Publications

July 06, 2009

Sensors may be able to differentiate between cancerous and healthy cells

HealthDay (6/26,McKeever) reported, "Researchers at Georgia Institute of Technology and the University of Massachusetts at Amherst say they have developed highly sensitive sensors that pick up subtle differences on the surface of a cell that indicate if it is healthy or cancerous, even whether the cancer is metastatic or not." According to the joint paper published in the Proceedings of the National Academy of Sciences, the "sensors use the polymer PPE, or para-phenyleneethynylene, and three gold nanoparticles that tend to bond with the surface of chemically abnormal cells. When an abnormal cell surface grabs on to the gold nanoparticles, the PPE breaks off and glows," and the resulting "glowing PPE pattern helps scientists identify the cell type, as a cancer cell has slightly different proportions of biomarkers on its surface than a healthy cell." The authors say the next step involves testing "the chemical nose on real animal tissue, as opposed to cultured tissue," and refining "their ability to decipher the information the detection system gives them."

June 23, 2009

Blog content now syndicated on Newstex

Newstex offers aggregated, real-time content from new sources, blogs and videos to distributors who deliver that content to end-user customers. While content might be customized by each distributor to meet the needs of different audiences, several things always stay in effect — most importantly, links back to the original sources and publisher agreements.

Newstex provides three primary products: News On Demand, Blogs On Demand and Video On Demand.

News On Demand

what-we-do-newsThe flagship Newstex product is News On Demand, which collects content from thousands of online and offline news sources, adds value to it with stock tickers, people tags, and more, and then delivers it to distributors such as LexisNexis and Amazon Kindle, who customize it and provide it to end-users.

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Blogs On Demand

what-we-do-blogsNewstex collects content from premium blogs then delivers that content through full-text feeds with added stock tickers, people tags and more to its distributors, who customize it and provide it to end-users. Blogs included in Blogs On Demand are editorially reviewed to ensure they meet Newstex’s strict quality requirements.

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Video On Demand

what-we-do-video_150x98pxIn 2008, Newstex added video and podcasts to its offerings through Video On Demand. Videos are collected from sources around the world, and then Newstex adds transcriptions, stock tickers, people tags, and more. That enhanced content is provided to distributors who deliver it to end-user customers.

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June 03, 2009

Mayo Clinic Finds New Pathology Tests Double Sensitivity to Detect Bile Duct and Pancreatic Cancers

Pancreatic cancer and bile duct cancer are difficult to diagnose and often fatal because they are discovered in the advanced stages of the disease. Researchers have developed new tests that double the ability to detect bile duct and pancreatic cancers, according to a Mayo Clinic study published in the June issue of Gastroenterology.

    -- Additional audio and video resources, including excerpts from an interview with Dr. Lewis Roberts describing the research, are available on the Mayo Clinic News Blog, password: fish059.

Pancreatobiliary tumors such as bile duct cancer (cholangiocarcinoma) and pancreatic cancer often present as strictures, or a narrowing of the duct that can either be caused by benign inflammation or cancer. Physicians insert an endoscope down the throat and into the bile duct and pancreas region to examine possible tumors; however, the narrowness of the bile duct makes it difficult to distinguish benign and malignant strictures.

In this study, 498 patients with pancreatobiliary duct narrowing underwent an endoscopic procedure, and cell brushings were taken. Brushings were then analyzed by routine cytology, digital image analysis and fluorescence in situ hybridization (FISH) to determine the various tests' effectiveness and sensitivity in detecting and diagnosing cancer. While traditional cytology analysis relies on identifying abnormally shaped cells, the FISH test detects malignant cells using colored probes visible with a fluorescence microscope. Since cancer cells have an abnormal amount of DNA, by FISH these cells show extra copies of the probes compared to normal cells. The Mayo research team found that the combination of cytology and FISH raised the detection rate of bile duct and pancreatic cancer from 20 percent to 43 percent. "Bile duct and pancreatic cancers are very difficult to diagnose," says Lewis Roberts, M.B.Ch.B., Ph.D., Mayo Clinic gastroenterologist and the study's senior author.

"We were very pleased to see that the combination of FISH and cytology significantly improved our chances of diagnosing patients reliably. The earlier we can diagnose a patient, the better the types of treatment we can offer and the more likely they are to have long-term survival after treatment."

Treatments for bile duct cancer vary with the size of the tumor and how far it has advanced. These tumors usually grow slowly and spread gradually. In many cases, bile duct cancers are diagnosed at later stages. Current treatments include surgery, liver transplantation, chemotherapy, radiation therapy, photodynamic therapyand biliary drainage with plastic or metal stents. If the cancer cannot be completely removed by surgery but has not spread outside the liver, chemotherapy and radiation followed by liver transplantation may be an option. Mayo Clinic is one of the few medical facilities that offers a liver transplant protocol for early-stage bile duct cancer patients.

Bile duct cancer is rare and is most common in people aged 50 to 70. Approximately 5,000 cases of bile duct cancer are diagnosed in the United States each year, and the incidence of bile duct cancer is on the rise. Between 35,000 and 40,000 cases of pancreatic cancer are diagnosed per year in the United States.

Dr. K. Halling and Mayo Clinic have a financial interest in technology used in this research. Dr. Halling and Mayo Clinic have received annual royalties greater than the federal threshold for significant financial interest from the licensing to Abbott Molecular of other technology related to this research.

Mayo Clinic's Division of Gastroenterology and Hepatology has been ranked #1 in the U.S. News & World Report Honor Roll of Top Hospitals since the rankings began 19 years ago.

Other members of the Mayo research team included Emily Barr Fritcher; Benjamin Kipp, Ph.D.; Kevin Halling, M.D., Ph.D.; Trynda Oberg; Sandra Bryant; Robert Tarrell; Gregory Gores, M.D.; Michael Levy, M.D.; Amy Clayton, M.D.; and Thomas Sebo, M.D., Ph.D.

June 01, 2009

The impact of digital imaging in the field of cytopathology

Interesting paper by Dr. Liron Pantanowitz and colleagues at Baystate Medical Center, Tufts University School of Medicine.

Abstract: With the introduction of digital imaging, pathology is undergoing a digital transformation. In the field of cytology, digital images are being used for telecytology, automated screening of Pap test slides, training and education (e.g. online digital atlases), and proficiency testing. To date, there has been no systematic review on the impact of digital imaging on the practice of cytopathology. This article critically addresses the emerging role of computer-assisted screening and the application of digital imaging to the field of cytology, including telecytology, virtual microscopy, and the impact of online cytology resources. The role of novel diagnostic techniques like image cytometry is also reviewed.

Keywords: Cytology, cytometry, digital, image, informatics, Pap test, proficiency testing, screening, telecytology, virtual image

Pantanowitz L, Hornish M, Goulart RA. The impact of digital imaging in the field of cytopathology. CytoJournal 2009;6:6 http://www.cytojournal.com/text.asp?2009/6/1/6/48606
Download CytoJournal616-8045693_222056.pdf (468.5K)

May 08, 2009

Recent paper on legal aspects of teleconsultation

One of our recent GI/liver pathology fellows completed a manuscript that addresses the key points of the legal and regulatory environment involving teleconsultation in pathology.  The paper will appear in an upcoming issue of Human Pathology

A pdf of the corrected proof can be downloaded here.

Download leungkaplan_humanpathology_medicolegalaspectsoftelepathology.pdf (109.1K)

Summary

A pathologist may practice telepathology in another room from the original slide using the hospital intranet, he/she may practice it if a CD-ROM is reviewed with a “virtual histologic image” or digital slide. As pathology becomes increasingly subspecialized, and pathologists are progressively more engaged in practices situations where they may not be in a centralized laboratory location, use of telepathology technology may be increasingly common. We touch on select medicolegal and reimbursement issues in the practice of telepathology. Primary and secondary legal sources are reviewed, as well as primary medical references. Telepathology is an evolving area of telemedicine. Guidelines for primary opinion telepathology should be driven from best practices in conventional laboratory procedures and can enhance the practice of pathology. However, it should be undertaken with the understanding that the legal and regulatory environment involving such practices is evolving as well.

April 02, 2009

BioImagene Launches New Ki-67 Algorithm For Prostate Image Analysis

From Medical News Today.  Time will tell if this is a useful marker in the clinical setting in prostate cancer.  What I find most interesting about the press release is the statement about expected "launch of a series of additional algorithms to serve the pathology and research communities".

"BioImagene, the leading provider of innovative digital pathology solutions announced the launch of a new Ki-67 prostate image analysis algorithm. The algorithm, which is part of Virtuoso TM, a comprehensive suite of web-based software applications for digital pathology, is used to detect and provide quantitative measurement of the protein biomarker Ki-67.

According to the Journal of Clinical Oncology, Cancer Research and other clinical journals, Ki-67 immunohistochemistry may be a valuable predictor of biochemical relapse and distant metastasis after prostatectomy and radiation therapy. Prostate cancer continues to be the most prevalent cancer in men, according to the American Cancer Society.

"The launch of the Ki-67 algorithm that can be used in a research setting illustrates the potential impact digital pathology can have on the practice of medicine," commented Dr. Ajit Singh, CEO BioImagene. "In the coming months, we expect to launch a series of additional algorithms to serve the pathology and research communities."

The launch of the Ki-67 algorithm adds to the company's growing offering of image analysis tools. BioImagene also has a PIN4 algorithm for prostate cancer research, and FDA cleared algorithms to assess HER2/neu immunohistochemistry status. The iScan Coreo and associated software are used to detect and provide a quantitative measurement of HER2/neu, a protein measured in breast cancer patients to determine their candidacy for treatment with the Genentech drug Herceptin™."

March 13, 2009

Recent article entitled "Digital Pathology is Growing Despite Fears"

With many thanks to David Shenkenberg, Features Editor of Photonics Spectra and Biophotonics I am able to provide a recent article courtesy of Biophotonics magazine last month. 

David's article hits several high points and touches on technology offered by Definiens, in particular, TissueMap, a software application which identifies and relates objects on pathology slides in a way that is designed to be intuitive.

Download "Digital Pathology is Growing Despite Fears" from February issue of Biophotonics magazine.

Definiens1 
Definiens2

March 03, 2009

Impact of digital image manipulation in cytology specimens

Recent paper on impact of digital image manipulation in cytology specimens.

Download article

Jeffery Pinco, MD; Robert A. Goulart, MD; Christopher N. Otis, MD; Jane Garb, MS; Liron Pantanowitz, MD

From the Departments of Pathology (Drs Pinco, Goulart, Otis, and Pantanowitz) and Surgery (Dr Garb), Baystate Medical Center, Tufts University School of Medicine, Springfield, Mass

Context.—Digital images have become an important component of cytology practice. They are used in telecytology, automated screening, educational material, and Web sites and have potential for use in proficiency testing. However, there has been no formal evaluation to date to determine if digital image manipulation (intentional or unintentional) can affect their interpretation.

Objective.—To investigate whether alteration of digital cytology images affects diagnosis.

Design.—Acquired digital images of ThinPrep Papanicolaou test slides were manipulated (rotated 90;dg and brightness, contrast, red-green-blue color, and luminosity adjusted) using Photoshop. A test composed of these altered images, along with their original (unaltered) image and exact duplicates was given to 22 cytologists (13 cytotechnologists, 8 cytopathologists, and 1 fellow). All images were rated as negative, atypical (atypical squamous cells of undetermined significance), low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, or positive for cancer. Weighted κ and heterogeneity χ2 statistics were used to measure levels of agreement and assess concordance between groups.

Results.—The level of agreement for identical duplicate images was excellent (κ = 0.81), compared with the poor agreement for manipulated image pairs (κ = 0.21), a statistically significant difference (P < .001). For all altered image types agreement was poor. There was no significant difference between cytotechnologists and cytopathologists in level of agreement (P = .56).

Conclusions.—Manipulation of a Papanicolaou test digital image, irrespective of the specific category of cytologic material photographed, significantly affects its interpretation by both cytotechnologists and cytopathologists. This suggests that care needs to be taken when digital cytology images are used, to specifically ensure that their alteration does not affect diagnosis.

 

February 26, 2009

The Anxiety of the Biopsy from NY Times Health Blog

Came across this post from NY Times Health blog this week.  Couple of thoughts:

Biopsies required to fix for certain time should need for certain IHC (i.e. HER2) required.  Formal guidelines coming on ER/PR as well just as we know have ASCO/CAP guidelines for HER2 testing.  Despite the time requirement, processing can and often occurs in 1 day and can be signed out the following day.  I would gather most laboratories will complete majority of sign-outs in one day.  We do it routinely here otherwise get calls from clinicians by mid-day asking for results.  Of course some require additional levels, review, consultation and/or IHC but the exception, not the rule.  2.5 day turn around time seems excessive.  5 days for 73 of 126 women not to have a result seems protracted. I would have hoped the patients' clinician explained reason for delay but this did not seem to occur either. 

Nonetheless, in the laboratory industry the goals are to have high diagnostic accuracy, rapid turnaround time and cost control; said another way, you can have it right, fast or cheap, pick any two.  If given a choice, I gather all of us would choose the right answer in a timely fashion at a reasonable cost. Nonetheless, it sometimes takes a little longer to ensure the right answer & may involve more tests increasing costs.  Having been on both sides of this equation I would rather have the right answer even if it costs more and takes longer.  I wonder what happens to cortisol levels with misdiagnoses and inappropriate, unnecessary or unindicated therapy...

Post and abstract from paper published below.

Waiting days for the results of a breast biopsy appears to affect stress hormone levels just as much as finding out you have cancer does, a new study shows.

Harvard researchers tracked 126 women who were undergoing breast biopsy, monitoring their levels of the stress hormone cortisol while they waited.

One of the most surprising findings, researchers said, was how long many women had to wait before receiving their results. While the average wait time was 2.5 days, many women had to wait five days or longer. By the fifth day, 37 women learned their biopsy was benign, 16 learned they had cancer and 73 still did not have a result, according to the report, which appeared in the medical journal Radiology. Most of the women who did not have a diagnosis had not received any information or explanation for the delay.

Women who were still uncertain about their diagnosis had abnormal cortisol levels that were “essentially indistinguishable’’ from the cortisol profiles of the women who were told they had cancer. And women without a diagnosis had significantly worse cortisol profiles compared to women who had received benign test results.

“If you talk to any woman who has had a biopsy who has had to wait for results, she will tell you it’s a horrible roller coaster,’’ said Dr. Elvira V. Lang, associate professor of radiology at Harvard Medical School and Beth Israel Deaconess Medical Center. “Even when patients hear they have a cancer, they can start doing something. But if you hang in there for five days and you still don’t know what direction it goes, it’s just very stressful.’’

The concern, Dr. Lang said, is that cortisol levels can influence wound healing and immune response, raising a woman’s potential health risks if she ultimately needs to be treated for cancer. And the stress and anxiety of waiting also affects the quality of life of a woman, her family and her ability to function well at work, she said.

Dr. Lang said the research should spur hospitals to focus not only on speeding up test results, but on improving communication and possibly offering psychological services to women who are waiting for a diagnosis. The study was funded by the Department of Defense breast cancer research program. Dr. Lang has a financial interest in a consulting firm that trains medical personnel how to improve communication with patients.

“We have to work much faster to get results to women,’’ Dr. Lang said. “You want to keep stressors as profound as this as short as possible.’’



Large-Core Breast Biopsy: Abnormal Salivary Cortisol Profiles Associated with Uncertainty of Diagnosis

Elvira V. Lang, MD, FSIR, FSCEH, Kevin S. Berbaum, PhD, and Susan K. Lutgendorf, PhD


From the Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02115 (E.V.L.); and Departments of Radiology (K.S.B.) and Psychology (S.K.L.), University of Iowa, Iowa City, Iowa. Received June 19, 2008; revision requested July 22; revision received July 31; accepted August 27; final version accepted September 16. Supported by the U.S. Army Research and Materiel Command DAMD 17-01-01. E-mail: elang@bidmc.harvard.edu.

Purpose: To determine whether uncertainty of the diagnosis after large-core breast biopsy (LCBB) adversely affects biochemical stress levels.

Materials and Methods: This study was institutional review board approved and HIPAA compliant, and all patients gave written informed consent. One hundred fifty women aged 18–86 years collected four salivary cortisol samples per day for 5 days after LCBB. t Tests were used to compare diurnal cortisol slopes among three groups: patients who did not have a final diagnosis (uncertain group), patients who knew they had cancer (known malignant group), and patients who knew they had benign disease (known benign group).

Results: Women learned their diagnosis on days 1–6 (mean, day 2.4) after LCBB. Analysis was truncated at day 5, when the data from a sufficient number of patients from each group were available for meaningful analysis: 16 patients from the known malignant group, 37 from the known benign group, and 73 from the uncertain group, which totaled 126 patients. The mean cortisol slope for the women with an uncertain diagnosis (–0.092 ln [µg/dL]/hr; 95% confidence interval [CI]: –0.113 ln [µg/dL]/hr, –0.072 ln [µg/dL]/hr) was significantly flatter (less desirable) than that for the women who learned that they had benign disease (–0.154 ln [µg/dL]/hr; 95% CI: –0.197 ln [µg/dL]/hr, –0.111 ln [µg/dL]/hr; P = .014) but not significantly different from that for the women who learned that they had malignant disease (–0.110 ln [µg/dL]/hr; 95% CI: –0.147 ln [µg/dL]/hr, –0.073 ln [µg/dL]/hr; P = .421).

Conclusion: Uncertainty about the final diagnosis after LCBB is associated with substantial biochemical distress, which may have adverse effects on immune defense and wound healing. Results indicate the need for more rapid communication of biopsy results.

© RSNA, 2009

February 25, 2009

Raman Molecular Imaging For Digital Pathology

The use of digital pathology techniques without stains or reagents is gaining traction for use in clinical practice, particularly for "gray" diagnostic areas where tride-and-true physical stains and or chemicals may not provide high enough specificity for diagnosis.  I have been following the work being done by ChemImage and their clinical projects with some exciting results.  Check out their offerings and results with Raman and hyperspectral imaging.

Accurate interpretation of pathology specimens can be very challenging for a number of tissue and disease types. Traditional pathological evaluation of tissues and cells is a relatively subjective evaluation of spatially complex stained tissue samples. Since a physician makes treatment decisions based on the evaluation of tissue by a pathologist, accuracy is of the utmost importance.

ChemImage’s Raman Molecular Imaging (RMI) approach using the FALCON II™ enables the objective assessment of tissues without the use of stains or reagents.

Img-digital-stained             Img-digital-unstained 

H&E Stained Prostate Tissue         Raman Image of Unstained Prostate Tissue

(Performed in collaboration with the Mayo Clinic and Allegheny General Hospital)

Raman Molecular Imaging Gives Pathologists:

Raman molecular images are acquired from tissue samples illuminated by a laser in a microscope. The images are analyzed using chemometric-based classification algorithms to objectively classify the sample in terms of disease state. RMI is used to create, in effect, a digital stain of tissues and cells—without the use of reagents.

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