Rhinophyma in women: a case series.

Rosacea has an overall female predominance; however, rhinophyma, a feature attributed to advanced rosacea, is exceedingly rare in females. The impact of this condition on quality of life can be profound. Multiple treatment modalities have been described. However fully ablative carbon dioxide (CO2) laser for moderate-severe rhinophyma has been shown to be most effective with good cosmetic outcome and high patient satisfaction. We describe a series of 7 female patients presenting with rhinophyma to a tertiary NHS laser centre and a private dermatology clinic. A retrospective case review of rhinophyma management was performed, assessing presentation, treatments and outcomes. The mean age at presentation was 47 years (27-62 years). Three patients developed rhinophyma before the age of 30 years. One patient had severe, 2 patients had moderate and 4 patients had minor rhinophyma. Four patients underwent fractional CO2 laser treatment with a good cosmetic outcome. Two further patients developed scarring following fully ablative CO2 laser. Long-term low-dose oral isotretinoin was used in 3 patients following laser treatment, to prevent relapse. One patient solely received isotretinoin with a good outcome. In our experience, females suffering with rhinophyma presented for treatment at an early age and stage of severity. Fractional or fully ablative CO2 laser alone or in combination with oral isotretinoin is a very effective treatment modality.

A rare case of isolated cauda equina Nocardia farcinica infection.

Nocardia is a Gram-positive, partially acid-fast, catalase-positive, and urease-positive bacterium that grows aerobically. We present an extremely rare case of cauda equina syndrome due to isolated intramedullary Nocardia farcinica infection. A 44-year-old male presented with low backache and gradually progressive weakness in bilateral lower limbs followed by paraplegia. He was found to have a well-defined, sharply demarcated ring-enhancing lesion located from T11-T12 to L3 vertebral body. He underwent laminectomy and decompression. The histopathological examination revealed a Gram-positive filamentous organism that looks like Nocardia. The culture report was suggestive of Nocardia farcinica. He was then treated with antibiotics and had a remarkable clinical and radiological improvement.

Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia.

Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase that regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD) that plays a vital role in energy metabolism. Here, we show that KPT-9274 strongly inhibits B-ALL cell growth regardless of cytogenetic abnormalities. We also demonstrate the potent in vivo efficacy and tolerability of KPT-9274 in a patient-derived xenograft murine model of B-ALL. Interestingly, although KPT-9274 is a dual PAK4/NAMPT inhibitor, B-ALL cell growth inhibition by KPT-9274 was largely abolished with nicotinic acid supplementation, indicating that the inhibitory effects on B-ALL cells are mainly exerted by NAD+ depletion through NAMPT inhibition. Moreover, we have found that the extreme susceptibility of B-ALL cells to NAMPT inhibition is related to the reduced cellular NAD+ reserve. NAD+ depletion may be a promising alternative approach to treating patients with B-ALL.

Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD).

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

NF-κB/STAT5/miR-155 network targets PU.1 in FLT3-ITD-driven acute myeloid leukemia.

Almost 30% of all acute myeloid leukemias (AML) are associated with an internal tandem duplication (ITD) in the juxtamembrane domain of FMS-like tyrosine kinase 3 receptor (FLT3). Patients with FLT3-ITD mutations tend to have a poor prognosis. MicroRNAs (miRNAs) have a pivotal role in myeloid differentiation and leukemia. MiRNA-155 (MiR-155) was found to be upregulated in FLT3-ITD-associated AMLs. In this study, we discovered that FLT3-ITD signaling induces the oncogenic miR-155. We show in vitro and in vivo that miR-155 expression is regulated by FLT3-ITD downstream targets nuclear factor-κB (p65) and signal transducer and activator of transcription 5 (STAT5). Further, we demonstrate that miR-155 targets the myeloid transcription factor PU.1. Knockdown of miR-155 or overexpression of PU.1 blocks proliferation and induces apoptosis of FLT3-ITD-associated leukemic cells. Our data demonstrate a novel network in which FLT3-ITD signaling induces oncogenic miR-155 by p65 and STAT5 in AML, thereby targeting transcription factor PU.1.

Cervical Spinal Meningeal Melanocytoma Presenting as Intracranial Superficial Siderosis.

Meningeal melanocytoma is a rare pigmented tumor of the leptomeningeal melanocytes. This rare entity results in diagnostic difficulty in imaging unless clinical and histopathology correlation is performed. In this case report, we describe a case of meningeal melanocytoma of the cervical region presenting with superficial siderosis. Extensive neuroradiological examination is necessary to locate the source of the bleeding in such patients. Usually, the patient will be cured by the complete surgical excision of the lesion.

Acne conglobata and adalimumab: use of tumour necrosis factor-α antagonists in treatment-resistant acne conglobata, and review of the literature.

Acne conglobata (AC) is a chronic, severe, inflammatory variant of acne characterized by development of cystic nodules, abscesses and sinus tracts. AC may prove resistant to conventional acne therapy. The off-label use of adalimumab for the treatment of AC has been reported recently. We present a 26-year-old man with AC resistant to conventional treatment, who was treated with 40 mg adalimumab every other week, with significant clinical improvement. We review the evidence for the use of tumour necrosis factor antagonists in AC and related conditions. This case provides further evidence supporting the role of adalimumab in the treatment of AC.

Our perspective of the treatment of naevus of Ota with 1,064-, 755- and 532-nm wavelength lasers.

Naevus of Ota (NO) is a disfiguring pigmentary disorder affecting the face. Q-switched neodymium-doped yttrium aluminium garnet (QS Nd:YAG)-1,064 nm is a standard laser treatment because it causes highly selective destruction of melanin within the aberrant dermal melanocytes. However, not all lesions respond. This study aims to evaluate the efficacy/safety of QS Nd:YAG-1,064 nm and the shorter wavelength QS Alexandrite-755 nm and QS Nd:YAG-532 nm lasers in treating NO. Data were evaluated from 21 patients treated in our laser centre from 2004 to 2012. Lesional skin was irradiated with QS-532 nm/QS-755 nm/QS-1,064 nm, with settings titrated according to responses. All received initial test patches to direct initial wavelength choice, with subsequent treatments at 3-monthly intervals until clearance/lack of further response. Laser modality was switched following repeated test patches if there was no or no sustained improvement. Two thirds of patients had ≥ 90% improvement compared to baseline photographs. In 20% of patients, QS-1,064 nm was most efficacious with 97% mean improvement. The mean improvement was 80% for those in whom QS-755 nm was superior, and 90% for QS-532 nm. Median number of overall laser treatments was 8 (range 4-13). Number of treatments required varied significantly according to lesional colour and site: grey lesions and those on the forehead/temple were most resistant. We confirm successful treatment of NO with QS Nd:YAG-1,064 nm and the shorter wavelength QS-755 nm/QS-532 nm lasers without serious or irreversible side effects. We recommend judicious test patch analysis before treatment and a modality switch if complete clearance is not obtained.

Favre-Racouchot syndrome: a novel two-step treatment approach using the carbon dioxide laser.

BACKGROUND: Favre-Racouchot syndrome (FRS) is both disfiguring and difficult to treat. Available medical and surgical therapies are of variable efficacy. Most treatments do not achieve complete resolution and do not show maintenance of therapeutic response. OBJECTIVES: To assess the response to a novel two-step treatment using the CO2 laser in patients with FRS. METHODS: Seven patients with FRS were treated with the CO2 laser in resurfacing mode with manual expression of comedones under infiltrative local anaesthesia. The procedure was completed in one treatment session lasting 30 min and the wound was left to heal by secondary intention. A topical antibiotic was applied to treated areas, which were covered with a nonadherent dressing. All patients were assessed 3 months postoperatively by the operating laser surgeon and a visual assessment of clinical response to treatment in comparison with pretreatment photographs was made. Patient satisfaction was also recorded. RESULTS: All patients achieved complete resolution of FRS. The follow-up duration for our cohort ranged from 8 months to 3 years. Two patients required further treatment within a 2-3-year period from initial treatment. Disease relapse was noted over 1 year after the primary treatment; both these cases were smokers and repeat treatment with similar laser parameters maintained reproducible results. Our longest disease-free follow-up duration was 3 years postprimary treatment. The laser surgeons and patients reported high levels of therapeutic benefit and satisfaction with the results. CONCLUSIONS: This two-step treatment of FRS (CO2 laser resurfacing and manual pressure-induced expression of comedones) is an effective and durable treatment for FRS with an excellent cosmetic outcome. Long-term follow-up beyond 3 years is planned to determine whether later recurrence occurs with this technique.

Echinococcal cyst of the left vas deferens - a case report and literature review.

UNLABELLED: Cystic echinococcosis or hydatid disease is an important public health issue, mainly in developing countries, due to its high prevalence. Echinococcus granulosus, a cyclophyllid cestode, the pathogenic parasite found in humans, their intermediate host in its way to the final host, the members of canidae family. The main sites of infection in humans are the liver and the lungs. There have been recorded Rare locations such as the heart, spleen, muscles or retroperitoneal have also been recorded. CASE PRESENTATION: We present the case of a 29-year-old man, living in rural environment, who was admitted in our Clinic for a pelvic cystic tumor and intermittent ureterohydronephrosis. The blood work showed positive antibodies for Echinococcus granulosus. An urethrocystoscopy and the excision of the tumor were performed. CONCLUSIONS: Although rare, the involvement of the male genitourinary tract in cystic echinococcosis is possible and can pose important diagnostic challenges.

Left renal cyst - left duplex kidney with compromised superior renal unit and ectopic ureteral orifice in the prostatic urethra.

UNLABELLED: The urinary abnormalities are an important health problem. If they are not recognized in due time, they usually lead to the loss of the renal unit function. In many cases, the diagnosis is late and incidental. CASE PRESENTATION: We present the case of M.I., a 74-year-old male admitted in our surgical unit with diffuse left lumbar pain, low urinary tract symptoms and slow increase in abdomen volume in the past 4 years. Computer tomography scan and ecography showed a large left lumbar cyst like mass with a dilated supernumerary ureter with ectopic ureteral orifice in the prostatic urethra and apparently normal anatomic inferior renal unit. The goal was the excision of the "cyst like" mass (superior left renal unit) but because of the anatomical particularities (extensive fibrosis and local topographical changes) total nephrectomy was performed. CONCLUSIONS: Given a normal contralateral kidney, the discovery of a urinary abnormality can be a real challenge, their evolution being a silent one. This type of disease can be suspected only with the development of clinical symptoms. The anatomic particularities (duplex kidney) together with the long evolution of the disease changed the local topography making the preservation of the inferior left renal unit a difficult, almost impossible task for the surgeon.