Outcomes and characteristics of nonmelanoma skin cancers in patients with myeloproliferative neoplasms on ruxolitinib.

ABSTRACT: Nonmelanoma skin cancers (NMSCs) in ruxolitinib-treated patients with myeloproliferative neoplasms behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis. Vigilant skin assessment, counseling on NMSC risks, and prospective ruxolitinib-NMSC studies are crucial.

Capture-based targeted sequencing using a T-cell control in myeloid malignancies and idiopathic cytopenias.

We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.

Prostate SBRT using O-Ring Halcyon Linac - Plan quality, delivery efficiency, and accuracy.

Cone beam CT-guided prostate stereotactic body radiotherapy (SBRT) treatment on the recently installed novel O-ring coplanar geometry Halcyon Linac with a single energy 6MV-flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for early stage low- and intermediate-risk prostate cancer patients. Following the RTOG-0938 compliance criteria and utilizing two-full arc geometry, VMAT prostate SBRT plans were generated for ten consecutive patients using advanced Acuros-based algorithm for heterogeneity corrections with Halcyon couch insert. Halcyon VMAT plans with the stacked and staggered multileaf collimators (MLC) produced highly conformal SBRT dose distributions to the prostate, lower intermediate dose spillage and similar dose to adjacent organs-at-risks (OARs) compared to SBRT-dedicated Truebeam VMAT plans. Due to lower monitor units per fraction and less MLC modulation through the target, the Halcyon VMAT plan can deliver prostate SBRT fractions in and overall treatment time of less than 10 minutes (for 36.25 Gy in five fractions), significantly improving patient compliance and clinic workflow. Pretreatment quality assurance results were similar to Truebeam VMAT plans. We have implemented Halcyon Linac for prostate SBRT treatment in our institution. We recommend that others use Halcyon for prostate SBRT treatments to expand the access of curative hypofractionated treatments to other clinics only equipped with a Halcyon Linac. Clinical follow-up results for patients who underwent prostate SBRT treatment on our Halcyon Linac is underway.

Clinical Value of Single-photon Emission Computed Tomography Combined With Computed Tomography for Sentinel Lymph Node Identification in Melanoma.

INTRODUCTION: Melanoma is the deadliest form of skin cancer and has the ability to metastasize widely. Accurate diagnosis of sentinel lymph nodes (SLN) is crucial to its management. The gold standard for SLN identification is planar lymphoscintigraphy. Recently, single-photon emission computed tomography combined with computed tomography (SPECT/CT) has been used as a hybrid method to map lymphatic drainage networks. We aim to better characterize the utility of this tool in head and neck melanoma by evaluating its effectiveness in the preoperative setting for melanoma patients undergoing sentinel lymph node biopsy (SLNB). METHODS: We performed a retrospective chart review at the West Haven Veterans Affairs Hospital. Inclusion criteria were patients with melanoma with a thickness greater than 0.75 mm and SPECT/CT use before operative sentinel lymph node excision. Exclusion criteria included clinically palpable lymph nodes, evidence of distant metastatic disease, melanoma with a Breslow depth less than 0.75 mm, and melanoma in situ. Our primary endpoints were correlation with intraoperative findings and whether the test had any influence on the operative plan. RESULTS: Thirty-five patients between 2011 and 2017 met our criteria. SPECT/CT correlated with the sentinel node biopsy based on intraoperative lymphoscintigraphy in 30 (86%) of 35 cases, and there were no changes to the operative plan after SPECT/CT was performed. Sentinel lymph nodes were correctly identified in all 35 cases. CONCLUSIONS: The role of SPECT/CT in SLNB is uncertain. According to some studies, SPECT/CT can help decision making and change surgical approach in up to 35% of patients. However, other studies have reported questionable correlation with intraoperative findings and no added intraoperative value in over 50% of patients. We have demonstrated that preoperative SPECT/CT was consistent with intraoperative findings in 86.0% of cases but did not change the surgical approach for the SLNB. Surveillance over a period of 12 months did not reveal any signs of melanoma recurrence. A possible advantage of SPECT/CT is potentially decreasing costs by lowering operative time. However, financial cost in the literature suggests SPECT/CT is costlier than lymphoscintigraphy and therefore this must be weighed against any potential benefit. Overall, we did not find that SPECT/CT gives added value when compared with lymphoscintigraphy.

Idiopathic Pneumatosis Intestinalis Requiring Decompressive Laparotomy.

INTRODUCTION: Pneumatosis intestinalis (PI) and hepatic portal venous gas (HPVG) are radiographic signs of questionable bowel ischemia. Pneumatosis intestinalis can be associated with possible benign conditions such as obstructive airway disease. We present a patient who demonstrated clinical signs of overt sepsis with corresponding radiological findings of PI and HPVG concering for possible small or large bowel ischemia. However at exploration, no sign of small or large bowel injury or ischemia could be detected. CASE PRESENTATION: A 36-year-old male with a history of alcohol abuse presented to Danbury Hospital as a trauma alert after he slid on his motorcycle. He had a complete transection of the thoracic spinal cord which required multilevel laminectomies and a spinal fusion. He developed overt signs of sepsis with vital signs of a temperature of 38.5 degrees C (101.4 degrees F), heart rate of 141 bpm, white blood cell (WBC) count of 24.7 c/mcL, and lactic acid of 2.4 mg/dL. A CT scan of the abdomen and pelvis revealed a pneumatosis and hepatic portal venous gas. An exploratory laparotomy was performed which showed distended small bowel, but no evidence for ischemia or injury. An ABthera Open Abdomen Negative Pressure Therapy System (Kinetic Concepts, Inc., San Antonio, TX) was placed due to the fact that the abdominal wall could not be closed. A second look laparotomy revealed no injury or ischemia, and the patient's abdomen was closed primarily. CONCLUSION: Pneumatosis intestinalis and hepatic portal venous gas are radiographic findings that can be associated with bowel ischemia. The clinical status of the patient should guide operative management. There is no evidence to suggest that there is an association with spinal trauma and pneumatosis intestinalis or hepatic portal venous gas.

Cranial Nerve Palsies: A Rare, Long-Term Complication of Radiotherapy for Nasopharyngeal Carcinoma.

UNLABELLED: Cranial nerves (CN) are believed to be relatively resistant to radiotherapy (RT); however, there have been case reports of cranial nerve palsy (CNP) following RT. We present a case of a gentleman with cranial nerve palsy of CN V and VII after RT for nasopharyngeal carcinoma (NPC). CASE PRESENTATION: A 54-year-old male presented to our clinic with masticatory difficulty, facial hypoesthesia, and dysphagia. In 1998, he was treated with external beam RT for NPC. He underwent sural nerve grafting, anastomosing his functioning hypoglossal nerve to the buccal branch of the facial nerve in an end-to-side fashion, and direct implantation of a nerve graft from the spinal accessory to the masseter muscle. He unfortunately was unable to regain masticatory function postoperatively. CONCLUSION: Cranial nerve palsies are severely debilitating to patients and difficult to treat. Radiation-induced CNP is important to consider in the differential diagnosis in patients previously treated for NPC.

CNL and aCML should be considered as a single entity based on molecular profiles and outcomes.

Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences between these disorders, we undertook a multicenter international study of one of the largest case series (CNL, n = 24; aCML, n = 37 cases, respectively), focusing on the clinical and mutational profiles (n = 53 with molecular data) of these diseases. We found no differences in clinical presentations or outcomes of both entities. As previously described, both CNL and aCML share a complex mutational profile with mutations in genes involved in epigenetic regulation, splicing, and signaling pathways. Apart from CSF3R, only EZH2 and TET2 were differentially mutated between them. The molecular profiles support the notion of CNL and aCML being a continuum of the same disease that may fit best within the myelodysplastic/myeloproliferative neoplasms. We identified 4 high-risk mutated genes, specifically CEBPA (ß = 2.26, hazard ratio [HR] = 9.54, P = .003), EZH2 (ß = 1.12, HR = 3.062, P = .009), NRAS (ß = 1.29, HR = 3.63, P = .048), and U2AF1 (ß = 1.75, HR = 5.74, P = .013) using multivariate analysis. Our findings underscore the relevance of molecular-risk classification in CNL/aCML as well as the importance of CSF3R mutations in these diseases.

Eating Disorder Day Programs: Is There a Best Format?

The use of a Day Program (DP) format (i.e., intensive daily treatment with no overnight admission) has been shown to be an effective treatment for eating disorders (EDs). The disadvantages, however, include higher cost than outpatient treatment (including costs of meals and staff), greater disruption to patients' lives, and the use of a highly structured and strict schedule that may interrupt the development of patients' autonomy in taking responsibility for their recovery. This study investigated whether reducing costs of a DP and the disruption to patients' lives, and increasing opportunity to develop autonomy, impacted clinical outcomes. Three sequential DP formats were compared in the current study: Format 1 was the most expensive (provision of supported dinners three times/week and extended staff hours); Format 2 included only one dinner/week and provision of a take-home meal. Both formats gave greater support to patients who were not progressing well (i.e., extended admission and extensive support from staff when experiencing feelings of suicidality or self-harm). Format 3 did not provide this greater support but established pre-determined admission lengths and required the patient to step out of the program temporarily when feeling suicidal. Fifty-six patients were included in the analyses: 45% were underweight (body mass index (BMI) < 18.5), 96.4% were female, 63% were given a primary diagnosis of anorexia nervosa (or atypical anorexia nervosa), and mean age was 25.57 years. Clinical outcomes were assessed using self-reported measures of disordered eating, psychosocial impairment, and negative mood, but BMI was recorded by staff. Over admission, 4- and 8-week post-admission, and discharge there were no significant differences between any of the clinical outcomes across the three formats. We can tentatively conclude that decreasing costs and increasing the opportunities for autonomy did not negatively impact patient outcomes, but future research should seek to replicate these results in other and larger populations that allow conclusions to be drawn for different eating disorder diagnostic groups.

Entrapment Neuropathy Causing Persistent Headache Symptoms after Nonsurgical Rhinoplasty.

The frequency of nonsurgical rhinoplasty has increased in recent years. The occurrence of headaches or migraine symptoms, and their treatment following nonsurgical rhinoplasty, have been scarcely described in the literature. Here, we present a patient who presented with subjective complaints of a new onset headache immediately after nonsurgical rhinoplasty, with subsequent reversal of her symptoms using hylauronidase. Furthermore, a literature review was conducted to establish a possible anatomical pathophysiologic mechanism of these symptoms seen in this patient. METHODS: A case report of a patient who developed persistent headache symptoms after nonsurgical rhinoplasty, with reversal of symptoms using hylaronidase, is described. A literature review of studies on patients developing headaches or migraine-like symptoms after nonsurgical rhinoplasty was conducted, along with a review of the anatomic causes of migraines. RESULTS: Of the 147 relevant citations identified in our search, only 1 individual case report describes a patient who developed a migraine headache after undergoing a nonsurgical rhinoplasty via an injection of hyaluronic acid filler. This was promptly resolved with the utilization of a hyaluronidase injection. The majority of the relevant articles in our search focused on the alarming and most feared complication of vascular compromise of the nasal tissue and intravascular embolization. Within the literature, there was no case series of nonsurgical-rhinoplasty-induced migraines taking into account our inclusion criteria. CONCLUSIONS: This article demonstrates the paucity of literature regarding nonsurgical-rhinoplasty-induced headaches. Although a causation effect cannot be linked, our study highlights a rare phenomenon associated with this ever-increasing aesthetic procedure.

Breast Reconstruction Utilizing Buried Dermato-cutaneous Skin Flaps and Immediate Adipocyte Transfer: A Minimally Invasive Autologous Breast Reconstruction Technique.

Autologous breast reconstruction historically required flaps that were invasive, required prolonged operative times and recoveries, and resulted in varying degrees of donor site morbidity. We present our early results with a minimally invasive completely autologous breast reconstruction technique utilizing buried dermato-cutaneous (DMC) flaps and immediate fat grafting. A 25-patient, 43-breast consecutive case series is presented. METHODS: Select patients desiring autologous breast reconstruction who had sufficient breast ptosis and fat donor tissue were offered breast reconstruction with buried folded over DMC flaps with adipocyte transfer (DCAT). A Wise pattern mastectomy was performed, and fat was transferred into an inferiorly based, buried and folded DMC flap. Fat was also immediately grafted into the pectoralis, subpectoral space, and below pectoralis and serratus fascia. Most patients underwent additional fat grafting at 3-month intervals to complete the reconstruction. RESULTS: Twenty-five consecutive patients (43 breasts) underwent the DCAT procedure with 18 (42%) free nipple grafts. Eight patients (8 breasts) had prior breast radiation, and 2 patients (2 breasts) required postmastectomy radiation. Average fat grafted at initial mastectomy was 70 mL per breast (range 50-103 mL). Nineteen patients (76%) underwent additional outpatient fat grafting. Two additional outpatient fat graft sessions (range 0-3) at 3-month intervals completed the reconstruction. Average fat grafted at the second stage was 217 mL (range 50-320 mL). Average follow-up was 20 months from DCAT and 12 months from last fat graft. CONCLUSION: The DCAT procedure appears to provide a minimally invasive, autologous breast reconstruction alternative in select patients.

Immunoassay detection of fly artifacts produced by several species of necrophagous flies following feeding on human blood.

Foraging behavior of necrophagous flies commonly leads to distortion of human bloodstains and production of artifacts that confound reconstruction efforts at crime scenes. Currently there is no reliable method for detection of fly-derived stains or distinction of the artifacts from human bloodstains. To overcome these deficiencies, a confirmatory test was developed based on immunological detection of cathepsin D found in digestive fluids of Musca domestica and Protophormia terraenovae. Anti-serum (anti-md3 serum) was generated toward a 17-amino acid synthetic peptide based upon predicted antigenic amino acid sequences for the propeptide and mature enzyme of cathepsin D proteinase from larvae of M. domestica. The serum was used to test the hypothesis that digestive artifacts produced by an array of necrophagous flies associated with human decomposition could be detected with the immunoassay. Anti-md3 serum was able to bind artifacts from 27 species of flies representing 9 families. The antiserum reacted with both regurgitate and defecatory stains, but not transfer patterns. Stains from 4 fly species displayed no reactivity with anti-serum in dot blot assays. Anti-md3 serum did not bind to either human or bovine blood stains on filter paper. However, when both types of blood were spiked with synthetic md3 peptide the antiserum was able to bind. Dot blot assays displayed positive reactions with stains produced from larvae and teneral adults of Sarcophaga bullata, and with artifacts as old as 7-years after deposition. These observations indicate that the immunoassay permits distinction of artifacts from a wide range of species from human bloodstains, from multiple development stages, and from artifacts that remain at crime scenes for many months to years after deposition. Further work is needed to determine whether the detection of fly artifacts using the antiserum is suitable for non-laboratory conditions.

Efficiency and Health Economic Evaluations of BD OneFlow™ Flow Cytometry Reagents for Diagnosing Chronic Lymphoid Leukemia.

REASON FOR THE STUDY: To standardize the use of flow cytometry for classifying hematological malignancies and make the results reliable and reproducible across laboratories, the EuroFlow™ Consortium published a comprehensive specification of antibody-fluorochrome conjugates, standard protocols, and algorithms for analysis. The BD OneFlow™ system builds on, and further standardizes, the EuroFlow protocols. We aimed to assess the effects on safety, efficiency, and costs for laboratories of adopting the BD OneFlow reagent tubes (LST and B-CLPD T1) for diagnosing chronic lymphocytic leukemia. METHODS: We compared in-house laboratory processes and results with those using the LST and B-CLPD T1 reagent tubes with, and without, blood film morphology. Outcome measures included concordance in classification results, and efficiency within the laboratory, that is, resource usage, staff time, unwanted events, and cost-consequences. RESULTS: There was 100% concordance between the classifications made with in-house flow cytometry and those with the BD OneFlow reagent tubes. Using BD OneFlow tubes required 13 hours less staff time per month (i.e. for 100 samples) than the in-house process. Sensitivity analyses explored the effects of uncertainties in the price of the BD OneFlow tubes and the prevalence of CLL and identified the thresholds at which laboratories might expect cost-savings from adopting the BD OneFlow system. Laboratory and clinical staff considered the BD OneFlow system to be safe and effective. CONCLUSIONS: Laboratories adopting the BD OneFlow system for classifying patients with suspected CLL can expect safe, efficient processes that can be cost saving if the discount on the list price, and prevalence of CLL (which will both vary between sites and countries), is within the thresholds suggested by the health economics sensitivity analysis. © 2019 International Clinical Cytometry Society.

Use of an Insulin Pump in the Elderly Surgical Patient: Tolerance of Total Pancreatectomy After Neoadjuvant Chemotherapy for Multifocal Pancreatic Cancer.

Introduction: Pancreatic cancer is one of the most fatal cancers if not caught early and is associated with late disease presentation. Multifocal pancreatic cancer is particularly difficult to treat as cases that are amenable to surgical resection require total pancreatectomy. Such patients will develop brittle diabetes as they require exogenous insulin after surgery and in the apancreatic state lose counter-regulatory homeostatic mechanisms (i.e., glucagon). We present an elderly patient who underwent neoadjuvant chemotherapy and total pancreatectomy. The patient has adequate glycemic control postoperatively being managed with an insulin pump and remains disease free at 3 years and 3 months after resection. Case Presentation: A 72-year-old male presented with two tumors, in the head and tail of the pancreas, respectively, which were consistent with pancreatic adenocarcinoma by endoscopic ultrasound biopsy. Neoadjuvant FOLFIRINOX had been administered and total pancreatectomy was performed. The patient did well postoperatively and was discharged on postoperative day 8. The patient was seen by endocrinology pre- and postoperatively who started an insulin pump for glycemic management 2 weeks postoperatively. The patient's HbA1c was 7.9% at 3 months. The patient remains disease free at 3 years and 3 months with an HbA1c of 7.0% and a normal CA19-9. Conclusion: This case highlights that glycemic control after total pancreatectomy with the use of an insulin pump in the elderly population is achievable. Elderly patients can struggle with certain technologies and selecting appropriate patients for insulin pump therapy after total pancreatectomy is imperative.

Morphological Features of Regurgitate and Defecatory Stains Deposited by Five Species of Necrophagous Flies are Influenced by Adult Diets and Body Size.

The morphological characteristics of artifacts from five species of necrophagous flies were examined following feeding on several types of diets. Four types of insect stains were produced by each species: regurgitate, defecatory, translocation, and tarsal tracks. Regurgitate was the most frequent type deposited (70.9 ± 2.4%), followed by defecatory (19.8 ± 4.0%), tarsal tracks (8.6 ± 1.2%), and translocation (0.7 ± 0.1%). Artifact shapes, sizes, and color were highly variable and species and diet specific. Calliphora vicina and Sarcophaga bullata consistently deposited the largest artifacts after feeding, whereas Chrysomya rufifacies and Ch. megacephala produced more tarsal tracks than the other species examined. Artifacts with tails were infrequently observed (4.1 ± 0.6% of all stains) but occurred as either defecatory or regurgitate stains. The widely variable morphologies of all types of fly artifacts underscores the view that insect stains cannot be distinguished from human bloodstains based on morphology alone.