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Gun violence results in approximately 40,000 deaths in the United States each year, yet physicians rarely discuss gun access and firearm safety with patients. Lack of education about how to have these conversations is an important barrier, particularly among trainees.A 2-part training curriculum was developed for first-year residents. It included (1) a didactic presentation outlining a framework to understand types of firearm-related violence, describing institutional resources, and reviewing strategies for approaching discussions about firearms with patients, and (2) interactive case scenarios, adjusted for clinical disciplines, with standardized patients. Before and after the training, participants completed surveys on the training's relevance, efficacy, and benefit. Standardized patients provided real-time feedback to participants and completed assessments based on prespecified learning objectives.In June-August 2019, 148 first-year residents in internal medicine (n = 74), general surgery (n = 12), emergency medicine (n = 15), pediatrics (n = 22), psychiatry (n = 16), and OB/GYN (n = 9) completed the training. Most (70%, n = 104) reported having no prior exposure to gun violence prevention education. Knowledge about available resources increased among participants from 3% (n = 5) pretraining to 97% (n = 143) post-training. Awareness about relevant laws, such as Extreme Risk Protection Orders, and their appropriate use increased from 3% (n = 4) pretraining to 98% (n = 145) post-training. Comfort discussing access to guns and gun safety with patients increased from a median of 5 pretraining to 8 post-training (on a scale of 1-10, with higher scores indicating more comfort).Delivery of a case-based gun violence prevention training program was effective and feasible in a single institution. Next steps include expanding the training to other learners (across undergraduate and graduate medical education) and institutions and assessing how the program changes practice over time.

PDF file - 486KB, Figure S1 (A) Average statistics for depth of coverage at 20X, 30X and 40X of all MOC lines. Robust reads were obtained in all samples with a range of 97-98 percent for 20X, 93-95 percent for 30X and 88-92 percent for 40X. (B) Putative SNVs, nsSNVs (Table S1 and S2) and Indels (Table S4) of all MOC lines. Figure S2 Oncoprints from cBio of AKAP9, MED12L, THSD7A, MUC5B, MYH6, LAMA1, LRP2, and 3 RAS (Table S6) genes representing other candidate tumor promoters as compared to the 3 RAS genes. Note that for AKAPs and MED components, we found 9 AKAP family member mutations in 20.4 percent of tumors, with AKAP9 changes in 7 percent (Fig. 1D). Six components of the mediator complex were mutated in 14.7% of cases, with MED12L changes in 5% (Fig. 1E). Figure S3 Number of nsSNV's per node negative (N0) and node positive (N+) tumor in (A) all TCGA OSCC (note that patient TCGA-D6-6516 (N0) with 1463 mutations is not included in this graph) and (B) TCGA OSCC patients who had smoking history reported. There was no significant difference in the average number of mutations between N0 (3272 nsSNVs) and N+ (3097 nsSNVs) patients regardless of smoking status (Tables S8, S9). This analysis showed 17 genes commonly mutated in mouse indolent and human N0 tumors and 55 common genes mutated in mouse aggressive and human N+ tumors (Supplementary Table S10). However, none of these common genes were mutated at high frequency in the human N0 or N+ datasets (Supplementary Table S11 and 12). Finally, comparing N0 and N+ tumors from human TCGA data also showed that specific mutations occur infrequently in both the metastatic and non-metastatic tumors (data not shown). Figure S4 SAM plotsheet of MOC line microarray data with estimated miss rates for delta=4.68 Figure S5 (A) GSEA data of OCAMP-A on UW/FHCRC data with (B) first condensation of enriched genes. (C) GSEA data of OCAMP-A on MDA data with (D) first condensation of enriched genes. (E) GSEA data of OCAMP-A on TCGA data with (F) first condensation of enriched genes. Figure S6 (A) Disease specific survival (DSS) after weighted voting classification of OCAMP-B signature on the MD Anderson dataset shows worse outcome for those with aggressive classification (p=0.028). Figure S7 (A) Disease specific survival (DSS) and (B) overall survival (OS) after weighted voting classification of OCAMP-B signature on the UW/FHCRC dataset shows worse outcome for those with aggressive classification (p

Purpose: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance.Experimental Design: Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes, and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature, and we assessed its representation in four independent human datasets comprising 324 patients using weighted voting and gene set enrichment analysis. Kaplan–Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A quantitative real-time PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy.Results: NGS revealed conservation of human driver pathway mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase, phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L, and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in four independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified patients with OSCC with a 93.5% accuracy.Conclusions: These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. Clin Cancer Res; 20(11); 2873–84. ©2014 AACR.

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XLS file - 6534KB, S1 SNVs indolent lines. S2 SNVs aggressive lines. S3 Distribution of nucleotide changes. S4 MOC line mutations have similarity to 32 most common HNSCC TCGA mutations. S5 MOC line conservation with human OSCC drivers and novel mutations. S6 Indels all MOC lines. S7 Comparison of predicted changes between aggressive and indolent lines. S8 MOC line common mutations. S9 Unique aggressive MOC line mutations. S10 Comparison of MOC line mutations with TCGA N0 and N+ mutations. S11 TCGA mutation burden per tumor in N0 and N+ specimens. S12 MOC line and TCGA common mutations. S13 Rate of alterations of aggressive MOC/TCGA N+ mutations from Table S10. S14 Rate of alterations of indolent MOC/TCGA N0 mutations from Table S10. S15 SAM analysis of aggressive versus indolent expression data. S16 Compiled rank metric scores of OCAMP-A genes across three human datasets. S17 Cross tabulation and multivariable analysis of OCAMP-B on MD dataset. S18 Weighted voting classification with OCAMP-B on independent UPENN dataset. S19 SVM output data for training and test sets. S20 OCAMP-A comparison to three published signatures.

Liver transplantation (LT) provides better outcome than surgical resection (SR) although both are acceptable surgical options for hepatocellular carcinoma (HCC). It is unclear whether non-clinical factors drive treatment decisions. Our goal is to identify factors that may affect treatment decisions.Patients aged 18-74 with T2 HCC undergoing either LT or SR in Surveillance, Epidemiology, and End Results Database from 2004 to 2014 were included. Healthcare resources data were analyzed to assess factors that predict utilization of LT versus SR, adjusted for demographic, clinical outcomes, and socioeconomic factors.51% of patients (Total N = 2616) received LT, with a substantial state-level variation in LT rates (0.0%-66.9%). Higher LT center density [OR = 1.04 per 1% increment, P 0.01], male gender (OR = 1.38, P = 0.02), and numbers of potential donors (OR = 1.19, P = 0.03) were positively associated with LT utilization. Conversely, higher incidence of chronic liver disease/cirrhosis (OR = 0.41 per one additional case per 100,000 populations, P = 0.001) and minority populations were negatively correlated with LT utilization. Notably, short-term surgical outcomes (in-hospital LTSR mortality) were not associated with LT utilization.Liver transplant center density and organ availability, but not surgical outcomes, affect utilization of LT. Future studies should focus on increasing availability of resources.

Solid organ transplantation has experienced incredible success over the past half century in rescuing patients with end-stage organ failure and bestowing them with a high quality of life. This success in large part is the result of advances in immunosuppression, however, these regimens come with significant costs including opportunistic infections, and in some cases, direct toxicity to the newly transplanted organs. Further advances are needed. Immunosuppression and tolerance based on regulatory T cells provide an attractive alternative because of their ability to target these immunomodulatory functions specifically to the anti-allograft immune response.

Purpose of review Human islet transplantation has proven to be a highly effective treatment for patients with labile type 1 diabetes mellitus, which can free patients from daily glucose monitoring and insulin injections. However, the shortage of islet donors limits its' broad application. Porcine islet xenotransplantation presents a solution to the donor shortage and recent advances in genetic modification and immunosuppressive regimens provide renewed enthusiasm for the potential of this treatment. Recent findings Advances in genetic editing technology are leading to multigene modified porcine islet donors with alterations in expression of known xenoantigens, modifications of their complement and coagulation systems, and modifications to gain improved immunological compatibility. Recent NHP-based trials of costimulation blockade using CD154 blockade show promising improvements in islet survival, whereas results targeting CD40 are less consistent. Furthermore, trials using IL-6 receptor antagonism have yet to demonstrate improvement in glucose control and suffer from poor graft revascularization. Summary This review will detail the current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and review barriers to translation of xenoislets to the clinic.

Through multiple mechanisms, regulatory B cells (Breg) have been shown to play an important role in the development of allograft tolerance. However, a careful understanding of the role of antigen-specificity in Breg-mediated allograft tolerance has remained elusive. In experimental models of islet and cardiac transplantation, it has been established that Bregs can be induced in vivo by anti-CD45RB ± anti-TIM1antibody treatment, resulting in prolonged, Breg-dependent allograft tolerance. The importance of Breg antigen recognition has been suggested but not confirmed through adoptive transfer experiments, using tolerant WT C57BL/6 animals challenged with either BALB/c or C3H grafts. However, the importance of receptor-specificity has not been formally tested. Here, we utilize the novel ovalbumin-specific B cell receptor transnuclear (OBI) mice in multiple primary tolerance and adoptive transfer experiments to establish that Breg-dependent allograft tolerance relies on antigen recognition by B cells. Additionally, we identify that this Breg-dependent tolerance relies on the function of transforming growth factor-β. Together, these experiments mark important progress toward understanding how best to improve Breg-mediated allograft tolerance.

Clinical islet transplantation has relied almost exclusively on intraportal administration of pancreatic islets, as it has been the only consistent approach to achieve robust graft function in human recipients. However, this approach suffers from significant loss of islet mass from a potent immediate blood-mediated inflammatory response (IBMIR) and a hypoxic environment. To avoid these negative aspects of the portal site, we explored an alternative approach in which allogeneic islets were transplanted into the intrapleural space of a non-human primate (NHP), treated with an immunosuppression regimen previously reported to secure routine survival and tolerance to allogeneic islets in NHP. Robust glycemic control and graft survival were achieved for the planned study period of >90 days. Our observations suggest the intrapleural space provides an attractive locale for islet transplantation due to its higher oxygen tension, ability to accommodate large transplant tissue volumes, and a lack of IBMIR-mediated islet damage. Our preliminary results reveal the promise of the intrapleural space as an alternative site for clinical islet transplantation in the treatment of type 1 diabetes.

Regulatory B cells (Bregs) have shown promise as anti-rejection therapy applied to organ transplantation. However, less is known about their effect on other B cell populations that are involved in chronic graft rejection. We recently uncovered that naive B cells, stimulated by TLR ligand agonists, converted into B cells with regulatory properties (Bregs-TLR) that prevented allograft rejection. Here, we examine the granular phenotype and regulatory properties of Breg-TLR cells suppressing B cells. Cocultures of Bregs-TLR with LPS-activated B cells showed a dose-dependent suppression of targeted B cell proliferation. Adoptive transfers of Bregs-TLR induced a decline in antibody responses to antigenically disparate skin grafts. The role of Breg BCR specificity in regulation was assessed using B cell-deficient mice replenished with transgenic BCR (OB1) and TCR (OT-II) lymphocytes of matching antigenic specificity. Results indicated that proliferation of OB1 B cells, mediated through help from CD4+ OT-II cells, was suppressed by OB1 Bregs of similar specificity. Transcriptomic analyses indicated that Bregs-TLR suppression is associated with a block in targeted B cell differentiation controlled by PRDM1 (Blimp1). This work uncovered the regulatory properties of a new brand of Breg cells and provided mechanistic insights into potential applications of Breg therapy in transplantation.

Porcine cells devoid of three major carbohydrate xenoantigens, αGal, Neu5GC, and SDa (TKO) exhibit markedly reduced binding of human natural antibodies. Therefore, it is anticipated that TKO pigs will be better donors for human xenotransplantation. However, previous studies on TKO pigs using old world monkeys (OWMs) have been disappointing because of higher anti-TKO pig antibodies in OWMs than humans. Here, we show that long-term survival of renal xenografts from TKO pigs that express additional human transgenes (hTGs) can be achieved in cynomolgus monkeys. Kidney xenografts from TKO-hTG pigs were transplanted into eight cynomolgus recipients without pre-screening for low anti-pig antibody titers. Two recipients of TKO-hTG xenografts with low expression of human complement regulatory proteins (CRPs) (TKO-A) survived for 2 and 61 days, whereas six recipients of TKO-hTG xenografts with high CRP expression (TKO-B) survived for 15, 20, 71, 135, 265, and 316 days. Prolonged CD4+ T cell depletion and low anti-pig antibody titers, which were previously reported important for long-term survival of αGal knock-out (GTKO) xenografts, were not always required for long-term survival of TKO-hTG renal xenografts. This study indicates that OWMs such as cynomolgus monkeys can be used as a relevant model for clinical application of xenotransplantation using TKO pigs.

Regulatory B cells contribute to the regulation of immune responses in cancer, autoimmune disorders, allergic conditions and inflammatory diseases. Although most studies focus on regulatory B lymphocytes expressing interleukin‐10, there is growing evidence that B cells producing transforming growth factor β (TGF‐β) can also regulate T‐cell immunity in inflammatory diseases and promote the emergence of regulatory T cells that contribute to the induction and maintenance of natural and induced immune tolerance. Most research on TGF‐β+ regulatory B cells has been conducted in models of allergy, cancer and autoimmune diseases, but there has, as yet, been limited scrutiny of their role in the transplant setting. Herein, we review recent investigations seeking to understand how TGF‐β‐producing B cells direct the immune response in various inflammatory diseases and whether these regulatory cells may have a role in fostering tolerance in transplantation., Transforming growth factor‐β (TGF‐β)‐producing B cells can regulate T‐cell immunity and induce Tregs independently of interleukin‐10. Most research on TGF‐β+ regulatory B cells has been conducted in various inflammatory diseases but less in the transplant setting. Herein, we review recent investigations seeking to understand how TGF‐β‐producing B cells direct the immune response in various inflammatory diseases and whether these cells may have a role in fostering tolerance in transplantation.

Precise analyses of alloreactive T cell phenotype and function can inform both the nature and intensity of adaptive responses to transplant antigens. However, alloreactive T cells are sparse and difficult to detect, particularly in cryopreserved peripheral blood mononuclear cells (PBMCs) and from hypo-responsive individuals. An assay to identify and phenotype alloreactive cells would be particularly valuable, especially for multi-center clinical trials that often store frozen samples for batch analysis. Herein we demonstrate consistent and reproducible alloreactive T cell detection in cryopreserved PBMC following a short-term mixed lymphocyte reaction (MLR). The inherent background expression levels of activation markers on responder T cells were minimized by including a resting period prior to the assay. Stimulator cells were activated before inclusion in the MLR by addition of CD40L and IL-4. The time frame and markers to identify and phenotype alloreactive T cells following stimulation were optimized using short term co-cultures. We defined subsets of CD4+ and CD8+ T cells co-expressing CD69 and either CD154 or CD137 following allostimulation as alloreactive, and further phenotyped these cells with a variety of surface markers such as PD-1, LAG-3, and TIM-3. This assay may allow for the monitoring of donor-specific T cells in transplant recipients with longitudinally collected and cryopreserved PBMCs and provide a useful tool to identify biomarkers associated with tolerance. These biomarkers may add to mechanistic insights in immune recognition of transplanted tissues and/or cells.

Islet transplantation has potential to dramatically alter the treatment strategy for both type 1 and type 2 diabetes mellitus. In contrast to exogenous insulin administration, islet transplantation offers a curative therapy through the islets’ natural ability to monitor blood glucose levels and deliver the appropriate amount of insulin. However, several challenges hinder the widespread adoption of islet transplantation as a primary treatment for diabetes. Aside from the challenges of islet hypoxia and a lack of readily available donor islets, immune-mediated rejection of the transplanted islets represents a significant challenge, preventing widespread adoption of islet transplantation as a mainstay of diabetes treatment. As with any allogeneic transplantation, the decision to perform isle transplants must carefully weigh the benefits of the new, healthy tissue (i.e., superior glucose control) against the risks of life-long systemic immunosuppression. Because of the life-saving advances in exogenous insulin production and delivery over the last 100 years, islet transplantation and whole pancreas transplant are currently reserved for individuals who have exhibited life threatening, severe hypoglycemic episodes or are already immunosuppressed for an additional, concurrent organ transplant, most commonly kidney transplant recipients. Additionally, several of the most common immunosuppressants are diabetogenic and toxic to pancreatic beta cells. For these reasons, the risks of the immunosuppressive regimen typically outweigh the benefit for the average diabetic patient. However, induction of immunologic tolerance to the transplanted islet grafts has become a very attractive alternative to pharmacologic immunosuppression because it holds the promise of the benefit of the transplant without the risks of the immunosuppression. Islet transplant tolerance has, thus, become a very active area of research. Speaking generally, transplant tolerance is an immunological state in which the recipient immune system ignores the nonself-tissue, while the immune system maintains reactivity to other agents, such as bacterial or viruses. Immunologic tolerance would, therefore, establish the long-term survival of the transplanted islets without the sequalae of systemic immunosuppression. This chapter provides an overview of current clinical approaches to tolerance induction as well as preclinical strategies being studied for islet tolerance. Because islets are transplanted as an organized cluster of cells, they lend themselves to additional immunoprotective strategies that large organ transplants do not, such as encapsulation and stem-cell-derived production. The potential immunological impact of these technologies and how they work into tolerance strategies will also be discussed.

Purpose of review Immunological tolerance has long been considered the 'holy grail' of organ transplantation. Although tolerance has been an active area of research for 70 years, its clinical application has only been possible in the last two decades and widespread use remains an, as yet, unattained goal. Recent advances in the understanding of immune regulation have identified many new approaches to tolerance induction and several clinical trials are currently aimed at bringing this treatment to more patients. Recent findings Mixed chimerism remains the most successful approach to tolerance induction. However, many treatments, including adoptive transfer of regulatory T cells, regulatory B cells, and immune suppressive dendritic cells and myeloid derived suppressor cells have shown great promise in preclinical models. Recent clinical studies have found that both kidney and liver operational tolerance are achievable in the appropriate settings. Furthermore, combining multiple tolerance approaches has shown potential to produce durable and safer tolerance. Summary Tolerance to protect kidney and liver allografts has become a valuable therapy in the correct circumstances. Through further clinical trials and an improved understanding of immune regulatory components, tolerance is poised to have a significant impact on transplantation in the years to come.

Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape. Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells. Using class I prediction algorithms, we identify mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting.

Vidian nerve schwannomas are highly unusual, with only two reported cases in the world literature, and present with a constellation of symptoms that may be extremely vague. In the reported cases, open techniques have been utilized that required significant dismantling of the midfacial skeleton to access and manage these skull base lesions. Over the last 15 years, a paradigm shift in base of skull surgery has evolved with the advent of transnasal endoscopic techniques and instrumentation, improved surgical access and resectability of most skull-based pathologies, including vidian nerve lesions as reported here. We describe the varied clinical presentation and radiologic findings in two patients with such rare lesions. In addition, in one of these patients, we report on the first use of an expanded endonasal technique to access and remove vidian nerve schwannomas entirely endoscopically.

Purpose: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance. Experimental Design: Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes, and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature, and we assessed its representation in four independent human datasets comprising 324 patients using weighted voting and gene set enrichment analysis. Kaplan–Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A quantitative real-time PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy. Results: NGS revealed conservation of human driver pathway mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase, phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L, and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in four independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified patients with OSCC with a 93.5% accuracy. Conclusions: These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. Clin Cancer Res; 20(11); 2873–84. ©2014 AACR.

We previously reported that STAT1 expression is frequently abrogated in human estrogen receptor-α-positive (ERα+) breast cancers and mice lacking STAT1 spontaneously develop ERα+ mammary tumors. However, the precise mechanism by which STAT1 suppresses mammary gland tumorigenesis has not been fully elucidated. Here we show that STAT1-deficient mammary epithelial cells (MECs) display persistent prolactin receptor (PrlR) signaling, resulting in activation of JAK2, STAT3 and STAT5A/5B, expansion of CD61+ luminal progenitor cells and development of ERα+ mammary tumors. A failure to upregulate SOCS1, a STAT1-induced inhibitor of JAK2, leads to unopposed oncogenic PrlR signaling in STAT1−/− MECs. Prophylactic use of a pharmacological JAK2 inhibitor restrains the proportion of luminal progenitors and prevents disease induction. Systemic inhibition of activated JAK2 induces tumor cell death and produces therapeutic regression of pre-existing endocrine-sensitive and refractory mammary tumors. Thus, STAT1 suppresses tumor formation in mammary glands by preventing the natural developmental function of a growth factor signaling pathway from becoming pro-oncogenic. In addition, targeted inhibition of JAK2 may have significant therapeutic potential in controlling ERα+ breast cancer in humans.

Vidian nerve schwannomas are highly unusual, with only two reported cases in the world literature, and present with a constellation of symptoms that may be extremely vague. In the reported cases, open techniques have been utilized that required significant dismantling of the midfacial skeleton to access and manage these skull base lesions. Over the last 15 years, a paradigm shift in base of skull surgery has evolved with the advent of transnasal endoscopic techniques and instrumentation, improved surgical access and resectability of most skull-based pathologies, including vidian nerve lesions as reported here. We describe the varied clinical presentation and radiologic findings in two patients with such rare lesions. In addition, in one of these patients, we report on the first use of an expanded endonasal technique to access and remove vidian nerve schwannomas entirely endoscopically.