Do, Thanh-Toan; Zhou, Yiren; Zheng, Haitian; Cheung, Ngai-Man; Koh, Dawn
We research a mobile imaging system for early diagnosis of melanoma. Different from previous work, we focus on smartphone-captured images, and propose a detection system that runs entirely on the smartphone. Smartphone-captured images taken under loosely-controlled conditions introduce new challenges for melanoma detection, while processing performed on the smartphone is subject to computation and memory constraints. To address these challenges, we propose to localize the skin lesion by combining fast skin detection and fusion of two fast segmentation results. We propose new features to capture color variation and border irregularity which are useful for smartphone-captured images. We also propose a new feature selection criterion to select a small set of good features used in the final lightweight system. Our evaluation confirms the effectiveness of proposed algorithms and features. In addition, we present our system prototype which computes selected visual features from a user-captured skin lesion image, and analyzes them to estimate the likelihood of malignance, all on an off-the-shelf smartphone.
The chapter deals with the diagnosis of the malignant melanoma of the skin. This aggressive type of cancer with steadily growing incidence in white populations can hundred percent be cured if it is detected in an early stage. Imaging techniques, in particular dermoscopy, have contributed significantly to improvement of diagnostic accuracy in clinical settings, achieving sensitivities for melanoma experts of beyond 95% at specificities of 90% and more. Automatic computer analysis of dermoscopy images has, in preliminary studies, achieved classification rates comparable to those of experts. However, the diagnosis of melanoma requires a lot of training and experience, and at the time being, average numbers of lesions excised per histology-proven melanoma are around 30, a number which clearly is too high. Further improvements in computer dermoscopy systems and their competent use in clinical settings certainly have the potential to support efforts of improving this situation. In the chapter, medical basics, current state of melanoma diagnosis, image analysis methods, commercial dermoscopy systems, evaluation of systems, and methods and future directions are presented.
Orzan, OA; Șandru, A; Jecan, CR
Cutaneous melanoma (CM) is a disease with an unpredictable evolution mainly due to its high metastatic ability. The steadily increasing incidence and the poor outcome in advanced stages made this cancer an interesting field for many research groups. Given that CM is a curable disease in early stages, efforts have been made to detect it as soon as possible, which led to the diversification and refining of diagnosis methods and therapies. But, as the data from trials have been published, doubts about the indications and efficacy of established treatments have arisen. In fact, there is probably no single aspect of early CM that has not given birth to controversy. This article intends to present the current disputes regarding the early detection, diagnosis, treatment and postoperative follow-up of patients with localized CM. After analyzing both pros and cons, several conclusions were drawn, that reflect our experience in managing patients with early CM. PMID:25866567
Fernandez-Flores, Angel; Cassarino, David S
Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.
Rogers, Tova; Pulitzer, Melissa; Marino, Maria L; Marghoob, Ashfaq A; Zivanovic, Oliver; Marchetti, Michael A
There are limited studies on the dermoscopic features of mucosal melanoma, particularly early-stage lesions. Described criteria include the presence of blue, gray, or white colors, with a reported sensitivity of 100%. It is unclear if these features will aid in the detection of early mucosal melanoma or improve diagnostic accuracy compared to naked-eye examination alone. An Asian female in her fifties was referred for evaluation of an asymptomatic, irregularly pigmented patch of the clitoral hood and labia minora of unknown duration. Her past medical history was notable for Stage IV non-small cell lung cancer. She denied a personal or family history of skin cancer. Dermoscopic evaluation of the vulvar lesion revealed heterogeneous brown and black pigmentation mostly composed of thick lines. There were no other colors or structures present. As the differential diagnosis included vulvar melanosis and mucosal melanoma, the patient was recommended to undergo biopsy, which was delayed due to complications from her underlying lung cancer. Repeat dermoscopic imaging performed three months later revealed significant changes concerning for melanoma, including increase in size, asymmetric darkening, and the appearance of structureless areas and central blue and pink colors. Histopathological examination of a biopsy and subsequent resection confirmed the diagnosis of melanoma in situ. Previously described dermoscopic features for mucosal melanoma may not have high sensitivity for early melanomas. Additional studies are needed to define the dermoscopic characteristics of mucosal melanomas that aid in early detection. Health care providers should have a low threshold for biopsy of mucosal lesions that show any clinical or dermoscopic features of melanoma, especially in older women.
Chatelain, Clément; Amar, Martine Ben
Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.
Chen, Steven T; Li, Xin; Han, Jiali
Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC). We followed 77,288 female American nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥0.8 mm or Clark's levels of IV and V according to history of NMSC. We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05-2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55-1.37)), Breslow thickness ≥0.8 mm (0.85 (0.59-1.21)) and Clark's levels IV and V (0.81(0.52-1.24)). Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from melanoma. © 2017 UICC.
Brackmann, Derald E; Doherty, Joni K
Melanoma rarely invades the cerebellopontine angle (CPA) and can evade accurate diagnosis, which may alter management decisions. Diagnosis may be facilitated via careful history, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) analysis. Retrospective case review. Tertiary referral center. Thirteen internal auditory canal/CPA lesions in eight patients who presented with CPA syndrome and who had a pathological diagnosis consistent with malignant melanoma. There were four bilateral and four unilateral lesions. Six of eight patients had a history of melanoma. One was apparently primary CPA lesion, whereas all others were metastatic. T1- and T2-weighted precontrast and postcontrast gadolinium-enhanced MRI were obtained, including fat suppression and fluid-attenuated inversion recovery sequence images in two patients; lumbar puncture with CSF centrifugation and cytological analysis confirmed the diagnosis in two patients. Translabyrinthine craniotomy was performed for tumor extirpation in five patients. Symptoms at presentation, MRI findings, presence of malignant cells in CSF, tumor progression, intraoperative findings, response to treatment, time interval from initial diagnosis of melanoma elsewhere, and survival. Seven of eight patients had history and/or MRI findings suggestive of malignancy in the internal auditory canal and/or CPA, and diagnosis was confirmed via CSF analysis in two patients. In one patient, diagnosis was made at surgery. Internal auditory canal melanoma portends a grim prognosis, can occur up to 17 years after initial melanoma diagnosis/treatment, and can be detected with appropriate MRI sequences, especially enhanced fluid-attenuated inversion recovery images. In disseminated cases, diagnosis can be confirmed with lumbar puncture demonstrating malignant cells. Management includes tumor resection when melanoma seems to be solitary and malignant cells are not present in CSF. Intrathecal chemotherapy and radiation are
Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L
Melanoma patients are advised to perform regular risk-reduction practices, including sun protection as well as skin self-examinations (SSEs) and physician-led examinations. Melanoma-specific communication regarding family risk and screening may promote such behaviors. To this end, associations between patients' melanoma-specific communication and risk reduction were examined. Melanoma patients (N = 169) drawn from a population-based cancer registry reported their current risk-reduction practices, perceived risk of future melanoma, and communication with physicians and relatives about melanoma risk and screening. Patients were, on average, 56 years old and 6.7 years' post diagnosis; 51% were male, 93% reported "fair/very fair" skin color, 75% completed at least some college, and 22% reported a family history of melanoma. Patients reported varying levels of regular (always/nearly always) sun protection: sunscreen use (79%), shade seeking (60%), hat use (54%), and long-sleeve shirt use (30%). Only 28% performed thorough SSE regularly, whereas 92% reported undergoing physician-led skin examinations within the past year. Participants who were female, younger, and had a higher perceived risk of future melanoma were more likely to report past communication. In adjusted analyses, communication remained uniquely associated with increased sunscreen use and SSE. Encouraging melanoma patients to have a more active role in discussions concerning melanoma risk and screening with relatives and physicians alike may be a useful strategy to promote 2 key risk-reduction practices post melanoma diagnosis and treatment. Future research is needed to identify additional strategies to improve comprehensive risk reduction in long-term melanoma patients. Copyright © 2016 John Wiley & Sons, Ltd.
Simionescu, Olga; Costache, Mariana; Testori, Alessandro
Cutaneous melanoma is a “perfid”, aggressive and hard to be treated malignant tumor in case of delayed diagnosis. However, patients still have a chance to escape progressive disease if the lesion is recognized early, when the surgical approach is curative. Dermoscopy has the important advantage of rapidity and non-invasivity in a field with (still) contradictory algorithms of diagnosis and treatment. The recognition of the elementary dermoscopic lesions enables accurate diagnosis for cutaneous melanoma. In our opinion, dermoscopy appears compulsory in the routine derma-tologic examination. In vivo microscopy (dermoscopy) together with histopathology (plus or minus immunohisto-chemistry) seem, at present, to provide the most reliable diagnosis of melanoma. PMID:17125600
Mierzwa-Dobranowska, Marzena; Romanowska-Dixon, Bozena
This study will show a comparison of two groups of patients with uveal melanoma; one group with multiple primary cancer, and a second group with no identifiable second cancer, in terms of education and occupation. Study concerns 240 patients, who were isolated from patients being treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology Jagiellonian University Medical College in the period from 1998 to 2007. On the basis of medical history and medical records 97 patients were diagnosed with the one or more independent primary cancers. These patients were subjected to comparative analysis with a group of 143 patients with uveal melanoma as a control group. Analyzing the impact of education on the recognition of multiple primary cancer, there were significantly more frequent diagnoses of second primary cancers among patients with secondary and higher education than among those who had primary and vocational education. Among the obtained data on patients in the study group, the largest occupational group (according to the ISCO-88 (COM)) constituted "professionals". In the control group prevailed "craft and related trades workers". The results suggest the great importance of knowledge about risk factors for the development of cancer among patients with uveal melanoma and the ensuing more scrupulous search for succesive primary neoplasm and indicate the neccesity of organizing broad prophylactic actions. uveal melanoma, multiple primary cancer.
Mar, Victoria J; Chamberlain, Alex J; Kelly, John W; Murray, William K; Thompson, John F
A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.
Golobardes, Elisabet; Corral, Guiomar; Puig, Susana; Malvehy, Josep
The number of melanoma cancer-related death has increased over the last few years due to the new solar habits. Early diagnosis has become the best prevention method. This work presents a melanoma diagnosis architecture based on the collaboration of several multilabel case-based reasoning subsystems called DERMA. The system has to face up several challenges that include data characterization, pattern matching, reliable diagnosis, and self-explanation capabilities. Experiments using subsystems specialized in confocal and dermoscopy images have provided promising results for helping experts to assess melanoma diagnosis. PMID:24578629
Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F
Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.
Goodson, Agnessa G.; Grossman, Douglas
Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Although there are no non-invasive techniques for definitive diagnosis of melanoma, and the “gold standard” remains biopsy with histologic examination, a variety of modalities may facilitate early melanoma diagnosis and the detection of new and changing nevi. This article reviews general clinical principles of early melanoma detection, and various modalities that are currently available or on the horizon, providing the clinician with an up-to-date understanding of management strategies for their patients with numerous or atypical nevi. Learning objectives At the conclusion of this learning activity, participants should: 1) understand the clinical importance of early melanoma detection; 2) appreciate the challenges of early melanoma diagnosis and which patients are at highest risk; 3) know general principles of early melanoma detection; 4) be familiar with current and emerging modalities that may facilitate early melanoma diagnosis and the detection of new and changing nevi; 5) know the advantages and limitations of each modality; and 6) be able to practice a combined approach to the patient with numerous or clinically atypical nevi. PMID:19389517
Fuller, Collin; Cellura, A Paul; Hibler, Brian P; Burris, Katy
The computer-assisted diagnosis of melanoma is an exciting area of research where imaging techniques are combined with diagnostic algorithms in an attempt to improve detection and outcomes for patients with skin lesions suspicious for malignancy. Once an image has been acquired, it undergoes a processing pathway which includes preprocessing, enhancement, segmentation, feature extraction, feature selection, change detection, and ultimately classification. Practicality for everyday clinical use remains a vital question. A successful model must obtain results that are on par or outperform experienced dermatologists, keep costs at a minimum, be user-friendly, and be time efficient with high sensitivity and specificity. ©2015 Frontline Medical Communications.
Background Spectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection. Methods During a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade® MHT S.p.A., Verona, Italy). Results Among the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively. Conclusions Although SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions. PMID:20707921
Ascierto, Paolo A; Palla, Marco; Ayala, Fabrizio; De Michele, Ileana; Caracò, Corrado; Daponte, Antonio; Simeone, Ester; Mori, Stefano; Del Giudice, Maurizio; Satriano, Rocco A; Vozza, Antonio; Palmieri, Giuseppe; Mozzillo, Nicola
Spectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection. During a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade MHT S.p.A., Verona, Italy). Among the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively. Although SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions.
Gottvaldová, M; Jedličková, H; Poprach, A; Vašků, V
Melanoma is a malignant skin disease. The tumor development is caused by an uncontrollable proliferation of melanocytes. The most common occurrence is on the skin, but melanoma may also develop on the mucous membrane, meninges, and eyes. Some melanomas develop from melanocytic nevus. Acral lentiginous melanoma occurs on palms, feet, fingers and under nails, and is the most common type of melanoma for phototype VI. The most important factor for successful treatment of malignant melanoma is an early detection, excision of the primary tumor and histological staging. Surgical treatment of an early-stage melanoma is a key to successful therapy; however, many patients (mostly men) do not seek medical attention before it istoo late. This case study presents a 59-year-old patient, who suffers from white coat syndrome and whose finger was amputated for alleged gangrene. Subsequently, brownish black nodules appeared across his arm. Histological examination proved metastases of malignant melanoma. It was only at this phase, when the patient admitted a nevus at the tip of his amputated finger, from which ulceration and gangrene gradually emerged. This case demonstrates a combination of multiple unfavorable factors, which led to delayed diagnosis and therapy.
Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions.
Bono, Aldo; Bartoli, Cesare; Cascinelli, Natale; Lualdi, Manuela; Maurichi, Andrea; Moglia, Daniele; Tragni, Gabrina; Tomatis, Stefano; Marchesini, Renato
Successful treatment of melanoma depends directly on early diagnosis. Such a diagnosis is based on clinical examination and dermatoscopy. Recently, automated instruments for melanoma detection are under development. To prospectively evaluate the diagnostic possibilities provided by clinical and dermatoscopic examinations and by a computerized telespectrophotometric system (TS). The study involves a consecutive series of 298 patients with 313 cutaneous pigmented lesions (66 melanomas and 247 non-melanoma lesions). Each lesion was subjected to the triple diagnostic evaluation, before surgery. Results were expressed in terms of sensitivity and specificity of each kind of evaluation. Clinical evaluation had sensitivity and specificity values of 86 and 77%, respectively, whereas dermatoscopy gave corresponding values of 91 and 74%. TS assessment resulted in a sensitivity of 80% and a specificity of 49%. Differences between clinical and dermatoscopic diagnoses lacked statistical significance (p = 0.22), whereas there was a significant difference comparing both clinical and TS evaluations (p < 0.01) and dermatoscopic and TS evaluations (p < 0.01). Combining clinical and dermatoscopic evaluations, a sensitivity of 97% was achieved. Addition of TS has not changed this figure. Results of this study confirm and stress the importance of dermatoscopy in the diagnosis of melanoma. Clinical evaluation coupled with dermatoscopy can be considered the cornerstone of such a diagnosis. Although TS is able to achieve interesting results, at present it cannot significantly compete with any of the other tested methods. Copyright 2002 S. Karger AG, Basel
Barzegari, Masoomeh; Ghaninezhad, Haiedeh; Mansoori, Parisa; Taheri, Arash; Naraghi, Zahra S; Asgari, Masood
Background Computer-aided dermoscopy using artificial neural networks has been reported to be an accurate tool for the evaluation of pigmented skin lesions. We set out to determine the sensitivity and specificity of a computer-aided dermoscopy system for diagnosis of melanoma in Iranian patients. Methods We studied 122 pigmented skin lesions which were referred for diagnostic evaluation or cosmetic reasons. Each lesion was examined by two clinicians with naked eyes and all of their clinical diagnostic considerations were recorded. The lesions were analyzed using a microDERM® dermoscopy unit. The output value of the software for each lesion was a score between 0 and 10. All of the lesions were excised and examined histologically. Results Histopathological examination revealed melanoma in six lesions. Considering only the most likely clinical diagnosis, sensitivity and specificity of clinical examination for diagnosis of melanoma were 83% and 96%, respectively. Considering all clinical diagnostic considerations, the sensitivity and specificity were 100% and 89%. Choosing a cut-off point of 7.88 for dermoscopy score, the sensitivity and specificity of the score for diagnosis of melanoma were 83% and 96%, respectively. Setting the cut-off point at 7.34, the sensitivity and specificity were 100% and 90%. Conclusion The diagnostic accuracy of the dermoscopy system was at the level of clinical examination by dermatologists with naked eyes. This system may represent a useful tool for screening of melanoma, particularly at centers not experienced in the field of pigmented skin lesions. PMID:16000171
Puza, Charles J; Barbas, Andrew S; Mosca, Paul J
A history of melanoma within the preceding 5 years is commonly considered a contraindication to solid organ transplantation. We investigated how a pretransplant history of melanoma impacts patient survival and melanoma recurrence. Institutional Review Board approval was obtained, and Duke's retrospective database was used to identify 4552 patients who underwent a solid organ transplant at Duke University from 1 January 2001 to 31 December 2016. Data with regard to the transplant, melanoma characteristics, rejection episodes, and survival were recorded. Of 4552 patients who underwent a solid organ transplant, 12 (0.3%) had a history of melanoma before transplant (six with melanoma in situ and six with stage I disease). The median time between melanoma diagnosis and transplant was 4.13 years (range: 1.1-13.3 years). The study cohort consisted of four liver transplants, four lung transplants, one kidney transplant, one heart transplant, one small bowel transplant, and one multivisceral transplant. At the median follow-up time of 2.8 years, 10 (83.3%) patients were alive. In nonmelanoma cohorts, the 3-year survival is 70% for thoracic transplants, 78% for liver transplants, and 88% for kidney transplants. In well-selected patients with a history of early-stage melanoma and an appropriate time interval between melanoma treatment and transplant, post-transplant outcomes are favorable.
Drakaki, E.; Sianoudis, IA; Zois, EN; Makropoulou, M.; Serafetinides, AA; Dessinioti, C.; Stefanaki, E.; Stratigos, AJ; Antoniou, C.; Katsambas, A.; Christofidou, E.
The number of non-melanoma skin cancers is increasing worldwide and has become an important health and economic issue. Early detection and treatment of skin cancer can significantly improve patient outcome. Therefore there is an increase in the demand for proper management and effective non-invasive diagnostic modalities in order to avoid relapses or unnecessary treatments. Although the gold standard of diagnosis for non-melanoma skin cancers is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of non-melanoma skin cancers include high-definition optical coherence tomography, fluorescence spectroscopy, oblique incidence diffuse reflectance spectrometry among others spectroscopic techniques. Our findings establish how those spectrometric techniques can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic.
Psaty, Estee L.; Halpern, Allan C.
Relative to other specialties, dermatologists have been slow to adopt advanced technologic diagnostic aids. After all, most skin disease can be diagnosed by simple visual inspection, and the skin is readily accessible for a diagnostic biopsy. Diagnostic aids such as total body photography and dermoscopy improve the clinician's ability to diagnose melanoma beyond unaided visual inspection, however, and are now considered mainstream methods for early detection. Emerging technologies such as in vivo reflectance confocal microscopy are currently being investigated to determine their utility for noninvasive diagnosis of melanoma. This review summarizes the currently available cutaneous imaging devices and new frontiers in noninvasive diagnosis of skin disease. We anticipate that multimodal systems that combine different imaging technologies will further improve our ability to detect, at the bedside, melanoma at an earlier stage. PMID:19095152
Campagne, C; Julé, S; Alleaume, C; Bernex, F; Ezagal, J; Château-Joubert, S; Estrada, M; Aubin-Houzelstein, G; Panthier, J-J; Egidy, G
Melanoma diagnosis in dogs can be challenging due to the variety of histological appearances of canine melanocytic neoplasms. Markers of malignancy are needed. Receptor for activated C-kinase 1 (RACK1) was found to characterize melanomas in other mammals. We investigated the value of RACK1 detection in the classification of 19 cutaneous and 5 mucosal melanocytic neoplasms in dogs. These tumors were categorized as melanocytomas or benign and melanomas or malignant after evaluation of their morphology, mitotic index, and Ki-67 growth fraction. Using immunofluorescence, we confirmed microphthalmia-associated transcription factor (MITF) as a marker of normal and transformed melanocytic cells in dog tissues. All control (n = 10) and tumoral (n = 24) samples stained positively for MITF (34/34, 100%). Whereas RACK1 was not detected in healthy skin melanocytes, melanocytic lesions were all positive for RACK1 signal (24/24, 100%). RACK1 cytoplasmic staining appeared with 2 distinct distribution patterns: strong, diffuse, and homogeneous or granular and heterogeneous. All melanoma samples (13/13, 100%) stained homogeneously for RACK1. All melanocytomas (11/11, 100%) stained heterogeneously for RACK1. Immunohistochemistry was less consistent than immunofluorescence for all labelings in melanocytic lesions, which were often very pigmented. Thus, the fluorescent RACK1-MITF labeling pattern helped to distinguish melanomas from melanocytomas. Furthermore, RACK1 labeling correlated with 2 of 11 morphological features linked to malignancy: cell and nuclear size. These results suggest that RACK1 may be used as a marker in dog melanomas.
Salerni, Gabriel; Carrera, Cristina; Lovatto, Louise; Puig-Butille, Joan Anton; Badenas, Celia; Plana, Estel; Puig, Susana; Malvehy, Josep
Background Early detection of melanoma is the best way to improve prognosis. Digital follow up (DFU) programs of high-risk populations could be an efficient strategy for detecting early melanomas with low morbidity. Objective to report the added value of the use of the “two-step method” (digital total-body photography and digital dermoscopy) Methods Analysis of the surveillance of 618 high-risk melanoma patients included in our DFU-program from 1999 to 2008. Results A total of 11396 lesions were monitored (mean 18.44 per patient) during a median follow-up of 96 months (median 10 visits per patient). 1152 lesions, 1.86 per patient, were excised. Almost 70% (798) were lesions previously registered at least twice, while 356 (30%) were detected and removed in the same visit. During follow-up, 98 melanomas (8.5% of excised lesions) were diagnosed in 78 patients (12.6%). 53 melanomas were in situ (53.3%), while invasive (45) showed a Breslow index of less than 1 mm (median 0.5 mm) and none was ulcerated. Limitations Since there are no control groups we cannot convey if the combined use of total-body photography and digital dermoscopy is more beneficial than these techniques used separately. Conclusion DFU with Total-Body Photography and Dermoscopy in a selected high-risk population demonstrated the early detection of melanomas with a low rate of excisions. Long-term follow-up is required to allow the detection of slow growing melanomas. Based on our 10-year experience, melanomas can be diagnosed at any time, suggesting that in high-risk population, DFU should be maintained with time. PMID:21683472
Dessinioti, Clio; Geller, Alan C; Stergiopoulou, Aravella; Swetter, Susan M; Baltas, Eszter; Mayer, Jonathan E; Johnson, Timothy M; Talaganis, John; Trakatelli, Myrto; Tsoutsos, Dimitrios; Tsourouflis, Gerasimos; Stratigos, Alexander J
Early melanoma detection strategies include skin self-examination (SSE), physician skin examination (PSE), and promotion of patient knowledge about skin cancer. To investigate the association of SSE, PSE, and patient attitudes with the detection of thinner superficial spreading melanoma (SSM) and nodular melanoma (NM), the latter of which tends to elude early detection. This cross-sectional, questionnaire-based, multicenter study identified patients with newly diagnosed cutaneous melanoma at 4 referral hospital centers in the United States, Greece, and Hungary. Among 920 patients with a primary invasive melanoma, 685 patients with SSM or NM subtype were included. A standardized questionnaire was used to record sociodemographic information, SSE and PSE practices, and patient perceptions in the year prior to diagnosis. Data were analyzed according to histologic thickness, with a 2-mm cutoff for thinner SSM and NM. Of 685 participants (mean [SD] age, 55.6 [15.1] years; 318 [46%] female), thinner melanoma was detected in 437 of 538 SSM (81%) and in 40 of 147 NM (27%). Patients who routinely performed SSE were more likely to be diagnosed with thinner SSM (odds ratio [OR], 2.61; 95% CI, 1.14-5.40) but not thinner NM (OR, 2.39; 95% CI, 0.84-6.80). Self-detected clinical warning signs (eg, elevation and onset of pain) were markers of thicker SSM and NM. Whole-body PSE was associated with a 2-fold increase in detection of thinner SSM (OR, 2.25; 95% CI, 1.16-4.35) and thinner NM (OR, 2.67; 95% CI, 1.05-6.82). Patient attitudes and perceptions focusing on increased interest in skin cancer were associated with the detection of thinner NM. Our findings underscore the importance of complementary practices by patients and physicians for the early detection of melanoma, including regular whole-body PSE, SSE, and increased patient awareness.
Kandolf-Sekulović, Lidija; Babović, Nada; Jokić, Neven; Nikolin, Borislava; Nikolić, Dejan; Janjić, Zlata; Mijugković, Zeljko; Rajović, Milica; Novaković, Marijan; Pejcić, Ivica; Kovaević, Predrag; Mihajlović, Dragan; Roganović, Tatjana; Ferenc, Vicko; Nikolić, Jelena; Marinković, Marija; Bizetić, Zorana
Treatment options for metastatic melanoma in Serbia are limited due to the lack of newly approved biologic agents and the lack of clinical studies. Also, there is a paucity of data regarding the treatment approaches in different tertiary centers and efficacy of available chemotherapy protocols. The aim of this study was to obtain more detailed data about treatment protocols in Serbia based on structured survey in tertiary oncology centers. Data about the melanoma patients treated in 2011 were analyzed from hospital databases in 6 referent oncology centers in Serbia, based on the structured survey, with the focus on metastatic melanoma patients (unresectable stage IIIC and IV). A total of 986 (79-315 in different centers) patients were treated, with 320 (32.45%) newly diagnosed patients. There were 317 patients in stage IIIC/IV, 77/317 aged < 50 years. At the time of diagnosis 47.3% of patients were < 60 years of age (24.2% < 40 years, 23% 50-59 years, 52.6% > 60 years). At initial diagnosis 12.5% of patients were in stage III and 4.5% in stage IV. The most common type was superficial spreading melanoma (50-660), followed by nodular melanoma (23.5-50%). Apart from the regional and distant lymph node metastases, the most frequent organs involved in stage IV disease were distant skin and soft tissues (12-55%), lungs (19-55.5%), liver (10-60%), and bones (3-10%). The first line therapy in stage IV metastatic melanoma was dacarbazine (DTIC) dimethyl-triazenoimidozole-carboxamide in 61-93% of the patients, while the second line varied between the centers. Disease control (complete response + partial response + stable disease) was achieved in 25.7% of the patients treated with the first line chemotherapy and 23.1% of the patients treated with the second line therapy, but the duration of response was short, in first-line therapy 6.66 +/- 3.36 months (median 6.75 months). More than 90% of patients were treated outside the clinical trials. Based on this survey, there is a
Bhowmik, Arka; Repaka, Ramjee; Mishra, Subhash C
A theoretical study on vascularized skin model to predict the thermal evaluation criteria of early melanoma using the dynamic thermal imaging technique is presented in this article. Thermographic evaluation of melanoma has been carried out during the thermal recovery of skin from undercooled condition. During thermal recovery, the skin has been exposed to natural convection, radiation, and evaporation. The thermal responses of melanoma have been evaluated by integrating the bioheat model for multi-layered skin with the momentum as well as energy conservation equations for blood flow. Differential changes in the surface thermal response of various melanoma stages except that of the early stage have been determined. It has been predicted that the thermal response due to subsurface blood flow overpowers the response of early melanoma. Hence, the study suggests that the quantification of early melanoma diagnosis using thermography has not reached a matured stage yet. Therefore, the study presents a systematic analysis of various intermediate melanoma stages to determine the thermal evaluation criteria of early melanoma. The comprehensive modeling effort made in this work supports the prediction of the disease outcome and relates the thermal response with the variation in patho-physiological, thermal and geometrical parameters. Copyright © 2014 Elsevier Ltd. All rights reserved.
Gershenwald, J E
The presentations at the American Society of Clinical Oncology 2001 meeting reported or updated the results of phase I, II, and III randomized trials and also reported important meta-analyses and retrospective studies impacting on the management of patients with melanoma. In the treatment of early stage melanoma, the prognostic significance of pathologic status of sentinel lymph nodes was affirmed. With respect to regional nodal involvement (American Joint Committee on Cancer [AJCC] stage III), investigators presented the interim results of the United Kingdom randomized low-dose interferon (IFN) trial, and up-to-date meta-analyses of several IFN trials including a pooled analysis of the Eastern Cooperative Oncology Group trials evaluating interferon in the adjuvant setting. In the advanced disease setting (AJCC stage IV), several studies elucidated the pros and cons of biochemotherapy in patients with metastatic melanoma, with an emphasis on seeking to improve response in the central nervous system and durability of response in general. Thought provoking was new data regarding the potential for lovastatin to act as a chemopreventive agent for melanoma. Translational studies were presented, one supporting the importance of HLA-typing in developing targeted vaccine therapy. Finally, the results of a novel experimental melanoma vaccine were presented using autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96).
Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...
Bhattacharya, Abhishek; Young, Albert; Wong, Andrew; Stalling, Simone; Wei, Maria; Hadley, Dexter
Melanoma will affect an estimated 73,000 new cases this year and result in 9,000 deaths, yet precise diagnosis remains a serious problem. Without early detection and preventative care, melanoma can quickly spread to become fatal (Stage IV 5-year survival rate is 20-10%) from a once localized skin lesion (Stage IA 5- year survival rate is 97%). There is no biomarker for melanoma in clinical use, and the current diagnostic criteria for skin lesions remains subjective and imprecise. Accurate diagnosis of melanoma relies on a histopathologic gold standard; thus, aggressive excision of melanocytic skin lesions has been the mainstay of treatment. It is estimated that 36 biopsies are performed for every melanoma confirmed by pathology among excised lesions. There is significant morbidity in misdiagnosing melanoma such as progression of the disease for a false negative prediction vs the risks of unnecessary surgery for a false positive prediction. Every year, poor diagnostic precision adds an estimated $673 million in overall cost to manage the disease. Currently, manual dermatoscopic imaging is the standard of care in selecting atypical skin lesions for biopsy, and at best it achieves 90% sensitivity but only 59% specificity when performed by an expert dermatologist. Many computer vision (CV) algorithms perform better than dermatologists in classifying skin lesions although not significantly so in clinical practice. Meanwhile, open source deep learning (DL) techniques in CV have been gaining dominance since 2012 for image classification, and today DL can outperform humans in classifying millions of digital images with less than 5% error rates. Moreover, DL algorithms are readily run on commoditized hardware and have a strong online community of developers supporting their rapid adoption. In this work, we performed a successful pilot study to show proof of concept to DL skin pathology from images. However, DL algorithms must be trained on very large labelled datasets of
Grange, F; Barbe, C; Mas, L; Granel-Brocard, F; Lipsker, D; Aubin, F; Velten, M; Dalac, S; Truchetet, F; Michel, C; Mitschler, A; Arnoult, G; Buemi, A; Dalle, S; Reuter, G; Bernard, P; Woronoff, A S; Arnold, F
Little data are available concerning the role of general practitioners (GPs) in the diagnosis of melanoma. To evaluate the actual role of GPs in a population-based study covering five regions of France and 8·2 million inhabitants. A survey of cancer registries and pathology laboratories, and questionnaires to practitioners were used to identify incident melanomas in 2008, and evaluate characteristics of patients (age, sex, area of residence, social isolation), tumours (Breslow, ulceration, location, histological type), and GPs (training, conditions of practice), and their influence on patterns of diagnosis and Breslow thickness. Among 898 melanomas, 376 (42%) were first diagnosed in a general practice setting (GP group). Breslow thickness was much higher in the GP group than in other melanomas (median: 0·95 vs. 0·61 mm, P < 0·0001). Multivariate analysis identified an older age, lower limb location, nodular subtype and Breslow thickness as factors associated with the GP group. Within this group, 52·5% of melanomas were detected by patients (median Breslow thickness: 1·30 mm) and 47·5% by GPs (median Breslow thickness: 0·80 mm, P = 0·0009), including 8% during a systematic full-body skin examination. Previous GP training on melanoma was associated with active detection by GPs. Male sex and social isolation of patients were associated with thicker melanomas, whereas active detection by GPs was associated with thinner CMs. GPs play a key role in melanoma diagnosis in France, but still frequently detect thick tumours. Increasing awareness and training of GPs and focusing attention on male and/or socially isolated patients should help to improve early detection of melanoma. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.
Karagiannis, Georgios T.; Grivas, Ioannis; Tsingotjidou, Anastasia; Apostolidis, Georgios K.; Grigoriadou, Ifigeneia; Dori, I.; Poulatsidou, Kyriaki-Nefeli; Doumas, Argyrios; Wesarg, Stefan; Georgoulias, Panagiotis
Malignant melanoma is a form of skin cancer, with increasing incidence worldwide. Early diagnosis is crucial for the prognosis and treatment of the disease. The objective of this study is to develop a novel animal model of melanoma and apply a combination of the non-invasive imaging techniques acoustic microscopy, infrared (IR) and Raman spectroscopies, for the detection of developing tumors. Acoustic microscopy provides information about the 3D structure of the tumor, whereas, both spectroscopic modalities give qualitative insight of biochemical changes during melanoma development. In order to efficiently set up the final devices, propagation of ultrasonic and electromagnetic waves in normal skin and melanoma simulated structures was performed. Synthetic and grape-extracted melanin (simulated tumors), endermally injected, were scanned and compared to normal skin. For both cases acoustic microscopy with central operating frequencies of 110MHz and 175MHz were used, resulting to the tomographic imaging of the simulated tumor, while with the spectroscopic modalities IR and Raman differences among spectra of normal and melanin- injected sites were identified in skin depth. Subsequently, growth of actual tumors in an animal melanoma model, with the use of human malignant melanoma cells was achieved. Acoustic microscopy and IR and Raman spectroscopies were also applied. The development of tumors at different time points was displayed using acoustic microscopy. Moreover, the changes of the IR and Raman spectra were studied between the melanoma tumors and adjacent healthy skin. The most significant changes between healthy skin and the melanoma area were observed in the range of 900-1800cm-1 and 350-2000cm-1, respectively.
von der Maase, H; Osterlind, A; Drzewiecki, K T; Dahlstrøm, K K; Geertsen, P F; Gjedde, S B; Hastrup, N C; Holmberg, S B; Krag, C; Lock-Andersen, J
About 700 new cases of malignant melanoma of the skin are registered annually in Denmark. The incidence is increasing rapidly and the number of new cases increases by more than 5% per annum. The most important phenotypical risk factors are the number of acquired pigmented naevi and exposure to sunlight is the most important risk factor in the external environment so that severe sunburn in children and intermittent intense exposure to sunlight increase the risk of melanoma. The thickness of the tumour at the time of the diagnosis is the most important prognostic factor. The prognosis deteriorates with increasing thickness. Treatment is primarily surgical. In cases of inoperable local melanoma and regional recurrences, irradiation may be administered. Chemotherapy and/or immunotherapy are of experimental character. In the light of the rapidly increasing incidence, it is important that knowledge of risk factors for development of the disease and the clinical characteristics of early melanoma is spread to not only the medical profession but also to the general public.
Garway-Heath, David F
This chapter reviews the evidence for the clinical application of vision function tests and imaging devices to identify early glaucoma, and sets out a scheme for the appropriate use and interpretation of test results in screening/case-finding and clinic settings. In early glaucoma, signs may be equivocal and the diagnosis is often uncertain. Either structural damage or vision function loss may be the first sign of glaucoma; neither one is consistently apparent before the other. Quantitative tests of visual function and measurements of optic-nerve head and retinal nerve fiber layer anatomy are useful to either raise or lower the probability that glaucoma is present. The posttest probability for glaucoma may be calculated from the pretest probability and the likelihood ratio of the diagnostic criterion, and the output of several diagnostic devices may be combined to achieve a final probability. However, clinicians need to understand how these diagnostic devices make their measurements, so that the validity of each test result can be adequately assessed. Only then should the result be used, together with the patient history and clinical examination, to derive a diagnosis.
Cicchiello, Mark; Lin, Matthew J; Pan, Yan; McLean, Catriona; Kelly, John W
Missed opportunities in the diagnosis of nodular melanoma (NM) carry high prognostic penalties due to the rapid rate of NM growth. To date, an assessment of the pathways to diagnosis of NM versus superficial spreading melanoma (SSM) specifically comparing numbers of opportunities missed to undertake biopsy has not been performed. A retrospective questionnaire of 120 patients (60 NM patients, age and sex matched to 60 SSM patients) from the Victorian Melanoma Service (VMS) database was undertaken to assess pathways to diagnosis. The numbers of opportunities missed to undertake a biopsy and doctor behaviour at such encounters were recorded. Diagnostic delay (overall, patient's and doctor's delay) in terms of time was assessed. Significant differences in opportunities missed to make a diagnosis of NM compared to SSM were found. In all, 43% of NM were biopsied at a first encounter compared to 70% of SSM. All SSM were diagnosed within three reviews. Overall, 33% of NM required at least three and up six reviews until biopsy. Patients with NM were more likely than those with SSM to be reassured that their lesions were benign. No significant differences in terms of time delay to diagnosis between NM and SSM were found. NM contributes disproportionately to melanoma mortality in Australia. Addressing earlier diagnosis of NM with renewed focus may make the biggest impact on the overall mortality of melanoma. The message that a period of observation is not appropriate for patients re-presenting with lesions of concern must be more effectively communicated. © 2015 The Australasian College of Dermatologists.
Kuźbicki, Łukasz; Lange, Dariusz; Strączyńska-Niemiec, Anita; Chwirot, Barbara W
Early cutaneous melanomas may present a substantial diagnostic challenge. We have already reported that expression of cyclooxygenase-2 (COX-2) may be useful for differentiating between cutaneous melanomas and naevi. The purpose of this study was to examine the value of COX-2 in a challenging task of differential diagnosis of early melanomas and melanocytic naevi considered by histopathologists as morphologically difficult to unequivocally diagnose as benign lesions. The material for the study comprised formalin-fixed paraffin-embedded samples of 46 naevi (including 27 cases of dysplastic, Spitz and Reed naevi) and 30 early human cutaneous melanomas. The expression of COX-2 was detected immunohistochemically. Melanomas expressed COX-2 significantly more strongly compared with naevi. The test, on the basis of determination of the percentage fractions of COX-2-positive cells, allows for differentiation of early skin melanomas and naevi with high sensitivity and specificity. Receiver operating characteristic analysis of the test results yielded areas under receiver operating characteristics curves (AUC)=0.946±0.030 for central regions and AUC=0.941±0.031 for the peripheries of the lesions. The performance of the test in differentiating between melanomas and the naevi group comprising dysplastic, Spitz and Reed naevi was also good, with AUC=0.933±0.034 and 0.923±0.037 for the central and the border regions of the lesions, respectively. Using a more complex diagnostic algorithm also accounting for the staining intensity did not result in an improvement in the resolving power of the assay. A diagnostic algorithm using differences in the percentage fractions of cells expressing COX-2 may serve as a useful tool in aiding the differential diagnosis of 'histopathologically difficult' benign melanocytic skin lesions and early melanomas.
von Schuckmann, Lena A; Smith, David; Hughes, Maria Celia B; Malt, Maryrose; van der Pols, Jolieke C; Khosrotehrani, Kiarash; Smithers, Bernard M; Green, Adele C
Ulcerated primary melanomas are associated with an inflammatory tumor microenvironment. We hypothesized that systemic proinflammatory states and anti-inflammatory medications are also associated with a diagnosis of ulcerated melanoma. In a cross-sectional study of 787 patients with newly diagnosed clinical stage IB or II melanoma, we estimated odds ratios for the association of proinflammatory factors (high body mass index, diabetes, cardiovascular disease, hypertension, and smoking) or the use of anti-inflammatory medications (statins, aspirin, corticosteroids, and nonsteroidal anti-inflammatory drugs), with ulcerated primary melanoma using regression models and subgroup analyses to control for melanoma thickness and mitotic rate. On the basis of information from 194 patients with ulcerated and 593 patients with nonulcerated primary melanomas, regular statin users had lower likelihood of a diagnosis of ulcerated primary melanoma (odds ratio 0.67, 95% confidence interval 0.45-0.99), and this association remained after adjusting for age, sex, thickness, and mitosis. When analysis was limited to melanomas that were ≤2 mm thick and had ≤2 mitoses/mm 2 (40 ulcerated; 289 without ulceration), patients with diabetes had significantly raised odds of diagnosis of ulcerated melanoma (odds ratio 2.90, 95% confidence interval 1.07-7.90), adjusted for age, sex, body mass index, and statin use. These findings support our hypotheses that statin use is inversely associated, and diabetes is positively associated, with ulcerated melanoma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Drew, Mark S.
Cutaneous melanoma is the most life-threatening form of skin cancer. Although advanced melanoma is often considered as incurable, if detected and excised early, the prognosis is promising. Today, clinicians use computer vision in an increasing number of applications to aid early detection of melanoma through dermatological image analysis (dermoscopy images, in particular). Colour assessment is essential for the clinical diagnosis of skin cancers. Due to this diagnostic importance, many studies have either focused on or employed colour features as a constituent part of their skin lesion analysis systems. These studies range from using low-level colour features, such as simple statistical measures of colours occurring in the lesion, to availing themselves of high-level semantic features such as the presence of blue-white veil, globules, or colour variegation in the lesion. This paper provides a retrospective survey and critical analysis of contributions in this research direction. PMID:28096807
Gautam, Diwakar; Ahmed, Mushtaq; Meena, Yogesh Kumar; Ul Haq, Ahtesham
Cancer bears a poisoning threat to human society. Melanoma, the skin cancer, originates from skin layers and penetrates deep into subcutaneous layers. There exists an extensive research in melanoma diagnosis using dermatoscopic images captured through a dermatoscope. While designing a diagnostic model for general handheld imaging systems is an emerging trend, this article proposes a computer-aided decision support system for macro images captured by a general-purpose camera. General imaging conditions are adversely affected by nonuniform illumination, which further affects the extraction of relevant information. To mitigate it, we process an image to define a smooth illumination surface using the multistage illumination compensation approach, and the infected region is extracted using the proposed multimode segmentation method. The lesion information is numerated as a feature set comprising geometry, photometry, border series, and texture measures. The redundancy in feature set is reduced using information theory methods, and a classification boundary is modeled to distinguish benign and malignant samples using support vector machine, random forest, neural network, and fast discriminative mixed-membership-based naive Bayesian classifiers. Moreover, the experimental outcome is supported by hypothesis testing and boxplot representation for classification losses. The simulation results prove the significance of the proposed model that shows an improved performance as compared with competing arts. Copyright © 2017 John Wiley & Sons, Ltd.
Craine, Eric R.; Craine, Brian L.
The recognized incidence of cutaneous malignant melanoma in the United States is now rising faster than any other cancer, increasing by 83% from 1980 to 1987. Recent revelations that depletion of the earth's ozone layer is accelerating at a more rapid rate than previously believed can only exacerbate current projections for the increased incidence of this deadly disease. Because there is no good treatment for metastatic melanoma even small cancers often prove fatal if not detected early. Melanoma allowed to invade the subcutaneous tissue is associated with a five-year survival rate of only 44%. Ironically, few cancers provide a greater opportunity for early discovery and cure. Cutaneous melanoma is not only located where it is readily observed, but typically undergoes a `radial growth' phase prior to metastasis. During this phase the net growth is superficial and circumferential, gradually increasing the area of the lesion and changing its coloration. Screening measures for the early detection of melanoma must concentrate on two primary tasks: (1) detection of lesion changes indicative of the radial growth stage of malignancy and (2) alerting the patient and physician to the existence of a new or changed lesion on the skin. To accomplish these goals we have experimented with the applicability of a microcomputer based video imaging system which stores an image archive of historical reference images for each patient. With the acquisition of new images of the patient, easily registered with the archival images through a technique we have developed we are able to perform a blink comparison of the image pairs. This technique appears to be far more effective than currently used techniques for detecting changed lesions on a comprehensive basis.
van Ginkel, Paul R; Darjatmoko, Soesiawati R; Sareen, Dhruv; Subramanian, Lalita; Bhattacharya, Saswati; Lindstrom, Mary J; Albert, Daniel M; Polans, Arthur S
To test the efficacy of resveratrol, a nontoxic plant product, in the treatment of uveal melanoma. The effect of oral administration and peritumor injection of resveratrol was tested on tumor growth in two animal models of uveal melanoma. The mechanism of resveratrol action on uveal melanoma cells was studied in vitro in a cell-viability assay: with JC-1 dye, to measure mitochondrial membrane potential; by Western blot analysis, to analyze the cellular redistribution of cytochrome c and Smac/diablo; and in a fluorescence assay with specific substrates, to measure activation of different caspases. Resveratrol treatment inhibited tumor growth in animal models of uveal melanoma. Since oral administration resulted in relatively low bioavailability of resveratrol, the effect of increased local levels was tested by peritumor injection of the drug. This method resulted in tumor cell death and tumor regression. In vitro experiments with multiple uveal melanoma cell lines demonstrate that resveratrol causes a decrease in cell viability, resulting at least in part from an increase in apoptosis through a mitochondrial pathway. An early event in drug action is the direct targeting of mitochondria by resveratrol, which leads to a decrease in mitochondrial membrane potential and the eventual activation of caspase-3. These data suggest that resveratrol can inhibit tumor growth and can induce apoptosis via the intrinsic mitochondrial pathway and that by further increasing bioavailability of resveratrol the potency of the drug can be increased, leading to tumor regression. The nontoxic nature of the drug at levels needed for therapy make resveratrol an attractive candidate for the treatment of uveal melanoma.
Ramji, Rajan; Valdes-Gonzalez, Guillermo; Oakley, Amanda; Rademaker, Marius
To describe the dermoscopic features of melanoma in situ using the Chaos and Clues method. Histologically proven primary melanoma in situ (MIS) diagnosed through a specialist teledermoscopy clinic were reviewed by three dermatologists. By consensus they agreed on the global dermoscopic pattern, colours, presence of chaos (asymmetry of colour and structure and more than one pattern), and each of the nine clues described for malignancy. One hundred MIS in 92 patients of European ethnicity (45 males) were assessed. Mean age was 67.3 years (range 20-95). The mean dimensions of the lesions were 11.1 × 12.0 mm (range 2.5-31.3 × 2.3-32.3 mm). Using pattern analysis, 82% of the lesions had three or more patterns (multicomponent) and the rest had 2 patterns. Colours included light brown (100%), dark brown (98%) and grey (75%). All MIS demonstrated chaos. The most prevalent clues were thick lines (88%), eccentric structureless areas (88%), and grey or blue structures (75%). Dermoscopy can be very helpful in the early diagnosis of melanoma and MIS. The Chaos and Clues method is simple to use. Its unambiguous descriptors can be successfully used to describe MIS. The presence of chaos and clues to malignancy (including thick lines, eccentric structureless areas, and blue/grey structures) should raise a red flag and lead to referral or excision. © 2017 The Australasian College of Dermatologists.
Glotsos, Dimitris; Kostopoulos, Spiros; Lalissidou, Stella; Sidiropoulos, Konstantinos; Asvestas, Pantelis; Konstandinou, Christos; Xenogiannopoulos, George; Konstantina Nikolatou, Eirini; Perakis, Konstantinos; Bouras, Thanassis; Cavouras, Dionisis
The purpose of this study was to design a decision support system for assisting the diagnosis of melanoma in dermatoscopy images. Clinical material comprised images of 44 dysplastic (clark's nevi) and 44 malignant melanoma lesions, obtained from the dermatology database Dermnet. Initially, images were processed for hair removal and background correction using the Dull Razor algorithm. Processed images were segmented to isolate moles from surrounding background, using a combination of level sets and an automated thresholding approach. Morphological (area, size, shape) and textural features (first and second order) were calculated from each one of the segmented moles. Extracted features were fed to a pattern recognition system assembled with the Probabilistic Neural Network Classifier, which was trained to distinguish between benign and malignant cases, using the exhaustive search and the leave one out method. The system was designed on the GPU card (GeForce 580GTX) using CUDA programming framework and C++ programming language. Results showed that the designed system discriminated benign from malignant moles with 88.6% accuracy employing morphological and textural features. The proposed system could be used for analysing moles depicted on smart phone images after appropriate training with smartphone images cases. This could assist towards early detection of melanoma cases, if suspicious moles were to be captured on smartphone by patients and be transferred to the physician together with an assessment of the mole's nature.
Oka, Hiroshi; Tanaka, Masaru; Kobayashi, Seiichiro; Argenziano, Giuseppe; Soyer, H Peter; Nishikawa, Takeji
As a first step to develop a screening system for pigmented skin lesions, we performed digital discriminant analyses between early melanomas and Clark naevi. A total of 59 cases of melanoma, including 23 melanoma in situ and 36 thin invasive melanomas (Breslow thickness < or =0.75 mm), and 188 clinically equivocal, histopathologically diagnosed Clark naevi were used in our study. After calculating 62 mathematical variables related to the colour, texture, asymmetry and circularity based on the dermoscopic findings of the pigmented skin lesions, we performed multivariate stepwise discriminant analysis using these variables to differentiate melanomas from naevi. The sensitivities and specificities of our model were 94.4 and 98.4%, respectively, for discriminating between melanomas (Breslow thickness < or =0.75 mm) and Clark naevi, and 73.9 and 85.6%, respectively, for discriminating between melanoma in situ and Clark naevi. Our algorithm accurately discriminated invasive melanomas from Clark naevi, but not melanomas in situ from Clark naevi.
Rajaram, Narasimhan; Reichenberg, Jason S; Migden, Michael R; Nguyen, Tri H; Tunnell, James W
Several research groups have demonstrated the non-invasive diagnostic potential of diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques for early cancer detection. By combining both modalities, one can simultaneously measure quantitative parameters related to the morphology, function and biochemical composition of tissue and use them to diagnose malignancy. The objective of this study was to use a quantitative reflectance/fluorescence spectroscopic technique to determine the optical properties of normal skin and non-melanoma skin cancers and the ability to accurately classify them. An additional goal was to determine the ability of the technique to differentiate non-melanoma skin cancers from normal skin. The study comprised 48 lesions measured from 40 patients scheduled for a biopsy of suspected non-melanoma skin cancers. White light reflectance and laser-induced fluorescence spectra (wavelength range = 350-700 nm) were collected from each suspected lesion and adjacent clinically normal skin using a custom-built, optical fiber-based clinical instrument. After measurement, the skin sites were biopsied and categorized according to histopathology. Using a quantitative model, we extracted various optical parameters from the measured spectra that could be correlated to the physiological state of tissue. Scattering from cancerous lesions was significantly lower than normal skin for every lesion group, whereas absorption parameters were significantly higher. Using numerical cut-offs for our optical parameters, our clinical instrument could classify basal cell carcinomas with a sensitivity and specificity of 94% and 89%, respectively. Similarly, the instrument classified actinic keratoses and squamous cell carcinomas with a sensitivity of 100% and specificity of 50%. The measured optical properties and fluorophore contributions of normal skin and non-melanoma skin cancers are significantly different from each other and correlate well
Karagiannis, Georgios; Apostolidis, Georgios; Georgoulias, Panagiotis
Melanoma is a very malicious type of cancer as it metastasizes early and hence its late diagnosis leads to death. Consequently, early diagnosis of melanoma and its removal is considered the most effective way of treatment. We present a design of a high frequency acoustic microscopy and infrared reflectance system for the early detection of melanoma. Specifically, the identification of morphological changes related to carcinogenesis is required. In this work, we simulate of the propagation of the ultrasonic waves of the order of 100 MHz as well as of electromagnetic waves of the order of 100 THz in melanoma structures targeting to the estimation and optimization of the basic characteristics of the systems. The simulation results of the acoustic microscopy subsystem aim to provide information such as the geometry of the transducer, the center frequency of operation, the focal length where the power transmittance is optimum and the spot size in focal length. As far as the infrared is concerned the optimal frequency range and the spot illumination size of the external probe is provided. This information is next used to assemble a properly designed system which is applied to melanoma phantoms as well as real skin lesions. Finally, the measurement data are visualized to reveal the information of the experimented structures, proving noteworthy accuracy.
Hill, David S; Robinson, Neil D P; Caley, Matthew P; Chen, Mei; O’Toole, Edel A; Armstrong, Jane L; Przyborski, Stefan; Lovat, Penny E
Metastatic melanoma remains incurable, emphasising the acute need for improved research models to investigate the underlying biological mechanisms mediating tumour invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully-humanised 3D skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumour invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth phase melanoma invasion. PMID:26330548
Sladden, Michael J; Nieweg, Omgo E; Howle, Julie; Coventry, Brendon J; Thompson, John F
Definitive management of primary cutaneous melanoma consists of surgical excision of the melanoma with the aim of curing the patient. The melanoma is widely excised together with a safety margin of surrounding skin and subcutaneous tissue, after the diagnosis and Breslow thickness have been established by histological assessment of the initial excision biopsy specimen. Sentinel lymph node biopsy should be discussed for melanomas ≥ 1 mm thickness (≥ 0.8 mm if other high risk features) in which case lymphoscintigraphy must be performed before wider excision of the primary melanoma site. The 2008 evidence-based clinical practice guidelines for the management of melanoma (http://www.cancer.org.au/content/pdf/HealthProfessionals/ClinicalGuidelines/ClinicalPracticeGuidelines-ManagementofMelanoma.pdf) are currently being revised and updated in a staged process by a multidisciplinary working party established by Cancer Council Australia. The guidelines for definitive excision margins for primary melanomas have been revised as part of this process. Main recommendations: The recommendations for definitive wide local excision of primary cutaneous melanoma are: melanoma in situ: 5-10 mm margins invasive melanoma (pT1) ≤ 1.0 mm thick: 1 cm margins invasive melanoma (pT2) 1.01-2.00 mm thick: 1-2 cm margins invasive melanoma (pT3) 2.01-4.00 mm thick: 1-2 cm margins invasive melanoma (pT4) > 4.0 mm thick: 2 cm margins Changes in management as a result of the guideline: Based on currently available evidence, excision margins for invasive melanoma have been left unchanged compared with the 2008 guidelines. However, melanoma in situ should be excised with 5-10 mm margins, with the aim of achieving complete histological clearance. Minimum clearances from all margins should be assessed and stated. Consideration should be given to further excision if necessary; positive or close histological margins are unacceptable.
Liu, Zhao; Zerubia, Josiane
The presence of illumination variation in dermatological images has a negative impact on the automatic detection and analysis of cutaneous lesions. This paper proposes a new illumination modeling and chromophore identification method to correct lighting variation in skin lesion images, as well as to extract melanin and hemoglobin concentrations of human skin, based on an adaptive bilateral decomposition and a weighted polynomial curve fitting, with the knowledge of a multi-layered skin model. Different from state-of-the-art approaches based on the Lambert law, the proposed method, considering both specular reflection and diffuse reflection of the skin, enables us to address highlight and strong shading effects usually existing in skin color images captured in an uncontrolled environment. The derived melanin and hemoglobin indices, directly relating to the pathological tissue conditions, tend to be less influenced by external imaging factors and are more efficient in describing pigmentation distributions. Experiments show that the proposed method gave better visual results and superior lesion segmentation, when compared to two other illumination correction algorithms, both designed specifically for dermatological images. For computer-aided diagnosis of melanoma, sensitivity achieves 85.52% when using our chromophore descriptors, which is 8~20% higher than those derived from other color descriptors. This demonstrates the benefit of the proposed method for automatic skin disease analysis.
... flat or raised, large or small, light or dark, and can appear anywhere on our bodies. Sometimes, ... can still get melanoma even if they're dark skinned, young, and have no family history. Even ...
Spinks, Jean; Janda, Monika; Soyer, H Peter; Whitty, Jennifer A
'Store and forward' teledermoscopy is a technology with potential advantages for melanoma screening. Any large-scale implementation of this technology is dependent on consumer acceptance. To investigate preferences for melanoma screening options compared with skin self-examination in adults considered to be at increased risk of developing skin cancer. A discrete choice experiment was completed by 35 consumers, all of whom had prior experience with the use of teledermoscopy, in Queensland, Australia. Participants made 12 choices between screening alternatives described by seven attributes including monetary cost. A mixed logit model was used to estimate the relative weights that consumers place on different aspects of screening, along with the marginal willingness to pay for teledermoscopy as opposed to screening at a clinic. Overall, participants preferred screening/diagnosis by a health professional rather than skin self-examination. Key drivers of screening choice were for results to be reviewed by a dermatologist; a higher detection rate; fewer non-cancerous moles being removed in relation to every skin cancer detected; and less time spent away from usual activities. On average, participants were willing to pay AUD110 to have teledermoscopy with dermatologist review available to them as a screening option. Consumers preferentially value aspects of care that are more feasible with a teledermoscopy screening model, as compared with other skin cancer screening and diagnosis options. This study adds to previous literature in the area which has relied on the use of consumer satisfaction scales to assess the acceptability of teledermoscopy. © The Author(s) 2015.
Thomas, Luc; Puig, Susana
Early detection is a key strategy for reducing the mortality and economic burden associated with melanoma. Dermoscopy is a non-invasive and cost-effective tool for melanoma diagnosis, which has been shown to be a reliable and sensitive method for detecting early-stage skin cancer and reducing the number of unnecessary excisions. Patients at high risk of developing melanoma require long-term surveillance. Use of digital dermoscopy follow-up of these patients has led to improved outcomes. Combined follow-up programmes using total-body photography and digital dermoscopy have led to further improvements in early diagnosis and diagnostic accuracy. Dermoscopy is now widely used by dermatologists, but the public health impact of this tool is yet to be evaluated. Despite the clear advantages of dermoscopy and digital follow-up meth-ods, dermoscopy training and access to digital dermoscopy among dermatologists and general practitioners needs to be improved.
Becker, Georg; Müller, Antje; Braune, Stefan; Büttner, Thomas; Benecke, Reiner; Greulich, Wolfgang; Klein, Wolfgang; Mark, Günter; Rieke, Jürgen; Thümler, Reiner
In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an 'advanced stage' of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection. The discovery of several genetic mutations associated with IPD raises the possibility that these, or other biomarkers, of the disease may help to identify persons at risk of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related to an increased iron load of the substantia nigra. In the early clinical phase, a number of motor and particularly non-motor signs emerge, which can be identified by the patients and physicians years before the diagnosis is made, notably olfactory dysfunction, depression, or 'soft' motor signs such as changes in handwriting, speech or reduced ambulatory arm motion. These signs of the early, prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer tests. As one single instrument will not be sensitive enough, a battery of tests has to be composed measuring independent parameters of the incipient disease. Subjects with abnormal findings in this test battery should than be submitted to nuclear medicine examinations to quantify the extent of dopaminergic injury and to reach the goal of a reliable, early diagnosis.
Glossmann, Jan-Peter; Skoetz, Nicole; Starbatty, Barbara; Bischoff, Martina; Leyvraz, Serge; Westekemper, Henrike; Heindl, Ludwig M
In cases of rare cancer entities, such as malignant melanoma of the conjunctiva, there are often no evidence-based national guidelines available. Standard operating procedures (SOP) are an alternative in these cases. The aim of this project was to develop a consensus SOP for diagnosis, treatment, and follow-up care of conjunctival melanomas between the 14 Centers of Excellence in Germany supported by German Cancer Aid. The SOP was prepared according to a defined process including timelines, flow of information, and roles. This is the first consensus SOP of the Centers of Excellence in Germany (certified by the German Cancer Aid) regarding diagnosis, treatment, and follow-up for malignant melanomas of the conjunctiva.
Klotz, Barbara; Kneitz, Susanne; Regensburger, Martina; Hahn, Lena; Dannemann, Michael; Kelso, Janet; Nickel, Birgit; Lu, Yuan; Boswell, William; Postlethwait, John; Warren, Wesley; Kunz, Manfred; Walter, Ronald B; Schartl, Manfred
Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown. To contribute to a better understanding of the molecular processes of melanoma formation, we use a transgenic medaka melanoma model that is well suited for the investigation of melanoma tumor development because fish and human melanocytes are both localized in the epidermis. The purpose of our study was to gain insights into melanoma development from the first steps of tumor formation up to melanoma progression and to identify gene expression patterns that will be useful for monitoring treatment effects in drug screening approaches. Comparing transcriptomes from juvenile fish at the tumor initiating stage with nevi and advanced melanoma of adults, we identified stage specific expression signatures and pathways that are characteristic for the development of medaka melanoma, and are also found in human malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.
Murali, Rajmohan; Doubrovsky, Anna; Watson, Geoffrey F; McKenzie, Paul R; Lee, C Soon; McLeod, Duncan J; Uren, Roger F; Stretch, Jonathan R; Saw, Robyn P M; Thompson, John F; Scolyer, Richard A
Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such asfibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost-effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases.
Ow, Thomas J; Grethlein, Sara Jo; Schmalbach, Cecelia E
The following article is the next installment of the series "Do You Know Your Guidelines?" presented by the Education Committee of the American Head and Neck Society. Guidelines for the prevention, diagnosis, workup, and management of cutaneous melanoma are reviewed in an evidence-based fashion. © 2018 Wiley Periodicals, Inc.
Belics, Zoran; Gérecz, Balázs; Csákány, M György
Ectopic pregnancy is a high-risk condition that occurs in 2% of reported pregnancies. This percentage is fivefold higher than that registered in the 1970s. Since 1970 there has been a two-fold increase in the ratio of ectopic pregnancies to all reported pregnancies in Hungary and in 2012 7.4 ectopic pregnancies per thousand registered pregnancies were reported. Recently, the majority (80%) of cases can be diagnosed in early stage, and the related mortality objectively decreased in the past few decades to 3.8/10,000 ectopic pregnancies. If a woman with positive pregnancy test has abdominal pain and/or vaginal bleeding the physician should perform a work-up to safely exclude the possibility of ectopic pregnancy. The basis of diagnosis is ultrasonography, especially vaginal ultrasound examination and measurement of the β-subunit of human chorionic gonadotropin. The ultrasound diagnosis is based on the visualization of an ectopic mass rather than the inability to visualize an intrauterine pregnancy. In some questionable cases the diagnostic uterine curettage or laparoscopy may be useful. The actuality of this topic is justified by practical difficulties in obtaining correct diagnosis, especially in the early gestational time.
Ferris, Laura K.; Harris, Ryan J.
Synopsis Detection of melanoma at an early stage is crucial to improving survival rates in melanoma. Accurate diagnosis by current techniques including dermatoscopy remains difficult, and new tools are needed to improve our diagnostic abilities. This article discusses recent advances in diagnostic techniques including confocal scanning laser microscopy, MelaFind, Siascopy, noninvasive genomic detection, as well as other future possibilities to aid in diagnosing melanoma. Advantages and barriers to implementation of the various technologies are discussed as well. PMID:22800557
Corrias, Maria Valeria; Levreri, Isabella; Scaruffi, Paola; Raffaghello, Lizzia; Carlini, Barbara; Bocca, Paola; Prigione, Ignazia; Stigliani, Sara; Amoroso, Loredana; Ferrone, Soldano; Pistoia, Vito
The high molecular weight melanoma-associated antigen (HMW-MAA) and the cytoplasmic melanoma-associated antigen (cyt-MAA/LGALS3BP) are expressed in melanoma. Their serum levels are increased in melanoma patients and correlate with clinical outcome. We investigated whether these molecules can serve as prognostic markers for neuroblastoma (NB) patients. Expression of cyt-MAA and HMW-MAA was evaluated by flow cytometry in NB cell lines, patients’ neuroblasts (FI-NB), and short-term cultures of these latter cells (cNB). LGALS3BP gene expression was evaluated by RT–qPCR on FI-NB, cNB, and primary tumor specimens. Soluble HMW-MAA and cyt-MAA were tested by ELISA. Cyt-MAA and HMW-MAA were expressed in NB cell lines, cNB, and FI-NB samples. LGALS3BP gene expression was higher in primary tumors and cNB than in FI-NB samples. Soluble cyt-MAA, but not HMW-MAA, was detected in NB cell lines and cNBs supernatants. NB patients’ serum levels of both antigens were higher than those of the healthy children. High cyt-MAA serum levels at diagnosis associated with higher incidence of relapse, independently from other known risk factors. In conclusion, both HMW-MAA and cyt-MAA antigens, and LGALS3BP gene, were expressed by NB cell lines and patients’ neuroblasts, and both antigens’ serum levels were increased in NB patients. Elevated serum levels of cyt-MAA at diagnosis correlated with relapse, supporting that cyt-MAA may serve as early serological biomarker to individuate patients at higher risk of relapse that may require a more careful follow-up, after being validated in a larger cohort of patients at different time-points during follow-up. Given its immunogenicity, cyt-MAA may also be a potential target for NB immunotherapy. PMID:21660451
McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R
Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.
Rajpara, S M; Botello, A P; Townend, J; Ormerod, A D
Dermoscopy improves diagnostic accuracy of the unaided eye for melanoma, and digital dermoscopy with artificial intelligence or computer diagnosis has also been shown useful for the diagnosis of melanoma. At present there is no clear evidence regarding the diagnostic accuracy of dermoscopy compared with artificial intelligence. To evaluate the diagnostic accuracy of dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis and to compare the diagnostic accuracy of the different dermoscopic algorithms with each other and with digital dermoscopy/artificial intelligence for the detection of melanoma. A literature search on dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis was performed using several databases. Titles and abstracts of the retrieved articles were screened using a literature evaluation form. A quality assessment form was developed to assess the quality of the included studies. Heterogeneity among the studies was assessed. Pooled data were analysed using meta-analytical methods and comparisons between different algorithms were performed. Of 765 articles retrieved, 30 studies were eligible for meta-analysis. Pooled sensitivity for artificial intelligence was slightly higher than for dermoscopy (91% vs. 88%; P = 0.076). Pooled specificity for dermoscopy was significantly better than artificial intelligence (86% vs. 79%; P < 0.001). Pooled diagnostic odds ratio was 51.5 for dermoscopy and 57.8 for artificial intelligence, which were not significantly different (P = 0.783). There were no significance differences in diagnostic odds ratio among the different dermoscopic diagnostic algorithms. Dermoscopy and artificial intelligence performed equally well for diagnosis of melanocytic skin lesions. There was no significant difference in the diagnostic performance of various dermoscopy algorithms. The three-point checklist, the seven-point checklist and Menzies score had better diagnostic odds ratios than the
Castro, Luiz Guilherme Martins; Bakos, Renato Marchiori; Duprat Neto, João Pedreira; Bittencourt, Flávia Vasques; Giacomo, Thais Helena Bello Di; Serpa, Sérgio Schrader; Messina, Maria Cristina de Lorenzo; Loureiro, Walter Refkalefsky; Macarenco, Ricardo Silvestre e Silva; Stolf, Hamilton Ometto; Gontijo, Gabriel
The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed? PMID:26982779
Mun, J-H; Kim, G-W; Jwa, S-W; Song, M; Kim, H-S; Ko, H-C; Kim, B-S; Kim, M-B
Subungual haemorrhages are characterized by well-circumscribed dots or blotches with a red to red-black pigmentation, but some cases can be difficult to distinguish from subungual melanoma by the naked eye alone. Dermoscopy has proven to be a useful, noninvasive tool in the diagnosis of pigmented lesions in the nail; however, few dermoscopic studies of subungual haemorrhages have been reported. To investigate characteristic dermoscopic patterns of subungual haemorrhages, and to find distinctive features that can differentiate them from nail-unit melanomas. Patients with a confirmed diagnosis of either subungual haemorrhage or nail-unit melanoma at a tertiary university hospital were included in the study. Clinical features and dermoscopic patterns were evaluated. Sixty-four patients with a total of 90 lesions of subungual haemorrhage were enrolled in the study. The majority of cases (84%) showed combinations of more than one colour, while 16% had only one colour. The most common colour of the subungual haemorrhages was purple-black, in 37% of cases. A homogeneous pattern was observed in 92% of cases, globular patterns in 42% and streaks in 39%. Peripheral fading and periungual haemorrhages were found in 54% and 22% of cases, respectively. Destruction or dystrophy of the nail plate was observed in 16% of cases. In the 16 cases of nail-unit melanomas, Hutchinson sign, longitudinal irregular bands or lines, triangular shape of bands, vascular pattern, and ulcerations were found in 100%, 81%, 25%, 6% and 81% of cases, respectively. In contrast, these features were not found in subungual haemorrhages. Dermoscopy provides valuable information for the diagnosis of subungual haemorrhage and aids in the differential diagnosis from nail-unit melanoma. © 2013 The Authors. BJD © 2013 British Association of Dermatologists.
Dominiak, Nicole R; Wick, Mark R; Smith, M Timothy
Melanoma of the skin is the fifth leading new cancer diagnosis, having accounted for almost 77,000 cases and more than 9000 deaths in the United States in 2013. Although cutaneous neoplasms of this type are relatively common, their mucosal counterparts are not. Mucosal melanomas comprise approximately 1.3% of all melanocytic malignancies. Although they are rare, these lesions present at an advanced stage with more adverse prognoses. In addition, at a molecular level, they have proven to be distinct entities because they possess genetic mutations not usually seen in their cutaneous counterparts. Conversely, a sizable proportion of mucosal melanomas lack the gene aberrations seen in cutaneous melanomas. Such findings indicate different pathways in tumorigenesis for the two subtypes. Because melanomas arising from the mucosae are not often encountered, very little has been published on staging guidelines and prognostic factors. This causes dilemmas for both patients and physicians. Further work is necessary to define staging systems for all mucosal locations, so that accurate prognoses can be assigned to such lesions. Copyright © 2016 Elsevier Inc. All rights reserved.
Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.
Abstract. The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device. PMID:25375350
Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.
The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%;/100%;, for SCC and BCC versus AK (57 versus 14 lesions) was 95%;/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.
Shields, J.A.; Hagler, W.S.; Federman, J.L.
Several reports in the ophthalmic literature have emphasized the difficulties which may occur in the clinical diagnosis of malignant melanomas of the posterior uvea. As a result of such difficulties, the radioactive phosphorus uptake test (/sup 32/P) was introduced into ophthalmology a number of years ago as a diagnostic adjunct. One of the early problems encountered by physicians utilizing this test was the inability to localize accurately and place the probe over lesions in the posterior segment of the globe. Although certain investigators attempted to use a conjunctival incision and curved probe for gaining access to these posterior lesions, themore » test eventually fell into disfavor. Between 1965 and 1970, articles on this test became scarce in the ophthalmic literature. In 1970, Hagler et al. reintroduced the test into ophthalmology with emphasis on careful localization of the lesion with indirect ophthalmoscopy, a conjunctival incision, and a curved probe for evaluating posteriorly located lesions. Subsequently, the test has enjoyed increasing popularity and is now being utilized with enthusiasm in a number of centers.« less
Castro, Luiz Guilherme Martins; Messina, Maria Cristina; Loureiro, Walter; Macarenco, Ricardo Silvestre; Duprat Neto, João Pedreira; Giacomo, Thais Helena Bello Di; Bittencourt, Flávia Vasques; Bakos, Renato Marchiori; Serpa, Sérgio Schrader; Stolf, Hamilton Ometto; Gontijo, Gabriel
The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute to diagnosis and treatment of primary cutaneous melanoma? What margins should be used to treat lentigo maligna melanoma and melanoma in situ? PMID:26734867
Selchuk, V. Y.; Rodionova, O. V.; Sukhova, O. G.; Polyakov, E. V.; Grebennikova, O. P.; Burov, D. A.; Emelianova, G. S.
The method of building of information systems for the diagnosis of skin melanoma is described in the presented work. Malignant tumors at the level of macro - and microimages in combination with clinical data are investigated. The development is made with the use of MySQL. An information system is a result of joint activities of the National research nuclear University “MEPhI” (Moscow Engineering Physics Institute) with N. N. Blokhin Russian Cancer Scientific Center.
Campagne, Cécile; Julé, Sophia; Bernex, Florence; Estrada, Mercedes; Aubin-Houzelstein, Geneviève; Panthier, Jean-Jacques; Egidy, Giorgia
Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses. Using immunofluorescence, we report here that both MITF (Microphthalmia-associated transcription factor) and PAX3 (Paired box 3) allow the identification of melanocytic cells in horse skin samples. Importantly, RACK1 was detected in melanocytic lesions but not in healthy skin melanocytes. Finally, we found that RACK1 labeling can be used in horses to distinguish benign melanocytic tumors from melanomas. Indeed, RACK1 labeling appeared more informative to assess malignancy than individual histomorphological features. This study confirms that horses provide an interesting model for melanoma genesis studies. It establishes MITF and PAX3 as markers of horse melanocytic cells. RACK1 emerges as an important marker of malignancy which may contribute to progress in the diagnosis of melanomas in both human and veterinary medicine.
Background Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses. Results Using immunofluorescence, we report here that both MITF (Microphthalmia-associated transcription factor) and PAX3 (Paired box 3) allow the identification of melanocytic cells in horse skin samples. Importantly, RACK1 was detected in melanocytic lesions but not in healthy skin melanocytes. Finally, we found that RACK1 labeling can be used in horses to distinguish benign melanocytic tumors from melanomas. Indeed, RACK1 labeling appeared more informative to assess malignancy than individual histomorphological features. Conclusions This study confirms that horses provide an interesting model for melanoma genesis studies. It establishes MITF and PAX3 as markers of horse melanocytic cells. RACK1 emerges as an important marker of malignancy which may contribute to progress in the diagnosis of melanomas in both human and veterinary medicine. PMID:22747534
Zhang, Yuqian; Yang, Dongliang; Weng, Lixing; Wang, Lianhui
Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. PMID:23892596
Saunders, Richard A; Killick, Rowena S; Barrows, Michelle G; Bowlt, Kelly A; Denk, Daniella
Dermal melanocytic neoplasms are common in some even-toed ungulates (Artiodactyla), yet this entity has not been reported in the pygmy hippopotamus to date. Concurrent occurrence of multiple benign and malignant melanocytic neoplasms is unusual. Malignant transformation occurs in a small percentage of benign melanocytic tumours in people but this phenomenon has not been well documented in animals. To report the diagnosis and treatment of concurrent dermal melanocytomas and malignant melanomas in a pygmy hippopotamus. A 36-year-old intact male pygmy hippopotamus, part of a zoological collection, housed with a 10-year-old female of the same species, presented with multiple raised and pigmented skin masses. Initial impression smears of one ulcerated lesion were consistent with inflammation; subsequent histopathological findings from a skin biopsy revealed an underlying malignant melanoma. The animal was anaesthetised, ultrasonographic imaging of the local lymph nodes indicated no local involvement and all skin lesions were removed. Recovery from anaesthesia was unremarkable, skin healing was within normal limits for the species. There was no sign of recurrence 34 months post-surgery. A diagnosis of malignant melanomas and concurrent melanocytomas was made on histopathological evaluation. To the best of the authors' knowledge, this is the first reported case of melanocytic neoplasia in the pygmy hippopotamus. The occurrence of both benign and malignant melanocytic skin tumours should be considered in this species. © 2017 ESVD and ACVD.
Garnavi, Rahil; Aldeen, Mohammad; Bailey, James
This paper presents a novel computer-aided diagnosis system for melanoma. The novelty lies in the optimised selection and integration of features derived from textural, borderbased and geometrical properties of the melanoma lesion. The texture features are derived from using wavelet-decomposition, the border features are derived from constructing a boundaryseries model of the lesion border and analysing it in spatial and frequency domains, and the geometry features are derived from shape indexes. The optimised selection of features is achieved by using the Gain-Ratio method, which is shown to be computationally efficient for melanoma diagnosis application. Classification is done through the use of four classifiers; namely, Support Vector Machine, Random Forest, Logistic Model Tree and Hidden Naive Bayes. The proposed diagnostic system is applied on a set of 289 dermoscopy images (114 malignant, 175 benign) partitioned into train, validation and test image sets. The system achieves and accuracy of 91.26% and AUC value of 0.937, when 23 features are used. Other important findings include (i) the clear advantage gained in complementing texture with border and geometry features, compared to using texture information only, and (ii) higher contribution of texture features than border-based features in the optimised feature set.
Robinson, June K.; Wayne, Jeffrey D.; Martini, Mary C.; Hultgren, Brittney A.; Mallett, Kimberly A.; Turrisi, Rob
IMPORTANCE More than 1 million patients with melanoma in the United States are at risk to develop a second primary melanoma. Early detection of melanoma improves survival. Patients with melanoma may be able to self-manage care with their skin-check partners (“partners”) and alert the physician when a concerning lesion is identified, thus providing an important adjunct to yearly skin examinations by a physician. OBJECTIVE To evaluate the effect of a structured skin self-examination (SSE) intervention for patients with melanoma and their partners (“dyads”) on SSE performance and the detection of new melanomas by the dyad or the physician. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial with 24-month follow-up assessments. Patients with stage 0 to IIB melanoma and their skin-check partners participated from June 6, 2011, to April 24, 2015. INTERVENTIONS Dyads of patients and their partners were randomly assigned to receive the skills training intervention or customary care (control group). MAIN OUTCOMES AND MEASURES The main outcome was frequency of SSE performance. The secondary outcome was detection of a new or recurrent melanoma by the dyad or physician. The tertiary outcome was the number of unscheduled physician appointments for concerning lesions. RESULTS The study cohort comprised 494 participants. The patient population was 51.2% (253 of 494) female and had a mean (SD) age of 55 (10) years. Patients in the intervention arms had significantly increased SSEs with their partners at 4, 12, and 24 months (P < .001 for all) compared with the control group (mean differences, 1.57 [95% CI, 1.29–1.85], 0.72 [95% CI, 0.39–1.06], and 0.94 [95% CI, 0.58–1.30], respectively). Patients in the intervention arms identified new melanomas more than those in the control group ( χ12=28.77, P < .01 [n = 51 melanomas in situ] and χ12=6.43, P < .05 [n = 18 invasive melanomas]) and did not increase physician visits. CONCLUSIONS AND RELEVANCE Patients with
Shields, J.A.; Packer, S.
The most frequently used radioisotope in ophthalmology is radioactive phosphorus (/sup 32/P). Since its introduction into ophthalmology in 1951, it has been used primarily as an aid in the diagnosis of malignant melanoma of the choroid. During the thirty years of clinical use, the indications for this test have been clearly defined. The maximum tissue penetration of /sup 32/P is 7 mm. Surgical dissection is therefore frequently necessary to enable the ophthalmologist to place the Geiger-Muller probe on the sclera in proximity to the tumor. False positive and false negative results are unusual and the test is between 96% andmore » 100% accurate.« less
Gallegos-Hernández, José Francisco; Ortiz-Maldonado, Alma Lilia; Minauro-Muñoz, Gerardo Gabriel; Arias-Ceballos, Héctor; Hernández-Sanjuan, Martín
The mortality of cutaneous melanoma has not declined over the past 50 years. The only interventions that can reduce mortality are primary prevention and early diagnosis, and the dermoscopic evaluation is essential to achieve this. Dermoscopy identifies characteristics of melanoma that would go unnoticed to the naked eye. The aim of this paper is to report the most frequent dermoscopic findings in patients diagnosed with in situ and invasive melanoma. An observational and retrospective study of contact dermoscopy was performed using LED DermliteTM and camera DermliteTM dermoscope. The findings evaluated were: asymmetry in two axes, association of colours, lack of pigment, irregular points, atypical network, pseudopods, blue veil, ulceration, and peri-lesional pink ring. These dermoscopic findings were compared with the histological diagnosis. The study included 65 patients with cutaneous melanoma; 10 in situ, and 55 invasive. The mean Breslow in invasive melanoma was 3 mm. Most patients (35) had localization in extremities. In all patients, the most frequent dermoscopic finding was asymmetry in two axes, followed by association of two or more colours; in melanoma in situ, asymmetry was the most frequent, followed by atypical-irregular points. In invasive melanoma asymmetry in two axes, the association of two or more colours, and pseudopods, were the most frequent findings. Asymmetry in two axes is the most common dermoscopic finding in in situ and invasive melanoma. The presence of two or more colours in a pigmented lesion should be suspected in an invasive melanoma. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
Ballester Sánchez, R; de Unamuno Bustos, B; Navarro Mira, M; Botella Estrada, R
Mucosal melanoma is a rare melanoma subtype that differs from the cutaneous form of the tumor in its biology, clinical manifestations, and management. Diagnosis is usually late due to a lack of early or specific signs and the location of lesions in areas that are difficult to access on physical examination. Surgical excision is the treatment of choice for localized disease. The value of sentinel lymph node biopsy and lymphadenectomy is still unclear. Radiotherapy can be used as adjuvant therapy for the control of local disease. c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.
Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.
Steeil, James C; Schumacher, Juergen; Baine, Katherine; Ramsay, Edward C; Sura, Patricia; Hodshon, Rebecca; Donnell, Robert L; Lee, Nathan D
A 13-yr-old intact male African lion (Panthera leo) presented with a 4-mo history of left maxillary lip swelling. On physical examination, a 10-cm-diameter, ulcerated, round, firm, and pigmented mass at the level of the left maxillary canine tooth was noticed. All other organ systems examined were within normal limits. Multiple biopsies of the mass were collected and fixed in 10% neutral buffered formalin. Histopathologic evaluation of the biopsies revealed a malignant dermal melanoma. Hematologic and plasma biochemical parameters were within normal reference ranges. Thoracic radiographs taken 3 days following initial presentation showed no evidence of metastasis of the tumor. Computed tomography of the skull and neck was performed to evaluate local tumor invasion and to plan for hypofractionated radiation therapy. Therapy included four weekly treatments of 8 gray external-beam hypofractionated radiation and four bimonthly immunotherapy treatments. Following this treatment regime, the tumor size was reduced by 50%, and surgical excision was performed. No major side effects associated with radiation or immunotherapy were seen. Six months after diagnosis, hematologic and plasma biochemical parameters were within normal limits, thoracic radiographs showed no evidence of metastasis, and the lion showed no clinical signs of disease. The lion will continue to receive immunotherapy every 6 mo for the rest of its life. To the authors' knowledge, this is the first report of a successful treatment of a malignant dermal melanoma with external-beam hypofractionated radiation, immunotherapy, and surgical excision in an African lion.
Liu, Zhao; Sun, Jiuai; Smith, Lyndon; Smith, Melvyn; Warr, Robert
Computerised analysis on skin lesion images has been reported to be helpful in achieving objective and reproducible diagnosis of melanoma. In particular, asymmetry in shape, colour and structure reflects the irregular growth of melanin under the skin and is of great importance for diagnosing the malignancy of skin lesions. This paper proposes a novel asymmetry analysis based on a newly developed pigmentation elevation model and the global point signatures (GPSs). Specifically, the pigmentation elevation model was first constructed by computer-based analysis of dermoscopy images, for the identification of melanin and haemoglobin. Asymmetry of skin lesions was then assessed through quantifying distributions of the pigmentation elevation model using the GPSs, derived from a Laplace-Beltrami operator. This new approach allows quantifying the shape and pigmentation distributions of cutaneous lesions simultaneously. Algorithm performance was tested on 351 dermoscopy images, including 88 malignant melanomas and 263 benign naevi, employing a support vector machine (SVM) with tenfold cross-validation strategy. Competitive diagnostic results were achieved using the proposed asymmetry descriptor only, presenting 86.36 % sensitivity, 82.13 % specificity and overall 83.43 % accuracy, respectively. In addition, the proposed GPS-based asymmetry analysis enables working on dermoscopy images from different databases and is approved to be inherently robust to the external imaging variations. These advantages suggested that the proposed method has good potential for follow-up treatment.
Dvořánková, Barbora; Szabo, Pavol; Kodet, Ondřej; Strnad, Hynek; Kolář, Michal; Lacina, Lukáš; Krejčí, Eliška; Naňka, Ondřej; Šedo, Aleksi; Smetana, Karel
Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.
Chattopahdyay, Chandrani; Kim, Dae Won; Gombos, Dan; Oba, Junna; Qin, Yong; Williams, Michelle; Esmaeli, Bita; Grimm, Elizabeth; Wargo, Jennifer; Woodman, Scott; Patel, Sapna
Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the U.S., an age-adjusted risk of 5 per million. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomical spread, molecular changes, and responses to systemic therapy. Once metastatic, therapy options are limited, and often extrapolated from cutaneous melanoma therapies despite routine exclusion of uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress and data from these well-designed investigations will help guide future directions in this orphan disease. PMID:26991400
Wei, Erin X.; Qureshi, Abrar A.; Han, Jiali; Li, Tricia Y.; Cho, Eunyoung; Lin, Jennifer Y.; Li, Wen-Qing
Background The incidence of melanoma in situ is rising, but little is known about its characteristics. Objective To determine trends in diagnosis and clinical features of melanoma in situ. Methods Incident cases of melanoma were collected prospectively from the Nurses’ Health Study from 1976–2010 and Health Professionals Follow-up Study from 1986–2010. Results MIS incidence increased from 2 to 42 per 100,000-person-year (100KPY) among women, and from 11 to 73 per 100KPY among men, exceeding the rate of increase of invasive melanomas. Melanoma mortality initially increased during the follow-up period then plateaued. Men were more likely than women to develop in situ melanomas on upper half of the body (p<0.001). Invasive melanomas were diagnosed at a younger age than melanoma in situ (p<0.001), and were more likely to be found on the lower extremities than in situ melanomas (p<0.001). Limitations This is a strictly descriptive study without examination into mechanisms. Conclusion We found epidemiologic and clinical differences in in situ and invasive melanomas, which support further examination into the variations in etiologic pathways. The lack of improvement in mortality despite increase in detection of in situ relative to invasive lesions further highlight the need to improve invasive melanoma-specific clinical screening features. PMID:27436155
Autism Spectrum Disorders have for some time been the focus of intense interest for clinicians and researchers because of the high prevalence of the disorders among children in the community (approximately 1%), their severity and pervasiveness. Particular attention has been paid to the early diagnosis of the disorder and to the intensive therapeutic intervention. Currently the best prognosis for autism lays in the early diagnosis and intervention. Postponing the diagnosis and the intervention beyond infancy is considered loss of precious time. The diagnosis of autism, which begins early in life, was until recently considered that could be reliability made at the age of 3 years. Recent follow up studies however on children at risk for autism (children who had an older sibling with autism) have shown that the clinical signs of autism emerge at the end of the first year and become distinct by the end of the second year when the diagnosis can reliably be made. From a clinical perspective it is noted that the early clinical signs of risk for autism are related to social communication (e.g. limited or absent response when calling his/her name and to joint attention), stereotype behaviours and body movements or unusual handling of objects (e.g. intensive observation of objects and stereotype movements of hands and tapping or spinning), incongruent regulation of emotions (reduced positive and increased negative emotion). There is also delay in developmental characteristics such as the language (both receptive and expressive) and motor (particularly in postural control - characteristic is the drop of the head backwards when the infant is held in horizontal position). Studies on various aspects of the endophenotype of certain clinical signs among infants at risk for Autism Spectrum Disorders, such as avoidance of eye contact, delay in verbal communication and increase of the head circumference, may provide useful information and may assist the clinician on follow up in the
Müller, Judith; Krijgsman, Oscar; Tsoi, Jennifer; Robert, Lidia; Hugo, Willy; Song, Chunying; Kong, Xiangju; Possik, Patricia A; Cornelissen-Steijger, Paulien D M; Geukes Foppen, Marnix H; Kemper, Kristel; Goding, Colin R; McDermott, Ultan; Blank, Christian; Haanen, John; Graeber, Thomas G; Ribas, Antoni; Lo, Roger S; Peeper, Daniel S
Increased expression of the Microphthalmia-associated transcription factor (MITF) contributes to melanoma progression and resistance to BRAF pathway inhibition. Here we show that the lack of MITF is associated with more severe resistance to a range of inhibitors, while its presence is required for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlate with the expression of several activated receptor tyrosine kinases, most frequently AXL. The MITF-low/AXL-high/drug-resistance phenotype is common among mutant BRAF and NRAS melanoma cell lines. The dichotomous behaviour of MITF in drug response is corroborated in vemurafenib-resistant biopsies, including MITF-high and -low clones in a relapsed patient. Furthermore, drug cocktails containing AXL inhibitor enhance melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas.
Scheri, Randall P.; Pruitt, Scott K.; Herndon, James E.; Marcello, Jennifer; Tyler, Douglas S.; Abernethy, Amy P.
Background While curable at early stages, few treatment options exist for advanced melanoma. Currently, no consensus exists regarding the optimal surveillance strategy for patients after resection. The objectives of this study were to identify patterns of metastatic recurrence, to determine the influence of metastatic site on survival, and to identify high-risk periods for recurrence. Methods A retrospective review of the Duke Melanoma Database from 1970 to 2004 was conducted that focused on patients who were initially diagnosed without metastatic disease. The time to first recurrence was computed from the date of diagnosis, and the associated hazard function was examined to determine the peak risk period of recurrence. Metastatic sites were coded by the American Joint Committee on Cancer (AJCC) system including local skin, distant skin and nodes (M1a), lung (M1b), and other distant (M1c). Results Of 11,615 patients initially diagnosed without metastatic disease, 4616 (40%) had at least one recurrence. Overall the risk of initial recurrence peaked at 12 months. The risk of initial recurrence at the local skin, distant skin, and nodes peaked at 8 months, and the risk at lung and other distant sites peaked at 24 months. Patients with a cutaneous or nodal recurrence had improved survival compared to other recurrence types. Conclusions The risk of developing recurrent melanoma peaked at one year, and the site of first recurrence had a significant impact on survival. Defining the timing and expected patterns of recurrence will be important in creating an optimized surveillance strategy for this patient population. PMID:23516415
Gandini, Sara; De Vries, Esther; Tosti, Giulio; Botteri, Edoardo; Spadola, Giuseppe; Maisonneuve, Patrick; Martinoli, Chiara; Joosse, Arjen; Ferrucci, Pier Francesco; Baldini, Federica; Cocorocchio, Emilia; Pennacchioli, Elisabetta; Cataldo, Francesco; Bazolli, Barbara; Clerici, Alessandra; Barberis, Massimo; Bataille, Veronique; Testori, Alessandro
Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort. A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival. Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results.
Gandini, Sara; De Vries, Esther; Tosti, Giulio; Botteri, Edoardo; Spadola, Giuseppe; Maisonneuve, Patrick; Martinoli, Chiara; Joosse, Arjen; Ferrucci, Pier Francesco; Baldini, Federica; Cocorocchio, Emilia; Pennacchioli, Elisabetta; Cataldo, Francesco; Bazolli, Barbara; Clerici, Alessandra; Barberis, Massimo
Background Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort. Methods A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival. Results Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results. PMID:24223851
Alomari, Ahmed K; Glusac, Earl J; Choi, Jennifer; Hui, Pei; Seeley, Erin H; Caprioli, Richard M; Watsky, Kalman L; Urban, Jennifer; Lazova, Rossitza
A 37-year-old pregnant woman presented with a 2-cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2-mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm(2) and no ulceration. Following induction of labor, the patient underwent re-excision with sentinel lymph node biopsy. This showed no residual melanoma and no lymph node metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of which were large and irregular. Two were biopsied and histologic examination showed dense dermal proliferation of medium sized melanocytes with multiple mitotic figures and no maturation with their descent into the dermis, raising suspicion of transplacental metastases. Examination of the placenta failed to show metastatic lesions. Multiplex polymerase chain reaction (PCR)-based genotyping, including testing for amelogenin locus for sex chromosome determination, demonstrated the presence of Y chromosome material in the melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis of the mother's lesion showed proteomic signature expression indicative of malignant melanoma, whereas the two lesions in the newborn showed changes indicative of nevi. This case demonstrates the utility of genotyping and Mass Spectrometry analysis in this challenging clinical scenario. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Leong, Stanley P. L.; Mihm, Martin C.; Murphy, George F.; Hoon, Dave S. B.; Kashani-Sabet, Mohammed; Agarwala, Sanjiv S.; Zager, Jonathan S.; Hauschild, Axel; Sondak, Vernon K.; Guild, Valerie; Kirkwood, John M.
The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials. PMID:22892755
Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav
Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas. PMID:23071856
Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav
Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas.
Orlow, Irene; Shi, Yang; Kanetsky, Peter A; Thomas, Nancy E; Luo, Li; Corrales-Guerrero, Sergio; Cust, Anne E; Sacchetto, Lidia; Zanetti, Roberto; Rosso, Stefano; Armstrong, Bruce K; Dwyer, Terence; Venn, Alison; Gallagher, Richard P; Gruber, Stephen B; Marrett, Loraine D; Anton-Culver, Hoda; Busam, Klaus; Begg, Colin B; Berwick, Marianne
Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p < .05). These SNPs, and a haplotype, had a statistically significant association with survival among subjects exposed to high UVB in multivariable regression models and exerted their effect in the opposite direction among those with low UVB. SNPs rs1544410/BsmI and rs731236/TaqI remained significant after adjustment for multiple testing. These results suggest that the association between VDR and melanoma-specific survival is modified by sun exposure around diagnosis, and require validation in an independent study. Whether the observed effects are dependent or independent of vitamin D activation remains to be determined. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Gleason, Briana C; Nascimento, Alessandra F
Granular cell tumors (GCTs), especially if atypical or malignant, may share cytomorphologic and architectural features with malignant melanoma, when the latter shows granular cell change. In many cases, these neoplasms can be differentiated from each other on histologic grounds, but distinction may sometimes be challenging. By immunohistochemistry, both tumors are strongly positive for S-100 protein and frequently express other nonspecific markers such as CD68, NSE, and NKIC3. In the current study, we reviewed 60 cases of conventional cutaneous, mucosal, and visceral GCT and studied the use of immunoperoxidase staining for the differential diagnosis between malignant melanoma and GCT. Immunohistochemical stains for S-100 protein, A, HMB-45, and microphthalmia transcription factor (MITF) were performed in all cases. All of the tumors were positive for S-100 protein. MITF immunostaining was diffusely positive in 53 (88%) cases, focally positive in three (5%) cases, and negative in four (7%). Fifty-seven (95%) tumors were negative for Melan-A, one case was focally positive, and two cases showed rare positive tumor cells. None of the tumors expressed HMB-45. In conclusion, GCT and malignant melanoma can be reliably differentiated on the basis of immunohistochemical stains in the majority of cases. Although not always positive in malignant melanoma, in this context, HMB-45 expression seems to be 100% specific for the diagnosis of melanoma. Melan-A is slightly less specific, with rare cases of GCT showing focal positivity. MITF is not useful in this differential-93% of the GCTs in our series showed nuclear reactivity for this marker. The latter finding highlights the limited specificity of this antibody in the diagnosis of melanocytic tumors.
Eriksson, H; Lyth, J; Månsson-Brahme, E; Frohm-Nilsson, M; Ingvar, C; Lindholm, C; Naredi, P; Stierner, U; Wagenius, G; Carstensen, J; Hansson, J
A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden. We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010. The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis. Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.
Chew, Jessica; Silverman, Daniel H S
FDG-PET is a valuable tool that will continue to aid in identifying AD in its prodromal and early dementia stages, distinguishing it from other causes of dementia, and tracking progression of the disease. As brain FDG-PET scans and well-trained readers of these scans are becoming more widely available to clinicians who are becoming more informed about the role FDG-PET can play in early AD diagnosis, its use is expected to increase. Copyright © 2013 Elsevier Inc. All rights reserved.
Wani, Sajad A.; Mufti, Gowher N.; Bhat, Nisar A.; Baba, Ajaz A.
Intralobar sequestration is characterized by aberrant formation of nonfunctional lung tissue that has no communication with the bronchial tree and receives systemic arterial blood supply. Failure of earlier diagnosis can lead to recurrent pneumonia, failure to thrive, multiple hospital admissions, and more morbidity. The aim of this case report is to increase the awareness about the lung sequestration, to diagnose and treat it early, so that it is resected before repeated infection, and prevent the morbidity and mortality. PMID:26273485
This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP). CP describes a group of disorders of the development of movement and posture, causing activity limitation that is attributed to disturbances that occurred in the fetal or infant brain. Therefore, the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuroimaging techniques, and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group, best prediction is achieved with the combination of neuroimaging and the assessment of general movements, in the latter group, best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high-risk infants without CP. In these infants, early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is urgently needed
Wang, Hequn; Osseiran, Sam; Roider, Elisabeth; Fisher, David E.; Evans, Conor L.
Recently, pheomelanin has been found to play a critical role in melanoma progression given its pro-oxidant chemical properties as well as its marked presence in pre-cancerous and malignant melanoma lesions, even in the absence of ultraviolet radiation. In addition, epidemiological evidence indicates a strong correlation between melanoma incidence and skin type, with the highest incidence occurring in individuals of the red-haired/fair-skinned phenotype. Interestingly, nevus count correlates well with melanoma incidence and skin type, except in the population most prone to developing melanoma, where nevus count strikingly drops. As such, a current hypothesis proposes that fair-skinned red-haired individuals, who are unable to stimulate production of eumelanin due to a mutation in MC1R in melanocytes, may actually harbor numerous "invisible", pheomelanin-rich nevi that evade clinical detection, supporting the high incidence of melanoma in that population. Here, we show for the very first time that melanocytes extracted from genetically modified MC1R-mutant, red-haired mice displayed bright perinuclear distributions of signal within the cells under coherent anti-Stokes Raman scattering (CARS) microscopy. Changes in pheomelanin production in siRNA knockdowns of cultured human melanoma cells were also sensed. We then successfully imaged pheomelanin distributions in both ex vivo and in vivo mouse ear skin. Finally, melanosomes within amelanotic melanoma patient tissue sections were found to show bright pheomelanin signals. This is the first time, to our knowledge, that pheomelanin has been found spatially localized in a human amelanotic melanoma sample. These pheomelanotic CARS features may be used as potential biomarkers for melanoma detection, especially for amelanotic melanomas.
Sarmiento, A.; Sanchez-Morillo, D.; Jiménez, S.; Alemany, P.
Glaucoma is a degenerative disease that constitutes the second cause of blindness in developed countries. Although it cannot be cured, its progression can be prevented through early diagnosis. In this paper, we propose a new algorithm for automatic glaucoma diagnosis based on retinal colour images. We focus on capturing the inherent colour changes of optic disc (OD) and cup borders by computing several colour derivatives in CIE L∗a∗b∗ colour space with CIE94 colour distance. In addition, we consider spatial information retaining these colour derivatives and the original CIE L∗a∗b∗ values of the pixel and adding other characteristics such as its distance to the OD centre. The proposed strategy is robust due to a simple structure that does not need neither initial segmentation nor removal of the vascular tree or detection of vessel bends. The method has been extensively validated with two datasets (one public and one private), each one comprising 60 images of high variability of appearances. Achieved class-wise-averaged accuracy of 95.02% and 81.19% demonstrates that this automated approach could support physicians in the diagnosis of glaucoma in its early stage, and therefore, it could be seen as an opportunity for developing low-cost solutions for mass screening programs. PMID:29279773
Puig-Butille, Joan Anton; Escámez, María José; Garcia-Garcia, Francisco; Tell-Marti, Gemma; Fabra, Àngels; Martínez-Santamaría, Lucía; Badenas, Celia; Aguilera, Paula; Pevida, Marta; Dopazo, Joaquín; del Río, Marcela; Puig, Susana
Germline mutations in CDKN2A and/or red hair color variants in MC1R genes are associated with an increased susceptibility to develop cutaneous melanoma or non melanoma skin cancer. We studied the impact of the CDKN2A germinal mutation p.G101W and MC1R variants on gene expression and transcription profiles associated with skin cancer. To this end we set-up primary skin cell co-cultures from siblings of melanoma prone-families that were later analyzed using the expression array approach. As a result, we found that 1535 transcripts were deregulated in CDKN2A mutated cells, with over-expression of immunity-related genes (HLA-DPB1, CLEC2B, IFI44, IFI44L, IFI27, IFIT1, IFIT2, SP110 and IFNK) and down-regulation of genes playing a role in the Notch signaling pathway. 3570 transcripts were deregulated in MC1R variant carriers. In particular, genes related to oxidative stress and DNA damage pathways were up-regulated as well as genes associated with neurodegenerative diseases such as Parkinson’s, Alzheimer and Huntington. Finally, we observed that the expression signatures indentified in phenotypically normal cells carrying CDKN2A mutations or MC1R variants are maintained in skin cancer tumors (melanoma and squamous cell carcinoma). These results indicate that transcriptome deregulation represents an early event critical for skin cancer development. PMID:24742402
Sharon, Cimarron E; Sinnamon, Andrew J; Ming, Michael E; Chu, Emily Y; Fraker, Douglas L; Karakousis, Giorgos C
Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients. This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017. Marital status, categorized as married, never married, divorced, or widowed. Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm. A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married
Sciubba, J J
Oral cancer is an important health issue. The WHO predicts a continuing worldwide increase in the number of patients with oral cancer, extending this trend well into the next several decades. In the US the projected number of new cases of oral and oropharyngeal cancer will exceed 31,000 per year. Mortality due to cancers in this region exceeds the annual death rate is the US caused by either cutaneous melanoma or cervical cancer. Significant agents involved in the etiology of oral cancer in Western countries include sunlight exposure, smoking and alcohol consumption. Use of the areca or betel nut in many cultures is a major etiological factor outside of the USA. Other etiologic factors associated with oral squamous cell carcinoma, but far less significant statistically, include syphilis and sideropenic dysphagia. Recently, strong evidence for an etiological relationship between human papilloma virus and a subset of head and neck cancers has been noted. It is generally accepted that most sporadic tumors are the result of a multi-step process of accumulated genetic alterations. These alterations affect epithelial cell behavior by way of loss of chromosomal heterozygosity which in turn leads to a series of events progressing to the ultimate stage of invasive squamous cell carcinoma. The corresponding genetic alterations are reflected in clinical and microscopic pathology from hyperplasia through invasiveness. A wide range of mucosal alternations fall within the rubric of leukoplakia. Proliferative verrucous leukoplakia represents a relatively new type of leukoplakia that is separate from the more common or less innocuous form of this condition. Erythroplakia is particularly relevant considering its almost certain relationship with dysplasia or invasive carcinoma. Squamous cell carcinoma will develop from antecedent dysplastic oral mucosal lesions if an early diagnosis has not been made and treatment given. Early diagnosis within stages I and II correspond to a vastly
Rayner, Jenna E; Laino, Antonia M; Nufer, Kaitlin L; Adams, Laura; Raphael, Anthony P; Menzies, Scott W; Soyer, H Peter
Melanoma incidence continues to increase across many populations globally and there is significant mortality associated with advanced disease. However, if detected early, patients have a very promising prognosis. The methods that have been utilized for early detection include clinician and patient skin examinations, dermoscopy (static and sequential imaging), and total body photography via 2D imaging. Total body photography has recently witnessed an evolution from 2D imaging with the ability to now create a 3D representation of the patient linked with dermoscopy images of individual lesions. 3D total body photography is a particularly beneficial screening tool for patients at high risk due to their personal or family history or those with multiple dysplastic naevi-the latter can make monitoring especially difficult without the assistance of technology. In this perspective, we discuss clinical examples utilizing 3D total body photography, associated advantages and limitations, and future directions of the technology. The optimal system for melanoma screening should improve diagnostic accuracy, be time and cost efficient, and accessible to patients across all demographic and socioeconomic groups. 3D total body photography has the potential to address these criteria and, most importantly, optimize crucial early detection.
Turner, Greg; Abbott, Sarah; Eglinton, Tim; Wakeman, Chris; Frizelle, Frank
Melanoma of the anorectum is a rare malignancy which is particularly aggressive compared to cutaneous melanoma. Due to its presenting symptoms, location and rarity there is often a delay in diagnosis. The purpose of this paper is to raise awareness of anorectal melanoma in New Zealand by presenting our institution's experience of four cases. The presentation, management and outcomes of four cases are described. A review of the literature surrounding anorectal melanoma was also carried out. The four cases (3 male, 1 female, aged 30-87 years) all presented with haemorrhoidal symptoms of anal discomfort and/or outlet rectal bleeding. Three patients had metastatic disease at presentation, and the remaining patient was found to have a concurrent lymphoma which was treated with chemotherapy before he underwent excision of the melanoma. Surgical excision is the mainstay of treatment and recent literature suggests transanal excision of the primary tumour to have equivalent overall survival to abdominoperineal resection. Anorectal melanoma is rare tumour with a poor prognosis. Patients are commonly misdiagnosed as having haemorrhoids; therefore a high index of suspicion is needed to enable early diagnosis. Metastatic disease is common at presentation, and the key prognostic indicator. Local control can be obtained with transanal excision, avoiding the morbidity of abdominoperineal resection. Adjuvant therapies available at present provide little survival advantage.
Kyriakidou, Maria; Anastassopoulou, Jane; Tsakiris, Aristeidis; Koui, Maria; Theophanides, Theophile
Mid-infrared spectroscopy (4000-500 cm -1 ) was used to analyze the spectral changes and differences of the characteristic absorption bands of the skin components due to cancer development for early clinical diagnosis. Human biopsies from basal cell carcinoma, malignant melanoma, and nevus were used, while normal skin tissue served as a control. The high quality of Fourier-transform infrared (FT-IR) spectra showed that upon cancer development the intensity of the absorption band at approximately 3062 cm -1 was increased, indicating that most of the proteins had the configuration of amide B and the β-sheet protein structure predominated. The stretching vibration bands of vCH 2 in the region 2950-2850 cm -1 were increased in melanoma and nevus, while were less pronounced in basal cell carcinoma due to the increased lipophilic environment. In addition, the intensity of a new band at 1744 cm -1 , which is assigned to aldehyde, was increased in melanoma and nevus and appeared as a shoulder in the spectra of normal skin. The absorption band of amide I at 1650 cm -1 was split into two bands, at 1650 cm -1 and 1633 cm -1 , due to the presence of both α-helix and random coil protein conformations for melanoma and nevus. This was confirmed from the amide II band at 1550 cm -1 , which shifted to lower frequencies at 1536 cm -1 and 1540 cm -1 for basal cell carcinoma and melanoma, respectively, indicating a damage of the native structure of proteins. The bands at 841 and 815 cm -1 , which are assigned to B-DNA and Z-DNA, respectively, indicated that only the bands of the cancerous Z-DNA form are pronounced in melanoma, while in BCC both the characteristic bands of B-DNA and Z-DNA forms are found. It is proposed that the bands described above could be used as "diagnostic marker" bands for DNA forms, in the diagnosis of skin cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Kaplan, Frederick S.; Xu, Meiqi; Glaser, David L.; Collins, Felicity; Connor, Michael; Kitterman, Joseph; Sillence, David; Zackai, Elaine; Ravitsky, Vardit; Zasloff, Michael; Ganguly, Arupa; Shore, Eileen M.
BACKGROUND Fibrodysplasia ossificans progressiva is a rare and disabling genetic condition characterized by congenital malformation of the great toes and by progressive heterotopic ossification in specific anatomic patterns. Most patients with fibrodys-plasia ossificans progressiva are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures that can cause lifelong disability. Recently, the genetic cause of fibrodysplasia ossificans progressiva was identified, and definitive genetic testing for fibrodysplasia ossificans progressiva is now available before the appearance of heterotopic ossification. METHODS We recently evaluated 7 children for diagnosis of fibrodysplasia ossificans progressiva before the onset of heterotopic ossification. A medical history, physical examination, and skeletal survey were obtained on all of the patients, as well as clinical genetic testing for the canonical fibrodysplasia ossificans progressiva mutation. RESULTS All 7 of the children (4 girls and 3 boys; ages 3 months to 6 years) had congenital malformations of the great toes, but none had radiographic evidence of heterotopic ossification at the time of evaluation. Five of the 7 children had soft tissue lesions of the neck and back, suggestive of early fibrodysplasia ossificans progressiva flare-ups, 3 of whom had undergone invasive diagnostic procedures that exacerbated their condition. Two children had no history or signs of soft tissue swelling or flare-ups. DNA sequence analysis found that all 7 of the children had the recurrent fibrodysplasia ossificans progressiva missense mutation, a single nucleotide substitution (c.617G>A) at codon 206 in the glycine-serine activation domain of activin receptor IA, a bone morphogenetic protein type 1 receptor. CONCLUSION Clinical suspicion of fibrodysplasia ossificans progressiva early in life on the basis of malformed great toes can lead to early clinical diagnosis, confirmatory
Buja, Alessandra; Sartor, Gino; Scioni, Manuela; Vecchiato, Antonella; Bolzan, Mario; Rebba, Vincenzo; Sileni, Vanna Chiarion; Palozzo, Angelo Claudio; Montesco, Maria; Del Fiore, Paolo; Baldo, Vincenzo; Rossi, Carlo Riccardo
Cutaneous melanoma is a major concern in terms of healthcare systems and economics. The aim of this study was to estimate the direct costs of melanoma by disease stage, phase of diagnosis, and treatment according to the pre-set clinical guidelines drafted by the AIOM (Italian Medical Oncological Association). Based on the AIOM guidelines for malignant cutaneous melanoma, a highly detailed decision-making model was developed describing the patient's pathway from diagnosis through the subsequent phases of disease staging, surgical and medical treatment, and follow-up. The model associates each phase potentially involving medical procedures with a likelihood measure and a cost, thus enabling an estimation of the expected costs by disease stage and clinical phase of melanoma diagnosis and treatment according to the clinical guidelines. The mean per-patient cost of the whole melanoma pathway (including one year of follow-up) ranged from €149 for stage 0 disease to €66,950 for stage IV disease. The costs relating to each phase of the disease's diagnosis and treatment depended on disease stage. It is essential to calculate the direct costs of managing malignant cutaneous melanoma according to clinical guidelines in order to estimate the economic burden of this disease and to enable policy-makers to allocate appropriate resources.
Robinson, E S; Hubbard, G B; Colon, G; Vandeberg, J L
Suckling young of opossums (Monodelphis domestica) were exposed to ultraviolet radiation (UVR, predominantly UVB: 290-320 nm) in part to determine an optimal protocol for induction and progression of melanoma in this species. In all, 620 litters were introduced to one of seven protocols. The lowest dose (175 J/m2) administered three times a week for almost three weeks led to the highest incidence of melanotic lesions with melanoma potential (8.1%) among young (5-month-old) adults. Among 101 much older animals (> 17 months at necropsy), 43% showed metastatic melanoma to the lymph nodes and almost one-third of these had progressed to widespread dissemination. Three of the latter animals, from a total of 13 obtained so far, were selected for detailed histological examination of disseminated disease. At necropsy, all three showed widespread metastases beyond the lymph nodes to the spleen, lungs, and other distant sites. Histological changes typical of malignant melanoma included junctional activity, mitotic figures, and nerve and vessel invasion. This novel finding leads us to conclude that UVR can act as a complete carcinogen for progression to widely disseminated disease and that exposure of sucklings can lead, in old age, to widespread metastatic melanoma in this model. The results are thus not inconsistent with the view that, in humans, early exposure to sunlight might act as an initiating factor in a later progression to malignant melanoma.
Katus, Hugo; Ziegler, André; Ekinci, Okan; Giannitsis, Evangelos; Stough, Wendy Gattis; Achenbach, Stephan; Blankenberg, Stefan; Brueckmann, Martina; Collinson, Paul; Comaniciu, Dorin; Crea, Filippo; Dinh, Wilfried; Ducrocq, Grégory; Flachskampf, Frank A; Fox, Keith A A; Friedrich, Matthias G; Hebert, Kathy A; Himmelmann, Anders; Hlatky, Mark; Lautsch, Dominik; Lindahl, Bertil; Lindholm, Daniel; Mills, Nicholas L; Minotti, Giorgio; Möckel, Martin; Omland, Torbjørn; Semjonow, Véronique
The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients with symptoms and high-sensitivity troponin <99th percentile but above the limit of detection; (iii) patients with symptoms and high-sensitivity troponin >99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: firstname.lastname@example.org.
Rawicz, Andrew H.; Melnyk, Ivan; Oldham, Bradley
An optical system injecting light directly to the skin and collecting the backscattered portion of the light that has been spectrally modified within the skin has been designed and fabricated. This method reduces the noise generated by the specular component practically to zero. The initial device involved a single channel, optical-fibre-based illuminator and collector connected with a spectroscope. The single channel probing head scanned the skin using a mechanical shifting device. Seven clinical tests performed on patients with suspect skin lesions have been tested with our device, and later biopsy was taken as a "gold standard" procedure. Three cases proved to be melanoma and our spectra indicated differences from those collected from non-melanoma lesions. The process of collecting spectral data was time consuming (about 30 min) and thus not acceptable for a medical procedure. To accelerate the process of data collection from the skin, using the same principle of diffuse spectroscopy, an imaging device was conceived which is able to collect the skin spectral response at once from a relatively sizeable skin area. The requirement of negligible specular component was considered of paramount importance. Two possible approaches are feasible to satisfy this requirement: 1. Collection of backscattered light directly from the skin 2. Injection of illuminating light directly to the skin without creating reflections directly from skin. We decided to use the second approach and construct a circular, circumferential illuminator with angled light injection. Before fabricating this illuminator, a thorough analysis was performed to optimize its radius and angle of injection in order to receive the highest uniformity of diffuse light in the skin. Monte-Carlo simulation was applied to a three layer skin approximation. Only three layers were considered due to the assumption that the device must be able to diagnose early melanoma before reaching metastasis. The results of the
Novak, Iona; Morgan, Cathy; Adde, Lars; Blackman, James; Boyd, Roslyn N; Brunstrom-Hernandez, Janice; Cioni, Giovanni; Damiano, Diane; Darrah, Johanna; Eliasson, Ann-Christin; de Vries, Linda S; Einspieler, Christa; Fahey, Michael; Fehlings, Darcy; Ferriero, Donna M; Fetters, Linda; Fiori, Simona; Forssberg, Hans; Gordon, Andrew M; Greaves, Susan; Guzzetta, Andrea; Hadders-Algra, Mijna; Harbourne, Regina; Kakooza-Mwesige, Angelina; Karlsson, Petra; Krumlinde-Sundholm, Lena; Latal, Beatrice; Loughran-Fowlds, Alison; Maitre, Nathalie; McIntyre, Sarah; Noritz, Garey; Pennington, Lindsay; Romeo, Domenico M; Shepherd, Roberta; Spittle, Alicia J; Thornton, Marelle; Valentine, Jane; Walker, Karen; White, Robert; Badawi, Nadia
Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age. To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86
Bae, Soo Hyeon; Seon, Hyun Ju; Choi, Yoo Duk; Shim, Hyun-Jeong; Lee, Jee-Bum; Yun, Sook Jung
Although other primary systemic cancers in patients with melanoma have been studied, there have been few focusing on acral melanomas. We assessed other primary systemic cancers in patients with acral and nonacral melanomas. We analyzed other primary cancers in 452 patients with melanoma from 1994 to 2013. Metachronous cancers were defined as those given a diagnosis more than 2 months after diagnosis of melanoma. The others were considered prechronous or synchronous cancers. Among 51 cases of other primary cancers, gastrointestinal cancer (35.3%, n = 18/51) was the most common, followed by thyroid (17.6%), lung (11.8%), and breast (5.9%). Those were more prevalent in the acral melanoma group (12.8%, n = 31/243) compared with the nonacral melanoma group (9.6%, n = 20/209). Of 23 cases of metachronous cancer, the risk was the highest in bone marrow, followed by oral cavity, bladder, colon, lung, and thyroid. Among 28 cases of prechronous or synchronous cancers, gastrointestinal tract (35.7%, n = 10/28) was the most common site, followed by thyroid (17.9%), breast (10.7%), and lung (7.1%). The study is limited by a small number of patients. Careful follow-up and imaging studies are necessary for early detection of other primary cancers and metastatic lesions in patients with melanoma. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Almazán-Fernández, F M; Serrano-Ortega, S; Moreno-Villalonga, J J
Every year, health expenditure in Spain increases and, with it, the resources dedicated to cancer treatment. Cutaneous melanoma is the skin cancer with the highest morbidity and mortality. We performed a descriptive study of the costs, based on a theoretical model, to determine the healthcare expenditure for patients with cutaneous melanoma; the objective was to define the overall costs (direct and indirect) of the diagnostic and treatment process of cutaneous melanoma, divided into different stages or diagnostic-therapeutic steps, and the possible variations in these costs. For this purpose, we used the Andalusian analytical accountancy program of hospitals and districts (COAN-hyd) and the total costs module of the COAN for 2007, applied to the protocol we use in the melanoma unit of our hospital. The most important conclusions were that the greatest health care expenditure was observed inpatients with more advanced melanomas, with a poor prognosis. Management of the diagnostic-therapeutic process by dermatologists, the appropriate use of complementary tests, and operations performed by dermatologists reduce costs.
Rastgoo, Mojdeh; Morel, Olivier; Marzani, Franck; Garcia, Rafael
Melanoma is the deadliest type of skin cancer, yet it is the most treatable kind depending on its early diagnosis. The early prognosis of melanoma is a challenging task for both clinicians and dermatologists. Due to the importance of early diagnosis and in order to assist the dermatologists, we propose an automated framework based on ensemble learning methods and dermoscopy images to differentiate melanoma from dysplastic and benign lesions. The evaluation of our framework on the recent and public dermoscopy benchmark (PH2 dataset) indicates the potential of proposed method. Our evaluation, using only global features, revealed that ensembles such as random forest perform better than single learner. Using random forest ensemble and combination of color and texture features, our framework achieved the highest sensitivity of 94% and specificity of 92%.
Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T
The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.
Ahlgrimm-Siess, Verena; Laimer, Martin; Arzberger, Edith; Hofmann-Wellenhof, Rainer
Early detection of melanoma remains crucial to ensuring a favorable prognosis. Dermoscopy and total body photography are well-established noninvasive aids that increase the diagnostic accuracy of dermatologists in their daily routine, beyond that of a naked-eye examination. New noninvasive diagnostic techniques, such as reflectance confocal microscopy, multispectral digital imaging and RNA microarrays, are currently being investigated to determine their utility for melanoma detection. This review presents emerging technologies for noninvasive melanoma diagnosis, and discusses their advantages and limitations.
Kim, Dam; Choi, Chan-Bum; Lee, Jiyoung; Cho, Soo-Kyung; Won, Soyoung; Bang, So-Young; Cha, Hoon-Suk; Choe, Jung-Yoon; Chung, Won Tae; Hong, Seung-Jae; Jun, Jae-Bum; Jung, Young Ok; Kim, Jinseok; Kim, Seong-Kyu; Kim, Tae-Hwan; Kim, Tae-Jong; Koh, Eunmi; Lee, Hye-Soon; Lee, Jaejoon; Lee, Jisoo; Lee, Sang-Heon; Lee, Shin-Seok; Lee, Sung Won; Shim, Seung-Cheol; Yoo, Dae-Hyun; Yoon, Bo Young; Sung, Yoon-Kyoung; Bae, Sang-Cheol
Background/Aims To determine whether early diagnosis is beneficial for functional status of various disease durations in rheumatoid arthritis (RA) patients. Methods A total of 4,540 RA patients were enrolled as part of the Korean Observational Study Network for Arthritis (KORONA). We defined early diagnosis as a lag time between symptom onset and RA diagnosis of ≤ 12 months, whereas patients with a longer lag time comprised the delayed diagnosis group. Demographic characteristics and outcomes were compared between early and delayed diagnosis groups. Logistic regression analyses were performed to identify the impact of early diagnosis on the development of functional disability in RA patients. Results A total of 2,597 patients (57.2%) were included in the early diagnosis group. The average Health Assessment Questionnaire-Disability Index (HAQ-DI) score was higher in the delayed diagnosis group (0.64 ± 0.63 vs. 0.70 ± 0.66, p < 0.01), and the proportion of patients with no functional disability (HAQ = 0) was higher in the early diagnosis group (22.9% vs. 20.0%, p = 0.02). In multivariable analyses, early diagnosis was independently associated with no functional disability (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40). In a subgroup analysis according to disease duration, early diagnosis was associated with no functional disability in patients with disease duration < 5 years (OR, 1.37; 95% CI, 1.09 to 1.72) but not in patients with longer disease duration (for 5 to 10 years: OR, 1.07; 95% CI, 0.75 to 1.52; for ≥ 10 years: OR, 0.92; 95% CI, 0.65 to 1.28). Conclusions Early diagnosis is associated with no functional disability, especially in patients with shorter disease duration. PMID:27618867
Portilho, Filipe Leal; Helal-Neto, Edward; Cabezas, Santiago Sánchez; Pinto, Suyene Rocha; Dos Santos, Sofia Nascimento; Pozzo, Lorena; Sancenón, Félix; Martínez-Máñez, Ramón; Santos-Oliveira, Ralph
Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography. The results demonstrated the ability of the magnetic core-mesoporous silica to be efficiently (>98%) doped with dacarbazine and also efficiently labelled with 99mTc (technetium 99 m) (>99%). The in vivo test, using inducted mice with melanoma, demonstrated the EPR effect of the magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable when injected intratumorally and the possibility to be used as systemic injection too. In both cases, magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable showed to be a reliable and efficient nano-imaging agent for melanoma.
Blessing, Andreas; Studer, Anna; Gross, Amelie; Gruss, L Forest; Schneider, Roland; Dammann, Gerhard
There is a debate concerning risks and benefits of early intervention in psychosis, especially concerning diagnosis disclosure. The present study reports preliminary findings on self-reported locus of control and psychological distress after the disclosure of diagnosis in an early recognition center. We compared the ratings of the locus of control and psychological distress before and after communication of diagnosis. The study included individuals with an at-risk mental state (ARMS) (n = 10), schizophrenia (n = 9), and other psychiatric disorders (n = 11). Results indicate greater endorsement of the internal locus of control in individuals with ARMS after communication of diagnosis in contrast to the other groups. Our results suggest that disclosure of diagnosis in an early recognition center leads to a reduction of psychological distress and increased feelings of control over one's health. Persons with ARMS seem to particularly benefit from disclosure of diagnosis as part of early intervention.
Thomas, Nancy E; Kricker, Anne; Waxweiler, Weston T; Dillon, Patrick M; Busman, Klaus J; From, Lynn; Groben, Pamela A; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Marrett, Loraine D; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A; Orlow, Irene; Paine, Susan; Ollila, David W; Reiner, Anne S; Luo, Li; Hao, Honglin; Frank, Jill S; Begg, Colin B; Berwick, Marianne
, anatomic site, and study design variables, but survival did not differ once AJCC tumor stage was also taken into account (HR, 0.8; 95%CI, 0.5-1.2)(P = .36).CONCLUSIONS AND RELEVANCE At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biological properties of amelanotic melanoma are warranted.
Thomas, Nancy E.; Kricker, Anne; Waxweiler, Weston T.; Dillon, Patrick M.; Busam, Klaus J.; From, Lynn; Groben, Pamela A.; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Marrett, Loraine D.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Orlow, Drs. Irene; Paine, Susan; Ollila, David W.; Reiner, Anne S.; Luo, Li; Hao, Honglin; Frank, Jill S.; Begg, Colin B.; Berwick, Marianne
, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biology of amelanotic melanoma are warranted. PMID:25162299
Merlino, Glenn; Herlyn, Meenhard; Fisher, David E.; Bastian, Boris C.; Flaherty, Keith T.; Davies, Michael A.; Wargo, Jennifer A.; Curiel-Lewandrowski, Clara; Weber, Michael J.; Leachman, Sancy A.; Soengas, Maria S.; McMahon, Martin; Harbour, J. William; Swetter, Susan M.; Aplin, Andrew E.; Atkins, Michael B.; Bosenberg, Marcus W.; Dummer, Reinhard; Gershenwald, Jeff; Halpern, Allan C.; Herlyn, Dorothee; Karakousis, Giorgos C.; Kirkwood, John M.; Krauthammer, Michael; Lo, Roger S.; Long, Georgina V.; McArthur, Grant; Ribas, Antoni; Schuchter, Lynn; Sosman, Jeffrey A.; Smalley, Keiran S.; Steeg, Patricia; Thomas, Nancy E.; Tsao, Hensin; Tueting, Thomas; Weeraratna, Ashani; Xu, George; Lomax, Randy; Martin, Alison; Silverstein, Steve; Turnham, Tim; Ronai, Ze’ev A.
The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas—diagnosis/early detection, prevention, tumor cell dormancy (including metastasis) and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November. Each of the four groups has outlined their thoughts per the current status, challenges and opportunities in the four respective areas. The current state and immediate and long-term needs of the melanoma field, from basic research to clinical management, are presented in the following report. PMID:27087480
Cole-Clark, D; Nair-Shalliker, V; Bang, A; Rasiah, K; Chalasani, V; Smith, D P
Emerging evidence suggests that a diagnosis of cutaneous melanoma (CM) may be associated with prostate cancer (PC) incidence. We examined if the incidence of CM was associated with an increased subsequent risk of PC. We used data from the New South Wales Cancer Registry for all CM and PC cases diagnosed between January 1972 and December 2008. We calculated the age standardized incidence ratio (SIR) and 95% confidence intervals (95% CI) for PC incidence following a CM diagnosis, applying age- and calendar- specific rates to the appropriate person years at risk. We determined rate ratio (RR) and 95% CI of PC incidence according to specified socio-demographic categories and disease related characteristics, using a negative binomial model. There were 143,594 men diagnosed with PC or CM in the study period and of these 101,198 and 42,396 were diagnosed with PC and CM, respectively, as first primary cancers. Risk of PC incidence increased following CM diagnosis (n = 2,114; SIR = 1.25; 95% CI:1.20.8-1.31: p < 0.0001), with the increased risk apparent in men diagnosed with localised CM (n = 1,862;SIR = 1.26; 95% CI:1.20-1.32). CM diagnosis increased the subsequent risk of PC incidence. This raises the potential for future PC risk to be discussed with newly diagnosed males with CM.
Prieto-Torres, Lucía; Alegría-Landa, Victoria; Llanos, Concepción; Córdoba, Alicia; Kutzner, Heinz; Requena, Luis
Divergent differentiation or metaplastic change is a rare feature exhibited occasionally in malignant melanoma (MM), which is characterized by the development of morphologically, immunochemically, and/or ultrastructurally nonmelanocytic cells within the tumor. Smooth muscle differentiation in MM is an exceedingly rare phenomenon reported only in a few cases in the literature. We report the case of a 69-year-old woman who presented with a pure dermal amelanotic MM with smooth muscle cell differentiation and an area of rhabdoid morphology, which made the accurate histopathologic diagnostic of MM challenging.
Han, Dale; Thomas, Daniel C; Zager, Jonathan S; Pockaj, Barbara; White, Richard L; Leong, Stanley PL
An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient’s nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN. PMID:27081640
Paridaens, A D; McCartney, A C; Hungerford, J L
Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure. Images PMID:1540561
Paridaens, A D; McCartney, A C; Hungerford, J L
Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure.
Bonmarin, Mathias; Le Gal, Frédérique-Anne
This paper theoretically evaluates lock-in thermal imaging for the early-stage detection of cutaneous melanoma. Lock-in thermal imaging is based on the periodic thermal excitation of the specimen under test. Resulting surface temperature oscillations are recorded with an infrared camera and allow the detection of variations of the sample's thermophysical properties under the surface. In this paper, the steady-state and transient skin surface temperatures are numerically derived for a different stage of development of the melanoma lesion using a two-dimensional axisymmetric multilayer heat-transfer model. The transient skin surface temperature signals are demodulated according to the digital lock-in principle to compute both a phase and an amplitude image of the lesions. The phase image can be advantageously used to accurately detect cutaneous melanoma at an early stage of development while the maximal phase shift can give precious information about the lesion invasion depth. The ability of lock-in thermal imaging to suppress disturbing subcutaneous thermal signals is demonstrated. The method is compared with the previously proposed pulse-based approaches, and the influence of the modulation frequency is further discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
Schuster, Cornelia; Eikesdal, Hans P; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E; Akslen, Lars A; Straume, Oddbjørn
VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12-49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. ClinicalTrials.gov NCT00139360.
Schuster, Cornelia; Eikesdal, Hans P.; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E.; Akslen, Lars A.; Straume, Oddbjørn
Background VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. Trial Registration ClinicalTrials.gov NCT00139360. PMID:22719881
Ong, C L; Wong, T H; Rauff, A
Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls. PMID:1885081
Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Saito, Keigo; Uemura, Yasushi; Nakatsura, Tetsuya
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the 5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α-fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers, such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article, we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC. PMID:26457017
Guthrie, Whitney; Swineford, Lauren B.; Nottke, Charly; Wetherby, Amy M.
Background: Although a diagnosis of autism spectrum disorder (ASD) appears to be stable in children as young as age three, few studies have explored stability of a diagnosis in younger children. Predictive value of diagnostic tools for toddlers and patterns of symptom change are important considerations for clinicians making early diagnoses. Most…
Pierro, L; Capoferri, C; Brancato, R
A hereditary retinoblastoma (RTB) was identified by ocular echography in a newborn, whose predisposition to RTB had been assessed based on the family history and DNA testing of the chorionic villi at the eighth week of pregnancy. Ultrasonography was performed during pregnancies without an abnormality being demonstrated. On the third day of life a B-scan examination showed a small membranous lesion in the nasal parapapillary area, whilst on A-scan, the lesion appeared as a hyperreflective peak. Thanks to its early identification, the tumor was successfully treated by photocoagulation.
Balhara, Ashok K; Gupta, Meenakshi; Singh, Surender; Mohanty, Ashok K; Singh, Inderjeet
An early and accurate diagnosis of reproductive dysfunctions or aberrations is crucial to better reproductive management in livestock. High reproductive efficiency is a prerequisite for high life-time production in dairy animals. Early pregnancy diagnosis is key to shorten the calving interval through early identification of open animals and their timely treatment and rebreeding so as to maintain a postpartum barren interval close to 60 days. A buffalo, the most important dairy animal in the Indian subcontinent, is known for problems related to high calving interval, late puberty, and high incidence of anestrus. Lack of reliable cow-side early pregnancy diagnosis methods further aggravates the situation. Several methods of pregnancy diagnosis are being practiced in bovine species, yet none qualifies as the ideal pregnancy diagnosis method due to the inherent limitations of sensitivity, accuracy, specificity, speed, and ease of performing the test. The advancement of molecular techniques like proteomics and their applications in animal research has given a new hope to look for pregnancy biomarker molecules in these animals. This review attempts to examine common pregnancy diagnosis methods available for dairy animals, while assessing the usefulness of the modern technologies in detecting novel pregnancy markers and designing future strategies for research in this area.
Gupta, Meenakshi; Singh, Surender; Mohanty, Ashok K.; Singh, Inderjeet
An early and accurate diagnosis of reproductive dysfunctions or aberrations is crucial to better reproductive management in livestock. High reproductive efficiency is a prerequisite for high life-time production in dairy animals. Early pregnancy diagnosis is key to shorten the calving interval through early identification of open animals and their timely treatment and rebreeding so as to maintain a postpartum barren interval close to 60 days. A buffalo, the most important dairy animal in the Indian subcontinent, is known for problems related to high calving interval, late puberty, and high incidence of anestrus. Lack of reliable cow-side early pregnancy diagnosis methods further aggravates the situation. Several methods of pregnancy diagnosis are being practiced in bovine species, yet none qualifies as the ideal pregnancy diagnosis method due to the inherent limitations of sensitivity, accuracy, specificity, speed, and ease of performing the test. The advancement of molecular techniques like proteomics and their applications in animal research has given a new hope to look for pregnancy biomarker molecules in these animals. This review attempts to examine common pregnancy diagnosis methods available for dairy animals, while assessing the usefulness of the modern technologies in detecting novel pregnancy markers and designing future strategies for research in this area. PMID:24382949
He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi
Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.
Carey, Kai A.; Menyaev, Yulian A.; Nedosekin, Dmitry A.; Sarimollaoglu, Mustafa; Galanzha, Ekaterina I.; Stumhofer, Jason S.; Zharov, Vladimir P.
Roughly 0.6 million people die each year from malaria due to lack of early diagnosis and well-timed treatment. Our previous study demonstrated great potential of in vivo photoacoustic (PA) flow cytometry (PAFC) for early diagnosis of deadly diseases with focus on cancer and thromboembolic complications. Here we demonstrate potential of advanced PAFC platforms using new laser, ultrasound transducer array and recording system to detect infected red blood cells (iRBCs) with malaria-associated pigment hemozoin which has a higher PA contrast than blood background. Mature parasites of human infecting species such as P. falciparum characteristically sequester mature iRBCs in the capillary bed and display synchrony in their reproductive cycle. To address this issue prior to clinical application, new PAFC platform was verified in a pre-clinical study using new animal models. Specifically, we used P. chabaudi (a rodent malaria species that mimics the characteristics of the most virulent human counterpart) to estimate the detection sensitivity with immature ring-stage parasites in peripheral blood, compared PA signals from the differing species, and examined the relationship between PA signal amplitudes and level of blood oxygenation. Based on previous successful trials on melanoma patients with melanin as an intrinsic PA marker, which has similar absorption as hemozoin, we believe that after additional malaria-related clinical trials, PAFC with a small 1064 nm laser and wearable a cost-effective, easy-to-use, watch-like, safe PA probe will provide malaria diagnosis in humans at parasitemia levels 10e4 -times lower than the current gold standard of diagnosis, the Giemsa-stained blood smear. It can reduce malaria-related mortality by well-timed treatment, especially in children in malaria-endemic countries.
Pasechnikov, Victor; Chukov, Sergej; Fedorov, Evgeny; Kikuste, Ilze; Leja, Marcis
Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach. PMID:25320521
The diagnosis of liver involvement in early syphilis has always posed problems because of its rarity and the difficulty of excluding coincidental liver disease caused by a multitude of pathogens. Case reports deal predominantly with jaundiced homosexual men in whom syphilis is discovered later, and the prospective studies of patients with early syphilis disclose only mild biochemical abnormalities in liver function test results. There is no single characteristic feature attributable to early syphilitic hepatitis. Even liver histologic findings are variable. At least in those patients who have jaundice, there is a likelihood of coincidental viral hepatitis. Therefore, the evidence to implicate Treponema pallidum as a liver pathogen in early syphilis is not convincing.
Yakut, Zeynep Ilerisoy; Bas, Ahmet Yagmur; Turan, Aynur; Demirel, Nihal; Demirkan, Tulin Hakan
Neurocutaneous melanosis (NCM) is a rare, congenital non-hereditary syndrome, characterized by multiple pigmented nevi. We report the radiologic findings of a newborn who had extensive cutaneous melanotic nevus with satellite lesions in the brain. Ultrasound showed multiple echogenic foci in the cerebral parenchyma. Subsequent MRI confirmed these lesions as characteristic deposits of melanin. The infant was asymptomatic, but presence of risk factors such as malign transformation or neurological manifestations makes early diagnosis very important. We present this case to emphasize on the radiological findings of this syndrome in order to reach an early diagnosis. PMID:25780540
Lee, So-Yeon; Park, Hee Jin; Kwag, Hyon Joo; Hong, Hyun-Pyo; Park, Hae-Won; Lee, Yong-Rae; Yoon, Kyung Jae; Lee, Yong-Taek
The purpose of this study was to investigate whether ultrasound (US) elastography is useful for the early diagnosis of plantar fasciitis. We retrospectively reviewed US elastography findings of 18 feet with a clinical history and physical examination highly suggestive of plantar fasciitis but with normal findings on conventional US imaging as well as 18 asymptomatic feet. Softening of the plantar fascia was significantly greater in the patient than in the control group [Reviewers 1 and 2: 89% (16/18) vs. 50% (9/18), P=.027, respectively]. US elastography is useful for the early diagnosis of plantar fasciitis. Copyright © 2014 Elsevier Inc. All rights reserved.
Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Merlemis, N.; Kalatzis, I.; Sianoudis, I. A.; Batsi, O.; Christofidou, E.; Stratigos, A. J.; Katsambas, A. D.; Antoniou, Ch.
Non melanoma skin cancer is one of the most frequent malignant tumors among humans. A non-invasive technique, with high sensitivity and high specificity, would be the most suitable method for basal cell carcinoma (BCC) or other malignancies diagnostics, instead of the well established biopsy and histopathology examination. In the last decades, a non-invasive, spectroscopic diagnostic method was introduced, the laser induced fluorescence (LIF), which could generate an image contrast between different states of skin tissue. The noninvasiveness consists in that this biophotonic method do not require tissue sample excision, what is necessary in histopathology characterization and biochemical analysis of the skin tissue samples, which is worldwide used as an evaluation gold standard. The object of this study is to establish the possibilities of a relatively portable system for laser induced skin autofluorescence to differentiate malignant from nonmalignant skin lesions. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a Nd:YAG-3ω laser (λ=355 nm, 6 ns), used as an excitation source for the autofluorescence measurements. A portable fiber-based spectrometer was used to record fluorescence spectra of the sites of interest. The ex vivo results, obtained with this spectroscopic technique, were correlated with the histopathology results. After the analysis of the fluorescence spectra of almost 60 skin tissue areas, we developed an algorithm to distinguish different types of malignant lesions, including inflammatory areas. Optimization of the data analysis and potential use of LIF spectroscopy with 355 nm Nd:YAG laser excitation of tissue autofluorescence for clinical applications are discussed.
Alonso-Curbelo, Direna; Osterloh, Lisa; Cañón, Estela; Calvo, Tonantzin G.; Martínez-Herranz, Raúl; Karras, Panagiotis; Martínez, Sonia; Riveiro-Falkenbach, Erica; Romero, Pablo-Ortiz; Rodríguez-Peralto, José Luis; Pastor, Joaquín; Soengas, María S.
Derailed endolysosomal trafficking is emerging as a widespread feature of aggressive neoplasms. However, the oncogenic signals that alter membrane homeostasis and their specific contribution to cancer progression remain unclear. Understanding the upstream drivers and downstream regulators of aberrant vesicular trafficking is distinctly important in melanoma. This disease is notorious for its inter- and intra-tumoral heterogeneity. Nevertheless, melanomas uniformly overexpress a cluster of endolysosomal genes, being particularly addicted to the membrane traffic regulator RAB7. Still, the underlying mechanisms and temporal determinants of this dependency have yet to be defined. Here we addressed these questions by combining electron microscopy, real time imaging and mechanistic analyses of vesicular trafficking in normal and malignant human melanocytic cells. This strategy revealed Class I PI3K as the key trigger of a hyperactive influx of macropinosomes that melanoma cells counteract via RAB7-mediated lysosomal degradation. In addition, gain- and loss-of-function in vitro studies followed by histopathological validation in clinical biopsies and genetically-engineered mouse models, traced back the requirement of RAB7 to the suppression of premature cellular senescence traits elicited in melanocytes by PI3K-inducing oncogenes. Together, these results provide new insight into the regulators and modes of action of RAB7, broadening the impact of endosomal fitness on melanoma development. PMID:26008978
Silveira, Landulfo; Silveira, Fabrício Luiz; Bodanese, Benito; Zângaro, Renato Amaro; Pacheco, Marcos Tadeu T.
Raman spectroscopy has been employed to identify differences in the biochemical constitution of malignant [basal cell carcinoma (BCC) and melanoma (MEL)] cells compared to normal skin tissues, with the goal of skin cancer diagnosis. We collected Raman spectra from compounds such as proteins, lipids, and nucleic acids, which are expected to be represented in human skin spectra, and developed a linear least-squares fitting model to estimate the contributions of these compounds to the tissue spectra. We used a set of 145 spectra from biopsy fragments of normal (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues, collected using a near-infrared Raman spectrometer (830 nm, 50 to 200 mW, and 20 s exposure time) coupled to a Raman probe. We applied the best-fitting model to the spectra of biochemicals and tissues, hypothesizing that the relative spectral contribution of each compound to the tissue Raman spectrum changes according to the disease. We verified that actin, collagen, elastin, and triolein were the most important biochemicals representing the spectral features of skin tissues. A classification model applied to the relative contribution of collagen III, elastin, and melanin using Euclidean distance as a discriminator could differentiate normal from BCC and MEL.
Frikh, Rachid; Oumakhir, Siham; Chahdi, Hafsa; Oukabli, Mohammed; Albouzidi, Abderrahmane; Baba, Noureddine; Hjira, Naoufal; Boui, Mohammed
Soft tissue melanoma was first described by Enzinger in 1965 under the name of clear cell sarcoma. In 1983, Chung and Enzinger renamed it soft tissue melanoma due to its immunohistochemical similarities with melanoma. We here report the case of a 22-year old young man with this rare type of melanoma, presenting with molluscoid lesion on his ankle without any clinical sign of malignancy. Histology examination confirmed the diagnosis of soft tissue melanoma.
Barak, Vivian; Frenkel, Shahar; Valyi-Nagy, Klara; Leach, Lu; Apushkin, Marsha A; Lin, Amy Y; Kalickman, Inna; Baumann, Nikola A; Pe'er, Jacob; Maniotis, Andrew J; Folberg, Robert
To develop a method to screen for serum biomarkers of early hepatic metastasis from uveal melanoma. Cytokeratin 18 (TPS) was identified from gene expression profiles as protein generated by highly invasive uveal melanoma cells. Sera were collected from two groups of 15 SCID mice 2 weeks after injection of either tissue culture medium or MUM2B human metastatic uveal melanoma cells into the mouse liver. Serum TPS levels were assayed in 53 healthy human controls, 64 uveal melanoma patients who were disease free for at least 10 years, and 37 patients with metastatic uveal melanoma. After 2 weeks, small hepatic nodules (0.1-2.8 mm; mean, 0.80 mm) developed in 11 of 15 mice injected with MUM2B cells. Serum TPS levels in media-injected mice (84.7 U/L) were substantially lower than levels in MUM2B-injected mice (601 mug/L). TPS levels were significantly higher (P < 0.0001) in patients with metastatic uveal melanoma (139.63 +/- 22.20) than in healthy controls (54.23 +/- 0.01) or in patients free of disease (69.29 +/- 9.76). Significant differences were found between TPS levels before and after the development of hepatic metastases (P < 0.01), and serum TPS levels became elevated in four patients at least 6 months before the detection of hepatic metastases by abdominal ultrasonography. The direct-injection model of uveal melanoma in the mouse liver may be used to screen for potential serum biomarkers of metastatic uveal melanoma.
Colliot, O; Hamelin, L; Sarazin, M
A major challenge for neuroimaging is to contribute to the early diagnosis of Alzheimer's disease (AD). In particular, magnetic resonance imaging (MRI) allows detecting different types of structural and functional abnormalities at an early stage of the disease. Anatomical MRI is the most widely used technique and provides local and global measures of atrophy. The recent diagnostic criteria of "mild cognitive impairment due to AD" include hippocampal atrophy, which is considered a marker of neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in the hippocampus and throughout the whole brain. Recent modalities such as diffusion-tensor imaging and resting-state functional MRI provide additional measures that could contribute to the early diagnosis but require further validation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Lipworth, Adam D; Park, Jong Min; Trefrey, Brie L; Rubin, Krista M; Geller, Alan C; Sober, Arthur J; Tsao, Hensin
As melanoma rates increase, and the supply of dermatologists remains suboptimal to meet demand for services, detection of early melanoma has become an increasingly difficult challenge. Some authors advocate for shifting dermatologic resources from routine appointments to urgent visits for those with lesions concerning for melanoma. We sought to investigate the potential of an urgent access track (UAT) embedded within a pigmented lesion clinic to improve early melanoma detection. We conducted a retrospective review of patient records from a tertiary care hospital's pigmented lesion clinic and the associated UAT. Results of procedures for all 4495 patient visits to the routine track and all 316 visits to the UAT during the 21-month study period were included, as were detailed chart reviews of all UAT patient visits. UAT visits were more than 4 times as likely (4.1% vs 1.0%) to yield a diagnosis of melanoma as routine track visits (odds ratio 4.24; 95% confidence interval 2.28-7.88; P < .0001), and almost 25 times as likely (2.2% vs 0.1%) to yield a diagnosis of metastatic melanoma (odds ratio 25.4; 95% confidence interval 7.4-87.4; P < .0001). This was a preliminary analysis with only limited data extracted from the routine track pigmented lesion clinic patient visits. This initial analysis of UAT strategy suggests that UATs have potential to detect patients with earlier melanomas; further research is needed to specifically delineate how resources should be best allocated between routine surveillance and urgent care to maximize melanoma early detection and survival. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Furdová, Alena; Sramka, Miron; Thurzo, Andrej; Furdová, Adriana
Objective The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery. Methods The software for segmentation (3D Slicer) created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D®) and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid. Results In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient’s eye with intraocular tumor. In the period 2001–2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma) were treated. The median tumor volume was 0.5 cm3 (0.2–1.6 cm3). The radiation dose was 35.0 Gy by 99% of dose volume histogram. Conclusion The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures. PMID:28203052
Screening, early detection, education, and trends for melanoma: current status (2007-2013) and future directions: Part I. Epidemiology, high-risk groups, clinical strategies, and diagnostic technology.
Mayer, Jonathan E; Swetter, Susan M; Fu, Teresa; Geller, Alan C
While most cancers have shown both decreased incidence and mortality over the past several decades, the incidence of melanoma has continued to grow, and mortality has only recently stabilized in the United States and in many other countries. Certain populations, such as men >60 years of age and lower socioeconomic status groups, face a greater burden from disease. For any given stage and across all ages, men have shown worse melanoma survival than women, and low socioeconomic status groups have increased levels of mortality. Novel risk factors can help identify populations at greatest risk for melanoma and can aid in targeted early detection. Risk assessment tools have been created to identify high-risk patients based on various factors, and these tools can reduce the number of patients needed to screen for melanoma detection. Diagnostic techniques, such as dermatoscopy and total body photography, and new technologies, such as multispectral imaging, may increase the accuracy and reliability of early melanoma detection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Rychetnik, Lucie; McCaffery, Kirsten; Morton, Rachael L; Thompson, John F; Menzies, Scott W; Irwig, Les
There is limited evidence on the relative effectiveness of different follow-up schedules for patients with AJCC stage I or II melanoma, but less frequent follow-up than is currently recommended has been proposed. To describe melanoma clinicians' perspectives on the functions of follow-up, factors that influence follow-up intervals, and important considerations for extending intervals. Qualitative interviews with 16 clinicians (surgical oncologists, dermatologists, melanoma unit physicians) who conduct follow-up at two of Australia's largest specialist centers. Follow-up is conducted for early detection of recurrences or new primary melanomas, to manage patient anxiety, support patient self-care, and as part of shared care. Recommended intervals are based on guidelines but account for each patient's clinical risk profile, level of anxiety, patient education requirements, capacity to engage in skin self-examination, and how the clinician prefers to manage any suspicious lesions. To revise guidelines and implement change it is important to understand the rationale underpinning existing practice. Extended follow-up intervals for early stage melanoma are more likely to be adopted after the first year when patients are less anxious and sufficiently prepared to conduct self-examination. Clinicians may retain existing schedules for highly anxious patients or those unable to examine themselves. Copyright © 2012 Wiley Periodicals, Inc.
Afifi, Shereen; GholamHosseini, Hamid; Sinha, Roopak
Support Vector Machine (SVM) is a common classifier used for efficient classification with high accuracy. SVM shows high accuracy for classifying melanoma (skin cancer) clinical images within computer-aided diagnosis systems used by skin cancer specialists to detect melanoma early and save lives. We aim to develop a medical low-cost handheld device that runs a real-time embedded SVM-based diagnosis system for use in primary care for early detection of melanoma. In this paper, an optimized SVM classifier is implemented onto a recent FPGA platform using the latest design methodology to be embedded into the proposed device for realizing online efficient melanoma detection on a single system on chip/device. The hardware implementation results demonstrate a high classification accuracy of 97.9% and a significant acceleration factor of 26 from equivalent software implementation on an embedded processor, with 34% of resources utilization and 2 watts for power consumption. Consequently, the implemented system meets crucial embedded systems constraints of high performance and low cost, resources utilization and power consumption, while achieving high classification accuracy.
Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C
Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.
Ahmad, Shamail; Orrell, Martin; Iliffe, Steve; Gracie, Antonia
Background In primary care, the diagnosis of dementia is often delayed and the 2007 National Audit Office Report concluded action was needed to improve patient care and value for money. Aim To investigate the attitudes, awareness, and practice of GPs in England regarding early diagnosis and management of patients with dementia, and perceptions of local specialist services, to identify training or support needs. Design of study Secondary analysis of survey data that capture the above attitudes, awareness, and practice. Setting Online survey, targeting GP members of medeConnect. Method Survey data were obtained using an anonymised online self-completion questionnaire, and then analysed using standard data-analysis software. Results A total of 1011 GPs across the eight English regions responded. Older GPs were more confident in diagnosing and giving advice about dementia, but less likely to feel that early diagnosis was beneficial, and more likely to feel that patients with dementia can be a drain on resources with little positive outcome. Younger GPs were more positive and felt that much could be done to improve quality of life. Attitudes had no correlation with sex. GPs in general felt they had not had sufficient basic and post-qualifying training in dementia, and overall knowledge about dementia was low. Conclusion Much could be done to improve GPs' knowledge of dementia, and the confidence of older GPs could be an educational resource. However, greater experience may create scepticism about early diagnosis because of the perceived poor quality of specialist services. PMID:20849686
Gao, Wei; Chen, Dawei; Ran, Xingwu
Acral lentiginous melanoma (AML) does not exhibit the classic signs of malignant melanoma. ALM is frequently misdiagnosed because of its unusual sites and atypical clinical morphologies, which lead to poor prognosis. A female patient aged 78 years was presented to our center with two ulcers on her right foot. Diabetic foot ulcer was considered as the primary diagnosis. The ulcers failed to improve after 2 weeks' therapy. An incisional biopsy of the lesion revealed malignant melanoma. The patient received wide excision, skin grafting as well as biotherapy. The lesion was healed and no other metastasis has been founded until now. Clinicians must maintain a high level of suspicion in distinguishing malignant melanoma from other more benign skin lesions of the foot. The need for early biopsy of ulcer, even when clinical suspicion is low, can not be overemphasized. Only in this way can we reduce misdiagnosis rate and improve survival rate in patients with foot ulcer.
Zhang, X X; Fang, Y; Xu, L B; Xu, S F; Zhao, Z G; Sun, C; Ma, P Q; Liu, T; Yu, S J; Zhang, W J
Objective: To evaluate the clinical value of preoperative (18)F-Fludeoxyglucose ((18)F-FDG PET-CT) in lymphatic metastasis diagnosis of cutaneous melanoma on extremities and trunk. Methods: 112 patients with cutaneous melanoma pathologically of extremities and trunk from January 2006 to December 2016, who received (18)F-FDG PET-CT examination preoperatively, were retrospectively reviewed. The correlations between the maximal diameters of lymph nodes, the maximal standard uptake value (SUV) and the diagnostic impression grades of PET-CT examination, and the final pathological diagnosis were analyzed. The correlations between Breslow thickness of primary lesions and the diagnostic impression of PET-CT examination were also analyzed. All the above were analyzed with Receiver Operating Characteristic (ROC) curve to get the cut-off value. Based on the final results of pathological diagnosis of lymph nodes as the golden standard, the statistically significant indicators of ROC curve analysis were used to evaluate the diagnostic effect, as well as to calculate the sensitivity, specificity and accuracy. With gender, age, maximal diameter of lymph nodes, maximal SUV, diagnosis impressions, and Breslow thickness as the independent variables and pathological diagnosis results of lymph nodes as the dependent variable, two-class stepwise Logistic regression analysis was used to determine the independence of diagnostic indicators. ROC curve analysis and log rank test were used to analyze the relationship between Breslow thickness and patient survival. Results: To evaluate melanoma patients' lymph node status, the results of ROC curve analysis showed that the area under the curve of lymph node maximal diameter, maximal SUV, diagnosis impression of PET-CT examinations were 0.789, 0.786 and 0.816, respectively (all P <0.05). The cut-off values were 0.85 cm, 1.45 and 2.5, respectively. The sensitivity of the cut-off values to determine the status of lymph nodes in melanoma patients
Chiarugi, Alessandra; Nardini, Paolo; Borgognoni, Lorenzo; Brandani, Paola; Gerlini, Gianni; Rubegni, Pietro; Lamberti, Arianna; Salvini, Camilla; Lo Scocco, Giovanni; Cecchi, Roberto; Sirna, Riccardo; Lorenzi, Stefano; Gattai, Riccardo; Battistini, Silvio; Crocetti, Emanuele
The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type life style, where there is a progressive increasing incidence and a low but not decreasing mor- tality, or somewhere an increase too, especially in the older age groups. Also in Tuscany there is a steady rise in incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case- case study, thin and thick melanoma cases, trying to find out those personal and tumour characteristics which may help to customize preventive interventions. RESULTS The results confirmed the age and the lower edu- cation level are associated with a later detection. The habit to perform skin self-examination is resulted protec- tive forward thick melanoma and also the diagnosis by a doctor. The elements emerging from the survey allow to hypothesize a group of subjects resulting at higher risk for a late diagnosis, aged over 50 and carrier of a fewer constitutional and environmental risk factors: few total and few atypical nevi, and lower sun exposure and burning. It is assumable that a part of people did not be reached from messages of prevention because does not recognize oneself in the categories of people at risk for skin cancers described in educational cam- paigns. If we want to obtain better results on diagnosis of skin melanoma we have to think a new strategy. At least to think over the educational messages discriminating people more at risk of incidence of melanoma from people more at risk to die from melanoma, and to renewed active involvement of the Gen- eral Practitioners .
O'Rorke, M A; Black, C; Murray, L J; Cardwell, C R; Gavin, A T; Cantwell, M M
Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (<25 years) parental age at birth and both a higher birth order and greater household density OR 0.61 (95% CI 0.37-0.99) and OR 0.56 (95% CI 0.30-1.0) respectively. This large study of early onset melanoma supports a positive association with higher birth weight (imperatively gestational age adjusted) and CMM risk which may be related to factors which drive intrauterine foetal growth. Strong inverse associations observed with higher birth order and household density suggest that early-life immune modulation may confer protection; findings which warrant further investigation in prospective analyses. Copyright © 2012 Elsevier Ltd. All rights reserved.
Eltayef, Khalid; Li, Yongmin; Liu, Xiaohui
Malignant melanoma is the most hazardous type of human skin cancer and its incidence has been rapidly increasing. Early detection of malignant melanoma in dermoscopy images is very important and critical, since its detection in the early stage can be helpful to cure it. Computer Aided Diagnosis systems can be very helpful to facilitate the early detection of cancers for dermatologists. In this paper, we present a novel method for the detection of melanoma skin cancer. To detect the hair and several noises from images, pre-processing step is carried out by applying a bank of directional filters. And therefore, Image inpainting method is implemented to fill in the unknown regions. Fuzzy C-Means and Markov Random Field methods are used to delineate the border of the lesion area in the images. The method was evaluated on a dataset of 200 dermoscopic images, and superior results were produced compared to alternative methods.
Yu, Chuan-Hang; Chen, Huang-Hsu; Liu, Chia-Ming; Jeng, Yung-Ming; Wang, Jeng-Tzung; Wang, Yi-Ping; Liu, Bu-Yuan; Sun, Andy; Chiang, Chun-Pin
Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three. This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers. Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 +/- 43%) was significantly lower than that of HMB-45 (83 +/- 28%, P = 0.0065) or of S-100 (79 +/- 33%, P = 0.0237). Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.
Vasefi, Fartash; MacKinnon, Nicholas B.; Booth, Nicholas; Farkas, Daniel L.
Purpose: To determine the performance of a multimode dermoscopy system (SkinSpect) designed to quantify and 3-D map in vivo melanin and hemoglobin concentrations in skin and its melanoma scoring system, and compare the results accuracy with SIAscopy, and histopathology. Methods: A multimode imaging dermoscope is presented that combines polarization, fluorescence and hyperspectral imaging to accurately map the distribution of skin melanin, collagen and hemoglobin in pigmented lesions. We combine two depth-sensitive techniques: polarization, and hyperspectral imaging, to determine the spatial distribution of melanin and hemoglobin oxygenation in a skin lesion. By quantifying melanin absorption in pigmented areas, we can also more accurately estimate fluorescence emission distribution mainly from skin collagen. Results and discussion: We compared in vivo features of melanocytic lesions (N = 10) extracted by non-invasive SkinSpect and SIMSYS-MoleMate SIAscope, and correlate them to pathology report. Melanin distribution at different depths as well as hemodynamics including abnormal vascularity we detected will be discussed. We will adapt SkinSpect scoring with ABCDE (asymmetry , border, color, diameter, evolution) and seven point dermatologic checklist including: (1) atypical pigment network, (2) blue-whitish veil, (3) atypical vascular pattern, (4) irregular streaks, (5) irregular pigmentation, (6) irregular dots and globules, (7) regression structures estimated by dermatologist. Conclusion: Distinctive, diagnostic features seen by SkinSpect in melanoma vs. normal pigmented lesions will be compared by SIAscopy and results from histopathology.
Levin, Lotan; Srour, Shani; Gartner, Jared; Kapitansky, Oxana; Qutob, Nouar; Dror, Shani; Golan, Tamar; Dayan, Roy; Brener, Ronen; Ziv, Tamar; Khaled, Mehdi; Schueler-Furman, Ora; Samuels, Yardena; Levy, Carmit
Epidemiological studies suggest a direct link between melanoma and Parkinson's disease (PD); however, the underlying molecular basis is unknown. Since mutations in Parkin are the major driver of early-onset PD and Parkin was recently reported to play a role in cancer development, we hypothesized that Parkin links melanoma and PD. By analyzing whole exome/genome sequencing of Parkin from 246 melanoma patients, we identified five non-synonymous mutations, three synonymous mutations, and one splice region variant in Parkin in 3.6% of the samples. In vitro analysis showed that wild-type Parkin plays a tumor suppressive role in melanoma development resulting in cell-cycle arrest, reduction of metabolic activity, and apoptosis. Using a mass spectrometry-based analysis, we identified potential Parkin substrates in melanoma and generated a functional protein association network. The activity of mutated Parkin was assessed by protein structure modeling and examination of Parkin E3 ligase activity. The Parkin-E28K mutation impairs Parkin ubiquitination activity and abolishes its tumor suppressive effect. Taken together, our analysis of genomic sequence and in vitro data indicate that Parkin is a potential link between melanoma and Parkinson's disease. Our findings suggest new approaches for early diagnosis and treatment against both diseases. Copyright © 2016. Published by Elsevier Ltd.
Al-Qazzaz, Noor Kamal; Ali, Sawal Hamid; Ahmad, Siti Anom; Islam, Shabiul
The early detection of poststroke dementia (PSD) is important for medical practitioners to customize patient treatment programs based on cognitive consequences and disease severity progression. The aim is to diagnose and detect brain degenerative disorders as early as possible to help stroke survivors obtain early treatment benefits before significant mental impairment occurs. Neuropsychological assessments are widely used to assess cognitive decline following a stroke diagnosis. This study reviews the function of the available neuropsychological assessments in the early detection of PSD, particularly vascular dementia (VaD). The review starts from cognitive impairment and dementia prevalence, followed by PSD types and the cognitive spectrum. Finally, the most usable neuropsychological assessments to detect VaD were identified. This study was performed through a PubMed and ScienceDirect database search spanning the last 10 years with the following keywords: “post-stroke”; “dementia”; “neuro-psychological”; and “assessments”. This study focuses on assessing VaD patients on the basis of their stroke risk factors and cognitive function within the first 3 months after stroke onset. The search strategy yielded 535 articles. After application of inclusion and exclusion criteria, only five articles were considered. A manual search was performed and yielded 14 articles. Twelve articles were included in the study design and seven articles were associated with early dementia detection. This review may provide a means to identify the role of neuropsychological assessments as early PSD detection tests. PMID:25246795
Santo, Marco Aurelio; Pajecki, Denis; Riccioppo, Daniel; Cleva, Roberto; Kawamoto, Flavio; Cecconello, Ivan
Bariatric surgery has proven to be the most effective method of treating severe obesity. Nevertheless, the acceptance of bariatric surgery is still questioned. The surgical complications observed in the early postoperative period following surgeries performed to treat severe obesity are similar to those associated with other major surgeries of the gastrointestinal tract. However, given the more frequent occurrence of medical comorbidities, these patients require special attention in the early postoperative follow-up. Early diagnosis and appropriate treatment of these complications are directly associated with a greater probability of control. The medical records of 538 morbidly obese patients who underwent surgical treatment (Roux-en-Y gastric bypass surgery) were reviewed. Ninety-three (17.2%) patients were male and 445 (82.8%) were female. The ages of the patients ranged from 18 to 70 years (average = 46), and their body mass indices ranged from 34.6 to 77 kg/m2. Early complications occurred in 9.6% and were distributed as follows: 2.6% presented bleeding, intestinal obstruction occurred in 1.1%, peritoneal infections occurred in 3.2%, and 2.2% developed abdominal wall infections that required hospitalization. Three (0.5%) patients experienced pulmonary thromboembolism. The mortality rate was 0,55%. The incidence of early complications was low. The diagnosis of these complications was mostly clinical, based on the presence of signs and symptoms. The value of the clinical signs and early treatment, specially in cases of sepsis, were essential to the favorable surgical outcome. The mortality was mainly related to thromboembolism and advanced age, over 65 years.
Kobayashi, Junya; Fujimoto, Daisuke; Murakami, Makoto; Hirono, Yasuo; Goi, Takanori
The present case study reported of amelanotic malignant melanoma of the esophagus. A 68-year-old man underwent laparoscopic distal gastrectomy for early gastric cancer diagnosis. After gastrectomy, endoscopic examination revealed a protruded lesion lying adjacent to the melanosis area of the esophagus. Histology of the biopsy specimen suggested malignancy, but the diagnosis could not be made. The patient underwent trans-thoraco-abdominal curative subtotal esophagectomy. Immunohistochemical examination of the resected specimen was negative for HBM-45 and Melan-A. However, immunohistochemical examinations of SOX10 (Sry-related HMg-Box gene 10) and KBA.62, which are not associated with melanosome, were strongly positive, and tyrosinase was notably positive. A diagnosis primary of amelanotic malignant melanoma of the esophagus that consisted of only premelanosomes was made. The present findings suggest that, in the diagnosis of malignant melanoma, SOX10 and KBA.62 may be useful, particularly in diagnosing amelanotic malignant melanoma.
Fisher, Nina M; Schaffer, Julie V; Berwick, Marianne; Bolognia, Jean L
Because the early detection of cutaneous melanoma can dramatically improve survival, identification and surveillance of persons at risk have received much attention. Our purpose was to examine the influences of personal or family history, patterns of detection, and prior skin biopsies (considered to be a measurement of surveillance by medical personnel) on the Breslow depth of cutaneous melanomas. A retrospective cohort analysis of 218 patients with a history of at least one invasive cutaneous melanoma who visited the Yale Pigmented Lesion Clinic between January 1995 and January 1996 was performed. Data on patterns of detection, melanocytic nevi, and skin biopsies before and after the initial diagnosis of melanoma were collected, and patients with a family history of melanoma were compared with sporadic patients. Initial melanomas discovered by dermatologists were more likely to be 0.75 mm or less in depth than those found by other physicians (P = .03). Although patients detected 45% of the initial primary melanomas (98/218), dermatologists discovered 80% of the second primary tumors (33/41; P = .001). A personal history of melanoma was predictive of a thinner Breslow depth (P = .01), but a family history of melanoma was not. Having a biopsy of any type or combination of types of skin lesion(s) performed in the 5 years, 2 years, or 1 year before the first diagnosis of melanoma did not predict a melanoma of thinner Breslow depth among either familial or sporadic patients. The mean number of skin biopsies performed per patient was 8 times higher in the 5-year period after (5.6) versus the 5-year period before (0.7) the initial diagnosis of melanoma, with a peak in the first year after the diagnosis (2.3 vs 0.25 in the prior year). In 27 patients, one or more skin biopsies were performed in the year before the initial diagnosis of melanoma; 41% of these biopsies (23/56) were of lesions in normally exposed sites (eg, the face, neck, and forearms) compared with 22% of
Kaliki, S; Shields, C L
Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival. PMID:27911450
Miura, Yoshinobu; Mikada, Mamoru; Ouchi, Tomoki; Horie, Sachiko; Takeda, Kazu; Yamaki, Teppei; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya
Regional lymph node status is an important prognostic indicator of tumor aggressiveness. However, early diagnosis of metastasis using intranodal pressure, at a stage when lymph node size has not changed significantly, has not been investigated. Here, we use an MXH10/Mo-lpr/lpr mouse model of lymph node metastasis to show that intranodal pressure increases in both the subiliac lymph node and proper axillary lymph node, which are connected by lymphatic vessels, when tumor cells are injected into the subiliac lymph node to induce metastasis to the proper axillary lymph node. We found that intranodal pressure in the subiliac lymph node increased at the stage when metastasis was detected by in vivo bioluminescence, but when proper axillary lymph node volume (measured by high-frequency ultrasound imaging) had not increased significantly. Intravenously injected liposomes, encapsulating indocyanine green, were detected in solid tumors by in vivo bioluminescence, but not in the proper axillary lymph node. Basic blood vessel and lymphatic channel structures were maintained in the proper axillary lymph node, although sinus histiocytosis was detected. These results show that intranodal pressure in the proper axillary lymph node increases at early stages when metastatic tumor cells have not fully proliferated. Intranodal pressure may be a useful parameter for facilitating early diagnosis of lymph node metastasis. © 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
de Sousa, E B; Dos Santos, G C; Duarte, M E L; Moura, V; Aguiar, D P
Osteoarthritis (OA) is the main cause of disability worldwide, due to progressive articular cartilage loss and degeneration. According to recent research, OA is more than just a degenerative disease due to some metabolic components associated to its pathogenesis. However, no biomarker has been identified to detect this disease at early stages or to track its development. Metabolomics is an emerging field and has the potential to detect many metabolites in a single spectrum using high resolution nuclear magnetic resonance (NMR) techniques or mass spectrometry (MS). NMR is a reproducible and reliable non-destructive analytical method. On the other hand, MS has a lower detection limit and is more destructive, but it is more sensitive. NMR and MS are useful for biological fluids, such as urine, blood plasma, serum, or synovial fluid, and have been used for metabolic profiling in dogs, mice, sheep, and humans. Thus, many metabolites have been listed as possibly associated to OA pathogenesis. The goal of this review is to provide an overview of the studies in animal models and humans, regarding the use of metabolomics as a tool for early osteoarthritis diagnosis. The concept of osteoarthritis as a metabolic disease and the importance of detecting a biomarker for its early diagnosis are highlighted. Then, some studies in plasma and synovial tissues are shown, and finally the application of metabolomics in the evaluation of synovial fluid is described.
Cai, Chengzhong; Carey, Kai A; Nedosekin, Dmitry A; Menyaev, Yulian A; Sarimollaoglu, Mustafa; Galanzha, Ekaterina I; Stumhofer, Jason S; Zharov, Vladimir P
In vivo photoacoustic (PA) flow cytometry (PAFC) has already demonstrated a great potential for the diagnosis of deadly diseases through ultrasensitive detection of rare disease-associated circulating markers in whole blood volume. Here, we demonstrate the first application of this powerful technique for early diagnosis of malaria through label-free detection of malaria parasite-produced hemozoin in infected red blood cells (iRBCs) as high-contrast PA agent. The existing malaria tests using blood smears can detect the disease at 0.001-0.1% of parasitemia. On the contrary, linear PAFC showed a potential for noninvasive malaria diagnosis at an extremely low level of parasitemia of 0.0000001%, which is ∼10(3) times better than the existing tests. Multicolor time-of-flight PAFC with high-pulse repetition rate lasers at wavelengths of 532, 671, and 820 nm demonstrated rapid spectral and spatial identification and quantitative enumeration of individual iRBCs. Integration of PAFC with fluorescence flow cytometry (FFC) provided real-time simultaneous detection of single iRBCs and parasites expressing green fluorescence proteins, respectively. A combination of linear and nonlinear nanobubble-based multicolor PAFC showed capability to real-time control therapy efficiency by counting of iRBCs before, during, and after treatment. Our results suggest that high-sensitivity, high-resolution ultrafast PAFC-FFC platform represents a powerful research tool to provide the insight on malaria progression through dynamic study of parasite-cell interactions directly in bloodstream, whereas portable hand-worn PAFC device could be broadly used in humans for early malaria diagnosis. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.
Nurdin, D. S.; Isa, M. N.; Ismail, R. C.; Ahmad, M. I.
This paper presents an optimized design of Processing Element (PE) of Systolic Array (SA) which implements affine gap penalty Smith Waterman (SW) algorithm on the Xilinx Virtex-6 XC6VLX75T Field Programmable Gate Array (FPGA) for Deoxyribonucleic Acid (DNA) sequence alignment. The PE optimization aims to reduce PE logic resources to increase number of PEs in FPGA for higher degree of parallelism during alignment matrix computations. This is useful for aligning long DNA-based disease sequence such as Breast Cancer (BC) for early diagnosis. The optimized PE architecture has the smallest PE area with 15 slices in a PE and 776 PEs implemented in the Virtex - 6 FPGA.
Di Giusto, M; Lazzari, R; Giorgetti, T; Paesano, R; Pachi, A
The early discovery of a fetal pathology creates a "crisis" situation fraught with psychic problems for the couple who must live through it. The Authors observed a group of patients in the second trimester of pregnancy. They had all requested therapeutic abortion since serious malformation of the fetus had been confirmed. By means of a questionnaire constructed for the purpose, certain characteristics of fetal malformation and of pregnancy were evidenced, as well as the way these were experienced by the patients. The immediate and delayed reactions to the diagnosis of malformation were also studied, as was the experience lived when faced with the choice of abortion.
Waller, D. A.; Hasan, A.; Forty, J.; Morritt, G. N.
We report our experience using the new technique of videothoracoscopy in the diagnosis of intrathoracic pathology. In the last 12 months, 40 patients (24 male; 16 female) have undergone investigation by this method. Lung biopsy has been performed in 17 patients, pleural biopsy in 20 patients and mediastinal biopsy in three patients. The majority had been referred after other investigations had been inconclusive. All biopsies were diagnostic except one mediastinal biopsy. This early experience suggests that videothoracoscopic biopsy is a well-tolerated technique with high diagnostic yield. PMID:8154806
Casaroto, Ana R; Loures, Daniela C N Rocha; Moreschi, Eduardo; Veltrini, Vanessa C; Trento, Cleverson L; Gottardo, Vilmar D; Lara, Vanessa S
The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by keratocystic odontogenic tumors (KCOT) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article paper reports the case of a patient, a 10-year-old boy with NBCCS, emphasizing its clinical and radiographic manifestations. This study highlights the importance of health professionals in the early diagnosis of NBCCS and in a preventive multidisciplinary approach to provide a better prognosis for the patient.
Wong, Ngai Sze; Huang, Shujie; Zheng, Heping; Chen, Lei; Zhao, Peizhen; Tucker, Joseph D; Yang, Li Gang; Goh, Beng Tin; Yang, Bin
Early diagnosis of syphilis and timely treatment can effectively reduce ongoing syphilis transmission and morbidity. We examined the factors associated with the early diagnosis of syphilis to inform syphilis screening strategic planning. In an observational study, we analyzed reported syphilis cases in Guangdong Province, China (from 2014 to mid-2015) accessed from the national case-based surveillance system. We categorized primary and secondary syphilis cases as early diagnosis and categorized latent and tertiary syphilis as delayed diagnosis. Univariate analyses and multivariable logistic regressions were performed to identify the factors associated with early diagnosis. We also examined the factors associated with early diagnosis at the individual and city levels in multilevel logistic regression models with cases nested by city (n = 21), adjusted for age at diagnosis and gender. Among 83,944 diagnosed syphilis cases, 22% were early diagnoses. The city-level early diagnosis rate ranged from 7 to 46%, consistent with substantial geographic variation as shown in the multilevel model. Early diagnosis was associated with cases presenting to specialist clinics for screening, being male and attaining higher education level. Cases received syphilis testing in institutions and hospitals, and diagnosed in hospitals were less likely to be in early diagnosis. At the city-level, cases living in a city equipped with more hospitals per capita were less likely to be early diagnosis. To enhance early diagnosis of syphilis, city-specific syphilis screening strategies with a mix of passive and client/provider-initiated testing might be a useful approach.
Early diagnosis of primary open-angle glaucoma has not been clear and consistent in concepts and methods. At present, according to the pathophysiology process of optic nerve damage and its detection technology, early diagnosis on the concept still belongs to the early clinical diagnosis instead of preclinical diagnosis, and on the method depends on the fundus as morphological index combined with the visual field as functional index. The direction of early clinical diagnosis mainly lies in exploring more effective diagnosis index, rather than blindly adopt new diagnostic technology.
Manzoor Atta, Babar; Saleem, M.; Ali, Hina; Arshad, Hafiz Muhammad Imran; Ahmed, M.
The current study was designed to identify the stage for the diagnosis of disease before visible symptoms appeared. Fluorescence spectroscopy has been employed to identify disease signatures for its early diagnosis in rice plant leaves. Bacterial leaf blight (BLB) diseased and healthy leaf samples were collected from the rice fields in September, 2017 which were then used to record spectra using an excitation wavelength at 410 nm. The spectral range of emission was set from 420 to 800 nm which covers the blue–green and the chlorophyll bands. It was found that diseased leaves have a narrower ‘chlorophyll a’ band than healthy ones, and furthermore, that the emission band at 730 nm was either declined or depleted in the sample with high infection symptoms. In contrast, the blue–green region was observed to increase due to the emergence of disease. As the band intensity of chlorophyll decreases during infection, this decrease in chlorophyll content and increase in the blue–green spectral region could provide a new approach for predicting BLB at an early stage. The important finding was that the chlorophyll degradation and rise in the blue–green region take place in leaves with BLB or during BLB infection. Principal component analysis has been applied to spectral data which successfully separated diseased samples from healthy ones even with very small spectral variations.
We are developing micropreconcentrators based on micro/nanotechnology to detect trace levels of volatile organic compound (VOC) gases contained in human and canine exhaled breath. The possibility of using exhaled VOC gases as biomarkers for various cancer diagnoses has been previously discussed. For early cancer diagnosis, detection of trace levels of VOC gas is indispensable. Using micropreconcentrators based on MEMS technology or nanotechnology is very promising for detection of VOC gas. A micropreconcentrator based breath analysis technique also has advantages from the viewpoints of cost performance and availability for various cancers diagnosis. In this paper, we introduce design, fabrication and evaluation results of our MEMS and nanotechnology based micropreconcentrators. In the MEMS based device, we propose a flower leaf type Si microstructure, and its shape and configuration are optimized quantitatively by finite element method simulation. The nanotechnology based micropreconcentrator consists of carbon nanotube (CNT) structures. As a result, we achieve ppb level VOC gas detection with our micropreconcentrators and usual gas chromatography system that can detect on the order of ppm VOC in gas samples. In performance evaluation, we also confirm that the CNT based micropreconcentrator shows 115 times better concentration ratio than that of the Si based micropreconcentrator. Moreover, we discuss a commercialization idea for new cancer diagnosis using breath analysis. Future work and preliminary clinical testing in dogs is also discussed.
Parida, Pradipta; Nirmal, Nirmal Shanmugasundaram; Gopalakrishnan, Surianarayanan; Saxena, Sunil Kumar
To study the clinical and radiological findings to make early diagnosis of foreign body (FB) aspiration in children. This prospective study was conducted on 45 children below 12 years of age with a clinical diagnosis of FB aspiration undergone rigid bronchoscopy from September 2008 to may 2010. Bronchoscopy was positive for FB in 37 children. The results of these 37 children (15 female and 22 male) were analyzed. 81% of children were in age group of 1-3 years. Penetration syndrome (sudden onset coughing, choking and gagging when the child is having something in the mouth) (89.2%) and decreased breath sounds (86.5%) were the most common clinical features. Cough, respiratory difficulty and fever were present in 83.8%, 78.4% and 27% respectively. Tachypnoea, tachycardia, chest retractions, decreased chest movements and wheeze were present in 83.3%, 83.3%, 83.3%, 51.4% and 43.2% respectively. Unilateral hyperinflation (64.9%), mediastinal shift (45.9%), and collapse (21.6%) were common radiological sign on chest radiograph and in 13.5% patients the chest X-rays were normal. Sites of FB lodgments were larynx, trachea, right main bronchus, left main bronchus and bilateral bronchi in 10.8%, 10.8%, 35.1%, 37.8 and 5.5% respectively. Food related FBs were present in 30 cases (peanut in 54.1%) and inorganic FBs were present in 7 cases. FBs were removed successfully by rigid bronchoscopy in all cases without any mortality. Penetration syndrome, localized decreased breath sounds, unilateral hyperinflation and/or mediastinal shift on radiology are predictors for early diagnosis of FB aspiration.
Dye, Danielle E.; Medic, Sandra; Ziman, Mel; Coombe, Deirdre R.
The majority of patients diagnosed with melanoma present with thin lesions and generally these patients have a good prognosis. However, 5% of patients with early melanoma (<1 mm thick) will have recurrence and die within 10 years, despite no evidence of local or metastatic spread at the time of diagnosis. Thus, there is a need for additional prognostic markers to help identify those patients that may be at risk of recurrent disease. Many studies and several meta-analyses have compared gene and protein expression in melanocytes, naevi, primary, and metastatic melanoma in an attempt to find informative prognostic markers for these patients. However, although a large number of putative biomarkers have been described, few of these molecules are informative when used in isolation. The best approach is likely to involve a combination of molecules. We believe one approach could be to analyze the expression of a group of interacting proteins that regulate different aspects of the metastatic pathway. This is because a primary lesion expressing proteins involved in multiple stages of metastasis may be more likely to lead to secondary disease than one that does not. This review focuses on five putative biomarkers – melanoma cell adhesion molecule (MCAM), galectin-3 (gal-3), matrix metalloproteinase 2 (MMP-2), chondroitin sulfate proteoglycan 4 (CSPG4), and paired box 3 (PAX3). The goal is to provide context around what is known about the contribution of these biomarkers to melanoma biology and metastasis. Although each of these molecules have been independently identified as likely biomarkers, it is clear from our analyses that each are closely linked with each other, with intertwined roles in melanoma biology. PMID:24069584
Liu, Feng; Bessonova, Leona; Taylor, Thomas H.; Ziogas, Argyrios; Meyskens, Frank L.; Anton-Culver, Hoda
Summary Using US SEER17 Registry data, age-specific melanoma incidence rates were calculated and comparisons were made between males and females. Relative Risk (RR) for males and females in each age group was computed and compared with that from Nordic Cancer Registry data set and to that for non-melanoma skin cancer (NMSC). For age groups 44 and younger, females showed higher incidence rates, with a peak difference at age 20–24 (RR = 2.01, 95% CI = 1.21–3.33). Males exhibited higher incidence rates after age 44. The same bimodal gender difference was confirmed by the Nordic Cancer Registry data set, but it was not observed for NMSC, which is known to be strongly associated with cumulative exposure to solar UV radiation. We conclude that exposure to solar ultraviolet (UV) radiation is the major causative factor for melanoma at older age (>44 yr), but that other factors may play a role in early onset melanomas, particularly in females. PMID:23095171
Kaufman, Charles K
Melanoma skin cancer is a potentially deadly disease in humans and has remained extremely difficult to treat once it has metastasized. In just the last 10 years, a number of models of melanoma have been developed in the zebrafish that are biologically faithful to the human disease and have already yielded important insights into the fundamental biology of melanoma and offered new potential avenues for treatment. With the diversity and breadth of the molecular genetic tools available in the zebrafish, these melanoma models will continue to be refined and expanded upon to keep pace with the rapidly evolving field of melanoma biology.
Distler, Oliver; Allanore, Yannick; Denton, Christopher P; Matucci-Cerinic, Marco; Pope, Janet E; Hinzmann, Barbara; Davies, Siobhan; de Oliveira Pena, Janethe; Khanna, Dinesh
To gain insight into clinical practice regarding referral, early diagnosis and other aspects of the management of patients with dcSSc in Europe and the USA. Semi-structured interviews were conducted with 84 rheumatologists (or internal medicine physicians) and 40 dermatologists in different countries (the UK, France, Germany, Italy, Spain and the USA). Physicians were asked to identify key steps in the patient pathway relating to patient presentation, diagnosis and referral, in addition to other treatment and follow-up processes. The interviewed physicians reported that late presentation with dcSSc was common, with some patients presenting to primary care physicians after symptoms had persisted for up to 1 year. Awareness of dcSSc is reported to vary widely among primary care physicians. Final diagnosis, generally following guideline-based recommendations, was by rheumatologists in most cases (or internal medicine physicians in France) and they remained responsible for global patient management, with lesser involvement in diagnosis and management by dermatologists. Specialist centres were not well defined and did not exist in all countries. Patients and primary healthcare providers can be unaware of the symptoms of dcSSc, therefore presentation and referral to specialist care are often late. Thus, improved awareness among patients and primary care physicians is necessary to facilitate earlier referral and diagnosis. Once referred, more consistent use of the modified Rodnan skin score at diagnosis and follow-up may help to monitor disease progression. Furthermore, establishing specialist centres may help to promote such changes and improve patient care.
Boskabadi, Hassan; Omidian, Masoud; Tavallai, Shima; Mohammadi, Shabnam; Parizadeh, Mostafa; Ghayour Mobarhan, Majid; Ferns, Gordon Aa
Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve. A significant difference between the serum concentrations
Boskabadi, Hassan; Omidian, Masoud; Tavallai, Shima; Mohammadi, Shabnam; Parizadeh, Mostafa; Ghayour Mobarhan, Majid; Ferns, Gordon AA
Background: Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. Objectives: Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. Patients and Methods: In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). Results: The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve
Petrelli, Fausto; Coinu, Andrea; Cabiddu, Mary; Borgonovo, Karen; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro
Recent major phase III trials led to the approval of immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab) in metastatic malignant melanoma (MM). We aim to assess whether median progression-free survival, and 1 and 2-year overall survival (OS) rates are reliable surrogate endpoints for median OS through a meta-analysis of published trials involving immunotherapy. A systematic literature search in PubMed, EMBASE, Web of Science, and SCOPUS of published phase II to III trials with immunotherapy as the treatment for MM was conducted. Adjusted weighted linear regression was used to calculate Pearson correlations (R) between surrogates and median OS, and between treatment effects on surrogates and median OS. A total of 13 studies involving 3373 patients with MM were identified. The correlation of progression-free survival with OS was not significant (R = 0.45, P = .11). Conversely, the correlation between 1-year OS and median OS was very strong (R = 0.93, 95% confidence interval [CI] 0.84-0.96, P < .00001), as was the correlation between 2-year OS and OS (R = 0.79, 95% CI 0.51-0.91, P = .0001). The correlation between the treatment effects on 1-year OS and OS was also significant (R = -0.86, 95% CI -0.3 to 0.97, P = .01). Similar results were obtained for 2-year OS. According to the available study data, 1-year OS rate could be regarded as a potential surrogate for median OS in novel immunotherapy trials of metastatic MM. Waiting for ongoing studies (e.g., pembrolizumab), we suggest that this intermediate endpoint could be considered as a potential primary endpoint in future clinical trials.
Friedman, Robert J; Gutkowicz-Krusin, Dina; Farber, Michele J; Warycha, Melanie; Schneider-Kels, Lori; Papastathis, Nicole; Mihm, Martin C; Googe, Paul; King, Roy; Prieto, Victor G; Kopf, Alfred W; Polsky, David; Rabinovitz, Harold; Oliviero, Margaret; Cognetta, Armand; Rigel, Darrell S; Marghoob, Ashfaq; Rivers, Jason; Johr, Robert; Grant-Kels, Jane M; Tsao, Hensin
To evaluate the performance of dermoscopists in diagnosing small pigmented skin lesions (diameter = 6 mm) compared with an automatic multispectral computer-vision system. Blinded comparison study. Dermatologic hospital-based clinics and private practice offices. Patients From a computerized skin imaging database of 990 small (= 6-mm) pigmented skin lesions, all 49 melanomas from 49 patients were included in this study. Fifty randomly selected nonmelanomas from 46 patients served as a control. Ten dermoscopists independently examined dermoscopic images of 99 pigmented skin lesions and decided whether they identified the lesions as melanoma and whether they would recommend biopsy to rule out melanoma. Diagnostic and biopsy sensitivity and specificity were computed and then compared with the results of the computer-vision system. Dermoscopists were able to correctly identify small melanomas with an average diagnostic sensitivity of 39% and a specificity of 82% and recommended small melanomas for biopsy with a sensitivity of 71% and specificity of 49%, with only fair interobserver agreement (kappa = 0.31 for diagnosis and 0.34 for biopsy). In comparison, in recommending biopsy to rule out melanoma, the computer-vision system achieved 98% sensitivity and 44% specificity. Differentiation of small melanomas from small benign pigmented lesions challenges even expert physicians. Computer-vision systems can facilitate early detection of small melanomas and may limit the number of biopsies to rule out melanoma performed on benign lesions.
Osborne, Lisa A.; McHugh, Louise; Saunders, Jo; Reed, Phil
The current study investigated the impact of diagnosis of Autistic Spectrum Conditions (ASCs) in children on parenting stress. While there is increasing pressure to provide early diagnosis of ASC, there is a lack of evidence relating to the impact of early diagnosis on the parents. The parents of 85 children with ASC completed measures of their…
Sato, Ko; Watanabe, Oshi; Ohmiya, Suguru; Chiba, Fumiko; Suzuki, Akira; Okamoto, Michiko; Younghuang, Jiang; Hata, Akihiro; Nonaka, Hiroyuki; Kitaoka, Setsuko; Nagai, Yukio; Kawamura, Kazuhisa; Hayashi, Masahiro; Kumaki, Satoru; Suzuki, Tamio; Kawakami, Kazuyoshi; Nishimura, Hidekazu
Isolation of human metapneumovirus (HMPV) from clinical specimens is currently inefficient because of the lack of a cell culture system in which a distinct cytopathic effect (CPE) occurs. The cell lines LLC-MK2, Vero and Vero E6 are used for isolation of HMPV; however, the CPE in these cell lines is subtle and usually requires a long observation period and sometimes blind passages. Thus, a cell line in which an early and distinct CPE occurs following HMPV inoculation is highly desired by clinical virology laboratories. In this study, it was demonstrated that, in the human malignant melanoma cell line MNT-1, obvious syncytium formation occurs shortly after inoculation with HMPV-positive clinical specimens. In addition, the growth and efficiency of isolation of HMPV were greater using MNT-1 than using any other conventional cell line. Addition of this cell line to our routine viral isolation system for clinical specimens markedly enhanced isolation frequency, allowing isolation-based surveillance. MNT-1 has the potential to facilitate clinical and epidemiological studies of HMPV. © 2017 The Societies and John Wiley & Sons Australia, Ltd.
Proverbio, Maria Renata; Lamba, Marta; Rossi, Alessandro; Siani, Paolo
Foodborne botulism is a neuroparalytic disease caused by ingestion of food contaminated with botulinum toxins. Despite rare the mortality rate is high if untreated. Diagnosis of botulism is still a challenge for clinician, due to the variability of clinical manifestations and disease course. We report on a child with type B botulin intoxication who was early diagnosed and treated underlining that clinical suspicion is crucial to start prompt treatment. An 11-year-old boy presented with bilateral ptosis and mydriasis, dry mouth, difficulty in swallowing, dysphonia, urine retention and constipation. Clear sensorium and no fever were observed. Immediately the suspicion of botulism was risen and botulinum antitoxin was administered. 3 days later serum and rectal samples tested positive for Clostridium botulinum. The patient completely recovered when discharged from hospital. Foodborne botulism is still possible in developed countries. The confirmation test of botulism requires some days. To avoid long delays between intoxication and diagnosis prompt clinical suspicion is thus crucial. The outcome depends on rapid implementation of appropriate management with intensive respiratory care and antitoxin administration. Copyright © 2015 Elsevier Ltd. All rights reserved.
Reda, Islam; Khalil, Ashraf; Elmogy, Mohammed; Abou El-Fetouh, Ahmed; Shalaby, Ahmed; Abou El-Ghar, Mohamed; Elmaghraby, Adel; Ghazal, Mohammed; El-Baz, Ayman
The objective of this work is to develop a computer-aided diagnostic system for early diagnosis of prostate cancer. The presented system integrates both clinical biomarkers (prostate-specific antigen) and extracted features from diffusion-weighted magnetic resonance imaging collected at multiple b values. The presented system performs 3 major processing steps. First, prostate delineation using a hybrid approach that combines a level-set model with nonnegative matrix factorization. Second, estimation and normalization of diffusion parameters, which are the apparent diffusion coefficients of the delineated prostate volumes at different b values followed by refinement of those apparent diffusion coefficients using a generalized Gaussian Markov random field model. Then, construction of the cumulative distribution functions of the processed apparent diffusion coefficients at multiple b values. In parallel, a K-nearest neighbor classifier is employed to transform the prostate-specific antigen results into diagnostic probabilities. Finally, those prostate-specific antigen–based probabilities are integrated with the initial diagnostic probabilities obtained using stacked nonnegativity constraint sparse autoencoders that employ apparent diffusion coefficient–cumulative distribution functions for better diagnostic accuracy. Experiments conducted on 18 diffusion-weighted magnetic resonance imaging data sets achieved 94.4% diagnosis accuracy (sensitivity = 88.9% and specificity = 100%), which indicate the promising results of the presented computer-aided diagnostic system. PMID:29804518
Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri; Pottegård, Anton; Friis, Søren; Hölmich, Lisbet Rosenkrantz; Gaist, David
The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.
Shimamura, Yuto; Ikeya, Takashi; Marcon, Norman; Mosko, Jeffrey D
Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality. It carries a poor prognosis as more than half of patients present with advanced and unresectable disease. One contributing factor is the increased risk of lymph node metastases at early stages of disease. As such, it is essential to detect squamous cell neoplasia (SCN) at an early stage. In order to risk stratify lesions, endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol’s chromoendoscopy. The assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to treatment. Endoscopic mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective use. Radiofrequency ablation and other endoscopic treatments are currently available although should not be considered first line at this time. Our objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN. PMID:28979708
Moreno Nogueira, J. A.; Valero Arbizu, M.; Pérez Temprano, R.
Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50–80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon-α2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas. PMID:23476798
Jay, V; Font, R L
The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. Case report. Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.
Doubrovsky, Anna; Scolyer, Richard A; Murali, Rajmohan; McKenzie, Paul R; Watson, Geoffrey F; Lee, C Soon; McLeod, Duncan J; McCarthy, William H; Uren, Roger F; Stretch, Jonathan R; Saw, Robyn P; Thompson, John F
The use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated. A retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up. FNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results. FNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma.
Doubrovsky, Anna; Scolyer, Richard A.; Murali, Rajmohan; McKenzie, Paul R.; Watson, Geoffrey F.; Lee, C. Soon; McLeod, Duncan J.; McCarthy, William H.; Uren, Roger F.; Stretch, Jonathan R.; Saw, Robyn P.
Background The use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated. Methods A retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up. Results FNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results. Conclusions FNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma. PMID:17990041
Bhutani, Namita; Kajal, Pradeep; Pawar, Devendra
Melanoma is a malignant tumor that can affect any area of the anatomical economy. Its occurance in the female urethra is extremely rare. We report a case of primary malignant urethral melanoma developed in an elderly female patient. A 70 years old female presented with dysuria, poor stream, gross haematuria, intermittent blood spots, and a painful mass. On physical examination, there were no suspicious lesions on the skin. On external genital examination, a lesion at the level of the urethral meatus was observed. The mass was removed by wide local excision under spinal anaesthesia. The pathological diagnosis was malignant melanoma of the urethra. The common presentations include bleeding and/or discharge per urethra, voiding dysfunction and the presence of tumor mass. Survival depends on the stage, location and size of the neoplasm at the time of diagnosis. Despite major surgery, radiotherapy or immunotherapy; malignant melanoma usually has a poor prognosis. Melanoma of the female urethra is an extremely uncommon pathology leading to paucity of literature and any definite recommendations regarding management. The histological and immunohistochemical findings can be helpful in making an early and accurate diagnosis of malignant melanoma in the urogenital region. Copyright © 2017. Published by Elsevier Ltd.
Oliveria, Susan A; Hay, Jennifer L; Geller, Alan C; Heneghan, Maureen K; McCabe, Mary S; Halpern, Allan C
The rising incidence and mortality rates of melanoma, the most fatal form of skin cancer, are among the greatest increases of all preventable cancers over the past decade. However, because of recent advances in early detection, secondary prevention efforts, and treatment, the number of melanoma survivors is increasing. Little research has been conducted on melanoma survivors and important opportunities exist for research in this understudied population. Here, we outline the important research opportunities related to the study of melanoma survivorship and summarize the paucity of literature currently available. A computerized literature search was performed of the MEDLINE database of the National Library of Medicine from 1966-2005. The scope of the search was limited to those studies published in English. The search was conducted using the following MeSH headings: melanoma, neoplasms, skin neoplasms, survival, and survival rate. The reference lists of relevant book chapters and review articles were further reviewed, and printed materials from recent scientific meetings addressing this topic were obtained. Several factors that affect melanoma survivors warrant further study, including: physiologic long-term effects; psychosocial, behavioral, and cognitive factors; demographic characteristics; surveillance practices; recurrences, secondary primaries, and other cancers; family members of survivors; and economic issues, access to health care/life insurance. Understanding recurrence and second primary cancer risk, psychosocial and cognitive characteristics, behaviors, surveillance patterns, economic sequelae, and family issues of melanoma survivors is important from a public health standpoint to promote the health and well-being of this cohort. Melanoma is an understudied cancer, and the incidence and mortality of this disease are increasing. Describing the long term burden of this cancer and identifying factors that contribute to them will facilitate efforts to develop
Lévêque, L; Dalac, S; Dompmartin, A; Louvet, S; Euvrard, S; Catteau, B; Hazan, M; Schollhamer, M; Aubin, F; Dreno, B; Daguin, P; Chevrant-Breton, J; Frances, C; Bismuth, M J; Tanter, Y; Lambert, D
The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean
Mataca, Ema; Migaldi, Mario; Cesinaro, Anna M
Equivocal pigmented lesions of the head are usually biopsied to avoid inappropriate treatment. Clinical approach has evolved from simple visual examination to sophisticated techniques for selecting the biopsy sites. This study aimed to retrospectively evaluate the efficiency of dermoscopy (DE) and reflectance confocal microscopy (RCM) in sampling a histopathologically representative focus of lentigo maligna/lentigo maligna melanoma. Punch biopsies and surgical excisions of 72 patients, 37 men and 35 women (median age 70.6 years, range 39-90 years), affected by lentigo maligna/lentigo maligna melanoma of the head, sent from a single dermatology clinic, were reviewed for the presence of 5 histopathologic criteria: atypical junctional melanocytes, increased junctional melanocytes, follicular colonization, pagetoid spread and melanocytic junctional nests, plus other minor features. Forty-two patients were biopsied under DE and 30 under RCM guidance. Accuracy of the 2 techniques in sampling a representative tissue overlapped in most cases, although RCM selected sites to biopsy with more histopathologic criteria, in particular pagetoid spread and melanocytic nests. Interestingly, with RCM, inflammation and melanophages were observed more in biopsy than in excision. False positive cases were not registered. Compared with the sampling at naked eye, our results show that DE and RCM help selecting the most appropriate areas for biopsies, thus allowing not only more robust histopathologic diagnoses, but also a more accurate microstaging of tumor.
Takuma, Kensuke; Kamisawa, Terumi; Tabata, Taku; Hara, Seiichi; Kuruma, Sawako; Inaba, Yoshihiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Horiguchi, Shin-ichiro; Igarashi, Yoshinori
AIM: To clarify the strategy for early diagnosis of pancreaticobiliary maljunction (PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops. METHODS: The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography (ERCP). Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM. Of these, patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation. The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated. Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted. RESULTS: Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain (n = 16) or jaundice (n = 12). Radical surgery for gallbladder cancer was only possible in 11 patients (31%) and only 4 patients (11%) survived for 5 years. Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography (MRCP). The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer. All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred. Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls, and hyperplastic changes, hypertrophic muscular layer, subserosal fibrosis, and adenomyomatosis were detected in 7 (88%), 5 (63%), 7 (88%) and 5 (63%) patients, respectively. Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients
Melanoma treatment options include excision, immunotherapy, targeted therapy, chemotherapy, intralesional therapy and palliative local therapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent melanoma in this summary for clinicians.
Intraocular (uveal) melanoma treatment options include observation, surgery, radiation therapy, and transpupillary thermotherapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent intraocular melanoma in this summary for clinicians.
Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen
Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). © 2016 APMIS. Published by John Wiley & Sons Ltd.
de Souza, Camila Ferreira; Xander, Patrícia; Monteiro, Ana Carolina; Silva, Amanda Gonçalves dos Santos; da Silva, Débora Castanheira Pereira; Mai, Sabine; Bernardo, Viviane; Lopes, José Daniel; Jasiulionis, Miriam Galvonas
Background Metastatic melanoma is a highly aggressive skin cancer and currently resistant to systemic therapy. Melanomas may involve genetic, epigenetic and metabolic abnormalities. Evidence is emerging that epigenetic changes might play a significant role in tumor cell plasticity and metastatic phenotype of melanoma cells. Principal findings In this study, we developed a systematic approach to identify genes implicated in melanoma progression. To do this, we used the Affymetrix GeneChip Arrays to screen 34,000 mouse transcripts in melan-a melanocytes, 4C pre-malignant melanocytes, 4C11− non-metastatic and 4C11+ metastatic melanoma cell lines. The genome-wide association studies revealed pathways commonly over-represented in the transition from immortalized to pre-malignant stage, and under-represented in the transition from non-metastatic to metastatic stage. Additionally, the treatment of cells with 10 µM 5-aza-2′-deoxycytidine (5AzaCdR) for 48 hours allowed us to identify genes differentially re-expressed at specific stages of melan-a malignant transformation. Treatment of human primary melanocytes with the demethylating agent 5AzaCdR in combination to the histone deacetylase inhibitor Trichostatin A (TSA) revealed changes on melanocyte morphology and gene expression which could be an indicator of epigenetic flexibility in normal melanocytes. Moreover, changes on gene expression recognized by affecting the melanocyte biology (NDRG2 and VDR), phenotype of metastatic melanoma cells (HSPB1 and SERPINE1) and response to cancer therapy (CTCF, NSD1 and SRC) were found when Mel-2 and/or Mel-3-derived patient metastases were exposed to 5AzaCdR plus TSA treatment. Hierarchical clustering and network analyses in a panel of five patient-derived metastatic melanoma cells showed gene interactions that have never been described in melanomas. Significance Despite the heterogeneity observed in melanomas, this study demonstrates the utility of our murine melanoma
Benito, Luisa; Coll-Vinent, Blanca; Gómez, Eva; Martí, David; Mitjavila, Joan; Torres, Ferran; Miró, Òscar; Sisó, Antoni; Mont, Lluís
Atrial fibrillation (AF) is associated with high morbidity and mortality. Early diagnosis is likely to improve therapy and prognosis. The study objective was to evaluate the usefulness of a programme for early diagnosis of AF in patients from an urban primary care centre. Participants were recruited from a randomized sample of patients not diagnosed with AF but having relevant risk factors: age ≥ 65 years, ischaemic and/or valvular heart disease, congestive heart failure, hypertension, and/or diabetes. Patients were randomly assigned to the intervention group (IG) or control group (CG). The intervention included (i) initial visit with clinical history, electrocardiogram, and instruction about pulse palpation and warning signs and (ii) electrocardiogram every 6 months during a 2-year follow-up. The main endpoint of the study was the proportion of new cases diagnosed at 6 months. Secondary endpoints were number of new AF diagnoses and complications associated with the arrhythmia in both groups. A total of 928 patients were included (463 IG and 465 CG). At 6 months, AF was diagnosed in 8 IG patients and 1 CG patient (1.7 vs. 0.2%, respectively, P = 0.018). After 2 years of follow-up, 11 IG patients and 6 CG patients had newly diagnosed AF (2.5 vs. 1.3%, respectively, P = 0.132). Time to first diagnosis of AF was shorter in IG patients [median (inter-quartile range): 7 (192) days vs. 227 (188.5) days in CG, P = 0.029]. The simple screening proposed could be useful for the early detection of AF in primary care. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: email@example.com.
Harrington, Emma; Clyne, Barbara; Wesseling, Nieneke; Sandhu, Harkiran; Armstrong, Laura; Bennett, Holly; Fahey, Tom
Malignant melanoma has high morbidity and mortality rates. Early diagnosis improves prognosis. Clinical prediction rules (CPRs) can be used to stratify patients with symptoms of suspected malignant melanoma to improve early diagnosis. We conducted a systematic review of CPRs for melanoma diagnosis in ambulatory care. Systematic review. A comprehensive search of PubMed, EMBASE, PROSPERO, CINAHL, the Cochrane Library and SCOPUS was conducted in May 2015, using combinations of keywords and medical subject headings (MeSH) terms. Studies deriving and validating, validating or assessing the impact of a CPR for predicting melanoma diagnosis in ambulatory care were included. Data extraction and methodological quality assessment were guided by the CHARMS checklist. From 16 334 studies reviewed, 51 were included, validating the performance of 24 unique CPRs. Three impact analysis studies were identified. Five studies were set in primary care. The most commonly evaluated CPRs were the ABCD, more than one or uneven distribution of Colour, or a large (greater than 6 mm) Diameter (ABCD) dermoscopy rule (at a cut-point of >4.75; 8 studies; pooled sensitivity 0.85, 95% CI 0.73 to 0.93, specificity 0.72, 95% CI 0.65 to 0.78) and the 7-point dermoscopy checklist (at a cut-point of ≥1 recommending ruling in melanoma; 11 studies; pooled sensitivity 0.77, 95% CI 0.61 to 0.88, specificity 0.80, 95% CI 0.59 to 0.92). The methodological quality of studies varied. At their recommended cut-points, the ABCD dermoscopy rule is more useful for ruling out melanoma than the 7-point dermoscopy checklist. A focus on impact analysis will help translate melanoma risk prediction rules into useful tools for clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Harrington, Emma; Clyne, Barbara; Wesseling, Nieneke; Sandhu, Harkiran; Armstrong, Laura; Bennett, Holly; Fahey, Tom
Objectives Malignant melanoma has high morbidity and mortality rates. Early diagnosis improves prognosis. Clinical prediction rules (CPRs) can be used to stratify patients with symptoms of suspected malignant melanoma to improve early diagnosis. We conducted a systematic review of CPRs for melanoma diagnosis in ambulatory care. Design Systematic review. Data sources A comprehensive search of PubMed, EMBASE, PROSPERO, CINAHL, the Cochrane Library and SCOPUS was conducted in May 2015, using combinations of keywords and medical subject headings (MeSH) terms. Study selection and data extraction Studies deriving and validating, validating or assessing the impact of a CPR for predicting melanoma diagnosis in ambulatory care were included. Data extraction and methodological quality assessment were guided by the CHARMS checklist. Results From 16 334 studies reviewed, 51 were included, validating the performance of 24 unique CPRs. Three impact analysis studies were identified. Five studies were set in primary care. The most commonly evaluated CPRs were the ABCD, more than one or uneven distribution of Colour, or a large (greater than 6 mm) Diameter (ABCD) dermoscopy rule (at a cut-point of >4.75; 8 studies; pooled sensitivity 0.85, 95% CI 0.73 to 0.93, specificity 0.72, 95% CI 0.65 to 0.78) and the 7-point dermoscopy checklist (at a cut-point of ≥1 recommending ruling in melanoma; 11 studies; pooled sensitivity 0.77, 95% CI 0.61 to 0.88, specificity 0.80, 95% CI 0.59 to 0.92). The methodological quality of studies varied. Conclusions At their recommended cut-points, the ABCD dermoscopy rule is more useful for ruling out melanoma than the 7-point dermoscopy checklist. A focus on impact analysis will help translate melanoma risk prediction rules into useful tools for clinical practice. PMID:28264830
Monshi, Babak; Vujic, Marin; Kivaranovic, Danijel; Sesti, Alma; Oberaigner, Willi; Vujic, Igor; Ortiz-Urda, Susana; Posch, Christian; Feichtinger, Hans; Hackl, Monika; Rappersberger, Klemens
Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. A total of 5246 patients were diagnosed with 1951 in-situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (≤1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p < 0.0001). In Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Malaguarnera, Giulia; Madeddu, Roberto; Catania, Vito Emanuele; Bertino, Gaetano; Morelli, Luca; Perrotta, Rosario Emanuele; Drago, Filippo; Malaguarnera, Michele; Latteri, Saverio
Anorectal melanoma is an uncommon and aggressive mucosal melanocytic malignancy. Due to its rarity, the pre-operative diagnosis remains difficult. The first symptoms are non-specific such as anal bleeding, anal mass or pain. Although anorectal melanoma carries a poor prognosis; optimal therapeutics strategies are unclear. Surgical resection remains the mainstay of treatment. The optimal surgical procedure for primary tumours is controversial and can vary from wide local excision or endoscopic mucosal resection (EMR) to an abdomino-perineal resection. A high degree of uncertainly exists regarding the benefit of radiation therapy or chemotherapy. The treatment of advanced melanoma is evolving rapidly with better understanding of the disease biology and immunology. Considerable effort has been devoted to the identification of molecular determinants of response to target therapies and immunotherapy. PMID:29492238
Wang, Bright L.
The electrical power system of a spacecraft plays a very critical role for space mission success. Such a modern power system may contain numerous hybrid DC/DC converters both inside the power system electronics (PSE) units and onboard most of the flight electronics modules. One of the faulty conditions for DC/DC converter that poses serious threats to mission safety is the random occurrence of oscillation related to inherent instability characteristics of the DC/DC converters and design deficiency of the power systems. To ensure the highest reliability of the power system, oscillations in any form shall be promptly detected during part level testing, system integration tests, flight health monitoring, and on-board fault diagnosis. The popular gain/phase margin analysis method is capable of predicting stability levels of DC/DC converters, but it is limited only to verification of designs and to part-level testing on some of the models. This method has to inject noise signals into the control loop circuitry as required, thus, interrupts the DC/DC converter's normal operation and increases risks of degrading and damaging the flight unit. A novel technique to detect oscillations at early stage for flight hybrid DC/DC converters was developed.
Holman, C D; Armstrong, B K; Heenan, P J
The relationships of different histologic types of cutaneous malignant melanoma to occupational and recreational sunlight exposure, habits of clothing, sunburn histories, and use of sunscreening agents were examined in a case-control study of 507 patients and 507 matched controls in Western Australia. Variations in relationships according to the primary site of melanoma were also examined. An increased incidence rate of superficial spreading melanoma was associated with low total outdoor exposure in early adulthood and frequent participation in boating and fishing. Superficial spreading melanoma of the trunk was also related to frequency of sunbathing at ages 15-24 years and of exposure of the trunk while working outdoors. In women the rate ratio for all types of melanoma occurring on the trunk was estimated at 13.0 (95% confidence interval, 2.0-83.9) in those who wore a bikini or bathed nude at ages 15-24 years compared with those wearing a conservative one-piece bathing suit. There was little evidence that sunbathing or wearing a bikini within 10 years of case diagnosis were risk factors for melanoma of the trunk. After control of confounding due to constitutional factors, only Hutchinson's melanotic freckle melanoma showed a relationship to severe sunburn. For nodular melanoma, sunburn appeared to be protective. Although many of the results supported the hypothesis that melanomas other than the Hutchinson's melanotic freckle type are related to occasional bursts of recreational sun exposure during a susceptible period in early adult life, little support for the hypothesis was obtained when recreational sun exposure was expressed as a proportion of total outdoor exposure, which had been considered a priori to be an index of intermittent sunlight exposure.
KALAMPOKAS, EMMANOUIL; KALAMPOKAS, THEODOROS; DAMASKOS, CHRISTOS
Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Conclusion: Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease. PMID:28064232
Hyman, Jennifer A; Koch, Seth A; Wilcock, Brian P
A 3-year-old-female, spayed Golden Retriever was examined for a unilateral retinal detachment with exophthalmos. Ultrasonographically, a mass was detected with intra- and extraocular extension. The orbit was exenterated and the dog recovered uneventfully. Histopathologic diagnosis was a primary choroidal melanoma with orbital extension, however, the behavioral and cytologic features were benign. Routine examinations postsurgically were nonremarkable. Twenty-one months after surgery the dog was euthanized for respiratory collapse with radiographic signs of metastasis. Necropsy revealed black lesions in the lung and liver. Histopathologic diagnosis was metastatic melanoma with morphology and behavior identical to the primary choroidal melanoma. This is the first definitive case of a canine choroidal melanoma with metastasis.
Desoete, Annemmie; De Weerd, Frauke; Vanderswalmen, Ruth; De Bond, Annemie
The study was conducted to look at differences between children who outgrew and did not outgrow an early diagnosis of mathematical learning disorder (MD; n=13), and peers without MD (n=13). Children were tested at 5, 6, 7 and 10 years of age. About 54% of the children with an early diagnosis of MD still experienced mathematical difficulties at the…
Jones, Blake C; Lipson, Evan J; Childers, Brandon; Fishman, Elliot K; Johnson, Pamela T
The incidence of melanoma has risen dramatically over the past several decades. Oncologists rely on the ability of radiologists to identify subtle radiographic changes representing metastatic and recurrent melanoma in uncommon locations on multidetector computed tomography (MDCT) as the front-line imaging surveillance tool. To accomplish this goal, MDCT acquisition and display must be optimized and radiologist interpretation and search patterns must be tailored to identify the unique and often subtle metastatic lesions of melanoma. This article describes MDCT acquisition and display techniques that optimize the visibility of melanoma lesions, such as high-contrast display windows and multiplanar reconstructions. In addition, innovative therapies for melanoma, such as immunotherapy and small-molecule therapy, have altered clinical management and outcomes and have also changed the spectrum of therapeutic complications that can be detected on MDCT. Recent advances in melanoma therapy and potential complications that the radiologist can identify on MDCT are reviewed.
Robinson, June K; Gaber, Rikki; Hultgren, Brittney; Eilers, Steven; Blatt, Hanz; Stapleton, Jerod; Mallett, Kimberly; Turrisi, Rob; Duffecy, Jenna; Begale, Mark; Martini, Mary; Bilimoria, Karl; Wayne, Jeffrey
Early detection of melanoma improves survival. Since many melanoma patients and their spouses seek the care of a physician after discovering their melanoma, an ongoing study will determine the efficacy of teaching at-risk melanoma patients and their skin check partner how to conduct skin self-examinations (SSEs). Internet-based health behavior interventions have proven efficacious in creating behavior change in patients to better prevent, detect, or cope with their health issues. The efficacy of electronic interactive SSE educational intervention provided on a tablet device has not previously been determined. The electronic interactive educational intervention was created to develop a scalable, effective intervention to enhance performance and accuracy of SSE among those at-risk to develop melanoma. The intervention in the office was conducted using one of the following three methods: (1) in-person through a facilitator, (2) with a paper workbook, or (3) with a tablet device used in the clinical office. Differences related to method of delivery were elucidated by having the melanoma patient and their skin check partner provide a self-report of their confidence in performing SSE and take a knowledge-based test immediately after receiving the intervention. The three interventions used 9 of the 26 behavioral change techniques defined by Abraham and Michie to promote planning of monthly SSE, encourage performing SSE, and reinforce self-efficacy by praising correct responses to knowledge-based decision making and offering helpful suggestions to improve performance. In creating the electronic interactive SSE educational intervention, the educational content was taken directly from both the scripted in-person presentation delivered with Microsoft PowerPoint by a trained facilitator and the paper workbook training arms of the study. Enrollment totaled 500 pairs (melanoma patient and their SSE partner) with randomization of 165 pairs to the in-person, 165 pairs to the
Vaclav Vojta (1917-2000) developed an early diagnostic method of the neurodevelopmental disorder of infants and came up with therapeutic concept consisting in releasing of global motor complexes by means of the stimulation of proper areas on patients body. In the diagnostics apart from very careful observation of the spontaneous movement of the infant and examination of the reflexes that are characteristic for the first weeks of human's life, Vojta applied the examination of the 7 postural reactions. Presence of the trouble in patterns and dynamics of the postural reactions Vojta called Central Nervous Coordination Disorder--CNCD and regarded as work diagnosis or alarm signal indicating necessity of application of the therapy, especially when asymmetry of the muscle tone and primitive reflexes beyond their physiological appearance period are observed or the number of the abnormal reactions exceeds 5. Global motor complexes as reflex locomotion--crawling and rotation--consist of all the partial motion patterns, which are gradually used by healthy infant in the process of postural and motor ontogenesis. Providing the central nervous system with proper external stimulation allows to, using neuronal plasticity, recreate an access to the human's postural development program and gradually replace pathological motor patterns by those more regular. Exercises repeated several times a day rebuilt support, erectile and vertical mechanisms, improve automatic postural control and phase lower limb movement. Affecting especially on autochtonic muscles of the spine exercises balance synergic cooperation of muscle groups in the trunk and those surrounding key body joints. This way they correct body's posture and peripheral motion and pathology of the outlasted primitive reflexes gradually withdraws.
Ferrari, Barbara; Salgarelli, Attilio C; Mandel, Victor D; Bellini, Pierantonio; Reggiani, Camilla; Farnetani, Francesca; Pellacani, Giovanni; Magnoni, Cristina
Non-melanoma skin cancer (NMSC) represents the most common cutaneous neoplasms of the head and neck. In recent years, novel non-invasive diagnostic tool have been developed, and among these we have the reflectance confocal microscopy (RCM), that offers the evaluation of the skin at real time with cellular resolution. Numerous studies have identified the main confocal features of skin tumours, demonstrating the good correlation of these features with certain dermatoscopic patterns and histologic findings. The aim of this analysis was to provide new insight into the role of RCM in the diagnosis and management of NMSC of the head and neck. Data comes from the most recent literature, taking into account previous essential reported information in this field. The study eligibility criteria were: studies providing update information, focusing on RCM findings in NMSC, without restrictions for age, sex, ethnicity. A search concerning the role of dermoscopy and RCM in the diagnosis of NMSC was performed on Medline. Duplicated studies, single case report and papers with language other than English were excluded from this study. RCM clues were analysed for NMSC in association with clinical, dermoscopic and histopathologic findings. Moreover, some new findings have been described and possible applications for NMSC of the head and neck have been discussed. RCM allows tissue imaging in vivo contributing to a more accurate diagnosis of NMSC of the head and neck, sparing time for the patient and costs for the public health system. RCM can also be used for selection of the biopsy site and it is helpful in defining the surgical safety margins to keep during the excision of skin cancers.
AWARD NUMBER: W81XWH-15-1-0157 TITLE: Nanotechnology -Based Detection of Novel microRNAs for Early Diagnosis of Prostate Cancer PRINCIPAL...TITLE AND SUBTITLE Nanotechnology -Based Detection of Novel microRNAs for Early Diagnosis of Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER...identify novel differentially expressed miRNAs in the body fluids (blood, urine, etc.) for an early detection of PCa. Advances in nanotechnology and
Strobel, Stephen L
The potential utilization of Demodex mites as delivery vectors for cytotoxic medications directed to early skin cancer is proposed. Potential benefits, proof of concept, and limitations are discussed. © 2017 by the Association of Clinical Scientists, Inc.
Gómez, Catalina; Herrera, Diana Sofia
Melanoma skin cancer diagnosis can be challenging due to the similarities of the early stage symptoms with regular moles. Standardized visual parameters can be determined and characterized to suspect a melanoma cancer type. The automation of this diagnosis could have an impact in the medical field by providing a tool to support the specialists with high accuracy. The objective of this study is to develop an algorithm trained to distinguish a highly probable melanoma from a non-dangerous mole by the segmentation and classification of dermoscopic mole images. We evaluate our approach on the dataset provided by the International Skin Imaging Collaboration used in the International Challenge Skin Lesion Analysis Towards Melanoma Detection. For the segmentation task, we apply a preprocessing algorithm and use Otsu's thresholding in the best performing color space; the average Jaccard Index in the test dataset is 70.05%. For the subsequent classification stage, we use joint histograms in the YCbCr color space, a RBF Gaussian SVM trained with five features concerning circularity and irregularity of the segmented lesion, and the Gray Level Co-occurrence matrix features for texture analysis. These features are combined to obtain an Average Classification Accuracy of 63.3% in the test dataset.
Dréau, Didier; Culberson, Cathy; Wyatt, Sharon; Holder, Walter D.
Objectives To evaluate melanoma biopsy specimens for human papilloma virus (HPV) and determine the relation between the presence of HPV, in vitro growth, and clinical progression of melanoma in the patients from whom the biopsy specimens were derived. Summary Background Data Ultraviolet radiation from sun exposure appears to be the primary causal agent in the development of cutaneous melanoma. However, other agents, including HPV, as observed in different epithelial carcinomas, may also play a role in melanoma development and progression. Methods Twelve melanoma biopsy specimens obtained from 12 patients with AJCC stage III and IV melanoma were stained with antibodies against gp-100 (HMB-45) and S-100 protein to confirm melanoma diagnosis and with a polyclonal HPV antibody. After mechanical dissociation, the melanoma specimen cells’ ability to grow in vitro was assessed. Patients were evaluated for melanoma progression with physical examination, complete blood count, and liver function tests every 3 months and a chest radiograph every 6 months. Results All biopsy specimens were positive for S-100, and nine (75%) were positive for gp-100. Seven of 12 (58%) were positive for HPV by immunohistochemistry. In vitro, none of the HPV-negative tumor cells grew from the tumor biopsies, whereas five of seven (71%) of the HPV-positive melanoma tumor cells grew very well. All patients with HPV-positive tumor cells had recurrences and died of melanoma progression, whereas four of five (80%) patients with HPV-negative tumor cells remained alive and without melanoma recurrence. Conclusions The presence of HPV was found in 58% of the biopsy specimens obtained from patients with stage III and IV melanoma and correlated with rapid melanoma progression. HPV may serve as a cofactor in the development of melanoma and may modulate a more aggressive phenotype in HPV-containing melanoma cells. PMID:10767787
Ranjith, S; Muralee, M; Sajeed, A; Arun, P M; Cherian, K; Nair, C K; Augustine, P; Ahamed, I
Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive disease, in which early diagnosis is difficult. The prognosis remains extremely poor, irrespective of the treatment. We share our experience in treating this malignancy at our centre in South India. Methods This study describes a retrospective analysis of 31 cases of anorectal melanoma presented to our centre between January 2001 and December 2013. Results Twenty-two patients (71%) presented with metastasis and had a median overall survival of nine months. None of the 22 patients survived for two years. Nine patients (29%) had curative surgery, in the form of abdominoperineal resection (six patients), abdominoperineal resection with bilateral inguinal node dissection (one patient), abdominoperineal resection with liver resection (one patient) and posterior exenteration (one patient). In patients who underwent curative surgery, the median overall survival was 15 months and disease-free survival was nine months, with a two-year overall survival of 22%. Conclusions Anorectal melanoma is an aggressive disease with a poor prognosis. The majority of patients present with distant metastases. Prognosis depends on stage at presentation. Early diagnosis and surgical resection may improve the overall outcome. Newer modalities such as immunotherapy and targeted therapies such as anti-CTLA4 monoclonal antibody and anti-programmed cell death protein 1 monoclonal antibodies have radically changed the management of mucosal melanoma and may, in the future, improve the overall prognosis of anorectal melanoma.
Yu, Chanki; Yang, Sejung; Kim, Wonoh; Jung, Jinwoong; Chung, Kee-Yang; Lee, Sang Wook; Oh, Byungho
Acral melanoma is the most common type of melanoma in Asians, and usually results in a poor prognosis due to late diagnosis. We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions. A total of 724 dermoscopy images comprising acral melanoma (350 images from 81 patients) and benign nevi (374 images from 194 patients), and confirmed by histopathological examination, were analyzed in this study. To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist's and non-expert's evaluation. The accuracy (percentage of true positive and true negative from all images) of the convolutional neural network was 83.51% and 80.23%, which was higher than the non-expert's evaluation (67.84%, 62.71%) and close to that of the expert (81.08%, 81.64%). Moreover, the convolutional neural network showed area-under-the-curve values like 0.8, 0.84 and Youden's index like 0.6795, 0.6073, which were similar score with the expert. Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet.
Shankaracharya; Odedra, Devang; Samanta, Subir; Vidyarthi, Ambarish S.
The development of an effective diabetes diagnosis system by taking advantage of computational intelligence is regarded as a primary goal nowadays. Many approaches based on artificial network and machine learning algorithms have been developed and tested against diabetes datasets, which were mostly related to individuals of Pima Indian origin. Yet, despite high accuracies of up to 99% in predicting the correct diabetes diagnosis, none of these approaches have reached clinical application so far. One reason for this failure may be that diabetologists or clinical investigators are sparsely informed about, or trained in the use of, computational diagnosis tools. Therefore, this article aims at sketching out an outline of the wide range of options, recent developments, and potentials in machine learning algorithms as diabetes diagnosis tools. One focus is on supervised and unsupervised methods, which have made significant impacts in the detection and diagnosis of diabetes at primary and advanced stages. Particular attention is paid to algorithms that show promise in improving diabetes diagnosis. A key advance has been the development of a more in-depth understanding and theoretical analysis of critical issues related to algorithmic construction and learning theory. These include trade-offs for maximizing generalization performance, use of physically realistic constraints, and incorporation of prior knowledge and uncertainty. The review presents and explains the most accurate algorithms, and discusses advantages and pitfalls of methodologies. This should provide a good resource for researchers from all backgrounds interested in computational intelligence-based diabetes diagnosis methods, and allows them to extend their knowledge into this kind of research. PMID:21713313
Shankaracharya; Odedra, Devang; Samanta, Subir; Vidyarthi, Ambarish S
The development of an effective diabetes diagnosis system by taking advantage of computational intelligence is regarded as a primary goal nowadays. Many approaches based on artificial network and machine learning algorithms have been developed and tested against diabetes datasets, which were mostly related to individuals of Pima Indian origin. Yet, despite high accuracies of up to 99% in predicting the correct diabetes diagnosis, none of these approaches have reached clinical application so far. One reason for this failure may be that diabetologists or clinical investigators are sparsely informed about, or trained in the use of, computational diagnosis tools. Therefore, this article aims at sketching out an outline of the wide range of options, recent developments, and potentials in machine learning algorithms as diabetes diagnosis tools. One focus is on supervised and unsupervised methods, which have made significant impacts in the detection and diagnosis of diabetes at primary and advanced stages. Particular attention is paid to algorithms that show promise in improving diabetes diagnosis. A key advance has been the development of a more in-depth understanding and theoretical analysis of critical issues related to algorithmic construction and learning theory. These include trade-offs for maximizing generalization performance, use of physically realistic constraints, and incorporation of prior knowledge and uncertainty. The review presents and explains the most accurate algorithms, and discusses advantages and pitfalls of methodologies. This should provide a good resource for researchers from all backgrounds interested in computational intelligence-based diabetes diagnosis methods, and allows them to extend their knowledge into this kind of research.
Trimble, E L; Lewis, J L; Williams, L L; Curtin, J P; Chapman, D; Woodruff, J M; Rubin, S C; Hoskins, W J
Considerable debate centers on the optimal treatment for vulvar melanoma, as well as those clinicopathological factors influencing prognosis. We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990. Primary tumors were assessed according to Chung (47 patients) and Breslow (65 patients) microstaging systems. Fifty-nine patients (76%) underwent radical vulvectomy, ten patients (13%) had a partial vulvectomy, and nine patients (12%) had a wide local excision. Fifty-six also underwent inguinal node dissection. Median follow-up was 193 months. Median survival was 63 months. Ten-year survival by Chung level was as follows: I 100%; II, 81%; III, 87%; IV, 11%; V, 33%. Ten-year survival by tumor thickness was as follows: 0.75 mm, 48%; 0.75-1.5 mm, 68%; 1.51-3.0 mm, 44%; greater than 3.0 mm, 22%. Increased depth of invasion was associated with increased incidence of inguinal node metastasis. Cox regression analysis demonstrated prognostic significance for tumor thickness (P less than 0.001), inguinal node metastasis (P less than 0.001), and older age at diagnosis (P less than 0.001). Radical vulvectomy did not seem to improve survival over less radical procedures. Based on this experience, we recommend radical local excision for patients with malignant melanoma of the vulva. Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection.
Smith, S L; Damato, B E; Scholes, A G M; Nunn, J; Field, J K; Heighway, J
The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT–PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours. British Journal of Cancer (2002) 87, 1308–1313. doi:10.1038/sj.bjc.6600620 www.bjcancer.com © 2002 Cancer Research UK PMID:12439722
Bostedt, H; Sieme, H; Bartmann, C-P; Handler, J; Sobiraj, A; Wehrend, A
This review describes stepwise the recto-manual and transrectal ultrasonographic evidence of early pregnancy detection in the horse. The morphological and physiological conditions in the individual phases of early pregnancy are presented in correlation to the potential clinical findings. The importance of embryonic and early foetal losses is presented. Communication and documentation of findings are also addressed. The final section is devoted to the evaluation of the examination effort. In this regard, it is emphasized that the gynaecological examination for the evaluation of the pregnancy status represents a service contract.
di Pietro, Massimiliano; Canto, Marcia I; Fitzgerald, Rebecca C
Because the esophagus is easily accessible with endoscopy, early diagnosis and curative treatment of esophageal cancer is possible. However, diagnosis is often delayed because symptoms are not specific during early stages of tumor development. The onset of dysphagia is associated with advanced disease, which has a survival at 5 years lower than 15%. Population screening by endoscopy is not cost-effective, but a number of alternative imaging and cell analysis technologies are under investigation. The ideal screening test should be inexpensive, well tolerated, and applicable to primary care. Over the past 10 years, significant progress has been made in endoscopic diagnosis and treatment of dysplasia (squamous and Barrett's), and early esophageal cancer using resection and ablation technologies supported by evidence from randomized controlled trials. We review the state-of-the-art technologies for early diagnosis and minimally invasive treatment, which together could reduce the burden of disease. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
1 AD _________________ AWARD NUMBER: W81XWH-15-1-0157 TITLE: Nanotechnology -Based Detection of Novel microRNAs for Early Diagnosis of Prostate...DATES COVERED 15 Jul 2015 - 14 Jul 2016 4. TITLE AND SUBTITLE Nanotechnology -Based Detection of Novel microRNAs for Early Diagnosis of Prostate Cancer...the expression level of deregulated miRNAs in mouse and human PCa tissues as well as serum samples using an advanced nanotechnology -based sensing
1 Award Number: W81XWH-12-2-0118 TITLE: Early Diagnosis and Intervention Strategies for Post -Traumatic Heterotopic Ossification in Severely...December 2016 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION...COVERED 30Sep2012 - 29Sep2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Early Diagnosis and Intervention Strategies for Post -Traumatic Heterotopic
Blasco, Patricia M.; And Others
This article provides an overview of procedures commonly used in prenatal screening and diagnosis including ultrasound, amniocentesis, chorionic villus biopsy, maternal serum alpha-fetoprotein, and deoxyribonucleic acid (DNA) analysis. Emphasis is on the role of the early interventionist in supporting families during prenatal diagnosis. (Author/DB)
Franklin, C; Livingstone, E; Roesch, A; Schilling, B; Schadendorf, D
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma. Ipilimumab, a monoclonal antibody against the cytotoxic T-lymphocyte antigen 4 (CTLA-4) as well as nivolumab and pembrolizumab which target the programmed cell death protein 1 (PD-1) have been shown to prolong overall survival in patients with advanced melanoma. The latter substances seem to have an increased response rate and more tolerable safety profile compared to ipilimumab. The combination of a CTLA-4 and a PD-1 inhibitor seems to be superior to the monotherapies, especially in patients with PD-L1 negative tumours. Checkpoint inhibitors are currently being tested in the adjuvant setting with initial data for ipilimumab suggesting efficacy in this context. Talimogene laherparepvec (TVEC) is the first oncolytic virus approved in the therapy of metastatic melanoma offering a treatment option especially for patients with limited disease. In this review, data on these recently developed and approved immunotherapies are presented. However, further studies are necessary to determine the optimal duration, sequencing and combinations of immunotherapies to further improve the outcome of patients with advanced melanoma. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Warner, Wayne A; Sookdeo, Vandana Devika; Umakanthan, Srikanth; Sarran, Kevin; Pran, Lemuel; Fortuné, Maurice; Greaves, Wesley; Narinesingh, Sharda; Harnanan, Dave; Maharaj, Ravi
Malignant melanoma of the heel is a rare melanoma subtype with incidence rates that reflect the complex relationship between sun exposure at certain geographic locations, individual melanin levels and overall melanoma risk. It is oftentimes characterized by poor prognosis because of delays in presentation resulting in longitudinal tumor invasion, lymph node involvement and metastasis. A 59-year-old woman was admitted to the Eric Williams Medical Sciences Complex, Trinidad and Tobago with a 5mm pruritic lesion on her left heel. At presentation, the lesion was asymmetric with border irregularities, color heterogeneity, with dynamics in elevation and overall size. She was subsequently diagnosed with malignant melanoma with left inguinal lymphadenopathy. A single stage wide local excision (WLE) of the left heel lesion with a split-thickness skin graft (STSG) and a left inguinal lymphadenectomy were performed. Dacarbazine (Bayer) was administered post operatively. Globally, the incidence of malignant melanoma is rapidly increasing, particularly, in countries like Trinidad and Tobago with a significant population of non-fair skinned individuals. There is need for strategic initiatives to increase patient adherence in these populations. The rarity of malignant heel melanomas heightens the need for increased patient awareness and greater clinical surveillance to ensure early diagnosis and treatment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Zhang, Chengcheng; Lin, Kuo-Shyan; Bénard, François
Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability. In this study, we summarized the development and the in vitro and in vivo characteristics of the radiolabeled αMSH analogues, including 99mTc-, 111In-, 67 Ga-, or 125I-labeled αMSH analogues for imaging with single-photon emission computed tomography; 68Ga-, 64Cu-, or 18F-labeled αMSH analogues for imaging with positron emission tomography; and 188Re-, 177Lu-, 90Y-, or 212Pb-labeled αMSH analogues for radionuclide therapy. These radiolabeled αMSH analogues showed promising results with high tumor uptake and rapid normal tissue activity clearance in the preclinical model of B16F1 and B16F10 mouse melanomas. These results highlight the potential of using radiolabeled αMSH analogues in clinical applications for molecular imaging and radionuclide therapy of melanoma. PMID:29182034
Cheung, Winson Y; Bayliss, Martha S; White, Michelle K; Stroupe, Angela; Lovley, Andrew; King-Kallimanis, Bellinda L; Lasch, Kathryn
Metastatic melanoma is a highly aggressive cancer, often striking in the prime of life. This study provides new information directly from advanced melanoma (stage III and IV) patients on how their disease impacts their health-related quality of life (HRQL). Twenty-nine in-depth, qualitative interviews were conducted with adult patients with advanced melanoma in Canada. A semi-structured interview guide was used. Interviews were transcribed verbatim and key concepts were identified using a grounded theory analytic approach. Many patients' journeys began with the startling diagnosis of an invasive disease and a vastly shortened life expectancy. By the time they reached an advanced stage of melanoma, these patients' overall functioning and quality of life had been greatly diminished by this quickly progressing cancer. The impact was described in terms of physical pain and disability, emotional distress, diminished interactions with friends and family, and burden on caregivers. Our findings provide evidence of signs, symptoms, and functional impacts of advanced melanoma. Signs and symptoms reported (physical, mental, and social) confirm and expand on those reported in the existing clinical literature. Primary care physicians should be better trained to identify melanomas early. Oncology care teams can improve on their current approaches for helping patients navigate treatment options, with information about ancillary services to mitigate disease impacts on HRQL, such as mental health and social supports, as well as employment or financial support services.
Rowe, Christopher C; Villemagne, Victor L
In vivo imaging of amyloid-β (Aβ) with positron emission tomography has moved from the research arena into clinical practice. Clinicians working with cognitive decline and dementia must become familiar with its benefits and limitations. Amyloid imaging allows earlier diagnosis of Alzheimer disease and better differential diagnosis of dementia and provides prognostic information for mild cognitive impairment. It also has an increasingly important role in therapeutic trial recruitment and for evaluation of anti-Aβ treatments. Longitudinal observations are required to elucidate the role of Aβ deposition in the course of Alzheimer disease and provide information needed to fully use the prognostic power of this investigation. Copyright © 2013 Elsevier Inc. All rights reserved.
Bay, Christiane; Kejs, Anne Mette Tranberg; Storm, Hans H; Engholm, Gerda
The incidence of melanoma of the skin has risen in Denmark in recent decades, the increase being steeper from 2004. It is unclear whether this represents a true rise in incidence or whether it is caused by an increased awareness of the condition. To assess whether the increase was characterised by early-stage melanomas and a higher proportion of melanomas with superficial spreading morphology, we studied all skin melanoma patients registered in the Danish Cancer Register 1989-2011 (n=27,010) and followed up for death through 2013. Trends in age-standardised incidence by sex, subsite and morphology, relative survival, TNM stage distribution and stage-specific relative survival from 2004 were analysed. The incidence of melanoma more than doubled over 23 years. A steeper increase from 2004 was driven mainly by superficial spreading tumours, but the proportion of nodular melanomas in patients 50 years of age and over also increased significantly. The largest increase occurred for stage I tumours and for tumours on the trunk. From 1989-1993 to 2009-2011 the 5-year relative survival increased at 12% and 6% points for male and female patients, respectively. Greater awareness, and thus lower stage at diagnosis (mediated by a large skin cancer prevention campaign from 2007), might explain part of the increase, but the increase in nodular melanoma also points to a genuine increase in the risk of melanoma. Copyright © 2014 Elsevier Ltd. All rights reserved.
Ribero, S; Podlipnik, S; Osella-Abate, S; Sportoletti-Baduel, E; Manubens, E; Barreiro, A; Caliendo, V; Chavez-Bourgeois, M; Carrera, C; Cassoni, P; Malvehy, J; Fierro, M T; Puig, S
Different protocols have been used to follow up melanoma patients in stage I-II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up. Analysis of two prospectively collected cohorts of melanoma patients in stage IB-IIA from two tertiary referral centres in Barcelona (clinical-based follow-up [C-FU]) and Turin (ultrasound-based follow-up [US-FU]). Kaplan-Meier curves were used to evaluate distant metastases-free survival (DMFS), disease-free interval (DFI), nodal metastases-free survival (NMFS) and melanoma-specific survival (MSS). A total of 1149 patients in the American Joint Committee on Cancer stage IB and IIA were included in this study, of which 554 subjects (48%) were enrolled for a C-FU, and 595 patients (52%) received a protocolised US-FU. The median age was 53.8 years (interquartile range [IQR] 41.5-65.2) with a median follow-up time of 4.14 years (IQR 1.2-7.6). During follow-up, 69 patients (12.5%) in C-FU and 72 patients (12.1%) in US-FU developed disease progression. Median time to relapse for the first metastatic site was 2.11 years (IQR 1.14-4.04) for skin metastases, 1.32 (IQR 0.57-3.29) for lymph node metastases and 2.84 (IQR 1.32-4.60) for distant metastases. The pattern of progression and the total proportion of metastases were not significantly different (P = .44) in the two centres. No difference in DFI, DMFS, NMFS and MSS was found between the two cohorts. Ultrasound-based follow-up does not increase the survival of melanoma patients in stage IB-IIA. Copyright © 2017 Elsevier Ltd. All rights reserved.
Verzi, Anna Eliza; Quan, Victor L; Walton, Kara E; Martini, Mary C; Marghoob, Ashfaq A; Garfield, Erin M; Kong, Betty Y; Isales, Maria Cristina; VandenBoom, Timothy; Zhang, Bin; West, Dennis P; Gerami, Pedram
Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi. We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions. Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation. Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P < .001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P = .009), and SWSs correlated with greater Breslow depth among melanomas (P = .007). This study was retrospective. Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Souza, Reynaldo José Sant'Anna Pereira de; Mattedi, Adriana P; Corrêa, Marcelo P; Rezende, Marcelo L; Ferreira, Ana Cláudia Andrade
The most common form of cancer in Brazil is non-melanoma skin cancer, which affects approximately 0.06% of the population. There are no public policies for its prevention and the economic impact of its diagnosis has yet to be established. To estimate the costs of the diagnosis and treatment of non-melanoma skin cancer in the state of São Paulo between 2000 and 2007 and to compare them with the costs associated with skin melanoma in the same period. The Clinical Practice Guidelines in Oncology (National Comprehensive Cancer Network) was used as a procedure model, adapted to the procedures at the SOBECCan Foundation at the Ribeirão Preto Cancer Hospital in São Paulo. The estimated costs were based on the costs of medical treatment in the public and private sectors in 2007. The mean annual costs of each individual treatment of non-melanoma skin cancer were much lower than those estimated for the treatment of skin melanoma. Nevertheless, when the total costs of the treatment of non-melanoma skin cancer were taken into consideration, it was found that the total cost of the 42,184 cases of this type of cancer in São Paulo within the study period was 14% higher than the costs of the 2,740 cases of skin melanoma registered in the same period within the Brazilian National Health Service (SUS). However, in the private sector, the total cost was approximately 34% less for the treatment of non-melanoma skin cancer compared to melanoma. The high number of cases of non-melanoma skin cancer in Brazil, with 114,000 new cases predicted for 2010, 95% of which are diagnosed at early stages, represents a financial burden to the public and private healthcare systems of around R$37 million and R$26 million annually, respectively.
Baade, Peter D.; Balanda, Kevin P.; Stanton, Warren R.; Lowe, John B.; Del Mar, Chris B.
Background: Melanoma can be curable if detected early. One component of detecting melanoma is an awareness of the important features of the disease. It is currently not clear which features the community view as indicative of melanoma. Objective: To investigate which features of the skin members of an urban community believe may indicate skin…
Rodrigues-Antunes, S; Borges, B N
Gastric cancer remains one of the most prevalent cancers in the world. Due to this, efforts are being made to improve the diagnosis of this neoplasm and the search for molecular markers that may be involved in its genesis. Within this perspective, the mitochondrial DNA is considered as a potential candidate, since it has several well documented changes and is readily accessible. However, numerous alterations have been reported in mtDNA, not facilitating the visualization of which alterations and molecular markers are truly involved with gastric carcinogenesis. This review presents a compilation of the main known changes relating mtDNA to gastric cancer and their clinical significance.
Barthes, C; Mezan De Malartic, C; Baumann, C; Rousseaux, H; Morel, O
Ultrasound examination plays a central role in case of suspected non-viable pregnancy. A wrong diagnosis might have major consequence in terms of inadequate care, especially in cases of false positive non-viable pregnancy diagnosis. Ultrasound criterions are today well defined. Our objective was to evaluate the feasibility and reproducibility of a novel image-quoting method of first-trimester non-viable pregnancy. Thirty images of non-viable pregnancy were twice evaluated with blinded proofreading. Two quotations were evaluated: the first for the images of gestational sacs without embryo (gestational sac score), the second for the images with embryo (embryo score). The ICC (interclass correlation coefficient) was>0.75 for inter- and intra-observer reproducibility both for the quotations of the gestational sac and for the embryo with a low variability. Reproducibility of quoting crown rump length measurements <5mm was low at first proofreading but after adjustment of the quoting modalities, ICC was also>0.75. The inter- and intra-observer reproducibility of our quoting methods is high with a low variability. They might be a useful tool in current practice in the future. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Devoy, Susan; Simpson, Ellen Elizabeth Anne
To identify factors that may increase intentions to seek help for an early dementia diagnosis. Early dementia diagnosis in Ireland is low, reducing the opportunity for intervention, which can delay progression, reduce psychological distress and increase social supports. Using the theory of planned behaviour (TPB), and a mixed methods approach, three focus groups were conducted (N = 22) to illicit attitudes and beliefs about help seeking for an early dementia diagnosis. The findings informed the development of the Help Seeking Intentions for Early Dementia Diagnosis (HSIEDD) questionnaire which was piloted and then administered to a sample of community dwelling adults from Dublin and Kildare (N = 95). Content analysis revealed participants held knowledge of the symptoms of dementia but not about available interventions. Facilitators of help seeking were family, friends and peers alongside well informed health professionals. Barriers to seeking help were a lack of knowledge, fear, loss, stigma and inaccessible services. The quantitative findings suggest the TPB constructs account for almost 28% of the variance in intentions to seek help for an early diagnosis of dementia, after controlling for sociodemographic variables and knowledge of dementia. In the final step of the regression analysis, the main predictors of help seeking were knowledge of dementia and subjective norm, accounting for 6% and 8% of the variance, respectively. Future interventions should aim to increase awareness of the support available to those experiencing early memory problems, and should highlight the supportive role that family, friends, peers and health professionals could provide.
Pampena, María B; Barrio, María M; Juliá, Estefanía P; Blanco, Paula A; von Euw, Erika M; Mordoh, José; Levy, Estrella Mariel
In a previous work, we showed that CSF-470 vaccine plus bacillus Calmette-Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs . IFN-α2b-treated high-risk cutaneous melanoma patients in a Phase II study. Immune monitoring demonstrated an increase in anti-tumor innate and adaptive immunities of vaccinated patients, with a striking increase in IFN-γ secreting lymphocytes specific for melanoma antigens (Ags). In an effort to dissect the first steps of the immune response elicited by CSF-470 vaccine plus adjuvants, we evaluated, in an in vitro model, leukocyte migration, cytokine production, and monocyte phagocytosis of vaccine cells. Our results demonstrate that leukocytes recruitment, mostly from the innate immune system, is an early event after CSF-470 vaccine plus BCG plus GM-CSF interaction with immune cells, possibly explained by the high expression of CCL2/MCP-1 and other chemokines by vaccine cells. Early release of TNF-α and IL-1β pro-inflammatory cytokines and efficient tumor Ags phagocytosis by monocytes take place and would probably create a favorable context for Ag processing and presentation. Although the presence of the vaccine cells hampered cytokines production stimulated by BCG in a mechanism partially mediated by TGF-β and IL-10, still significant levels of TNF-α and IL-1β could be detected. Thus, BCG was required to induce local inflammation in the presence of CSF-470 vaccine cells.
Garg, Amit; Wang, Joyce; Reddy, Shalini B; Powers, Jennifer; Jacob, Reza; Powers, Michael; Biello, Katie; Cayce, Rachael; Savory, Stephanie; Belazarian, Leah; Domingues, Erik; Korzenko, Adam; Wilson, Lindsay; Grant-Kels, Jane M; George, Paul; Robinson-Bostom, Leslie; Trotter, Shannon C; Geller, Alan C
Knowledge of the skin cancer examination (SCE) and its practice remain relevant competency gaps among medical students. We elaborate on a method of SCE known as the Integrated Skin Exam and discuss the development of an instructional film that illustrates its principles. We assess the tool's effect on knowledge, attitudes, and perceptions related to the SCE. Second-year students among 8 randomized schools viewed the film and completed pre-post questionnaires. After viewing The Integrated Skin Exam film, students demonstrated improved melanoma knowledge, including identification of high-risk demographic groups (61% vs 42.9%, P < .001), high-risk anatomic sites in women (88.6% vs 46.5%, P < .001) and men (92.1% vs 34.8%, P < .001), and the ABCDEs of melanoma (98.4% vs 91.2%, P < .001). Students demonstrated increased confidence in the SCE (66.93% vs 16.40%, P < .001) and augmented intentions to practice it (99.05% vs 13.9%, P < .001). A greater proportion (70.4% vs 41.9%, P < .001) of students thought less than 3 minutes were required to integrate SCE into the routine examination. Longitudinal impact of the film was not assessed. The Integrated Skin Exam film introduces an integrated approach to the SCE that addresses knowledge gaps, mitigates perceived barriers, and augments intention related to practice of the SCE. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Martin, Justin; Krueger, James; Gareau, Daniel
The 5-year survival rate for patients diagnosed with Melanoma, a deadly form of skin cancer, in its latest stages is about 15%, compared to over 90% for early detection and treatment. We present an imaging system and algorithm that can be used to automatically generate a melanoma risk score to aid clinicians in the early identification of this form of skin cancer. Our system images the patient's skin at a series of different wavelengths and then analyzes several key dermoscopic features to generate this risk score. We have found that shorter wavelengths of light are sensitive to information in the superficial areas of the skin while longer wavelengths can be used to gather information at greater depths. This accompanying diagnostic computer algorithm has demonstrated much higher sensitivity and specificity than the currently commercialized system in preliminary trials and has the potential to improve the early detection of melanoma.
Pristavu, Anda Ioana; Furnica, Cristina; Ifrim, Mona Mihaela; Popovici, Razvan Mihai
Lumbo-costo-vertebral syndrome (LCVS) is a rare type of lumbar hernia with associated abnormalities of the vertebral bodies, ribs, and trunk muscles. Only a few cases have been reported in the literature, all of which were diagnosed after birth. We present a case of LCVS diagnosed early in the second trimester of pregnancy using two- and three-dimensional ultrasound. In our case, the associated anomalies were: multiple costovertebral anomalies, lumbar hernia, anal imperforation, left hand supernumerary digit, and clubfoot.
Jimenez-Baez, Maria Valeria; Marquez-Gonzalez, Horacio; Barcenas-Contreras, Rodolfo; Morales Montoya, Carlos; Espinosa-Garcia, Laura Fatima
To evaluate the impact of a strategy for early detection of diabetic retinopathy in patients with type 2 diabetes mellitus (DMT2) in Quintana Roo, México. Study transversal, observational, prospective, analytical, eight primary care units from Mexican Social Security Institute in the northern delegation of the State of Quintana Roo, Mexico were included. A program for early detection of diabetic retinopathy (DR) in adult 376,169 was designed. Were diagnosed 683 cases of type 2 diabetes, in 105 patients randomized was conducted to direct ophthalmoscopy were subjected to a secondary hospital were assigned. Will determine the degree of diabetic retinopathy and macular edema was performed. In population were 55.2% female, mean age 48+11.1 years, 23.8 % had some degree of DR, 28.0% with mild non- proliferative diabetic retinopathy 48.0 % moderate 16.0% and severe and 8.0% showed proliferative diabetic retinopathy. Those over age 30 are 2.8 times more risk of developing DR, OR= 2.8; 95%CI: 0.42-18.0, and OR= 1.7; 95%CI: 1.02-2.95 women. The implementation of programs aimed at the early detection of debilitating conditions such as diabetic retinopathy health impact beneficiaries, effective links between primary care systems and provide second level positive health outcomes for patient diseases.
Jimenez-Baez, Maria Valeria; Barcenas-Contreras, Rodolfo; Morales Montoya, Carlos; Espinosa-Garcia, Laura Fatima
Objective: To evaluate the impact of a strategy for early detection of diabetic retinopathy in patients with type 2 diabetes mellitus (DMT2) in Quintana Roo, México. Methods: Study transversal, observational, prospective, analytical, eight primary care units from Mexican Social Security Institute in the northern delegation of the State of Quintana Roo, Mexico were included. A program for early detection of diabetic retinopathy (DR) in adult 376,169 was designed. Were diagnosed 683 cases of type 2 diabetes, in 105 patients randomized was conducted to direct ophthalmoscopy were subjected to a secondary hospital were assigned. Will determine the degree of diabetic retinopathy and macular edema was performed. Results: In population were 55.2% female, mean age 48+11.1 years, 23.8 % had some degree of DR, 28.0% with mild non- proliferative diabetic retinopathy 48.0 % moderate 16.0% and severe and 8.0% showed proliferative diabetic retinopathy. Those over age 30 are 2.8 times more risk of developing DR, OR= 2.8; 95%CI: 0.42-18.0, and OR= 1.7; 95%CI: 1.02-2.95 women. Conclusions: The implementation of programs aimed at the early detection of debilitating conditions such as diabetic retinopathy health impact beneficiaries, effective links between primary care systems and provide second level positive health outcomes for patient diseases. PMID:26019380
Pan, Yan; Adler, Nikki R; Wolfe, Rory; McLean, Catriona A; Kelly, John W
To determine the frequency of naevus-associated melanoma among superficial spreading and nodular subtypes; and to investigate associations between naevus-associated melanoma and other clinico-pathological characteristics. Cross-sectional study of all patients with nodular and superficial spreading melanomas diagnosed between 1994 and 2015 at the Victorian Melanoma Service, Melbourne. Clinical and pathological characteristics of naevus-associated and de novo melanomas were assessed in univariable and multivariable logistic regression analyses. Of 3678 primary melanomas, 1360 (37.0%) were histologically associated with a naevus and 2318 (63.0%) were de novo melanomas; 71 of 621 nodular (11.4%) and 1289 of 3057 superficial spreading melanomas (42.2%) were histologically associated with a naevus. In multivariable analyses, the odds of being associated with a naevus were higher for melanomas located on the trunk (v head and neck: adjusted odds ratio [OR], 2.27; 95% CI, 1.73-2.96; P < 0.001), while the odds were lower for thicker tumours (adjusted OR, 0.75 per millimetre increase in Breslow thickness; 95% CI, 0.69-0.81; P < 0.001), amelanotic/hypomelanotic melanomas (adjusted OR, 0.68; 95% CI, 0.48-0.97; P = 0.035), and older age (patients 70 years or older v patients under 30 at diagnosis: adjusted OR, 0.28; 95% CI, 0.20-0.40; P < 0.001). After adjusting for confounders, the odds of an associated naevus was three times as high for superficial spreading melanomas as for nodular melanomas (adjusted OR, 3.05; 95% CI, 2.24-4.17; P < 0.001). Melanomas are most likely to arise in the absence of a pre-existing naevus, particularly nodular melanomas. Public health campaigns should therefore emphasise the detection of suspicious de novo lesions, as well as of changing lesions.
Nader, Christelle Abou; Pellen, Fabrice; Loutfi, Hadi; Mansour, Rassoul; Jeune, Bernard Le; Brun, Guy Le; Abboud, Marie
Dental erosion starts with a chemical attack on dental tissue causing tooth demineralization, altering the tooth structure and making it more sensitive to mechanical erosion. Medical diagnosis of dental erosion is commonly achieved through a visual inspection by the dentist during dental checkups and is therefore highly dependent on the operator's experience. The detection of this disease at preliminary stages is important since, once the damage is done, cares become more complicated. We investigate the difference in light-scattering properties between healthy and eroded teeth. A change in light-scattering properties is observed and a transition from volume to surface backscattering is detected by means of polarized laser speckle imaging as teeth undergo acid etching, suggesting an increase in enamel surface roughness.
Hislop, T G; Coldman, A J; Skippen, D H
Shortly after diagnosis of breast cancer 416 patients were interviewed about their use of screening procedures and the method of tumour detection. Although 72% reported that they performed breast self-examination (BSE), only 12% actually inspected and palpated their breasts monthly. BSE was not significantly associated with tumour size or involvement of the lymph nodes; however, thorough inspection was associated with smaller tumours, and careful palpation with the absence of palpable nodes. Of those who no longer or never had examined their breasts 40% reported having annual breast examinations by their physician and had significantly smaller tumours than did the others. Most of the women (86%) reported having detected their own tumours, and BSE did not significantly increase the likelihood of self-detection. The frequency of use of screening procedures was similar in a sample of women without breast cancer. PMID:6498686
Malignant melanoma is one of the most deadly forms of skin cancer, which is one of the world's fastest-growing cancers. Early diagnosis and treatment is critical. In this study, a neural network structure is utilized to construct a broad and accurate basis for the diagnosis of skin cancer, thereby reducing screening errors. The technique is able to improve the efficacy for identification of normally indistinguishable lesions (such as pigment spots) versus clinically unknown lesions, and to ultimately improve the diagnostic accuracy. In the field of medical imaging, in general, using neural networks for image segmentation is relatively rare. The existing traditional machine-learning neural network algorithms still cannot completely solve the problem of information loss, nor detect the precise division of the boundary area. We use an improved neural network framework, described herein, to achieve efficacious feature learning, and satisfactory segmentation of melanoma images. The architecture of the network includes multiple convolution layers, dropout layers, softmax layers, multiple filters, and activation functions. The number of data sets can be increased via rotation of the training set. A non-linear activation function (such as ReLU and ELU) is employed to alleviate the problem of gradient disappearance, and RMSprop/Adam are incorporated to optimize the loss algorithm. A batch normalization layer is added between the convolution layer and the activation layer to solve the problem of gradient disappearance and explosion. Experiments, described herein, show that our improved neural network architecture achieves higher accuracy for segmentation of melanoma images as compared with existing processes.
Devescovi, Raffaella; Monasta, Lorenzo; Mancini, Alice; Bin, Maura; Vellante, Valerio; Carrozzi, Marco; Colombi, Costanza
Early diagnosis combined with an early intervention program, such as the Early Start Denver Model (ESDM), can positively influence the early natural history of autism spectrum disorders. This study evaluated the effectiveness of an early ESDM-inspired intervention, in a small group of toddlers, delivered at low intensity by the Italian Public Health System. Twenty-one toddlers at risk for autism spectrum disorders, aged 20-36 months, received 3 hours/wk of one-to-one ESDM-inspired intervention by trained therapists, combined with parents' and teachers' active engagement in ecological implementation of treatment. The mean duration of treatment was 15 months. Cognitive and communication skills, as well as severity of autism symptoms, were assessed by using standardized measures at pre-intervention (Time 0 [T0]; mean age =27 months) and post-intervention (Time 1 [T1]; mean age =42 months). Children made statistically significant improvements in the language and cognitive domains, as demonstrated by a series of nonparametric Wilcoxon tests for paired data. Regarding severity of autism symptoms, younger age at diagnosis was positively associated with greater improvement at post-assessment. Our results are consistent with the literature that underlines the importance of early diagnosis and early intervention, since prompt diagnosis can reduce the severity of autism symptoms and improve cognitive and language skills in younger children. Particularly in toddlers, it seems that an intervention model based on the ESDM principles, involving the active engagement of parents and nursery school teachers, may be effective even when the individual treatment is delivered at low intensity. Furthermore, our study supports the adaptation and the positive impact of the ESDM entirely sustained by the Italian Public Health System.
Bickle, Kelly; Smithberger, Erica; Lien, Mary H; Fenske, Neil Alan
The authors report a case of a Latin American woman who developed progressive pigmentation primarily involving two digits of her right hand. She was scheduled for amputation based on a presumptive histologic diagnosis of melanoma with regression. Dermatology consultation with repeat biopsies disclosed a lichenoid tissue reaction with marked pigment incontinence and no evidence of melanoma. This report should prompt physicians to include lichen planus pigmentosus in the differential diagnosis of acral lentiginous melanoma.
Zeppieri, Marco; Brusini, Paolo; Parisi, Lucia; Johnson, Chris A; Sampaolesi, Roberto; Salvetat, Maria Letizia
To assess the ability of Pulsar perimetry (Pulsar) in detecting early glaucomatous visual field (VF) damage in comparison with Frequency Doubling Technology (FDT), Scanning Laser Polarimetry (SLP, GDx VCC), and Heidelberg Retina Tomography (HRT). Prospective observational cross-sectional case study. This multicenter study included: 87 ocular hypertensives (OHT); 67 glaucomatous optic neuropathy (GON) patients; 75 primary open-angle glaucoma (POAG) patients; and 90 normals. All patients underwent standard automated perimetry (SAP) HFA 30-2, Pulsar T30W, FDT N-30, HRT II, and GDx VCC. Area under Receiver Operating Characteristic Curves (AROCs) for discriminating between healthy and glaucomatous eyes and agreement among instruments were determined. The best parameters for Pulsar, FDT, HRT, and GDx were, respectively: loss variance square root; no. of areas with P< 5%; Cup-Shape-Measure; and Nerve Fiber Indicator (NFI). In detecting POAG eyes, Pulsar (AROC, 0.90) appeared comparable with FDT (0.89) and significantly better than HRT (0.82) and GDx (0.79). For GON, Pulsar ability (0.74) was higher than GDx (0.69) and lower than FDT (0.80) and HRT (0.83). The agreement among instruments ranged from 0.12 to 0.56. Pulsar test duration was significantly shorter than SAP and FDT (P< .001). Pulsar T30W test is a rapid and easy perimetric method, showing higher sensitivity than SAP in detecting early glaucomatous VF loss. Its diagnostic ability is good for detecting early perimetric POAG eyes and fair for GON eyes. Pulsar performance was comparable with FDT, HRT, and GDx, even if the agreement between instruments was poor to fair. Copyright 2010 Elsevier Inc. All rights reserved.
Saiyed, Faiez K; Hamilton, Emma C; Austin, Mary T
The purpose of this review is to outline recent advancements in diagnosis, treatment, and prevention of pediatric melanoma. Despite the recent decline in incidence, it continues to be the deadliest form of skin cancer in children and adolescents. Pediatric melanoma presents differently from adult melanoma; thus, the traditional asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution (ABCDE) criteria have been modified to include features unique to pediatric melanoma (amelanotic, bleeding/bump, color uniformity, de novo/any diameter, evolution of mole). Surgical and medical management of pediatric melanoma continues to derive guidelines from adult melanoma treatment. However, more drug trials are being conducted to determine the specific impact of drug combinations on pediatric patients. Alongside medical and surgical treatment, prevention is a central component of battling the incidence, as ultraviolet (UV)-related mutations play a central role in the vast majority of pediatric melanoma cases. Aggressive prevention measures targeting sun safety and tanning bed usage have shown positive sun-safety behavior trends, as well as the potential to decrease melanomas that manifest later in life. As research into the field of pediatric melanoma continues to expand, a prevention paradigm needs to continue on a community-wide level. PMID:29388632
Picaud, A; Nlome-Nze, A R; Engongha-Beka, T; Ogowet-Igumu, N
The authors summarize the case of diprosopic syncephalic joined twins diagnosed at 22 weeks of pregnancy by ultrasonography performed because of hydramnios. The rate of separation anomalies of monozygotic twins is assessed by a review of the literature: from 1 to twenty to fifty thousands for joined twins to 1 per cent fifty thousand to fifteen millions for diprosopus. The etiology is the result of a late division of the egg between D12 and D16. Often an encephalic diprosopic joined twins cause elevated levels of maternal serum alpha protein. Early ultrasonography permits to consider a vaginal therapeutic abortion.
Sim, K. S.; Nia, M. E.; Ee, C. S.
In this paper, a detection assisting system for early infarct detection is developed. This new developed method is used to assist the medical practitioners to diagnose infarct from computed tomography images of brain. Using this assisting system, the infarct could be diagnosed at earlier stages. The non-contrast computed tomography (NCCT) brain images are the data set used for this system. Detection module extracts the pixel data from NCCT brain images, and produces the colourized version of images. The proposed method showed great potential in detecting infarct, and helps medical practitioners to make earlier and better diagnoses.
Palmigiano, Angelo; Barone, Rita; Sturiale, Luisa; Sanfilippo, Cristina; Bua, Rosaria Ornella; Romeo, Donata Agata; Messina, Angela; Capuana, Maria Luisa; Maci, Tiziana; Le Pira, Francesco; Zappia, Mario; Garozzo, Domenico
This work aims at exploring the human CSF (Cerebrospinal fluid) N-glycome by MALDI MS techniques, in order to assess specific glycosylation pattern(s) in patients with Alzheimer's disease (n:24) and in subjects with mild cognitive impairment (MCI) (n:11), these last as potential AD patients at a pre-dementia stage. For comparison, 21 healthy controls were studied. We identified a group of AD and MCI subjects (about 40-50% of the studied sample) showing significant alteration of CSF N-glycome profiling, consisting of a decrease in the overall sialylation degree and an increase in species bearing bisecting GlcNAc. Noteworthy, all the MCI patients that converted to AD within the clinical follow-up, had an abnormal CSF glycosylation profile. Based on the studied cohort, CSF glycosylation changes may occur before an AD clinical onset. Previous studies specifically focused on the key role of glycosyltransferase GnT-III on AD-pathogenesis, addressing the patho-mechanism to specific sugar modification of BACE-1 glycoprotein with bisecting GlcNAc. Our patients addressed protein N-glycosylation changes at an early phase of the whole biomolecular misregulation on AD, pointing to CSF N-glycome analyses as promising tool to enhance early detection of AD and also suggesting alternative therapeutics target molecules, such as specific glyco-enzymes. Copyright © 2015 Elsevier B.V. All rights reserved.
Ren, Ke; Dusad, Anand; Zhang, Yijia; Purdue, P Edward; Fehringer, Edward V; Garvin, Kevin L; Goldring, Steven R; Wang, Dong
To develop and evaluate diagnostic tools for early detection of wear particle-induced orthopaedic implant loosening. N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer was tagged with a near infrared dye and used to detect the inflammation induced by polymethylmethacrylate (PMMA) particles in a murine peri-implant osteolysis model. It was established by inserting an implant into the distal femur and challenging with routine PMMA particles infusion. The osteolysis was evaluated by micro-CT and histological analysis at different time points. Significant peri-implant osteolysis was found 3-month post PMMA particle challenge by micro-CT and histological analysis. At 1-month post challenge, when there was no significant peri-implant bone loss, the HPMA copolymer-near infrared dye conjugate was found to specifically target the femur with PMMA particles deposition, but not the contralateral control femur with phosphate buffered saline (PBS) infusion. The results from this study demonstrate the feasibility of utilizing the macromolecular diagnostic agent to detect particle-induced peri-implant inflammation prior to the development of detectable osteolysis. Recognition of this early pathological event would provide the window of opportunity for prevention of peri-implant osteolysis and subsequent orthopaedic implant failure.
Vaitkuviene, A.; Andersen-Engels, S.; Auksorius, E.; Bendsoe, N.; Gavriushin, V.; Gustafsson, U.; Oyama, J.; Palsson, S.; Soto Thompson, M.; Stenram, U.; Svanberg, K.; Viliunas, V.; De Weert, M. J.
Permanent infections recognized as oncogenic factor. STD is common concomitant diseases in early precancerous genital tract lesions. Simple optical detection of early regressive pre cancer in cervix is the aim of this study. Hereditary immunosupression most likely is risk factor for cervical cancer development. Light induced fluorescence point monitoring fitted to live cervical tissue diagnostics in 42 patients. Human papilloma virus DNR in cervix tested by means of Hybrid Capture II method. Ultraviolet (337 nm) laser excited fluorescence spectra in the live cervical tissue analyzed by Principal Component (PrC) regression method and spectra decomposition method. PCr method best discriminated pathology group "CIN I and inflammation"(AUC=75%) related to fluorescence emission in short wave region. Spectra decomposition method suggested a few possible fluorophores in a long wave region. Ultraviolet (398 nm) light excitation of live cervix proved sharp selective spectra intensity enhancement in region above 600nm for High-grade cervical lesion. Conclusion: PC analysis of UV (337 nm) light excitation fluorescence spectra gives opportunity to obtain local immunity and Low-grade cervical lesion related information. Addition of shorter and longer wavelengths is promising for multi wave LIF point monitoring method progress in cervical pre-cancer diagnostics and utility for cancer prevention especially in developing countries.
Walter, Jessica R; Xu, Shuai; Paller, Amy S; Choi, Jennifer N; Woodruff, Teresa K
Melanoma is the most common cancer diagnosed for patients ages 25 to 29 years, the group with the highest birth rates in the United States. Oncofertility is a new field addressing the reproductive needs of patients with cancer facing fertility-threatening treatments. We sought to assess gender-specific fertility risk for Food and Drug Administration (FDA)-approved melanoma therapies with a new risk category system. We conducted a retrospective review of FDA, European Union, and Health Canada regulatory filings, along with previously published reports to grade fertility risk of systemic melanoma therapies. The proposed fertility risk category system is analogous to the FDA's A/B/C/D/X/N pregnancy-risk categories. For female patients, 58% of treatments represent a fertility risk (Category C and D), 33% have unknown risk (Category N), and 1 therapy (vemurafenib) did not show animal ovarian toxicity (Category B). For male patients, 33% represented a fertility risk (Category C and D), 50% of treatments had unknown risk (Category N), and 17% did not show animal testicular toxicity (Category B). Data on fertility risk for melanoma therapies approved after 2009 are limited to preclinical animal studies. Dermatologists have an opportunity to discuss fertility preservation, make appropriate referrals, and steward registries on reproductive outcomes for patients with melanoma. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Afroze, Bushra; Yunus, Zabedah Mohammad
Glutaric aciduria type 1 is a rare inherited organic academia. Untreated patients characteristically develop dystonia secondary to striatal injury during early childhood, which results in high morbidity and mortality. In patients diagnosed during neonatal period, striatal injury can be prevented by metabolic treatment including low lysine diet, carnitine supplementation and aggressive emergency treatment during acute episode of inter current illnesses. However, after the onset of neurological damage initiation of treatment is generally not effective. Therefore; glutaric aciduria type 1 is included in newborn screening panel for inherited metabolic diseases in many countries. We describe two children in a family with glutaric aciduria type 1 and their different long term outcomes. The first child was diagnosed late leading to severe neurological damage. The second child was diagnosed in the neonatal period as a result of selective high-risk screening and was treated appropriately giving a normal growth.
Fernell, Elisabeth; Eriksson, Mats Anders; Gillberg, Christopher
Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008–2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband “early intervention” programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autism-friendly environment be “created” around affected individuals. PMID:23459124
Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M.; Gao, Feng; Xia, Younan; Wang, Lihong V.
Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bio-conjugated with [Nle4,D-Phe7]-α-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bio-conjugated AuNCs enhanced contrast ~300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS). PMID:20731439
Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M; Gao, Feng; Xia, Younan; Wang, Lihong V
Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bioconjugated with [Nle(4),D-Phe(7)]-alpha-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bioconjugated AuNCs enhanced contrast approximately 300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS).
Taylor, Nicholas J.; Thomas, Nancy E.; Anton-Culver, Hoda; Armstrong, Bruce K.; Begg, Colin B.; Busam, Klaus J.; Cust, Anne E.; Dwyer, Terence; From, Lynn; Gallagher, Richard P.; Gruber, Stephen B.; Nishri, Diane E.; Orlow, Irene; Rosso, Stefano; Venn, Alison J.; Zanetti, Roberto; Berwick, Marianne; Kanetsky, Peter A.
Although nevus count is an established risk factor for melanoma, relationships between nevus number and patient and tumor characteristics have not been well studied and the influence of nevus count on melanoma-specific survival is equivocal. Using data from the Genes, Environment, and Melanoma (GEM) study, a large population-based study of primary cutaneous melanoma, we evaluated associations between number of nevi and patient features, including sun-sensitivity summarized in a phenotypic index, and tumor characteristics, and we assessed the association of nevus count with melanoma-specific survival. Higher nevus counts were independently and positively associated with male gender and younger age at diagnosis and inversely associated with lentigo maligna histology. We observed a borderline significant trend of poorer melanoma-specific survival with increasing quartile of nevus count, but little or no association between number of nevi and pigmentary phenotypic characteristics or prognostic tumor features. PMID:27101944
Liu, Shuang; Wang, Bingqing; Yin, Biwei; Milner, Thomas E; Markey, Mia K; McKinnon, Stuart J; Rylander, Henry G
Compare performance of normalized reflectance index (NRI) and retinal nerve fiber layer thickness (RNFLT) parameters determined from optical coherence tomography (OCT) images for glaucoma and glaucoma suspect diagnosis. Seventy-five eyes from 71 human subjects were studied: 33 controls, 24 glaucomatous, and 18 glaucoma-suspects. RNFLT and NRI maps were measured using 2 custom-built OCT systems and the commercial instrument RTVue. Using area under the receiver operating characteristic curve, RNFLT and NRI measured in 7 RNFL locations were analyzed to distinguish between control, glaucomatous, and glaucoma-suspect eyes. The mean NRI of the control group was significantly larger than the means of glaucomatous and glaucoma-suspect groups in most RNFL locations for all 3 OCT systems (P<0.05 for all comparisons). NRI performs significantly better than RNFLT at distinguishing between glaucoma-suspect and control eyes using RTVue OCT (P=0.008). The performances of NRI and RNFLT for classifying glaucoma-suspect versus control eyes were statistically indistinguishable for PS-OCT-EIA (P=0.101) and PS-OCT-DEC (P=0.227). The performances of NRI and RNFLT for classifying glaucomatous versus control eyes were statistically indistinguishable (PS-OCT-EIA: P=0.379; PS-OCT-DEC: P=0.338; RTVue OCT: P=0.877). NRI is a promising measure for distinguishing between glaucoma-suspect and control eyes and may indicate disease in the preperimetric stage. Results of this pilot clinical study warrant a larger study to confirm the diagnostic power of NRI for diagnosing preperimetric glaucoma.
Xavier, Rose; Abraham, Bobby; Cherian, Vinod Jacob; Joseph, Jobin I.
Necrotising fasciitis (NF) is an extremely rare complication of a rather common paediatric viral exanthem varicella. Delayed diagnosis and treatment can lead to significant morbidity and mortality. Laboratory risk indicator of NF score aids in early clinical diagnosis in suspected cases of post-varicella NF thus enabling timely intervention. Surgery delayed for more than 24 hours, is an independent risk factor for death. Surgical debridement with good antibiotic coverage is the definitive treatment for NF. PMID:27251524
Eilers, R E; Oller, D K
To determine whether late onset of canonical babbling could be used as a criterion to determine risk of hearing impairment, we obtained vocalization samples longitudinally from 94 infants with normal hearing and 37 infants with severe to profound hearing impairment. Parents were instructed to report the onset of canonical babbling (the production of well-formed syllables such as "da," "na," "bee," "yaya"). Verification that the infants were producing canonical syllables was collected in laboratory audio recordings. Infants with normal hearing produced canonical vocalizations before 11 months of age (range, 3 to 10 months; mode, 7 months); infants who were deaf failed to produce canonical syllables until 11 months of age or older, often well into the third year of life (range, 11 to 49 months; mode, 24 months). The correlation between age at onset of the canonical stage and age at auditory amplification was 0.68, indicating that early identification and fitting of hearing aids is of significant benefit to infants learning language. The fact that there is no overlap in the distribution of the onset of canonical babbling between infants with normal hearing and infants with hearing impairment means that the failure of otherwise healthy infants to produce canonical syllables before 11 months of age should be considered a serious risk factor for hearing impairment and, when observed, should result in immediate referral for audiologic evaluation.
Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M
Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M
Background Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. Methods In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. Results The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. Conclusions In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. PMID:25908835
Miwa, Yasutsugu; Matsunaga, Satoru; Kato, Kumiko; Ogawa, Hiroyuki; Nakayama, Hiroyuki; Tsujimoto, Saori; Sasaki, Nobuo
A 7-year-old intact female golden Retriever was referred for evaluation of an intraorbital mass of the left eye. Based on ophthalmoscopy, ultrasonography and magnetic resonance imaging (MRI), the tentative diagnosis was made as an intraocular neoplasia, especially choroidal melanoma. The orbital exenteration of the affected eye was performed. The mass was histologically diagnosed as malignant choroidal melanoma. No signs of recurrence and metastasis were detected by thoracic radiographs, blood examinations and MR images, and the dog was clinically healthy for 23 months after operation.
Ali, Abder-Rahman A.; Deserno, Thomas M.
Malignant melanoma is the third most frequent type of skin cancer and one of the most malignant tumors, accounting for 79% of skin cancer deaths. Melanoma is highly curable if diagnosed early and treated properly as survival rate varies between 15% and 65% from early to terminal stages, respectively. So far, melanoma diagnosis is depending subjectively on the dermatologist's expertise. Computer-aided diagnosis (CAD) systems based on epiluminescense light microscopy can provide an objective second opinion on pigmented skin lesions (PSL). This work systematically analyzes the evidence of the effectiveness of automated melanoma detection in images from a dermatoscopic device. Automated CAD applications were analyzed to estimate their diagnostic outcome. Searching online databases for publication dates between 1985 and 2011, a total of 182 studies on dermatoscopic CAD were found. With respect to the systematic selection criterions, 9 studies were included, published between 2002 and 2011. Those studies formed databases of 14,421 dermatoscopic images including both malignant "melanoma" and benign "nevus", with 8,110 images being available ranging in resolution from 150 x 150 to 1568 x 1045 pixels. Maximum and minimum of sensitivity and specificity are 100.0% and 80.0% as well as 98.14% and 61.6%, respectively. Area under the receiver operator characteristics (AUC) and pooled sensitivity, specificity and diagnostics odds ratio are respectively 0.87, 0.90, 0.81, and 15.89. So, although that automated melanoma detection showed good accuracy in terms of sensitivity, specificity, and AUC, but diagnostic performance in terms of DOR was found to be poor. This might be due to the lack of dermatoscopic image resources (ground truth) that are needed for comprehensive assessment of diagnostic performance. In future work, we aim at testing this hypothesis by joining dermatoscopic images into a unified database that serves as a standard reference for dermatology related research in
Lin, Jing; Gu, Wei; Hou, Yanyan
To explore the gestational age of early-onset intrahepatic cholestasis (ICP) of pregnancy, and to analyze the relationship between the clinical biochemical indices and pregnancy outcomes in order to arrive at a reasonable diagnosis and administer appropriate treatment. This is a retrospective clinical study. We selected 47,260 pregnant women who received prenatal care and underwent childbirth at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiao Tong University from January 2014 to December 2016 for participating in this study. Of these 47,260 women, 407 developed ICP. To calculate the gestational week cutoff between early- and late-onset ICP by the receiver-operating characteristic (ROC) curve and Youden's index. Two independent samples t tests and chi square test were used to compare the differences in biochemical indices and pregnancy outcomes between the two groups. We found that 34 weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. Early-onset ICP is characterized by early onset, long disease duration and a higher incidence of preterm labor, fetal distress, and fetal low birth weight compared to late-onset ICP. Thirty-four weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. And to reduce the adverse pregnancy outcomes in cases of early-onset ICP, we suggest prolonging gestation up to 37 weeks as far as possible before selecting iatrogenic birth.
Blin-Rochemaure, N; Allani-Essid, N; Carlier, R; Laugel, V; Quijano-Roy, S
Two siblings affected with Cockayne syndrome (CS) are described: this diagnosis was suggested by the finding of a demyelinating neuropathy on electromyography in both children and consistent clinical features. CS is a rare genetic disorder with severe prognosis and a highly varied phenotype, making early diagnosis difficult. Taking into account these two cases and the literature, the current diagnosis criteria are insufficiently specific and appear late: the diagnosis may be delayed because multi-organ involvement and sensorial impairment suggests more frequent neurometabolic disorders. Neuroradiologic abnormalities are suggestive but may occur later. The finding of a demyelinating peripheral neuropathy seems to be a more useful marker to suspect this disorder in the presence of other clinical features. Further studies are required to better define the chronology of the symptoms, not only for adequate genetic counseling and eventual prenatal diagnosis, but also to assess the efficacy of future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Background and objectives The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. Material and Methods A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words “squamous cell carcinoma”, “early diagnosis” “oral cavity”, “Potentially Malignant Disorders” y “premalignant lesions”. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Results Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. Conclusions The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions. PMID:25662554
Evaluation of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: Results from the International Melanoma Pathology Study Group.
Lott, Jason P; Elmore, Joann G; Zhao, Ge A; Knezevich, Stevan R; Frederick, Paul D; Reisch, Lisa M; Chu, Emily Y; Cook, Martin G; Duncan, Lyn M; Elenitsas, Rosalie; Gerami, Pedram; Landman, Gilles; Lowe, Lori; Messina, Jane L; Mihm, Martin C; van den Oord, Joost J; Rabkin, Michael S; Schmidt, Birgitta; Shea, Christopher R; Yun, Sook Jung; Xu, George X; Piepkorn, Michael W; Elder, David E; Barnhill, Raymond L
Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. This was a small sample size of experienced pathologists in a testing situation. Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Le, Quynh; Norris, Diana; McClean, Catriona A; Mcguiness, Myra; Meani, Rowena; Kelly, John W; Pan, Yan
Paediatric melanoma is an uncommon presentation of melanoma that accounts for 3% of all paediatric cancers. The objective was to describe a series of paediatric melanoma cases presenting to a state-wide tertiary referral service over the past 19 years. A search of the Victorian Melanoma Service database was performed to identify all patients under the age of 20 years diagnosed with melanoma from 1994 to 2013. Histological, demographic and phenotypical information for each patient was collected. Patients were matched against the Victorian Death Registry to identify those who had died. Fisher's exact test was used to examine associations. Melanoma-specific survival was estimated using the Kaplan-Meier method. A total of 65 paediatric melanoma patients were included for analysis, in whom 72.3% of melanomas were diagnosed when they were 16-19 years of age with a mean age at diagnosis of 16 years. The mean Breslow thickness was 1.4 mm. It was greatest (3.4 mm) in the youngest age group (< 12 years of age). Ten patients developed nodal metastatic disease, eight of which progressed to visceral metastatic disease. The 5-year melanoma-specific survival rate was 96.8%. This is the first descriptive epidemiological study of paediatric melanoma in Victoria. Further large, population-based, multi-institutional studies of paediatric melanoma are warranted to provide a clearer understanding of this group of melanoma patients. © 2016 The Australasian College of Dermatologists.
Kaida, Toyoji; Inomata, Takayuki; Minami, Yoshiyasu; Yazaki, Mayu; Fujita, Teppei; Iida, Yuichiro; Ikeda, Yuki; Nabeta, Takeru; Ishii, Shunsuke; Naruke, Takashi; Maekawa, Emi; Koitabashi, Toshimi; Ako, Junya
Our aim is to clarify the factors for early diagnosis of cardiac sarcoidosis (CS) in patients with complete atrioventricular block (CAVB) and its impact on cardiac function after corticosteroid therapy.A total of 15 CS patients with CAVB who underwent corticosteroid therapy were retrospectively analyzed. Patients were divided into two groups according to the time from the first CAVB onset to the diagnosis of CS. Clinical characteristics and outcomes were compared between the early diagnosis group (within 1 year; group E, n = 10) and the late diagnosis group (over 1 year; group L, n = 5).The history of extracardiac sarcoidosis (60 versus 0%, P = 0.0440) and abnormal findings on echocardiography (70 versus 0%, P = 0.0256) at the CAVB onset were significantly more frequent in group E than in group L. The change of left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) levels was significantly better in group E than in group L (0.8 ± 2.8 versus -32.4 ± 3.9%, P < 0.0001; -11.1 ± 16.0 versus 161.8 ± 35.8 pg/mL, P = 0.0013, respectively). After corticosteroid therapy, the LVEF and BNP levels were also significantly better in group E than in group L (53.3 ± 10.7 versus 37.0 ± 9.3%, P = 0.0128; 63.0 ± 46.4 versus 458.8 ± 352.0 pg/mL, P = 0.0027).The diagnosis may be delayed in CS patients with CAVB without history of extracardiac sarcoidosis. Abnormal findings on echocardiography contributed to the early diagnosis of CS. Therefore, the diagnosis of CS may be missed or delayed in patients without them. Time delay from the CAVB onset to the CS diagnosis may exacerbate the cardiac function.
Klit, Anders; Lassen, Cecilie Brandt; Olsen, Caroline Holkmann; Lock-Andersen, Jørgen
The incidence of cutaneous malignant melanoma is rapidly increasing in Denmark like in other Northern and Western European countries. Our objective was to investigate the characteristics of current patients suffering from cutaneous malignant melanoma. We evaluated patient and tumour characteristics in a cross-sectional study based on data from the Danish Melanoma Register. We included all patients diagnosed with cutaneous malignant melanoma in Healthcare Region Zealand in 2012 and 2013. We identified 520 patients with invasive cutaneous malignant melanoma. More females than males suffered from cutaneous malignant melanoma. Furthermore, females were younger than males, and the anatomical distribution of malignant melanoma varied between the genders. Outcome of sentinel lymph node biopsy was associated with tumour thickness. When comparing findings in our study with earlier Danish studies, we see a trend towards an increase in age at diagnosis. Furthermore, tumour thickness is decreasing and the topical distribution of cutaneous malignant melanoma in females changes towards a male pattern. none. The study has been approved by the Danish National Data Protection Agency.
Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe
Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Mission, John F; Catov, Janet; Deihl, Tiffany E; Feghali, Maisa; Scifres, Christina
To evaluate the prevalence of early diabetes screening in pregnancy, rates of abnormal diabetes test results before 24 weeks of gestation, and factors associated with early diabetes screening. This was a retrospective cohort study of all singleton deliveries from 2012 to 2014 among diverse clinical practices at a large academic medical center. We assessed rates of early (less than 24 weeks of gestation) and routine (at or beyond 24 weeks of gestation) diabetes screening, with abnormal test results defined using the Carpenter-Coustan criteria, a 50-g glucose challenge test result greater than 200 mg/dL, or a hemoglobin A1C level greater than 6.5%. Univariate and multivariate analyses were used to evaluate clinical and demographic determinants of screening and diagnosis. Overall, 1,420 of 11,331 (12.5%) women underwent early screening. Increasing body mass index (BMI) category, race, public insurance, history of gestational diabetes mellitus, a family history of diabetes, and chronic hypertension were associated with early screening. Early screening rates rose with increasing BMI category, but only 268 of 551 (48.6%) of women with class III obesity underwent early screening. Among those screened early, 2.0% of normal-weight women, 4.0% of overweight women, 4.2% of class I obese women, 3.8% of class II obese women, and 9.0% of class III obese women had abnormal early test results (P<.001). Early diabetes screening is used inconsistently, and many women with risk factors do not undergo early screening. A significant proportion of women with class III obesity will test positive for gestational diabetes mellitus before 24 weeks of gestation, and studies are urgently needed to assess the effect of early diabetes screening and diagnosis on perinatal outcomes in high-risk women.
Rashid, Omar M; Zager, Jonathan S
Melanoma is increasing in incidence and represents an aggressive type of cancer. Efforts have focused on identifying genetic factors in melanoma carcinogenesis to guide prevention, screening, early detection, and targeted therapy. This article reviews the hereditary risk factors associated with melanoma and the known molecular pathways and genetic mutations associated with this disease. This article also explores the controversies associated with genetic testing and the latest advances in identifying genetic targets in melanoma, which offer promise for future application in the multidisciplinary management of melanoma. Copyright © 2015 Elsevier Inc. All rights reserved.
Xin, Lei; Gao, Jun; Wang, Dan; Lin, Jin-Huan; Liao, Zhuan; Ji, Jun-Tao; Du, Ting-Ting; Jiang, Fei; Hu, Liang-Hao; Li, Zhao-Shen
Chronic pancreatitis (CP) is an inflammatory disease characterized by progressive fibrosis of pancreas. Early diagnosis will improve the prognosis of patients. This study aimed to obtain serum miRNA biomarkers for early diagnosis of CP. In the current study, we analyzed the differentially expressed miRNAs (DEmiRs) of CP patients from Gene Expression Omnibus (GEO), and the DEmiRs in plasma of early CP patients (n = 10) from clinic by miRNA microarrays. Expression levels of DEmiRs were further tested in clinical samples including early CP patients (n = 20), late CP patients (n = 20) and healthy controls (n = 18). The primary endpoints were area under curve (AUC) and expression levels of DEmiRs. Four DEmiRs (hsa-miR-320a-d) were obtained from GEO CP, meanwhile two (hsa-miR-221 and hsa-miR-130a) were identified as distinct biomarkers of early CP by miRNA microarrays. When applied on clinical serum samples, hsa-miR-320a-d were accurate in predicting late CP, while hsa-miR-221 and hsa-miR-130a were accurate in predicting early CP with AUC of 100.0% and 87.5%. Our study indicates that miRNA expression profile is different in early and late CP. Hsa-miR-221 and hsa-miR-130a are biomarkers of early CP, and the panel of the above 6 serum miRNAs has the potential to be applied clinically for early diagnosis of CP. PMID:28074846
Simon, John L.; McArdle, Patricia
Early and Periodic Screening, Diagnosis and Treatment (EPSDT) is a program of preventive health services available to individuals under 21 years of age who are eligible for Medicaid benefits. As of July 1, 1973, all states operating a Medicaid program were required to provide EPSDT services to all those eligible. The purpose of this module is to…
Reilly, D J; Aksakal, G; Gilmour, R F; Gyorki, D E; Chauhan, A; Webb, A; Henderson, M A
Subungual melanoma is a rare subtype of cutaneous melanoma that arises from the structures of the nail apparatus. It presents most commonly in older patients and at an advanced stage. A retrospective review of all patients with subungual melanoma in a single institution over a 15-year period was performed. In total, 54 patients were included (26 males, average age 62.9 years), of which 28 cases involved the upper limb. Median tumour thickness was 4.5 mm. Eighteen patients had lymph node metastasis at diagnosis, including 11 of 36 patients with positive sentinel lymph node biopsy. Median survival was 4.6 years. Subungual melanoma has a poor prognosis that is strongly associated with presence of nodal disease at diagnosis. Sentinel lymph node biopsy should be considered to determine stage and prognosis. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Brandão, Maria Luiza; Oliveira Lima, Cíntia Maria; Moura, Heloísa Helena; Ishida, Cleide; Campos-do-Carmo, Gabriella; Cuzzi, Tullia; Ramos-E-Silva, Marcia
Cutaneous melanoma may in some instances be confused with seborrheic keratosis, which is a very common neoplasia, more often mistaken for actinic keratosis and verruca vulgaris. Melanoma may clinically resemble seborrheic keratosis and should be considered as its possible clinical simulator. We report a case of melanoma with dermatoscopic characteristics of seborrheic keratosis and emphasize the importance of the dermatoscopy algorithm in differentiating between a melanocytic and a non-melanocytic lesion, of the excisional biopsy for the establishment of the diagnosis of cutaneous tumors, and of the histopathologic examination in all surgically removed samples.
Kalampokas, Emmanouil; Kalampokas, Theodoros; Damaskos, Christos
Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Margue, Christiane; Philippidou, Demetra; Reinsbach, Susanne E; Schmitt, Martina; Behrmann, Iris; Kreis, Stephanie
The non-coding microRNAs (miRNA) have tissue- and disease-specific expression patterns. They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes. Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, prediction of progression for melanoma and other cancers and as promising drug targets, since they can easily be inhibited or replaced in a given cellular context. Before successfully manipulating miRNAs in clinical settings, their precise expression levels, endogenous functions and thus their target genes have to be determined. MiR-211, a melanocyte lineage-specific small non-coding miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia-associated transcription factor (MITF). By transcriptionally up-regulating TRPM1, MITF, which is critical for both melanocyte differentiation and survival and for melanoma progression, indirectly drives the expression of miR-211. Expression of this miRNA is often reduced in melanoma samples. Here, we investigated functional roles of miR-211 by identifying and studying new target genes. We show that MITF-correlated miR-211 expression levels are mostly but not always reduced in a panel of 11 melanoma cell lines and in primary and metastatic melanoma compared to normal melanocytes and nevi, respectively. MiR-211 itself only marginally impacted on cell invasion and migration, while perturbation of some new miR-211 target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased invasion. These results and the variable expression levels of miR-211 raise serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA and/or as a biomarker for melanoma.
Badenas, Celia; Aguilera, Paula; Puig-Butillé, Joan A.; Carrera, Cristina; Malvehy, Josep; Puig, Susana
Summary Genetic counselling may be offered to families with melanoma and to individuals with multiple melanomas to better understand the genetic susceptibility of the disease, the influence of environmental factors, the inheritance of the risk and behaviour that decreases the risk of dying from melanoma including specific dermatological follow-up such as total body photography and digital dermoscopy. Genetic testing may be offered to those individuals with more than a 10% chance of being a carrier of a mutation. This risk varies according to the incidence of melanoma in the country and sun behaviour. In countries with a low-medium incidence of melanoma, genetic testing should be offered to families with two cases of melanoma or an individual with two primary melanomas. In countries with a high incidence, families with three cases of melanoma, with two melanomas and one pancreatic adenocarcinoma, or patients with three primary melanomas may benefit from genetic testing. PMID:23046018
Feghali, Maisa N; Abebe, Kaleab Z; Comer, Diane M; Caritis, Steve; Catov, Janet M; Scifres, Christina M
To examine pregnancy outcomes in women with gestational diabetes mellitus (GDM) based on the timing of diagnosis. We compared demographics, blood sugars and outcomes between women diagnosed before (n = 167) or after 24 weeks' gestation (n = 1202) in a single hospital between 2009 and 2012. Because early screening is risk-based we used propensity score modelling and conditional logistic regression to account for systematic differences. Women diagnosed with GDM before 24 weeks were more likely to be obese and they were less likely to have excess gestational weight gain (35 vs. 45%, p = 0.04). Early diagnosis was associated with more frequent therapy including glyburide (65 vs. 56%, p < 0.001) and insulin (19 vs 6%, p < 0.001). After propensity score modelling and accounting for covariates, early diagnosis was associated with an increased risk for macrosomia (OR 2, 95% 1-4.15, p = 0.0498). Early diagnosis was not associated with other adverse outcomes. In a subgroup analysis comparing women treated with glyburide prior to 24 weeks compared to those diagnosed after 24 weeks, early diagnosis in women treated with glyburide was associated with an increased risk for macrosomia (OR 2.3, 95% CI 1.1-5.4, P = 0.04). Women diagnosed with GDM before 24 weeks have unique features, are at risk for adverse outcomes, and require targeted approaches to therapy. Copyright © 2018 Elsevier B.V. All rights reserved.
Zhao Jinsong; Huang Jianchao; Sun Wei
A fault detection and diagnosis framework is proposed in this paper for early fault detection and diagnosis (FDD) of municipal solid waste incinerators (MSWIs) in order to improve the safety and continuity of production. In this framework, principal component analysis (PCA), one of the multivariate statistical technologies, is used for detecting abnormal events, while rule-based reasoning performs the fault diagnosis and consequence prediction, and also generates recommendations for fault mitigation once an abnormal event is detected. A software package, SWIFT, is developed based on the proposed framework, and has been applied in an actual industrial MSWI. The application shows thatmore » automated real-time abnormal situation management (ASM) of the MSWI can be achieved by using SWIFT, resulting in an industrially acceptable low rate of wrong diagnosis, which has resulted in improved process continuity and environmental performance of the MSWI.« less
Elder, Jennifer Harrison; Kreider, Consuelo Maun; Brasher, Susan N; Ansell, Margaret
Autism spectrum disorder (ASD) refers to a lifelong condition that usually appears in late infancy or early childhood, and is characterized by social and communication deficits that impede optimal functioning. Despite widespread research and greater public awareness, ASD has an unclear etiology and no known cure, making it difficult to acquire accurate and timely diagnoses. In addition, once an ASD diagnosis is made, parents find it challenging to navigate the healthcare system and determine which interventions are most effective and appropriate for their child. A growing body of evidence supports the value of early diagnosis and treatment with evidence-based interventions, which can significantly improve the quality of life of individuals with ASD as well as of their carers and families. Particularly noteworthy are early interventions that occur in natural surroundings and can be modified to address age-related goals throughout the lifespan. Therefore, the purpose of this review is to: 1) provide readers with a brief background related to ASD; 2) describe commonly used screening instruments and tools for early diagnosis; 3) describe early interventions that have empirical support; and 4) discuss how the parent-child and family relationships can be affected through this process. This information can provide professionals with information they can use to assist families who make critical and potentially life-changing decisions for children with ASD.
Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma
Bernauer, W; Duguid, G I; Dart, J K
Acanthamoeba keratitis is an uncommon condition which is usually associated with contact lens wear. The use of home made saline and poor hygiene are important risk factors. Early diagnosis is crucial since these cases respond well to medical therapy. The purpose of this paper is to describe and demonstrate early clinical signs. Between September 1992 and October 1994, 70 cases of acanthamoeba keratitis, one of them bilateral, were prospectively monitored at Moorfields Eye Hospital in London. A database of all patients was set up and the clinical findings, diagnostic methods, therapeutic interventions and the outcome were recorded. 66 patients (96%) were contact lens wearers, 64 of them (97%) wore soft lenses. The mean interval between first symptoms and correct diagnosis was 42%. The most frequent initial diagnoses were "unclear keratoconjunctivitis" and "herpetic keratitis". Early corneal findings included punctate keratopathy (n = 14; 20%), pseudodendrites (n = 4; 6%), epithelial infiltrates (n = 17; 24%), diffuse or focal sub-epithelial infiltrates (n = 36; 51%) and radial keratoneuritis (n = 5; 7%). Ring infiltrates (n = 13; 18%) and corneal ulceration (n = 13) were late signs. When the above corneal findings are observed, particularly in contact lens wearers, the diagnosis of acanthamoeba keratitis should be considered. The diagnosis of "herpetic keratitis" in association with contact lens wear should be encountered with scepticism.
Extraocular Extension Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma
Paolacci, Lucia; Giannandrea, David; Mecocci, Patrizia; Parnetti, Lucilla
In recent years, many efforts have been spent to identify sensitive biomarkers able to improve the accuracy of Alzheimer's disease (AD) diagnosis. Two different workgroups (NIA-AA and IWG) included cerebrospinal fluid (CSF) and neuroimaging findings in their sets of criteria in order to improve diagnostic accuracy as well as early diagnosis. The number of subjects with cognitive impairment increases with aging but the oldest old (≥85 years of age), the fastest growing age group, is still the most unknown from a biological point of view. For this reason, the aim of our narrative mini-review is to evaluate the pertinence of the new criteria for AD diagnosis in the oldest old. Moreover, since different subgroups of oldest old have been described in scientific literature (escapers, delayers, survivors), we want to outline the clinical profile of the oldest old who could really benefit from the use of biomarkers for early diagnosis. Reviewing the literature on biomarkers included in the diagnostic criteria, we did not find a high degree of evidence for their use in the oldest old, although CSF biomarkers seem to be still the most useful for excluding AD diagnosis in the "fit" subgroup of oldest old subjects, due to the high negative predictive value maintained in this age group.
Morgan, Debra; Funk, Melanie; Crossley, Margaret; Basran, Jenny; Kirk, Andrew; Bello-Haas, Vanina Dal
Early differential diagnosis of dementia is becoming increasingly important as new pharmacologic therapies are developed, as these treatments are not equally effective for all types of dementia. Early detection and differential diagnosis also facilitates informed family decision making and timely access to appropriate services. Information about…
Jovanovic, Predrag; Mihajlovic, Marija; Djordjevic-Jocic, Jasmina; Vlajkovic, Slobodan; Cekic, Sonja; Stefanovic, Vladisav
Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease. PMID:23826405
Seror, Jeremy; Lefevre, Guillaume; Berkane, Nathalie; Richard, Frederic; Bornes, Marie; Uzan, Serge; Berkane, Nadia
Calcium-channel blockers administered to pregnant women as tocolytic agents can cause acute pulmonary edema. The first signs of this severe complication can be atypical and so delay introduction of appropriate therapy. We describe three cases in whom B-type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema. B-type natriuretic peptide measurement in this setting could contribute to timely diagnosis and improve follow-up. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.
The increase in incidence of malignant melanoma, early diagnosis activities increasingly reaching ever larger population groups and mortality remaining at a constant level in trend comprise the background of the study. We aimed at answering the question whether the early diagnosis can have an influence on the increase in incidence and how one can one judge the effect on the reduction of the mortality. The study is based on data from official tumour registries of the regions Saarland, Schleswig-Holstein, the administrative district Münster, the former GDR and the New Dfederal states (Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt, Thüringen), as well as that of Queensland (Australia). Parallel to the increasing incidence, there is also an increase in the number of melanomas detected at early stages. Hence, it is obvious to assume that this increase in incidence is due to a large extent to screening programmes. In a non-determinable number of cases, overdiagnostics could have contributed to the increase in incidence. In the period of observation mortality remained constant in the regions described in this study. It can be assumed the mortality risk is influenced by tumours with a high degree of malignancy whose share in the number of melanomas remains roughly constant. The early diagnosis of cancer, the inclusion of increasingly larger groups of the populations in the regions described, and constant mortality rates for men and women during the period of observation all relate the use of early diagnosis. If the efficiency of population screening is measured against the outcome reduction of the mortality rate, it appears to be sufficient to continue cancer early detection according to SGB V § 25. A preventive check-up is indicated for risk groups, e. g., those with a positive familiar history or if potentially malignant skin alterations have been diagnosed. © Georg Thieme Verlag KG Stuttgart · New York.
Mugambi, Melissa Latigo; Deo, Sarang; Kekitiinwa, Adeodata; Kiyaga, Charles; Singer, Mendel E.
Background There is scant evidence on the association between diagnosis delays and the receipt of test results in HIV Early Infant Diagnosis (EID) programs. We determine the association between diagnosis delays and other health care system and patient factors on result receipt. Methods We reviewed 703 infant HIV test records for tests performed between January 2008 and February 2009 at a regional referral hospital and level four health center in Uganda. The main outcome was caregiver receipt of the test result. The primary study variable was turnaround time (time between sample collection and result availability at the health facility). Additional variables included clinic entry point, infant age at sample collection, reported HIV status and receipt of antiretroviral prophylaxis for prevention of mother-to-child transmission. We conducted a pooled analysis in addition to separate analyses for each facility. We estimated the relative risk of result receipt using modified Poisson regression with robust standard errors. Results Overall, the median result turnaround time, was 38 days. 59% of caregivers received infant test results. Caregivers were less likely to receive results at turnaround times greater than 49 days compared to 28 days or fewer (ARR = 0.83; 95% CI = 0.70–0.98). Caregivers were more likely to receive results at the PMTCT clinic (ARR = 1.81; 95% CI = 1.40–2.33) and less likely at the pediatric ward (ARR = 0.54; 95% CI = 0.37–0.81) compared to the immunization clinic. At the level four health center, result receipt was half as likely among infants older than 9 months compared to 3 months and younger (ARR= 0.47; 95% CI = 0.25–0.93). Conclusion In this study setting, we find evidence that longer turnaround times, clinic entry point and age at sample collection may be associated with receipt of infant HIV test results. PMID:24282502
Soura, E.; Eliades, P.; Shannon, K.; Stratigos, A.; Tsao, H.
Malignant melanoma is considered the most lethal skin cancer if not detected and treated at its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (i.e. unilateral lineage, multi-generational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. Such patients have a high risk of developing multiple primary melanomas and internal organ malignancies especially pancreatic cancer; thus, a multidisciplinary approach is necessary in many cases. The value of dermoscopy examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. But, this must be performed with care and only by qualified individuals trained in cancer risk analysis. PMID:26892650
Lisowska, Anna; Rekik, Islem
Diagnosis of brain dementia, particularly early mild cognitive impairment (eMCI), is critical for early intervention to prevent the onset of Alzheimer's Disease (AD), where cognitive decline is severe and irreversible. There is a large body of machine-learning based research investigating how dementia alters brain connectivity, mainly using structural (derived from diffusion MRI) and functional (derived from resting-state functional MRI) brain connectomic data. However, how early dementia affects cortical brain connections in morphology remains largely unexplored. To ﬁll this gap, we propose a joint morphological brain multiplexes pairing and mapping strategy for early MCI detection, where a brain multiplex not only encodes the similarity in morphology between pairs of brain regions, but also a pair of brain morphological networks. Experimental results conﬁrm that the proposed framework outperforms in classification accuracy several state-of-the-art methods. More importantly, we unprecedentedly identiﬁed most discriminative brain morphological networks between eMCI and NC, which included the paired views derived from maximum principal curvature and the sulcal depth for the left hemisphere and sulcal depth and the average curvature for the right hemisphere. We also identified the most highly correlated morphological brain connections in our cohort, which included the (pericalcarine cortex, insula cortex) on the maximum principal curvature view, (entorhinal cortex, insula cortex) on the mean sulcal depth view, and (entorhinal cortex, pericalcarine cortex) on the mean average curvature view, for both hemispheres. These highly correlated morphological connections might serve as biomarkers for early MCI diagnosis.
Yao, Yibing; Fan, Yu; Wu, Jun; Wan, Haisu; Wang, Jing; Lam, Stephen; Lam, Wan L.; Girard, Luc; Gazdar, Adi F.; Wu, Zhihao; Zhou, Qinghua
To identify a panel of tumor associated autoantibodies which can potentially be used as biomarkers for the early diagnosis of non-small cell lung cancer (NSCLC). Thirty-five unique and in-frame expressed phage proteins were isolated. Based on the gene expression profiling, four proteins were selected for further study. Both receiver operating characteristic curve analysis and leave-one-out method revealed that combined measurements of four antibodies produced have better predictive accuracies than any single marker alone. Leave-one-out validation also showed significant relevance with all stages of NSCLC patients. The panel of autoantibodies has a high potential for detecting early stage NSCLC. PMID:22713465
Shapira, Yehoshua; Finkelstein, Tamar; Kadry, Rana; Schonberger, Shirley; Shpack, Nir
Bilateral mandibular tooth transposition is a relatively rare dental anomaly caused by distal migration of the mandibular lateral incisors and can be detected in the early mixed dentition by radiographic examination. Early diagnosis and interceptive intervention may reduce the risk of possible transposition between the mandibular canine and lateral incisor. This report illustrates the orthodontic management of bilateral mandibular canine-lateral incisor transposition. Correct positioning of the affected teeth was achieved on the left side while teeth on the right side were aligned in their transposed position. It demonstrates the outcome of good alignment of the teeth in the dental arch.
Turkmen, G G; Karçaaltıncaba, D; Isık, H; Fidancı, V; Kaayalp, D; Tımur, H; Batıoglu, S
Early diagnosis of ectopic pregnancy (EP) is important due to life-threatening consequences in the first trimester of pregnancy. In this study we aimed to investigate the role of adenosine deaminase (ADA) activity in the prediction of EP. Forty-one patients with unruptured ectopic pregnancy comprised the case group and forty-two first trimester pregnant women with shown foetal heart beating in ultrasound comprised the control group. The mean ADA level in EP (10.9 ± 3.0 IU/L) was higher than that in control group (9.2 ± 3.6 IU/L) (p = 0.018). Receiver operating characteristics or ROC curve identified ADA value of 10.95 IU/L as optimal threshold for the prediction of EP with 56% sensitivity and 67% specificity. High ADA levels are valuable in the early diagnosis of EP. However more comprehensive studies are required.
Xie, Dan-dan; Li, Xiao-song; Liu, Yuan-yuan
To determine the value of blink reflex in early diagnosis and prognosis evaluation of Bell palsy. Blink reflex and facial nerve conduction were examined in 58 patients with Bell palsy within one week after symptom onset. The patients without response of R1 , R2 and R2 ' waves were classified as complete efferent retardarce (Group A, 30 cases), and those with response of R1 , R2 and R2 ' waves were classified as incomplete efferent anomalies (Group B, 28 cases). The clinical outcomes after three months of systemic therapy were evaluated using the House-Blackmann (H-B) scale. Efferent anomalies of blink reflex occurred in ail of the 58 patients. Abnormal results of facial nerve conduction appeared in 23 (39. 7%) patients. The three months therapy was effective in 93% patients in Group B and 70% patients in Group A (P<0. 05). Blink reflex can play a significant role in early diagnosis and prognosis evaluation of Bell palsy.
Wang, Xian-Ling; Li, Cun-Jiang
To explore the early diagnosis of germinoma originating from the basal ganglia (BG) and thalamus during juveniles. Retrospective analysis was done with the clinical cases of germinomas in BG and thalamus from 2000 to 2009. The symptoms, signs, neuroimaging, cerebrospinal fluid (CSF) findings were analyzed and related literature were reviewed. Eight patents were collected. The main symptoms were hemiplegia, associated with aphasia and/or impaired cognition. Brain CT showed high density and calcification. Abnormal T1 and T2 signal were found in brain MRI frequently associated with ipsilateral hemisphere atrophy. MRS showed increased choline and decreased N-acetylaspartate level. Elevated CSF human chorionic gonadotrophin level were found in two of them. Germinoma in BG and thalamus predominates in a boy. The neuroimaging features are very informative for early diagnosis.
Chopra, G S; Narula, A S; Reddy, P S; Bhardwaj, J R
A total of 86 renal transplant patients who were transplanted with live related donor (LRD) and live unrelated donor (LURD) kidneys were studied for opportunistic infections. Immune diagnosis of Toxoplasma, Cytomegalovirus (CMV), Herpes-simplex virus type II (HSV-2), Aspergillosis and Tuberculosis was carried out in these patients along with sputum examination, CSF studies and biopsy of lymphnode and other tissues in few cases. A high degree of Toxoplasma, CMV & HSV-2 positivity was seen in transplanted patients. However sensitivity of serological diagnosis of tuberculos was found to be low with standard criteria, which increased significantly when modified criteria were used. It is concluded that regular immunological monitoring should be carried out in transplanted patients so as to reach an early diagnosis and management of opportunistic infections.
Sutcliffe, Catherine G.; van Dijk, Janneke H.; Hamangaba, Francis; Mayani, Felix; Moss, William J.
Background Early infant HIV diagnosis is challenging in sub-Saharan Africa, particularly in rural areas where laboratory capacity is limited. Specimens must be transported to central laboratories for testing, leading to delays in diagnosis and initiation of antiretroviral therapy. This study was undertaken in rural Zambia to measure the turnaround time for confirmation of HIV infection and identify delays in diagnosis. Methods Chart reviews were conducted from 2010–2012 for children undergoing early infant HIV diagnosis at Macha Hospital in Zambia. Relevant dates, receipt of drugs by mother and child for the prevention of mother-to-child transmission (PMTCT), and test results were abstracted. Results 403 infants provided 476 samples for early infant diagnosis. The median age at the “6-week” and “6-month” assessments was 8.1 weeks and 7.0 months, respectively. The majority of mothers (80%) and infants (67%) received PMTCT. The median time between sample collection and arrival at the central laboratory in Lusaka was 17 days (IQR: 10, 28); arrival at the central laboratory to testing was 6 days (IQR: 5, 11); testing to return of results to the clinic was 29 days (IQR: 17, 36); arrival of results at the clinic to return of results to the caregiver was 45 days (IQR: 24, 79). The total median time from sample collection to return of results to the caregiver was 92 days (IQR: 84, 145). The proportion of HIV PCR positive samples was 12%. The total median turnaround time was shorter for HIV PCR positive as compared to negative or invalid samples (85 vs. 92 days; p = 0.08). Conclusions Delays in processing and communicating test results were identified, particularly in returning results from the central laboratory to the clinic and from the clinic to the caregiver. A more efficient process is needed so that caregivers can be provided test results more rapidly, potentially resulting in earlier treatment initiation and better outcomes for HIV-infected infants
Kiong, Kimberley L.; Tan, Ngian Chye; Skanthakumar, Thakshayeni; Teo, Constance E.H.; Soo, Khee Chee; Tan, Hiang Khoon; Roche, Elizabeth; Yee, Kaisin
Objective Orocutaneous and pharyngocutaneous fistula (OPCF) is a debilitating complication of head and neck surgery for squamous cell carcinoma (SCC), resulting in delayed adjuvant treatment and prolonged hospitalization. As yet, there is no established test that can help in prompt and accurate diagnosis of OPCF. This study aims to determine the accuracy of bedside blue dye testing and its role as part of an algorithm for early diagnosis. We also analyze the risk factors predisposing to OPCF. Study Design Retrospective cohort study from 2012 to 2014. Methods Patients with head and neck SCC who underwent major resection and reconstruction, at risk of OPCF, were included. Results of blue‐dye and video‐fluoroscopic swallow‐studies (VFSS) testing for OPCF were recorded. For the patients that were noted to develop OPCF, the length of time to diagnosis of fistula and subsequent mode of management were examined. Results Of the 93 patients in this study, 25 (26.9%) developed OPCF. Advanced T‐classification (T3/T4) was the only significant predisposing risk factor (p = 0.013). The sensitivity and specificity of the bedside blue dye testing was found to be 36.4% and 100%, respectively. The test positive patients were diagnosed with OPCF at a median of postoperative day (POD) 9.5 as compared to POD 13 for the test negative patients (p = 0.001). Early diagnosis was associated with faster fistula resolution with treatment. Conclusion Blue dye testing is a simple bedside test that can assist in the early diagnosis of OPCF in patients, allowing treatment to be instituted earlier with improved outcomes. Level of Evidence 3 PMID:29299509
Chang, Chih-Chao; Chang, Chih-Hsien; Shen, Chih-Chieh; Chen, Chuan-Lin; Liu, Ren-Shyan; Lin, Ming-Hsien; Wang, Hsin-Ell
Malignant melanoma expresses a highly aggressive metastasis. Early diagnosis of malignant melanoma is important for patient survival. Radiolabeled benzamides and nicotinamides have been reported to be attractive candidates for malignant melanoma diagnosis as they bind to melanin, a characteristic substance that displays in malignant melanoma, and show high tumor accumulation and retention. Herein, we designed and synthesized a novel (123/131)I-labeled nicotinamide derivative that specifically binds to melanin. (123/131)I-Iochlonicotinamide was prepared with good radiochemical yield (50-70%, decay corrected) and high specific radioactivity (50-80 GBq/μmol). (131)I-Iochlonicotinamide exhibited good in vitro stability (radiochemical purity >95% after a 24-h incubation) in human serum. High uptake of (123/131)I-Iochlonicotinamide in B16F0 melanoma cells compared to that in A375 amelanotic cells demonstrated its selective binding to melanin. Intravenous administration of (123/131)I-Iochlonicotinamide in a melanoma-bearing mouse model revealed high uptake in melanotic melanoma and high tumor-to-muscle ratio. MicroSPECT scan of (123/131)I-Iochlonicotinamide injected mice also displayed high contrast tumor imaging as compared with normal organs. The radiation-absorbed dose projection for the administration of (131)I-Iochlonicotinamide to human was based on the results of biodistribution study. The effective dose appears to be approximately 0.44 mSv/MBq(-1). The specific binding of (123/131)I-Iochlonicotinamide to melanin along with a prolonged tumor retention and acceptable projected human dosimetry suggest that it may be a promising theranostic agent for treating malignant melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.
study will recruit wounded warriors with severe extremity trauma, which places them at high risk for heterotopic ossification (HO); bone formation at...involved in HO; 2) to define accurate and practical methods to predict where HO will develop; and 3) to define potential therapies for prevention or...elicit HO. These tools also need to provide effective methods for early diagnosis or risk assessment (prediction) so that therapies for prevention or
Xie, Hong-Bo; Peng, Zi-Lai; Liu, Xu-Bang; Chen, Lian
To summarize early diagnosis and treatment methods of 20 patients with compartment syndrome caused by landslides during coal mine accidents in order to improve the level of diagnosis and treatment of compartment syndrome and reduce disability. From September 2006 to April 2010,20 patients with compartment syndrome were treated with the methods of early decompression, systemic support. All the patients were male with an average age of 42 years (ranged, 23 to 54). All the patients with high tension limb swelling, pain, referred pain passive positive; 5 extremities feeling diminish or disappear and the distal blood vessel beat were normal or weakened or disappeared; myoglobinuria, hyperkalemia, serum urea nitrogen and creatinine increased in 5 cases and oliguria in occurred 1 case. The function of affected limbs was observed according to disability ratings. Three cases complicated with infection of affected limb and 6 cases occurred with renal function insufficiency. Total recovery was in 16 cases, basically recovery in 3, amputation in 1 case. All patients were followed up for 6-15 months with an average of 12 months. The ability to work according to national standard identification--Employee work-related injuries and occupational disability rating classification (GB/T16180-2006) to assess, grade 5 was in 1 case, grade 8 in 2 cases, grade 10 in 1 case, no grade in 16 cases. Arteriopalmus of dorsalis pedis weaken and vanished can not be regard as an evidence in early diagnosis of compartment syndrome. Early diagnosis and decompression, systemic support and treatment is the key in reducing disability.
the study for the presence or absence of ectopic bone formation at the indicated time points post injury (Table 1.). 8 Table 1. Incidence of HO...1 Award Number: W81XWH-12-2-0119 TITLE: Early Diagnosis and Intervention Strategies for Post -Traumatic Heterotopic Ossification in Severely...2016 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT
Jia, Xiongfei; Gan, Chengjun; Xiao, Ke; He, Weifeng; Zhang, Tao; Huang, Cibing; Wu, Xiongfei; Luo, Gaoxing; Wang, Xiaojuan; Hu, Jie; Tan, Jiangling; Zhang, Xiaorong; Larsen, Peter Mose; Wu, Jun
Acute allograft rejection has been recognized as a major impediment to improved success in renal transplantation. Timely detection and control of rejection are very important for the improvement in long-term renal allograft survival. Thus, biomarkers for early diagnosis of acute rejection are required urgently to clinical medication. This study seeks to search for such biomarker candidates by comparing patients' pre-treatment urinary protein profiling with their post-treatment urinary protein profiling. A total of 15 significantly and consistently down-regulated protein candidates were identified. Among them, alpha-1-antichymotrypsin precursor (AACT), tumor rejection antigen gp96 (GP96) and Zn-Alpha-2-Glycoprotein (ZAG) were selected for further analysis. The results indicated that Western Blot assay of AACT, GP96 and ZAG had advanced the diagnosis time of acute renal rejection by 3 days, compared with current standard clinical observation and laboratory examination. Furthermore, the double-blind detection revealed that the accuracy, sensitivity and specificity of the diagnosis of acute renal rejection of AACT, GP96 and ZAG were 66.67%/100%/60%, 83.33%/100%/80% and 66.67%/100%/60%, respectively, and 100%/100%/100% in combination. In conclusion, urinary protein AACT, GP96 and ZAG could be a set of potential biomarkers for early non-invasive diagnosis of the acute rejection after renal transplantation. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P
To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.
Kako, Peninnah M.; Stevens, Patricia E.; Mkandawire-Valhmu, Lucy; Kibicho, Jennifer; Karani, Anna K.; Dressel, Anne
Early HIV testing is critical to prevention and timely treatment. Missed opportunities for HIV diagnosis can result in unnecessary deaths at a time when access to antiretroviral treatment proves life saving. While HIV prevention and treatment research has increased, less research exists on women's experiences with HIV diagnosis, despite the fact that women are most affected. Insights from local women are critical in designing culturally meaningful interventions that thwart missed opportunities for early HIV diagnosis. The purpose of our study was to uncover steps women took to know their HIV diagnosis. Using narrative inquiry methodology informed by post-colonial feminism, we interviewed 40 HIV- positive women in Kenya. Five themes emerged related to uptake of HIV testing for women: (a) spouse's critical illness or death; (b) years of suffering from HIV-related symptoms; (c) sick children; (d) prenatal testing; and (e) personal desire to know one's HIV status. These findings centered on women experiences provide an important basis for health promotion interventions related to HIV prevention, earlier detection, and treatment. PMID:24273455
Job, C K
In histopathological studies in leprosy, two important areas were identified in recently published work. They are early diagnosis and neuropathy. In histopathological examination, finding of M. leprae in tissues and/or granulomatous destruction of nerves are the two important findings to confirm the diagnosis. Immunopathological staining of M. leprae, PCR amplification of M. leprae antigen and S100 staining of Schwaann cells have considerably enhanced the sensitivity of histopathological diagnosis. If the two clinical findings such as hypopigmented patches with impaired sensation and thickened nerves accompanied by loss of sensation are the only ones that are taken into account for diagnosis, then a significant number of early patients will be missed. It is pointed out that biopsy examination of skin and nerves, when necessary, and skin-smear studies are indispensable diagnostic procedures. In the study of leprous neuropathy, there are several studies trying to decipher the entry of M. leprae into Schwann cells. The sharing of antigens between M. leprae and surface membrane of Schwann cells may be an important factor. However, there is much more to be learned in this area. In the control and prevention of neuritis, although corticosteroids administered along with multi-drug therapy was helpful, the benefit was not sustained.
Altieri, Lisa; Wong, Michael K; Peng, David H; Cockburn, Myles
Mucosal melanomas are rare, poorly understood neoplasms without a consensus standard of care. We sought to define mucosal melanoma tumor characteristics and the racial/ethnic attributes of patients with mucosal melanomas. We analyzed 130,920 cutaneous melanomas and 1919 mucosal melanomas recorded in the population-based California Cancer Registry from 1988 to 2013. Although only 1% of melanomas occurring in nonHispanic whites were mucosal, other racial/ethnic groups had a higher proportion of mucosal melanomas (15% for Asian/Pacific Islanders, 9% for nonHispanic blacks, and 4% for Hispanics). Anorectal mucosal melanomas were most common in female Asian/Pacific Islanders, whereas genitourinary mucosal melanomas were highest in nonHispanic whites, and head and neck tumors were most common among Hispanics. Stage at presentation was not uniform among racial/ethnic groups, with Asian/Pacific Islanders having the highest rates of metastasis. The lack of a standardized staging system for mucosal melanomas confounds classification and knowledge regarding metastasis. Small sample size limits comparative analysis across race, stage, site, and depth. Mucosal melanomas differ by race/ethnicity with regard to anatomic site, stage, and depth. Because early detection offers the best chance of increased survival, greater awareness will aid clinicians who care for patients at risk for these aggressive tumors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Gold, Mark S.; Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R.
Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor self-esteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with > 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches. PMID:24393762
Taşçi-Duran, Emel; Unsal-Atan, Şenay
The purpose of this descriptive study was to investigate attitudes women of towards cervical cancer prevention applications and early diagnosis, and whether or not their hopelessness levels had any influence. The present study was carried out in Isparta with a descriptive design. A sample of 251 individuals was recruited from January 2011 through May 2011 in the largest tea garden (restaurant- cafe). The data collection tool consisted of two parts: a "Questionnaire Form" identifying women; and the "Beck Hopelessness Scale". Data were analyzed using the Statistical Package for the Social Sciences (SPSS version 16.0 for Windows for the numerical and percentage distribution, average, standard deviation with the ANOVA and Mann-Whitney tests. Some 70.2 % of the woman indicated that they had not taken the Pap test. There was a significant relationship between the hopelessness level and women believing that they could protect themselves from getting cervical cancer (F=10.11 p=0.00). There was a significant relationship between hopelessness levels and believing whether or not early diagnosis tests are deterministic (F=8.781 p=0.00). Our study concluded that the hopelessness level of women had an effect on their thoughts about cervical cancer prevention and early diagnosis.
Gold, Mark S; Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R
Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor selfesteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with ≥ 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.
Brorstad, Alette; Oscarsson, Kristina Bergstedt; Ahlm, Clas
Hantavirus infections are emerging infections that cause either Hantavirus pulmonary syndrome or haemorrhagic fever with renal syndrome (HFRS). A recent Swedish outbreak of nephropathia epidemica, a European HFRS, was analysed to study the patient flow and clinical picture and to investigate the value of an early diagnosis in general practice. Design. In a retrospective design, medical records of verified cases of Hantavirus infection were studied. The study was conducted in the county of Norrbotten, Sweden. Data from Hantavirus patients diagnosed between 2006 and 2008 were analysed. Demographic data, level of care, treatment, clinical symptoms, and laboratory findings were obtained. In total, 456 cases were included (58% males and 42% females). The majority of patients first saw their general practitioner and were exclusively treated in general practice (83% and 56%, respectively). When diagnosed correctly at the first visit, antibiotics and hospitalization were significantly lowered compared with delayed diagnosis (14% vs. 53% and 30% vs. 54%, respectively; p < 0.0001). The clinical picture was diverse. Early thrombocytopenia was found in 65% of the patients, and haemorrhagic manifestations were documented in a few cases. Signs of renal involvement--haematuria, proteinuria, and raised levels of serum creatinine--were found in a majority of patients. Raised awareness in general practice regarding emerging infections and better diagnostic tools are desirable. This study of a Hantavirus outbreak shows that general practitioners are frontline doctors during outbreaks and through early and correct diagnosis they can reduce antibiotic treatment and hospitalization.
Núñez-Batalla, Faustino; Jáudenes-Casaubón, Carmen; Sequí-Canet, Jose Miguel; Vivanco-Allende, Ana; Zubicaray-Ugarteche, Jose
The latest scientific literature considers early diagnosis of deafness as the key element to define the educational and inclusive prognosis of the deaf child, because it allows taking advantage of the critical period of development (0-4 years). Highly significant differences exist between deaf people who have been stimulated early and those who have received late or improper intervention. Early identification of late-onset disorders requires special attention and knowledge on the part of every childcare professional. Programs and additional actions beyond neonatal screening should be designed and planed to ensure that every child with a significant hearing loss is detected early. For this purpose, the CODEPEH would like to highlight the need for continuous monitoring of children's auditory health. Consequently, CODEPEH has drafted the recommendations included in the present document. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.
Vaccari, Sabina; Barisani, Alessia; Dika, Emi; Fanti, Pier A; DE Iaco, Pierandrea; Gurioli, Carlotta; Tosti, Giulio
The melanoma of the genital mucosa is a rare melanocytic neoplasm that affects both sexes. The diagnosis is often delayed; videodermatoscopy may represent a useful diagnostic tool. The treatment is complex and multidisciplinary. We report the main diagnostic features and therapeutic approaches for mucosal melanoma of the genital tract.
Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S. W.; Fortin, Claude; Coutlée, François; Roger, Michel
The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS. PMID:24088852
Dumaresq, Jeannot; Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S W; Fortin, Claude; Coutlée, François; Roger, Michel
The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.
Naves, Lucas B; Dhand, Chetna; Venugopal, Jayarama Reddy; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Almeida, Luis
Melanoma is the most aggressive type of skin cancer and has very high rates of mortality. An early stage melanoma can be surgically removed, with a survival rate of 99%. This literature review intends to elucidate the possibilities to treat melanoma skin cancer using hybrid nanofibers developed by advanced electrospinning process. In this review we have shown that the enhanced permeability and retention is the basis for using nanotechnology, aiming topical drug delivery. The importance of the detection of skin cancer in the early stages is directly related to non-metastatic effects and survival rates of melanoma cells. Inhibitors of protein kinase are already available in the market for melanoma treatment and are approved by the FDA; these agents are cobimetinib, dabrafenib, ipilimumab, nivolumab, trametinib, and vemurafenib. We also report a case study involving two different approaches for targeting melanoma skin cancer therapy, namely, magnetic-based core-shell particles and electrospun mats.
Chen, J G; Zhang, Y H; Zhu, J; Lu, J H; Wang, J B; Sun, Y; Xue, X F; Lu, L L; Chen, Y S; Wu, Y; Jiang, X P; Ding, L L; Zhang, Q N; Zhu, Y R
Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B
Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro
The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified. PMID:28300909
Oude Ophuis, Charlotte M C; van Akkooi, Alexander C J; Rutkowski, Piotr; Voit, Christiane A; Stepniak, Joanna; Erler, Nicole S; Eggermont, Alexander M M; Wouters, Michel W J M; Grünhagen, Dirk J; Verhoef, Cornelis Kees
Sentinel node biopsy (SNB) is essential for adequate melanoma staging. Most melanoma guidelines advocate to perform wide local excision and SNB as soon as possible, causing time pressure. To investigate the role of time interval between melanoma diagnosis and SNB on sentinel node (SN) positivity and survival. This is a retrospective observational study concerning a cohort of melanoma patients from four European Organization for Research and Treatment of Cancer Melanoma Group tertiary referral centres from 1997 to 2013. A total of 4124 melanoma patients underwent SNB. Patients were selected if date of diagnosis and follow-up (FU) information were available, and SNB was performed in <180 d. A total of 3546 patients were included. Multivariable logistic regression and Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to positivity rate, disease-free survival (DFS) and melanoma-specific survival (MSS). Median time interval was 43 d (interquartile range [IQR] 29-60 d), and 705 (19.9%) of 3546 patients had a positive SN. Sentinel node positivity was equal for early surgery (≤43 d) versus late surgery (>43 d): 19.7% versus 20.1% (p = 0.771). Median FU was 50 months (IQR 24-84 months). Sentinel node metastasis (hazard ratio [HR] 3.17, 95% confidence interval [95% CI] 2.53-3.97), ulceration (HR 1.99, 95% CI 1.58-2.51), Breslow thickness (HR 1.06, 95% CI 1.04-1.08), and male gender (HR 1.58, 95% CI 1.26-1.98) (all p < 0.00001) were independently associated with worse MSS and DFS; time interval was not. No effect of time interval between melanoma diagnosis and SNB on 5-year survival or SN positivity rate was found for a time interval of up to 3 months. This information can be used to counsel patients and remove strict time limits from melanoma guidelines. Copyright © 2016 Elsevier Ltd. All rights reserved.
This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.
... Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Go to Health Professional Version Key ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...
Tissue-based analyses of precursors, melanoma tumors and metastases within existing study populations to further understanding of the heterogeneity of melanoma and determine a predictive pattern of progression for dysplastic nevi.
Jones, Claire EL; Maben, Jill; Jack, Ruth H; Davies, Elizabeth A; Forbes, Lindsay JL; Lucas, Grace; Ream, Emma
Objective To explore barriers to early presentation and diagnosis with breast cancer among black women. Design Systematic review. Methods We searched multiple bibliographic databases (January 1991–February 2013) for primary research, published in English, conducted in developed countries and investigating barriers to early presentation and diagnosis with symptomatic breast cancer among black women (≥18 years). Studies were excluded if they did not report separate findings by ethnic group or gender, only reported differences in time to presentation/diagnosis, or reported on interventions and barriers to cancer screening. We followed Cochrane and PRISMA guidance to identify relevant research. Findings were integrated through thematic synthesis. Designs of quantitative studies made meta-analysis impossible. Results We identified 18 studies (6183 participants). Delay was multifactorial, individual and complex. Factors contributing to delay included: poor symptom and risk factor knowledge; fear of detecting breast abnormality; fear of cancer treatments; fear of partner abandonment; embarrassment disclosing symptoms to healthcare professionals; taboo and stigmatism. Presentation appears quicker following disclosure. Influence of fatalism and religiosity on delay is unclear from evidence in these studies. We compared older studies (≥10 years) with newer ones (<10 years) to determine changes over time. In older studies, delaying factors included: inaccessibility of healthcare services; competing priorities and concerns about partner abandonment. Partner abandonment was studied in older studies but not in newer ones. Comparisons of healthy women and cancer populations revealed differences between how people perceive they would behave, and actually behave, on finding breast abnormality. Conclusions Strategies to improve early presentation and diagnosis with breast cancer among black women need to address symptom recognition and interpretation of risk, as well as
Brown, J; Kopf, A W; Rigel, D S; Friedman, R J
In a consecutive series of 1,067 patients entered into the data base of the Melanoma Cooperative Group at New York University School of Medicine between 1972 and 1980, 120 men were of draft age (18-31 years) during World War II (1941-1945). Questionnaires were sent to these 120 individuals; 89 responded. Simultaneously, a control (nonmelanoma) population of 65 men of similar age was queried. Each subject in both groups was asked whether he had served in the armed forces during World War II and, if so, what were his theaters of operation. Based on the response, 83% (74 of 89) of the melanoma group compared with 76% (49 of 65) of the control group had served in the armed forces during World War II; however, a significantly (p = 0.0002) greater percent of the melanoma patients (34%) served in the tropics than did the control subjects (6%). Further, overrepresented in the melanoma group that served in the tropics (compared with the melanoma group who served in the armed forces in nontropical theaters) were malignant melanomas that had their origin in nevocytic nevi. The findings suggest that Caucasian individuals heavily exposed to sunlight in the tropics for several years during early life may be at higher risk to the subsequent development of cutaneous malignant melanoma. In some individuals this may be a two-step phenomenon, in which the first step is the solar induction of nevocytic nevi and the second is malignant transformation within them.
Mafee, M.F.; Peyman, G.A.; McKusick, M.A.
Forty-four patients with intraocular disease were studied by computed tomography (CT); in 19 cases malignant uveal melanoma was considered the likely diagnosis. CT proved to be accurate in determining the location and size of uveal melanomas, demonstrating scleral invasion, and differentiating melanoma from choroidal detachment or angioma, toxocariasis, and senile macular degeneration. On CT, uveal melanomas appeared as hyperdense lesions with slight to moderate contrast enhancement. Tumors thinner than 2 mm could not be seen. Using dynamic CT, the authors noted moderate peak amplitude, normal or delayed tissue transit time, and persistently elevated washout phase (downslope), indicating increased permeability asmore » the result of an impaired tumor blood barrier. Histological types of uveal melanoma could not be differentiated on the basis of circulatory patterns. Dynamic CT may be useful in distinguishing uveal melanoma from choroidal hemangioma or hematoma.« less
Tovoli, Francesco; Granito, Alessandro; Giampaolo, Luca; Frisoni, Magda; Volta, Umberto; Fusconi, Marco; Masi, Chiara; Lenzi, Marco
Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune diseases, including systemic sclerosis (SSc). In the last years many efforts have been dedicated to the research of widely accepted criteria for the early diagnosis of SSc. Since studies on the prevalence of early SSc in PBC patients are lacking, our aim was to investigate its hitherto unknown prevalence in a large cohort of PBC patients. We studied 80 PBC patients and 72 patients with other chronic liver diseases. Diagnostic workup included research into signs of connective tissue disease, determination of autoantibody profile, and examination of capillary abnormalities through nailfold videocapillaroscopy. Ten PBC patients (12.5%) satisfied diagnostic criteria for early SSc and 5 (6.3%) had definite SSc. None of the patients in the control group were diagnosed either with early or definite SSc. No differences were observed in terms of aminotransferases, alkaline phosphatase, and liver function tests between PBC patients with and without associated SSc. Early SSc is significantly frequent in PBC patients. The detection of early SSc in PBC patients may lead to a prompt treatment of its complications, preventing inabilities and preserving the chance of liver transplantation.
Li, P; Huang, Y; Li, Y; Cai, L; Ji, G H; Zheng, Y; Chen, Z Q
Objective: To evaluate the value of multi-parametric MRI (Mp-MRI) in the diagnosis and differential diagnosis of early prostate cancer(PCa) in the peripheral zone(PZ) and low T 2 WI signal intensity of prostatitis. Methods: A total of 40 patients with PZ early PCa and 37 with prostatitis of hypointense T 2 WI signal in PZ were retrospectively analyzed, which were collected from the General Hospital of Ningxia Medical University from Janurary 2009 to June 2015, who underwent T 2 WI, DWI, and DCE-MRI examination and all patients were confirmed by pathology. All the data was transferred to GE Advanced Workstation AW4.3, the indexes divided into cancerous and prostatitis regions were calculated by Functool2 of signal intensity-time(SI-T) curve and ADC value, to calcuate the time to minimum(T max ), the whole enhancment degree (SI max ). ROC cure was used to determine the cutoff value for PCa detection with the ADC value. Result: On T 2 WI, 57.5% of PCa (23/40) showed focal nodular homogeneous low signal intensity, 70.3% of prostatitis(26/37) showed diffuse inhomogeneous low signal intensity. DCE-MRI, the distribution of curve types for malignant tumors was type Ⅰ 2.5%(1/40), typeⅡ32.5%(13/40) and type Ⅲ 65.0% (26/40). While the numbers for prostatitis was type Ⅰ 16.2%(6/37) , type Ⅱ 56.8% (21/37) and type Ⅲ 27.0% (10/37)respectively.The patterns of curve types in malignant lesions were different from benign lesions significantly(χ 2 =12.32, P <0.01). The mean values of T max , SI max in cancerous and prostatitis regions were (17.96±2.91)s, 1.76%±0.23% and (21.19±3.59)s, 1.53%±0.18%, respectively ( t =5.37, 6.10; P <0.01). On DWI, The mean ADC values in cancerous and prostatitis regions were (0.95±0.13)×10 -3 mm 2 /s and (1.12±0.13)×10 -3 mm 2 /s, respectively ( t =7.10, P <0.01). According to the ROC analysis, when the cutoff value was 1.01×10 -3 mm 2 /s, the early PCa of diagnostic sensitivity, specificity and accuracy was 79.1%, 72.7% and 76
Mucosal Melanoma; Recurrent Melanoma; Recurrent Uveal Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma
Iskandar, Agustin; Arthamin, Maimun Z; Indriana, Kristin; Anshory, Muhammad; Hur, Mina; Di Somma, Salvatore
Neonatal sepsis remains worldwide one of the leading causes of morbidity and mortality in both term and preterm infants. Lower mortality rates are related to timely diagnostic evaluation and prompt initiation of empiric antibiotic therapy. Blood culture, as gold standard examination for sepsis, has several limitations for early diagnosis, so that sepsis biomarkers could play an important role in this regard. This study was aimed to compare the value of the two biomarkers presepsin and procalcitonin in early diagnosis of neonatal sepsis. This was a prospective cross-sectional study performed, in Saiful Anwar General Hospital Malang, Indonesia, in 51 neonates that fulfill the criteria of systemic inflammatory response syndrome (SIRS) with blood culture as diagnostic gold standard for sepsis. At reviewer operating characteristic (ROC) curve analyses, using a presepsin cutoff of 706,5 pg/mL, the obtained area under the curve (AUCs) were: sensitivity = 85.7%, specificity = 68.8%, positive predictive value = 85.7%, negative predictive value = 68.8%, positive likelihood ratio = 2.75, negative likelihood ratio = 0.21, and accuracy = 80.4%. On the other hand, with a procalcitonin cutoff value of 161.33 pg/mL the obtained AUCs showed: sensitivity = 68.6%, specificity = 62.5%, positive predictive value = 80%, negative predictive value = 47.6%, positive likelihood ratio = 1.83, the odds ratio negative = 0.5, and accuracy = 66.7%. In early diagnosis of neonatal sepsis, compared with procalcitonin, presepsin seems to provide better early diagnostic value with consequent possible faster therapeutical decision making and possible positive impact on outcome of neonates.
Alexandrescu, Doru Traian
The rapidly increasing incidence of melanoma occurs at the same time as an increase in general healthcare costs, particularly the expenses associated with cancer care. Previous cost estimates in melanoma have not utilized a dynamic model considering the evolution of the disease and have not integrated the multiple costs associated with different aspects of medical interventions and patient-related factors. Futhermore, previous calculations have not been updated to reflect the modern tendencies in healthcare costs. We designed a comprehensive model of expenses in melanoma that considers the dynamic costs generated by the natural progression of the disease, which produces costs associated with treatment, surveillance, loss of income, and terminal care. The complete range of initial clinical (TNM) stages of the disease and initial tumor stages were analyzed in this model and the total healthcare costs for the five years following melanoma presentation at each particular stage were calculated. We have observed dramatic incremental total costs associated with progressively higher initial stages of the disease, ranging from a total of $4,648.48 for in situ tumors to $159,808.17 for Stage IV melanoma. By stage, early lesions associate 30-55 percent of their costs for the treatment of the primary tumor, due to a low rate of recurrence (local, regional, or distant), which limits the need for additional interventions. For in situ melanoma, T1a, and T1b, surveillance is an important contributor to the medical costs, accounting for more than 25 percent of the total cost over 5 years. In contrast, late lesions incur a much larger proportion of their associated costs (up to 80-85%) from the diagnosis and treatment of metastatic disease because of the increased propensity of those lesions to disseminate. This cost increases with increasing tumor stage (from $2,442.17 for T1a to $6,678.00 for T4b). The most expensive items in the medical care of patients with melanoma consist of
Khan, S; Harish, B N; Menezes, G A; Acharya, N S; Parija, S C
Typhoid fever caused by Salmonella Typhi continues to be a major health problem in spite of the use of antibiotics and the development of newer antibacterial drugs. Inability to make an early laboratory diagnosis and resort to empirical therapy, often lead to increased morbidity and mortality in cases of typhoid fever. This study was aimed to optimize a nested PCR for early diagnosis of typhoid fever and using it as a diagnostic tool in culture negative cases of suspected typhoid fever. Eighty patients with clinical diagnosis of typhoid fever and 40 controls were included in the study. The blood samples collected were subjected to culture, Widal and nested PCR targeting the flagellin gene of S. Typhi. The sensitivity of PCR on blood was found to be 100 per cent whereas the specificity was 76.9 per cent. The positive predictive value (PPV) of PCR was calculated to be 76.9 per cent with an accuracy of 86 per cent. None of the 40 control samples gave a positive PCR. Due to its high sensitivity and specificity nested PCR can be used as a useful tool to diagnose clinically suspected, culture negative cases of typhoid fever.
Cottin, Vincent; Richeldi, Luca
In idiopathic pulmonary fibrosis (IPF), some facts or concepts based on substantial evidence, whilst implicit for learned subspecialists, have previously been neglected and/or not explicitly formulated or made accessible to a wider audience. IPF is strongly associated with cigarette smoking and is predominantly a disease of ageing. However, its cause(s) remain elusive and, thus, it is one of the most challenging diseases for the development of novel effective and safe therapies. With the approval of pirfenidone for patients with mild-to-moderate IPF, an earlier diagnosis of IPF is a prerequisite for earlier treatment and, potentially, improvement of the long-term clinical outcome of this progressive and ultimately fatal disease. An earlier diagnosis may be achieved in IPF by promoting thin-slice chest high-resolution computed tomography screening of interstitial lung disease as a "by-product" of large-scale lung cancer screening strategies in smokers, but other techniques, which have been neglected in the past, are now available. Lung auscultation and early identification of "velcro" crackles has been proposed as a key component of early diagnosis of IPF. An ongoing study is exploring correlations between lung sounds on auscultation obtained using electronic stethoscopes and high-resolution computed tomography patterns.
Obeidat, Rana Fakhri; Lally, Robin M; Dickerson, Suzanne S
Currently, limited literature addresses Arab American women's responses to the impact of breast cancer and its treatments. The objective of the study was to understand the experience of being diagnosed with and undergoing surgical treatment for early-stage breast cancer among Arab American women. A qualitative interpretive phenomenological research design was used for this study. A purposive sample of 10 Arab American women who were surgically treated for early-stage breast cancer in the United States was recruited. Data were collected using individual interviews and analyzed using the Heideggerian hermeneutical methodology. Arab American women accepted breast cancer diagnosis as something in God's hands that they had no control over. Although they were content with God's will, the women believed that the diagnosis was a challenge that they should confront. The women confronted this challenge by accessing the healthcare system for treatment, putting trust in their physicians, participating when able in treatment decisions, using religious practices for coping, maintaining a positive attitude toward the diagnosis and the treatment, and seeking information. Arab American women's fatalistic beliefs did not prevent them from seeking care and desiring treatment information and options when diagnosed with breast cancer. It is important that healthcare providers encourage patients to express meanings they attribute to their illness to provide them with appropriate supportive interventions. They should also individually assess patients' decision-making preferences, invite them to participate in decision making, and provide them with tailored means necessary for such participation without making any assumptions based on patients' ethnic/cultural background.
Hastrup, N; Osterlind, A; Drzewiecki, K T; Hou-Jensen, K
We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.
Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Mucosal Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIC Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma
Raciborski, Filip; Kłak, Anna; Maślińska, Maria; Gryglewicz, Jerzy
Musculoskeletal pain is a very common complaint, affecting 30–40% of the European population. It is estimated that approximately 400,000 Poles suffer from inflammatory rheumatic diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, and a vast majority of those affected are working-age individuals. Patients with suspected arthritis require prompt diagnosis and treatment, as any delays may result in irreversible joint destruction and disability. Currently in Poland, the lag time between the onset of symptoms and diagnosis is, on average, as much as 35 weeks. In this paper, we review the current state of specialist rheumatology care in Poland and propose a reorganised care model that includes early diagnosis of inflammatory arthritis. The main goal we wish to achieve with our reorganised model is to enhance access to outpatient specialist rheumatology care for patients with suspected arthritis. We believe that our model should make it possible to considerably reduce the lag time between GP referral and the diagnosis and treatment by a rheumatologist to as little as 3 to 4 weeks. This article provides a proposal of changes that would achieve this goal and is a summary of the report published by the Institute of Rheumatology in September 2014. PMID:27407218
Cortés-Vicente, Elena; Pradas, Jesús; Marín-Lahoz, Juan; De Luna, Noemi; Clarimón, Jordi; Turon-Sans, Janina; Gelpí, Ellen; Díaz-Manera, Jordi; Illa, Isabel; Rojas-Garcia, Ricard
To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis. We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation. Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA). Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.
Puszkiel, Alicja; White-Koning, Mélanie; Dupin, Nicolas; Kramkimel, Nora; Thomas-Schoemann, Audrey; Noé, Gaëlle; Chapuis, Nicolas; Vidal, Michel; Goldwasser, François; Chatelut, Etienne; Blanchet, Benoit
The therapeutic response to vemurafenib, a BRAF serine-threonine kinase inhibitor, exhibits large variations between patients. Evaluation of factors predicting the clinical efficacy of vemurafenib may help to identify patients at high risk of non-response in the early phase of treatment. The aim of this study was to analyze the pharmacokinetics of vemurafenib by a population approach and to evaluate the relationship between plasma drug exposure and pre-treatment plasma hepatocyte growth factor (HGF) levels with clinical effects (progression-free survival (PFS), peripheral lymphocytes depletion) in patients with metastatic BRAF V600 mutated melanoma treated with single agent vemurafenib. Concentration-time data (n=332) obtained in 44 patients were analyzed using the NONMEM program. Pre-treatment plasma levels of HGF (n=36) were assayed by ELISA method. A Cox model was used to identify prognostic factors associated with progression-free survival (PFS), and a linear regression to identify factors contributing to the depletion of peripheral lymphocytes at day 15. Steady-state pharmacokinetics of vemurafenib was described by a one compartment model with first order absorption and first order elimination. None of the tested covariates explained the inter-patient variability in CL/F. A significant decrease in total lymphocytes count was observed within the first 15days (median ratio Day15/Day0=0.66, p<0.0001). Patients with Day15/Day0 ratio below 0.66 had longer PFS (14 vs 4 months, HR=0.41, CI95%=[0.15-0.77], p=0.0095). In the multivariate Cox model analysis, ECOG PS was the only parameter independently associated with PFS (grade 1 vs 0, HR=3.26, CI95%=[1.29-8.22], p=0.01 and grade ≥2 vs 0, HR=4.77, CI95%=[1.52-14.95], p=0.007). Plasma vemurafenib exposure (p=0.046) and pre-treatment HGF levels (p=0.003) were independently associated with the total lymphocyte ratio Day15/Day0. These findings show that plasma vemurafenib exposure and pre-treatment HGF levels are two
Buragohain, Lukumoni; Nanda, Trilok; Ghosh, Arnab; Ghosh, Mayukh; Kumar, Rajesh; Kumar, Sunil; Gupta, Sambhu Sharan; Bharali, Arpita; Mohanty, Ashok K; Singh, Inderjeet; Balhara, Ashok Kumar
Improper or delayed pregnancy diagnosis has significant impact over animal production, particularly in buffaloes which inherently suffer from several reproductive inefficiencies. Thus the present study has undertaken to identify serum protein markers pertaining to early pregnancy diagnosis in buffaloes. Serum samples were collected from 10 pregnant Murrah Buffalo heifers at weekly intervals from days 0-35 post-artificial insemination and from 12 inseminated non-pregnant cyclic buffalo heifers on days 0, 7, 14 and 21. Two-dimensional gel electrophoresis and densitometric analysis revealed the presence of five protein spots showing average density fold change of ≥4 during early pregnancy. Mass spectrometry analysis identified these up-regulated proteins as anti-testosterone antibody light chain, apolipoprotein A-II precursor, serum amyloid A, cytokeratin type II, component IV isoform 1, which are have established roles in embryogenesis, but over-expression of the fifth identified protein immunoglobulin lambda light chain in pregnancy has been elucidated as a novel finding in the current study. Further, with bioinformatics analysis, potential antigenic B-cell epitopes were predicted for all these five proteins. An antibody cocktail-based approach involving antibodies against all these five up-regulated entire proteins or their epitopes could be developed for early detection of pregnancy in buffaloes. © 2016 Japanese Society of Animal Science. © 2016 Japanese Society of Animal Science.
Wu, Lan; Jiang, Xiaoqin; Ni, Juan
Splenic ectopic pregnancy (SEP), a special abdominal pregnancy, is extremely rare but carries a high risk of potentially uncontrollable, life-threatening intraperitoneal bleeding at early gestation, which is equivalent to the spontaneous rupture of the spleen. Therefore, early diagnosis of SEP is crucial and may avoid life-threatening situation. A 29-year-old G3P2 woman presented with 50 days of amenorrhea and positive serum β-human gonadotropin (β-HCG) was enrolled into the hospital due to the absence of gestational sac located in the uterine cavity. A pan-abdominal ultrasound scan revealed a 2.6 cm ×1.6 cm hyperechoic mass inferior to the spleen with color Doppler signal surrounding and 0.9 cm anechoic inside. The gynecologist found the gestational sac was located in the dorsal pole of the spleen through the exploratory laparoscopy. Total splenectomy was performed uneventfully to avoid the hemorrhage shock. The patient discharged with no complications and normal 1-month follow-up. It highlights that fully understanding of the knowledge about abdominal pregnancy, especially splenic pregnancy, and early imaging study with ultrasonography could reduce or avoid the misdiagnosis and miss-diagnosis of SEP.
Cheng, Bo; Liu, Mingxia; Shen, Dinggang; Li, Zuoyong; Zhang, Daoqiang
Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer's Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multi-domain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods.
Cheng, Bo; Liu, Mingxia; Li, Zuoyong
Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer’s Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multidomain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods. PMID:27928657
Seo, Yu-Mi; Kang, Hyun-Mi; Lee, Sung-Churl; Yu, Jae-Won; Kil, Hong-Ryang; Rhim, Jung-Woo; Han, Ji-Whan; Lee, Kyung-Yil
This study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients. Clinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204). The mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other. The severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.
Vázquez-López, María Esther; Fernández, Gonzalo; Díaz, Pablo; Díez-Morrondo, Carolina; Pego-Reigosa, Robustiano; Coira-Nieto, Amparo
The main aim of this study was to determine the usefulness of an early diagnosis of Lyme disease (LD) in Primary Health Care Centres (PHCC) using the ELISA test as serological screening technique. A retrospective study (2006-2013) was performed in order to determine the anti-Borrelia seropositivity in 2,842 people at risk of having LD. The possible relationship between the environment and the area of residence with anti-Borrelia seropositivity was also studied according to the origin of the specimens (PHCC/Hospital). Overall, 15.2% of samples were positive to Borrelia spp. Seropositivity was significantly higher in samples sent by PHCC doctors than those sent by Hospital doctors. Seropositivity was significantly higher in rural than in urban populations and in those who live in mountainous or flat areas. The percentage of seropositivity has increased over the years. The role of the PHCC doctor is essential for achieving an early diagnosis of Lyme disease, as a higher percentage of seropositives was detected in samples submitted from PHCC. Furthermore, most early localised LD patients were diagnosed in PHCC, avoiding the appearance of sequelae. Therefore, detection of Borrelia specific antibodies using an ELISA assay is a useful screening test for patients at risk of LD. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Olivo, Malini; Bhuvaneswari, Ramaswamy; Keogh, Ivan
Oral cancer is among the most common malignancies worldwide, therefore early detection and treatment is imperative. The 5-year survival rate has remained at a dismal 50% for the past several decades. The main reason for the poor survival rate is the fact that most of the oral cancers, despite the general accessibility of the oral cavity, are not diagnosed until the advanced stage. Early detection of the oral tumors and its precursor lesions may be the most effective means to improve clinical outcome and cure most patients. One of the emerging technologies is the use of non-invasive in vivo tissue imaging to capture the molecular changes at high-resolution to improve the detection capability of early stage disease. This review will discuss the use of optical probes and highlight the role of optical imaging such as autofluorescence, fluorescence diagnosis (FD), laser confocal endomicroscopy (LCE), surface enhanced Raman spectroscopy (SERS), optical coherence tomography (OCT) and confocal reflectance microscopy (CRM) in early oral cancer detection. FD is a promising method to differentiate cancerous lesions from benign, thus helping in the determination of adequate resolution of surgical resection margin. LCE offers in vivo cellular imaging of tissue structures from surface to subsurface layers and has demonstrated the potential to be used as a minimally invasive optical biopsy technique for early diagnosis of oral cancer lesions. SERS was able to differentiate between normal and oral cancer patients based on the spectra acquired from saliva of patients. OCT has been used to visualize the detailed histological features of the oral lesions with an imaging depth down to 2–3 mm. CRM is an optical tool to noninvasively image tissue with near histological resolution. These comprehensive diagnostic modalities can also be used to define surgical margin and to provide a direct assessment of the therapeutic effectiveness. PMID:24310585
Wang, Bright L.
This paper describes a novel fault detection technique for hybrid DC/DC converter oscillation diagnosis. The technique is based on principles of feedback control loop oscillation and RF signal modulations, and Is realized by using signal spectral analysis. Real-circuit simulation and analytical study reveal critical factors of the oscillation and indicate significant correlations between the spectral analysis method and the gain/phase margin method. A stability diagnosis index (SDI) is developed as a quantitative measure to accurately assign a degree of stability to the DC/DC converter. This technique Is capable of detecting oscillation at an early stage without interfering with DC/DC converter's normal operation and without limitations of probing to the converter.
Couto, Daíne Vargas; Medeiros, Marcelo Zanolli; Hans, Gunter; de Lima, Alexandre Moretti; Barbosa, Aline Blanco; Vicari, Carolina Faria Santos
Brazilian spotted fever is an acute febrile infectious disease caused by Rickettsia rickettsii, transmitted by tick bite. As this disease is rare and has high mortality rates in Brazil, the clinical aspects and epidemiological data may help the diagnosis. We report a case of Brazilian spotted fever in a 19-year-old patient who presented maculopapular exanthema in the palmar region and upper limbs, lymphadenopathy, fever, chills, headache, conjunctival hyperemia, nausea, vomiting, dyspnea, myalgia, developing neurological signs and abdominal pain. He was treated with doxycycline with clinical improvement. We emphasize the importance of the recognition of this disease by dermatologists as cutaneous manifestations are the key findings to establish early diagnosis and prevent complications. PMID:25830998
Shields, Jerry A; Shields, Carol L
To review the management of ciliary body and choroidal melanoma (posterior uveal melanoma [PUM]) over the last century with an emphasis on changing concepts. Retrospective review. Review of personal experience over 40 years and pertinent literature on management of PUM. Diagnosis and therapy for PUM. Patient survival. In the early 1900s, most patients presented with a large symptomatic melanoma that necessitated enucleation, and the systemic prognosis was poor. In the 1970s, controversy erupted regarding the role of enucleation for PUM. Some authorities advocated prompt enucleation, and others proposed that enucleation promoted metastasis, known as the "Zimmerman hypothesis." Others recommended observation, withholding treatment until tumor growth was documented. During the 1970s, there was a trend toward eye-saving procedures, including laser photocoagulation, surgical removal of tumor, and techniques of radiotherapy. Despite local treatment success, systemic prognosis remained guarded with approximately 40% mortality overall. However, there was convincing evidence that smaller tumors offered a significantly better prognosis. Currently, there is a movement toward earlier identification and treatment of small melanomas using clinical factors predictive of malignant potential, in keeping with similar philosophy regarding other cancers. Further understanding of melanoma cytogenetics and molecular pathways have helped to recognize patients at risk for metastasis. At-risk patients are offered systemic therapeutic trials to prevent metastasis. We anticipate that the future management of PUM will focus on detection of clinical and imaging clues for earliest diagnosis, prompt local tumor treatment, and systemic targeted therapies for microscopic metastasis or prevention of metastasis. Personalized evaluation of patient-specific melanoma molecular pathway signature could allow for therapeutic intervention at a site specific to the pathway abnormality that leads to the
Bogdanowski, T; Gluza, J; Rasiewicz, D
The role of fluorescein angiography in early diagnosis of lesions on fundus of the eye at pseudoxanthoma elasticum patients has been shown. The authors show angiographic changes on the basis of three cases of pseudoxanthoma elasticum patients.
Rahman, Md. Mahmudur; Alpaslan, Nuh
Melanoma is considered a major health problem since it is the deadliest form of skin cancer. The early diagnosis through periodic screening with dermoscopic images can significantly improve the survival rate as well as reduce the treatment cost and consequent suffering of patients. Dermoscopy or skin surface microscopy provides in vivo inspection of color and morphologic structures of pigmented skin lesions (PSLs), rendering higher accuracy for detecting suspicious cases than it is possible via inspecting with naked eye. However, interpretation of dermoscopic images is time consuming and subjective, even for trained dermatologists. Therefore, there is currently a great interest in the development of computeraided diagnosis (CAD) systems for automated melanoma recognition. However, the majority of the CAD systems are still in the early development stage with lack of descriptive feature generation and benchmark evaluation in ground-truth datasets. This work is focusing on by addressing the various issues related to the development of such a CAD system with effective feature extraction from Non-Subsampled Contourlet Transform (NSCT) and Eig(Hess) histogram of oriented gradients (HOG) and lesion classification with efficient Extreme Learning Machine (ELM) due to its good generalization abilities and a high learning efficiency and evaluating its effectiveness in a benchmark data set of dermoscopic images towards the goal of realistic comparison and real clinical integration. The proposed research on melanoma recognition has huge potential for offering powerful services that would significantly benefit the present Biomedical Information Systems.
Aralica, Gorana; Milošević, Danko; Konjevoda, Paško; Seiwerth, Sven; Štambuk, Nikola
Medical differential diagnosis is a method of identifying the presence of a particular entity (disease) within a set of multiple possible alternatives. The significant problem in dermatology and pathology is the differential diagnosis of malignant melanoma and other pigmented skin lesions, especially of dysplastic nevi. Malignant melanoma is the most malignant skin neoplasma, with increasing incidence in various parts of the world. It is hoped that the methods of quantitative pathology, i.e. morphometry, can help objectification of the diagnostic process, since early discovery of melanoma results in 10-year survival rate of 90%. The aim of the study was to use fractal dimension calculated from the perimeter-area relation of the cell nuclei as a tool for the differential diagnosis of pigmented skin lesions. We analyzed hemalaun-eosin stained pathohistological slides of pigmented skin lesions: intradermal naevi (n = 45), dysplastic naevi (n = 47), and malignant melanoma (n = 50). It was found that fractal dimension of malignant melanoma cell nuclei differs significantly from the intradermal and dysplastic naevi (p ≤ 0. 001, Steel-Dwass Multiple Comparison Test). Additionaly, ROC analysis confirmed the value of fractal dimension based evaluation. It is suggested that the estimation of fractal dimension from the perimeter-area relation of the cell nuclei may be a potentially useful morphometric parameter in the medical differential diagnosis of pigmented skin lesions.
Wu, Yixiao; Yang, Ran; Jia, Sen; Li, Zhanjun; Zhou, Zhiyang; Lou, Ting
This work was aimed at studying the method of computer-aided diagnosis of early knee OA (OA: osteoarthritis). Based on the technique of MRI (MRI: Magnetic Resonance Imaging) T2 Mapping, through computer image processing, feature extraction, calculation and analysis via constructing a classifier, an effective computer-aided diagnosis method for knee OA was created to assist doctors in their accurate, timely and convenient detection of potential risk of OA. In order to evaluate this method, a total of 1380 data from the MRI images of 46 samples of knee joints were collected. These data were then modeled through linear regression on an offline general platform by the use of the ImageJ software, and a map of the physical parameter T2 was reconstructed. After the image processing, the T2 values of ten regions in the WORMS (WORMS: Whole-organ Magnetic Resonance Imaging Score) areas of the articular cartilage were extracted to be used as the eigenvalues in data mining. Then,a RBF (RBF: Radical Basis Function) network classifier was built to classify and identify the collected data. The classifier exhibited a final identification accuracy of 75%, indicating a good result of assisting diagnosis. Since the knee OA classifier constituted by a weights-directly-determined RBF neural network didn't require any iteration, our results demonstrated that the optimal weights, appropriate center and variance could be yielded through simple procedures. Furthermore, the accuracy for both the training samples and the testing samples from the normal group could reach 100%. Finally, the classifier was superior both in time efficiency and classification performance to the frequently used classifiers based on iterative learning. Thus it was suitable to be used as an aid to computer-aided diagnosis of early knee OA.
Teipel, Stefan; Kilimann, Ingo; Thyrian, Jochen R; Kloppel, Stefan; Hoffmann, Wolfgang
The use of imaging markers for the diagnosis of predementia and early dementia stages of Alzheimer's disease (AD) has widely been explored in research settings and specialized care. The use of these markers in primary care has yet to be established. Summarize current evidence for the usefulness of imaging markers for AD in primary compared to specialized care settings. Selective overview of the literature, and pilot data on the use of MRI-based hippocampus and basal forebrain volumetry for the discrimination of AD dementia and mild cognitive impairment (MCI) cases from healthy controls in 58 cases from a primary care cohort and 58 matched cases from a memory clinic's sample. Molecular imaging marker of amyloid pathology, and volumetric markers of regional and whole brain atrophy support the diagnosis of AD dementia and MCI due to AD, and contribute to confidence in the differential diagnosis of AD and non-AD related dementias in specialized care. Limited evidence from the literature and our primary care cohort suggests that the diagnostic accuracy of volumetric imaging markers may be similar in the dementia stage of AD, but may be inferior for cases with MCI in primary compared with specialized care. Evidence is still widely lacking on the use of imaging markers for early and differential diagnosis of AD dementia, and detection of prodromal AD in primary care. Further progress to fill this gap will depend on the availability of international multimodal data from well-defined primary care cohorts. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Oshaug, Katja; Halvorsen, Peder A; Melbye, Hasse
Background Although proven to be associated with bronchial obstruction, chest signs are not listed among cues that should prompt spirometry in the early diagnosis of chronic obstructive pulmonary disease (COPD) in established guidelines. Aims We aimed to explore how chest findings add to respiratory symptoms and a history of smoking in the diagnosis of COPD. Methods In a cross-sectional study, patients aged 40 years or older, previously diagnosed with either asthma or COPD in primary care, answered questionnaires and underwent physical chest examination and spirometry. Results Among the 375 patients included, 39.7% had forced expiratory volume in 1 second/forced vital capacity <0.7. Hyperresonance to percussion was the strongest predictor of COPD, with a sensitivity of 20.8, a specificity of 97.8, and likelihood ratio of 9.5. In multivariate logistic regression, where pack-years, shortness of breath, and chest findings were among the explanatory variables, three physical chest findings were independent predictors of COPD. Hyperresonance to percussion yielded the highest odds ratio (OR = 6.7), followed by diminished breath sounds (OR = 5.0), and thirdly wheezes (OR = 2.3). These three chest signs also gave significant diagnostic information when added to shortness of breath and pack-years in receiver operating-characteristic curve analysis. Conclusion We found that chest signs may add to respiratory symptoms and a history of smoking in the diagnosis of COPD, and we conclude that chest signs should be reinstated as cues to early diagnosis of COPD in patients 40 years or older. PMID:23983462
Yang, Jun; Hou, Ziming; Wang, Changjiang; Wang, Hao; Zhang, Hongbing
Adamantinomatous craniopharyngioma (ACP) is an aggressive brain tumor that occurs predominantly in the pediatric population. Conventional diagnosis method and standard therapy cannot treat ACPs effectively. In this paper, we aimed to identify key genes for ACP early diagnosis and treatment. Datasets GSE94349 and GSE68015 were obtained from Gene Expression Omnibus database. Consensus clustering was applied to discover the gene clusters in the expression data of GSE94349 and functional enrichment analysis was performed on gene set in each cluster. The protein-protein interaction (PPI) network was built by the Search Tool for the Retrieval of Interacting Genes, and hubs were selected. Support vector machine (SVM) model was built based on the signature genes identified from enrichment analysis and PPI network. Dataset GSE94349 was used for training and testing, and GSE68015 was used for validation. Besides, RT-qPCR analysis was performed to analyze the expression of signature genes in ACP samples compared with normal controls. Seven gene clusters were discovered in the differentially expressed genes identified from GSE94349 dataset. Enrichment analysis of each cluster identified 25 pathways that highly associated with ACP. PPI network was built and 46 hubs were determined. Twenty-five pathway-related genes that overlapped with the hubs in PPI network were used as signatures to establish the SVM diagnosis model for ACP. The prediction accuracy of SVM model for training, testing, and validation data were 94, 85, and 74%, respectively. The expression of CDH1, CCL2, ITGA2, COL8A1, COL6A2, and COL6A3 were significantly upregulated in ACP tumor samples, while CAMK2A, RIMS1, NEFL, SYT1, and STX1A were significantly downregulated, which were consistent with the differentially expressed gene analysis. SVM model is a promising classification tool for screening and early diagnosis of ACP. The ACP-related pathways and signature genes will advance our knowledge of ACP pathogenesis
Zabotti, Alen; Errichetti, Enzo; Zuliani, Francesca; Quartuccio, Luca; Sacco, Stefania; Stinco, Giuseppe; De Vita, Salvatore
Exclusion of psoriatic skin/nail lesions is important in differentiating early seronegative rheumatoid arthritis (ERA) from early polyarticular psoriatic arthritis (EPsA) and such manifestations may go unnoticed in atypical or minimally expressed cases. The aim of this study is to assess the usefulness of integrated rheumatological-dermatological evaluation in highlighting dermatological lesions missed on rheumatological examination and to investigate the role of ultrasonography (US) and dermoscopy in improving the recognition of subclinical psoriatic findings. Patients with a new diagnosis of seropositive or seronegative ERA and EPsA with prevalent hands involvement were recruited. All were reassessed for the presence of psoriatic lesions during an integrated rheumatological-dermatological clinical evaluation and underwent hands US and proximal nailfold dermoscopy. Seventy-three consecutive subjects were included in the study: 25 with seropositive ERA, 23 with seronegative ERA, and 25 with EPsA. One-fourth of the subjects initially diagnosed as seronegative ERA presented cutaneous or nail psoriasis on integrated rheumatological-dermatological evaluation, thereby being reclassified as EPsA. The presence of at least 1 extrasynovial feature on hand US and dotted vessels on proximal nailfold dermoscopy was significantly associated with EPsA, with a sensitivity of 68.0% and 96.0% and a specificity of 88.1% and 83.3% for US and dermoscopy, respectively. When used together, specificity for PsA diagnosis raised to 90.5%. Integrated rheumatological-dermatological clinical evaluation may be helpful in identifying patients with EPsA misclassified as seronegative ERA. Additionally, US and dermoscopy may be used as supportive tools in identifying subclinical psoriatic features, which may come in handy in distinguishing EPsA from ERA.
Si, Ming-Jue; Gui, Shuang; Fan, Qin; Han, Hong-Xiu; Zhao, Qian-Qian; Li, Zhi-Xin; Zhao, Jiang-Min
To determine the role of MRI in the early diagnosis of tubal ectopic pregnancy (EP). Clinical and MRI features of 27 cases of tubal pregnancy were reviewed. A thick-walled gestational sac (GS)-like structure was demonstrated lateral to the uterus in all cases. On T2-weighted images, the thick wall typically exhibited 3 discrete rings in 22 cases (81 %), among which 17 cases (63 %) displayed small vessels and 6 cases (33 %) exhibited small areas of fresh haemorrhage inside the thick wall. The contents demonstrated non-specific liquid in 26 %, papillary solid components in 56 %, and fresh blood or fluid-fluid level in 19 % of the cases. Dilatation of the affected fallopian tube associated with hematosalpinx was demonstrated in 18 cases (67 %) and marked enhancement of the tubal wall was observed in 22 cases (81 %). No correlation was found between the size of the GS and the estimated gestational age (r = 0.056). MRI plays an important role in the early diagnosis and management of tubal pregnancy. The characteristic MRI features include a GS-like structure with a "three rings" appearance on T2-weighted images, presence of solid components in the sac, dilatation of the affected fallopian tube with hematosalpinx, and tubal wall enhancement. • MR imaging has served as a problem-solving procedure in ectopic pregnancy. • MR imaging features can be criteria for early diagnosis of tubal pregnancy. • Detailed assessment of ectopic implantation is necessary for management decision-making.
Baert, A.L.; Fevery, J.; Marchal, G.
In 5 patients with Budd-Chiari syndrome, computed tomography after intravenous bolus injection of iodinated contrast agents demonstrated images not previously seen in other diseases. The images are compatible with stagnation of contrast material at the periphery of the liver. In 3 of the 5 cases, grey-scale ultrasonography failed to document the normal hepatic veins draining into the inferior caval vein, but showed an intrahepatic network of comma-shaped venous structures. It is proposed that these two noninvasive approaches can help in establishing an early diagnosis.
With ageing populations and an increasing lifetime risk of cancer, primary care will continue to play an increasingly important role in early diagnosis and cancer survivorship, especially with the lowering of risk thresholds for referral and diagnostic investigations. However, primary care in many countries is in crisis with increasing workloads for primary care physicians. Potential solutions to these challenges will be outlined including development of multidisciplinary teams, diagnostic decision support, increasing access to diagnostics and cost-effective referral pathways. © 2017 John Wiley & Sons Ltd.
Hesch, R D; Harms, H; Rittinghaus, E F; Brabant, G
A paradigma of osteoporosis pathology is discussed, at the center of which is the hormone-related disturbance of the osteoblast/osteoclast functional unit. A liberal replacement of estrogen-gestagen in post-menopausal women is advocated. Early diagnosis with the aid of quantitative computed tomography makes it possible to establish the indication for timely hormonal treatment in the future, which can result in a measureable increase in bone mass. Late therapy, that is, treatment initiated after the occurrence of fractures, has proven largely ineffective.
Rotenstreich, Ygal; Ben-Ner, Daniel; Sharvit-Ginon, Inbal; Ravona-Springer, Ramit; Beeri, Michal; Sher, Ifat
The pupil responses of 15 cognitively normal subjects (ages 60-74) were examined in response to 76 focal red and blue light stimuli using a chromatic multifocal pupillometer (CMP). Subjects with low cognitive scores as determined as by Montreal Cognitive Assessment testing, presented significantly weaker and sluggish pupil responses in peripheral and central locations of the visual field in response to red and blue light. Our findings suggests that the CMP may present a novel objective, non-invasive, low cost technique for early diagnosis of cognitive decline that may serve for Alzheimer Disease prevention and as sensitive outcome measure of therapeutic effects.
Frankenburg, William K.; North, A. Frederick, Jr.
The manual was designed to help public officials, physicians, nurses, and others to plan and implement an Early and Periodic Screening, Diagnosis and Treatment (EPSDT) program under Medicaid. Procedures for carrying out components of an EPSDT program are recommended. Part 1 discusses organization and administration of screening, diagnosis, and…
Volta, Bibiana Julieta; Perrone, Alina Elizabet; Rivero, Rocío; Scollo, Karenina; Bustos, Patricia Laura; Bua, Jacqueline
Trypanosoma cruzi , the causing agent of Chagas disease, can be transmitted to the offspring of infected pregnant women, thus being an epidemiologically important way of parasite transmission in humans. In addition, the migration of infected women from endemic areas to nonendemic countries may export this parasite infection. The diagnosis of congenital Chagas disease relies on the detection of the parasite because maternal antibodies are passively transferred to infants during pregnancy. The diagnosis of congenital infection can also be confirmed by detection of infant-specific anti- T cruzi antibodies at 10 months after delivery. Because early detection of T cruzi infection in newborns allows an efficient trypanocidal treatment and cure, more sensitive molecular techniques such as DNA amplification are being used for a prompt parasitological diagnosis of children born to seropositive mothers. In this report, we describe a diagnosis case of a child congenitally infected with T cruzi who tested negative for parasite detection both by microscopic observation and DNA amplification at 20 days and 6 months after delivery. However, at 7 months of age, a hemoculture was made from the infant's blood, and the infective parasite was finally isolated and classified as T cruzi discrete typing unit I. In a retrospective study, real-time polymerase chain reaction also allowed detecting the parasite but failed to detect any parasite load in earlier control samples. This case report stresses that even when molecular techniques are negative, a long-term follow-up is necessary for the diagnosis of infants congenitally infected with T cruzi . Copyright © 2018 by the American Academy of Pediatrics.
Cabral, Luís; Afreixo, Vera; Santos, Filipe; Almeida, Luís; Paiva, José Artur
The gold standard for sepsis diagnosis in burn patient still relies on microbiological cultures, which take 48-72h to provide results, delaying the start of antimicrobial therapy. Thus, biomarkers allowing an earlier sepsis diagnosis in burn patients are needed. This retrospective observational study included 150 burn patients with total burned surface area ≥15%. Clinical diagnosis of sepsis among these patients was done according to the American Burn Association criteria. Biomarker (procalcitonin, white blood cells and platelet countings, prothrombinemia, D-dimers, C-reactive protein, blood lactate and temperature) values were available for 48 patients without sepsis (2767 timepoints) and 102 patients with sepsis (652 timepoints). Quantitative variables were compared with Mann-Whitney tests and qualitative variables were compared with Pearson chi-square test. Effect size was measured by the probability of superiority. Receiver operating characteristic (ROC) curves evaluate capacity for sepsis diagnosis. Sensitivity, specificity, positive and negative predictive values were calculated for some cut-off values, including the best cut-off defined by the maximum of Youden index. Statistically significant differences between the groups of septic and non-septic patients, with medium to large effect size, were detected for all the biomarkers considered, except temperature. PCT was the biomarker with the largest AUC and effect size (AUC=0.71). Analysis of the PCT ROC curve showed that 0.5ng/mL cut-off presented highest sensitivity and lowest specificity, whereas 1.5ng/mL cut-off was associated with lowest sensitivity and highest specificity. Procalcitonin showed to be the best of the biomarkers studied for an early diagnosis of sepsis. Its use should be considered in antimicrobial stewardship programs in Burn Units. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.
Petruk, V. G.; Ivanov, A. P.; Kvaternyuk, S. M.; Barun, V. V.
We have designed an experimental setup, based on two integrating spheres, that lets us measure the optical diffuse reflectance spectra (diffuse reflection coefficient vs. wavelength) of human skin quickly under clinical conditions in vivo. For the wavelength interval 520-1100 nm, we give the values of the diffuse reflection coefficient for healthy tissue, skin with a benign nevus, and skin with a malignant melanoma for a large group of test subjects. We experimentally established a number of wavelengths in the red-near IR region of the spectrum which can be used for early differential diagnosis of nevi and melanoma in patient cancer screening. According to the Kramer-Welch test, the probability of the diffuse reflection coefficient for skin with melanoma and a nevus having different distributions is >0.94, and at many wavelengths it is >0.999. By solving the inverse problem, we estimated the changes in a number of structural and biophysical parameters of the tissue on going from healthy skin to nevus and melanoma. The results obtained can provide a basis for developing a clinical approach to identifying the risk of malignant transformation of the skin before surgery and histological analysis of the tissue.
Törö, Krisztina; Balázs, Judit
Reading Disorder (RD) belongs to Specific Learning Disorders within the chapter of Neurodevelopmental Disorders in the Diagnostic and Statistic Manual of Mental Disorders 5th edition. Previous research shows that the time of the diagnosis of RD - early (before starting school) or late - has a great impact on the prognosis. In the current paper we present the cases of two children diagnosed with RD. Our cases demonstrate that if RD is diagnosed in early childhood, the child's and his/her family's quality of life can be influenced in a positive direction, while late recognition of RD might influence the child's and the family's quality of life negatively. For these reasons it is important that experts recognize RD in time, start appropriate treatment and give proper support to children diagnosed with RD and their families.
Cauduro, Alberto; Paolo, Favole; Asperio, Roberto M; Rossini, Valeria; Dondi, Maurizio; Simonetto, Lucia A; Cantile, Carlo; Lorenzo, Valentina
The medical records of two dogs that were diagnosed with masticatory muscle myositis (MMM) were reviewed. The reported clinical signs included intense pain when opening the mouth and restricted jaw movement. MRI detected widespread, symmetrical, and inhomogeneously hyperintense areas in the masticatory muscle. Electromyography (EMG) demonstrated severe and spontaneous pathologic activity in the temporal and masseter muscles. With early therapeutic treatment, remission of symptoms occurred within 2 mo, and no relapses were observed for the subsequent 2 yr. The gold standard for the diagnosis of MMM is the 2M antibody test, but the purpose of this study was to evaluate the use of MRI as an accurate and efficient diagnostic tool for the initiation of early therapy for the treatment of muscle myositis.
Bourguet, Aurélie; Piccicuto, Virginie; Donzel, Elise; Carlus, Marine; Chahory, Sabine
This report describes the clinical presentation, diagnosis, histological lesions, and prognosis of a primary choroidal malignant melanoma in a 15-year-old cat. The animal was presented for unilateral blindness. On ocular examination, a raised pigmented mass protruding from the posterior pole into the vitreous body was observed by diffuse transillumination and indirect ophthalmoscopy. Ocular ultrasound and computer tomography (CT) scan confirmed localization of the tumor to the posterior segment. The diagnosis of primary choroidal melanoma was confirmed by histopathology after enucleation. To our knowledge, this is the first reported case of a feline malignant melanoma with a primary choroidal localization without iris involvement. © 2014 American College of Veterinary Ophthalmologists.
Wang, Bi; Yu, Lei; Yang, Guo-Zhen; Luo, Xin; Huang, Lin
To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). Serum and fresh tissue samples were collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes. Methylation levels of tissues were assessed by multiplex nested methylated specific PCR, the results being compared with those for carcinoma antigen 125 (CA125). The serum free deoxyribose nucleic acid (DNA) methylation spectrum of EOC patients was completely contained in the DNA spectrum of cancer tissues, providing an accurate reflection of tumor DNA methylation conditions. Serum levels of CA125 and free DNA methylation in the EOC group were evidently higher than those in benign lesion and control groups (p<0.05). Patients with early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05), but there was no significant difference in free DNA methylation (p>0.05). The sensitivity, specificity and positive predicative value (PPV) of multiplex nested methylated specific PCR were significantly higher for detection of all patients and those with early EOC than those for CA125 (p<0.05). In the detection of patients with advanced EOC, the PPV of CA125 detection was obviously lower than that of multiplex nested methylated specific PCR (p>0.05), but there was no significant difference in sensitivity (p>0.05). Serum free DNA methylation can be used as a biological marker for EOC and multiplex nested methylated specific PCR should be considered for early diagnosis since it can accurately determine tumor methylation conditions.
Wang, Li-Xin; Li, Yang; Chen, Guan-Zhi
Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach. The differentially expressed genes (DEGs) were screened by the EdgeR package of R software. A weighted gene co-expression network analysis (WGCNA) was used for the identification of DEGs in the special gene modules and hub genes. Subsequently, a protein-protein interaction network was constructed to extract hub genes associated with gene modules. Finally, twenty-four important hub genes (RASGRP2, IKZF1, CXCR5, LTB, BLK, LINGO3, CCR6, P2RY10, RHOH, JUP, KRT14, PLA2G3, SPRR1A, KRT78, SFN, CLDN4, IL1RN, PKP3, CBLC, KRT16, TMEM79, KLK8, LYPD3 and LYPD5) were treated as valuable factors involved in the immune response and tumor cell development in tumorigenesis. In addition, a transcriptional regulatory network was constructed for these specific modules or hub genes, and a few core transcriptional regulators were found to be mostly associated with our hub genes, including GATA1, STAT1, SP1, and PSG1. In summary, our findings enhance our understanding of the biological process of malignant melanoma metastasis, enabling us to identify specific genes to use for diagnostic and prognostic markers and possibly for targeted therapy.
Carro, Eva; Bartolomé, Fernando; Bermejo-Pareja, Félix; Villarejo-Galende, Alberto; Molina, José Antonio; Ortiz, Pablo; Calero, Miguel; Rabano, Alberto; Cantero, José Luis; Orive, Gorka
The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid β (Aβ) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity. Here, we show a novel, straight-forward, and noninvasive approach for assessment of early stages of cognitive decline. Salivary samples from cases of amnestic mild cognitive impairment (aMCI) and AD, and neurology controls were analyzed. We have discovered and validated a new single saliva biomarker, lactoferrin, which in our cross-sectional investigation perfectly discriminates clinically diagnosed aMCI and AD patients from a cognitively healthy control group. The accuracy for AD diagnosis shown by salivary lactoferrin was greater than that obtained from core cerebrospinal fluid (CSF) biomarkers, including total tau and CSF Aβ 42 . Furthermore, salivary lactoferrin can be used for population screening and for identifying those underdiagnosed subjects with very early stages of mild cognitive impairment and AD. This biomarker may offer new insights in the early diagnostics for AD.
Pavlović-Ružić, Ira; Jonjić, Nives; Zamolo, Gordana; Zuvić-Butorac, Marta; Katunarić, Miljenko; Pečanić, Sanja
There is a global rising incidence of melanoma. For different reasons, the patterns of the incidence, appearance, gender, anatomical distribution and outcome vary among different geographic areas. Screening programs have led to better early detection of melanoma in Australia and some world areas. National Cancer Registry and practice data show the incidence in Croatia to be constantly rising. Despite public education programs about early detection, at clinical departments there are still many new advanced stage melanoma patients. We analyzed data on 157 patients treated and followed up for 10 years for T1b-T4aN0 skin melanoma. There was a difference in anatomical distribution of melanoma lesions in correlation with patient age (ANOVA test, F=3.51, p=0.009). A higher prevalence of shoulder melanoma was found in young people and of head/neck melanoma in the elderly (post-hoc Sheffe test, p=0.038). T4 lesions were more commonly found in men and T1 mainly in women (Pearson χ(2)-test, χ(2)=12.08, p=0.016). There was no difference in Clark level, but a significantly higher Breslow stage was found in men (t=-2.52, p=0.013). Men were much more prone to have head and neck, body and shoulder melanoma, whereas women had more melanoma on their legs and arms. Clark and Breslow levels were strongly correlated in leg melanoma; head localization showed no correlation at all. In conclusion, more attention should be devoted to improve the results in melanoma detection in men, especially considering the prevalence of body (back) and head/neck localizations, sometimes not readily accessible for visual detection. The pattern of distribution also pointed to the need for more attention to pay to shoulder melanoma in younger people.
Schwartz, Robert A; Kist, Joseph M; Thomas, Isabelle; Fernández, Geover; Cruz, Manuel A; Koziorynska, Ewa I; Lambert, W Clark
Cutaneous metastatic disease is an important finding that may represent the first sign of systemic cancer, or, if already known, that may change tumor staging and thus dramatically altered therapeutic plans. Although cutaneous metastases are relatively frequent in patients with cutaneous melanoma, they are less so from ocular melanoma. To demonstrate the value of HMB-45, staining in the detection of ocular melanoma metastatic to skin. The immunohistochemical stain HMB-45 a monoclonal antibody directed against intact human melanoma cells, was employed on a skin biopsy specimen from a cutaneous tumor. HMB-45 staining was positive in the atypical hyperchromatic cells of the deep dermis. HMB-45 may be of value in the detection of ocular melanoma metastatic to skin. Cutaneous metastatic disease is a somewhat common and extremely important diagnosis. Although cutaneous metastases from cutaneous melanoma are relatively frequent, those from ocular melanomas are less so. Use of histochemical staining, especially the HMB-45 stain, allows confirmation of the diagnosis.
Salvatore, Christian; Cerasa, Antonio; Battista, Petronilla; Gilardi, Maria C; Quattrone, Aldo; Castiglioni, Isabella
Determination of sensitive and specific markers of very early AD progression is intended to aid researchers and clinicians to develop new treatments and monitor their effectiveness, as well as to lessen the time and cost of clinical trials. Magnetic Resonance (MR)-related biomarkers have been recently identified by the use of machine learning methods for the in vivo differential diagnosis of AD. However, the vast majority of neuroimaging papers investigating this topic are focused on the difference between AD and patients with mild cognitive impairment (MCI), not considering the impact of MCI patients who will (MCIc) or not convert (MCInc) to AD. Morphological T1-weighted MRIs of 137 AD, 76 MCIc, 134 MCInc, and 162 healthy controls (CN) selected from the Alzheimer's disease neuroimaging initiative (ADNI) cohort, were used by an optimized machine learning algorithm. Voxels influencing the classification between these AD-related pre-clinical phases involved hippocampus, entorhinal cortex, basal ganglia, gyrus rectus, precuneus, and cerebellum, all critical regions known to be strongly involved in the pathophysiological mechanisms of AD. Classification accuracy was 76% AD vs. CN, 72% MCIc vs. CN, 66% MCIc vs. MCInc (nested 20-fold cross validation). Our data encourage the application of computer-based diagnosis in clinical practice of AD opening new prospective in the early management of AD patients.
Soler, Maria; Estevez, M-Carmen; Villar-Vazquez, Roi; Casal, J Ignacio; Lechuga, Laura M
Colorectal cancer is treatable and curable when detected at early stages. However there is a lack of less invasive and more specific screening and diagnosis methods which would facilitate its prompt identification. Blood circulating autoantibodies which are immediately produced by the immune system at tumor appearance have become valuable biomarkers for preclinical diagnosis of cancer. In this work, we present the rapid and label-free detection of colorectal cancer autoantibodies directly in blood serum or plasma using a recently developed nanoplasmonic biosensor. Our nanoplasmonic device offers sensitive and real-time quantification of autoantibodies with excellent selectivity and reproducibility, achieving limits of detection around 1 nM (150-160 ng mL(-1)). A preliminary evaluation of clinical samples of colorectal cancer patients has shown good correlation with ELISA. These results demonstrate the reliability of the nanobiosensor strategy and pave the way towards the achievement of a sensitive diagnostic tool for early detection of colorectal cancer. Copyright © 2016 Elsevier B.V. All rights reserved.
Bohîlțea, R E; Ancăr, V; Cirstoiu, M M; Rădoi, V; Bohîlțea, L C; Furtunescu, F
Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania, reaching in 2013 the average value of 8.06/ 100,000 women, and 15.97/ 100,000 women within the highest risk age range, having in recent years an increasing trend, being higher in urban than in rural population. Annually, approximately 800 new cases are registered in our country. The estimated lifetime risk of a woman to develop endometrial cancer is of about 1,03%. Based on an abnormal uterine bleeding, 35% of the endometrial cancers are diagnosed in an advanced stage of the disease, with significantly diminished lifetime expectancy. Drafting a national program for the early diagnosis of endometrial cancer. We proposed a standardization of the diagnostic steps and focused on 4 key elements for the early diagnosis of endometrial cancer: investigation of abnormal uterine bleeding occurring in pre/ post-menopausal women, investigating features/ anomalies of cervical cytology examination, diagnosis, treatment and proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR = International Normalized Ratio, MSI = Microsatellites instability, MSI
Grogan, Martha; Dispenzieri, Angela; Gertz, Morie A
Amyloid light chain (AL) amyloidosis is a systemic disease characterised by the aggregation of misfolded immunoglobulin light chain (LC), predominantly in the heart and kidneys, causing organ failure. If untreated, the median survival of patients with cardiac AL amyloidosis is 6 months from the onset of heart failure. Protracted time to establish a diagnosis, often lasting >1 year, is a frequent factor in poor treatment outcomes. Cardiologists, to whom patients are often referred, frequently miss the opportunity to diagnose cardiac AL amyloidosis. Nearly all typical cardiac support measures, with the exception of diuretics, are ineffective and may even worsen clinical symptoms, emphasising the need for accurate diagnosis. Patients with severe cardiac involvement face poor outcomes; heart transplantation is rarely an option because of multiorgan involvement, rapid clinical decline and challenges in predicting which patients will respond to treatment of the underlying plasma cell disorder. Early diagnosis and prompt treatment with Ã¢â‚¬Ëœsource therapiesÃ¢â‚¬â„¢ that limit the production of amyloidogenic LC are associated with better survival and improvement in organ function after a median of 2.4 months following haematological complete response. However, organ recovery is often incomplete because these source therapies do not directly target deposited amyloid. Emerging amyloid-directed therapies may attenuate, and potentially reverse, organ dysfunction by clearing existing amyloid and inhibiting fibril formation of circulating aggregates. Improved recognition of AL amyloidosis by cardiologists allows for earlier treatment and improved outcomes. PMID:28456755
Bell, R J
The aim of this review was to examine the benefits and harms of organized screening mammography, with particular reference to data from Australia. Published literature was examined relating to the impact of screening mammography on breast cancer-specific mortality, the trends in use of adjuvant treatments for breast cancer, the effectiveness of adjuvant treatment in terms of breast cancer-specific mortality, the impact of breast cancer treatment on non-breast cancer mortality and the magnitude of the issue of over-diagnosis. Most of the recent reduction in breast cancer-specific mortality is explained by use of adjuvant therapy rather than screening mammography. The impact of screening mammography in countries where women present with early disease and have access to adjuvant treatment is modest. There is a wide range of estimates for the magnitude of over-diagnosis. All-cause mortality (rather than breast cancer-specific mortality) should be used when assessing the impact of mammographic screening as otherwise the harm of breast cancer treatment in women who are over-diagnosed will be missed. The benefits and harms of screening mammography are finely balanced. The impact of screening mammography is at best neutral but may result in overall harm. Women should be informed of the issue of over-diagnosis. It is time to review whether organized mammographic screening programs should continue.
Silva, J N; Miranda, L H M; Menezes, R C; Gremião, I D F; Oliveira, R V C; Vieira, S M M; Conceição-Silva, F; Ferreiro, L; Pereira, S A
Sporotrichosis is caused by species of fungi within the Sporothrix schenckii complex that infect man and animals. In Rio de Janeiro, Brazil, an epidemic has been observed since 1998, with most of the cases being related to transmission from infected cats. Although the definitive diagnosis of feline sporotrichosis is made by fungal culture, cytopathological and histopathological examinations are used routinely, because the long culture period may delay treatment onset. However, alternative methods are desirable in cases of low fungal burden. Immunohistochemistry (IHC) has been described as a sensitive method for diagnosing human and canine sporotrichosis, but there are no reports of its application to cats. The aim of this study was to analyse the sensitivity of cytopathological examination (Quick Panoptic method), histopathology (Grocott silver stain) and anti-Sporothrix IHC by blinded comparisons, using fungal culture as the reference standard. Samples were collected from 184 cats with sporotrichosis that exhibited skin ulcers. The sensitivities of Grocott silver stain, cytopathological examination and IHC were 91.3%, 87.0% and 88.6%, respectively. Grocott silver stain showed the best performance. IHC showed high sensitivity, as did cytopathological examination and these may be considered as alternative methodologies. When the three methods were combined, the diagnosis was established in 180 (97.8%) out of 184 cases. Taken together, these findings indicate the need to implement these methods as routine tools for the early diagnosis of sporotrichosis in cats, notably when fungal culture is not available. Copyright © 2018 Elsevier Ltd. All rights reserved.
Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald
Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085
Rabbie, Roy; Rashid, Mamunur; Arance, Ana M; Sánchez, Marcelo; Tell-Marti, Gemma; Potrony, Miriam; Conill, Carles; van Doorn, Remco; Dentro, Stefan; Gruis, Nelleke A; Corrie, Pippa; Iyer, Vivek; Robles-Espinoza, Carla Daniela; Puig-Butille, Joan A; Puig, Susana; Adams, David J
Melanoma in young children is rare; however, its incidence in adolescents and young adults is rising. We describe the clinical course of a 15-year-old female diagnosed with AJCC stage IB non-ulcerated primary melanoma, who died from metastatic disease 4 years after diagnosis despite three lines of modern systemic therapy. We also present the complete genomic profile of her tumour and compare this to a further series of 13 adolescent melanomas and 275 adult cutaneous melanomas. A somatic BRAF V 600E mutation and a high mutational load equivalent to that found in adult melanoma and composed primarily of C>T mutations were observed. A germline genomic analysis alongside a series of 23 children and adolescents with melanoma revealed no mutations in known germline melanoma-predisposing genes. Adolescent melanomas appear to have genomes that are as complex as those arising in adulthood and their clinical course can, as with adults, be unpredictable. © 2017 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.
Blum, Andreas; Beck-Zoul, Ulrike; Held, Laura; Haase, Sylvie
Background Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. Case A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. Conclusion Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion. PMID:27867742
Mimoz, O; Karim, A; Mazoit, J X; Edouard, A; Leprince, S; Nordmann, P
We evaluated prospectively the use of Gram staining of protected pulmonary specimens to allow the early diagnosis of ventilator-associated pneumonia (VAP), compared with the use of 60 bronchoscopic protected specimen brushes (PSB) and 126 blinded plugged telescopic catheters (PTC) obtained from 134 patients. Gram stains were from Cytospin slides; they were studied for the presence of microorganisms in 10 and 50 fields by two independent observers and classified according to their Gram stain morphology. Quantitative cultures were performed after serial dilution and plating on appropriate culture medium. A final diagnosis of VAP, based on a culture of > or = 10(3) c.f.u. ml-1, was established after 81 (44%) samplings. When 10 fields were analysed, a strong relationship was found between the presence of bacteria on Gram staining and the final diagnosis of VAP (for PSB and PTC respectively: sensitivity 74 and 81%, specificity 94 and 100%, positive predictive value 91 and 100%, negative predictive value 82 and 88%). The correlation was less when we compared the morphology of microorganisms observed on Gram staining with those of bacteria obtained from quantitative cultures (for PSB and PTC respectively: sensitivity 54 and 69%, specificity 86 and 89%, positive predictive value 72 and 78%, negative predictive value 74 and 84%). Increasing the number of fields read to 50 was associated with a slight decrease in specificity and positive predictive value of Gram staining, but with a small increase in its sensitivity and negative predictive value. The results obtained by the two observers were similar to each other for both numbers of fields analysed. Gram staining of protected pulmonary specimens performed on 10 fields predicted the presence of VAP and partially identified (using Gram stain morphology) the microorganisms growing at significant concentrations, and could help in the early choice of the treatment of VAP. Increasing the number of fields read or having the Gram
Feliciano, K V; Kovacs, M H; Alzate, A
This paper presents the results of a descriptive study carried out in the city of Recife, state of Pernambuco, Brazil, between March and September 1994. The study aimed at health services available for performing early diagnosis of Hansen's disease with emphasis on accessibility and quality of the services provided. The sample consisted of 32 health clinics visited for diagnostic purposes by 183 patients with Hansen's disease. Information on organizational infrastructures was collected by means of interviews with health clinic managers. Information regarding routine procedures in the 32 clinics was collected by observation, with special attention given to archival and inspection activities. A total of 1,998 patients were interviewed to determine accessibility of services. Time spent in consultation with the physician was determined for 1,000 patients who were seen by 123 physicians at the clinics during the interviews. To explore physicians' attitude and knowledge regarding Hansen's disease, 133 were randomly selected from a list of names. The following factors were identified as hindering early diagnosis of Hansen's disease: the large number of people seeking service who could not be seen by a physician on the same day; the long time elapsed between appointment scheduling and the actual visit (for those not seen on the same day); the long wait for the consultation; the brevity of the consultation; the low availability of trained personnel; the low proportion of physicians who examined all body surfaces; difficulties in the clinical recognition of the disease; and physicians not prepared to make a differential diagnosis. These obstacles can precipitate the physical deterioration of Hansen's disease patients and stimulate the persistence of transmissibility; therefore, they need to be overcome if Hansen's disease is to be eliminated.
San Juan, R; Aguado, J M; López, M J; Lumbreras, C; Enriquez, F; Sanz, F; Chaves, F; López-Medrano, F; Lizasoain, M; Rufilanchas, J J
Postsurgical mediastinitis (PSM) remains a major cause of morbidity and mortality in patients undergoing cardiac surgery procedures. Although prompt diagnosis is crucial in these patients, neither clinical data nor imaging techniques have shown enough sensitivity or specificity for early diagnosis of PSM. The aim of the present study was to assess the validity of blood cultures as a diagnostic test for the early detection of PSM in patients who become febrile after cardiac surgery procedures. During a 4-year period (1999-2002), patients who developed fever (>37.8 degrees C) in the first 60 days after a cardiac surgery procedure were evaluated. Blood cultures were drawn from these patients. PSM was defined as deep infection involving retrosternal tissue and/or the sternal bone directly observed by the surgeon and confirmed microbiologically. Three criteria for positivity of blood cultures were applied: bacteremia, staphylococcal bacteremia, or Staphylococcus aureus bacteremia. For purposes of the analysis, a positive blood culture in patients with PSM was considered a true-positive test and a negative blood culture a false-negative test. Otherwise, in febrile patients without PSM in the postsurgery period, a positive blood culture was considered a false-positive test and a negative blood culture a true-negative test. Blood cultures were drawn from 266 febrile patients in the postsurgery period. PSM occurred in 38 patients (26 cases due to S. aureus, 8 to Staphylococcus epidermidis, 3 to gram-negative enteric bacteria, and one to Pseudomonas aeruginosa). Within the 60-day postsurgical period, blood culture as a diagnostic test was most accurate in patients with S. aureus bacteremia, providing 68% sensitivity, 98% specificity, a positive predictive value of 87%, and a negative predictive value of 95%. If the analysis was limited to the period during which patients are at maximum risk for PSM (day 7-20), the values in patients with S. aureus bacteremia were as follows
Kardynal, Agnieszka; Olszewska, Małgorzata; de Carvalho, Nathalie; Walecka, Irena; Pellacani, Giovanni; Rudnicka, Lidia
In vivo reflectance confocal microscopy (RCM) plays an increasingly important role in differential diagnosis of melanoma. The aim of the study was to assess typical confocal features of thin (≤1mm according to Breslow index) versus thick (>1mm) melanomas. 30 patients with histopathologically confirmed cutaneous melanoma were included in the study. Reflectance confocal microscopy was performed with Vivascope equipment prior to excision. Fifteen melanomas were thin (Breslow thickness ≤ 1mm) and 15 were thick melanomas (Breslow thickness >1mm). In the RCM examination, the following features were more frequently observed in thin compared to thick melanomas: edged papillae (26.7% vs 0%, p=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs 6.7%, p=0.068). Both features are present in benign melanocytic lesions, so in melanoma are good prognostic factors. The group of thick melanomas compared to the group of thin melanomas in the RCM images presented with greater frequency of roundish cells (100% vs 40%, p=0.001), non-edged papillae (100% vs 60%, p=0.006), numerous pagetoid cells (73.3% vs 33.3%, p=0.028), numerous atypical cells at dermal-epidermal junction (53.3% vs 20%, p=0.058) and epidermal disarray (93.3% vs 66.7%, p=0.068). Non-invasive imaging methods helps in deepening of knowledge about the evolution and biology of melanoma. The most characteristic features for thin melanomas in confocal examination are: fragments of cobblestone or honeycomb pattern and edged papillae (as good prognostic factors). The features of thick melanomas in RCM examination are: roundish cells, non-edged papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal disarray.
Mostafavi, Ehsan; Pourhossein, Behzad; Chinikar, Sadegh
Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease, which is usually transmitted to humans by tick bites or contact with blood or other infected tissues of livestock. Patients suffering from CCHF demonstrate an extensive spectrum of clinical symptoms. As it can take considerable time from suspecting the disease in hospital until reaching a definitive diagnosis in the laboratory, understanding the clinical symptoms and laboratory findings of CCHF patients is of paramount importance for clinicians. The data were collected from patients who were referred to the Laboratory of Arboviruses and Viral Hemorrhagic Fevers at the Pasteur institute of Iran with a primary diagnosis of CCHF between 1999 and 2012 and were assessed by molecular and serologic tests. Referred patients were divided into two groups: patients with a CCHF positive result and patients with a CCHF negative result. The laboratory and clinical findings of these two groups were then compared. Two-thousand five hundred thirty-six probable cases of CCHF were referred to the laboratory, of which 871 cases (34.3%) were confirmed to be CCHF. Contact with infected humans and animals increased the CCHF infection risk (P < 0.001). A tick bite was not a risk factor. Fever; bleeding, vomiting, leucopoenia, thrombocytopenia, and increases in alanine transaminase (ALT) and aspartate transaminase (AST) levels were also indicative of CCHF infection. Accurate and speedy diagnosis of CCHF and appropriate treatment play an important role in patient survival and the application of the findings of this study can prove helpful as a key for early diagnosis. © 2014 Wiley Periodicals, Inc.
Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma
Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection. PMID:23272999
Xie, Yao; Zhi, Xiao; Su, Haichuan; Wang, Kan; Yan, Zhen; He, Nongyue; Zhang, Jingpu; Chen, Di; Cui, Daxiang
Early diagnosis is very important to improve the survival rate of patients with gastric cancer and to understand the biology of cancer. In order to meet the clinical demands for early diagnosis of gastric cancer, we developed a disposable easy-to-use electrochemical microfluidic chip combined with multiple antibodies against six kinds of biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), Helicobacter pylori CagA protein (H.P.), P53oncoprotein (P53), pepsinogen I (PG I), and PG-II). The six kinds of biomarkers related to gastric cancer can be detected sensitively and synchronously in a short time. The specially designed three electrodes system enables cross-contamination to be avoided effectively. The linear ranges of detection of the electrochemical microfluidic chip were as follows: 0.37-90 ng mL-1 for CEA, 10.75-172 U mL-1 for CA19-9, 10-160 U L-1 for H.P., 35-560 ng mL-1 for P53, 37.5-600 ng mL-1 for PG I, and 2.5-80 ng mL-1for PG II. This method owns better sensitivity compared with enzyme-linked immunosorbent assay (ELISA) results of 394 specimens of gastric cancer sera. Furthermore, we established a multi-index prediction model based on the six kinds of biomarkers for predicting risk of gastric cancer. In conclusion, the electrochemical microfluidic chip for detecting multiple biomarkers has great potential in applications such as early screening of gastric cancer patients, and therapeutic evaluation, and real-time dynamic monitoring the progress of gastric cancer in near future.
Jellinger, Kurt A; Janetzky, Bernd; Attems, Johannes; Kienzl, Elisabeth
Simple, non-invasive tests for an early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers (plasma/serum, platelets, urine, connective tissue) for the early diagnosis of Alzheimer disease (AD) are available. In disease stages with evident cognitive disturbances, the clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. Diagnostic sensitivity and specificity even in early disease stages are improved by CSF markers, in particular combined tau and amyloid beta peptides (Abeta) and plasma markers (eg, Abeta-42/Abeta-40 ratio). Recently, a novel gene/protein--ALZAS (Alzheimer Associated Protein)--with a 79 amino acid sequence, containing the amyloid beta-42 fragment (Abeta-42), the amyloid precursor protein (APP) transmembrane signal and a 12 amino acid C-terminal, not present in any other known APP alleles, has been discovered on chromosome 21 within the APP region. Reverse transcriptase-PCR revealed the expression of the transcript of this protein in the cortex and hippocampal regions as well as in lymphocytes of human AD patients. The expression of ALZAS is mirrored by a specific autoimmune response in AD patients, directed against the ct-12 end of the ALZAS-peptide but not against the Abeta-sequence. ELISA studies of plasma detected highest titers of ALZAS in patients with mild cognitive impairment (presymptomatic AD), but only moderately increased titers in autopsy-confirmed AD, whereas low or undetectable ct-12 titers were found in cognitively intact age-matched subjects and young controls. The antigen, ALZAS protein, was detected in plasma in later clinical stages of AD. It is suggested that ALZAS represents an indicator in a dynamic equilibrium between both peripheral and brain degenerative changes in AD and may become a useful "non-invasive" diagnostic marker via a simple blood test.
Ao, Lu; Zhang, Zimei; Guan, Qingzhou; Guo, Yating; Guo, You; Zhang, Jiahui; Lv, Xingwei; Huang, Haiyan; Zhang, Huarong; Wang, Xianlong; Guo, Zheng
Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate. Based on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients. A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics. The signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early
Seo, Kwang Il; Moon, Won; Kim, Sung Eun; Park, Moo In; Park, Seun Ja
Inflammatory bowel disease (IBD) is characterized by recurrent or chronic inflammation of the gastrointestinal tract, which results in increased risk of developing cancer. Anorectal malignant melanoma is often misdiagnosed as either hemorrhoids or benign anorectal conditions in inflammatory bowel disease. Therefore, the overall prognosis and survival of IBD are poor. To date, the best treatment strategy remains controversial. Only early diagnosis and complete excision yield survival benefit. Here, we report a 64-year-old woman with ulcerative colitis, who was found to have anal malignant melanoma on routine colonoscopy. The lesion was confined to the mucosa with no distant metastasis. She underwent complete trans-anal excision. There was no recurrence at the four-year follow-up. Physicians should be aware of increased risk of cancer development in IBD patients and remember the importance of meticulous inspection of the anal canal.
Cook, Rebecca E; Ciampa, Philip J; Sidat, Mohsin; Blevins, Meridith; Burlison, Janeen; Davidson, Mario A; Arroz, Jorge A; Vergara, Alfredo E; Vermund, Sten H; Moon, Troy D
A key challenge inhibiting the timely initiation of pediatric antiretroviral treatment is the loss to follow-up of mothers and their infants between the time of mothers' HIV diagnoses in pregnancy and return after delivery for early infant diagnosis of HIV. We sought to identify barriers to follow-up of HIV-exposed infants in rural Zambézia Province, Mozambique. We determined follow-up rates for early infant diagnosis and age at first test in a retrospective cohort of 443 HIV-infected mothers and their infants. Multivariable logistic regression models were used to identify factors associated with successful follow-up. Of the 443 mother-infant pairs, 217 (49%) mothers enrolled in the adult HIV care clinic, and only 110 (25%) infants were brought for early infant diagnosis. The predictors of follow-up for early infant diagnosis were larger household size (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.09-1.53), independent maternal source of income (OR, 10.8; 95% CI, 3.42-34.0), greater distance from the hospital (OR, 2.14; 95% CI, 1.01-4.51), and maternal receipt of antiretroviral therapy (OR, 3.15; 95% CI, 1.02-9.73). The median age at first test among 105 infants was 5 months (interquartile range, 2-7); 16% of the tested infants were infected. Three of four HIV-infected women in rural Mozambique did not bring their children for early infant HIV diagnosis. Maternal receipt of antiretroviral therapy has favorable implications for maternal health that will increase the likelihood of early infant diagnosis. We are working with local health authorities to improve the linkage of HIV-infected women to HIV care to maximize early infant diagnosis and care.
Saketkoo, Lesley Ann; Magnus, Jeanette H.; Doyle, Mittie K.
Systemic sclerosis (SSc) is a disease of unknown etiology that manifests as a heterogeneous group of multi-organ system manifestations and is characterized by vasculopathy and fibrosis of the skin and internal organs, with mortality related to pulmonary, cardiac, renal or gastrointestinal involvement. The prevalence of SSc may be underestimated in the general population. Cases are often undiagnosed or misdiagnosed, particularly cases with mild or no skin manifestations. Due to late referrals to rheumatologic care, many moderate-to-severe cases progress to irreversible end-organ damage that might have been prevented by early diagnosis. Early diagnosis of SSc with initiation of appropriate treatment is essential, with great impact on morbidity and mortality. This review examines presenting features, ensuing complications and treatment providing a focus on SSc as a treatable disease. Primary care providers play a pivotal role in recognizing initial symptoms associated with SSc and securing early diagnosis through early referral to specialists. PMID:24366221
Oliveria, S A; Saraiya, M; Geller, A C; Heneghan, M K; Jorgensen, C
Background As skin cancer education programmes directed to children and adolescents continue to expand, an epidemiological basis for these programmes is necessary to target efforts and plan for further evaluation. Aims To summarise the epidemiological evidence on sun exposure during childhood and adolescence and melanoma risk. Methods A literature review was conducted using Medline (1966 to December 2004) to identify articles relating to sun exposure and melanoma. The review was restricted to studies that included sun exposure information on subjects 18 years of age or younger. Results Migrant studies generally indicate an increased melanoma risk in individuals who spent childhood in sunny geographical locations, and decreasing melanoma risk with older age at arrival. Individuals who resided in geographical locations close to the equator or close to the coast during childhood and/or adolescence have an increased melanoma risk compared to those who lived at higher latitudes or never lived near the coast. The intermittent exposure hypothesis remains controversial; some studies indicate that children and adolescents who received intermittent sun exposure during vacation, recreation, or occupation are at increased melanoma risk as adults, but more recent studies suggest intermittent exposure to have a protective effect. The majority of sunburn studies suggest a positive association between early age sunburn and subsequent risk of melanoma. Conclusion Future research efforts should focus on: (1) clarifying the relation between sun exposure and melanoma; (2) conducting prospective studies; (3) assessing sun exposure during different time periods of life using a reliable and quantitative method; (4) obtaining information on protective measures; and (5) examining the interrelations between ability to tan, propensity to burn, skin type, history of sunburns, timing and pattern of sun exposure, number of nevi, and other host factors in the child and adolescent populations
Goldstein, Alisa M.; Tucker, Margaret A.
Dysplastic nevi (DN) are described as being on a continuum between common acquired nevi and melanoma because they are morphologically and biologically intermediate between these two entities. Since initially being reported as histologic lesions observed in melanoma-prone families, there has been considerable debate about the definition of dysplastic nevi, the histologic and clinical criteria used to define them, and their biological importance. Their role as precursor lesions for melanoma is not their primary role in their relationship to melanoma because of the rarity of transformation of any individual nevus to a melanoma. Although there is still no single universally agreed upon histologic or clinical definition or even name for these nevi, dysplastic nevi should be considered important because of their association with an increased risk for melanoma. PMID:23549396
Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma
Di, Lianjun; Wu, Huichao; Zhu, Rong; Li, Youfeng; Wu, Xinglong; Xie, Rui; Li, Hongping; Wang, Haibo; Zhang, Hua; Xiao, Hong; Chen, Hui; Zhen, Hong; Zhao, Kui; Yang, Xuefeng; Xie, Ming; Tuo, Bigung
Gastric cancer is a frequent malignant tumor worldwide and its early detection is crucial for curing the disease and enhancing patients' survival rate. This study aimed to assess whether the multi-disciplinary team (MDT) can improve the detection rate of early gastric cancer (EGC). The detection rate of EGC at the Digestive Endoscopy Center, Affiliated Hospital, Zunyi Medical College, China between September 2013 and September 2015 was analyzed. MDT for the diagnosis of EGC in the hospital was established in September 2014. The study was divided into 2 time periods: September 1, 2013 to August 31, 2014 (period 1) and September 1, 2014 to September 1, 2015 (period 2). A total of 60,800 patients' gastroscopies were performed during the two years. 61 of these patients (0.1%) were diagnosed as EGC, accounting for 16.44% (61/371) of total patients with gastric cancer. The EGC detection rate before MDT (period 1) was 0.05% (16/29403), accounting for 9.09% (16/176) of total patients with gastric cancer during this period. In comparison, the EGC detection rate during MDT (period 2) was 0.15% (45/31397), accounting for 23% (45/195) of total patients with gastric cancer during this period (P < 0.05). Univariate and multivariate logistic analyses showed that intensive gastroscopy for high risk patients of gastric cancer enhanced the detection rate of EGC in cooperation with Department of Pathology (OR = 10.1, 95% CI 2.39-43.3, P < 0.05). MDT could improve the endoscopic detection rate of EGC.
Wang, Long; Hu, Ya-Qian; Zhao, Zhuo-Jie; Zhang, Hong-Yang; Gao, Bo; Lu, Wei-Guang; Xu, Xiao-Long; Lin, Xi-Sheng; Wang, Jin-Peng; Jie, Qiang; Luo, Zhuo-Jing; Yang, Liu
Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.
McMullen, Richard J.; Clode, Alison B.; Pandiri, Arun Kumar R.; Malarkey, David E.; Michau, Tammy Miller; Gilger, Brian C.
A case of epibulbar melanoma in a 6-month-old, gelded, chestnut Hanoverian foal is reported. The location and clinical appearance upon initial presentation led to the tentative diagnosis of staphyloma or a congenital mass of unknown origin. An attempt was made to surgically excise the mass under general anesthesia, but due to its infiltrative nature and intraoperative appearance, most, but not all was removed without compromising the integrity of the globe. Histopathological evaluation revealed a multinodular to packeted, poorly demarcated, unencapsulated, infiltrative exophytic melanocytic neoplasm composed of bundles and nests of plump spindloid to polygonal heavily pigmented epithelioid neoplastic cells interspersed with pigment-laden macrophages within a fine fibrovascular stroma. Upon examination after enucleation, neoplastic cells were found to infiltrate into the lateral cornea, sclera and the choroid. This is a unique case of an epibulbar melanoma with choroidal invasion in a foal. Based on the sudden onset and rapid growth as well as the histological evidence of invasion, well-differentiated features, heavy pigmentation, and no apparent mitoses, this neoplasm was considered to be a low-grade malignant melanoma. At 14 months after excision there is no evidence of recurrence. PMID:19046269
Wasif, Nabil; Etzioni, David; Haddad, Dana; Gray, Richard J; Bagaria, Sanjay P; Pockaj, Barbara A
Routine cross-sectional imaging for staging of early-stage cutaneous melanoma is not recommended. This study sought to investigate the use of imaging for staging of cutaneous melanoma in the United States. Patients with nonmetastatic cutaneous melanoma newly diagnosed between 2000 and 2007 were identified from the Surveillance Epidemiology End Results-Medicare registry. Any imaging study performed within 90 days after diagnosis was considered a staging study. The study identified 25,643 patients, 3,116 (12.2 %) of whom underwent cross-sectional imaging: positron emission tomography (PET) (7.2 %), computed tomography (CT) (5.9 %), and magnetic resonance imaging (MRI) (0.6 %). From 2000 to 2007, the use of cross-sectional imaging increased from 8.7 to 16.1 % (p < 0.001), driven predominantly by increased usage of PET (4.2-12.1 %). Stratification by T and N classification showed that cross-sectional imaging was used for 8.6 % of T1, 14.3 % of T2, 18.6 % of T3, and 26.7 % of T4 tumors (p < 0.001) and for 33.3 % of node-positive patients versus 11.1 % of node-negative patients (p < 0.001). Factors predictive of cross-sectional imaging included T classification [odds ratio (OR) for T4 vs T1, 2.66; 95 % confidence interval (CI) 2.33-3.03], node positivity (OR 2.70; 95 % CI 2.36-3.10), more recent year of diagnosis (OR 2.05 for 2007 vs 2000; 95 % CI 1.74-2.42), atypical histology, and non-Caucasian race (OR 1.32; 95 % CI 1.02-1.73). The use of cross-sectional imaging for staging of early-stage cutaneous melanoma is increasing in the Medicare population. Better dissemination of guidelines and judicious use of imaging should be encouraged.
Sirirungsi, Wasna; Khamduang, Woottichai; Collins, Intira Jeannie; Pusamang, Artit; Leechanachai, Pranee; Chaivooth, Suchada; Ngo-Giang-Huong, Nicole; Samleerat, Tanawan
Early infant diagnosis of HIV is crucial for timely initiation of antiretroviral therapy (ART) in infected children who are at high risk of mortality. Early infant diagnosis with dried blood spot testing was provided by the National AIDS Programme in Thailand from 2007. We report ART initiation and vital status in children with HIV after 7 years of rollout in Thailand. Dried blood spot samples were collected from HIV-exposed children in hospitals in Thailand and mailed to the Faculty of Associated Medical Sciences, Chiang Mai University, where HIV DNA was assessed with real-time PCR to establish HIV infection. We linked data from children with an HIV infection to the National AIDS Programme database to ascertain ART and vital status. Between April 5, 2007, and Oct 1, 2014, 16 046 dried blood spot samples were sent from 8859 children in 364 hospitals in Thailand. Median age at first dried blood spot test was 2·1 (IQR 1·8-2·5) months. Of 7174 (81%) children with two or more samples, 223 (3%) were HIV positive (including five unconfirmed). Of 1685 (19%) children with one sample, 70 (4%) were unconfirmed positive. Of 293 (3%) children who were HIV positive, 220 (75%) registered for HIV care and 170 (58%) initiated ART. Median age at ART initiation decreased from 14·2 months (IQR 10·2-25·6) in 2007 to 6·1 months (4·2-9·2) in 2013, and the number of children initiating ART aged younger than 1 year increased from five (33%) of 15 children initiating ART in 2007 to ten (83%) of 12 initiating ART in 2013. 15 (9%) of 170 children who initiated ART died and 16 (32%) of 50 who had no ART record died. Early infant diagnosis with dried blood spot testing had high uptake in primary care settings. Further improvement of linkage to HIV care is needed to ensure timely treatment of all children with an HIV infection. None. Copyright © 2016 Elsevier Ltd. All rights reserved.
Lenne, X; Allenet, B; Laurent, P; Lebrun, T; Wemeau, J L
The aim of the study was to assess the economic consequences of the early screening and management for overt hypothyrodism in elderly women suffering from hypercholesterolaemia. A cost analysis was performed using screening decision tree followed by a Markov model, targeted on an hypothetical cohort of elderly women (i.e. > or = 55 years of age) suffering from hypercholesterolaemia. Two arms were compared, "no diagnosis", patients being treated by lipid lowering drugs in the long run, "diagnosis", patients being screened for thyroid disturbance and proposed adequate correction by hormone treatment. Relevant clinical data introduced into the model were obtained from published data and from experts. At the end of the initial diagnostic, patients could enter three different health states: euthyroidism, subclinical hypothyroidism or overt hypothyroidism. During 30 years, patients were assumed to be seen each year by a general practitioner for clinical examination and cholesterol dosage, plus, according to the health state evolution, TSH and T4 screening. In the baseline analysis, euthyroidian patients who had a inexplicable degradation of hypercholesterolaemia control were tested for TSH and, if abnormal, T4 serum; for subclinical hypothyroidian patients, TSH and T4 were measured every year. The direct costs taken into account were concerning medical supervision, drug treatment and biologic exams. Costs were analysed from the societal perspective and were expressed in 1998 French Francs (FF) with an accounting rate of 5% by year. A sensitivity analysis was also performed. The total cost at 30-year was equal to 25,006 F for "diagnosis" strategy, to 24,390 F for "no diagnosis" strategy. The incremental cost of the first strategy decreased according to the time horizon. It was 6.8% at 5-year and 2.5% at 30-year. Results were sensitive to variation in response rate of hypercholesterolaemic patients to hormone treatment of hypothyroidism (0.25 in base-case). The investment
Richman, Ilana; Asch, Steven M; Bendavid, Eran; Bhattacharya, Jay; Owens, Douglas K
Twenty-eight states have passed breast density notification laws, which require physicians to inform women of a finding of dense breasts on mammography. To evaluate changes in breast cancer stage at diagnosis after enactment of breast density notification legislation. Using a difference-in-differences analysis, we examined changes in stage at diagnosis among women with breast cancer in Connecticut, the first state to enact legislation, compared to changes among women in control states. We used data from the Surveillance, Epidemiology, and End Results Program (SEER) registry, 2005-2013. Women ages 40-74 with breast cancer. Breast density notification legislation, enacted in Connecticut in October of 2009. Breast cancer stage at diagnosis. Our study included 466,930 women, 25,592 of whom lived in Connecticut. Legislation was associated with a 1.38-percentage-point (95 % CI 0.12 to 2.63) increase in the proportion of women in Connecticut versus control states who had localized invasive cancer at the time of diagnosis, and a 1.12-percentage-point (95 % CI -2.21 to -0.08) decline in the proportion of women with ductal carcinoma in situ at diagnosis. Breast density notification legislation was not associated with a change in the proportion of women in Connecticut versus control states with regional-stage (-0.09 percentage points, 95 % CI -1.01 to 1.02) or metastatic disease (-0.24, 95 % CI -0.75 to 0.28). County-level analyses and analyses limited to women younger than 50 found no statistically significant associations. Single intervention state, limited follow-up, potential confounding from unobserved trends. Breast density notification legislation in Connecticut was associated with a small increase in the proportion of women diagnosed with localized invasive breast cancer in individual-level but not county-level analyses. Whether this finding reflects potentially beneficial early detection or potentially harmful overdiagnosis is not known. Legislation was not
Camacho, V; Estorch, M; Marquié, M; Domènech, A; Flotats, A; Fernández, A; Duch, J; Geraldo, L L; Deportos, J; Artigas, C; Lleó, A; Carrió, I
The importance of accurate and early diagnosis of dementia with Lewy bodies (DLB) lies in its pharmacological management. Delayed imaging of cardiac (123)I-MIBG scintigraphy allows differentiation between DLB and other neurodegenerative diseases with cognitive impairment. The aim of this study was to assess the utility of early imaging of cardiac (123)I-MIBG scintigraphy for differentiating DLB from others neurodegenerative disease with cognitive impairment. We assess retrospectively 106 patients (51 men, mean age 78 years) with cognitive impairment that underwent a cardiac (123)I-MIBG study. Planar images were acquired in anterior view of the thorax 15min (early) and 4h (delayed) after tracer administration. The heart-to-mediastinum ratios (HMR) at 15m (HMR15m) and at 4h (HMR4h) were obtained. After four years, 52 patients were diagnosed of DLB.HMR15m and HMR4h were significantly inferior in DLB respect to the others neurodegenerative diseases (1,27±0,15 vs 1,76±0,15,p<0,05) and (1,14±0,13 vs 1,68±0,19,p<0.01), respectively. The ROC analysis showed a HMR15m cut off point of 1.56 to differentiated DLB from the other dementias with a sensitivity and a specificity of 98%. Early imaging of cardiac (123)I-MIBG scintigraphy can help to differentiate DLB from other neurodegenerative diseases with cognitive impairment. Copyright © 2012 Elsevier España, S.L. y SEMNIM. All rights reserved.
Rahimi-Nedjat, Roman Kia; Al-Nawas, Bilal; Tuettenberg, Andrea; Sagheb, Keyvan; Grabbe, Stephan; Walter, Christian
The aim of this retrospective study was to investigate sentinel lymph node biopsy in patients with head and neck melanoma. Patients who underwent SLNB between 2010 and 2016 were comprised. Epidemiological, radiological, and surgical data were collected and compared to histological findings. Patients who underwent primary complete lymph node dissection were excluded. 74 patients underwent SLNB during this period. The most common tumor localizations were the cheek (20.4%) and ears (20.4%). Overall, 256 sentinel lymph nodes (SLN) were detected and removed, most frequently in Robbins-levels IIA and IIB as well as in the surrounding of the parotid gland. 12.3% of the SLN showed a microscopic or macroscopic metastasis. In preoperative imaging all lymph nodes with macroscopic metastasis were described as suspect but only 4 of 11 lymph nodes with microscopic metastases were described as such. SLNB is an especially good procedure for the diagnosis of microscopically metastases as disease status is an important diagnostic and prognostic factor in early-stage melanoma patients. However, due to the complex lymphatic system in head and neck melanoma, a short follow-up interval is necessary in order to prevent delayed diagnosis of a nodal recurrence due to a false-negative SLN. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Gündüz, K; Shields, C L; Shields, J A
Varix of the vortex vein ampulla is a condition that can cause diagnostic confusion with choroidal melanoma. A case series review was performed from the Ocular Oncology Service, Wills Eye Hospital. In all four cases, the patients were referred with the diagnosis of a small choroidal melanoma. The lesions were located in the nasal quadrant of the fundus near the equator. One patient had two lesions in the same quadrant. In all cases, the fundus lesion became more prominent when the eye gazed in the direction of the lesion and diminished in primary gaze. The mass measured up to 6.0 mm in base diameter and 2.5 mm in thickness in proper gaze. B-scan ultrasonography showed acoustic solidity and gaze-evoked dynamic enlargement of the lesion. Indocyanine green angiography demonstrated early pooling of dye and gaze-evoked fluctuation of the hyperfluorescence in the lesion. Color Doppler imaging, performed in one patient, showed a vascular lesion of venous origin that filled when the eye was placed in the direction of the lesion. Varix of the vortex vein is a condition that should be considered in the differential diagnosis of equatorial small choroidal melanoma. The dynamic nature of the lesion is characteristic and diagnostic.
Sato, Kaori; Saji, Tsutomu; Kaneko, Taku; Takahashi, Kei; Sugi, Kaoru
To report a case of unexpected pulmonary hypertensive crisis caused by endothelin release from melanoma cells after surgery for choroidal melanoma. A 56-year-old man suddenly developed dyspnea after resection of choroidal melanoma. Worsening hypoxia required intensive treatment, including percutaneous cardiopulmonary support, after which a series of tests were immediately performed. The tentative diagnosis was idiopathic pulmonary arterial hypertension. Previous studies noted a significant association between melanoma and endothelin (ET)-1. We hypothesized that a substantial amount of ET-1 had been released from malignant melanoma cells during resection, thus triggering the pulmonary hypertensive crisis in our patient. The patient fully recovered after intensive treatment and administration of the endothelin receptor antagonist bosentan. The success of bosentan treatment, along with the extremely high level of ET-1 on pathologic analysis, confirmed our hypothesis regarding the increase in plasma ET-1 level. Copyright © 2014 Elsevier Inc. All rights reserved.
Kataoka, Hiroyuki; Saito, Keita; Kato, Hisato; Masuda, Kazufumi
Early disease diagnosis is crucial for human healthcare and successful therapy. Since any changes in homeostatic balance can alter human emanations, the components of breath exhalations and skin emissions may be diagnostic biomarkers for various diseases and metabolic disorders. Since hundreds of endogenous and exogenous volatile organic compounds (VOCs) are released from the human body, analysis of these VOCs may be a noninvasive, painless, and easy diagnostic tool. Sampling and preconcentration by sorbent tubes/traps and solid-phase microextraction, in combination with GC or GC-MS, are usually used to analyze VOCs. In addition, GC-MS-olfactometry is useful for simultaneous analysis of odorants and odor quality. Direct MS techniques are also useful for the online real-time detection of VOCs. This review focuses on recent developments in sampling and analysis of volatile biomarkers in human odors and/or emanations, and discusses future use of VOC analysis.
Nigenda, Gustavo; Caballero, Marta; González-Robledo, Luz María
To identify social, cultural and health service barriers that prevent timely access to early detection of breast cancer in two regions: Mexico City Federal District and the state of Oaxaca. An exploratory cross-sectional qualitative study was carried out in 2008 among women under 25 years of age without pathology, with pathological diagnosis, their male partners and managers of several public and private institutions. Information was collected by focus groups and through interviews that were recorded and transcribed after having received informed consent. Initial exploration allowed the identification of access barriers in three main areas: a) the availability of information for the general population, b) training of first-contact general practitioners and gynecologists, and c) fears among couples and families. Barriers in the three levels identified are relevant as they reveal important deficiencies in the dissemination of information both to the general population and to health providers.
Villar, José R; González, Silvia; Sedano, Javier; Chira, Camelia; Trejo-Gabriel-Galan, Jose M
The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices.
Goto, Masami; Aoki, Shigeki; Abe, Osamu; Masumoto, Tomohiko; Watanabe, Yasushi; Satake, Yoshiroh; Nishida, Katsuji; Ino, Kenji; Yano, Keiichi; Iida, Kyohhito; Mima, Kazuo; Ohtomo, Kuni
In recent years, voxel-based morphometry (VBM) has become a popular tool for the early diagnosis of Alzheimer disease. The Voxel-Based Specific Regional Analysis System for Alzheimer's Disease (VSRAD), a VBM system that uses MRI, has been reported to be clinically useful. The able-bodied person database (DB) of VSRAD, which employs sagittal plane imaging, is not suitable for analysis by axial plane imaging. However, axial plane imaging is useful for avoiding motion artifacts from the eyeball. Therefore, we created an able-bodied person DB by axial plane imaging and examined its utility. We also analyzed groups of able-bodied persons and persons with dementia by axial plane imaging and reviewed the validity. After using the DB of axial plane imaging, the Z-score of the intrahippocampal region improved by 8 in 13 instances. In all brains, the Z-score improved by 13 in all instances.
Moorman, J. Randall; Delos, John B.; Flower, Abigail A.; Cao, Hanqing; Kovatchev, Boris P.; Richman, Joshua S.; Lake, Douglas E.
We have applied principles of statistical signal processing and non-linear dynamics to analyze heart rate time series from premature newborn infants in order to assist in the early diagnosis of sepsis, a common and potentially deadly bacterial infection of the bloodstream. We began with the observation of reduced variability and transient decelerations in heart rate interval time series for hours up to days prior to clinical signs of illness. We find that measurements of standard deviation, sample asymmetry and sample entropy are highly related to imminent clinical illness. We developed multivariable statistical predictive models, and an interface to display the real-time results to clinicians. Using this approach, we have observed numerous cases in which incipient neonatal sepsis was diagnosed and treated without any clinical illness at all. This review focuses on the mathematical and statistical time series approaches used to detect these abnormal heart rate characteristics and present predictive monitoring information to the clinician. PMID:22026974
Heeney, J L
Public awareness of the human health risks of zoonotic infections has grown in recent years. Currently, concern of H5N1 flu transmission from migratory bird populations has increased with foci of fatal human cases. This comes on the heels of other major zoonotic viral epidemics in the last decade. These include other acute emerging or re-emerging viral diseases such as severe acute respiratory syndrome (SARS), West-Nile virus, Ebola virus, monkeypox, as well as the more inapparent insidious slow viral and prion diseases. Virus infections with zoonotic potential can become serious killers once they are able to establish the necessary adaptations for efficient human-to-human transmission under circumstances sufficient to reach epidemic proportions. The monitoring and early diagnosis of these potential risks are overlapping frontiers of human and veterinary medicine. Here, current viral zoonotics and evolving threats are reviewed.
Chen, Wen; Tang, Ming
The abnormal temperature rise is the precursor of the defective composite insulator in power transmission line. However no consolidated techniques or methodologies can on line monitor its internal temperature now. Thus a new method using embedding fiber Bragg grating (FBG) in fiber reinforced polymer (FRP) rod is adopted to monitor its internal temperature. To correctly demodulate the internal temperature of FRP rod from the Bragg wavelength shift of FBG, the conversion coefficient between them is deduced theoretically based on comprehensive investigation on the thermal stresses of the metal-composite joint, as well as its material and structural properties. Theoretical model shows that the conversion coefficients of FBG embedded in different positions will be different because of non-uniform thermal stress distribution, which is verified by an experiment. This work lays the theoretical foundation of monitoring the internal temperature of composite insulator with embedding FBG, which is of great importance to its health structural monitoring, especially early diagnosis.
Rachid, Bahiri; El Zorkany, Bassel; Youseif, Ehab; Tikly, Mohammed
Ankylosing spondylitis (AS) is the prototype for spondyloarthritis primarily affecting young men. Geographic and ethnic variations exist in the prevalence and severity of AS and relate to the wide disparity in the frequency of human leukocyte antigen (HLA)-B27, a major genetic risk factor. The strength of the disease association with HLA-B27 is lower in most Arab populations (25-75 %) than in Western European populations (>90 %), and there is no association in sub-Saharan Africa, where the prevalence of HLA-B27 is <1 %. Other epidemiologic differences between European and African populations are the apparent later age at presentation in sub-Saharan Africa, and the high rate of spondyloarthropathies associated with human immunodeficiency virus infection. Diagnosis of AS is often delayed 8-10 years; potential reasons for the delay in Africa and the Middle East include low awareness among physicians and patients, the requirement for radiographic evidence of sacroiliitis for diagnosis, and limited access to magnetic resonance imaging in some countries. Treatment should be initiated early to prevent or reduce skeletal deformity and physical disability. Nonsteroidal anti-inflammatory drugs are effective first-line treatment and anti-tumor necrosis factor-α drugs are indicated for patients who have an inadequate response to first-line therapy. In Africa and the Middle East, such treatments may be precluded either by cost or contraindicated because of the high prevalence of latent tuberculosis infection. Research is sorely needed to develop cost-effective tools to diagnose AS early as well as effective, inexpensive, and safe treatments for these developing regions.
Gallego-Jutglà, Esteve; Solé-Casals, Jordi; Vialatte, François-Benoît; Elgendi, Mohamed; Cichocki, Andrzej; Dauwels, Justin
Objective. Recently, significant advances have been made in the early diagnosis of Alzheimer’s disease (AD) from electroencephalography (EEG). However, choosing suitable measures is a challenging task. Among other measures, frequency relative power (RP) and loss of complexity have been used with promising results. In the present study we investigate the early diagnosis of AD using synchrony measures and frequency RP on EEG signals, examining the changes found in different frequency ranges. Approach. We first explore the use of a single feature for computing the classification rate (CR), looking for the best frequency range. Then, we present a multiple feature classification system that outperforms all previous results using a feature selection strategy. These two approaches are tested in two different databases, one containing mild cognitive impairment (MCI) and healthy subjects (patients age: 71.9 ± 10.2, healthy subjects age: 71.7 ± 8.3), and the other containing Mild AD and healthy subjects (patients age: 77.6 ± 10.0 healthy subjects age: 69.4 ± 11.5). Main results. Using a single feature to compute CRs we achieve a performance of 78.33% for the MCI data set and of 97.56% for Mild AD. Results are clearly improved using the multiple feature classification, where a CR of 95% is found for the MCI data set using 11 features, and 100% for the Mild AD data set using four features. Significance. The new features selection method described in this work may be a reliable tool that could help to design a realistic system that does not require prior knowledge of a patient's status. With that aim, we explore the standardization of features for MCI and Mild AD data sets with promising results.
Cheng, Yu-Hsiang; Lin, Chih-Feng; Shih, Ting-Fang; Sun, Chi-Kuang
Oral cancer is one of the most frequently diagnosed human cancers and leading causes of cancer death all over the world, but the prognosis and overall survival rate are still poor because of delay in diagnosis and lack of early intervention. The failure of early diagnosis is due to insufficiency of proper diagnostic and screening tools and most patients are reluctant to undergo biopsy. Optical virtual biopsy techniques, for imaging cells and tissues at microscopic details capable of differentiating benign from malignant lesions non-invasively, are thus highly desirable. A novel multi-harmonic generation microscope, excited by a 1260 nm Cr:forsterite laser, with second and third harmonic signals demonstrating collagen fiber distribution and cell morphology in a sub-micron resolution, was developed for clinical use. To achieve invivo observation inside the human oral cavity, a small objective probe with a suction capability was carefully designed for patients' comfort and stability. By remotely changing its focus point, the same objective can image the mucosa surface with a low magnification, illuminated by side light-emitting diodes, with a charge-coupled device (CCD) for site location selection before the harmonic generation biopsy was applied. Furthermore, the slow galvanometer mirror and the fast resonant mirror provide a 30 fps frame rate for high-speed real-time observation and the z-motor of this system is triggered at the same rate to provide fast 3D scanning, again ensuring patients' comfort. Focusing on the special cytological and morphological changes of the oral epithelial cells, our preliminary result disclosed excellent consistency with traditional histopathology studies.
Ben-Rebeh, Imen; Grati, Mhamed; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber
Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient's early childhood is of utmost importance, allowing better educational and therapeutic management.
Ben-Rebeh, Imen; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber
Purpose Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. Methods In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Results Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. Conclusions We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient’s early childhood is of utmost importance, allowing better educational and therapeutic management. PMID:27440999
Chaves, R.; Górriz, J. M.; Ramírez, J.; Illán, I. A.; Salas-Gonzalez, D.; Gómez-Río, M.
In this paper, a novel technique based on association rules (ARs) is presented in order to find relations among activated brain areas in single photon emission computed tomography (SPECT) imaging. In this sense, the aim of this work is to discover associations among attributes which characterize the perfusion patterns of normal subjects and to make use of them for the early diagnosis of Alzheimer's disease (AD). Firstly, voxel-as-feature-based activation estimation methods are used to find the tridimensional activated brain regions of interest (ROIs) for each patient. These ROIs serve as input to secondly mine ARs with a minimum support and confidence among activation blocks by using a set of controls. In this context, support and confidence measures are related to the proportion of functional areas which are singularly and mutually activated across the brain. Finally, we perform image classification by comparing the number of ARs verified by each subject under test to a given threshold that depends on the number of previously mined rules. Several classification experiments were carried out in order to evaluate the proposed methods using a SPECT database that consists of 41 controls (NOR) and 56 AD patients labeled by trained physicians. The proposed methods were validated by means of the leave-one-out cross validation strategy, yielding up to 94.87% classification accuracy, thus outperforming recent developed methods for computer aided diagnosis of AD.
Urrego, Juliana; Ko, Albert I.; da Silva Santos Carbone, Andrea; Paião, Dayse Sanchez Guimarães; Sgarbi, Renata Viebrantz Enne; Yeckel, Catherine W.; Andrews, Jason R.; Croda, Julio
Prisoners have among the highest incidence of tuberculosis (TB) globally. However, the contribution of the prison environment on transmission is not well understood and structural characteristics have received little attention as effective epidemiological interventions in TB control. We evaluated architectural characteristics and estimated ventilation rates in 141 cells in three prisons in central west Brazil using steady-state exhaled carbon dioxide (CO2) levels. We used a modified Wells–Riley equation to estimate the probability of infection for inmates sharing a cell with an infectious case and projected the impact of interventions, including early diagnosis and improved ventilation. Overall, prison cells were densely populated (mean 2.1 m2 per occupant) and poorly ventilated, with only three cells meeting World Health Organization (WHO) standards for per-person ventilation (60 L/s) applied in infection control settings. In the absence of interventions, projected mean risk of infection was 78.0% during a 6-month period. Decreasing time-to-diagnosis by 25% reduced transmission risk by 8.3%. Improving ventilation to WHO standards decreased transmission by 38.2%, whereas optimizing cross-ventilation reduced transmission by 64.4%. Prison environments promote high infection risk over short-time intervals. In this context, enhanced diagnostics have a limited impact on reducing transmission. Improving natural ventilation may be required to effectively control TB in prisons. PMID:26195459
Urrego, Juliana; Ko, Albert I; da Silva Santos Carbone, Andrea; Paião, Dayse Sanchez Guimarães; Sgarbi, Renata Viebrantz Enne; Yeckel, Catherine W; Andrews, Jason R; Croda, Julio
Prisoners have among the highest incidence of tuberculosis (TB) globally. However, the contribution of the prison environment on transmission is not well understood and structural characteristics have received little attention as effective epidemiological interventions in TB control. We evaluated architectural characteristics and estimated ventilation rates in 141 cells in three prisons in central west Brazil using steady-state exhaled carbon dioxide (CO2) levels. We used a modified Wells-Riley equation to estimate the probability of infection for inmates sharing a cell with an infectious case and projected the impact of interventions, including early diagnosis and improved ventilation. Overall, prison cells were densely populated (mean 2.1 m(2) per occupant) and poorly ventilated, with only three cells meeting World Health Organization (WHO) standards for per-person ventilation (60 L/s) applied in infection control settings. In the absence of interventions, projected mean risk of infection was 78.0% during a 6-month period. Decreasing time-to-diagnosis by 25% reduced transmission risk by 8.3%. Improving ventilation to WHO standards decreased transmission by 38.2%, whereas optimizing cross-ventilation reduced transmission by 64.4%. Prison environments promote high infection risk over short-time intervals. In this context, enhanced diagnostics have a limited impact on reducing transmission. Improving natural ventilation may be required to effectively control TB in prisons. © The American Society of Tropical Medicine and Hygiene.