Improving Interdisciplinary Communication and Pathology Reporting for Head and Neck Cancer Resections: 3D Visualizations and Margin Reconciliation.

Purpose: Surgical pathology reports play an integral role in postoperative management of head and neck cancer patients. Pathology reports of complex head and neck resections must convey critical information to all involved clinicians. Previously, we demonstrated the utility of 3D specimen and defect scanning for communicating margin status and documenting the location of supplemental margins.

The Impact of Hospital Safety-Net Burden Status on Patients with HPV-Positive Oropharyngeal Cancer.

Objectives: The objective of this study was to compare treatment characteristics and outcomes between patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) treated at hospitals of varying safety-net burden status.

Methods: Patients with cT1-4, N0-3, M0 HPV-positive OPSCC who underwent definitive surgery or radiation were included. Patients were grouped based on their treating hospital safety-net burden status, defined as the percentage of uninsured and Medicaid-insured patients with OPSCC treated at the facility and stratified as low burden (LBH: 0-25th percentile), medium burden (MBH: 25th-75th percentile), or high burden (HBH: 75th-100th percentile).

iPad Annotation of 3D Surgical Models Using Procreate®: Novel Documentation of Supplemental Margins.

We present a novel, efficient approach to demonstrating supplemental margins during oncologic resection. Surgeons and pathologists annotated 10 virtual models of surgical defects and resection specimens in 3D using an iPad-based application, Procreate®. Incorporating this method into the surgical workflow can improve interdepartmental communication and provide visual documentation of surgical steps taken to address at-risk margins.

Intraoperative three-dimensional scanning of head and neck surgical defects: Enhanced communication and documentation of harvested supplemental margins.

Background: We have demonstrated the effectiveness of 3D resection specimen scanning for communicating margin results. We now address the corresponding surgical defect by debuting 3D defect models, which allow for accurate annotations of harvested supplemental margins.

Methods: Surgical defects were rendered into 3D models, which were annotated to document the precise location of harvested supplemental margins.

Frozen Section Timeout: Pilot Study to Reconcile Margins Using 3D Resected Specimen and Defect Scans.

Objective: Opportunities exist to improve intraoperative communication and documentation of resection margin details. We instituted a "frozen section timeout" that centers around visualization of the paired resection specimen and surgical defect-facilitating effective, bidirectional exchange of information.

Methods: We designed an interactive form for use during the "frozen section timeout" including annotated 3D virtual models of the resected specimen and surgical defect, plus a "line-item" table for primary and supplemental margin results.

A rare case of canalicular adenoma in the parotid gland: Highlighting diagnostic limitations of fine-needle aspiration.

Background: Canalicular adenoma is a rare, benign tumor of primarily salivary gland origin that presents mostly in the upper lip. However, there are only six reports in the English literature detailing canalicular adenoma of the parotid gland, none of which discuss discrepancy between preoperative cytology and surgical pathology. In this report, we present a rare case of parotid gland canalicular adenoma where preoperative ultrasound-guided fine-needle aspiration (USFNA) suggested malignancy.

Extratumoral invasion: A unique phenomenon of aggressive recurrent oropharyngeal squamous cell carcinoma.

Background: Oropharyngeal squamous carcinomas cause significant morbidity and mortality. Poor prognosticators include lymphovascular and perineural invasion. Extratumoral phenotypes of these histologic findings confer worse prognoses.

A 3D-Printed Self-Learning Three-Linked-Sphere Robot for Autonomous Confined-Space Navigation.

Reinforcement learning control methods can impart robots with the ability to discover effective behavior, reducing their modeling and sensing requirements, and enabling their ability to adapt to environmental changes. However, it remains challenging for a robot to achieve navigation in confined and dynamic environments, which are characteristic of a broad range of biomedical applications, such as endoscopy with ingestible electronics. Herein, a compact, 3D-printed three-linked-sphere robot synergistically integrated with a reinforcement learning algorithm that can perform adaptable, autonomous crawling in a confined channel is demonstrated.

Degradation of gap junction connexins is regulated by the interaction with Cx43-interacting protein of 75 kDa (CIP75).

Connexins are a family of transmembrane proteins that form gap junction channels. These proteins undergo both proteasomal and lysosomal degradation, mechanisms that serve to regulate connexin levels. Our previous work described CIP75 [connexin43 (Cx43)-interacting protein of 75 kDa], a protein involved in proteasomal degradation, as a novel Cx43-interacting protein.

Connexins: mechanisms regulating protein levels and intercellular communication.

Intercellular communication can occur through gap junction channels, which are comprised of connexin proteins. Therefore, levels of connexins can directly correlate with gap junctional intercellular communication. Because gap junctions have a critical role in maintaining cellular homeostasis, the regulation of connexin protein levels is important.

CIP75 (connexin43-interacting protein of 75 kDa) mediates the endoplasmic reticulum dislocation of connexin43.

Gap junctions are intercellular channels that comprise connexin proteins such as Cx43 (connexin43). The level of gap junctional intercellular communication can be regulated by Cx43 turnover mediated through various degradation pathways. The UbL (ubiquitin-like) domain-UBA (ubiquitin-associated) domain protein, CIP75 (connexin43-interacting protein of 75 kDa), regulates the proteasomal degradation of Cx43.

The connexin43-interacting protein, CIP85, mediates the internalization of connexin43 from the plasma membrane.

CIP85 was previously identified as a connexin43 (Cx43)-interacting protein that is ubiquitously expressed in multiple mammalian tissues and cell types. The interaction between the SH3 domain of CIP85 and a proline-rich region of Cx43 has previously been associated with an increased rate of Cx43 turnover through lysosomal mechanisms. This report presents biochemical and immunofluorescence evidence that overexpression of CIP85 reduced the presence of Cx43 in gap junction plaques at the plasma membrane.

Degradation of connexins through the proteasomal, endolysosomal and phagolysosomal pathways.

Connexins comprise gap junction channels, which create a direct conduit between the cytoplasms of adjacent cells and provide for intercellular communication. Therefore, the level of total cellular connexin protein can have a direct influence on the level of intercellular communication. Control of connexin protein levels can occur through different mechanisms during the connexin life cycle, such as by regulation of connexin gene expression and turnover of existing protein.

Ubiquitination, intracellular trafficking, and degradation of connexins.

Gap junction channels provide a conduit for communication between neighboring cells. The function of gap junction channels is regulated by posttranslational modifications of connexins, the proteins that comprise these channels. Ubiquitination of connexins has increasingly been viewed as one mechanism by which cells regulate the level of connexins present in cells, as well as the corresponding intercellular communication.

Activation of Akt, not connexin 43 protein ubiquitination, regulates gap junction stability.

The pore-forming gap junctional protein connexin 43 (Cx43) has a short (1-3 h) half-life in cells in tissue culture and in whole tissues. Although critical for cellular function in all tissues, the process of gap junction turnover is not well understood because treatment of cells with a proteasomal inhibitor results in larger gap junctions but little change in total Cx43 protein whereas lysosomal inhibitors increase total, mostly nonjunctional Cx43. To better understand turnover and identify potential sites of Cx43 ubiquitination, we prepared constructs of Cx43 with different lysines converted to arginines.

Ubiquitin-independent proteasomal degradation of endoplasmic reticulum-localized connexin43 mediated by CIP75.

Connexin43 (Cx43) is a transmembrane protein that forms gap junction channels. Regulation of Cx43 turnover is one mechanism to control the level of intercellular communication that occurs through gap junction channels. Proteasomal degradation of Cx43 is regulated in part through CIP75, a ubiquitin-like and ubiquitin-associated domain containing protein.

Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation.

The ubiquitin-proteasome pathway of protein degradation is one of the major mechanisms that are involved in the maintenance of the proper levels of cellular proteins. The regulation of proteasomal degradation thus ensures proper cell functions. The family of proteins containing ubiquitin-like (UbL) and ubiquitin-associated (UBA) domains has been implicated in proteasomal degradation.

Generation and characterization of mouse monoclonal antibodies against CIP75, an UbL-UBA domain-containing protein.

CIP75 is a member of the UbL(ubiquitin-like)-UBA (ubiquitin-associated) domain containing protein family, which has a variety of functions. One specific role described for several members of the UbL-UBA family is the involvement in the proteasomal degradation of target proteins. We have reported that CIP75 interacts with the gap junction protein, connexin43 (Cx43), and that CIP75 may modulate the proteasomal degradation of Cx43.

A novel connexin43-interacting protein, CIP75, which belongs to the UbL-UBA protein family, regulates the turnover of connexin43.

The degradation of connexin43 (Cx43) has been reported to involve both lysosomal and proteasomal degradation pathways; however, very little is known about the mechanisms regulating these Cx43 degradation pathways. Using yeast two-hybrid, glutathione S-transferase pull-down, and co-immunoprecipitation approaches, we have identified a novel Cx43-interacting protein of approximately 75 kDa, CIP75. Laser confocal microscopy showed that CIP75 is located primarily at the endoplasmic reticulum, as indicated by the calnexin marker, with Cx43 co-localization in this perinuclear region.

Quantitative analysis of Hedgehog gradient formation using an inducible expression system.

Background: The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh.