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Prostate Biopsy Processing:  An Innovative Model for Reducing Cost, Test Time and Improving Diagnostic Material

Dip Shukla¹, Jennifer Morocho2, Deanne Smith¹, Drew Sciacca¹, Meghan Pickard¹, Michelle Wahlsten2, Ashley Gunderson2, Andy Thompson¹, Badrinath Konety1, Christopher Warlick¹, Paari Murugan¹

1University of Minnesota and 2Fairview Laboratories, Minneapolis, MN

107th Annual Meeting of the United States and Canadian Academy of Pathology, March 17-23, 2018, Vancouver, BC, Canada

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Disclosure

  • Nothing To Disclose – The authors of this abstract have indicated that they have no conflicts of interest that relate to the contents of this abstract/study.

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Background

  • Prostate cancer is the 2nd highest-incident cancer in American men, with a rising rate of diagnosis over the last 60 years
  • Evaluation involves: prostate-specific-antigen blood tests, physical examination, imaging, and, most importantly, prostate needle biopsy

www.aviva.co.uk

Biopsy Gun

Rep image of TRUS prostate biopsy;

However, there are several concerns that exist with this procedure.

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Prostate Needle Biopsy Concerns

  • Process waste
    • Conventional protocol for processing twelve biopsies per case is uneconomical, time consuming and cumbersome

  • Fragmentation
    • Tissue fragmentation and loss, reported in ~30% of cases, compromises cancer quantitation and diagnostic accuracy

http://www.prostrcision.com

These include process waste and tissue fragmentation.

These concerns are Unique to the prostate, as it is the Only organ that is subject to multiple and repeated systematic biopsies due to the multifocal nature of the disease.

The conventional protocol…

The other concern is fragmentation.…compromises BOTH cancer quantitation and diagnostic accuracy

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Process Waste

  • Formalin containers, tissue cassettes, slides, coverslips are consumed rapidly for 12+ cores per biopsy procedure
  • Redundancy of grossing, embedding and sectioning at least 6x per case
  • Excessive slides for pathologist interpretation (6 – 12 parts 3x levels each resulting in 18 -36 slides)
  • IHC cost on multiple slides
  • Storage

To elaborate on process waste, here we can see the large amount of materials consumed for each biopsy case.

This leads to Redundancy of non-automated processes: like grossing, embedding, and sectioning

And excessive slides for path..

And 3 or 4 cases can easily add up to this stack that most of you are familiar with

The cost of IHC and storage space also increases -Antithesis of LEAN lab practice

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Tissue Fragmentation

  • Tissue handling
    • Specimen procurement
    • Grossing
    • Embedding

  • Delicate needle cores often fragment

Tissue fragmentation is also of great concern. It is seen at various steps of processing, where the specimen is handled by forceps. Specifically during specimen procurement (where to-and-fro movement is used to dislodge the sample from the biopsy gun). Fragmentation is also seen in grossing and embedding.

The delicate needle cores, especially when they contain cancer, fragment due to the high gland to stromal ratio, typical of high grade cancer.

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Price of Fragmentation

  • Diagnostic error
    • Quantitation of amount of cancer in a core

  • Diagnostic error
    • Number of cores with cancer

With fragmentation, Two types of diagnostic errors lead to inappropriate patient management.

Artificially elevate cancer quantitation.

Both of these errors could potentially lead to a difference in management.

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Baseline Data

  • Average cost per case (~500 cases per year):
    • Processing materials: $8
    • Histotech/PA Time: $16
    • IHC: $23
  • Time per case (48 cases):
    • Grossing: 4.7 min
    • Embedding: 6.3 min
    • Sectioning: 23.0 min
  • Fragmentation rate (48 cases):
    • Linear: 43.7%
    • Non-linear: 60.4%

Linear fragments

Non-linear fragment

Baseline data was obtained to characterize the issue. At the UMN we process about 500 cases annually and these were used to inform our initial understanding of the issue.

We evaluated 3 main metrics, the first …

We also evaluated the time and fragmentation rate in 48 test cases:

The time metric focused on…

While the last and most important metric characterized the fragmentation.

Linear fragmentation is defined as in-line separation of the core.

Non-linear fragmentation was defined as fragmentation that is out of plane from the core, creating uncertainty about which core it originated from.

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Design

  • Utilize innovative technology to improve prostate biopsy processing and diagnosis by:

    • Reducing cost, processing, and reading time

    • Increasing diagnostic accuracy by reducing tissue fragmentation and loss

A study design was crafted to… utilize new technology to improve biopsy processing. Metrics targeted focused on cost, processing, slide evaluation, and diagnostic material quality/integrity.

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Proposed Solution with New Technology

  • Proprietary biomimetic matrix
  • Processed, embedded, and sectioned like tissue
  • Linear 22 mm x 1 mm grooves separated by color coded ridges
  • Six needle core tissue samples on single chip
  • Transferred from needle by capillary action

Biopsy Chip

BxChipTM Leavitt Medical Inc.

The proposed intervention was the use of a proprietary biomimetic matrix chip that can be…

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Protocol

  • Sample radical prostatectomy cases
    • Using needle biopsy gun in gross room
    • Two biopsy sets from near identical locations
    • Process with standard method and new biopsy chip method in parallel
    • Compare parameters

6 pairs only instead of 12 due to logistic issues

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STANDARD

NEW

The first set of bx samples were transferred to 6 filter papers, then 6 formalin containers, as per the standard method. And the second set was inserted into 1 biopsy chip and then only 1 container for fixation.

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STANDARD

NEW

Processing continued with embedding and sectioning. Standard processing included embedding 6 times, and sectioning 6 times. While the new method, involved embedding once and sectioning once.

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STANDARD

NEW

And ultimately, the standard processing produced at least 18 slides in a typical case, with potential fragmentation. And the experimental method produced 3 slides, AND you can see intact cores separated by colored ridges on a single slide.

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Balancing Measures

  • New laboratory SOP development
  • Buy in and training for clinical nursing / lab staff
  • Potential technical issues in non-standard technology

While conducting this study, there were several balancing measures taken into consideration. …For example, here you can see a smudging of the biomimetic matrix., which was not see in newer versions of the product.

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Project Results (n = 48)

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An evaluation of outcomes strongly favored the new method. For the cost metric, our results showed a sig. decrease in cost in terms of materials, tech time, and IHC estimate, off setting the cost of the biopsy chip.

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Project Results (n = 48)

1)For the Processing time metric, we saw a significant dec. across all parameters, including…

2)Finally, even though the linear fragmentation rate was the roughly the same, the chip processing method resulted in complete absence of non-linear fragmentation (the key parameter that leads to diagnostic errors) . We also saw a sig. inc. in tissue length.

IHC estimate: Cases with IHC on 2 or more blocks

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Project Results

  • Reduced cost and processing time
    • Up to 6 biopsies travel through process as 1 sample
    • Estimated $8,800 per year saved
    • Overall > 3 fold reduction in processing time
  • Reduced degree of fragmentation
    • Tissue collected directly into chip eliminated handling at collection, gross dissection, and embedding
    • Accurate percentage cancer involvement
  • Additional benefits
    • Increased tissue length
      • Potential cancer detection rate
    • Reduced storage space by 6 fold

1)To summarize project outcomes, we reduced cost and processing time By processing 6 biopsies as 1 sample, which resulted in a >3 fold reduction in processing time.

2)The degree of fragmentation was reduced by eliminating specimen handling at collection, dissection, and embedding. Increasing the accuracy in determining %cancer involvement.

3)Additional benefits included an inc. in tissue length and decreased storage space.

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Thank You