Relevance of Tumor Budding and Pattern of Invasion in Oral Squamous Cell Carcinoma.

Background: Standard histopathological parameters such as depth of invasion (DOI), lymphovascular invasion (LVI), and perineural invasion (PNI) are known parameters that can correlate with the prognosis and aggressiveness of oral squamous cell carcinomas (OSCCs). Tumor budding (TB) (≤5 tumor cells at infiltrating borders) and pattern of invasion (POI) are emerging histopathological parameters that have shown promising results as reliable risk factors in predicting nodal metastasis in early OSCCs. Aim: The aim of the study was to assess TB and POI in OSCCs. Materials and Methods: A total of 33 surgical resection specimens of OSCC, including buccal mucosa and tongue with neck dissection, were selected. TB and POI along with standard parameters such as grade, DOI, LVI, PNI, lymph node status, and pathological staging were evaluated. These parameters were analyzed in comparison with lymph node involvement and pathological stage of the tumor using the Chi-square and Fischer's exact test. The SPSS software, v21, was used for statistical analyses. Results: Most of OSCC were moderately differentiated tumors (63.64%). TB was present in 23 cases, in which 69.57% of cases showed low TB (<5 buds), while 30.43% of cases had higher TB (>5 buds). The worst POI (Patterns 4 and 5) was seen in 75.76% of cases. TB, POI, grade, PNI, DOI, and stromal pattern were significantly associated with the pathological stage of the tumor. Conclusion: TB and POI are important and reliable in histopathological parameters in OSCCs.

Safety of botulinum toxin injections in children less than one year old: A retrospective chart review.

PURPOSE: Infants can have muscle hypertonia due to cerebral palsy, muscle strength imbalances due to brachial plexus palsy, refractory clubfoot, and torticollis. These muscle problems can cause significant development impairments. A child with severe sialorrhea and dysphagia from leukodystrophy can aspirate, causing respiratory problems. Botulinum toxin (BoNT) injections can improve these conditions but may lead to adverse effects from the toxin spreading to non-targeted muscles, potentially impacting breathing, swallowing, and overall strength. This is particularly concerning in infants. This study assessed the safety of BoNT injections in children less than one year of age. METHODS: This was a retrospective cohort study. RESULTS: Forty-seven patients (22 male, 25 female) received BoNT injections before one year of age (three to 12 months). Thirty-seven received one round of injections and 10 were injected on multiple occasions. Forty-five received onabotulinumtoxinA (15-100 units [U], 1.9-15.2 U/kg), one received abobotulinumtoxinA (70 U, 9.0 U/kg), and one received incobotulinumtoxinA (25 U, 3.5 U/kg). Lower extremities were treated in 15 patients, upper extremities in 38, the sternocleidomastoid in two, and the salivary glands in one. Forty-five patients had no reported complications. One experienced transient fever, vomiting, and diarrhea. The parent of another reported subjective weakness in one muscle. CONCLUSION: BoNT injections in children less than one year of age appear to be safe.

Pretreatment hematological parameters as predictors of tumor granulocyte-colony-stimulating factor expression in patients of head-and-neck squamous cell carcinoma.

Background: Tumor secreting granulocyte-colony-stimulating factor (G-CSF) and/or G-CSF therapy has been documented as a poor prognostic factor. Tumor G-CSF study is a relatively costly and sparsely available investigation. Therefore, this study was undertaken to predict tumor G-CSF score from pretreatment hematological parameters (PTHP) in patients of head-and-neck squamous cell carcinoma (HNSCC). Materials and Methods: This pilot study was performed after institutional ethics committee approval. Consecutive nonmetastatic HNSCC patients of oral cavity, oropharynx, hypopharynx, and larynx registered from February to December 2019 were analyzed. Patients whose PTHP and formalin-fixed-paraffin-embedded tissue were available, were included. PTHP (absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute lymphocyte count [ALC], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) done before any active oncology treatment, were noted. A semiquantitative tumor G-CSF score was calculated. Tumor G-CSF score and PTHP were correlated with clinicopathological factors. Statistical analysis was performed using SYSTAT version 12. Results: Data of 47 eligible patients were analyzed. The median age at presentation was 60 years. The male-to-female ratio was 43:4. The most common head-and-neck subsite was oropharynx (31.92%), and majority of patients presented with Stage IVA disease (51.1%). Higher tumor G-CSF score was significantly associated with a higher T-stage (P = 0.013). Tumor G-CSF score was directly proportional to ANC, AMC, and ALC while it was inversely proportional to NLR and PLR. Regression equations to predict the tumor G-CSF score when PTHP are known, were determined. Conclusions: PTHP can predict the tumor G-CSF score which may guide G-CSF-directed therapy. Future studies with large number of patients are needed to elucidate its clinical use.

µRALP and Beyond: Micro-Technologies and Systems for Robot-Assisted Endoscopic Laser Microsurgery.

Laser microsurgery is the current gold standard surgical technique for the treatment of selected diseases in delicate organs such as the larynx. However, the operations require large surgical expertise and dexterity, and face significant limitations imposed by available technology, such as the requirement for direct line of sight to the surgical field, restricted access, and direct manual control of the surgical instruments. To change this status quo, the European project µRALP pioneered research towards a complete redesign of current laser microsurgery systems, focusing on the development of robotic micro-technologies to enable endoscopic operations. This has fostered awareness and interest in this field, which presents a unique set of needs, requirements and constraints, leading to research and technological developments beyond µRALP and its research consortium. This paper reviews the achievements and key contributions of such research, providing an overview of the current state of the art in robot-assisted endoscopic laser microsurgery. The primary target application considered is phonomicrosurgery, which is a representative use case involving highly challenging microsurgical techniques for the treatment of glottic diseases. The paper starts by presenting the motivations and rationale for endoscopic laser microsurgery, which leads to the introduction of robotics as an enabling technology for improved surgical field accessibility, visualization and management. Then, research goals, achievements, and current state of different technologies that can build-up to an effective robotic system for endoscopic laser microsurgery are presented. This includes research in micro-robotic laser steering, flexible robotic endoscopes, augmented imaging, assistive surgeon-robot interfaces, and cognitive surgical systems. Innovations in each of these areas are shown to provide sizable progress towards more precise, safer and higher quality endoscopic laser microsurgeries. Yet, major impact is really expected from the full integration of such individual contributions into a complete clinical surgical robotic system, as illustrated in the end of this paper with a description of preliminary cadaver trials conducted with the integrated µRALP system. Overall, the contribution of this paper lays in outlining the current state of the art and open challenges in the area of robot-assisted endoscopic laser microsurgery, which has important clinical applications even beyond laryngology.

Exploring the Embodiment of a Virtual Hand in a Spatially Augmented Respiratory Biofeedback Setting.

Enhancing the embodiment of artificial limbs-the individuals' feeling that a virtual or robotic limb is integrated in their own body scheme-is an impactful strategy for improving prosthetic technology acceptance and human-machine interaction. Most studies so far focused on visuo-tactile strategies to empower the embodiment processes. However, novel approaches could emerge from self-regulation techniques able to change the psychophysiological conditions of an individual. Accordingly, this pilot study investigates the effects of a self-regulated breathing exercise on the processes of body ownership underlying the embodiment of a virtual right hand within a Spatially Augmented Respiratory Biofeedback (SARB) setting. This investigation also aims at evaluating the feasibility of the breathing exercise enabled by a low-cost SARB implementation designed for upcoming remote studies (a need emerged during the COVID-19 pandemic). Twenty-two subjects without impairments, and two transradial prosthesis users for a preparatory test, were asked (in each condition of a within-group design) to maintain a normal (about 14 breaths/min) or slow (about 6 breaths/min) respiratory rate to keep a static virtual right hand "visible" on a screen. Meanwhile, a computer-generated sphere moved from left to right toward the virtual hand during each trial (1 min) of 16. If the participant's breathing rate was within the target (slow or normal) range, a visuo-tactile event was triggered by the sphere passing under the virtual hand (the subjects observed it shaking while they perceived a vibratory feedback generated by a smartphone). Our results-mainly based on questionnaire scores and proprioceptive drift-highlight that the slow breathing condition induced higher embodiment than the normal one. This preliminary study reveals the feasibility and potential of a novel psychophysiological training strategy to enhance the embodiment of artificial limbs. Future studies are needed to further investigate mechanisms, efficacy and generalizability of the SARB techniques in training a bionic limb embodiment.

Osteotome-mediated sinus floor elevation using an in situ hardening biphasic calcium phosphate bone graft substitute compared to xenograft: A randomized controlled clinical trial.

AIM: To assess osteotome-mediated sinus floor elevation (OMSFE) with simultaneous implant placement using an in situ hardening biphasic calcium phosphate (BCP) compared to xenograft as a control. METHODS: Patient in need for sinus floor augmentation in one or both sinuses were selected for this randomised controlled clinical trial. Sites presenting a residual sinus floor height of 3-6 mm and eligible for OMSFE were randomly assigned to receive either BCP (test) or xenograft particles (control). CBCT scans were performed before and at the time of implant loading (180 days). The difference in sinus floor height gain between the two groups was set as the primary endpoint parameter for equivalence testing. The implant insertion torque (ITV) was recorded and Implant stability quotients (ISQ) was assessed upon implant placement, abutment connection (160 days) and implant loading (180 days). RESULTS: A total of 54 sinus lifts were performed in 42 patients including 12 bilateral cases. Four implants failed (two in each group) and a total of six patients were lost to follow-up. Statistical analysis of sinus floor height revealed no significant differences (p < 0.05) between groups at baseline nor at 180 days after augmentation. There was no statistical difference in sinus floor height gain between the two groups as supported by the 90% confidence intervals of the difference between groups. Good primary implant stability was confirmed in both treatment groups by ITV and ISQ measurements. CONCLUSIONS: Within the limits of this study, it can be concluded that OMSFE using in situ hardening BCP particles results in equivalent sinus floor height gain than using xenograft particles but offers an easier application.

Detection of early reflections from a binaural activity map using neural networks.

Human listeners localize sounds to their sources despite competing directional cues from early room reflections. Binaural activity maps computed from a running signal can provide useful information about the presence of room reflections, but must be inspected visually to estimate auditory cues. A model was constructed using machine learning to validate the presence of and perform the extraction of these cues. The model uses the running signal output of a binaurally integrated cross-correlation/autocorrelation mechanism (BICAM) to analyze a lead/lag stimulus and generate a binaural activity map. System reflections are visually presented on the binaural display as correlation peaks with increased amplitude. Three independent neural networks estimate the location of the direct sound, the time delay of the reflection, and the location of the reflection from binaural activity maps displayed by BICAM. Depending on the task, neural network accuracies on test data sets vary from 84.1% to 98.5%.

A robotic microsurgical forceps for transoral laser microsurgery.

PURPOSE: In transoral laser microsurgery (TLM), the close curved cylindrical structure of the laryngeal region offers functional challenges to surgeons who operate on its malignancies with rigid, single degree-of-freedom (DOF) forceps. These challenges include surgeon hand tremors, poor reachability, poor tissue surface perception, and reduced ergonomy in design. The integrated robotic microsurgical forceps presented here is capable of addressing the above challenges through tele-operated tissue manipulation in TLM. METHODS: The proposed device is designed in compliance with the spatial constraints in TLM. It incorporates a novel 2-DOF motorized microsurgical forceps end-effector, which is integrated with a commercial 6-DOF serial robotic manipulator. The integrated device is tele-operated through the haptic master interface, Omega.7. The device is augmented with a force sensor to measure tissue gripping force. The device is called RMF-2F, i.e. robotic microsurgical forceps with 2-DOF end-effector and force sensing. RMF-2F is evaluated through validation trials and pick-n-place experiments with subjects. Furthermore, the device is trialled with expert surgeons through preliminary tasks in a simulated surgical scenario. RESULTS: RMF-2F shows a motion tracking error of less than 400 µm. User trials demonstrate the device's accuracy in task completion and ease of manoeuvrability using the Omega.7 through improved trajectory following and execution times. The tissue gripping force shows better regulation with haptic feedback (1.624 N) than without haptic feedback (2.116 N). Surgeons positively evaluated the device with appreciation for improved access in the larynx and gripping force feedback. CONCLUSIONS: RMF-2F offers an ergonomic and intuitive interface for intraoperative tissue manipulation in TLM. The device performance, usability, and haptic feedback capability were positively evaluated by users as well as expert surgeons. RMF-2F introduces the benefits of robotic teleoperation including, (i) overcoming hand tremors and wrist excursions, (ii) improved reachability and accuracy, and (iii) tissue gripping feedback for safe tissue manipulation.

Design and Study of a Next-Generation Computer-Assisted System for Transoral Laser Microsurgery.

OBJECTIVE: To present a new computer-assisted system for improved usability, intuitiveness, efficiency, and controllability in transoral laser microsurgery (TLM). STUDY DESIGN: Pilot technology feasibility study. SETTING: A dedicated room with a simulated TLM surgical setup: surgical microscope, surgical laser system, instruments, ex vivo pig larynxes, and computer-assisted system. SUBJECTS AND METHODS: The computer-assisted laser microsurgery (CALM) system consists of a novel motorized laser micromanipulator and a tablet- and stylus-based control interface. The system setup includes the Leica 2 surgical microscope and the DEKA HiScan Surgical laser system. The system was validated through a first-of-its-kind observational study with 57 international surgeons with varied experience in TLM. The subjects performed real surgical tasks on ex vivo pig larynxes in a simulated TLM scenario. The qualitative aspects were established with a newly devised questionnaire assessing the usability, efficiency, and suitability of the system. RESULTS: The surgeons evaluated the CALM system with an average score of 6.29 (out of 7) in ease of use and ease of learning, while an average score of 5.96 was assigned for controllability and safety. A score of 1.51 indicated reduced workload for the subjects. Of 57 subjects, 41 stated that the CALM system allows better surgical quality than the existing TLM systems. CONCLUSIONS: The CALM system augments the usability, controllability, and efficiency in TLM. It enhances the ergonomics and accuracy beyond the current state of the art, potentially improving the surgical safety and quality. The system offers the intraoperative automated scanning of customized long incisions achieving uniform resections at the surgical site.

Evaluation of cases of membranoproliferative glomerulonephritis according to newer classification: A retrospective record-based study.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) has traditionally been classified on electron microscopy (EM) into different types based on the location of the immune complexes. Sethi et al. subsequently suggested a more relevant etiology-based and clinically useful classification based on immunofluorescence. METHODS: In this retrospective study, 18 diagnosed cases of MPGN over a one-year period for which direct immunofluorescence (DIF) study results were available, were selected. Cases without archived records of immunofluorescence photographs/reports were excluded. Histological diagnosis of MPGN was confirmed and DIF results were analyzed with reference to antibodies to IgG, IgA, IgM, C3, C1q, kappa, and lambda light chains. RESULTS: Evaluation of cases revealed 8 males and 10 females with age range from 11 to 66 years. Fifteen cases presented with nephrotic syndrome. On evaluation, 88.89% cases (16/18) were immune complex mediated while two (11.11%) were of complement mediated type of MPGN. Among immune complex-mediated cases, a single case of monoclonal gammopathy associated or light chain mediated MPGN was present. CONCLUSION: The classification described by Sethi et al. is easy to use since it relies on DIF instead of EM which is not readily available. Most of the cases were immune complex mediated whereas incidence of complement mediated MPGN, that is, C3 glomerulopathy was low (11.11%). Application of the new classification allows more relevant categorization of cases based on etiology and without the requirement of EM.

Blind localization and segregation of two sources including a binaural head movement model.

This study investigates how virtual head rotations can improve a binaural model's ability to segregate speech signals. The model takes two mixed speech sources spatialized to unique azimuth positions and localizes them. The model virtually rotates its head to orient itself for the maximum signal-to-noise ratio for extracting the target. An equalization-cancellation approach is used to generate a binary mask for the target based on localization cues. The mask is then overlaid onto the mixed signal's spectrogram to extract the target from the mixture. Improvement in signal-to-noise ratios from head rotation approaches over 30 dB.

Ridge preservation using an in situ hardening biphasic calcium phosphate (ß-TCP/HA) bone graft substitute-a clinical, radiological, and histological study.

BACKGROUND: Post-Extraction ridge preservation using bone graft substitutes is a conservative technique to maintain the width of the alveolar ridge. The objective of the present study was to evaluate an in situ hardening biphasic (HA/ß-TCP) bone graft substitutes for ridge preservation without primary wound closure or a dental membrane. METHODS: A total of 15 patients reported for tooth extraction were enrolled in this study. Implants were placed in average 5.2 ± 2 months after socket grafting. At this visit, Cone Beam CT (CBCT) images and core biopsies were taken. Implant stability (ISQ) was assessed at the insertion as well as at the day of final restoration. RESULTS: CBCT data revealed 0.79 ± 0.73 mm ridge width reduction from grafting to implant placement. Histomorphometric analysis of core biopsy samples revealed in average 21.34 ± 9.14% of new bone in the grafted sites. Primary implant stability was high (ISQ levels 70.3 ± 9.6) and further increased until final restoration. CONCLUSIONS: The results of this study show that grafting of intact post-extraction sockets using a biphasic in situ hardening bone graft substitute results in an effective preservation of the ridge contour and sufficient new bone formation in the grafted sites, which is imperative for successful implant placement.

Robot-assisted microsurgical forceps with haptic feedback for transoral laser microsurgery.

In this paper, a novel, motorized, multi-degrees-of-freedom (DoF), microsurgical forceps tool is presented, which is based on a master-slave teleoperation architecture. The slave device is a 7-DoF manipulator with: (i) 6-DoF positioning and orientation, (ii) 1 open/close gripper DoF; and (iii) an integrated force/torque sensor for tissue grip-force measurement. The master device is a 7-DoF haptic interface which teleoperates the slave device, and provides haptic feedback in its gripper interface. The combination of the device and the surgeon interface replaces the manual, hand-held device providing easy-to-use and ergonomic tissue control, simplifying the surgical tasks. This makes the system suitable to real surgical scenarios in the operating room (OR). The performance of the system was analysed through the evaluation of teleoperation control and characterization of gripping force. The new system offers an overall positioning error of less than 400 µm demonstrating its safety and accuracy. Improved system precision, usability, and ergonomics point to the potential suitability of the device for the OR and its ability to advance haptic-feedback-enhanced transoral laser microsurgeries.

Novel modular 2-DOF microsurgical forceps for transoral laser microsurgeries: Ergonomic design and preliminary evaluation.

Transoral Laser Microsurgeries (TLM) demand a great level of control and precision in intraoperative tissue manipulation. The optimal eradication of the diseased tissue is possible only with coordinated control of the laser aiming for incision and the microsurgical tools for orienting and stretching the tissue. However, the traditional microsurgical tools are long, single purpose, one degree-of-freedom (DOF), rigid tools with small range of motion and a normal grasping handle inducing non-ergonomic usage. This paper presents a novel, modular microsurgical tool to overcome the challenges of the traditional tools and improve the surgeon-tool usage experience. The novel design adds a rotational DOF to expand the reach and functionality of the tool. The device is provided with an ergonomic grasping handle that avoids extreme wrist excursions and is capable of adapting to the variety of tools used in TLM within the same design. The performance of the new microsurgical tool was evaluated through a subjective assessment with both medical students and expert surgeons. The evaluation demonstrated a general acceptance of the new forceps tool, with the expert surgeons providing positive appraisals for the improved functionality and user experience with the tool, which indicates towards the potential suitability of the device for TLM. The parameters assessed in the preliminary evaluation not only provide a sense of the advantages of the novel design, but also guide future evolution of the tool design.

A novel computerized surgeon-machine interface for robot-assisted laser phonomicrosurgery.

OBJECTIVES/HYPOTHESIS: To introduce a novel computerized surgical system for improved usability, intuitiveness, accuracy, and controllability in robot-assisted laser phonomicrosurgery. STUDY DESIGN: Pilot technology assessment. METHODS: The novel system was developed involving a newly designed motorized laser micromanipulator, a touch-screen display, and a graphics stylus. The system allows the control of a CO2 laser through interaction between the stylus and the live video of the surgical area. This empowers the stylus with the ability to have actual effect on the surgical site. Surgical enhancements afforded by this system were established through a pilot technology assessment using randomized trials comparing its performance with a state-of-the-art laser microsurgery system. Resident surgeons and medical students were chosen as subjects in performing sets of trajectory-following exercises. Image processing-based techniques were used for an objective performance assessment. A System Usability Scale-based questionnaire was used for the qualitative assessment. RESULTS: The computerized interface demonstrated superiority in usability, accuracy, and controllability over the state-of-the-art system. Significant ease of use and learning experienced by the subjects were demonstrated by the usability score assigned to the two compared interfaces: computerized interface = 83.96% versus state-of-the-art = 68.02%. The objective analysis showed a significant enhancement in accuracy and controllability: computerized interface = 90.02% versus state-of-the-art = 75.59%. CONCLUSIONS: The novel system significantly enhances the accuracy, usability, and controllability in laser phonomicrosurgery. The design provides an opportunity to improve the ergonomics and safety of current surgical setups.

The evolving role of CT colonography.

Colorectal cancer (CRC) screening is widely recommended as part of standard preventive care. All average risk persons over the age of 50 y are eligible. Various authorities have advocated fecal occult blood testing, flexible sigmoidoscopy, barium enema and colonoscopy at varying intervals as acceptable screening options. Despite the array of choices, CRC screening lags in frequency behind other cancer screening maneuvers like mammography or Pap smear. Of late, there is growing interest in CT colonography (CTC) as another screening option. CTC, or virtual colonoscopy, may represent an attractive, non-invasive method of CRC screening that provides images akin to traditional colonoscopy. Improvements in CTC performance, especially when coupled with declining costs, suggest that CTC's role in average risk screening will increase in the future. This review summarizes available data about the efficacy of CTC in average and high risk screening populations. Current indications as well as limitations to this technology are discussed, as are practical issues like the cost-effectiveness of CTC for widespread use.