between the 2 groups. Results The best correlation of stiffness with the SWE modulus of the PD muscle of the supraspinatus was R = 0.69, and the correlation of stiffness with the Goutallier stage on MRI was R = 0.48. The SWE value of the PD region was greater in the incomplete footprint coverage group than in the complete footprint coverage group, although the Goutallier stage was not significantly different. Conclusions The highest correlation with stiffness of the supraspinatus musculotendinous unit was with the SWE modulus of the PD muscle, as compared with SWE evaluation of the other regions or the Goutallier stage on MRI. Ultrasound SWE can predict the stiffness of the supraspinatus musculotendinous unit best. Clinical Relevance Rotator cuff retraction adds difficulty to arthroscopic rotator cuff repair. Ultrasound SWE may be used for presurgical planning.

A wide range of materials have been used for the development of intervertebral cages. Poly(propylene fumarate) (PPF) has been shown to be an excellent biomaterial with characteristics similar to trabecular bone. Hydroxyapatite (HA) has been shown to enhance biocompatibility and mechanical properties of PPF. The purpose of this study was to characterize the effect of PPF augmented with HA (PPF:HA) and evaluate the feasibility of this material for the development of cervical cages. PPF was synthesized and combined with HA at PPF:HA wt:wt ratios of 100:0, 80:20, 70:30, and 60:40. Molds were fabricated for testing PPF:HA bulk materials in compression, bending, tension, and hardness according to ASTM standards, and also for cage preparation. The cages were fabricated with and without holes and with porosity created by salt leaching. The samples as well as the cages were mechanically tested using a materials testing frame. All elastic moduli as well as the hardness increased significantly by adding HA to PPF (p < 0.0001). The 20 wt % HA increased the moduli significantly compared to pure PPF (p < 0.0001). Compressive stiffness of all cages also increased with the addition of HA. HA increased the failure load of the porous cages significantly (p = 0.0018) compared with nonporous cages. PPF:HA wt:wt ratio of 80:20 proved to be significantly stiffer and stronger than pure PPF. The current results suggest that this polymeric composite can be a suitable candidate material for intervertebral body cages.