RATIONAL LABORATORY DIAGNOSTIC AND POSSIBILITIES OF INADEQUATE ANALYSES APPLICATION

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RATIONAL LABORATORY DIAGNOSTIC AND POSSIBILITIES
OF INADEQUATE ANALYSES APPLICATION

• Danica Popovic
• Clinical Center of Montenegro

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To improve the health
Laboratory diagnostic
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• 60 information
• ? doctors use to set the diagnoses
• information obtained in
• laboratories
• Lot of researches ? aim to improve the
  diagnostic system
• ? to find the
  possibility for
• more complex analyses

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Improvement of laboratory diagnostic

• Standardization of laboratory procedure
• Simplification of laboratory procedure
• Reduction of time necessary for analyses
• Application of computer sample processing
• The aim ? both to reduce the possibility of
  errors caused by human factor
• ? protect the staff during the work

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• Big demands can be justified only
• To receive patients with special pathology
• When where are special protocols in treatment
• In periodical controls of patients in some
  chronic program

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• Big and unjustified demand
• ? not for specific
  parameters
• ? for all and everything
• Less clear situation ? this way can HELP
• Insufficient education and experience
• "Not to miss something
• More experience and knowledge ? less analyses,
  specific analyses ? useful information

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• When you ask for analysis there should be clearly
  defined question and the analysis should give
  you the answer.
• Infection bacterial or viral? ? ESR, WBC,
  differential count, or more specific C reactive
  proteins, or more specific procalcitonin
  (screening diagnostic)

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Conclusion

• method
• Induction Deduction
• to make more analyses which help to confirm or to
  exclude certain opinions

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• Tumor markers compounds that make and excrete
  tumor cells in more guantity than normal cells
• Tumor marker is any compound whose
  concentration can be increased in the presence of
  malignant disease
• ESR and the activity of LDH are the classical
  tumor markers. These markers are also increased
  in inflammation and necrosis process, and that is
  why they are highly nonspecific for malignancy

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• Tumor markers are macromolecules and their
  concentration is related to the presence and
  diffusion of malignant tumor
• Tumor markers are very important to follow the
  treatment efficiency, as well to predict the
  response to the therapy

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Application is limited

• in the field of screening
• in the diagnostics of localization and stage
• tracking and prognoses of malignamcy

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Ideal tumor marker

• specific for tested tumor (malignant process)
• correlation with tumor mass
• level in tested sample is increased in presence
  of metastases (in the stage when physician nor
  methods currently available can not detect their
  presence)
• if it is present in plasma of healthy person its
  concentration is lower than in certain stage of
  cancer
• indicate the terapy effect
• concentration is in accordance with prognosis
  state
• metods for their determination in body fluids are
  simple and not expensive

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• Criteria for ideal tumor marker, which would have
  sensitivity and specificity 100 have not been
  fulfilled by any known tumor marker
• Use can be helpful to diagnose the cancer but it
  can not to be the only criteria

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• Problem sensitivity and specificity ? connected
  with chosen upper limits of referential range
• Lower cut-off value ? higher sensitivity, lower
  specificity
• High cut-off value ? higher specificity, lower
  sensitivity

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Estimation the value of tumor marker

• population of healthy people
• patients with benign disease
• patients with different types of cancer
• Example There should be taken patients with
  hronic gastritis when we define referential
  values of tumor markers for stomach cancer

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• Examination patients with specific cancer ? the
  various stages of cancer should be included
• Tumor markers are used to follow the therapy ?
  the set of samples should be taken to estimate
  the efficiency of tumor markers
• To value markers ? it is necessary to determine
  referential values, to calculate predictive
  values, distribution of marker's values and
  significance in disease estimation

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• This discovery leads
• to better results in patient tracking after
  radical surgery
• adequate treatment or
• better results of illness

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• Tumor markerS with few exceptions are not
  adequate for primary diagnosis of malignancy.
  They do not show enough sensitivity and specifity
  for their purpose. False positive results in
  cancer diagnosis can lead to lot of psycho trauma
  while false negative results postpone the terapy,
  which can be fatal.
• For various kinds of cancer, tumor markers are
  use as choice of first, that is second order. The
  combination of markers may increase diagnostic
  sensitivity
• Insufficient specificity of a tumor marker,
  sometimes exclude its use in detection of tumor
  location, while sometimes it can be useful
• For the state and prognosis, persistently
  extremly high concentration indicates the
  progress of illness and bad prognosis. There are
  significant individual variations in value level,
  so the values in the referential range do not
  exclude for sure the malignancy

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Tumor markers that are frequently used in routine
work

• Onkofetal proteins
• Carcinoembryonic antigen (CEA)
• Alpha-fetoprotein (AFP)
• Human chorionic gonadotropin (hCG)
• Carbohydrate antigen
• CA-125
• CA-19-9
• CA-15-3 and CA 27-29
• CA- 72-4
• Enzymes
• Creatin kinasa
• Lactat dehidrogenasa
• Prostata acid phosphatase
• Prostate specific antigen (PSA)
• Neuron-specific enolasa (NSE)
• Amylase

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• Hormones and hormone receptors
• ACTH and other endocrine hormones
• Brest estrogen and progesterone receptors
• Proteins as tumor markers
• ?2- microglobulin
• C-peptid
• Feritin
• Tireoglobulin
• Other markers
• Cytokeratin-19 (CYFRA 21-1)
• Tissue polypeptide-antigen (TPA)
• Tissue polypeptide-specific (TPS) antigen
• Squamous cell carcinoma (SCC) antigen

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Most of the freqently used tumor markers

• Substances which only tumors excrete in different
  body parts
• Markers which both malign and benign tissues
  excrete (PSA)
• Tumor markers whose effect we track trough
  receptors increase (HER-2/neu)

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Origin and control of preanalitic variation

• The affects of preanalycal factors (abide the
  standard procedure regarding the preparation of
  patients, taking and processing of the samples
  for analyses)
• Affects to analytic factors (are reduced to the
  least possible rate by using the quality control)
• Results of clinical biochemical determination
  are interpreted by comparing with the referential
  values, and so the conclusion is made by
  comparing method. In order to perform this
  process properly, referential values for each
  specific parameter are necessary to exist.

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Cyclic biological variable

• Cyclic variation ? changes in the concentration
  of the analyte in certain period of day, week,
  month
• Circadial variation (occurs during the course of
  a single day)
• melantoin
• iron, acid phosphatase
• most electrolite (Na, K, P) in urine
• hormons of hypophysis

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• Intradian variation (over a period greater than 1
  day)
• menstrual cycle ? ovary hormones, Ca, Mg,
  cholesterol, PTH, renin, aldosterone,
  antidiuretic hormone
• Intraindividual variation
• electrolite, proteins, alkaline phosphatase (5)
• bilirubin, creatine kinase, tryglicerides, most
  steroid hormone (20)
• creatinine in urine (10)
• Seasonal changes in nutrition and climate
  variation
• 1,25-dihidroxy-vitamin D
• urinary oxalate
• bone alkaline phosphatase

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VariationS caused by patient's state

• Physical activity
• Food ingestion
• Stress (of any kind)

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VariationS that are result of sample collecting

• The technique of blood collecting
• The type of the sample (arterial blood, venous
  blood, capillary blood)
• Use of preserving agents and anticoagulants
• Inadequate identification of sample and patient
• Sample collecting with infants (sample collecting
  for metabolic errors, gathering of capillary
  blood)
• Variations during urin collecting (biological,
  time of collecting, stability of sample)

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Errors that can occur after sample collecting

• Transport of samples
• Preparation of samples (centrifugation)
• Sample storage

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Conclusion

• Inadequate preparation of patient for a certain
  analysis and disrespect of rules referring
  preparation and sample analyzing, can lead to
  drastic deviation of results from the real
  values. Thus obtained results of analyses can be
  badly interpreted or abused in several ways and
  for different purposes, whether by doctor who
  asked for them or by patient himself.