Multidisciplinary approach to severe intracranial, intraorbital allergic fungal sinusitis.

BACKGROUND: Allergic fungal sinusitis (AFS) is a form of paranasal mycosis that often involves bone destruction and can extend into the orbit and anterior skull base. Intracranial and intraorbital involvement are published but not both in each included patient of a series. The purpose of the present study was to review cases of extensive AFS with orbital or/and skull base erosion, including the presenting symptoms, patient socioeconomic background, imaging features, surgical technique, and post-operative outcomes. METHODS: The records of 30 patients with the histological diagnosis of AFS and both intracranial and intraorbital involvement were reviewed. RESULTS: The average age of the patients was 25.2 years. 83 % of patients were male. 70 % were African American. 66 % of patients had Medicaid or were uninsured. Presenting symptoms were headaches (80 %), nasal obstruction (33 %), proptosis (40 %), vision change (23 %), facial pressure (10 %), and decreased sense of smell (7 %). 100 % of patients had bone erosion observed on computerized tomography scans with disease extending intracranially through the anterior skull base or posterior wall of the frontal sinus along with disease that eroded through the lamina papyracea. All patients had failed medical management. All patients underwent surgery by Otolaryngology, Ophthalmology, and Neurosurgery with transnasal endoscopic approaches and orbitotomy. 80 % also underwent a bifrontal craniotomy for removal of intracranial extradural disease with cranialization. 53 % of patients had orbital implants remaining after surgery; 23 % had nasal stents. There were no postoperative cerebrospinal fluid leaks. Average hospital stay was 4.8 days. Preoperatively, 13 % of patients underwent allergy testing. 94 % saw an Allergist postoperatively. 21 % required follow up surgery. CONCLUSIONS: A team approach of Otolaryngologists, Ophthalmologists, and Neurosurgeons is recommended for this slowly growing but locally destructive disease. Most patients with AFS will present with headaches and nasal obstruction. While most cases of AFS can be successfully managed with transnasal endoscopic techniques, orbitotomy and craniotomy represents an effective treatment for severe AFS cases with extensive intracranial and intraorbital involvement. This disease is found most commonly in young African American males and in the underinsured.

Characterisation of RAET1E/ULBP4 exon 4 and 3' untranslated region genetic architecture reveals further diversity and allelic polymorphism.

NKG2D is a natural killer cell activating receptor recognising ligands on infected or tumorigenic cells, leading to their cytolysis. There are eight known genes encoding NKG2D ligands: MICA, MICB and ULBP1-6. MICA and MICB are highly polymorphic and well characterised, whilst ULBP ligands are less polymorphic and the functional implication of their diversity is not well understood. Using International HLA and Immunogenetics Workshop (IHIW) cell line DNA, we previously characterised alleles of the RAET1E gene (encoding ULBP4 proteins), including the 5' UTR promoter region and exons 1-3. We found 11 promoter haplotypes associating with alleles based on exons 1-3, revealing 19 alleles overall. The current study extends this analysis using 87 individual DNA samples from IHIW cell lines or cord blood to include RAET1E exon 4 and the 3' UTR, as polymorphism in these regions have not been previously investigated. We found two novel exon 4 polymorphisms encoding amino acid substitutions altering the transmembrane domain. An amino acid substitution at residue 233 was unique to the RAET1E*008 allele whereas the substitution at residue 237 was shared between groups of alleles. Additionally, four haplotypes were found based on 3' UTR sequences, which were unique to certain alleles or shared with allele groups based on exons 1-4 polymorphisms. Furthermore, putative microRNAs were identified that may interact with these polymorphic sites, repressing transcription and potentially affecting expression levels.

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases.

OBJECTIVES: NKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome. METHODS: We retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes. RESULTS: In adult patients, LNK1 homozygous CB significantly improved 60-day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4-0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60-day engraftment (HR 0.4; 95% CI 0.2-0.7; p = .003), as did MICA-129 methionine+ CB grafts (HR 1.7 95% CI 1.1-2.6; p = .02). CONCLUSION: CB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.

A Review of Voice Disorders in School-Aged Children.

OBJECTIVES: The purpose of this study was to review literature concerning voice disorders in school-aged children. STUDY DESIGN: Integrative review. MATERIALS AND METHODS: A database search was conducted using PubMed, Web of Science, Academic Search Complete, CINAHL Complete, and Medline. All records included in this review were peer-reviewed journal articles that discussed voice disorders in children, conducted in the United States or Canada, written in English, and published between 2009 and 2019. RESULTS: Database searching identified 1,771 records and 551 duplicates were removed. A total of 1,220 records were screened and 949 records were excluded. Two hundred and seventy-one full-text records were screened and 12 records met inclusion criteria. Vocal fold nodules were the most commonly reported vocal fold pathology. The Consensus Auditory Perceptual Evaluation of Voice and endoscopy were the most commonly reported assessments. However, variations in practice patterns and access to voice services may exist. CONCLUSIONS: The findings highlight that school-aged children may face barriers in accessing voice services. As a result, continued analyses of the potential barriers that hinder identification and treatment of voice disorders in this population appear warranted.

Racial and Ethnic Disparities in Laryngeal Cancer Care.

There is a long history of racial and ethnic disparities in healthcare and they continue to persist in contemporary society. These disparities have the potential to negatively affect morbidity and mortality in racial and ethnic minorities diagnosed with laryngeal cancer. Diagnosis, medical treatment, and rehabilitation for laryngeal cancer have improved considerably, leading to improvements in overall survival rates and physical, social, and psychological functioning. Yet members of minority and underrepresented groups are at an increased risk for experiencing reduced access to quality care and delays between diagnosis and treatment, and as a result have lower survival rates. Increasing health providers' awareness of racial and ethnic disparities in laryngeal cancer is necessary to facilitate changes in patient and provider education, clinical practice, and health policies. The purpose of this review is to summarize current literature on disparities in laryngeal cancer diagnosis, treatment, and rehabilitation among Black and Hispanic patients. We present recent data from the Surveillance, Epidemiology, and End Results database to examine trends in laryngeal cancer and patient, provider, and health systems factors that may perpetuate these disparities. In addition, we offer interventions to address racism and other racial and ethnic biases in laryngeal cancer care and describe research and legislative actions that are needed to reduce disparities in this area.

Cord blood and amniotic membrane extract eye drop preparations display immune-suppressive and regenerative properties.

Diseases and injuries that compromise the ocular surface cause considerable patient distress and have long term consequences for their quality of life. Treatment modalities that can address the delicate balance of tissue regeneration, inflammation and maintenance of corneal transparency are therefore needed. We have recently formulated two novel eye drops from placental tissues: cord blood platelet lysate (CBED) and amniotic membrane extract eye drops (AMED), which can be used to treat severe ocular disorders. Here we characterise these two preparations by measuring: (a) growth factors (GF) and cytokines composition, (b) promotion of human corneal epithelial cell (HCEC) growth and (c) effects on immune cells in a lymphocyte culture assay. Finally, their bioavailability was assayed in an ex vivo porcine corneal model. We show that both preparations contain GF and cytokines that were able to promote the in vitro growth of HCEC and support repair in an in vitro scratch test. When assessed in a lymphocyte culture, both favoured immune suppression reducing the cellular expression of NKG2D and CD107a as well as the production of interferon gamma (IFN-γ) in natural killer, NKT and T cells. Regarding bioavailability, CBED active molecules were found mainly in the pre-corneal fraction with some penetration into the corneal fraction, in an ex vivo model. In summary, both placental-derived allogeneic preparations, CBED and AMED, display regenerative and immunomodulatory capabilities. These results will help define mechanisms of action and the best indications and doses of each product for use in a particular patient and support the development of off-the-shelf therapies for ocular surface pathologies in which wound healing defects and inflammatory events are contributing factors.

A semantic similarity based methodology for predicting protein-protein interactions: Evaluation with P53-interacting kinases.

Biomedical literature contains unstructured, rich information regarding proteins, ligands, diseases as well as biological pathways in which they are involved. Systematically analyzing such textual corpus has the potential for biomedical discovery of new protein-protein interactions and hidden drug indications. For this purpose, we have investigated a methodology that is based on a well-established text mining tool, Word2Vec, for the analysis of PubMed full text articles to derive word embeddings, and the use of a simple semantic similarity comparison either by itself or in conjunction with k-Nearest Neighbor (kNN) technique for the prediction of new relationships. To test this methodology, three lines of retrospective analyses of a dataset with known P53-interacting proteins have been conducted. First, we demonstrated that Word2Vec semantic similarity can infer functional relatedness among all kinases known to interact with P53. Second, in a series of time-split experiments, we demonstrated that both a simple similarity comparison and kNN models built with papers published up to a certain year were able to discover P53 interactors described in later publications. Third, in a different scenario of time-split experiments, we examined the predictions of P53-interacting proteins based on the kNN models built on data prior to a certain split year for different time ranges past that year, and found that the cumulative number of correct predictions was indeed increasing with time. We conclude that text mining of research papers in the PubMed literature based on Word2Vec analysis followed by a simple similarity comparison or kNN modeling affords excellent predictions of protein-protein interactions between P53 and kinases, and should have wide applications in translational biomedical studies such as repurposing of existing drugs, drug-drug interaction, and elucidation of mechanisms of action for drugs.

Management of Vocal Fold Paralysis and Dysphagia for Neurologic Malignancies in Children.

OBJECTIVES: To evaluate our experience with a significant number of brain malignancy-related vocal fold paralysis patients and their response to vocal cord-related therapies. BACKGROUND: Vocal fold paralysis is a potentially devastating complication of various types of pediatric diseases and surgeries that can lead to significant vocal and swallowing difficulties. While there is significant data in the literature on outcomes of children treated for vocal fold paralysis following cardiac or thyroid surgery, there is a scarcity of such information on children following the treatment of neurologic malignancy. METHODS: Records of 19 patients at a tertiary center who were treated for neurologic malignancies and developed either unilateral or bilateral vocal fold paralysis were reviewed for vocal fold pathology and vocal fold paralysis treatment-related variables, including initial diagnosis, management with observation or speech therapy, duration of therapy, pre- and postintervention swallow studies, and surgical intervention. RESULTS: Bilateral vocal fold paralysis was noted in 26% (5/19) patients. Eighty-four percent (16/19) of patients had stable or improved ability to vocalize and swallow following therapy. There was no statistically significant difference in speech or swallowing improvement after speech therapy alone or speech therapy in combination with injection laryngoplasty (P = .25). No complications were noted with surgical intervention. CONCLUSIONS: Patients with vocal fold paralysis secondary to neurologic malignancy can have an improvement in speech and swallowing after a variety of treatments, including speech therapy or early injection laryngoplasty. There was no statistically significant difference in improvement based on the type of intervention utilized. A larger sample size is needed to conclude whether surgical intervention combined with speech therapy leads to more rapid and significant functional improvement than speech therapy alone.

Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes.

MICA and MICB genes encode ligands that interact with the natural killer (NK) cell activating receptor, NKG2D. These ligands display a highly polymorphic allelic repertoire, although the true functional significance of this polymorphism remains elusive. We previously reported additional polymorphism in the 5' untranslated region (UTR) proximal promoter region of these genes by sequencing international histocompatibility workshop (IHW) cell line DNA promoter and coding regions. The present study extends this analysis by further characterising the 3'UTR region of the same IHW reference panel to achieve a more complete understanding of MICA and MICB haplotype diversity and possible functional relevance. We found 17 extended MICA haplotypes encompassing the coding region and 3'UTR, including four novel haplotypes identified in IHW cell line DNA. This increased to 21 when also considering the 5'UTR proximal promoter region. Analysis of the MICB 3'UTR revealed two novel sequences in cell lines KLO and WIN designated MICB-UTR8 and UTR9, respectively. A total of 11 MICB haplotypes were identified in this study and five were unique. The present study, characterising MICA/B 3'UTR polymorphism utilising IHW reference cell lines, could be useful for future studies investigating the role of microRNA in post-transcriptional repression of gene expression and for immunotherapy strategies to combat cancer progression.

Functional Characterisation and Analysis of the Soluble NKG2D Ligand Repertoire Detected in Umbilical Cord Blood Plasma.

We previously reported that cord blood plasma (CBP) contains significantly more soluble NKG2D ligands (sNKG2DLs), such as sMICB and sULBP1, than healthy adult plasma. Viral infection or malignant transformation upregulates expression of NKG2D ligand on affected cells, leading to NK group 2, member D (NKG2D)-mediated natural killer (NK) cell lysis. Conversely, sNKG2DL engagement of NKG2D decreases NK cell cytotoxicity leading to viral or tumour immune escape. We hypothesised that sNKG2DLs detected in CBP may represent an additional fetal-maternal tolerance mechanism. To further understand the role of sNKG2DL in pregnancy and individual contributions of the various ligand types, we carried out functional analysis using 181 CBP samples. To test the ability of CBP to suppress the function of NK cells in vitro, we measured expression of NKG2D, CD107a, and IFN-γ in NK cells from control donors after exposure to 181 individual CBP samples and characterised the sMICA, sMICB, and sULBP1 content of each one. Furthermore, to detect possible allelic differences between samples that may also affect function, we carried out umbilical cord blood typing for MHC class I-related chain A (MICA) and MHC class I-related chain B (MICB) coding and promoter allelic types. Strongest functional correlations related to increasing concentration of exosomal sULBP1, which was present in all CBP samples tested. In addition, common MICB alleles, such as MICB*005:02, resulted in increased concentration of sMICB. Interestingly, MICB*005:02 uniquely associated with eight different promoter types. Among promoter polymorphisms, P2 resulted in the highest expression of sMICB and P9 the least and was confirmed using luciferase reporter assays. Higher levels of sMICB associated with lower IFN-γ production, indicating that sMICB also suppressed NK cell function. We also examined the MICA functional dimorphism encoding methionine (met) or valine (val) at residue 129 associated with strong or weak NKG2D binding, respectively. Most sMICA associated with val/val, some with met/val but none with met/met and, counter-intuitively, the presence of sMICA in CBP increased NK cell cytotoxicity. We propose a model for fetal-maternal tolerance, whereby NK cell activity is limited by sULBP1 and sMICB in CBP. The release of 129val sMICA with weak NKG2D signalling may reduce the overall net suppressive signal and break tolerance thus allowing fetal NK cells to overcome immunological threats in utero.

Giant siliconoma mimicking locally advanced breast cancer: A case report and review of literature.

INTRODUCTION: Silicone prosthetics are widely used for breast augmentation and reconstruction. These devices may extrude free silicone into surrounding tissue, stimulating a granulomatous foreign body reaction. The resulting mass can mimic breast cancer. PRESENTATION OF CASE: 71 year old female with a history of a ruptured silicone implant presents with an enlarging left breast mass. Exam demonstrated and ulcerated, fungating mass with active infection. CT scan demonstrated a 23 × 15 cm mass involving the breast and chest wall with axillary lymphadenopathy. Preoperative biopsies were inconclusive and the patient underwent a modified radical mastectomy. Pathology demonstrated a siliconoma. DISCUSSION: While benign, silicone granulomas of the breast can present similarly to malignancy and are an important differential in the diagnosis of a breast or axillary mass for appropriate patients. MRI is the study of choice and core needle biopsies cannot always establish the diagnosis preoperatively. PET scans can be falsely positive and the diagnosis requires an extensive workup to rule out cancer. CONCLUSION: Siliconomas develop as a result of implant rupture and present with many of the signs and symptoms of breast cancer. The majority of patients should undergo surgery for symptom relief or to rule out cancer.

Primary intrahepatic mesotheliomas: A case presentation and literature review.

INTRODUCTION: Primary Intrahepatic mesotheliomas are malignant tumors arising from the mesothelial cell layer covering Glisson's capsule of the liver. They are exceedingly rare with only fourteen cases reported in the literature. They have nonspecific signs and symptoms and need a high index of suspicion and an extensive workup prior to surgery. Surgery remains the mainstay of treatment. PRESENTATION OF CASE: 48 year old male presented with a 3 months history of abdominal pain, productive cough, anemia and weight loss. He had no history of asbestos exposure. A computed tomography scan and magnetic resonance study demonstrated a heterogeneous subscapular mass within the dome of the right hepatic lobe measuring 11.3 × 6.1 cm involving the diaphragm. Combined resection of the liver and diaphragm was performed to achieve negative margins. Pathology demonstrated an epithelioid necrotic intrahepatic mesothelioma that stained positive for calretinin, CK AE1/AE3, WT-1, D2-40 and CK7. DISCUSSION: Primary intrahepatic mesotheliomas originate from the mesothelial cells lining Glisson's capsule of the liver. They predominantly invade the liver but may also abut or involve the diaphragm. Surgery should include a diagnostic laparoscopy to rule out occult disease or diffuse peritoneal mesothelioma. Complete resection with negative margins should be attempted while maintaining an adequate future liver remnant. Attempts at dissecting the tumor off the involved diaphragm will result in excessive bleeding and may leave residual disease behind. CONCLUSION: Intrahepatic mesotheliomas are rare peripherally-located malignant tumors of the liver. They require a high index of suspicion and a comprehensive workup prior to operative intervention.

Using endoscopy to minimize the extent of resection in the management of giant GISTs of the stomach.

INTRODUCTION: The stomach is the most common site for GISTs. Wide local resection to achieve negative margins is the standard of care. Giants GISTs requiring extensive resection are usually managed with neo-adjuvant therapy followed by partial or total gastrectomy. PRESENTATION OF CASE: We present a case report of a giant GIST on the lesser curvature of the stomach. Neo-adjuvant therapy was administered. Intra-operative endoscopy was used to reduce the extent of gastric resection. DISCUSSION: Simultaneous intra-operative endoscopy demonstrated a 2mm fistula on the lesser curvature of the stomach. A stapler was used to encompass the mass and the fistulous opening. A frozen-section showed clear margins and the endoscope was used to perform an air-leak test. The patient recovered without complications. CONCLUSION: Intra-operative endoscopy can reduce the extent of gastric resection for large GISTs while maintaining the oncologic principles of negative margins and minimal tissue handling.

The morbidity and mortality of hepaticojejunostomies for complex bile duct injuries: a multi-institutional analysis of risk factors and outcomes using NSQIP.

INTRODUCTION: Bile duct injury (BDI) is an infrequent but morbid complication of cholecystectomy. High-grade BDI repairs requiring hepaticojejunostomies are complex and associated with increased morbidity and mortality. This study sought to establish the increased risk associated with complex bile duct repair at a multi-institutional level in the United States. METHODS: Using the ACS-NSQIP Participant Use File, all patients who underwent a hepaticojejunostomy for bile duct repair between 2005 and 2012 were identified. Clinical data, perioperative risk factors and morbidity and mortality rates were calculated. RESULTS: Of the 293 BDI patients, 102 (65.2%) were female and the mean age was 49.8 years. The 30-day morbidity and mortality rates were 26.3% and 2%, respectively. Univariable analysis identified male gender, ASA class, functional status, diabetes, hypertension and chronic steroid use to be associated with increased morbidity. A higher ASA class was associated with increased postoperative sepsis and chronic steroid use was associated with increased overall morbidity on multivariable analysis. The morbidity rates for BDI repair within 30 days of injury vs. later repair were similar (24% vs. 23%), but the mortality rate was higher for the earlier repair group (5% vs. 0%, p = 0.012). CONCLUSIONS: Within the largest multi-institutional analysis of 30-day outcomes after hepaticojejunostomies for BDI in the US, morbidity and mortality rates were established at 26.3% and 2% respectively. ASA class and preoperative functional status remain the main risk factors for surgery. Earlier repair in the face of ongoing sepsis and disability is associated with worse outcomes. A multidisciplinary approach at a specialized center aimed at controlling infection and improving functional status prior to surgical reconstruction is recommended.

Spontaneous endometriosis associated with an umbilical hernia: A case report and review of the literature.

INTRODUCTION: Umbilical endometriosis occurring in the presence of an underlying hernia is extremely rare and presents a diagnostic challenge for the general surgeon. We present an interesting case and perform a comprehensive review of the literature. METHODS: Medline and PubMed were queried for all cases of spontaneous umbilical endometriosis associated with an umbilical hernia. Data was analyzed and is presented along with an interesting case. RESULTS: Only 7 cases have been reported in the literature. Median age was 38 years. Time to presentation was long (up to 5 years) and the majority had cyclical symptoms related to menstruation. All patients, including our case, were treated surgically. DISCUSSION: Spontaneous umbilical endometriosis with an underlying hernia is often missed preoperatively. Preoperative suspicion warrants axial imaging for better operative planning and patient counseling. Surgery consists of enbloc excision of the umbilicus, implant and the hernia sac to avoid residual disease and reduce recurrence. The hernia defect can be repaired primarily or using mesh and the umbilicus reconstructed using skin flaps if necessary. CONCLUSIONS: Surgery is the mainstay of therapy for umbilical endometriosis associated with an underlying hernia. Clinical suspicion warrants preoperative imaging, and follow-up with a gynecologist is essential to address any pelvic disease.

Intestinal stenosis of Garré: A rare cause of small bowel obstruction in the virgin abdomen.

INTRODUCTION: Small bowel obstruction (SBO) in the virgin abdomen usually requires operative intervention. Intestinal stenosis of Garré is a rare and frequently missed cause of SBO following hernia repair. METHODS: We describe a case of intestinal stenosis of Garré and provide a comprehensive review of the literature. Statistical analysis was performed using IBM SPSS Statistics V.22 software and included descriptive analysis. RESULTS: Most males developed a delayed stricture following an inguinal hernia repair (93.3%). 84.6% of females, on the other hand, developed intestinal stenosis following repair of a femoral hernia. 87.5% of strictures developed on the right side. The timing of development of a bowel obstruction is very variable and ranges from 5days to 22 years. 22 patients (68.8%), however, presented with an obstruction within 5 months of hernia repair. CONCLUSIONS: Intestinal stenosis of Garré is an under-reported cause of delayed stricture formation.It is most common following right inguinal hernia repair in men and right femoral hernia repair in women.

Optimal management of GIST tumors located near the gastroesophageal junction: Case report and review of the literature.

INTRODUCTION: The safety and oncologic outcome of laparoscopic gastric GIST resection is well established especially for lesions <5cm in diameter. The optimal management of GIST tumors near the GE junction remains unclear. METHODS: We present a case-report of a 4.7cm GIST tumor near the GE junction managed by endoscopically-assisted laparoscopic wedge resection (EAWR). We present a review of the literature highlighting the various combined laparo-endoscopic techniques available. RESULTS: We used the non-touch lesion-lifting method to laparoscopically resect the GIST tumor under endoscopic guidance. There were no complications and the patient was discharged on postoperative day 3. CONCLUSIONS: Endoscopically-assisted laparoscopic wedge resections are feasible and safe for GIST tumors near the GE junction.

Novel Multidisciplinary Management of a Retropharyngeal Hematoma With Pulmonary Stenting.

Retropharyngeal hematomas (RHs) represents a rare airway obstruction that requires timely intervention to avoid a fatal outcome. Further complicating this malady, RHs of massive proportions can complicate the decision of management selection. After comprehensive literature search, there has been no mention of pulmonary stenting as an intervention for RH. The following case presentation will demonstrate the importance of multidisciplinary management of a 60-year-old presenting with a RH causing airway obstruction, with the use of a novel approach. Airway stenting is a novel, conservative approach for successfully managing patients presenting with massive RH.

Characterization of 5' promoter and exon 1-3 polymorphism of the RAET1E gene.

NKG2D is an activating receptor utilized by natural killer (NK) cells that recognizes upregulated ligands on infected, tumorigenic and damaged cells, leading to their cytolysis. However, the NKG2D ligand (NKG2DL) system is very complex with eight known gene loci encoding slightly different molecules. Furthermore, most NKG2DL gene loci such as MICA and MICB are highly polymorphic with potential for functional differences. NKG2DL expression on tumors varies depending on the malignancy and tumors can also release soluble NKG2DL that exert anergic effects on NK cells when engagement with NKG2D occurs, allowing escape from NK cell immunosurveillance. We carried out RAET1E typing of IHW cell line DNA, including a 580 bp proximal promoter fragment and exons 1-3 identifying 13 of 15 known RAET1E alleles. We determined 7 polymorphisms within the promoter region, including 2 already known that contributed to 9 promoter types. RAET1E alleles with variability in the extracellular region also differed with respect to promoter type and one allele, RAET1E(∗)003, associated with 5 promoter types. We then identified putative transcription factor binding sites for RAET1E, and found 5 of the 7 promoter polymorphisms may disrupt these sites, abrogating binding of transcription factors and varying the potential level of expression.