Real-life practice of reflectance confocal microscopy in France: A prospective multicenter study.

BACKGROUND: Studies demonstrating the potential utility of reflectance confocal microscopy (RCM) have been performed under experimental conditions. OBJECTIVE: To provide an overview of RCM practice in real-life. METHODS: A multicenter, prospective study carried out in 10 university dermatology departments in France. RESULTS: Overall, 410 patients were enrolled. One-half of the patients (48%) were referred by private practice dermatologists. They were referred for diagnosis (84.9%) or presurgical mapping (13%). For diagnosis, the lesions were located on the face (62%), arms and legs (14.9%), and trunk (13.6%), and presurgical mapping was almost exclusively on the face (90.9%). Among those referred for diagnosis, the main indication was suspicion of a skin tumor (92.8%). Of these, 50.6% were spared biopsies after RCM. When RCM indicated surgery, histology revealed malignant lesions in 72.7% of cases. The correlation between RCM and histopathology was high, with a correlation rate of 82.76% and a kappa coefficient of 0.73 (0.63; 0.82). LIMITATIONS: This study was performed in the settings of French tertiary referral hospitals. CONCLUSION: This study shows that in real-life RCM can be integrated into the workflow of a public private network, which enables a less invasive diagnostic procedure for patients.

Optical imaging guided- 'precision' biopsy of skin tumors: a novel approach for targeted sampling and histopathologic correlation.

Dermoscopy and reflectance confocal microscopy (RCM) are two noninvasive, optical imaging tools used to facilitate clinical diagnosis. A biopsy technique that produces exact correlation with optical imaging features is not previously reported. To evaluate the applications of a novel feature-focused 'precision biopsy' technique that correlates clinical-dermoscopy-RCM findings with histopathology. This was a prospective case-series performed during August 2017 and June 2019 at a tertiary care cancer. We included consecutive patients requiring a precise dermoscopy-RCM-histopathologic correlation. We performed prebiopsy dermoscopy and both wide probe and handheld RCM of suspicious lesions. Features of interest were isolated with the aid of paper rings and a 2 mm punch biopsy was performed in the dermoscopy- or RCM-highlighted area. Tissue was processed either en face or with vertical sections. One-to-one correlation with histopathology was obtained. Twenty-three patients with 24 lesions were included in the study. The mean age was 64.6 years (range 22-91 years); there were 16 (69.6%) males, 14 (58.3%) lesions biopsied were on head and neck region. We achieved tissue-conservation diagnosis in 100% (24/24), 13 (54.2%) were clinically equivocal lesions, six (25%) were selected for 'feature correlation' of structures on dermoscopy or RCM, and five (20.8%) for 'correlation of new/unknown' RCM features seen on follow-up. The precision biopsy technique described herein is a novel method that facilitates direct histopathological correlation of dermoscopy and RCM features. With the aids of optical imaging devices, accurate diagnosis may be achieved by minimally invasive tissue extraction.

In vivo imaging characterization of basal cell carcinoma and cutaneous response to high-dose ionizing radiation therapy: A prospective study of reflectance confocal microscopy, dermoscopy, and ultrasonography.

BACKGROUND: Radiation therapy (RT) is a treatment option for select skin cancers. The histologic effects of RT on normal skin or skin cancers are not well characterized. Dermoscopy, high-frequency ultrasonography (HFUS), and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that may help characterize RT response. OBJECTIVES: To describe changes in the tumor and surrounding skin of patients with basal cell carcinoma (BCC) treated with RT. METHODS: The study was conducted between 2014 and 2018. Patients with biopsy-proven BCCs were treated with 42 Gy in 6 fractions using a commercially available brachytherapy device. Dermoscopy, HFUS, and RCM were performed before treatment and at 6 weeks, 3 months, and 12 months after RT. RESULTS: A total of 137 imaging assessments (RCM + dermoscopy + HFUS) were performed in 12 patients. BCC-specific features were present in 81.8%, 91%, and 17% of patients imaged with dermoscopy, RCM, and HFUS at baseline, respectively, before treatment. After treatment, the resolution of these features was noted in 33.4%, 91.7%, and 100% of patients imaged with the respective modalities. No recurrences were seen after a mean of 31.7 months of follow-up. LIMITATIONS: Small sample size and no histopathologic correlation. CONCLUSION: Dermoscopy and HFUS were not as reliable as RCM at characterizing BCC RT response.

Dark pigmented lesions: Diagnostic accuracy of dermoscopy and reflectance confocal microscopy in a tertiary referral center for skin cancer diagnosis.

BACKGROUND: There is lack of studies on the diagnostic accuracy of dermoscopy and reflectance confocal microscopy (RCM) for dark pigmented lesions. OBJECTIVE: To assess the diagnostic accuracy of dermoscopy plus confocal microscopy for melanoma diagnosis of dark pigmented lesions in real life. METHODS: Prospective analysis of difficult dark lesions with clinical/dermoscopic suspicion of melanoma referred for RCM for further analysis. The outcome could be excision or dermoscopic digital follow-up. RESULTS: We included 370 clinically dark lesions from 350 patients (median age, 45 y). Because of the clinical/dermoscopic/RCM approach, we saved 129 of 213 unnecessary biopsies (specificity of 60.6%), with a sensitivity of 98.1% (154/157). The number needed to excise with the addition of RCM was 1.5 for melanoma diagnosis. LIMITATIONS: Single institution based; Italian population only. CONCLUSIONS: This study showed that RCM coupled with dermoscopy increases the specificity for diagnosing melanoma, and it helps correctly identify benign lesions. Our findings provide the basis for subsequent prospective studies on melanocytic neoplasms belonging to patients in different countries.

Atypical cells on reflectance confocal microscopy may not represent melanoma: A case of axillary pigmented extramammary Paget disease.

Pigmented extramammary Paget disease (PEMPD) is a rare intraepithelial carcinoma which can clinically resemble other pigmented neoplasms. Similarities to melanoma on dermoscopy, histopathology, and reflectance confocal microscopy (RCM) increase the risk of misdiagnosis and, consequently, mismanagement. Here, we describe a case of a 67-year-old African American woman with a large, pigmented axillary patch that exhibited features of melanoma on RCM, guiding the clinician to perform an excisional biopsy. While traditional histopathology resembled melanoma, immunohistochemistry staining was performed and revealed PEMPD. We highlight an uncommon clinical presentation of PEMPD disease and identify morphologic mimickers of melanoma on RCM-as well as differentiating features.

Probe-based confocal laser endomicroscopy versus biopsies in the diagnostics of oesophageal and gastric lesions: A prospective, pathologist-blinded study.

BACKGROUND AND AIM: Probe-based confocal laser endomicroscopy (pCLE) provides real-time microscopic visualisation. Our aim was to compare the diagnostic accuracy of pCLE with standard biopsies in patients with visible oesophageal or gastric lesions. METHODS: This was a single-centre, prospective, pathologist-blinded study. Patients underwent high-resolution endoscopy, and lesions were examined by pCLE followed by standard biopsies. A definitive diagnosis was determined from resection specimen. Main outcomes were overall diagnostic accuracy, sensitivity, specificity and positive and negative predictive values. RESULTS: We examined 74 lesions in 67 patients. Definitive diagnoses revealed 34 malignant and 40 non-malignant lesions. pCLE diagnosis was correct in 89.2% (66/74), while diagnosis based on biopsy was correct in 85% (57/67; p = 0.6). The overall diagnostic accuracy of biopsies was 85% (76-94%) and that of pCLE was 89% (79-96%). pCLE correctly diagnosed malignant lesions, comprising oesophageal adenocarcinoma, oesophageal squamous-cell cancer or gastric adenocarcinoma, in 88.2% (30/34) of cases, while biopsy was correctly diagnosed in 75.9% (22/29; p = 0.3). Sensitivity and specificity to diagnose a malignant lesion were 75.9% (95% confidence interval (CI) 56-89%) and 100% (95% CI 90-100%) for biopsies and 88.2% (95% CI 72-97%) and 92% (95% CI 79-98%) for pCLE. No differences between biopsies and pCLE were found with regard to sensitivity, specificity to diagnose dysplastic and benign lesions (p > 0.2). CONCLUSION: pCLE provides satisfactory diagnostic accuracy comparable with standard biopsies in patients with oesophageal or gastric lesions. ClinicalTrials.gov identifier: NCT0292049).

Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions.

BACKGROUND AND AIM: The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs. METHODS: Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case. RESULTS: The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p < 0.001). nCLE significantly increased the interobserver agreement of 0.28 (p < 0.0001), from 0.36 (CI 95% 0.33-0.49) to 0.64 (CI 95% 0.61-0.67). nCLE improved the rates of full agreement among the five experts of 24% (p < 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76). CONCLUSION: The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133.

A study on confocal endomicroscopy in comparison with histopathology for polypoidal lesions of the gastrointestinal tract: A prospective single-centre experience.

BACKGROUND: Confocal laser endomicroscopy (CLE) has a potential to make optical diagnosis of neoplastic polypoidal lesions and may replace traditional histology in the proposed "diagnose and discard approach". The present study was planned to assess the accuracy of probe-based CLE in predicting histology of polypoidal lesions of gastrointestinal (GI) tract in vivo before their removal. METHODS: In this prospective single-centre study, patients with upper and/or lower GI polypoidal lesions were enrolled. After detection of polypoidal lesions with white light endoscopy, probe-based CLE examination was performed. Real-time and offline presumptive CLE diagnosis of polypoidal lesions was made as per Miami classification and was compared with histopathology as the gold standard. RESULTS: A total of 50 GI polyps from 50 patients (28 males) were assessed. The mean (±SD) size of polyps was 13.7 (± 8.5) mm. Most polyps were located at the cecum (24.0%) or stomach (24.0%). On histological examination, hyperplastic and adenomatous polyps, adenocarcinoma, and lipoma were seen in 54%, 26%, 18% and 2% patients, respectively. On comparison of real-time CLE examination with histopathology, 40 (83.3%) and 8 patients (16.7%) had concordant and discordant results, respectively. Two polyps were inconclusively diagnosed on CLE. On offline examination, concordance with histopathology was observed in 85.4% (n = 41) of polyps, which was marginally better than online examination, though the difference was not statistically significant (p = 0.45). On comparing the real-time and offline findings of CLE, concordance was found in 91.7% of the cases. Accuracy, sensitivity, specificity, positive and negative predictive values on real-time evaluation were 83.3%, 87.5%, 79.1%, 80.7%, and 86.3%, respectively. CONCLUSION: CLE is a useful tool for prediction of histology to assess the polypoidal lesions of the GI tract, and it may avoid polypectomy at least in some patients.

Probe-based confocal laser endomicroscopy for diagnosis of nasopharyngeal carcinoma in vivo.

OBJECTIVES/HYPOTHESIS: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique allowing real-time evaluation of the histological features of tissues in vivo at the cellular level. This study aimed to evaluate the feasibility of using pCLE in the diagnosis of nasopharyngeal carcinoma (NPC). STUDY DESIGN: Feasibility study. METHODS: In this study, the pCLE images of the lesions, as well as the surrounding or contralateral normal mucosa of the lesions, were acquired in vivo from each patient after intravenous injecting of 2.5 mL fluorescein. Biopsy specimens were collected at the imaged sites followed by a histopathological diagnosis by the pathologists, which was used as the gold standard. The pCLE images were compared to histopathological diagnosis of visualized sites by using sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). RESULTS: Diagnoses based on pCLE images correlated well with the gold standard diagnoses based on tissue histology. The overall sensitivity, specificity, PPV, and NPV for diagnosis of carcinoma versus nondysplasia were 93.8% (67.7%-99.7%), 90.5% (68.2%-98.3%), 88.2% (62.3%-97.9%), and 95.0% (73.1%-99.7%), respectively, and the four indices for pCLE diagnosis of dysplasia versus nondysplasia were 60.0% (17.0%-92.7%), 80.9% (57.4%-93.7%), 42.9% (11.8%-79.8%), and 89.5% (65.5%-98.2%), respectively. The overall sensitivity for diagnosis of carcinoma versus dysplasia was 93.8% (67.7%-99.7%), specificity was 40% (7.3%-83.0%), PPV was 83.3% (57.7%-95.6%), and the NPV was 66.7% (12.5%-98.2%). CONCLUSIONS: CLE is a suitable and valid method for otolaryngologists to diagnose of NPC in vivo. LEVEL OF EVIDENCE: NA Laryngoscope, 129:897-902, 2019.

Endocytoscopic classification can be predictive for relapse in ulcerative colitis.

The present study was conducted to explore the association of endocytoscopy (EC) classification with microscopic inflammatory features of ulcerative colitis (UC) and disease relapse.EC was performed for mild-to-moderate UC 32 cases from January 2010 to August 2016. EC appearance was stratified into 4 categories: EC-A, regular arrangement of round to oval pits; EC-B, irregular arrangement with/without enlarged spaces between regular pits; EC-C, deformed pits with distorted crypt lumen which are unordered in arrangement but not disrupted; and EC-D, disruptive or disappeared pits. We evaluated the association of EC classification with Mayo endoscopic subscores (MES) and the clinically active state. Microscopic features including the severity in mucosal inflammatory infiltrates the presence of crypt abscess and goblet cell depletion were assessed by an experienced pathologist who was blinded to clinical and endoscopic information. Clinical follow-up was provided for treating 22 UC patients more than 60 months after EC.There were 15 cases in EC-A, 8 in EC-B, 5 in EC-C, and 4 in EC-D. Interobserver agreement was excellent with κ value of 0.77. There were 13 patients in active disease stage, while 19 in remission. Each EC-A case was in clinically remission stage, while all the EC-C and EC-D cases were in the active stage. There were 4 and 4 EC-B cases in remission and active stage, respectively. The EC-A group consisted of 11 MES0 and 4 MES1 cases, whereas the EC-B group consisted of 2 MES0 and 6 MES1 cases. There were no cases of MES0 in the EC-C and -D groups. The EC stratification was significantly associated with pathognomonic microscopic features for UC. There were significant differences in the remission rate among the EC groups. None had relapse in the EC-A group during the follow-up period.EC stratification could be predictive for relapse in UC. Moreover, EC is reliable to assess UC specific microscopic features.

Síndrome iridocorneoendotelial: variedad Chandler / Iridocorneal endothelial syndrome in Chandler variety

En el síndrome iridocorneoendotelial se unifican diferentes variaciones clínicas de una misma entidad. El denominador común de todas ellas es una peculiar anormalidad de las células endoteliales, alteraciones del iris y el desarrollo de glaucoma, generalmente unilateral y más común en mujeres. Se presenta un caso clínico de la variedad Chandler, quien acudió a la consulta de catarata, con este diagnóstico en el ojo derecho. Se realiza cirugía de catarata en ambos ojos con excelentes resultados y control de la presión intraocular(AU)

Iridocorneal endothelial syndrome comprises different clinical variations of the same disease. The common features of all them are peculiar anomaly of the endothelial cells, alterations of the iris and the onset of glaucoma, generally unilateral and more common in women. A clinical case of the Chandler variety is presented, which is a woman with cataract, and iridocorneal endothelial syndrome diagnosis on the right eye. Cataract surgery was performed in both eyes with excellent results and control of the intraocular pressure(AU)

Influência de substâncias irrigadoras em gel sobre o biofilme microbiano / Influence of gel irrigant agents in oral biofilm

Objetivo: o objetivo do presente estudo foi avaliar a ação antimicrobiana do hipoclorito de sódio a 1%, da clorexidina a 2% e do EDTA a 24% ­ todos na forma de gel ­, sobre o biofilme oral. Métodos: blocos de dentina bovina estéreis foram inseridos em um dispositivo intrabucal, o qual foi utilizado por um voluntário durante 3 dias. Após a formação do biofilme, os blocos foram imersos em 100 µl das diferentes substâncias avaliadas, durante 5 minutos. Após o tratamento, as amostras foram coradas com 50 µl de uma solução com iodeto de propídio e SYTO 9, e avaliadas em um microscópio confocal imediatamente após a remoção do agente antimicrobiano, gerando um total de 50 imagens por grupo. Os dados foram analisados por meio dos testes de Kruskal-Wallis e Dunn (α = 0,05). Resultados: diferenças estatísticas entre os grupos experimentais e controle foram observadas. O hipoclorito de sódio a 1% foi mais eficaz do que as outras substâncias avaliadas (p < 0,05). Ainda, a clorexidina a 2% reduziu a porcentagem de células vivas de forma mais significativa, comparada ao EDTA (p < 0,05). Conclusões: os agentes irrigantes utilizados nesse estudo não apresentaram capacidade de dissolução do biofilme formado in situ. No entanto, o hipoclorito de sódio apresentou melhores resultados, quanto comparado à clorexidina e ao EDTA.

Combined in vivo reflectance confocal microscopy and digital dermoscopy for follow up of patients at high risk of malignant melanoma: A prospective case series study.

Digital dermoscopy (DD) follow up is a useful strategy for monitoring patients at high risk of melanoma. Reflectance confocal microscopy (RCM) is a valuable second-level examination after dermoscopy for the evaluation of difficult to diagnose lesions. The aim of this study was to assess the value of RCM in routine DD monitoring of patients at high risk of melanoma. In this prospective study, performed over 22 months, changing melanocytic lesions were detected by DD and excised. RCM imaging was performed before surgical excision of all the lesions, and histopathology used as the gold standard diagnostic test. Eighty-seven lesions, including 11 thin melanomas, were studied. Dermoscopic evaluation at follow up revealed a significant association between melanoma and asymmetry in two axes (P = 0.035). Enlargement and other changes in structure or color did not significantly differ between nevi and melanomas. Widespread pagetoid cells, non-edged papillae, irregular and dishomogeneous junctional clusters, and sheet-like structures were significantly associated with malignancy (P < 0.001). RCM allowed accurate diagnosis of melanoma in 10 of 11 cases (90.9%). The remaining case was classified as a dysplastic nevus. Forty-six lesions (52.8%) in which RCM revealed no atypia were deemed unnecessarily removed. This study was limited by sample size. In conclusion, combined DD and RCM facilitates the recognition of thin malignant melanomas and reduces unnecessary excisions.

Implementation of fluorescence confocal mosaicking microscopy by "early adopter" Mohs surgeons and dermatologists: recent progress.

Confocal mosaicking microscopy (CMM) enables rapid imaging of large areas of fresh tissue ex vivo without the processing that is necessary for conventional histology. When performed in fluorescence mode using acridine orange (nuclear specific dye), it enhances nuclei-to-dermis contrast that enables detection of all types of basal cell carcinomas (BCCs), including micronodular and thin strands of infiltrative types. So far, this technique has been mostly validated in research settings for the detection of residual BCC tumor margins with high sensitivity of 89% to 96% and specificity of 99% to 89%. Recently, CMM has advanced to implementation and testing in clinical settings by "early adopter" Mohs surgeons, as an adjunct to frozen section during Mohs surgery. We summarize the development of CMM guided imaging of ex vivo skin tissues from bench to bedside. We also present its current state of application in routine clinical workflow not only for the assessment of residual BCC margins in the Mohs surgical setting but also for some melanocytic lesions and other skin conditions in clinical dermatology settings. Last, we also discuss the potential limitations of this technology as well as future developments. As this technology advances further, it may serve as an adjunct to standard histology and enable rapid surgical pathology of skin cancers at the bedside.

Bimolecular Fluorescence Complementation (BiFC) Analysis of Protein-Protein Interactions and Assessment of Subcellular Localization in Live Cells.

Bimolecular fluorescence complementation (BiFC) is a fluorescence imaging technique used to visualize protein-protein interactions (PPIs) in live cells and animals. One unique application of BiFC is to reveal subcellular localization of PPIs. The superior signal-to-noise ratio of BiFC in comparison with fluorescence resonance energy transfer or bioluminescence resonance energy transfer enables its wide applications. Here, we describe how confocal microscopy can be used to detect and quantify PPIs and their subcellular localization. We use basic leucine zipper transcription factor proteins as an example to provide a step-by-step BiFC protocol using a Nikon A1 confocal microscope and NIS-Elements imaging software. The protocol given below can be readily adapted for use with other confocal microscopes or imaging software.

Prospective evaluation of the utility of intraoperative confocal laser endomicroscopy in patients with brain neoplasms using fluorescein sodium: experience with 74 cases.

OBJECTIVE: This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors. METHODS: CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging-matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard. RESULTS: CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3-73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas. CONCLUSIONS: CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.

Efectos del tratamiento cubano para la retinosis pigmentaria sobre vasos coroideos / Effects of the Cuban treatment for retinitis pigmentosa on the choroidal vessels

Objetivo: describir los efectos sobre los vasos coroideos generados por la primera aplicación del tratamiento multiterapéutico cubano en pacientes con retinosis pigmentaria. Métodos: se realizó una investigación descriptiva longitudinal prospectiva, donde se seleccionaron 32 pacientes con retinosis pigmentaria, a quienes se les aplicó el tratamiento multiterapéutico cubano para esta enfermedad. Se utilizó un video angiógrafo de Heidelberg tipo 2 para realizar oftalmoscopia confocal por barrido láser infrarrojo, para adquirir y procesar imágenes de la capa media de vasos coroideos antes del tratamiento, 15 días y un año después de realizar este. El análisis de los resultados se realizó mediante Statistica 6.0 y SPSS 15.0 sobre Windows. Resultados: se observaron aumentos significativos de los diámetros vasculares en los cuadrantes temporales inferiores. En los temporales superiores hubo disminución no significativa; en los nasales inferiores se observaron aumentos significativos, y en los nasales superiores disminución significativa. Conclusión: después de aplicar el tratamiento multiterapéutico cubano para la retinosis pigmentaria, aumentan de forma duradera los diámetros de los vasos coroideos de la capa media solamente en el cuadrante temporal inferior(AU)

Objective: to describe the effects on the choroidal vessels after the first application of the Cuban multi-therapeutic treatment for patients with retinitis pigmentosa. Methods: a prospective, longitudinal and descriptive study of 32 patients with retinitis pigmentosa, who had undergone the Cuban multi-therapeutic treatment for this disease. There was used Heidelberg Retinal Angiograph- 2 to perform infrared laser scanning confocal ophthalmoscopy in order to take and to process images from the medial layer of the choroidal vessels before, 15 days, and one year after treatment. The results were analyzed with Statistica 6.0 and SPSS 15.0 on Windows. Results: significant increases in vascular diameters of the lower temporal quadrants were observed whereas non-significant decrease occurred in the upper temporal quadrants. Additionally, the choroidal vascular diameters increased significantly in the lower nasal quadrants and decreased in a significant way in the upper nasal ones. Conclusions: the Cuban multi-therapeutic treatment for retinitis pigmentosa increases the diameter of choroidal vascular vessels in a permanent way just in the lower temporal quadrant(AU)

[Clinical utility of reflectance confocal microscopy for the non-invasive diagnosis of lentigo maligna melanoma].

BACKGROUND: Lentigo maligna melanoma (LMM), a melanoma subtype that arises on sun-damaged facial skin, is difficult to diagnose clinically. Patients and physicians are reluctant to perform unnecessary facial biopsies. Reflectance confocal microscopy (RCM) is a novel technique for non-invasive skin imaging at cellular-level resolution. RCM increases the accuracy of melanoma diagnosis. AIMS: To describe the diagnostic utility of RCM in cases of clinically and dermatoscopically equivocal pigmented skin lesions suspicious for LMM. METHODS: This is a retrospective case series derived from the population of patients undergoing periodic skin cancer screening at a tertiary hospital clinic that specializes in skin cancer diagnosis. All patients consented to RCM imaging as an ancillary test prior to the decision on performing a biopsy in the facial lesion. RESULTS: We report on four patients who presented clinically and dermatoscopically equivocal pigmented skin lesions in the head and neck region, with differential diagnosis of LMM. Furthermore, in two patients, a prior incisional biopsy indicated a benign diagnosis upon histopathological analysis. In all cases, RCM examination showed specific criteria for LMM. The RCM diagnosis of LMM allowed direct referral for excisional surgery in three patients. In another patient, RCM findings guided incisional biopsy-site selection to a focus that revealed histopathology clear-cut criteria for LMM. CONCLUSIONS: RCM is a very useful adjunct to the non-invasive diagnosis of LMM.

Analysis of interobserver variability for endomicroscopy of the gastrointestinal tract.

BACKGROUND: Endomicroscopy allows in vivo microscopic investigation of enteral mucosa during endoscopic examinations. The aim of this study was to determine interobserver variability in the evaluation of endomicroscopic pictures of several organs by groups of investigators composed of confocal experts, pathologists and students. METHODS: Twenty-five selected representative endomicroscopic pictures of the colon, stomach and oesophagus (total number, 75) were evaluated based on tissue, inflammatory and neoplastic changes (secondary endpoints). The endomicroscopic presence of neoplastic features was the primary endpoint and correlated with the final histological diagnosis. RESULTS: The kappa values for experts examining colon, stomach, and oesophagus pictures were 0.80, 0.91, and 0.488, respectively; for students 0.74, 0.684, and 0.527 and for pathologists 0.749, 0.633, and 0.346, respectively. Neoplasia was accurately diagnosed in 67-97% of patients with no significant differences between the 3 groups. Tissue differentiation was determined best by pathologists, whereas the degree of inflammation was better diagnosed by experts and students. In all 3 groups the diagnosis of oesophageal diseases was the most difficult. CONCLUSIONS: Endomicroscopic images can be interpreted with high concordance. In our study, the diagnostic reliability was not different between students, endomicroscopic experts, and pathologists. Thus, endomicroscopy could be an additional and reliable imaging modality for diagnosing mucosal neoplasia of the gut.

Interobserver agreement of confocal laser endomicroscopy for bladder cancer.

BACKGROUND AND PURPOSE: Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer. METHODS: Experienced CLE urologists (n=2), novice CLE urologists (n=6), pathologists (n=4), and nonclinical researchers (n=5) were recruited to participate in a 2-hour computer-based training consisting of a teaching and validation set of intraoperative white light cystoscopy (WLC) and CLE video sequences from patients undergoing transurethral resection of bladder tumor. Interobserver agreement was determined using the κ statistic. RESULTS: Of the 31 bladder regions analyzed, 19 were cancer and 12 were benign. For cancer diagnosis, experienced CLE urologists had substantial agreement for both CLE and WLC+CLE (90%, κ 0.80) compared with moderate agreement for WLC alone (74%, κ 0.46), while novice CLE urologists had moderate agreement for CLE (77%, κ 0.55), WLC (78%, κ 0.54), and WLC+CLE (80%, κ 0.59). Pathologists had substantial agreement for CLE (81%, κ 0.61), and nonclinical researchers had moderate agreement (77%, κ 0.49) in cancer diagnosis. For cancer grading, experienced CLE urologists had fair to moderate agreement for CLE (68%, κ 0.64), WLC (74%, κ 0.67), and WLC+CLE (53%, κ 0.33), as did novice CLE urologists for CLE (53%, κ 0.39), WLC (66%, κ 0.50), and WLC+CLE (61%, κ 0.49). Pathologists (65%, κ 0.55) and nonclinical researchers (61%, κ 0.56) both had moderate agreement for CLE in cancer grading. CONCLUSIONS: CLE is an adoptable technology for cancer diagnosis in novice CLE observers after a short training with moderate interobserver agreement and diagnostic accuracy similar to WLC alone. Experienced CLE observers may be capable of achieving substantial levels of agreement for cancer diagnosis that is higher than with WLC alone.