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Complete Pathology Reports

Posted in Clinical Diagnostics, Health Law & Patient Safety, HealthCare IT, tagged , , , , on January 16, 2015| Leave a Comment »

Larry Bernstein, MD, FCAP, Reporter

http://pharmaceuticalintelligence.com/1/16/2015/Complete-Pathology-Reports

Complete Pathology Reports and Their Importance for Clinical Decision Making

Posted by Michael Doyle on Jan 15, 2015 10:17:00 AM

Pathology reports provide care teams with crucial diagnostic and prognostic
data. For population-level research and quality assurance initiatives, it’s
important that reports are consistently complete. But report consistency
can also be important for the medical outcomes of a single person.

Today, I’ll discuss the unique experience of a friend of mine, and I’ll
explain how his isolated incident is connected to large-scale initiatives
in pathology reporting quality assurance.

Incomplete Pathology Reports

A friend of mine has particularly fair skin, and is at thus at increased
risk for skin cancers. His family physician has recommended he have
various moles removed to prevent the development of possible
skin cancers.

Over time, my friend and his family physician became troubled by
the inconsistencies they found in comparing the pathology reports
from his five different biopsies.

Five out of five reports identified that the moles were dysplastic—
irregular and potentially cancerous. Yet only three reports identified
that this dysplasia was in his skin’s basal cells as opposed to
squamous cells or melanocytes.

The the type of skin cells exhibiting dysplasia is important to clinical
decision making: dysplasia affecting melanocytes is the basis for
melanomas, the most serious forms of skin cancer. Lacking this
information makes it more difficult for care teams to develop the
comprehensive understanding of an individual’s medical history
that guides clinical decision making.

In response to the incompleteness of the pathology reports, the
family physician remarked, “I rarely have to query a pathologist
about what’s in a report. It’s usually about what’s left out.”

And it’s not just one physician who’s seeking better reports.

Synoptic Reporting for Complete Consistency in Pathology

For over 20 years, the College of American Pathologists (CAP)
has been developing protocols and templates to standardize
pathology reporting, substantially improving the completeness and
consistency of pathology reports through the use of the synoptic—
i.e. structured—format.

Synoptic reporting uses coded data templates to produce standardized
reports that are more complete and consistent than reports generated
using narrative methods. Since 2014, the use of synoptic reporting has
been among the CAP Laboratory Accreditation Program requirements.

Cancer Care Ontario introduced synoptic reporting for pathologist across
the province—the largest jurisdiction to do so. Clinicians have shown
over- whelming support for this initiative, finding that synoptic reports
have facilitated consistent intepretation of diagnostic and prognostic data.

The Canadian Partnership Against Cancer is building on Ontario’s
success to help implement synoptic pathology reporting across
Canada, strengthening provincial cancer registries and fostering
cross-jurisdictional research and quality assurance initiatives.

Clinical research has continually found that the use of synoptic reporting
improves the completeness of pathology reports [1, 2, 3, 4]. These
conclusions have been upheld in research on synoptic reporting
for surgery as well [5, 6].

An important goal of synoptic reporting implementation initiatives is equipping
pathologists and surgeons with clinical documentation software that enables
them to provide each other with specific, reliable and actionable data—through
complete and consistent reports.

  1. McLeod RS, Kirsh R. What impact has the introduction of synoptic
    reporting for rectal cancer had on reporting outcomes for specialist
    gastrointestinal and nongastrointestinal pathologists? Archives of
    Pathology & Lab Medicine2011;135(11):1471-5.
  2. Pignol JP, et al. Accuracy and completeness of pathology reporting–
    impact on partial breast irradiation eligibility. Clinical Oncology (Royal
    College of Radiology). 2012 Apr; 24(3):177-82.
  3. Branston LK, Greening S, Newcombe RG et al. The implementation
    of guidelines and computerised forms improves the completeness
    of cancer pathology reporting. The CROPS project: a randomised
    controlled trial in pathology. EuropeanJournal of Cancer
    2002;38(6):764-72
  4. Karim RZ et al. The advantage of using synoptic pathology report
    format for cutaneous Histopathology 2008 Jan;52(2);130-8.
  5. Edhemovic I, Temple WJ, de Gara CJ, Stuart GC. The computer
    synoptic operative report–a leap forward in the science of surgery.
    Annals of Surgical Oncology 2004;11(10):941-7.
  6. Donahoe L, Bennett S, et al. Completenes of dictated operative
    reports in breast cancer –the case for synoptic reporting.
    Journal of Surgical Oncology2012;106(1):79-83.

Topics: Pathology, Medical Reporting Errors

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The unfortunate ending of the Tower of Babel construction project and its effect on modern imaging-based cancer patients’ management

Posted in Imaging-based Cancer Patient Management, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on October 22, 2012| 4 Comments »

The unfortunate ending of the Tower of Babel construction project and its effect on modern imaging-based cancer patients’ management

Curator: Dror Nir, PhD

 

The story of the city of Babel is recorded in the book of Genesis 11 1-9. At that time, everyone on earth spoke the same language.

Picture: Pieter Bruegel the Elder: The Tower of Babel_(Vienna)

It is probably safe to assume that medical practitioners at that time were reporting the status of their patients in a standard manner. Although not mentioned, one might imagine that, at that time, ultrasound or MRI scans were also reported in a standard and transferrable manner. The people of Babel noticed the potential in uniform communication and tried to build a tower so high that it would  reach the gods. Unfortunately, God did not like that, so he went down (in person) and confounded people’s speech, so that they could not understand each another. Genesis 11:7–8.

This must be the explanation for our inability to come to a consensus on reporting of patients’ imaging-outcome. Progress in development of efficient imaging protocols and in clinical management of patients is withheld due to high variability and subjectivity of clinicians’ approach to this issue.

Clearly, a justification could be found for not reaching a consensus on imaging protocols: since the way imaging is performed affects the outcome, (i.e. the image and its interpretation) it takes a long process of trial-and-error to come up with the best protocol.  But, one might wonder, wouldn’t the search for the ultimate protocol converge faster if all practitioners around the world, who are conducting hundreds of clinical studies related to imaging-based management of cancer patients, report their results in a standardized and comparable manner?

Is there a reason for not reaching a consensus on imaging reporting? And I’m not referring only to intra-modality consensus, e.g. standardizing all MRI reports. I’m referring also to inter-modality consensus to enable comparison and matching of reports generated from scans of the same organ by different modalities, e.g. MRI, CT and ultrasound.

As developer of new imaging-based technologies, my personal contribution to promoting standardized and objective reporting was the implementation of preset reporting as part of the prostate-HistoScanning product design. For use-cases, as demonstrated below, in which prostate cancer patients were also scanned by MRI a dedicated reporting scheme enabled matching of the HistoScanning scan results with the prostate’s MRI results.

The MRI reporting scheme used as a reference is one of the schemes offered in a report by Miss Louise Dickinson on the following European consensus meeting : Magnetic Resonance Imaging for the Detection, Localisation, and Characterisation of Prostate Cancer: Recommendations from a European Consensus Meeting, Louise Dickinson a,b,c,*, Hashim U. Ahmed a,b, Clare Allen d, Jelle O. Barentsz e, Brendan Careyf, Jurgen J. Futterer e, Stijn W. Heijmink e, Peter J. Hoskin g, Alex Kirkham d, Anwar R. Padhani h, Raj Persad i, Philippe Puech j, Shonit Punwani d, Aslam S. Sohaib k, Bertrand Tomball,Arnauld Villers m, Jan van der Meulen c,n, Mark Emberton a,b,c,

http://www.europeanurology.com/article/S0302-2838(10)01187-5

Image of MRI reporting scheme taken from the report by Miss Louise Dickinson

The corresponding HistoScanning report is following the same prostate segmentation and the same analysis plans:


Preset reporting enabling matching of HistoScanning and MRI reporting of the same case.

It is my wish that already in the near-future, the main radiology societies (RSNA, ESR, etc..) will join together to build the clinical Imaging’s “Tower of Babel” to effectively address the issue of standardizing reporting of imaging procedures. This time it will not be destroyed…:-)

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Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-guided intervention?

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Imaging-based Cancer Patient Management, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on October 16, 2012| 23 Comments »

Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-guided intervention?

Author: Dror Nir, PhD

Article 9.6.Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-guided intervention?

Advances in techniques for cancer lesions’ detection and localisation [1-6] opened the road to methods of localised (“focused”) cancer treatment [7-10].  An obvious challenge on the road is reassuring that the imaging-guided treatment device indeed treats the region of interest and preferably, only it.

A step in that direction was taken by a group of investigators from Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada who evaluate the feasibility and safety of magnetic resonance (MR) imaging–controlled transurethral ultrasound therapy for prostate cancer in humans [7]. Their study’s objective was to prove that using real-time MRI guidance of HIFU treatment is possible and it guarantees that the location of ablated tissue indeed corresponds to the locations planned for treatment. Eight eligible patients were recruited.

 

The setup

 

Treatment protocol

 

The result

 

“There was excellent agreement between the zone targeted for treatment and the zone of thermal injury, with a targeting accuracy of ±2.6 mm. In addition, the temporal evolution of heating was very consistent across all patients, in part because of the ability of the system to adapt to changes in perfusion or absorption properties according to the temperature measurements along the target boundary.”

 

Technological problems to be resolved in the future:

“Future device designs could incorporate urinary drainage during the procedure, given the accumulation of urine in the bladder during treatment.”

“Sufficient temperature resolution could be achieved only by using 10-mm-thick sections. Our numeric studies suggest that 5-mm-thick sections are necessary for optimal three-dimensional conformal heating and are achievable by using endorectal imaging coils or by performing the treatment with a 3.0-T platform.”

Major limitation: “One of the limitations of the study was the inability to evaluate the efficacy of this treatment; however, because this represents, to our knowledge, the first use of this technology in human prostate, feasibility and safety were emphasized. In addition, the ability to target the entire prostate gland was not assessed, again for safety considerations. We have not attempted to evaluate the effectiveness of this treatment for eradicating cancer or achieving durable biochemical non-evidence of disease status.”

References

  1. SIMMONS (L.A.M.), AUTIER (P.), ZATURA (F.), BRAECKMAN (J.G.), PELTIER (A.), ROMICS (I.), STENZL (A.), TREURNICHT (K.), WALKER (T.), NIR (D.), MOORE (C.M.), EMBERTON (M.). Detection, localisation and characterisation of prostate cancer by Prostate HistoScanning.. British Journal of Urology International (BJUI). Issue 1 (July). Vol. 110, Page(s): 28-35
  2. WILKINSON (L.S.), COLEMAN (C.), SKIPPAGE (P.), GIVEN-WILSON (R.), THOMAS (V.). Breast HistoScanning: The development of a novel technique to improve tissue characterization during breast ultrasound. European Congress of Radiology (ECR), A.4030, C-0596, 03-07/03/2011.
  3. Hebert Alberto Vargas, MD, Tobias Franiel, MD,Yousef Mazaheri, PhD, Junting Zheng, MS, Chaya Moskowitz, PhD, Kazuma Udo, MD, James Eastham, MD and Hedvig Hricak, MD, PhD, Dr(hc) Diffusion-weighted Endorectal MR Imaging at 3 T for Prostate Cancer: Tumor Detection and Assessment of Aggressiveness. June 2011 Radiology, 259,775-784.
  4. Wendie A. Berg, Kathleen S. Madsen, Kathy Schilling, Marie Tartar, Etta D. Pisano, Linda Hovanessian Larsen, Deepa Narayanan, Al Ozonoff, Joel P. Miller, and Judith E. Kalinyak Breast Cancer: Comparative Effectiveness of Positron Emission Mammography and MR Imaging in Presurgical Planning for the Ipsilateral Breast Radiology January 2011 258:1 59-72.
  5. Anwar R. Padhani, Dow-Mu Koh, and David J. Collins Reviews and Commentary – State of the Art: Whole-Body Diffusion-weighted MR Imaging in Cancer: Current Status and Research Directions Radiology December 2011 261:3 700-718
  6. Eggener S, Salomon G, Scardino PT, De la Rosette J, Polascik TJ, Brewster S. Focal therapy for prostate cancer: possibilities and limitations. Eur Urol 2010;58(1):57–64).
  7. Rajiv Chopra, PhD, Alexandra Colquhoun, MD, Mathieu Burtnyk, PhD, William A. N’djin, PhD, Ilya Kobelevskiy, MSc, Aaron Boyes, BSc, Kashif Siddiqui, MD, Harry Foster, MD, Linda Sugar, MD, Masoom A. Haider, MD, Michael Bronskill, PhD and Laurence Klotz, MD. MR Imaging–controlled Transurethral Ultrasound Therapy for Conformal Treatment of Prostate Tissue: Initial Feasibility in Humans. October 2012 Radiology, 265,303-313.
  8. Black, Peter McL. M.D., Ph.D.; Alexander, Eben III M.D.; Martin, Claudia M.D.; Moriarty, Thomas M.D., Ph.D.; Nabavi, Arya M.D.; Wong, Terence Z. M.D., Ph.D.; Schwartz, Richard B. M.D., Ph.D.; Jolesz, Ferenc M.D.  Craniotomy for Tumor Treatment in an Intraoperative Magnetic Resonance Imaging Unit. Neurosurgery: September 1999 – Volume 45 – Issue 3 – p 423
  9. Medel, Ricky MD,  Monteith, Stephen J. MD, Elias, W. Jeffrey MD, Eames, Matthew PhD, Snell, John PhD, Sheehan, Jason P. MD, PhD, Wintermark, Max MD, MAS, Jolesz, Ferenc A. MD, Kassell, Neal F. MD. Neurosurgery: Magnetic Resonance–Guided Focused Ultrasound Surgery: Part 2: A Review of Current and Future Applications. October 2012 – Volume 71 – Issue 4 – p 755–763
  10. Bruno Quesson PhD, Jacco A. de Zwart PhD, Chrit T.W. Moonen PhD. Magnetic resonance temperature imaging for guidance of thermotherapy. Journal of Magnetic Resonance Imaging, Special Issue: Interventional MRI, Part 1, Volume 12, Issue 4, pages 525–533, October 2000

Writer: Dror Nir, PhD

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Introducing smart-imaging into radiologists’ daily practice.

Posted in Imaging-based Cancer Patient Management, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on October 9, 2012| 6 Comments »

Introducing smart-imaging into radiologists’ daily practice.

Author and Curator: Dror Nir, PhD

Article 11.3.1 Introducing smart imaging into radiologists daily practice

Radiology congresses are all about imaging in medicine. Interestingly, radiology originates from radiation. It was the discovery of X-ray radiation at the beginning of the 20th century that opened the road to “seeing” the inside of the human body without harming it (at that time that meant cutting into the body).

Radiology meetings are about sharing experience and knowhow on imaging-based management patients. The main topic is always image-interpretation: the bottom line of clinical radiology! This year’s European Congress of Radiology (ECR) dedicated few of its sessions to recent developments in image-interpretation tools. I chose to discuss the one that I consider contributing the most to the future of cancer patients’ management.

In the refresher course dedicated to computer application the discussion was aimed at understanding the question “How do image processing and CAD impact radiological daily practice?” Experts’ reviews gave the audience some background information on the following subjects:

  1. A.     The link between image reconstruction and image analysis.
  2. B.     Semantic web technologies for sharing and reusing imaging-related information
  3. C.     Image processing and CAD: workflow in clinical practice.

I find item A to be a fundamental education item. Not once did I hear a radiologist saying: “I know this is the lesion because it’s different on the image”.  Being aware of the computational concepts behind image rendering, even if it is at a very high level and lacking deep understanding of the computational processes,  will contribute to more balanced interpretations.

Item B is addressing the dream of investigators worldwide. Imagine that we could perform a web search and find educating, curated materials linking visuals and related clinical information, including standardized pathology reporting. We would only need to remember that search engines used certain search methods and agree, worldwide, on the method and language to be used when describing things. Having such tools is a pre-requisite to successful pharmaceutical and bio-tech development.

I find item C strongly linked to A, as all methods for better image interpretation must fit into a workflow. This is a design goal that is not trivial to achieve. To understand what I mean by that, try to think about how you could integrate the following examples in your daily workflow: i.e. what kind of expertise is needed for execution, how much time it will take, do you have the infrastructure?

In the rest of this post, I would like to highlight, through examples that were discussed during ECR 2012, the aspect of improving cancer patients’ clinical assessment by using information fusion to support better image interpretation.

  • Adding up quantitative information from MR spectroscopy (quantifies biochemical property of a target lesion) and Dynamic Contrast Enhanced MR imaging (highlights lesion vasculature).

Image provided by: Dr. Pascal Baltzer, director of mammography at the centre for radiology at Friedrich Schiller University in Jena, Germany

 
  • Registration of images generated by different imaging modalities (Multi-modal imaging registration).

The following examples: Fig 2 demonstrates registration of a mammography image of a breast lesion to an MRI image of this lesion. Fig3 demonstrates registration of an ultrasound image of a breast lesion scanned by an Automatic Breast Ultrasound (ABUS) system and an MRI image of the same lesion.

Images provided by members of the HAMAM project (an EU, FP7 funded research project: Highly Accurate Breast Cancer Diagnosis through Integration of Biological Knowledge, Novel Imaging Modalities, and Modelling): http://www.hamam-project.org

 

 Multi-modality image registration is usually based on the alignment of image-features apparent in the scanned regions. For ABUS-MRI matching these were: the location of the nipple and the breast thickness; the posterior of the nipple in both modalities; the medial-lateral distance of the nipple to the breast edge on ultrasound; and an approximation of the rib­cage using a cylinder on the MRI. A mean accuracy of 14mm was achieved.

Also from the HAMAM project, registration of ABUS image to a mammography image:

registration of ABUS image to a mammography image, Image provided by members of the HAMAM project (an EU, FP7 funded research project: Highly Accurate Breast Cancer Diagnosis through Integration of Biological Knowledge, Novel Imaging Modalities, and Modelling): http://www.hamam-project.org

  • Automatic segmentation of suspicious regions of interest seen in breast MRI images

Segmentation of suspicious the lesions on the image is the preliminary step in tumor evaluation; e.g. finding its size and location. Since lesions have different signal/image character­istics to the rest of the breast tissue, it gives hope for the development of computerized segmentation techniques. If successful, such techniques bear the promise of enhancing standardization in the reporting of lesions size and location: Very important information for the success of the treatment step.

Roberta Fusco of the National Cancer Institute of Naples Pascal Foundation, Naples/IT suggested the following automatic method for suspi­cious ROI selection within the breast using dynamic-derived information from DCE-MRI data.

 

Automatic segmentation of suspicious ROI in breast MRI images, image provided by Roberta Fusco of the National Cancer Institute of Naples Pascal Foundation, Naples/IT

 

 Her algorithm includes three steps (Figure 2): (i) breast mask extraction by means of automatic intensity threshold estimation (Otsu Thresh-holding) on the par­ametric map obtained through the sum of intensity differences (SOD) calculated pixel by pixel; (ii) hole-filling and leakage repair by means of morphological operators: closing is required to fill the holes on the boundaries of breast mask, filling is required to fill the holes within the breasts, erosion is required to reduce the dilation obtained by the closing operation; (iii) suspicious ROIs extraction: a pixel is assigned to a suspicious ROI if it satisfies two conditions: the maximum of its normalized time-intensity curve should be greater than 0.3 and the maximum signal intensity should be reached before the end of the scan time. The first condition assures that the pixels within the ROI have a significant contrast agent uptake (thus excluding type I and type II curves) and the second condition is required for the time-intensity pattern to be of type IV or V (thus excluding type III curves).

Written by: Dror Nir, PhD

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Imaging-guided biopsies: Is there a preferred strategy to choose?

Posted in Bio Instrumentation in Experimental Life Sciences Research, CANCER BIOLOGY & Innovations in Cancer Therapy, Imaging-based Cancer Patient Management, Medical Devices R&D Investment, tagged , , , , , , , , , , , , , , , , , , , , , , , on September 29, 2012| 7 Comments »

Imaging-guided biopsies: Is there a preferred strategy to choose?

Author: Dror Nir, PhD

Article 11.3.3 Imaging guided biopsies Is there a preferred strategy to choose

The most stressful period in a cancer patients’ pathway is from the moment they fail a screening test or present with suspicious symptoms to the moment they are diagnosed. Today’s medical guidelines require histopathology findings as the only acceptable proof: positive results  mean you are a cancer patient, negative results mean, well…maybe you are and maybe you are not. You now enter into what might be a very long period, sometime years, of uncertainty regarding your health and prospects. And why?

Because the substance for histopathology is acquired by biopsies, and biopsies are known to be inaccurate. For example, breast and prostate biopsies  fail to find 25% to 35% of the cancer lesions at the first biopsy session.

Therefore, it is not surprising that from the beginning of this procedure,  medical practitioners look for ways to incorporate imaging into the workflow. In the last decade, significant progress has been made in the introduction of imaging-guided biopsies. The most common modalities were ultrasound and CT/mammography. Recently, as the industry solved the issues of magnetic field compatibility for biopsy needles and the introduction of open MRI systems, MRI-guided biopsies were also made  possible.

Ultrasound-guided biopsies are  by far the most commonly used procedure. Why? Because they  can be often performed as an office-based procedure. Here are some interesting links to YouTube videos describing such procedures:

  • Prostate

Prostate Ultrasound and Prostate Biopsy by Dr. Neil Baum

Transrectal ultrasound (Trus) Biopsy of the prostate

  • Breast

Ultrasound-Guided Breast Biopsy

Breast Tissue Biopsy

The main advantages: they are easily accessible, low cost and quick. The disadvantages of these procedures are  that they are very much operator dependent, rather than standardized, and there are no quality assurance guidelines attached. Efforts to standardize ultrasound-based biopsies and increase their efficiency are evident by recent introductions of ultrasound systems into the market ,  which support real-time guided biopsies and ultrasound applications that perform real-time biopsy tracking. But these systems are still far from being widely available. I will touch on this issue in my upcoming posts as I am part of these efforts.

CT and Mammography guided biopsies require more sophisticated equipment and well-trained operators. As an example:

Breast Biopsy – What To Expect

The main advantage: if you return to the same operator, the process is likely to be reproducible. The disadvantages are identical to that of ultrasound-based biopsies. It is worthwhile to note that, recently, radiologists who perform biopsies are required to go through a certification process. Still, such certification demands vary between the various radiology societies.

MRI-guided biopsies are an even more sophisticate and complex procedure:

  • Prostate:

DynaTRIM Video

DynaTRIM Intervention

An interesting quote from Dr. Hashim U. Ahmed, M.D., MRCS, Division of Urology  Department of Surgery, University College of London (https://mail.google.com/mail/u/1/?shva=1#label/Work%2FLinks%2FAuntMinnie/139d9c5bc6bda842): “Advocating the widespread use of MRI before biopsy in a population of men with risk parameters for harboring prostate cancer has a number of advantages, which might ultimately benefit the care these men undergo. Increasing the detection of prostate cancer that requires treatment while avoiding biopsy – and hence unnecessary treatment – in those with insignificant or no cancer are compelling arguments for this approach.”

  • Breast

MRI Breast Biopsy – Diagnostic and Biopsy Services for Breast Evaluation

I recommend reading the following article regarding the use of Open MRI to guide freehand biopsies of breast lesions. Especially interesting is the discussion where the authors give a good description of the difficulties in breast biopsies they are trying to overcome in order to achieve good lesion sampling.

MR-guided Freehand Biopsy of Breast Lesions in a 1.0-T Open MR Imager with a Near-Real-time Interactive Platform: Preliminary Experience Frank Fischbach, MD, et. al

http://radiology.rsna.org/content/early/2012/08/14/radiol.12110981.full?sid=bd45ceb4-9c8d-4ffc-b80b-0345ee679b4e

The question remains: which biopsy procedure is the best? And does this question have one coherent answer, i.e. one that will satisfy the patients, the doctors and the health-care insurers?  Will the answer to this question remain the subject of endless uncoordinated clinical studies?

If anyone who reads this post knows on methodological scientific or regulatory initiatives aimed at answering this question on a level of global guide lines  I would appreciate his comment.

Written by: Dror Nir, PhD.

 

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