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1.
JCO Clin Cancer Inform ; 5: 47-55, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33439728

RESUMO

The College of American Pathologists Cancer Protocols have offered guidance to pathologists for standard cancer pathology reporting for more than 35 years. The adoption of computer readable versions of these protocols by electronic health record and laboratory information system (LIS) vendors has provided a mechanism for pathologists to report within their LIS workflow, in addition to enabling standardized structured data capture and reporting to downstream consumers of these data such as the cancer surveillance community. This paper reviews the history of the Cancer Protocols and electronic Cancer Checklists, outlines the current use of these critically important cancer case reporting tools, and examines future directions, including plans to help improve the integration of the Cancer Protocols into clinical, public health, research, and other workflows.

3.
Mod Pathol ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879414

RESUMO

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma with characteristic histologic features and chromosomal alterations. Although typically indolent, a small subset of cases has been reported to exhibit aggressive clinical behavior. We retrospectively identified 33 patients with MTSCC, consisting of 10 cases of locally advanced/metastatic MTSCC (pT3 or N1 or M1) and 23 kidney-confined MTSCC (pT1/T2) without disease recurrence or progression. Utilizing a single-nucleotide polymorphism array and a targeted next-generation sequencing platform, we examined genome-wide molecular alterations in 24 cases, including 11 available samples from 8 patients with locally advanced/metastatic MTSCC. Ten patients with locally advanced/metastatic MTSCC were 8 females (80%) and 2 males (20%). At nephrectomy, 7 of these 10 cases (70%) were pT3 or pN1 while the remaining 3 (30%) were pT1/T2. Eight patients (80%) developed metastases and common sites included lymph node (4, 40%), bone (4, 40%), and retroperitoneum (3, 30%). Four patients died of disease (40%) during follow-up. Locally advanced/metastatic MTSCCs shared typical MTSCC genomic profiles with loss of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, while some exhibited additional complex genomic alterations, most frequently a relative gain of 1q (7/8). Homozygous loss of CDKN2A/B was observed in 3 (38%) locally advanced/metastatic MTSCCs. Tumor necrosis, solid nested/sheet pattern, irregular trabecular/single-file infiltration in a desmoplastic stroma, lymphovascular space invasion, and increased mitotic activity were associated with locally advanced/metastatic MTSCCs (all p < 0.05). Our findings reveal that MTSCCs with aggressive clinical behavior have progressed through clonal evolution; CDKN2A/B deletion and additional complex genomic abnormalities may contribute to this process. Recognizing the morphologic presentation of high-grade MTSCC and evaluating adverse histologic features seen in these tumors can help establish a definitive diagnosis and stratify patients for treatment and prognostication.

5.
Mod Pathol ; 33(11): 2169-2185, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32467650

RESUMO

Pathologists are responsible for rapidly providing a diagnosis on critical health issues. Challenging cases benefit from additional opinions of pathologist colleagues. In addition to on-site colleagues, there is an active worldwide community of pathologists on social media for complementary opinions. Such access to pathologists worldwide has the capacity to improve diagnostic accuracy and generate broader consensus on next steps in patient care. From Twitter we curate 13,626 images from 6,351 tweets from 25 pathologists from 13 countries. We supplement the Twitter data with 113,161 images from 1,074,484 PubMed articles. We develop machine learning and deep learning models to (i) accurately identify histopathology stains, (ii) discriminate between tissues, and (iii) differentiate disease states. Area Under Receiver Operating Characteristic (AUROC) is 0.805-0.996 for these tasks. We repurpose the disease classifier to search for similar disease states given an image and clinical covariates. We report precision@k = 1 = 0.7618 ± 0.0018 (chance 0.397 ± 0.004, mean ±stdev ). The classifiers find that texture and tissue are important clinico-visual features of disease. Deep features trained only on natural images (e.g., cats and dogs) substantially improved search performance, while pathology-specific deep features and cell nuclei features further improved search to a lesser extent. We implement a social media bot (@pathobot on Twitter) to use the trained classifiers to aid pathologists in obtaining real-time feedback on challenging cases. If a social media post containing pathology text and images mentions the bot, the bot generates quantitative predictions of disease state (normal/artifact/infection/injury/nontumor, preneoplastic/benign/low-grade-malignant-potential, or malignant) and lists similar cases across social media and PubMed. Our project has become a globally distributed expert system that facilitates pathological diagnosis and brings expertise to underserved regions or hospitals with less expertise in a particular disease. This is the first pan-tissue pan-disease (i.e., from infection to malignancy) method for prediction and search on social media, and the first pathology study prospectively tested in public on social media. We will share data through http://pathobotology.org . We expect our project to cultivate a more connected world of physicians and improve patient care worldwide.

6.
Arch Pathol Lab Med ; 144(3): 356-360, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31584841

RESUMO

CONTEXT.­: In prostate cancer, "tertiary" higher-grade patterns (TPs) have been associated with biochemical recurrence after radical prostatectomy. OBJECTIVE.­: To determine variation regarding definition and application of TPs. DESIGN.­: Online survey regarding TPs in a range of grading scenarios circulated to 105 experienced urologic pathologists. RESULTS.­: Among 95 respondents, 40 of 95 (42%) defined TPs as "third most common pattern" and 55 (58%) as "minor pattern/less than 5% of tumor." In a tumor with pattern 3 and less than 5% pattern 4, of the 95 respondents, 35 (37%) assigned 3 + 3 = 6 with TP4, while 56 (59%) assigned 3 + 4 = 7. In a tumor with pattern 4 and less than 5% pattern 5, of the 95 respondents, 51 (54%) assigned 4 + 4 = 8 with TP5, while 43 (45%) assigned 4 + 5 = 9. Six scenarios were presented in which the order of most common patterns was 3, 4, and 5 (Group 1) or 4, 3, and 5 (Group 2) with varying percentages. In both groups, when pattern 5 was less than 5%, we found that 98% and 93% of respondents would assign 3 + 4 = 7 or 4 + 3 = 7 with TP5. In scenarios with 15% or 25% pattern 5, most respondents (70% and 80%, respectively) would include pattern 5 as the secondary grade, that is, 3 + 5 = 8 (Group 1) or 4 + 5 = 9 (Group 2). For 85 of 95 (89%), a TP would not impact Grade Group assignment. CONCLUSIONS.­: This survey highlights substantial variation in practice patterns regarding definition and application of "tertiary" grading in radical prostatectomy specimens. High consistency was observed in 3 + 4 = 7/4 + 3 = 7 scenarios with truly minor pattern 5. These findings should inform future studies assessing the standardization and predictive value of "tertiary" patterns.


Assuntos
Patologistas/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/patologia , Relatório de Pesquisa , Inquéritos e Questionários/estatística & dados numéricos , Humanos , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia , Patologistas/normas , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/terapia
7.
Arch Pathol Lab Med ; 143(12): 1545-1555, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31173528

RESUMO

CONTEXT.­: Digital pathology (DP) implementations vary in scale, based on aims of intended operation. Few laboratories have completed a full-scale DP implementation, which may be due to high overhead costs that disrupt the traditional pathology workflow. Neither standardized criteria nor benchmark data have yet been published showing practical return on investment after implementing a DP platform. OBJECTIVE.­: To provide benchmark data and practical metrics to support operational efficiency and cost savings in a large academic center. DESIGN.­: Metrics reviewed include archived pathology asset retrieval; ancillary test request for recurrent/metastatic disease; cost analysis and turnaround time (TAT); and DP experience survey. RESULTS.­: Glass slide requests from the department slide archive and an off-site surgery center showed a 93% and 97% decrease, respectively. Ancillary immunohistochemical orders, compared in 2014 (52%)-before whole slide images (WSIs) were available in the laboratory information system-and 2017 (21%) showed $114 000/y in anticipated savings. Comprehensive comparative cost analysis showed a 5-year $1.3 million savings. Surgical resection cases with prior WSIs showed a 1-day decrease in TAT. A DP experience survey showed 80% of respondents agreed WSIs improved their clinical sign-out experience. CONCLUSIONS.­: Implementing a DP operation showed a noteworthy increase in efficiency and operational utility. Digital pathology deployments and operations may be gauged by the following metrics: number of glass slide requests as WSIs become available, decrease in confirmatory testing for patients with metastatic/recurrent disease, long-term decrease in off-site pathology asset costs, and faster TAT. Other departments may use our benchmark data and metrics to enhance patient care and demonstrate return on investment to justify adoption of DP.


Assuntos
Diagnóstico por Imagem/economia , Diagnóstico por Imagem/métodos , Patologia Clínica/economia , Patologia Clínica/métodos , Eficiência , Humanos , Fluxo de Trabalho
8.
Mod Pathol ; 32(9): 1329-1343, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30980040

RESUMO

Renal medullary carcinoma is a rare but highly aggressive type of renal cancer occurring in patients with sickle cell trait or rarely with other hemoglobinopathies. Loss of SMARCB1 protein expression, a core subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, has emerged as a key diagnostic feature of these tumors. However, the molecular mechanism underlying this loss remains unclear. We retrospectively identified 20 patients diagnosed with renal medullary carcinoma at two institutions from 1996 to 2017. All patients were confirmed to have sickle cell trait, and all tumors exhibited a loss of SMARCB1 protein expression by immunohistochemistry. The status of SMARCB1 locus was examined by fluorescence in situ hybridization (FISH) using 3-color probes, and somatic alterations were detected by targeted next-generation sequencing platforms. FISH analysis of all 20 cases revealed 11 (55%) with concurrent hemizygous loss and translocation of SMARCB1, 6 (30%) with homozygous loss of SMARCB1, and 3 (15%) without structural or copy number alterations of SMARCB1 despite protein loss. Targeted sequencing revealed a pathogenic somatic mutation of SMARCB1 in one of these 3 cases that were negative by FISH. Tumors in the 3 subsets with different FISH findings largely exhibited similar clinicopathologic features, however, homozygous SMARCB1 deletion was found to show a significant association with the solid growth pattern, whereas tumors dominated by reticular/cribriform growth were enriched for SMARCB1 translocation. Taken together, we demonstrate that different molecular mechanisms underlie the loss of SMARCB1 expression in renal medullary carcinoma. Biallelic inactivation of SMARCB1 occurs in a large majority of cases either via concurrent hemizygous loss and translocation disrupting SMARCB1 or by homozygous loss.


Assuntos
Carcinoma Medular/genética , Neoplasias Renais/genética , Proteína SMARCB1/genética , Proteína SMARCB1/metabolismo , Adolescente , Adulto , Carcinoma Medular/metabolismo , Criança , Feminino , Variação Genética , Humanos , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Mod Pathol ; 32(7): 916-928, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30778169

RESUMO

Whole slide imaging is Food and Drug Administration-approved for primary diagnosis in the United States of America; however, relatively few pathology departments in the country have fully implemented an enterprise wide digital pathology system enabled for primary diagnosis. Digital pathology has significant potential to transform pathology practice with several published studies documenting some level of diagnostic equivalence between digital and conventional systems. However, whole slide imaging also has significant potential to disrupt pathology practice, due to the differences in efficiency of manipulating digital images vis-à-vis glass slides, and studies on the efficiency of actual digital pathology workload are lacking. Our randomized, equivalency and efficiency study aimed to replicate clinical workflow, comparing conventional microscopy to a complete digital pathology signout using whole slide images, evaluating the equivalency and efficiency of glass slide to whole slide image reporting, reflective of true pathology practice workloads in the clinical setting. All glass slides representing an entire day's routine clinical signout workload for six different anatomic pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on Leica Aperio AT2 at ×40 (0.25 µm/pixel). Integration of whole slide images for each accessioned case is through an interface between the Leica eSlide manager database and the laboratory information system, Cerner CoPathPlus. Pathologists utilized a standard institution computer workstation and viewed whole slide images through an internally developed, vendor agnostic whole slide image viewer, named the "MSK Slide Viewer". Subspecialized pathologists first reported on glass slides from surgical pathology cases using routine clinical workflow. Glass slides were de-identified, scanned, and re-accessioned in the laboratory information system test environment. After a washout period of 13 weeks, pathologists reported the same clinical workload using whole slide image integrated within the laboratory information system. Intraobserver equivalency metrics included top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and the need to order ancillary testing (i.e., recuts, immunohistochemistry). Turnaround time (efficiency) evaluation was defined by the start of each case when opened in the laboratory information system and when the case was completed for that day (i.e., case sent to signout queue or pending ancillary studies). Eight pathologists participated from the following subspecialties: bone and soft tissue, genitourinary, gastrointestinal, breast, gynecologic, and dermatopathology. Glass slides signouts comprised of 204 cases, encompassing 2091 glass slides; and digital signouts comprised of 199 cases, encompassing 2073 whole slide images. The median whole slide image file size was 1.54 GB; scan time/slide, 6 min 24 s; and scan area 32.1 × 18.52 mm. Overall diagnostic equivalency (e.g., top-line diagnosis) was 99.3% between digital and glass slide signout; however, signout using whole slide images showed a median overall 19% decrease in efficiency per case. No significant difference by reader, subspecialty, or specimen type was identified. Our experience is the most comprehensive study to date and shows high intraobserver whole slide image to glass slide equivalence in reporting of true clinical workflows and workloads. Efficiency needs to improve for digital pathology to gain more traction among pathologists.


Assuntos
Patologia Clínica/métodos , Patologia Cirúrgica/métodos , Telepatologia/métodos , Humanos , Processamento de Imagem Assistida por Computador , Microscopia/métodos , Reprodutibilidade dos Testes
10.
J Urol ; 201(3): 535-540, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30300632

RESUMO

PURPOSE: We evaluated whether the prediction of biochemical recurrence after radical prostatectomy is enhanced by any of 6 parameters, including prostate volume, total tumor volume, high grade total tumor volume, the ratio of high grade total tumor volume to total tumor volume, the ratio of total tumor volume to prostate volume and/or the ratio of high grade total tumor volume to prostate volume. MATERIALS AND METHODS: A total of 1,261 patients who underwent radical prostatectomy during a 3-year period had tumor maps constructed with the Gleason pattern denoted as low-3 or high-4 or 5 and volumetric data generated using commercially available software. Univariate Cox regression models were used to assess whether each volume related parameter was associated with biochemical recurrence after radical prostatectomy. A multivariable Cox regression base model (age, prostate specific antigen, Gleason score/grade group, pathological stage and margin status) was compared with 6 additional models (base model plus each volume related parameter) to evaluate enhancement in predictive accuracy. Decision curve analysis was performed to determine the clinical utility of parameters that enhanced predictive accuracy. RESULTS: On univariate analysis each parameter was significantly associated with biochemical recurrence except prostate volume. Predictive accuracy of the multivariable base model was high (c-index = 0.861). Adding volume related parameters marginally enhanced discrimination. Decision curve analysis failed to show added benefit even for high grade total tumor volume/total tumor volume, which was the parameter with the highest discriminative improvement. CONCLUSIONS: Tumor volume related parameters are significantly associated with radical prostatectomy but do not add important discrimination to standard clinicopathological variables for radical prostatectomy prediction or provide benefit across a range of clinically relevant decision thresholds. Volume related measurement is not warranted in routine pathological evaluation and reporting.


Assuntos
Próstata/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Carga Tumoral , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Estudos Retrospectivos
11.
Am J Surg Pathol ; 43(1): 121-131, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30303819

RESUMO

The differential diagnosis of renal cell neoplasms with solid or nested architecture and eosinophilic cytoplasm has become increasingly complex. Despite recent advances in classifying a number of entities exhibiting this morphology, some tumors remain in the unclassified category. Here we describe a morphologically distinct group of sporadic renal cell carcinoma (RCC) with predominantly nested architecture, eosinophilic, and remarkably vacuolated cytoplasm retrospectively identified from a cohort of previously unclassified tumors. We examined the clinicopathologic and immunohistochemical features of these tumors and investigated their mutational and copy number alterations using a targeted next-generation sequencing platform. The study included 7 patients with a mean age of 54 years (range: 40 to 68 y) and a male to female ratio of 3:4. All patients presented with a solitary renal mass and had no prior medical or family history raising concern for syndromic conditions. Tumors were well-circumscribed, unencapsulated, and comprised of nests of eosinophilic cells in a hypocellular and often edematous stroma. Tumor cells had round nuclei with prominent nucleoli and granular cytoplasm with striking vacuolization. Thick-walled vessels and calcifications were also frequently present, whereas increased mitotic activity, necrosis, foamy histiocytes or lymphocytic infiltrates were not identified. All cases were positive for PAX8, had retained expression of SDHB and FH, and exhibited a CK7-/CK20- phenotype. While cathepsin-K was positive in 5 cases, none exhibited immunoreactivity to HMB45 or Melan A, or TFE3 immunostaining. Next-generation sequencing identified somatic inactivating mutations of TSC2 (3/5 tumors tested) or activating mutations of MTOR (2/5) as the primary molecular alterations, consistent with hyperactive mTOR complex 1 signaling which was further demonstrated by phospho-S6 and phospho-4E-BP1 immunostaining. Copy number analysis revealed a loss of chromosome 1 in both cases with MTOR mutation. These tumors represent a novel subset of sporadic RCC characterized by alterations in TSC1-TSC2 complex or the mTOR complex 1 pathway. Recognition of their characteristic morphologic and immunophenotypic features will allow them to be readily identified and separated from the unclassified RCC category.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Serina-Treonina Quinases TOR/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/patologia , Citoplasma/patologia , Feminino , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos
12.
J Urol ; 201(1): 77-82, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30076908

RESUMO

PURPOSE: To our knowledge the ideal methodology of quantifying secondary Gleason pattern 4 in men with Grade Group 2/Gleason score 3 + 4 = 7 on biopsy remains unknown. We compared various methods of Gleason pattern 4 quantification and evaluated associations with adverse pathology findings at radical prostatectomy. MATERIALS AND METHODS: A total of 457 men with Grade Group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy at our institution. Only patients with 12 or more reviewed cores were included in analysis. We evaluated 3 methods of quantifying Gleason pattern 4, including the maximum percent of Gleason pattern 4 in any single core, the overall percent of Gleason pattern 4 (Gleason pattern 4 mm/total cancer mm) and the total length of Gleason pattern 4 in mm across all cores. Adverse pathology features at radical prostatectomy were defined as Gleason score 4 + 3 = 7 or greater (Grade Group 3 or greater), and any extraprostatic extension, seminal vesical invasion and/or lymph node metastasis. A training/test set approach and multivariable logistic regression were used to determine whether Gleason pattern 4 quantification methods could aid in predicting adverse pathology. RESULTS: On multivariable analysis all Gleason pattern 4 quantification methods were significantly associated with an increased risk of adverse pathology (p <0.0001) and an increased AUC beyond the base model. The largest AUC increase was 0.044 for the total length of Gleason pattern 4 (AUC 0.728, 95% CI 0.663-0.793). Decision curve analysis demonstrated an increased clinical net benefit with the addition of Gleason pattern 4 quantification to the base model. The total length of Gleason pattern 4 clearly provided the largest net benefit. CONCLUSIONS: Our findings support the inclusion of Gleason pattern 4 quantification in the pathology reports and risk prediction models of patients with Grade Group 2/Gleason score 3 + 4 = 7 prostate cancer. The total length of Gleason pattern 4 across all cores provided the strongest benefit to predict adverse pathology features.


Assuntos
Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Biópsia , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Prognóstico , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/cirurgia , Curva ROC , Medição de Risco/métodos , Glândulas Seminais/patologia
13.
Diagn Cytopathol ; 47(1): 15-19, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29575752

RESUMO

BACKGROUND: Rapid on-site evaluation (ROSE) with cytology preparations plays a critical role in minimally invasive procedures. The time spent by a pathologist performing ROSE is unpredictable and could be used for more cost-effective activities. The solution encountered by several institutions to address this issue is the use of telecytology (TC). This study analyzes the experience of using telecytology for ROSE in a major cancer center over a period of over 2 years. METHODS: A retrospective analysis of all remote TC evaluations for adequacy on fine needle aspiration (FNA) and touch preparations (TP) of core biopsies (CB) performed at a major cancer center was performed. The preliminary adequacy assessment was then compared to the adequacy assessment at final diagnosis. RESULTS: A total of 12 949 adequacy assessments were analyzed. The most common sites biopsied in our institution were lymph node, lung, and liver. There were 7725 adequacy assessments for CB (59.7%), while adequacy assessment for FNA specimens represented 40.3% (n = 5224) of the total number of specimens evaluated by ROSE. Perfect concordance between initial adequacy assessment and the adequacy assessment at final cytologic diagnosis was 93% (12 049/12 949). The final diagnosis adequacy upgrade rate was 6.7% (n = 863), and the adequacy downgrade (a specimen considered adequate on-site that was determined to be nondiagnostic on final examination) was 0.3% (n = 37). CONCLUSIONS: TC can be easily implemented with the current technologies available. It is cost-effective and allows for better patient care with a more efficient use of the pathologist's time and laboratory resources.


Assuntos
Técnicas Citológicas/métodos , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Linfonodos/patologia , Masculino , Neoplasias/diagnóstico , Neoplasias/patologia , Estudos Retrospectivos
14.
Am Soc Clin Oncol Educ Book ; 38: 540-545, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30231354

RESUMO

Telemedicine uses telecommunications technology as a tool to deliver health care to populations with limited access to care. Telemedicine has been tested in multiple clinical settings, demonstrating at least equivalency to in-person care and high levels of patient and health professional satisfaction. Teleoncology has been demonstrated to improve access to care and decrease health care costs. Teleconsultations may take place in a synchronous, asynchronous, or blended format. Examples of successful teleoncology applications include cancer telegenetics, bundling of cancer-related teleapplications, remote chemotherapy supervision, symptom management, survivorship care, palliative care, and approaches to increase access to cancer clinical trials. Telepathology is critical to cancer care and may be accomplished synchronously and asynchronously for both cytology and tissue diagnoses. Mobile applications support symptom management, lifestyle modification, and medication adherence as a tool for home-based care. Telemedicine can support the oncologist with access to interactive tele-education. Teleoncology practice should maintain in-person professional standards, including documentation integrated into the patient's electronic health record. Telemedicine training is essential to facilitate rapport, maximize engagement, and conduct an accurate virtual exam. With the appropriate attachments, the only limitation to the virtual exam is palpation. The national telehealth resource centers can provide interested clinicians with the latest information on telemedicine reimbursement, parity, and practice. To experience the gains of teleoncology, appropriate training, education, as well as paying close attention to gaps, such as those inherent in the digital divide, are essential.


Assuntos
Oncologia , Telemedicina , Ensaios Clínicos como Assunto , Assistência à Saúde/legislação & jurisprudência , Assistência à Saúde/métodos , Educação Médica/métodos , Humanos , Comunicação Interdisciplinar , Oncologia/legislação & jurisprudência , Oncologia/métodos , Telemedicina/legislação & jurisprudência , Telemedicina/métodos , Telemetria , Fatores de Tempo
15.
Mol Cancer Res ; 16(11): 1687-1700, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30076241

RESUMO

Tumor cells require increased rates of cell metabolism to generate the macromolecules necessary to sustain proliferation. They rely heavily on NAD+ as a cofactor for multiple metabolic enzymes in anabolic and catabolic reactions. NAD+ also serves as a substrate for PARPs, sirtuins, and cyclic ADP-ribose synthases. Dysregulation of the cyclic ADP-ribose synthase CD38, the main NAD'ase in cells, is reported in multiple cancer types. This study demonstrates a novel connection between CD38, modulation of NAD+, and tumor cell metabolism in prostate cancer. CD38 expression inversely correlates with prostate cancer progression. Expressing CD38 in prostate cancer cells lowered intracellular NAD+, resulting in cell-cycle arrest and expression of p21Cip1 (CDKNA1). In parallel, CD38 diminishes glycolytic and mitochondrial metabolism, activates AMP-activated protein kinase (AMPK), and inhibits fatty acid and lipid synthesis. Pharmacologic inhibition of nicotinamide phosphoribosyltransferase (NAMPT) mimicked the metabolic consequences of CD38 expression, demonstrating similarity between CD38 expression and NAMPT inhibition. Modulation of NAD+ by CD38 also induces significant differential expression of the transcriptome, producing a gene expression signature indicative of a nonproliferative phenotype. Altogether, in the context of prostate cancer, the data establish a novel role for the CD38-NAD+ axis in the regulation of cell metabolism and development.Implications: This research establishes a mechanistic connection between CD38 and metabolic control. It also provides the foundation for the translation of agents that modulate NAD+ levels in cancer cells as therapeutics. Mol Cancer Res; 16(11); 1687-700. ©2018 AACR.


Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Glicoproteínas de Membrana/metabolismo , NAD/metabolismo , Neoplasias da Próstata/metabolismo , ADP-Ribosil Ciclase 1/biossíntese , Acrilamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Reprogramação Celular/fisiologia , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Ácidos Graxos/antagonistas & inibidores , Ácidos Graxos/biossíntese , Expressão Gênica , Humanos , Lipídeos/antagonistas & inibidores , Lipídeos/biossíntese , Masculino , Glicoproteínas de Membrana/biossíntese , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/metabolismo , Células PC-3 , Piperidinas/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Quinases/metabolismo , Transcriptoma , Transfecção , Tretinoína/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-29601065

RESUMO

Modern digital pathology departments have grown to produce whole-slide image data at petabyte scale, an unprecedented treasure chest for medical machine learning tasks. Unfortunately, most digital slides are not annotated at the image level, hindering large-scale application of supervised learning. Manual labeling is prohibitive, requiring pathologists with decades of training and outstanding clinical service responsibilities. This problem is further aggravated by the United States Food and Drug Administration's ruling that primary diagnosis must come from a glass slide rather than a digital image. We present the first end-to-end framework to overcome this problem, gathering annotations in a nonintrusive manner during a pathologist's routine clinical work: (i) microscope-specific 3D-printed commodity camera mounts are used to video record the glass-slide-based clinical diagnosis process; (ii) after routine scanning of the whole slide, the video frames are registered to the digital slide; (iii) motion and observation time are estimated to generate a spatial and temporal saliency map of the whole slide. Demonstrating the utility of these annotations, we train a convolutional neural network that detects diagnosis-relevant salient regions, then report accuracy of 85.15% in bladder and 91.40% in prostate, with 75.00% accuracy when training on prostate but predicting in bladder, despite different pathologists examining the different tissues. When training on one patient but testing on another, AUROC in bladder is 0.79±0.11 and in prostate is 0.96±0.04. Our tool is available at https://bitbucket.org/aschaumberg/deepscope.

19.
Clin Lab Med ; 36(1): 133-52, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26851670

RESUMO

This article provides surgical pathologists an overview of health information systems (HISs): what they are, what they do, and how such systems relate to the practice of surgical pathology. Much of this article is dedicated to the electronic medical record. Information, in how it is captured, transmitted, and conveyed, drives the effectiveness of such electronic medical record functionalities. So critical is information from pathology in integrated clinical care that surgical pathologists are becoming gatekeepers of not only tissue but also information. Better understanding of HISs can empower surgical pathologists to become stakeholders who have an impact on the future direction of quality integrated clinical care.

20.
Clin Lab Med ; 36(1): 153-81, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26851671

RESUMO

Translational bioinformatics and clinical research (biomedical) informatics are the primary domains related to informatics activities that support translational research. Translational bioinformatics focuses on computational techniques in genetics, molecular biology, and systems biology. Clinical research (biomedical) informatics involves the use of informatics in discovery and management of new knowledge relating to health and disease. This article details 3 projects that are hybrid applications of translational bioinformatics and clinical research (biomedical) informatics: The Cancer Genome Atlas, the cBioPortal for Cancer Genomics, and the Memorial Sloan Kettering Cancer Center clinical variants and results database, all designed to facilitate insights into cancer biology and clinical/therapeutic correlations.

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