Miliarial-type gout in association with chronic use of glucocorticoids.

A 59-year-old male patient with long-standing tophaceous gout (more than 30 years) characterized by polyarticular involvement and recurrent disseminated tophi formation; his past medical history is relevant for poor adherence to urate-lowering medications, as well as persistent use of self-prescribed systemic glucocorticoids. Despite achieving therapeutic goals for serum uric acid levels, new tophi formation with an intradermal location in the form of "miliarial-type gout" was documented. Due to functional limitations, the patient underwent surgical resection of the olecranon bursa. This case illustrates a widespread and recurrent tophi formation associated with long-standing gout and regular and sustained glucocorticoid use, despite an adequate disease control based on serum urate levels and involving an intradermal location of tophi presenting as "miliarial-type" lesions. In addition, the coexistence of urate and cholesterol crystal deposition disease in olecranon gouty bursitis is presented. Finally, a sonographic extended field of view of lesions distributed along the patient's extremities is presented as a novel characterization of this condition.

Vitamin D receptor (VDR) expression in different molecular subtypes of canine mammary carcinoma.

BACKGROUND: The molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research. Both in canines and humans, the triple-negative (TN) molecular subtype of mammary cancer is defined by a lack of expression of progesterone receptor (PR), oestrogen receptor (ER) and HER2. It has a poor prognosis; no effective targeted therapy is available. Vitamin D displays anticarcinogenic properties, and the expression of its receptor (VDR) has been found in different molecular subtypes, being about 30-40 % of TN breast cancer (TNBC) positive to it. We assessed the VDR expression in the different molecular subtypes of 58 CMCs from 45 female dogs using an immunohistochemical panel for the molecular classification of included: PR, ER, HER2, cytokeratin (CK) 5, CK14, and Ki67. In addition, we studied the relationship among the molecular subtypes of CMCs and clinicopathologic parameters. RESULTS: Investigation showed VDR positivity in 45.0 % of the triple-negative CMCs (TNCMCs), 27.3 % of luminal B and 19.0 % of luminal A. Luminal A was the most molecular subtype represented of the total tumours (36.2 %), followed of TNCMCs (34.5 %), luminal B (20.7 %) and HER2-overexpression (10.3 %). Both HER2-overexpression and TNCMC subtypes were positively related to lymphatic invasion (P = 0.028), simple histologic subtype (P = 0.007), a higher histological grade (P = 0.045) and a trend to higher proliferation index (P = 0.09). CONCLUSIONS: The highest VDR expression was observed in TNCMC, being almost half of them (45 %) positive to this receptor. VDR expression was absent in HER2-overexpression tumours and low in luminal A and B molecular subtypes.

Accuracy of synovial fluid analysis compared to histology for the identification of calcium pyrophosphate crystals: an ancillary study of the OMERACT US Working Group - CPPD subgroup.

The aim of this study was to evaluate the accuracy of synovial fluid analysis in the identification of calcium pyrophosphate dihydrate crystals compared to microscopic analysis of joint tissues as the reference standard. This is an ancillary study of an international, multicentre cross-sectional study performed by the calcium pyrophosphate deposition disease (CPPD) subgroup of the OMERACT Ultrasound working group. Consecutive patients with knee osteoarthritis (OA) waiting for total knee replacement surgery were enrolled in the study from 2 participating centres in Mexico and Romania. During the surgical procedures, synovial fluid, menisci and hyaline cartilage were collected and analysed within 48 hours from surgery under transmitted light microscopy and compensated polarised light microscopy for the presence/absence of calcium pyrophosphate crystals. All slides were analysed by expert examiners on site, blinded to other findings. A dichotomic score (absence/ presence) was used for scoring both synovial fluid and tissues. Microscopic analysis of knee tissues was considered the gold standard. Sensitivity, specificity, accuracy, positive and negative predictive values of synovial fluid analysis in the identification of calcium pyrophosphate crystals were calculated. 15 patients (53% female, mean age 68 yo ± 8.4) with OA of grade 3 or 4 according to Kellgren-Lawrence scoring were enrolled. 12 patients (80%) were positive for calcium pyrophosphate crystals at the synovial fluid analysis and 14 (93%) at the tissue microscopic analysis. The overall diagnostic accuracy of synovial fluid analysis compared with histology for CPPD was 87%, with a sensitivity of 86% and a specificity of 100%, the positive predictive value was 100% and the negative predictive value was 33%. In conclusion synovial fluid analysis proved to be an accurate test for the identification of calcium pyrophosphate dihydrate crystals in patients with advanced OA.

Nociceptive related microRNAs and their role in rheumatoid arthritis.

Rheumatoid Arthritis (RA) is an autoimmune disease with unknown etiology and a global incidence around 1%, a positive family history increases the risk of RA roughly three to five times. Pain is one of the first symptoms to appear in this disease. MicroRNAs (miRNAs) belong to the class of small non-coding RNAs; they regulate multiple cellular processes including embryonic development, cellular proliferation, differentiation and apoptosis among others. A great deal of evidence points to the employment of miRNAs as therapeutic targets and biomarkers for several pathologies. The main objective of this Review is to assess how miRNAs participate in the pathogenesis of RA. Two advanced searches were conducted in databases, one using "micro-RNA" and "rheumatoid arthritis" as key words, and another one with "micro-RNA", "pain" and "nociception". In this Review, we describe how six miRNAs: miR-16-5p, miR-23b-3b, miR-124-3p, miR-146a-5p, miR-155-5p and miR-223-3p, involved in the modulation and transmission of the nociceptive input are unregulated in RA patients. Key molecular pathways involved in nociception, inflammation and autoimmune responses, are regulated by these miRNAs; the NF-κB, TNF-α, interleukins and TLR4. By means of gene repression, the miRNAs here described modulate the nociceptive process as well as the autoimmune response that characterize this disease.

Major allergen from Amaranthus palmeri pollen is a profilin: Isolation, partial characterisation and IgE recognition.

BACKGROUND: Pollens represent a rich source of proteins that are also potential elicitors of IgE-mediated pollen allergy. Sensitisation to panallergens could play an important role in diagnosis and specific immunotherapy, because these molecules are present in different plant pollens and plant foods and have marked structural similarity in different species. Profilins are one of the most common panallergens to be studied because they are responsible for a large number of sensitisations and are clearly related to cross-reactivity and co-sensitisation. This study aimed to isolate and characterise a new allergen of Amaranthus palmeri pollen and to determine its allergenicity. METHODS: A. palmeri pollen profilin was purified using poly-l-proline-Sepharose affinity chromatography followed by anion exchanger chromatography. Identification of purified protein was carried out by mass spectrometry. Specific IgE was estimated in sera of patients with positive skin prick test to A. palmeri pollen extract, by enzyme-linked immunosorbent assay (ELISA). PRINCIPAL FINDINGS: Purified protein appeared as a single band at 14 kDa in SDS-PAGE gel. Mass spectrometric analysis of the gel band identified two highly conserved peptides corresponding to allergenic profilins from pollen of other plants. Sera from about 60% of allergic patients have IgE that recognises the purified A. palmeri protein. CONCLUSION: A 14 kDa protein of A. palmeri pollen was purified and identified as allergenic profilin, which was recognised by sera from pollen allergic patients.

Vitamin E protection of obesity-enhanced vascular calcification in uremic rats.

This study aimed to determine the extent of extraskeletal calcification in uremic Zucker rats, by comparing obese and lean phenotypes, and to evaluate the influence of vitamin E (VitE) on the development of calcifications in both uremic rats and human vascular smooth muscle cells (HVSMCs) cultured in vitro. Zucker rats of lean and obese phenotypes with normal renal function [control (C); C-lean and C-obese groups] and with uremia [5/6 nephrectomy (Nx); Nx-lean and Nx-obese groups] and uremic rats treated with VitE (Nx-lean + VitE and Nx-obese + VitE groups) were studied. Uremic groups were subjected to Nx, fed a 0.9% phosphorus diet, and treated with calcitriol (80 ng/kg ip). The aortic calcium concentration was significantly higher (P < 0.05) in Nx-obese rats (10.0 ± 2.1 mg/g tissue) than in Nx-lean rats (3.6 ± 1.3 mg/g tissue). A decrease in plasma glutathione peroxidase activity was observed in Nx-obese rats compared with Nx-lean rats (217.2 ± 18.2 vs. 382.3 ± 15.5 nmol·min(-1)·ml(-1), P < 0.05). Treatment with VitE restored glutathione peroxidase activity and reduced the aortic calcium concentration to 4.6 ± 1.3 mg/g tissue. The differences in mineral deposition between Nx-lean, Nx-obese, Nx-lean + VitE, and Nx-obese + VitE rats were also evidenced in other soft tissues. In HVSMCs incubated with high phosphate, VitE also prevented oxidative stress and reduced calcium content, bone alkaline phosphatase, and gene expression of core-binding factor-α1. In conclusion, uremic obese rats develop more severe calcifications than uremic lean rats and VitE reduces oxidative stress and vascular calcifications in both rats and cultures of HVSMCs.

[Neonatal sepsis by Citrobacter Freundii as a debut of cystic lymphatic malformation]. / Sepsis neonatal por Citrobacter Freundii como debut de malformación linfática quística.

Cystic lymphatic malformation (CLM) is a rare and benign entity caused by alterations in the embryological development of lymphatic structures. Its typical location is in the head and neck, although it has also been described at the abdominal level. It may not be evident in the first stages of life and its first manifestation may be a complication such as abdominal distension, hemorrhage, or sepsis, which may put the patient's life at risk. Surgical treatment is increasingly discussed, and less invasive techniques are proposed. OBJECTIVE: To describe an uncommon presentation of CLM, radiographic findings, complications, differential diagnosis, and both invasive and more conservative treatments. CLINICAL CASE: Newborn female infant consulted for fever and irritability, without specific signs on physical examination, with suspicion of sepsis. Ultrasonography showed a complex septate mass with cysts of different sizes encompassing the mesenteric vessels, supravesical location. In its most ante rior aspect, it presented a greater echogenicity that corresponded to the superinfected component. Magnetic resonance imaging identified a multitabulated cystic tumor corresponding to a complica ted mesenteric lymphangioma with signs of infection. Due to its size, which compressed the vena cava and the associated signs of complication, complete resection was decided with good subsequent evolution. CONCLUSION: The treatment of CLM in pediatric age is increasingly individualized and can vary from surgical resection to less invasive approaches that could reduce acute intraoperative or postoperative complications and mortality. In our case, the infection acted as sclerotherapy, mana ging to delimit the CLM and helping to improve the prognosis.

Experimental unconditional preparation and detection of a continuous bound entangled state of light.

Among the possibly most intriguing aspects of quantum entanglement is that it comes in free and bound instances. The existence of bound entangled states certifies an intrinsic irreversibility of entanglement in nature and suggests a connection with thermodynamics. In this Letter, we present a first unconditional, continuous-variable preparation and detection of a bound entangled state of light. We use convex optimization to identify regimes rendering its bound character well certifiable, and continuously produce a distributed bound entangled state with an extraordinary and unprecedented significance of more than 10 standard deviations away from both separability and distillability. Our results show that the approach chosen allows for the efficient and precise preparation of multimode entangled states of light with various applications in quantum information, quantum state engineering, and high precision metrology.

Structural damage in rheumatoid arthritis assessed by musculoskeletal ultrasound: A systematic literature review by the Structural Joint Damage Task Force of the OMERACT Ultrasound Working Group.

OBJECTIVES: To identify and synthesize the evidence for the use and measurement properties of musculoskeletal ultrasound in assessing structural joint damage in patients with rheumatoid arthritis (RA). METHODS: A systematic literature search (SLR) of the PubMed, Embase and Cochrane Library was performed. Original articles were included published in English reporting on ultrasound of bone erosion, cartilage damage and the measurement properties of ultrasound according to the OMERACT filter 2.1. RESULTS: Of the 1.495 identified articles 149 were included in the final review, most of which reported on cross-sectional studies and used the OMERACT definitions for ultrasonographic pathology. Among these, bone erosions were assessed in 139 (93.3%), cartilage damage in 24 (16.1%), enthesophytes in 8 (5.4%), osteophytes in 15 (10.1%) and malalignment and ankylosis in a single (0.9%) study, respectively. Most studies (126/149, 84.6%) assessed the joints of the hands. The overwhelming majority of studies (127/149, 85.2%) assessed structural joint damage bilaterally. Validity, reliability and responsiveness were assessed in 21 (14.1%), 34 (22.8%) and 17 (11.4%) studies, respectively. CONCLUSION: While the results of this SLR suggest that ultrasound is a sensitive, reliable and feasible tool to detect damage in RA, they also highlight the need for further research and validation. Findings of this SLR will inform the next steps of the OMERACT Ultrasound Working Group in developing an ultrasound score for assessing structural joint damage in patients with RA.

Pediatric Case of Li-Fraumeni Syndrome in Honduras.

Li-Fraumeni syndrome is an inherited, autosomal dominant disease. It is categorized as a rare disease caused by mutations of the TP53 gene, which causes increased susceptibility of the patients and their children to many types of cancer. Choroid plexus tumor is rare, which occurs in 0.3 cases per 1,000,000 people, of which 40% turn out to be carcinomas. We present a 12-year-old boy with a history of worsening headaches of more than one month, gait disturbance, projectile vomiting, and right hemiparesis. An intraventricular tumor was identified in the occipital of the left lateral ventricle, which turned out to be a TP53-mutant choroidal plexus carcinoma.

Use of coumarins as complementary medicine with an integrative approach against cervical cancer: background and mechanisms of action.

Cervical cancer is characterized by the cellular transformation caused by Human Papillomavirus (HPV), favoring cell proliferation, migration, invasion, and metastasis. Cervical cancer is conventionally treated with radiation therapy, and chemotherapy focused on the destruction of tumor cells. However, chemoresistance and low selectivity between tumor and non-tumor cells have been reported, causing side effects in patients. Metabolites of natural origin have shown selectivity against tumor cells, suggesting their use for reducing the side effects caused by drugs used in conventional therapy. Among these compounds, several natural coumarins stand out, such as auraptene, scopoletin, osthole, and praeruptorin, of which antiproliferative, anti-migratory, and anti-invasive activity have been reported. Auraptene, scopoletin, osthole, and praeruptorin show a cytotoxic or antiproliferative effect on cervical tumor cells, arresting the cell cycle by inducing the overexpression of negative regulators of the cell cycle, or inducing cell death by increasing the expression of pro-apoptotic proteins and decreasing that of anti-apoptotic proteins. On the other hand, auraptene, scopoletin, and praeruptorin inhibit the capacity for migration, invasion, and metastasis of cervical tumor cells, mainly by inhibiting the expression and activity of matrix metalloproteinase-2 and -9. The PI3K/Akt signal pathway appears to be central to the anti-tumor activity of the coumarins analyzed in this review. In addition, auraptene, osthole, and praeruptorin are useful in sensitizing tumor cells to radiotherapy or chemotherapeutic molecules, such as FOLFOX, cisplatin, or DOX. Coumarins offer an excellent possibility for developing new drugs as complementary medicine with an integrative approach against cervical cancer.

Cost of tuberculosis treatment in low- and middle-income countries: systematic review and meta-regression.

BACKGROUND: Despite a scarcity of tuberculosis (TB) cost data, a substantial body of evidence has been accumulating for drug-susceptible TB (DS-TB) treatment. In this study, we review unit costs for DS-TB treatment from a provider´s perspective. We also examine factors driving cost variations and extrapolate unit costs across low- and middle-income countries (LMICs).METHODS: We searched published and grey literature for any empirically collected TB cost estimates. We selected a subgroup of estimates looking at DS-TB treatment. We extracted information on activities and inputs included. We standardised costs into an average per person-month, fitted a multi-level regression model and cross-validated country-level predictions. We then extrapolated estimates for facility-based, directly observed DS-TB treatment across countries.RESULTS: We included 95 cost estimates from 28 studies across 17 countries. Costs predictions were sensitive to characteristics such as delivery mode, whether hospitalisation was included, and inputs accounted for, as well as gross domestic product per capita. Extrapolation results are presented with uncertainty intervals (UIs) for LMICs. Predicted median costs per 6 months of treatment were US$315.30 (95% CI US$222.60-US$417.20) for low-income, US$527.10 (95% CI US$395.70-US$743.70) for lower middle-income and US$896.40 (95% CI US$654.00-US$1214.40) for upper middle-income countries.CONCLUSIONS: Our study provides country-level DS-TB treatment cost estimates suitable for priority setting. These estimates, while not standing as a substitute for local high-quality primary data, can inform global, regional and national exercises.

Reliability of ultrasonography in detecting shoulder disease in patients with rheumatoid arthritis.

OBJECTIVE: To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI. METHODS: A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated. RESULTS: Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively. CONCLUSIONS: US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder.

Randomized trial of polychromatic blue-enriched light for circadian phase shifting, melatonin suppression, and alerting responses.

Wavelength comparisons have indicated that circadian phase-shifting and enhancement of subjective and EEG-correlates of alertness have a higher sensitivity to short wavelength visible light. The aim of the current study was to test whether polychromatic light enriched in the blue portion of the spectrum (17,000 K) has increased efficacy for melatonin suppression, circadian phase-shifting, and alertness as compared to an equal photon density exposure to a standard white polychromatic light (4000 K). Twenty healthy participants were studied in a time-free environment for 7 days. The protocol included two baseline days followed by a 26-h constant routine (CR1) to assess initial circadian phase. Following CR1, participants were exposed to a full-field fluorescent light (1 × 1014 photons/cm2/s, 4000 K or 17,000 K, n = 10/condition) for 6.5 h during the biological night. Following an 8 h recovery sleep, a second 30-h CR was performed. Melatonin suppression was assessed from the difference during the light exposure and the corresponding clock time 24 h earlier during CR1. Phase-shifts were calculated from the clock time difference in dim light melatonin onset time (DLMO) between CR1 and CR2. Blue-enriched light caused significantly greater suppression of melatonin than standard light ((mean ±â€¯SD) 70.9 ±â€¯19.6% and 42.8 ±â€¯29.1%, respectively, p < 0.05). There was no significant difference in the magnitude of phase delay shifts. Blue-enriched light significantly improved subjective alertness (p < 0.05) but no differences were found for objective alertness. These data contribute to the optimization of the short wavelength-enriched spectra and intensities needed for circadian, neuroendocrine and neurobehavioral regulation.

The causal role of the left parietal lobe in facilitation and inhibition of return.

Following non-informative peripheral cues, responses are facilitated at the cued compared to the uncued location at short cue-target intervals. This effect reverses at longer intervals, giving rise to Inhibition of Return (IOR). The integration-segregation hypothesis (Lupiáñez, 2010) suggests that peripheral cues always produce an onset-detection cost regardless the behavioral cueing effect that is measured - either facilitation or IOR. In the present study, we used transcranial magnetic stimulation (TMS) to investigate the causal contribution of this detection cost to performance. We used a cueing paradigm with a target discrimination task that was preceded by a non-informative peripheral cue. The presence-absence of a central intervening event was manipulated. Online TMS to the left superior parietal lobe (compared to an active vertex stimulation) lead to an overall more positive effect (faster responses for cued as compared to uncued trials), by putatively impairing the detection cost contribution to performance. The data revealed a strong association between overall RT and the TMS effect, and also between overall RT and the integrity of the first branch of the left superior longitudinal fascicule. These results have critical implications not only for the open debate about the mechanism/s underlying spatial orienting effects, but also for the growing literature demonstrating that white matter connectivity is crucial for explaining inter-individual behavioral variability.

PANLAR consensus statement on biosimilars.

INTRODUCTION: Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. OBJECTIVE: The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). METHODS: Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. RESULTS: Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. CONCLUSION: The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. KEY POINTS: • Biologics have improved the treatment of rheumatic diseases. • Their high cost limits access for many patients in both North America and Latin America. • Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. • PANLAR presents its consensus on biosimilars in rheumatology.

Correction to: PANLAR consensus statement on biosimilars.

The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".

Ultrasound in rheumatology. The Mexican experience.

Over the last few years, a growing number of rheumatologists has taken great interest in ultrasonography for its well known advantages and wide spectrum of validated applications in daily rheumatological practice. Most rheumatologists actively performing ultrasonography have had a training experience mainly based on attendance in sonographic courses and/or in radiological or rheumatological units. At present, in Mexico ultrasonography has a still limited diffusion among rheumatologists even if it may play a key role as a first line imaging technique also because of the restricted availability for rheumatic patients for other imaging modalities. This report describes the Mexican experience in education and training on musculoskeletal ultrasound. In 2003, the Mexican School of Musculoskeletal Ultrasound of the Mexican College of Rheumatology (ECOMER) was founded with the intention of joining efforts to launch musculoskeletal ultrasound in Mexico. Essential requirements shared by all the members of ECOMER include: to own an ultrasound machine, to incorporate ultrasonography into clinical daily practice and to keep up-to-date in musculoskeletal ultrasound. The motto of ECOMER is una clara imagen de la reumatologia which means a clear picture of rheumatology. The statute of ECOMER can be read in its web site: www.ecomer.org.mx. This web site also provides a forum for case discussion, consultation and image review.

Controversies in the management of anal high-grade squamous intraepithelial lesions.

Anal squamous dysplasia is recognized as a spectrum of disease that ranges from low-grade intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) to invasive anal squamous cell carcinoma (SCC). Recent reports have shown a significant increase in both the incidence and prevalence of both HSIL and anal SCC, particularly in immunocompromised patients and in men who have sex with men. These lesions are associated with chronic infection with the human papillomavirus. The natural history is unknown, yet reports of untreated patients have shown progression rates of up to 50% in high risk patients. There are controversies as to the optimal management of patients with HSIL. However, there is evidence that screening of high-risk patients with anal cytology is useful in identifying those that require further evaluation. Examination of the anorectal region is enhanced with the use of high resolution anoscopy. Treatment modalities vary in terms of morbidity and success rates. Wide local excision is associated with significant morbidity. Newer therapies such as topical immunomodulation, photodynamic therapy and therapeutic vaccines have been proposed, but long-term follow-up is unavailable. High resolution anoscopy can be used in the office or in the operating room to direct therapy. Using a comprehensive approach of cytology and office-based and/or operating room procedures directed with high resolution anoscopy results in clearance of HSIL in up to 80% of patients, malignant progression in 1%, and less morbidity than wide local excision.