An End-to-End Platform for Digital Pathology Using Hyperspectral Autofluorescence Microscopy and Deep Learning-Based Virtual Histology.

Conventional histopathology involves expensive and labor-intensive processes that often consume tissue samples, rendering them unavailable for other analyses. We present a novel end-to-end workflow for pathology powered by hyperspectral microscopy and deep learning. First, we developed a custom hyperspectral microscope to nondestructively image the autofluorescence of unstained tissue sections. We then trained a deep learning model to use autofluorescence to generate virtual histologic stains, which avoids the cost and variability of chemical staining procedures and conserves tissue samples. We showed that the virtual images reproduce the histologic features present in the real-stained images using a randomized nonalcoholic steatohepatitis (NASH) scoring comparison study, where both real and virtual stains are scored by pathologists (D.T., A.D.B., R.K.P.). The test showed moderate-to-good concordance between pathologists' scoring on corresponding real and virtual stains. Finally, we developed deep learning-based models for automated NASH Clinical Research Network score prediction. We showed that the end-to-end automated pathology platform is comparable with an independent panel of pathologists for NASH Clinical Research Network scoring when evaluated against the expert pathologist consensus scores. This study provides proof of concept for this virtual staining strategy, which could improve cost, efficiency, and reliability in pathology and enable novel approaches to spatial biology research.

Relevance of the correlation between tomography findings and laboratory test results in the accuracy of the diagnosis of pulmonary tuberculosis / Relevância da correlação entre achados tomográficos e laboratoriais na precisão diagnóstica da tuberculose pulmonar

Abstract Objective: To evaluate the correlation between multidetector computed tomography (MDCT) findings and laboratory test results in patients with pulmonary tuberculosis (PTB). Materials and Methods: A total of 57 patients were evaluated. Patients with suspected PTB were divided into groups according to the final diagnosis (confirmed or excluded), and the groups were compared in terms of sociodemographic variables, clinical symptoms, tomography findings, and laboratory test results. Results: Among the patients with a confirmed diagnosis of PTB, small pulmonary nodules with a peribronchovascular distribution were significantly more common in the patients with a positive sputum smear microscopy result (47.4% vs. 8.3%; p = 0.046), as were a miliary pattern (36.8% vs. 0.0%; p = 0.026), septal thickening (84.2% vs. 41.7%; p = 0.021), and lymph node enlargement (52.6% vs. 8.3%; p = 0.020). Small pulmonary nodules with a centrilobular distribution were significantly more common among the culture-positive patients (75.0% vs. 35.7%; p = 0.045), as was a tree-in-bud pattern (91.7% vs. 42.9%; p = 0.014). A tree-in-bud pattern, one of the main tomography findings characteristic of PTB, had a sensitivity, specificity, positive predictive value, and negative predictive value of 71.0%, 73.1%, 75.9%, and 67.9%, respectively. Conclusion: MDCT presented reliable predictive values for the main tomography findings in the diagnosis of PTB, being a safe tool for the diagnosis of PTB in patients with clinical suspicion of the disease. It also appears to be a suitable tool for the selection of patients who are candidates for more complex, invasive examinations from among those with high clinical suspicion of PTB and a negative sputum smear microscopy result.

Resumo Objetivo: Avaliar a correlação entre os achados na tomografia computadorizada multidetectores (TCMD) comparativamente aos resultados laboratoriais em pacientes com tuberculose pulmonar (TBP). Materiais e Métodos: Amostra de 57 pacientes foi avaliada. Pacientes com suspeita clínica de TBP foram divididos de acordo com a positividade do diagnóstico, e as variáveis sociodemográficas, sintomas clínicos e achados tomográficos e laboratoriais foram comparados. Resultados: Nos pacientes com TBP e baciloscopia positiva, foram verificadas frequências significativas para pequenos nódulos pulmonares com distribuição peribroncovascular (47,4% vs. 8,3%; p = 0,046) e miliar (36,8% vs. 0,0%; p = 0,026), espessamento septal (84,2% vs. 41,7%; p = 0,021) e linfonodomegalias (52,6% vs. 8,3%; p = 0,020). Em relação à cultura, os pequenos nódulos pulmonares com distribuição centrolobular (75,0% vs. 35,7%; p = 0,045) e opacidades em árvore em brotamento (91,7% vs. 42,9%; p = 0,014) apresentaram frequências significativamente superiores. Medidas de sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo para árvore em brotamento, um dos principais achados tomográficos característicos da TBP, foram, respectivamente, 71.0%, 73,1%, 75,9% e 67,9%. Conclusão: A TCMD apresentou medidas preditivas confiáveis para os principais achados tomográficos no diagnóstico de TBP, sendo uma ferramenta segura para o diagnóstico da doença em pacientes com suspeita clínica. Também se mostrou adequada para selecionar os pacientes para exames mais complexos e invasivos entre os com alta suspeita clínica de TBP e baciloscopia negativa.

Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease with no approved treatments. C-C chemokine receptor types 2 and 5 (CCR2/CCR5) play an important role in inflammation and fibrosis and are potential therapeutic targets for PSC. We evaluated the efficacy and safety of cenicriviroc (CVC), a dual antagonist of CCR2 and CCR5, for the treatment of PSC. This was a single-arm, open-label, exploratory study of CVC in adults with a clinical diagnosis of PSC, serum alkaline phosphatase (ALP) ≥1.5 times the upper limit of normal (ULN), with or without inflammatory bowel disease, across eight sites in the United States and Canada. The primary endpoint was percent change in ALP over 24 weeks; key secondary efficacy endpoints were proportion of participants who achieved ALP normalization and overall response (decrease to <1.5 times the ULN or 50% decrease). Of the 24 participants, 20 completed the study. The mean age was 43 years, 50% were female, and the mean body mass index was 25 kg/m2. From a median ALP baseline of 369 U/L (range: 173, 1,377 U/L), a median absolute reduction of 49.5 U/L (range: -460, 416 U/L) was achieved at week 24, corresponding to a median reduction of 18.0% (range: -46%, 89%). No participant achieved ALP normalization or a 50% decrease; 2 participants (10%) achieved a reduction in ALP to < 1.5 times the ULN, and 4 had ≥25% increase. Twenty participants (83.3%) reported at least one adverse event; most were mild to moderate in severity. The most frequent events were rash, fatigue, and dizziness. Conclusion: After 24 weeks of CVC treatment, adults with PSC achieved a modest reduction (median 18%) in the surrogate endpoint of ALP. CVC was well tolerated, and no new safety signals were observed. ClinicalTrials.gov identifier: NCT02653625.

Herlyn-Werner-Wunderlich Syndrome with Ureteric Remnant Abscess Managed Laparoscopically: A Case Report.

Herlyn-Werner-Wunderlich (HWW) syndrome is part of a spectrum of Müllerian duct anomalies that occur during embryonic development. The syndrome is characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Only few cases of this disease were reported worldwide. We present a 23-year-old female patient with chronic pelvic pain for years. The patient was diagnosed with HWW syndrome with a history of hematocolpos and vaginoplasty at the age of 12. Five months later, she sought urgent medical care due to intense pain, and a clinical picture suggestive of peritoneal irritation. Clinical condition deteriorated and the patient underwent an exploratory laparotomy, which failed to identify anything to justify the abdominal pain. Uroculture and blood culture were negative. A magnetic resonance imaging showed a tube-shaped formations extending from the right retrovesical region to the mesogastrium corresponding to the persistence of the mesonephric duct, related to ipsilateral renal agenesis. The patient underwent laparoscopic procedure, identifying a right ureteric remnant blind ending, with distal and proximal obliteration, filled with purulent secretion, which was totally resected. This case differs from the other reported cases due to pelvic pain secondary to infection and abscess in ureteric remnant. We did not find any case with similar clinical presentation.

Diffusion-Weighted MRI in the Assessment of Early Treatment Response in Patients with Squamous-Cell Carcinoma of the Head and Neck: Comparison with Morphological and PET/CT Findings.

OBJECTIVE: To evaluate changes in apparent diffusion coefficients (ADC) as measured by magnetic resonance imaging (MRI) before and after the treatment of primary tumors and cervical metastases in patients with squamous-cell carcinoma (SCC) of the head and neck, and to compare these values to the results of widely used morphological criteria and [18F]-FDG PET/CT findings. MATERIAL AND METHOD: This was a longitudinal, prospective, single-center nonrandomized trial involving patients with head and neck SCC treated with chemotherapy alone or in combination with radiotherapy. Imaging examinations ([18F]-FDG PET/CT and diffusion-weighted MRI) were performed on the same day, up to one day prior to the beginning of the first treatment cycle, and on the 14th day of the first chemotherapy cycle. Treatment response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) morphological criteria, as well as PET Response Criteria in Solid Tumors (PERCIST) metabolic criteria. RESULTS: Seventy-five lesions were examined in 23 patients. Pre- and post-treatment comparisons of data pertaining to all target lesions revealed reductions in tumor size and SUV, as well as increases in ADC values, all of which were statistically significant. The increase in ADC following treatment was significantly higher in patients classified as complete responders by both morphological criteria than that observed in any of the other patient groups of response. Patients with a complete metabolic response also showed greater increases in ADC values as compared to the remaining groups. CONCLUSION: The assessment of tumor response based on diffusion-weighted MRI showed an increase in the ADC of cervical lesions following treatment, which was corroborated by morphological and metabolic findings. Associations between changes in ADC values and treatment response categories using morphologic criteria and [18F]-FDG PET/CT were only identified in complete responders.

Hepatitis B e antigen status and hepatitis B DNA levels in women of childbearing age with chronic hepatitis B infection screening for clinical trials.

BACKGROUND: Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load. AIM: To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials. METHODS: Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18-69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive. RESULTS: Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load. CONCLUSIONS: Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load.

Hepatitis B screening and vaccination practices in asian american primary care.

BACKGROUND/AIMS: Screening for hepatitis B virus (HBV) is recommended in populations with anticipated prevalence ≥2%. This study surveyed HBV screening and vaccination practices of Asian American primary care providers (PCPs). METHODS: Approximately 15,000 PCPs with Asian surnames in the New York, Los Angeles, San Francisco, Houston, and Chicago areas were invited to participate in a web-based survey. Asian American PCPs with ≥25% Asian patients in their practice were eligible. RESULTS: Of 430 (2.9%) survey respondents, 217 completed the survey. Greater than 50% followed ≥200 Asian patients. Although 95% of PCPs claimed to have screened patients for HBV, 41% estimated that ≤25% of their adult Asian patients had ever been screened, and 50% did not routinely screen all Asian patients. In a multivariable analysis, the proportion of Asian patients in the practice, provider geographic origin and the number of liver cancers diagnosed in the preceding 12 months were significantly associated with a higher likelihood of screening for HBV. Over 80% of respondents reported that ≤50% of their adult Asian patients had received the HBV vaccine. CONCLUSIONS: Screening and vaccination for HBV in Asian American patients is inadequate. Measures to improve HBV knowledge and care by primary-care physicians are critically needed.

Computed tomography-guided percutaneous biopsy of pancreatic masses using pneumodissection / Biópsia percutânea de massas pancreáticas guiada por tomografia computadorizada com pneumodissecção

Objective To describe the technique of computed tomography-guided percutaneous biopsy of pancreatic tumors with pneumodissection. Materials and Methods In the period from June 2011 to May 2012, seven computed tomography-guided percutaneous biopsies of pancreatic tumors utilizing pneumodissection were performed in the authors' institution. All the procedures were performed with an automatic biopsy gun and coaxial system with Tru-core needles. The biopsy specimens were histologically assessed. Results In all the cases the pancreatic mass could not be directly approached by computed tomography without passing through major organs and structures. The injection of air allowed the displacement of adjacent structures and creation of a safe coaxial needle pathway toward the lesion. Biopsy was successfully performed in all the cases, yielding appropriate specimens for pathological analysis. Conclusion Pneumodissection is a safe, inexpensive and technically easy approach to perform percutaneous biopsy in selected cases where direct access to the pancreatic tumor is not feasible. .

Objetivo Descrever a técnica de biópsia percutânea de tumores pancreáticos guiada por tomografia computadorizada com pneumodissecção. Materiais e Métodos No período de junho de 2011 a maio de 2012, foram realizadas sete biópsias percutâneas de tumores pancreáticos guiadas por tomografia computadorizada utilizando a manobra de pneumodissecção em nossa instituição. Todas as biópsias foram realizadas utilizando pistola de disparo automático e sistema coaxial, com agulhas Tru-core. As amostras colhidas foram submetidas a avaliação histológica. Resultados Para todos os casos, não havia um acesso direto seguro pela tomografia computadorizada para atingir o tumor pancreático sem atravessar órgãos e estruturas importantes. A injeção de ar foi capaz de deslocar as estruturas adjacentes e criar uma nova rota de acesso, permitindo um trajeto seguro da agulha coaxial até a lesão, e a biópsia foi realizada com sucesso em todos os casos. Todas as biópsias forneceram material suficiente para análise histológica. Conclusão Esta técnica é segura, barata e tecnicamente fácil, podendo auxiliar na realização de biópsias percutâneas de tumores pancreáticos guiadas por tomografia computadorizada de casos selecionados em que não existe acesso direto à lesão. .

Ressonância magnética com sequências ponderadas em difusão, 18-FDG PET CT e critérios morfológicos na avaliação da resposta terapêutica de pacientes com carcinoma epidermóide de cabeça e pescoço / Diffusion-weithed magnetic resonance, 18-FDG PET-CT and morphological criteria in evaluation of the head and neck squamous cell carcinoma therapeutic response

Introdução: O tratamento dos carcinomas epidermoides de cabeça e pescoço é altamente complexo. Em geral, pacientes com tumores iniciais são tratados por cirurgia ou radioterapia, enquanto aqueles com tumores avançados recebem terapias combinadas, composto por cirurgia, radioterapia e quimioterapia, sendo que um fator primordial no tratamento dos tumores de cabeça e pescoço é a avaliação da resposta terapêutica. Tradicionalmente, a resposta terapêutica é avaliada por parâmetros morfológicos, como as dimensões das lesões, através de critérios de avaliação de resposta terapêutica, sendo que os mais usados são o RECIST e WHO. Nos últimos anos têm sido desenvolvidos métodos funcionais de avaliação por imagem de tumores, dentre os quais se destacam o 18FDG-PET-CT e a ressonância magnética com sequências ponderadas em difusão. O 18FDG-PET-CT é capaz de fornecer informações relacionadas ao metabolismo da glicose nos diversos órgãos e tecidos. As sequências ponderadas em difusão exploram o princípio do movimento randômico das moléculas de água nos tecidos do corpo humano. A movimentação das moléculas de água é mais restrita em tecidos com elevada celularidade, tais como alguns tecidos tumorais Há ainda carência de estudos na literatura sobre a avaliação de resposta terapêutica com difusão e são escassos os estudos na literatura comparando ambos os métodos. Objetivo Primário: Comparar a variação do Coeficiente Aparente de Difusão obtido por Ressonância Magnética antes e após o tratamento nas lesões primárias e metástases cervicais de pacientes portadores de carcinoma epidermóide de cabeça e pescoço submetidos a tratamento com quimioterapia e/ou radioterapia, bem como as variações nas dimensões e no valor de SUV calculado no 18FDG-PET-CT. Objetivos Secundários: Avaliar os valores de ADC em tecidos neoplásicos e normais, definindo ponto de corte para distinção destes, calculando sensibilidade, especificidade e acurácia; Comparar as variações dos valores do ADC...

Introduction: Head and Neck squamous cell carcinoma (HNSCC) treatment is a complex topic. Patients with initial tumors are usually treated by surgery or radiotherapy, while those with advanced tumors receiving combination therapy, consisting of surgery, radiation and chemotherapy, and a key factor is the evaluation of therapeutic response. Traditionally, the therapeutic response is assessed by morphological parameters such as the size of the lesions, and the most widely used is the RECIST criteria. In recent years functional methods have been developed, such as 18FDG-PET-CT and diffusion-weighted MRI. 18FDG-PET-CT is able to provide information related to glucose metabolism in various organs and tissues. The diffusion-weighted sequences exploiting the water molecules random motion principle in body tissues. Water molecules movement is more restricted in high cellularity tissues, such neoplastic tissues. There are few studies about diffusion MRI therapeutic response comparing this method with 18FDG-PET-CT. Methods: Were included 23 patients (75 lesions) with stage III and IV HNSCC, non-metastatic, with indication for neoadjuvant chemotherapy followed by radiotherapy or chemoradiotherapy or curative chemotherapy and concomitant radiotherapy. Images (18FDG-PET-CT and Diffusion) were performed before and after treatment and calculated ADC and SUV values and size of lesions. Patients were classified according to conventional response evaluation criteria (RECIST and WHO), PET-CT response criteria, and these values were compared with the ADC values. Primary Objective: To compare the Apparent Diffusion Coefficient (ADC) variation before and after treatment in primary lesions and cervical metastases HNSCC treated with chemotherapy and / or radiatiotherapy, as well as dimensions and SUV in 18FDG-PET-CT variations. Secondary Objectives: To evaluate ADC values in normal and neoplastic tissues, defining a cutoff value for distinguishing these by calculating sensitivity...

New applications of radioguided surgery in oncology.

OBJECTIVE: To report oncological cases (excluding those related to breast cancer) for which radioguided surgery has been used in combination with the Radioguided Occult Lesion Localization technique. INTRODUCTION: Radioguided surgery enables a surgeon to identify lesions or tissues that have been preoperatively marked with radioactive substances. The Radioguided Occult Lesion Localization technique has been widely used to identify the sentinel lymph node and occult lesions in patients with breast cancer. However, few studies have reported the use of this technique for non-breast cancer pathologies. METHODOLOGY: In all cases, injection of Technecium-99m sulfur colloid was performed, directly inside or near by the suspicious lesion, guided by ultrasound or computed tomography, up to 36 hours prior to the surgical procedure. Intraoperative lesion detection was carried out using a gamma-probe. RESULTS: We report five oncology cases in which preoperative markings of the lesions were carried out using the Radioguided Occult Lesion Localization technique. The patients presented with the following: recurrence of renal cell carcinoma, cervical recurrence of papillary carcinoma of the thyroid, recurrence of retroperitoneal sarcoma, lesions of the popliteal fossa, and recurrence of rhabdomyosarcoma of a thigh. In each case, the lesions that were marked preoperatively were ultimately successfully excised. CONCLUSIONS: Radioguided surgery has proven to be a safe and effective alternative for the management of oncology patients. The Radioguided Occult Lesion Localization technique can be useful in selected cases where suspect lesions may be difficult to identify intraoperatively, due to their dimensions or anatomical location. The procedure allows for more conservative excisions and reduces the surgery-related morbidity.

New applications of radioguided surgery in oncology

OBJECTIVE: To report oncological cases (excluding those related to breast cancer) for which radioguided surgery has been used in combination with the Radioguided Occult Lesion Localization technique. INTRODUCTION: Radioguided surgery enables a surgeon to identify lesions or tissues that have been preoperatively marked with radioactive substances. The Radioguided Occult Lesion Localization technique has been widely used to identify the sentinel lymph node and occult lesions in patients with breast cancer. However, few studies have reported the use of this technique for non-breast cancer pathologies. METHODOLOGY: In all cases, injection of Technecium-99m sulfur colloid was performed, directly inside or near by the suspicious lesion, guided by ultrasound or computed tomography, up to 36 hours prior to the surgical procedure. Intraoperative lesion detection was carried out using a gamma-probe. RESULTS: We report five oncology cases in which preoperative markings of the lesions were carried out using the Radioguided Occult Lesion Localization technique. The patients presented with the following: recurrence of renal cell carcinoma, cervical recurrence of papillary carcinoma of the thyroid, recurrence of retroperitoneal sarcoma, lesions of the popliteal fossa, and recurrence of rhabdomyosarcoma of a thigh. In each case, the lesions that were marked preoperatively were ultimately successfully excised. CONCLUSIONS: Radioguided surgery has proven to be a safe and effective alternative for the management of oncology patients. The Radioguided Occult Lesion Localization technique can be useful in selected cases where suspect lesions may be difficult to identify intraoperatively, due to their dimensions or anatomical location. The procedure allows for more conservative excisions and reduces the surgery-related morbidity.

Diabetes e cirurgia / Diabetes and surgery

Apresenta classificaçao do tipo de diabetes e a conduta necessaria ao controle de cada tipo. Destaca sobretudo os cuidados pre-operatorios e as complicaçoes inerentes a cada tipo de cirurgia e que podem ocorrer especialmente com doentes diabeticos