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Biobanking in low resource settings - a pathologist's view Rupert Langer Institute of Pathology University of Bern Switzerland
Biobanking in low resource settings - a pathologist's view situation of pathology in emerging countries why biobanking in emerging countries? Structural problems of tissue based biobanking in
emerging countries. proposal for a human tissue biobank model in low
resource settings
Critical Shortage of Healthcare in Emerging Countries
Angola Benin Burkina Faso Burundi Cape Verde Central African Republic Chad Comoros Congo Djibouti Equatorial Guinea Eritrea Ethiopia Gambia Guinea Guinea-Bissau Lesotho Liberia Madagascar Malawi Mali Mauritania Mozambique Niger Rwanda Sao Tome and Principe Senegal Sierra Leone Somalia Sudan Tanzania Togo Uganda Zambia Afghanistan Bangladesh Bhutan Cambodia Lao Maldives Myanmar Nepal Timor-Leste Yemen Pacific Kiribati Samoa Solomon Islands Tuvalu Vanuatu Haiti
Kumar P, N Engl J Med 2007; 356:2564-2567
Critical Shortage of Healthcare in Emerging Countries – general issues
Strong influence of socio-cultural, Economic and political factors on healthcare systems
Poor planning/poor implementation of health policies and programmes - problem: availability, - problem: accessibility - problem: afforability - problem: sustainability
Lack of facilities and equipment. Lack of human
resources (internal and external «brain drain»)
Critical Shortage of Healthcare in Emerging Countries – main fields
Reproductive health
Infectious diseases including HIV, Tuberculosis, Malaria,
parasitic diseases
Non-communicable diseases, including cancer,
cardiovascular diseases and diabetes
Water supply and quality
Nutrition, malnutrition and deficiency disorders
Surgical Pathology service in low resource settings
lack of trained personal and technical equipment, inefficient infrastructure (e.g. transport, communication etc.)
Main limitations: number of available, well trained and skilled pathologists.
(When available, often few in number and occupied by providing medical education, pathology service, and government/administrative responsibilities)
only a small amount of the potential caseload can be
reviewed by pathologists and is sent away for pathology examination
ECP - 2012
Adequate (accurate and timely) pathology service Fundamental to improvement in diagnosis and
treatment of non-communicable diseases.
Prerequisite to patient access to better, tailored, and potentially even curative therapies.
lead to the recognition of pathology as an integral part of a multidisciplinary healthcare setting. (E.g., consensus guideline on breast health care in low-resource settings requires pathologic diagnosis before treatment.1)
Provides more accurate epidemiological data.2 Provides insight into region-specific etiology of diseases.
1Anderson BO, et al. (2010) *Roberts DJ, et al. (2012) 2Msyamboza KP, et al. (2011)
Surgical Pathology service in low resource settings
Cancer in Africa
Case spectrum of Surgical Pathology in Sub-saharan Africa
405 cases/6weeks 175 cases non-tumoral conditions
(inflammatory lesions, e.g. schistosomiasis and tuberculosis)
39 cases benign tumors/tumor like lesions. 15 cases premalignant conditions (CIN). 140 cases malignancies (11 pediatric
tumors (e.g. rhabdomyosarcoma, small blue round cell tumors), and 129 adult tumors.
129 adult malignancies: High incidence of SCC - Cervix uteri HPV, HIV1
- Esophagus nutritive? HPV? HIV?2
- Conjunctiva Sun? HPV? HIV?3
- Bladder Schistosomiasis4 1Chirenje ZM, et al. (2005) 2Patel K, et al. (2011) 3Orem J, et al. (2004)
4Ross AGP, et al. (2002)
Cancer in Africa – most common cancer types
Cancer in Africa
Cancer in Africa – problematic aspects
CHALLENGES
Improvement of pathology service More, faster, better and more
accurate diagnoses Improvement of therapy (if ava-
ilable; demand driven therapy) More valid epidemiological data Basis of research efforts Need of biobanks associated with
(surgical) Pathology
ECP - 2012
most pathology departments are running fully diagnostic functional labs
Diagnostic stainings H&E, PAS, ZN on FFPE tissue Few have or are planing to implement basic IHC
Pathology Archives as Biobanks?
Tissue and Scientific Questions
epidemiological issues interaction infection-host histomorphology and
molecular genetics of tumoral conditions
-> Get knowledge about geographic specifities or similarities of diseases -> Improvment of future healthcare provision
Formalin fixed paraffin embedded (FFPE) - a great source for tissue based research. quality of the specimens most crucial - Current existing infrastructure mostly allows diagnostic standard staining only. Application of further molecular analysis hampered
by the lack of standardization of preanalytic tissue handling:
-variable fixation times (transport!), -unclear fixation agents, etc.
Pathology Archives as Biobanks?
Tissue Quality - Morphology
HE; standard formalin fixation HE; unclear formalin fixation
CD20; standard formalin fixation CD20; unclear formalin fixation
Tissue Quality - Immunoreactivity
250bp
ApoE; standard formalin fixation ApoE; unclear formalin fixation
Tissue Quality – nucleotides (DNA/RNA)
Standardization of preanalytical tissue handling
Basic Approach for Biobanking Structures in Low Resource Settings
Structuring and standardization of tissue processing - FFPE tissue firm base for scientific projects. Alternative non-formalin based fixation agents - alternatives for robust tissue preservation. high relevance of establishment of clinical data banks - documentation of relevant clinical information. Consideration of ethical issues - informed consent, respect of cultural aspects..
Malawi Biobank Project
Sabina Berezowska Rupert Langer Institute of Pathology, University of Bern, Switzerland
population: ~16 Million, rural areas democratic, multi-party government (President 2012: Joyce Banda) 40% living below the international poverty line economy essentially agricultural (mainly tobacco, tea, sugar) economically dependent on foreign aid (50% of GDP) health care: high burden of Malaria, Tuberculosis,
HIV (15 % estimated prevalence among 15-45 yo); Lack of health care personnel (in particular MDs), but constant improvement:
- Main health care services free of charge - life expectancy: 2009: 52.2 yrs (2000: <40 yrs)
Malawi - Factsheet
ECP - 2012
Surgical pathology service in Malawi
Department of Histopathology, Blantyre – College of Medicine:
- Dr. Steve Kamiza - Dr. Tamiwe Tomoka
Post mortems: - Dr. Charles Dzamalala
Kamuzu Central Hospital, Lilongwe: - Lab on the premises - signing out by Prof. George Liomba (emeritus)
ECP - 2012
2011 - Structured support project by Danny A. Milner Jr. and Partners in Health (Department of Pathology, Brigham and Women´s Hospital, Boston, USA)
1. supporting training of local pathologists (4 yrs residency programm in South Africa)
2. providing continuous on-site support by volunteers until local pathologists finish training - shortening turnover times - avoiding larger backloads
Surgical pathology service in Malawi
Malawi Biobank Project - conditions
Optimal conditions in the department of pathology (experienced pathologists and technicians)
Optimal conditions in the associated Queens Elizabeth Central Hospital (excellent surgery/endoscopy)
Existing personal contacts (volunteering) Motivated staff, ambitious and emerging medical
faculty (COM: research projects, medical students..)
Malawi Biobank Project - Aims
A) tissue bank Standardized retrieval of the material, processing and storage - In a first phase concentration on cooperation with the
department of surgery, in particular endoscopic surgery. - Fixation of the endoscopic samples in formalin. Ensurance of
standardized fixation conditions (formalin 10%). Rapid transportation into the institute of pathology to avoid overfixation. Storage: room temperature for FFPE.
- Evaluation of alternative fixation options (e.g. PaxGene, RNAlater etc.). Formalin and PaxGene samples in parallel. PaxGene favoured with regard to morphology and IHC. Storage: frigde (4°C); processing in Malawi or Bern
Malawi Biobank Project - Aims
A) tissue bank quality check on 20 mirror samples after first collecting
period*, evaluating in parallel the PaxGene and formalin fixed samples for:
- Morphology - DNA - RNA - miRNA - Immunhistochemistry ( panCK, Vimentin, LCA) - Protein possible for PaxGene fixed samples - the impact of storage-time on quality of PaxGene fixed samples (i.e.
repeated analyses after e.g. 3 months of storage)
*analyses will be conducted in Bern)
Malawi Biobank Project - Aims
B) Clinical and pathological data bank A basic data bank shall be installed in order to correlate
pathological, molecular and clinical data. All tissue samples shall be registered in a basic data storage
program (e.g. Excel). This data bank shall include relevant corresponding clinical data, such as:
- age, sex - family history - work (exposition to tabak, pesticides) - nutrition habits (maize, rice etc.) - HIV status - informed consent for the usage of human tissue for research - It might be necessary to conceive a separate questionnaire to retrieve all
data (and informed consent).
Malawi Biobank Project - Aims
C) Ethics commission The ethics commission of Blantyre
shall verify the project. (http://www.medcol.mw/comrec ).
preparation 1.Quartal 2.Quartal 3.Quartal 4.Quartal Following project
Intensive preparation together with pathology and surgery: -Hiring of personnel -Logistical questions -Generation of a patient questionnaire -Ethics commission
Initiating of the project on-site in Malawi -Initiation of the infrastructure -Transportation of material and fixation agents -Meeting with the ethics commission -Instruction of the hired personnel -Transfer of the first samples
Collection Short visit: -control of the operational sequences -Transportation of further fixation agents -Transfer of further samples -Start of the analytical work
Collection: Constant contact with on-site pathologists and personnel -Finalization of the analytical work
Final visit during the pilot phase.
Following collection of tissue samples, financed by subsequent grants
Preparation of a manuscript
Writing of a subsequent grant covering further financing of the tissue bank
Malawi Biobank Project - Schedule
Malawi Biobank Project
Sabina Berezowska Rupert Langer Institute of Pathology, University of Bern, Switzerland cooperation partners Dan Milner Brigham & Women's Hospital, Harvard Medical School, USA Tamiwe Tomoka, Steve Kamiza, Department of Histopathology, College of Medicine, University of Malawi Prof. Eric Borgstein, Queens Elizabeth Central Hospital, Department of Surgery, Blantyre, Malawi Daniel Grölz, Preanalytix/Qiagen