HCDCP NEWSLETTER

Hellenic Center for Disease Control and PreventionAgrafon 3- 5, Maroussi, 15123, Tel: +30 210 5212000,info@keelpno.gr, http://www.keelpno.gr

January 2011 ISSN 1792-9016Vol. 11/ Year 1stHCDCP

HELLENIC CENTER FORDISEASE CONTROL & PREVENTION

MINISTRY OF HEALTH &

SOCIAL SOLIDARITY

Contents:Editorial: The development of the Hellenic Cancer Registry 2-4Surveillance Data 5-7Invited articles 8-29HCDCP Departments Activities 30-31Recent publications 32Interesting activities 33-34Meet our editorial team 35Future conferences 36Quiz of the month 36Outbreaks around the world 37Interview 38-39Myths and truths 40Hellenic non- govern-mental organizations 41-42News from HCDCP Administration 43

The multi-award-winning professor of epidemiology Mr D. Trichopou-los states in his interview that the Mediterranean diet can lower the risk of cancer by 5–10%. He also notes that: ‘prevention will continue to play an important role, although in my opinion therapeu-tic medicine has better prospects. However, let us not forget that pre-vention and treatment are mutu-ally complementary and not mutu-ally exclusive’.

More on page 40

The operation of the National Can-cer Registry and Rare Disease Of-fice of HCDCP is the first action of the fifth intervention axis of the national intervention program for cancer for the years 2011–2015. In the three and a half years that the office has operated under HCDCP, a significant increase has been seen in the recorded cases at participat-ing hospitals. The basic mission of the National Cancer Registry and Rare Disease Office is the devel-opment, operation and continuous improvement of a national popu-lation system for the recording of new cases of metastatic cancer nationwide, from primary and sec-ondary sources from the public and private sectors, as well as the de-velopment of a mechanism for the processing and dissemination of the data collected.

More on page 2

Chief Editor:

Ch. Hadjichristodoulou

Scientific Board:

Ν. VakalisΕ. VogiatzakisP. Gargalianos- KakolirisΜ. Daimonakou- VatopoulouΙ. LekakisC. LionisΑ. PantazopoulouV. PapaevagelouG. SaroglouΑ. Tsakris

Editorial Board:

M. Angelopoulou

R. VorouPh. KoukouritakisΚ. MellouD. PapaventsisΤ. PatoucheasV. RoumeliotiV. SmetiCh. TsiaraΜ. FotineaΕ. Hadjipashali

Highlights

Developments in the fight against cancerCancer remains a major disease threat to developing nations, with serious impacts on human life, social cohesion and economic activity.Cancer incidence rates are increasing while cancer mortality rates are decreasing. An ageing population is the leading cause of the rise in incidence rates, and therapeutic advancements the leading cause of a reduction in mortality. The survival rate for people with cancer is increasing, with an absolute number of 25 million cases world-wide. Consequently, a new group of disabled people has been introduced.Prevention is of paramount importance to reduce the incidence of cancer in some countries, through anti-tobacco campaigns and vaccines against cancer. The early diagnosis of cancer, with the use of mammographic screening, PSA screening, spiral CT scans for smokers and Pap tests, has contributed to the increase in cured cancer cases, as well their long-term survival. From a therapeutic standpoint, the steps being taken are important and promising. Firstly, a cornerstone is the systematic and creative co-operation between oncology specialists. Secondly, the technological revolution in radiation therapy, new surgical procedures, the development of molecular biology and the introduction of a new generation of small molecule-targeted drugs have generated high hopes that soon the 5-year survival rate for cancer patients will exceed the current percentage of 65%. Finally, supportive and palliative care is an everyday practice and essential for patients with cancer to maintain the highest quality of life for them. In the current issue of the Hellenic Center for Disease Control and Prevention’s (HCDCP) newsletter, all the above topics have been analyzed by the oncology sector regarding cervical, colorectal and breast cancer, where developments in prevention, early diagnosis and treatment are obvious. However, much has still to be done in all sectors, in order to control cancer more effectively.

Paris A. Kosmidis

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Editorial

The development of the Hellenic Cancer Registry (HCR)

Cancer is a major public health issue and one of the leading causes of death in Greece, as well as world-wide. In Europe, it is estimated that, by 2020, 3.4 million European citizens are going to be diagnosed with cancer, while more than 2.1 million are going to die.

It is estimated that one in three Europeans will develop cancer in their lifetime, and one in four will die from the disease. In Greece alone, given the latest data from the International Agency for Research on Cancer (IARC), 37,000 new cancer cases are being diagnosed yearly, while human losses to cancer are estimated to be 24,000 per year [1].

Moreover, Greece shows a steady upwards trend in cancer mortality, with apparent geographical variations between the north and south for certain cancer types, in contrast with the declining patterns seen in the majority of developed countries since the mid-1980s [2].

Because of the alarming increase in the disease’s burden, fighting cancer officially became a priority in the European Union’s (EU) agenda in 2008, during the Slovenian presidency. The European committee (EC)’s conclusions [COM(2009)291-24.6.2009] [3] on the fight against cancer were focused and clearly referred to the following: (i) prevention and early diagnosis through population screening programs, and (ii) systematic collection of accurate and reliable data on cancer through the proper operation of population-based cancer registries for each member state of the EU, in order to capture the true size of the problem locally and to be able to compare results at a European level.

Therefore, the full operation of population-based cancer registries at a national level, the awareness and education of the public, as well as 100% population coverage of screening for breast, cervical and colorectal cancer, according to international recommendations, are considered and recommended by the EC to be integral to all national health policies of the member states. It is universally acknowledged that cancer registries are the invisible key to cancer control, and provide a means of evaluating the screening programs, treatment and survival of the population [4].

Greece has been the only EU member state without a reliable cancer registry. In 2005, with law number 3370, the responsibility of operating the Hellenic Cancer Registry (HCR) shifted to the Hellenic Center for Disease Control and Prevention (HCDCP) but, in fact, it only began to operate in June of 2008.

HCR was a continuation of two registration mechanisms run, initially, by the Hellenic Statistical Authority, called the Annual Statistical Survey of Cancer, from 1967 to 1982, and the Department of Hygiene of the Hellenic Ministry for Health and Social Solidarity, called the Hellenic Cancer Registry, for the period 1990–2005.

Another system published data only for the period 1990–91, but was not continued. The collected data were assessed as incomplete, and no electronic files had been kept for the period 1994–2008, 2008 being the year the HCDCP was recognized as the official body for operating the HCR.

Within the last 3 and half years during which HCR has been run under HCDCP, a significant increase in registered cases and participating hospitals has been observed. Nevertheless, the collected data remain incomplete and are estimated to represent just 30% of the new cancer cases in Greece each year. The current system of epidemiological registration is based on the voluntary participation of laboratories and clinics, a so-called passive surveillance system.

The organization and full operation of HCR is the first action of the fifth intervention axis of the National Cancer Plan 2011–2015.

The development of the ‘new’ HCR is the result of a thorough international literature review, studies of relevant material from the USA Surveillance Epidemiology End Points Results (SEER),

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the Middle Eastern Cancer Consortium (MECC) and the operation of other European national registries, such as the one of the Netherlands, and also the results of participating in European health programs such as Eurochip II & III.

In addition the development of HCR has been implemented in collaboration with a scientific committee of experts for the HCR, established by HCDCP, composed of Dr Petroula Arapantoni-Dadioti, Director of the Pathology Laboratory of ‘Metaxa’ hospital, Dr Maria Daimonakou-Vatopoulou, Director of the Pathology Laboratory of ‘Sismanogleio’ hospital, Dr Dimitris Karakasis, Director of the Hematology Department and Transplant Unit of ‘Evangelismos’ hospital, and Dr Paris Kosmidis, Director of the Second Clinic of Oncology of the ‘Hygeia’ hospital.

With the aim of complete cancer case registration and reliable population-based results, data will be collected by all public and private hospitals in Greece, as instructed by the ministerial decisions numbers 136216/9-12-2011 and 1010/12-2011.

Health officials, mainly health visitors, already employed as permanent hospital staff will carry out the registrations and will act as ‘cancer registrars’. The registrars will be responsible for collecting all the necessary and essential information required by HCR; for electronically entering the collected data in a single, web-based information system; and for working closely with the members of the oncology committees of the public hospitals and private clinics. The aforementioned committees are by law in charge of the proper operation of their health institutions’ cancer registry. Moreover, the registrars will be connected directly to and liaise with the HCR office in HCDCP, for continuous training, education and support. For the first 2 years, the registrars will be trained on a regular basis and educational seminars will be run for each health region, roughly every 6 months.

Cancer registration will be made online, with strict ground-rules to secure the privacy and safety of personal and health-sensitive data. The necessary tools for registration, the ‘registration form of malignant or marginally malignant neoplasm’, as well as the corresponding software for online data registration, have been developed by a team at HCR, after a thorough study of international standards and an in-depth review of best practices, at all times in co-operation with the HCDCP experts committee for HCR. The aforementioned tools will be tested during the first phase of the system’s application and improvements made as necessary. Moreover, during the first phase of implementation, the specifications of the software for the online cancer registration will be defined and set.

For the first 2 years, the project of developing HCR will be funded through the National Strategic Reference Network (NSRF) 2007–2013 program, and then the possibility of developing a cancer fund, enabling HCR’s viability, will be investigated.

In this context, HCR’s principal purpose and missions are to:

1. Develop, operate and constantly improve the national population-based mechanism for registering all new and metastatic cancer cases throughout Greece, reported by primary and secondary sources of the public and private networks.

2. Develop, operate and constantly improve the mechanisms for evaluation, assessment and proper dissemination of collected data and related results.

The co-operation of all health professionals and practitioners involved in the cancer diagnosis, treatment and therapy in our country is essential and absolutely necessary for the successful completion of this project, and we are looking forward to the outcome of this effort.

Last but not least, as the representative of HCR, I would like to thank warmly the doctors who have supported and continue to support the registry, the General Secretary for Public Health Dr Antonis Dimopoulos, and the President of the Board of Directors of HCDCP, Professor Mrs Jenny Kourea-Kremastinou, for their direct support and help when needed, as well as the members of the experts committee for HCR, Dr Petroula Arapantoni-Dadioti, Dr Maria Daimonakou-Vat-opoulou, Dr Dimitris Karakasis and Dr Paris Kosmidis, for their scientific guidance and help in this difficult project.

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References:

1. The GLOBOCAN Project. Fast Stats for Greece (2008). Available at: http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=300 [accessed on 20 December 2012].

2. Tzala E, Best N. Bayesian latent variable modelling of multivariate spatio-temporal variation in cancer mortality. Stat Methods Med Res 2008;17:97–118.

3. Council of the European Union. Council Conclusions on Reducing the Burden of Cancer. 2876th Employment, Social Policy Health and Consumers Affairs Council Meeting, Luxembourg, 10 June 2008.

4. Brewster DH, Coebergh JW, Storm HH. Population-based cancer registries: the invisible key to cancer control. Lancet Oncol 2005;6:193–195.

Lia Tzala, Head of Hellenic Cancer Registry and Rare Diseases Office

Useful Information

• The collection of reliable data through the operation of the HCR is the invisible key to cancer monitoring and control at a national level.

• HCR is the primary source for information for designing a coherent and targeted national anti-cancer policy.

• Cancer registries world-wide focus on data collection for the evaluation of the quality of therapy and care received by oncological patients.

• Prevention is the best therapy.

• Population screening programs, as claimed by scientific information in the international literature, are effective for breast, cervical and colorectal cancers.

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data

Surveillance dataTable 1: Number of notified cases in December 2011, median number and range of notified cases in

December for the years 2004−2010, Mandatory Notification System, Greece

Disease Number of notified cases

December 2011

Median number December 2004−2010 Range

Botulism 0 0 0-0Chickenpox with complications 0 1 1-4Anthrax 0 0 0-2Brucellosis 3 7 3-15Diphtheria 0 0 0-0Arbo-viral infections 0 0 0-0Malaria 2 1 0-3Rubella 0 0 0-0Smallpox 0 0 0-0Echinococcosis 1 2 0-6Hepatitis Α 3 12 4-35Hepatitis B, acute & HBsAg(+) in infants <12 months 3 5 1-18

Hepatitis C, acute & confirmed anti-HCV positive (1st diagnosis) 0 1 0-6

Measles 0 0 0-107Haemorrhagic fever 0 0 0-0Pertussis 0 1 0-2Legionellosis 1 1 0-3Leishmaniasis 1 5 1-10Leptospirosis 0 2 0-4Listeriosis 0 0 0-1EHEC infection 0 0 0-0Rabies 0 0 0-0Melioidosis/glanders 0 0 0-0Meningitis

aseptic 4 16 9-53bacterial (except meningococcal disease) 10 14 9-19

unknown etiology 0 0 0-3Meningococcal disease 2 9 3-15Plague 0 0 0-0Mumps 0 0 0-2Poliomyelitis 0 0 0-0Q Fever 0 0 0-1Salmonellosis (non-typhoid/paratyphoid) 32 31 11-94Shigellosis 4 1 1-9Severe acute respiratory syndrome 0 0 0-0Congenital rubella 0 0 0-0Congenital syphilis 0 0 0-1Congenital toxoplasmosis 0 0 0-0Cluster of foodborne/waterborne disease cases 3 1 0-5

Τetanus/neonatal tetanus 1 1 0-1Tularaemia 0 0 0-0Trichinosis 0 0 0-1Typhoid fever/paratyphoid 0 0 0-4Tuberculosis 18 49 34-88Cholera 0 0 0-0

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Surveillance dataTable 2: Number of notified cases by place of residence (region)*, December 2011, Mandatory Notification

System, Greece

Disease Number of notified cases

Region

Eas

tern

Mac

edonia

an

d T

hra

ce

Cen

tral

Mac

edonia

Wes

tern

Mac

edonia

Epirus

Thes

salia

Ionia

n isl

ands

Wes

tern

Gre

ece

Ste

rea

Gre

ece

Att

ica

Pelo

ponnes

e

Nort

her

n A

egea

n

South

ern A

egea

n

Cre

te

Unkn

ow

n

Brucellosis 1 0 0 0 1 0 1 0 0 0 0 0 0 0Malaria 0 0 0 0 0 0 0 0 1 1 0 0 0 0Echinococcosis 0 0 0 0 0 0 0 0 0 0 1 0 0 0Hepatitis Α 0 0 0 0 1 0 0 1 1 0 0 0 0 0Hepatitis B, acute & HBsAg(+) in infants <12 months

1 0 0 0 2 0 0 0 0 0 0 0 0 0

Legionellosis 0 1 0 0 0 0 0 0 0 0 0 0 0 0Leishmaniasis 0 0 0 0 0 0 0 0 1 0 0 0 0 0Meningitis

aseptic 0 0 0 0 1 0 1 1 0 0 0 0 1 0bacterial (except meningococcal disease) 1 1 0 0 0 1 0 0 7 0 0 0 0 0

Meningococcal disease 0 0 0 0 1 0 0 0 1 0 0 0 0 0Salmonellosis (non-typhoid/paratyphoid) 1 1 0 0 3 1 0 1 7 2 1 0 15 0Shigellosis 0 0 0 0 0 0 3 0 1 0 0 0 0 0Cluster of foodborne/waterborne disease cases

0 0 0 0 0 0 1 0 1 0 0 0 1 0

Τetanus/neonatal tetanus 0 0 0 0 0 1 0 0 0 0 0 0 0 0Tuberculosis 0 7 0 0 3 0 0 0 6 0 0 1 0 1

*The place of residence is defined as the home address of the patient.

Table 3: Number of notified cases by age group and gender*, December 2011, Mandatory Notification System, Greece

Disease Number of notified cases by age group (years) and gender

<1 1−4 5−14 15−24 25−34 35−44 45−54 55−64 65+ Un.M F M F M F M F M F M F M F M F M F M F

Brucellosis 0 0 0 0 1 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0Malaria 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0Echinococcosis 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0Hepatitis Α 0 0 1 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0Hepatitis B, acute & HBsAg(+) in infants <12 months

0 0 0 0 0 0 0 0 1 0 0 0 1 0 1 0 0 0 0 0

Legionellosis 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0Leishmaniasis 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0Meningitis

aseptic 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 2 0bacterial (except meningococcal disease)

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 3 2 4

Meningococcal disease 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0Salmonellosis (non-typhoid/paratyphoid)

3 3 8 2 3 3 1 0 0 1 1 0 2 1 0 2 2 0 0 0

Shigellosis 0 0 0 1 2 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0Τetanus/neonatal tetanus

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0

Tuberculosis 0 1 0 0 1 1 2 1 3 0 0 0 1 0 1 0 4 2 0 1

*M, : male; F, female.

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data

The data presented are derived from the Mandatory Notification System (MNS) of the Hellenic Center for Disease Control and Prevention (HCDCP). Forty-five infectious diseases are included in the list of mandatory notifiable diseases in Greece. Notification forms and case definitions can be found on HCDCP’s website (www.keelpno.gr).

It should be noted that the data for December 2011 are provisional, and may be slightly modified/corrected in the future, and also that data interpretation should be made with caution, as there are indications of under-reporting to the system.

Department of Epidemiological Surveillance and Intervention

Influenza season 2011-2012: surveillance data from week 40/2011 to 4/2012

The annual seasonal influenza surveillance at both the European level and for Greece started in week 40/2011 and will continue up to week 20/2012 (14–20 May 2012).

Since week 40/2011 (3–9 October 2011) up to 4/2012 (23–29 January 2012), seasonal influenza activity has remained low in Greece. An increasing trend in clinical activity has been noticed during the last week (4/2012) (Figure 1).

Up to week 4/2012 (22–29 January 2012), 213 clinical samples have been sent to the influenza reference laboratories. Of the 213 samples, 35 (16.1%) were positive for influenza viruses. Of the 35 influenza viruses typed, 15 (42.9%) were type A and 20 (57.1%) were type B. Of the 15 influenza A viruses, 14 were Α(Η3Ν2) and one was Α(Η1Ν1)2009.

Up to week 4/2012 (22–29 January 2012), six severe influenza cases have been admitted to intensive care units. Influenza virus B was identified in three of the cases (50%) and influenza virus A in three (50%). Of the three influenza virus A identified, two were A(Η1Ν1)2009 and one was A(Η3Ν2).

Figure 1: Number of ILI cases per 1000 visits per week. Greece, influenza seasons 2009–2010, 2010–2011 and 2011–2012

Respiratory Diseases Office

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Invited articles

Population screening program for cancer of the cervix: the spearhead of the National Action Plan for Cancer 2011–2015

The prevention and management of chronic non-communicable diseases, and cancer in particular, has been a priority for the Ministry of Health and Social Solidarity.

A year ago, on 16 December 2010, the Minister Mr A. Loverdos, the Deputy Minister Mr M. Timosidis and the General Secretary of Public Health Mr A. Dimopoulos presented the National Action Plan for Cancer 2011–2015 and launched a public consultation for this major issue. One year after its launch, we are able to present the first concrete results.

The National Action Plan for Cancer 2011–2015 is an integrated set of activities covering all aspects of cancer treatment, with dominant values emphasizing the importance of prevention and early diagnosis and treatment of the disease, as well as ensuring uniform, fair, scientifically sound and high-quality health care.

Special attention is given to prevention and early diagnosis of the most common cancers. The first major intervention has been to organize a national cervical cancer screening program. This program represents the first organized effort in our country to develop a comprehensive system of care, referral, treatment, testing and retesting for a disease and specifically for a type of cancer (cervical) that is a major public issue. Similar programs for the most common cancers are implemented at a national level in only few highly developed countries (Nordic countries and the United Kingdom), reflecting the difficulty of the project, which is hindered during the economic crisis.

A working group functioned to design the program; its members worked voluntarily and have undertaken the development of the program’s guidelines according to the respective European guidelines, and approved the pilot information system that will be launched in this first phase. The working group leader was Professor Ch. Lionis and members of the group were Professors P. Karakitsos, E. Paraskevaidis and G. Panagiotidis, as well as managers of the national health system (NHS) and specialists in pathology, epidemiology, health services and public administration.

Monitoring of the implementation is being carried out by the General Secretariat of Public Health. The implementation involves 140 primary health centers and dispensaries, 160 municipalities and all NHS hospitals where cytology and pathology laboratories (including those that perform colposcopy) operate. The program was launched on 1 July 2011 in the region of Sfakia in Crete, and was gradually extended throughout the country until October 2011. The design of the project, followed by the General Secretariat of Public Health, was based on the instructions of the working group, as follows.

• The municipalities’ social services send invitation letters to women aged 25–65 to motivate them to make an appointment for a Pap test at the nearest primary health care unit, NHS health center or community health center.

• The invitation letter will be sent every 3 years to women aged 25–55 and to women aged 55–65 with abnormal Pap smears. For women aged 55–65 with negative Pap test results, the invitation letter will be sent every 5 years.

• The first phase of the national program was implemented in remote areas and/or areas disadvantaged in accessing health services.

• Women who should be under treatment or have further diagnostic tests are referred to the nearest NHS hospital for the appropriate health services.

• After completing the approval process from the Association of Personal Data Protection, an integrated information system will operate via a web application, where the Pap tests results will be recorded to monitor the progress of women with abnormal findings and to facilitate prompt follow-up care.

• Assessment, assurance and continuous quality improvement are also provided.

The first results are extremely positive. Specifically, compared with the last year’s corresponding

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months, there was an increase in the number of women tested at the respective health centers of 60.31% in August, 53.2% in September, 55.07% in October, 78.84% in November and 128.73% in December 2011!

The implementation of the program has allowed the detection of severe pre-malignant lesions in many women who have been treated in accordance with good medical practice via the NHS. In particular, during the first 5 months of the program’s inception, 17 cases of cervical cancer and 121 cases of women with severe pre-cancerous lesions were diagnosed. Furthermore, 180 women were referred for biopsy and 439 women for colposcopy. Up to now, a total number of 19,292 women has been seen at the health centers.

It is worth noting that the program is supported solely by current employees without extending their standard working hours and without receiving extra pay, and is implemented within the available infrastructure of the NHS.

Based on our initial review of the plan, co-operation between the municipalities and health centers has improved; the NHS is more effective and efficient, and we are also strengthening the public primary health care and its ties with the community.

Other important activities regarding cancer are as follows.

1. In the coming months, a national population screening program for breast cancer will be launched.

2. We are making progress in implementing a national cancer registry in Greece. By late 2013, Greece will have a valuable tool for the epidemiologic study of cancer, as well as for increasing the effectiveness of our intervention against cancer, which will be linked to a health map and reference networks.

3. We have introduced protocols and guidelines in clinical practice. Prescription protocols for cancer patients have already been completed and approved by the central board of health, which includes all procedures and treatments related to the fight against cancer. We have developed and integrated all clinical protocols and guidelines for the main types of cancer. The expected benefits of the introduction of protocols in clinical practice are improvement in the quality of care and the achievement of greater equality and cost control.

4. A review of oncologic boards and committees for oncology hospitals is in progress. This is a necessary action to ensure the effective implementation of the policy, improving care and controlling costs.

5. Furthermore, we are organizing oncology networks (one per health district). The oncology network will consist of all NHS structures (health centers, general and specialist university hospitals and cancer hospitals). Our goals is to co-ordinate the fight against cancer better, monitor the implementation of our policy and support all health structures with specialized scientific knowledge.

6. In the coming months, the procurement process of appropriate biomedical equipment technology (in our hospitals) costing 69 million euros will be completed.

7. With regard to the creation of respite centers, recently a center for ambulatory patients in Pilea, Thessaloniki, has been opened with a capacity of 100 beds, which operates under the supervision of ‘Theageneio’ cancer hospital. Additionally, in collaboration with the Church of Greece and other governing bodies, we will make further centers available (e.g. hospices for final-stage patients and their carers in ‘Sotiria’ hospital).

8. Finally, we are integrating pain clinics within hospitals, institutional settings for home care and implementing training programs for health care professionals and the public.

For more details and information please visit the webpage of the National Action Plan for Cancer http://www.anticancer.gov.gr/.

Send your ideas and suggestions to the following e-mail address: anticancer@yyka.gov.gr

With the National Action Plan we will mobilize the forces of our country in the fight against cancer.

We emphasize prevention and early diagnosis; we organize treatment; we invest in research and education.

Aristomenis Syggelakis, Deputy Director of the 1st health region of Attica, Head of the National Action Plan for Cancer 2011–2015

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Breast cancer

Breast cancer is the most common cancer in women and comprises 27% of all cancers in the female population.

Although several guidelines exist regarding the frequency of mammography, the most accepted regime is to start soon after the age of 40 years and then annually until into the 70s [1]. Ultrasound and/or magnetic resonance imaging (MRI) are recommended in specific cases in addition to mammography. The final diagnosis of a breast lesion is made in bioptic material (FNA-B fine-needle biopsy, small core biopsy or surgical preparation), and FNA fine-needle aspiration is an acceptable method.

Pre-malignant and pre-invasive lesions place patients in high-risk groups for developing an invasive breast cancer, while high risk is also related to an overburdened family history of breast cancer, to first-degree female relatives with cancer at an early age.

The risk in patients with atypical epithelial hyperplasia (ducts or lobules) corresponds to lobular cancer in situ (LCIS) and ductal (DCIS) when a family history is present.

Breast cancer diagnosis includes a variety of histological subtypes, such as lobular, ductal, mucinous, myeloid, tubular apocrine, transformed, etc., with the most common being the non-specific-type ductal cancer. The tumor size, status of lymph nodes, histological classification and differentiation (grade) are related to the prognosis. In the absence of metastatic disease at the lymph nodes, the presence of tumor emboli in vessels is related to the prognosis (image 1).

The recognition and identification of predictive indicators of response to treatment brought about a significant change to the therapeutic approach for breast cancer patients. The detection by immunohistochemistry of estrogen receptors (ER) and progesterone (PR), and oncogenes HER2 (c-erbB2) and Ki67 (MIB1), are integrated into the data for diagnostic pathology [2] (image 2).

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Alongside this, the molecular classification of breast cancer, resulting from combinations of the status of the biomarkers ER, PR and HER2, is widely used in clinical practice. There are four types identified: luminal A (ER+/PR+/HER2–), luminal B (ER+/PR+/HER2+), triple-negative tumors, which are often basic type (ER–/PR–/HER2–), and HER2-enriched (ER–/PR–/HER2+).

These subtypes have epidemiological differences in prognosis, survival, metastatic potential and response to treatment. The Ki67 cellular proliferation index is important for the classification and discrimination of luminal A and B tumors from HER2– tumors. The luminal type carcinomas have a better prognosis, while the HER2+, basic type and triple-negative cancers are aggressive [3].

The administration of chemotherapy after surgery based on anthracyclines and taxanes in combination with biologic agents (trastuzumab) has significantly increased the survival of patients with breast cancer and has reduced substantially, in combination with mammography, deaths from this disease. A better understanding of the disease biology and knowledge of the molecular signature has attributed significantly to proper selection and individualization of adjuvant chemotherapy [4].

Another area where progress has been made is in hormonal therapy for operable breast cancer. Newer drugs, such as aromatase inhibitors (anastrozole, letrozole and exemestane), are safer than the hitherto used tamoxifen and much more effective for post-menopausal patients, while for pre-menopausal patients tamoxifen and analogs of gonadotropins (GN-RH) are still in use, alone or combined. There are several strategies of administration of aromatase inhibitors in combination or not with tamoxifen. The duration of administration varies but overall it is never less than 5 years [5].

The existence of targeted therapy with humanized monoclonal antibody trastuzumab (herceptin) for tumors with overexpression of HER2 receptor has changed the natural history of the disease. Patients who received trastuzumab had 50% fewer relapses than those who did not. The duration of trastuzumab administration every 1–3 weeks is 1 year and can be administered either concurrently with chemotherapy or radiotherapy, or after subsidiary chemotherapy. This treatment has significant costs but the survival benefit is important. Lapatinib is a small smart molecule; it has been proven to be effective in combination with chemotherapy in metastatic disease and has been tested intensively in early disease [4].

Chemotherapy is the right choice for most patients with metastatic breast cancer. Various drugs are administered alone or in combination. Their response rate ranges from 35% to 50% when administered as a single agent for first-line treatment. The duration of response is approximately 8–12 months. The most active agents are the anthracyclines and taxanes, which have proved their value (paclitaxel and docetaxel) in many clinical trials.

Combinations of paclitaxel with anthracyclines give responses in the order of 60–65%, while the time to progression of the disease ranges from 7.5 to 8 months. The overall survival is 20–24 months. Capecitabine, a newer agent, has a good safety profile and satisfactory responses, especially in combination with taxanes, with a response rate of 42% and time to progression of 6.1 months. Other drugs with significant efficacy are gemcitabine and vinorelbine [6]. Finally,

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older agents, such as doxorubicin, are administered encapsulated in liposome, a new drug formulation with many advantages, namely the same efficacy but with much less toxicity.

Recently biological therapies have been used, such as monoclonal antibodies against the HER2 receptor and against the vascular endothelial growth factor (VEGF). These agents provide a survival benefit with acceptable toxicity. The administration of trastuzumab (herceptin) with chemotherapy has improved the overall survival of patients, while the concomitant use of chemotherapy and bevacizumab (avastin) has offered a double response duration to patients. Lapatinib (tyverb), another anti-HER2 agent, has proven to be safe and very effective in the clinical setting, as treatment of metastatic breast cancer, and has the important advantages of oral administration and blood–brain penetration [7].

In patients with hormone-dependent tumors, the administration of aromatase inhibitors tamoxifen or fulvestrane, a pure destroyer of hormonal receptors, offers long-term survival with an exceptional quality of life without the need for chemotherapy.

Both for adjuvant treatment and metastatic disease, radiotherapy has a prominent role, administered for conservative breast surgeries or for high-risk patients, for local recurrence or for metastatic disease for palliative reasons.

Significant contributions to improving the quality of life of these patients offer factors that interfere with bone metabolism, the main representatives being zoledronic acid and a monoclonal antibody, denosumab, either in the treatment of bone metastases or for the prevention of iatrogenic bone absorption [8].

References:

1. Berg WA, Blume JD, Cormack JB. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA 2008;299:2151.

2. Hammond ME, Hayes DF, Dowsett M. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 2010;28:2784.

3. Perou CM, Sørlie T, Eisen MB, Molecular portraits of human breast tumours. Nature 2000;406:747.

4. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659.

5. Goldhirsch A, Ingle JN, Gelber RD. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol 2009;20:1319.

6. Gennari A, Conte P, Rosso R. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer 2005;104:1742.

7. Slamon DJ, Leyland-Jones B, Shak S. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783.

8. 8. Gralow JR, Biermann JS, Farooki A. NCCN task force report: bone health in cancer care. J Natl Compr Canc Netw 2009;7(Suppl 3):S1.

Petroula Arapandoni-Dadioti, Director of laboratory of pathological anatomy, ‘Metaxa’ cancer hospital Vasileios Barbounis, Director of oncology, oncology unit of general hospital ‘Hippokrateion’

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Carcinoma of the colon and rectum

Carcinoma of the colon and rectum (CRC) is the world’s third most common cancer in men and second in women, with more than 1.2 million new cases and 600,000 deaths annually. The incidence of colorectal cancer varies, with higher incidences to be found in Australia, New Zealand, Europe and North America, and the lowest in Central Asia and Africa. The incidence of disease increases significantly after the age of 40–50 years.

In recent years the mortality from colon cancer has decreased progressively. This is probably because of early diagnosis through screening and improvement of therapy (surgery, radiotherapy and chemotherapy).

The main clinical manifestations of disease include changes in bowel habits (diarrhea or constipation), abdominal pain, blood in the stool, anemia and weight loss.

Prevention

The guidelines for the prevention and early detection of the disease in the general popula-tion include colonoscopy from the age of 50 years and thereafter every 10 years, or sig-moidoscopy every 5 years. For individuals at high risk, control must begin earlier [1].

Precancerous lesions

Carcinogenesis is a long-term process during which many genetic events lead to the malfunction of cells. Proliferation, apoptosis and cell signaling are affected. A cell’s phenotype is changed and histology reveals morphological changes that are known as precancerous lesions. Precancerous lesions are important biomarkers for cancer surveillance.

Precancerous lesions for CRC are adenomas, sporadic and in familial polyposis syndrome, and epithelial dysplasia in inflammatory bowel disease (IBDA) [2,3].

Image 1: colorectal adenoma (HEX25)

Adenomas

The incidence of adenomas is not known because they are not included in cancer registries. They are common in populations with a high incidence of colon cancer, in males, except adenomas of the rectum, which affect both sexes equally. Adenomas are defined by the presence of dysplastic epithelium. Dysplasia can be low grade or high grade. Adenomas are tubular, villous, tubulovillous and serrated. The characteristics of adenomas that are associated with synchronous and metachronous adenocarcinomas are the size, grade of dysplasia and histological subtype [3].

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Epithelial dysplasia in inflammatory bowel disease (IBDA)

The risk for CRC in IBDA increases after the first decade. Epithelial dysplasia (ED) has a heterogeneous macroscopic morphology and usually appears as a slightly raised lesion. The diagnosis of ED is based on histology and relies on experienced pathologists. It is of low or high grade [2,3].

Histology of CRC

The incidence of CRC is higher in the left colon than in the right colon, where in recent years an increase has been noticed. The macroscopic appearance of CRC is variable, depending on the histological type, the natural history of the disease and the time of diagnosis. The two main types are exophytic and entophytic.

Image 2: colon adenocarcinoma (HEX100)

Colorectal adenocarcinoma is defined by the World Health Organization (WHO) as epithelial neoplasm that invades through the muscularis mucosae.

CRC are mainly adenocarcinomas composed of glandular structures that are lined by one or more rows of cancer cells with or without mucus production. CRC is also graded traditionally, as moderate and undifferentiated adenocarcinoma on the basis of glandular formation [2,3].

Prognostic and predictive factors in CRC

The strongest prognostic factors in CRC are the anatomic extent of the disease and complete excision. The plethora of published studies reporting molecular and immunochistochemical prognostic factors have not been adopted into routine clinical practice [2,3].

The local extent of the disease, through the wall of the large bowel wall (T), metastasis in regional lymph nodes (N), metastasis in other lymph nodes, organs and tissues (M), and extramural venous invasion (V), are the findings that are included in histopathology reports. These are the main biomarkers that prognosis and therapy rely on [2–4].

Other prognostic factors with less statistical value are CRC differentiation grading, the extent of resection, referring to the area of excision specimen cut by the surgeon or gastroenterologist, the extent of residual cancer after therapy, the type of invasive edge and the morphology correlated with microsatellite instability-high (MSI-H) [2,5].

Predictive factors are genes or biomarkers that indicate the likelihood of CRC response or resistance to specific therapies. K-ras mutation, diagnosed by molecular techniques on

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tissue samples, and MSI-H, diagnosed by immunochemistry on tissue sections, predict a poor response to specific therapies [2].

Treatment

Surgical removal of the tumor is the only radical treatment. This is followed by 6 months of adjuvant chemotherapy for patients with CRC stage III and high-risk stage II. The adjuvant treatment increases survival by reducing the likelihood of disease recurrence [6]. For patients with rectal cancer stages II and III, surgical treatment is complemented by pre-operative or post-operative chemoradiotherapy.

The chemotherapy regimen mainly used in adjuvant treatment is FOLFOX (5 Fu + LV + oxaliplatin) or, alternatively, for patients who cannot receive oxaliplatin, 5 Fu + LV or capecitabine. Metastatic disease is treated primarily with chemotherapy. The last decade has seen significant progress in addressing metastatic disease. The median survival of about 12 months has increased to more than 24 months. This is mainly because of the use of new chemotherapeutic drugs (oxaliplatin, irinotecan and capecitabine) and drugs for targeted treatment (bevacizumab, cetuximab and panitumumab).

The use of therapeutic combinations with new cytotoxic drugs has resulted in increased response rates to treatment (RR), increased time to disease progression (TTP) and increased overall survival of patients with metastatic disease (OS) [6,7].

The better knowledge of the molecular biology of colon cancer in recent years has led to the development of new biological drugs targeting specific molecules that have an important role in the survival and proliferation of tumor cells.

Image 3: colon adenocarcinoma (APAPX250)

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The two main classes of such drugs in CRC, already used in daily practice, are those directed against epidermal growth factor receptor (EGFR) (cetuximab and panitumumab) and against vascular endothelial growth factor (VEGF) (bevacizumab). The addition of these biological agents to the cytotoxic drugs has improved RR, TTP and for some OS [7].

Another very important development in the treatment of CRC is the increase of the proportion of patients with metastases to the liver and lungs undergoing metastasectomy, resulting in long-term survival in a high proportion of these patients (5-year survival rate 27–58%) [8].

This development has been helped by the existence of effective drugs and improved surgical techniques.

Personalized treatment

CRC, as for other primary cancers, is not the same disease in all patients. The molecular biology as known today allows us to see changes from patient to patient that differentiates prognosis and responsiveness to various treatments. The effort today is to find reliable prognostic and predictive factors that will allow us to determine which patients should receive adjuvant therapy, for example, and which not, and what individualized treatment should be given to each patient.

Known molecular prognostic and predictive factors for CRC are the MSI and other gene mutations, and mutations in the K-ras gene are a predictor factor for treatment with anti-EGFR biological agents.

Individualization of treatments will offer patients the best therapeutic effects with reduced toxicity, while avoiding undue financial burden on the health system.

References:

1. Rex DK, Johnson DA, Anderson JC, et al. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol 2009;104:739.

2. Hamilton SR, et al. Carcinoma of colon and rectum. In: WΗO Classification of Tumours of the Digestive System. Lyon, France: IARC Press; 2010, 132–146.

3. Williams G, Quirke P, Shepherd N. Dataset for Colorectal Cancer, 2nd edn. The Royal College of Pathologists, 2007. Available at http://www.rcpath.org

4. Sobin L, Cospodarowicz M, Wittekind C, eds. UICC TNM Classification of Malignant Tumors, 7th edn. Spain: Wiley-Blackwell; 2009, 101–109.

5. Hellenic GIT Pathology Group. Working team: Arapadoni P, Barbatis C, Demonakou M, Delladestima I, Kafiri Z, Manika Z, Patakiouta F, Patsiaoura C, Petraki C, Skopa C, Skopelitou A, Spiliadis C, Toliou T, Venizelos I, Vrettou H. Pilot European protocol for adenocarcinoma of large bowel (EPPALB): the Greek experience. Virc Arch 2001;439:238–239.

6. André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009;27:3109.

7. Masi G, Vasile E, Loupakis F, et al. Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis. J Natl Cancer Inst 2011;103:21.

8. Venook AP, Curley SA. Management of potentially resectable colorectal cancer liver metastases. Up-To-Date 2011;19:3.

Maria Demonakou-Vatopoulou, Director of the laboratory of pathological anatomy, ‘Sismanogleion’, general hospital of Athens, general secretary of the Hellenic society of anatomic pathology

Pavlos Papakostas, medical oncologist, Director of oncology department, ‘Hippokrateion’ hospital of Athens, general secretary of the Hellenic society of mastology

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Cancer of the uterine cervix and HPV vaccine

Cervical cancer is the third most common cancer among women and the fourth leading cause of female cancer deaths. There is wide variation in its incidence among different countries (15.4 ca/100,000 women, 95% confidence interval 5.5–44.4/100,000). Approximately 500,000 new cases are diagnosed world-wide.

The most common invasive cervical cancer is squamous cell carcinoma, which accounts for 75–90% of cases, while 15–20% are adenocarcinomas, the incidence of which has been rising during the last few years. Less common types are adenosquamous and neuroendocrine carcinomas, the minimal deviation adenocarcinoma and the mesonephric duct adenocarcinoma.

The prognosis and therapeutic management of cervical carcinomas are related to their degree of differentiation as well as the stage of the disease. Treatment is mainly surgical. A radical hysterectomy with pelvic lymphadenectomy should be performed. Nevertheless, stage 1A carcinoma, either from squamous or glandular cells, whose depth is no more than 5 mm and width no more than 7 mm, can be treated with cervical conization. Moreover, for young women who wish to preserve fertility, even cancer stage 1B1 can be treated with radical trachelectomy and pelvic lymphadenectomy. Identification by the pathologist of lymph vascular tumor emboli does not change the stage of the disease but it should be referred to in the report because it could influence the choice of the therapy. Finally, for advanced stage carcinomas, radiotherapy with concurrent chemotherapy is the preferred treatment.

Nearly all squamous and the great majority of cervical adenocarcinomas are attributed to a persistent infection from one or more human papilloma virus (HPV). Epidemiologic studies have classified HPV into high-risk, probably high-risk and low risk for developing carcinoma. High-risk or oncogenic viruses are represented by clones 16, 18, 31, 45, 33, 52, 58 and 35. Their integration into the host genome initiates molecular changes that lead to the neoplastic transformation of the cell. Namely, there is inhibition of p53 and Rb, which blocks apoptosis and abrogates cell-cycle arrest, respectively.

The HPV-induced pre-invasive lesions of the squamous epithelium are called dysplasia or intraepithelial neoplasia (cervical intraepithelial neoplasia; CIN) and are morphologically classified into three grades (CIN1, CIN2 and CIN3) depending on the degree of epithelial maturation. Immunohistochemistry with Ki67 and p16 helps a lot with correct diagnosis and the identification of an infection with a high-risk virus. Moreover, the immunohistochemical expression of HPV L1 capsid protein seems to be useful in the evaluation of the progression risk of low-grade cervical dysplasia.

Most cervical HPV infections are cleared or suppressed within 1–2 years of exposure. The lag time between infection and appearance of the first microscopic evidence of pre-cancer (CIN3) can be 5–10 years. Approximately the same time is needed for the lesion to become an invasive cancer.

Primary massive screening of the population, mainly using the Pap-smear test, has led to a drastic reduction in disease mortality, through early diagnosis of cervical lesions in a pre-invasive stage. That is why cervical cancer has been characterized by the World Health Organization (WHO) as ‘population primary screening indicator’ since 1985. Unfortunately, the actual coverage and sufficiency of the screening programs differ significantly from country to country.

Recent data from a large epidemiological study showed the etiologic relation of various HPV subtypes (16, 18, 31, 33, 45, 52, 58) with cervical carcinoma [1]. These results led to the manufacture of an HPV vaccine against the most oncogenic HPV subtypes 16 and 18 (known as high-high risk), aiming for protection from an active infection and consequently a reduction in new cases. The actual goal of HPV vaccination is to reduce high-grade intra-epithelial (non-invasive) cervical neoplasias, although the cure rate at this stage of disease is almost 100%.

With HPV vaccination a primary etiologic management of pre-cancerous and cancer cervical lesions has been established, offering a new (prophylactic) approach to the disease.

The basic population advantage of HPV vaccination is that, in lower and middle economic

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countries where screening programs are not available, it offers a relatively easy, cheap and effective method of cervical cancer prevention, while in developed countries it acts as a front-line defense against the disease (prevention), despite the fact that these cases will be diagnosed early thanks to the population screening programs.

A significant advantage of these vaccines is the way in which they are manufactured. Both of them contain only the immunostimulating L1 surface protein of the viral capsid, and no viral DNA, forming the virus-like particles (VLP), so they are not contagious nor oncogenic and are therefore safe to use [2,3].

So far, scientific data show a high protection rate (>90%) of the vaccines against high-grade intra-epithelial cervical neoplasias (HGSIL or CIN 2-3) 5 years after vaccination, and there is a strong indication of longer protection [4, 5]. These findings are early indications that in a few years we can expect a considerable reduction in cervical cancer prevalence, as long as HPV vaccination of girls and young women aged 12–26 years is applied generally.

References:

1. Muñoz N, Bosch FX, de Sanjosé S, et al. International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518–527.

2. Berzofsky JA, Ahlers JD, Janik J, et al. Progress on new vaccine strategies against chronic viral infections. J Clin Invest 2004;114:450–462.

3. Modis Y, Trus BL, Harrison SC. Atomic model of the papillomavirus capsid. EMBO J 2002;21:4754–4762.

4. Cuzick J. Long-term cervical cancer prevention strategies across the globe. Gynecol Oncol 2010.

5. Romanowski B, et al. Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet 2009.

K. Pavlaki, Associate Professor of pathology, medical school, university of Athens G. Vorgias, gynecologic oncologist, ‘Metaxa’ cancer hospital

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Lung cancer

Lung cancer is the second most common neoplasm after prostate cancer in men and breast cancer in women. Currently, lung cancer is the leading cause of all cancer deaths world-wide. The main predisposing factors for lung cancer development are tobacco smoking, atmospheric pollution, chronic pulmonary disease, genetic predisposition, and professional exposure to radiation, asbestos, chromium, rhodium, arsenium, nickel and tar. Fifteen percent of all smokers are expected to develop lung cancer [1]. The data concerning lung cancer incidence in Greece are alarming, as Greece is the second country (after Poland) within the European Union (EU) with the highest consumption of cigarettes and the country with the highest incidence of lung cancer among people less than 45 years of age.

Lung cancer can be completely asymptomatic in the early stages and the diagnosis can be made incidentally during chest radiography for other clinical indications. Symptoms can be attributed to local extension of the tumor, including coughing, dyspnea, chest pain and bloody sputum. In some cases, symptoms from extrathoracic metastases can predispose before diagnosis, i.e. bone pain as a result of bony metastases, or persistent headache, vomiting and seizures as a result of brain metastases. A variety of paraneoplastic syndromes, such as various neuromyopathies, hypertrophic pulmonary osteoarthropathy, hypercalcemia, cachexia and thrombophlebitis migrans, can develop and need special attention to establish a diagnosis of underlying lung cancer [2].

An initial diagnosis of lung cancer will be made according to clinical symptoms and radiologic findings from plain radiography and computed tomography (CT) of the chest. The definitive diagnosis will be made from tissue biopsy or cytology of the bronchial secretions obtained through fiber optic bronchoscopy in central neoplasms or CT-guided FNA/FNB (i.e. fine needle biopsy) in peripheral neoplasms. Tissue diagnosis can also be made using thoracoscopy, mediastinoscopy, scalene lymph node biopsy, exploratory thoracotomy and cytology of the sputum or the pleural fluid of any concomitant pleural effusion [2].

The three main therapeutic options in lung cancer are surgery, radiotherapy and chemotherapy. Surgery, when indicated, gives by far the best results. The choice of the appropriate treatment is associated with three factors.

1. Histology of the tumor and especially classification of the tumor as either a small cell lung carcinoma (SCLC) or non-small cell lung carcinoma (NSCLC). The classification of a tumor as SCLC or NSCLC is crucial for selection of the appropriate therapy because SCLC is an aggressive neoplasm that metastasizes early to mediastinal lymph nodes and/or distal organs and is rarely amenable to surgical resection [2–4].

2. The stage of the disease at the time of diagnosis is very important in NSCLC. The stage will delineate the role of surgery, which is indicated in the absence of distant metastases and/or of mediastinal lymph node invasion [2–5]. Evaluation of mediastinal lymph node status is currently made with PET/CT scans (i.e. positron emission tomography), the positive results of which should always be confirmed with an invasive method (mediastinoscopy, transbronchial or transesophageal ultrasound-guided biopsy) [5]. The PET/CT scan is considered today to be an important pretherapeutic facility in a large cohort of lung cancer patients. [2]

3. The performance status of the patient is the third factor that affects the choice of the appropriate treatment for each individual. Evaluation of the respiratory status, which is to a large degree estimated with spirometry and arterial blood gas determination, and of cardiac status is of major pretherapeutic importance. The majority of lung cancer patients are current or ex-smokers suffering from chronic obstructive pulmonary disease and/or coronary artery disease. All patients should be evaluated before pulmonary surgical resection with the THORACOSCORE, which accurately estimates the global risk of death after surgical intervention in the thorax [2].

According to the new lung cancer staging system established in 2009 (Table 1), the size of the tumor is of paramount prognostic importance (Table 2) [3]. Diagnosis of the tumor at an early stage, especially before metastasizing in mediastinal lymph nodes (Table 3), gives the best chance for long-term survival, and consequently all current and ex-smokers should be evaluated

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yearly with chest radiography or low-dose radiation CT scans. The ‘wait and watch’ tactic for pulmonary coin lesions should be abandoned and all suspicions of cancer coin lesions should be evaluated aggressively to exclude the possibility of early-stage lung cancer. According to the new lung cancer staging system, all locally advanced lung cancers (T3 or T4) without lymph node invasion are staged as IIB or IIIA and therefore could benefit from surgical resection, with or without the application of induction chemoradiotherapy. The final decision should always be made within a multidisciplinary oncology team [2–4].

Table 1: The new lung cancer staging system (2009) [3]

Stage Ι

Substage IA: tumor ≤2 cm (T1α) or tumor >2 cm but ≤2 cm (Τ1β) without lymph node involvement (Ν0)

Substage ΙΒ: tumor >3 cm but ≤5 cm (Τ2α) with Ν0

Stage ΙΙ

Substage ΙΙΑ: tumor ≤5 cm (Τ1α,β & Τ2α) with involvement of intrapulmonary or hilar nodes (Ν1) or tumor >5 cm but ≤7 cm (Τ2β) with Ν0

Substage ΙΙΒ: tumor >5 cm but ≤7 cm (Τ2β) with Ν1 or T3 tumor* with Ν0

T3 tumor*: tumor >7 cm or tumor directly invading chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium or tumor in the main bronchus <2 cm distal to the carina or atelectasis/obstructive pneumonitis of the entire lung or separate tumor nodules in the same lobe

Stage ΙΙΙ

Substage ΙΙΙΑ: tumor T1-3 with involvement of ipsilateral mediastinal lymph nodes (Ν2) or Τ3 tumor with Ν1 or Τ4 tumor* with Ν0 or Ν1

Substage ΙΙΙΒ: Τ4 tumor with Ν2 or any T tumor with involvement of contralateral mediastinal or hilar nodes or involvement of ipsilateral or contralateral scalene and subclavian nodes (Ν3)

*T4 tumor: tumor of any size with invasion of heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina or separate tumor nodules in a different ipsilateral lobe

Stage IV

Any T, any N tumor with metastatic nodules in the contralateral lung, or tumor with pleural nodules or malignant pleural dissemination (substage M1b) or

with distant metastasis (substage M1b)

Table 2: The 5-year survival rate of NSCLC according to the size of the primary tumor in patients without lymph node involvement (N0) and without distant metastases

Tumor size 5-year survival (%)≤2 cm 77

>2 cm and ≤3 cm 71>3 cm και ≤5 cm 58>5 cm και ≤7 cm 49

>7 cm 35

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Table 3: The 5-year survival rate of NSCLC patients according to the regional lymph node stage (N). These survival rates are independent of the T-stage of the tumor in N0 patients

N stage 5-year survival (%)Ν0 56Ν1 38Ν2 22Ν3 6

Lobectomy, bronchoplastic lobectomy and pneumonectomy with en bloc resection of all the surrounding invaded structures (chest wall, diaphragm, pericardium) plus mediastinal lymph node dissection is the standard of care for patients with stage I and II lung cancer [2–4]. Induction chemotherapy and/or radiotherapy are almost always indicated in stage IIIA tumors and superior sulcus tumors (Pancoast). Adjuvant therapy should be added in stage IB–IIIA neoplasms [2–4]. Limited pulmonary resection (wedge resection and typical segmentectomy) can be applied with good results in patients with stage I tumors who are more than 70 years old and who cannot tolerate lobectomy. Clear resection margins around the tumor after limited resection should be more than 1 cm wide [6]. Mortality rates should not exceed 3% for lobectomy and 7% for pneumonectomy [2].

The cumulative 5-year survival for all lung cancer patients still remains below 15%. Only 30–40% of patients who undergo curative resection will survive without local or distant recurrence for 5 years. In addition, long-term survivors after curative resection have a 15% chance of developing a second primary lung neoplasm, and consequently long-term follow-up is always warranted [1,4]. The evidence that development of lung cancer is strongly related to cigarette smoking and the overall low 5-year survival of the disease make it absolutely clear that prevention is the optimal treatment for the disease. Prevention of lung cancer necessitates a heavy anti-smoking campaign that has to begin early in life, preferably from the school classroom [7].

References:

1. Smith PW, Jones DR. Biology and epidemiology of lung cancer. In: Patterson AG, Cooper JD, Deslauriers J, et al. Pearson’s Thoracic and Esophageal Surgery, 3rd edn. Philadelphia: Churchill Livingstone Elsevier; 2008, 708–728.

2. Lung Cancer: The Diagnosis and Treatment of Lung Cancer. Available at http://www.nice.org.uk/guidance/CG121/Guidance [last accessed on 8/1/2012].

3. Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest 2009;136:260–271.

4. LoCicero J, Ponn RB, Daly BDT. Surgical treatment of non-small cell lung cancer. In: Shields TW, LoCicero J, Ponn RB. General Thoracic Surgery, 5th edn. Philadelphia: Lippincott Williams & Wilkins, 2000, 1311–1341.

5. DeLeyn P, Lardinois D, Van Schil P, et al. ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer. Eur J Cardiothorac Surg 2007;32:1–8.

6. Rami-Porta R, Tsuboi M. Sublobar resection for lung cancer. Eur Resp J 2009;33:426–435.

7. Barendregt JJ, Bonneux L, van der Maas PJ. The health care costs of smoking. N Engl J Med 1997;337:1052–1057.

Christophoros N. Foroulis, Assistant Professor of thoracic surgery, Aristotle university, medical school, AHEPA university hospital, department of cardiothoracic surgery, Thessaloniki

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Carcinoma of the lung: histopathology

Histological classification of lung carcinoma is important because it provides a basis for epidemiology, prognosis and therapeutic approach. The most recent classification of the World Health Organization (WHO) has been widelyaccepted.

The four major histological types of carcinoma of the lung are squamous cell carcinoma (SCC), adenocarcinoma (AD), smallcell carcinoma (SCLC) and largecell carcinoma (LCC). In some cases there can bea combination of histologicalpatterns (Table 1) [1, 3].

Table 1: Histological classification of lung carcinomas

Non-small cell carcinomas

Squamous cell carcinoma

Adenocarcinoma

Acinar, papillary, solid, bronchioloalveolar, mixed subtypes

Large cell carcinoma

Large cell neuroendocrine carcinomaSmall cell carcinoma

Recently, for therapeutic purposes, carcinomas have been classified into two groups on the basis of the likelihood of metastases and response to available therapies: SCLC (most often metastatic, high initial response to chemotherapy) and non-small cell carcinomas (NSCLC) (less often metastatic, less responsive) (Table1)[3].

Squamous cell carcinoma often begins with an area of squamous metaplasia or dysplasia in the bronchial epithelium, mainly of major bronchi, that progress to carcinoma in situ. Macroscopically, the tumor has an irregular, often friable, grey–white cut surface, commonly showing a large area of central necrosis, with or without cavitation. Histologically, SCC range from well-differentiated squamous cell neoplasm with keratin formation and intercellular bridges, to poorly differentiate with only minimal residual squamous cell features. Well-differentiated SCC tends to spread locally within the chest, directly involving adjacent mediastinal structures. Poorly differentiated carcinoma tends to metastasize early and to distant sites (Figure 1A) [1,4].

Adenocarcinoma is more peripherally located than SCC, and often arises in relation to peripheral lung scars and is the most common type of lung cancer in women and non-smokers.Histologically, AD varies with glandular differentiation or mucin production by tumor cells, and the patterns are acinar, papillary, bronchioloalveolar and solid with mucin formation.

Bronchioloalveolar carcinoma (BAC) has distinct gross, histological and clinical features. The tumor almost always occurs in the peripheral sites of the lung, either as a single nodule or, more often, as multiple diffuse nodules that sometimes coalesce to produce a pneumonia-like consolidation [1]. Histologically, the tumor is characterized by a bronchioloalveolar growth pattern. It is suggested that AD of the lung arises from atypical adenomatous hyperplasia progressing to BAC (Figure 1C) [1,2].

Patients with poorly differentiated AD have more local recurrences and lymph node metastases than patients with well or moderately differentiated tumors [5].

Large cell carcinoma is, by definition, a poorly differentiated malignant epithelial tumor. It consists of sheets or nests of large polygonal or giant multinuclear cells and probably represents SCC and AD. One histological variant is large cell neuroendocrine carcinoma, and confirmation of neuroendocrine differentiation is required using immune histochemical markers (Figure 1D).

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Small cell carcinoma of the lung is a malignant epithelial tumor derived from neuroendocrine cells of the bronchial epithelium that produces polypeptide hormones and causes paraneoplastic syndromes. Macroscopically, the tumor is a soft, friable, perihilar mass with extensive necrosis and frequent nodal involvement. Approximately 5% of SCLC present as peripheral coin lesions. The cells are round, oval or spindle-shaped with scant cytoplasm and ‘nuclear molding’, and often show fragmentation and a ‘crush artifact’ in small biopsies (Figure 1B)[3]. Immuno-histochemistry is positive for neuroendocrine markers.

Combined carcinoma: approximately 10% of all lung carcinomas have a combined histology, including two or more of the above types.

Figure 1: Histologic types of lung carcinoma. (A)SCC.(B)SCLC. (C)ADBAC type.(D)LCC.

A B

C D

Prognostic histopathological criteria

Histological grading is a qualitative assessment of tumor differentiation that is an important component of the pathology report and has prognostic value. Histological parameters that correlate with unfavorable prognosis include high histological grade, mitotic activity, extensive tumor necrosis and vascular invasion [5].

Genetic predictive factors

Many studies on lung carcinoma have been carried out to identify molecular predictors of the response to chemotherapy and survival. K-ras oncogene activation by point mutation correlates with poor survival and is also associated with the effect of chemotherapy at an advanced stage of NSCLC. Mutations in epidermal growth factor receptor (EGFR) are significantly related to stage, survival and response to treatment with EGFR inhibitors [6,7].

References:

1. Husain A, Kumar V. The lung. In: Robbins, Cotran. Pathologic Basis of Disease, 7th edn. Philadelphia: Saunders;2005, 711–772.

2. Moran C, Kevin L, Wick M. Non neuroendocrine carcinomas and salivary gland analogue tumors of the lung. In: Practical Pulmonary Pathology, 1st edn. Philadelphia: Churchill Livingstone; 2005, 561–601.

3. Maitra A, Kumar V. The lung. In: Robbins Basic Pathology, 8th edn. Philadelphia: Saunders; 2007, 479–539.

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4. Noguchi M, Shimosato Y. Pulmonary neoplasms. In: Sternberg’s Diagnostic Surgical Pathology, 5th edn. Philadelphia: Lippincott Williams and Wilkins; 2010, 1054–1095.

5. Travis W, Brambilla E, Müller–Hermelink HK, Harris C. In: Pathology and Genetics of Tumours of the Lung, Pleura Thymus and Heart.Lyon:WHO IARC;2004, 26–72.

6. Heist R, Christiani D. EGFR-targeted therapies in lung cancer: predictors of response and toxicity. Pharmacogenomics 2009; 10:59–68.

7. Andrade de Mello R, Marques DS, Medeiros R, Araùjo A.Epidermal growth factor receptor and K-RAS in non small cell lung cancer–molecular pathways involved and targeted therapies.World J Clin Oncol 2001;2:367–376.

Eleni Vrettou, Professor of pathology medical school, Aristotle university of Thessaloniki

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Hematological malignancies I: recent advances

Leukemias, lymphomas and multiple myeloma (MM) are highly heterogeneous malignancies of the hematopoietic and immune systems, arising from bone marrow or/and lymph nodes. In general, they are sensitive to chemotherapy, radiotherapy and immunotherapy, with a subsequent high cure rate even in advanced-stage disease.

The annual incidence in Greece is approximately 1400, 2000 and 400 new cases of leukemias, lymphomas and MM, respectively [1]. They are more frequent in the elderly of both sexes. Acute lymphoid leukemia (ALL) is the more frequent malignancy in children.

The more frequent leukemias are acute myeloid leukemia (AML), ALL, chronic myeloid leukemia (CML) and chronic lymphoid leukemia (CLL).

Lymphomas are divided into Hodgkin (HL) and non-Hodgkin lymphomas (NHL). NHL are subdivided into B-, T- and NK-lymphomas (i.e. natural killers), depending on their cell origin.

During the last decade our knowledge of the pathophysiology of these diseases has expanded greatly. Subsequently, new therapeutic modalities have emerged that can cure more patients. Some of them will be touched upon in the following paragraphs.

AΜL

The nucleophosmin gene (NPM1) is mutated in 30% of patients. Mutated NPM1 plays a key role in the development of AML, and confers a better prognosis for those patients bearing it [2,3].

ALL

Philadelphia chromosome (Ph+), found in 20% of adult ALL patients, confers a very poor prognosis [4]. During the last decade the introduction of tyrosine kinase inhibitors (imatinib, dasatinib and nilotinib) has greatly improved the outcome of Ph+ ALL patients [5].

CLL

The combination of chemo-immunotherapy with fludarabine, cyclophosphamide and rituximab has greatly improved the outcome for patients [6].

CML

All CML patients carry the cytogenetic abnormality called Ph+, which causes the fusion of bcr and abl genes. The bcr–abl fusion gene codes for a protein with constitutive tyrosine kinase activity that is the causative event of CML. First imatinib and then dasatinib and nilotinib, specific tyrosine kinase inhibitors, have been introduced during the last decade and have revolutionized the management of CML patients [7,8].

NHL

The combination of rituximab, an anti-CD20 monoclonal antibody, with standard chemotherapy has greatly improved the outcome for patients with NHL of B-cell origin [9].

HL

Positron emission tomography (PET) is currently the most sensitive imaging technique; it can reveal the involvement of both HL and NHL areas. It is believed that PET will prove to be a valuable tool for tailoring therapy according to a patient’ s need, thus minimizing the short- and long-term toxicity of standard therapy [10].

Recently, a new monoclonal antibody against CD30, a protein on the malignant cells of HL and a type of NHL, bound to a toxin has been used. The first results are very promising [11].

MM

The standard management is chemotherapy and autologous hematopoietic stem cell transplantation. Recently new drugs have been introduced (thalidomide, lenalidomide and bortezomib) that can improve survival [12].

Allogeneic hematopoietic stem cell transplantation

This is considered to be the treatment of choice for several patients with all kinds

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of hematological malignancies. Sometimes it is the only therapy with a curative potential. In 70% of cases a family donor is not available; an unrelated adult donor or umbilical cord blood can then be used [13].

References:

1. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010;116:3724.

2. Rockova V, Abbas S, Wouters BJ, et al. Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers. Blood 2011;118:1069.

3. Falini B, Martelli MP, Bolli N, et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood 2011;117:1109.

4. Westbrook CA, Hooberman AL, Spino C, et al. Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762). Blood 1992;80:2983.

5. Gruber F, Mustjoki S, Porkka K. Impact of tyrosine kinase inhibitors on patient outcomes in Philadelphia chromosome-positive acute lymphoblastic leukaemia. Br J Haematol 2009;145:581.

6. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376:1164.

7. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994.

8. Jabbour E, Kantarjian H, O’Brien S, et al. The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood 2011;118:4541.

9. Armitage JO. How I treat patients with diffuse large B-cell lymphoma. Blood 2007;110:29.

10. Naumann R, Vaic A, Beuthien-Baumann B, et al. Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Br J Haematol 2001;115:793.

11. Chen R, Gopal AK, Smith SE, et al. Results of a pivotal phase 2 study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma. Blood 2010;116:128.

12. Scott E, Reece D. What is the benefit of maintenance therapy with lenalidomide or bortezomib after autologous stem cell transplantation in multiple myeloma and what is the risk of developing a secondary primary malignancy? In: Hematology 2011. American Society of Hematology, Education Program Book.

13. Appelbaum FC. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia when a matched related donor is not available. In: Hematology 2008. American Society of Hematology, Education Program Book.

Dimitrios Karakasis, Director of bone marrow transplantation unit, ‘Evaggelismos’ hospital, Athens

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Hematological malignancies II

The 2008 WHO classification of lymphoid neoplasms and current pathological diagnostic approaches with clinicoprognostic implications

Ι. Introduction

Classifications of diseases provide the language of medicine, categorizing known entities in a way that facilitates understanding between workers in the field and providing a framework for both clinical practice and the generation of new knowledge. A characteristic example is the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, first published in 2001 and recently (2008) revised and updated. The latter initiative was a continuation of the 2001 WHO classification, which represented a world-wide consensus in terms of broad acceptance and general use during the preceding few years by hematopathologists, clinical hematologistis and general scientists from all over the world. The world-wide acceptance of this classification was the result of a major consensus built up among all the above-mentioned players based on a proposal that was biologically sound, clinically relevant and of practical use world-wide in different clinical settings.

The major principles of the 2001 and 2008 WHO classifications of lymphoid tumors are: a) stratification of the lymphoid tumors primarily according to the cell lineage (B/T/NK) and additionally according to their derivation from precursors or mature lymphoid cells, and b) the definition of distinct, clinically relevant, diseases based on a multiparameter clinicopathological diagnostic approach in the context of a combination of morphology, immunophenotype, and genetic, molecular and clinical manifestations, considered to be a solid framework into which new knowledge should be incorporated. The new knowledge gathered over the last few years (2001–2008) by different working groups highlighted several aspects of the WHO 2001 classification that needed to be revised and updated, and led to the revised 2008 WHO classification of lymphoid neoplasms.

II. New aspects of the updated 2008 WHO classification of lymphoid neoplasms

1) Refinement in definitions of ‘well-established’ diseases

Such diseases include chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), lymphoplasmacytic lymphoma (LPL) and Waldenstrom macroglobulinemia (WM).

a. CLL is now defined as the presence of 5 × 109/L monoclonal lymphocytes with a CLL phenotype in the peripheral blood.

b. PLL is defined as the presence of more than 55% prolymphocytes in the peripheral blood, but cases with the t(11;14) translocations, previously accepted in this category, are now excluded and better considered as leukemic mantle cell lymphoma.

c. The new WHO classification of 2008 recognizes that LPL and WM are not synonymous because of a) the absence of IgM paraprotein and b) the presence of another paraprotein, frequently IgG in some cases of LPL, respectively. Therefore the 2008 WHO classification recognizes a single entity under the term LPL.

2) Consensus on old controversies

Regarding follicular lymphoma (FL), the advances in old controversies include the recognition that: a) there are no major biological or clinical differences between grades 1 and 2, and they are treated similarly, and b) it is important to segregate grade 3b from 3a, because grade 3b may correspond to a category that may be closer to diffuse large B-cell lymphoma (DLBCL) than conventional FL.

3) Newly defined entities and categories

1) B-cell lymphomas

The category of diffuse large B-cell lymphoma, NOS (DLBCL), has recognized the important contribution of gene expression profiling, accepting the two molecular subtypes of germinal center and activated B-cell-derived DLBCL. In addition, different subtypes and new entities

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have been accepted, particularly among DLBCL with a terminal B-cell differentiation, such as ALK-positive DLBCL, DLBCL associated with chronic inflammation, plasmablastic lymphoma, large cell lymphoma arising in HHV-8-associated multicentric Castleman disease and EBV+ DLBCL of elderly patients.

2) Peripheral T-cell lymphomas

ALK-positive anaplastic large cell lymphoma (ALCL) is a specific entity that should be distinguished from tumors with similar morphology and phenotype that are ALK negative, which are considered to be a different provisional category. The diagnosis of subcutaneous Panniculitis–like T-cell lymphoma is now restricted to cases with an alpha/beta phenotype, and similar tumors with a gamma/delta phenotype are reclassified as primary cutaneous gamma/delta T-cell lymphoma, a category that appears to be more aggressive with frequent systemic dissemination.

4) New concepts

A) Early lesions and indolent forms of lymphomas

These may correspond to early stages of lymphomagenesis, such as monoclonal B-cell lymphocytosis, FL ‘in situ’ and mantle cell lymphoma ‘in situ’. The identification of these situations are of conceptual interest to investigate the early mechanisms in lymphomagenesis but are also of clinical importance because the patients may need a more conservative management in the context of watch and wait.

B) Age as a major identification of new entities

Pediatric follicular and nodal marginal zone lymphomas are characterized by their indolent course, in contrast to their adult counterparts, which require an immunochemotherapeutic approach. EBV+ DLBCL of elderly patients shows an aggressive clinical course. In addition, the 2008 WHO classification recognizes two uncommon T lymphoproliferative disorders with EBV in children, systemic EBV+ lymphoproliferative disease of children and hydroa vaccinifome-like lymphoma, with aggressive and indolent biological clinical courses respectively.

C) The importance of specific topographic sites

This idea has been now expanded to incorporate additional B- and T-cell primary cutaneous lymphomas and central nervous system (CNS) DLBCL, and also recognizes that FL originating in the duodenum are categories with specific clinicopathologic features, such as a very indolent prognosis in contrast to their nodal counterparts, which are disseminated at presentation and need immunochemotherapeutic regimens.

D) Lymphomas with overlapping features between different entities

These include a) the unclassifiable B-cell lymphoma, with features intermediate between DLBCL and Burkitt lymphoma, and b) the unclassifiable B-cell lymphoma, with features intermediate between DLBCL and classic Hodgkin lymphoma. The first subtype is an extremely aggressive B-cell lymphoma, the majority of cases being resistant to current therapies, and the second one is characterized by a more aggressive clinical course and poorer outcome than either CHL (i.e. classic Hodgkin lymphoma) or primary mediastinal DLBCL.

III. Open questions and future challenges

Some issues are not resolved in the 2008 WHO classification of lymphoid tumors. These include: a) provisional and emerging entities, b) the role of biomarkers in the prognosis of lymphoma, and c) the information generated by microarray expression-profiling studies in the identification of new lymphoma subtypes, or the potential clinicotherapeutical value of specific molecular pathogenetic pathways.

References:

1. Harris NL, Jaffe El, Banks PM, et al. A revised European American classification of lymphoid neoplasms: a proposal from the international lymphoma study group, Blood 1994;84:1361–1392.

2. Jaffe E, Harris NL, Stein H, et al. Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissue. World Health Organization Classification of Tumours. Lyon, France: IAPC Press, 2001.

3. Swerdow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and

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Lymphoid Tissues. Lyon, France: IAPC Press, 2008.

4. Jaffe ES, Harris H, Isaacson PG. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood 2008;112:4384–4399.

5. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasma and beyond: evolving concepts and practical applications. Blood 2011;117:5019–5032.

Theodora Papadaki, hematopathologist, Chief of the hematopathology department, ‘Evangelismos’ general hospital

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HCDCP departments activities

Cancer congress, 1 February 2012

One year after the public announcement and presentation of the National Cancer Plan 2011–2015, 50 years after the loss of Dr George Papanikolaou and in view of the World Cancer Day, a 1-day congress was organized by the Hellenic Center for Disease Control and Prevention (HCDCP), in collaboration with the General Secretary for Public Health Dr Antonis Dimopoulos. It was held on 1 February 2012 in the auditorium of the Ministry of Health and Social Solidarity premises in Marousi-Athens, under the title Cancer Prevention and Public Health Promotion: from the Formation of the Hellenic Cancer Registry to Today.

The congress was honored with the presence of the Deputy Minister of Health Mr Michalis Timosidis, the academic Professor Dr Dimitrios Trichopoulos, the General Director of Public Health and Quality of Life, the Directors of the 1st and 2nd health peripheries of Greece, members of the academic world, health institution managers and executives of national public and private hospitals and health centers of Greece. The current state of the national strategy against cancer of the Ministry of Health was presented to the congress, along with the primary outcomes. In particular, ministerial efforts were concentrated on the development of the Hellenic Cancer Registry (HCR) and the national screening program against cervical cancer.

After a long and inactive period, the foundations for the operation of a well-organized cancer registry that will follow international standards have been set. Within the last month, all the country’s health institutions, of both public and private sectors, have nominated employees, the so-called ‘cancer registrars’, to undertake cancer registration in Greece. Within the framework of the National Strategic Reference Framework (NSRF) 2007–2013, the team of the HCR of HCDCP will train and educate cancer registrars, on methods for reliable and timely data collection, over the next 2 years. By the end of 2013, and in accordance with the European Union (EU)’s recommendations, Greece will have a valuable tool for identifying and measuring the cancer burden in our country with a view to controlling cancer and increasing the efficacy of the ministry’s interventions against cancer, with multiple benefits.

At the same time, and for the first time ever in our country, a screening program for cervical cancer has been introduced, partially as a pilot from 1 July 2011, and nationally since 10 October 2011. In the first phase of the program, 160 municipalities and 140 health centers and municipality medical centers were involved in regions of the country that are either remote or disadvantaged and provide insufficient access to medical and health care services. The program targets women in the age range of 25–65 years.

The first results of the program have shown an impressive increase in health center participation (an increase of 60.31% in August, 53.2% in September, 55.07% in October, 78.84% in November and 128.73% in December of 2011), illustrating the need for educating the public to make use of the NHS services for early diagnosis. In total, so far 19,292 women have been tested, of whom 138 have been reported to have pre-cancerous lesions or cervical cancer; the vast majority of them will be cured because the disease was diagnosed at an early stage.

Two workshops took place at the congress, in parallel during the afternoon of the same day. The first one presented the new cancer registration system and was addressed in particular to the cancer registrars. In total 103 cancer registrars, from public and private hospitals of Greece, attended. The team of HCR, Mrs Sophia Tzala, Mrs Anthi Chrisostomou and Mr John Loukopoulos, presented the new cancer registration system, including the new epidemiological form and the web-based information system developed for this purpose. Dr Petroula Arapantoni-Dadioti, Dr Maria Demonakou and Dr Evangelia Tzala co-ordinated the workshop.

The second workshop dealt with the cervical cancer screening program and in particular, and according to European guidelines, the correct way to ensure collection and preparation of an adequate cervical cell sample, adequate handling and staining of the samples, presentation of the information system and management of screen-positive women. Dr Chris Lionis and Dr Euripides Bilirakis co-ordinated the workshop’s sessions. Dr Ioannis Panagiotidis, Dr Calliope Nasioutziki and Dr Maria Pappas acted as facilitators.

Evaggelia Tzala, Head of the National Cancer Registry and Rare Diseases Office

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Recent publications

Tumors light up in surgery Nature 2011;477:372 (22 September 2011)

A tumor-specific fluorescent label has allowed surgeons to remove ovarian cancer tissue that would have appeared normal to the naked eye. About 85–95% of ovarian cancers express large numbers of receptors for the molecule folate. So Gooitzen van Dam at the University of Groningen in the Netherlands, Vasilis Ntziachristos at the Technical University Munich in Germany and their colleagues tested a probe made up of folate bound to a fluorescent molecule. They injected 10 patients with this label and used a special camera and light source to ‘light up’ the cancer cells during surgery. Fluorescence appeared in patients with malignant tumors but not in those with benign growths. Furthermore, five surgeons asked to identify tumor deposits in color images detected more when aided by fluorescence.

Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study. Luo J, Margolis KL, Wactawski-Wende J, Horn K, Messina C, Stefanick ML, Tindle HA, Tong E, Rohan TE Br Med J 2011 Mar 1;342

In this large prospective and multi-center study in postmenopausal women (79,990 women aged 50–79 enrolled in 40 clinical centers in the USA), an elevated risk of breast cancer was observed in former smokers (9%) and current smokers (16%), associated particularly with smoking of high intensity, of long duration, and since an early age. Among former smokers, the time since quitting smoking was significantly inversely associated with breast cancer risk, and it took up to 20 years for a former smoker’s risk to return to baseline. Finally, an excess risk of 32% was observed for breast cancer associated with the most extensive exposure to passive smoking among women who had never been active smokers.

Joanna Laina, National Cancer Registry and Rare Diseases Office

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Interesting activities

European Code against Cancer (3rd version)

The ‘11 commandments’ for cancer prevention

Many aspects of general health can be improved and many cancer deaths prevented, if we adopt healthier lifestyles.

1. Do not smoke; if you smoke, stop doing so. If you fail to stop, do not smoke in the presence of non-smokers.

2. Avoid obesity.3. Undertake some brisk, physical activity every day.4. Increase your daily intake and variety of vegetables and fruits: eat at least five servings

daily. Limit your intake of foods containing fats from animal sources.5. If you drink alcohol, whether beer, wine or spirits, moderate your consumption to two

drinks per day if you are a man and one drink per day if you are a woman.6. Care must be taken to avoid excessive sun exposure. It is especially important to

protect children and adolescents. For individuals who have a tendency to burn in the sun, active protective measures must be taken throughout life.

7. Strictly apply any regulations aimed at preventing exposure to known cancer-causing substances. Follow all health and safety instructions on substances that may cause cancer. Follow the advice of national radiation protection offices.

There are public health programs that can help prevent cancers developing and increase the probability that a cancer may be cured.

8. Women from 25 years of age should participate in cervical screening. This should be within programs with quality control procedures in compliance with the European guidelines for quality assurance in cervical screening.

9. Women from 50 years of age should participate in breast screening. This should be within programs with quality control procedures in compliance with the European guidelines for quality assurance in mammography screening.

10. Men and women from 50 years of age should participate in colorectal screening. This should be within programs with built-in quality-assurance procedures.

11. Participate in vaccination programs against hepatitis B virus infection.

http://www.europeancancerleagues.org/ewac/european-code-against-cancer.pdf

National Cancer Registry and Rare Diseases Office

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Eurosurveillance 15-year anniversary (1996–2011)

On 8 November 2011, Eurosurveillance organized a scientific seminar with three specially invited speakers to celebrate its 15-year anniversary. Eurosurveillance is a European peer-reviewed scientific journal devoted to the epidemiology, surveillance, prevention and control of communicable diseases, focusing on topics that are of relevance to Europe. In the last 3 years (2009–2011) alone, more than 600 articles have been published from 29 countries in the European Union (EU)/EEA grouping and more than 30 countries in the rest of the world.

Presenting timely information regarding ongoing outbreaks, emerging and re-emerging entities, and relevant information on trends in infectious diseases from all European countries, to enable timely public health action, is one of Eurosurveillance’s main goals. During the 2009 H1N1 pandemic, the rapid turnover of concise, authoritative, peer-reviewed information received world-wide attention. By 10 August 2010, the official end of the pandemic, more than 120 papers had been published, mostly rapid communications. Eurosurveillance was founded in 1995 and jointly funded until March 2007 by the European Commission, the Institut de Veille Sanitaire (InVS) in Paris, France, and the Health Protection Agency (HPA) in London, United Kingdom. Since March 2007, Eurosurveillance has been published by the European Center for Disease Control (ECDC) in Stockholm, Sweden.

Since its beginning, the journal has been open-access and, as a non-profit publication, has no financial conflicts of interest; it is issued on a weekly basis, and in 2012 the 17th volume will be issued. The first impact is expected to be allocated in the course of 2012.

Regina Vorou, Office for Strategic Planning

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Meet our editorial team

Eleonora Hadjipaschali I was born in beautiful Ammochostos in Cyprus, but I was forced to leave because of the Turk-ish invasion. I was rather impressed with biology, which was my favorite subject at school. I chose France to start my studies, and then Greece. My interests moved into the management field, and I continued my studies in Brussels and Switzer-land. I worked for more than 20 years as a senior executive in multinational companies (Sanofi and Shering-Plough), where my achievements were acknowledged and honored. My professional experience has been enriched by occupying the administrator position in various hospitals (a hospital for chronic diseases and gen-eral hospital ‘A. Fleming’).I have worked at the Hellenic Center for Disease Control and Prevention (HCDCP) since 2005. I or-ganized the public health laboratory network and I currently hold the position of Deputy Director. I love sea and sports and I was a champion swim-mer. I am a fan of Anorthosis and Panathinaikos football teams. I am an Action Aid member and I sponsor a child in Africa. I have travelled across four continents, more than 27 countries and 170 cities. My first priority, however, is being the mother of two boys. My advice is to be optimistic, have a sense of humor and be good at heart.

Philipos Koukouritakis I was born, raised and still live in Athens, although my parents come from a beautiful region of south-ern Crete. I studied biology at the University of Athens and got a Masters in public health and health administration. Along with my studies, I worked for 5 years as a sports journalist (i.e. in live radio broadcasting of football and basketball games), and after finishing my military service I worked in Roche Hellas SA on clinical trials and biotechnology. However, my love has always been public health and I was given the opportunity to work for HCDCP in 2005. From the beginning of 2012 I am in charge of the office of electronic information for the public and health pro-fessionals, which, among other things, is responsible for publishing HCDCP’s newsletter. In the meantime, I am teaching health promotion issues at various education levels, as well as in organizations.In my free time I enjoy sea and sports. 2012 is a life-changing year for me: I am waiting for the birth of my daughter with excitement!I wish you courage and hope for the New Year and I hope that HCDCP’s newsletter will be a tool for disseminating health information, in order to im-prove the attitude to disease prevention.

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Future conferences and meetings

February 201224 February, 2012

Title: Educational Seminars on Diabetes

Country: Greece City: ThessalonikiVenue: Grand Hotel (live streaming at Karavel Hotel Athens)Phone: +30 210 6827405 Website: http://www.mastermind.gr/

24-27 February, 2012

Title: 3rd (Spring) Clinical Laboratory: Prevention & Confrontation of Cardiometabolic Danger Factors

Country: Greece City: AthensVenue: Hotel MontanaPhone: +30 210 7210001Website: http://www.congressworld.gr/en/arxiki.php

29 February, 2012

Title: The Microscopic Examination in the Diagnosis of Tuberculosis

Country: GreeceCity: Athens Venue: 1. Auditorium of the Oncology Clinic, 3rd Department of Internal Medicine of the Athens

Medical School, and 2. Microbiology Laboratory, National Reference Center for Mycobacteria, Building Z, General Hospital ‘Sotiria’, Phone: +30 210 7763302, Website: http://www.sotiria.gr/new/nrcm/index.htm

International Relations Office

Quiz of the month

What is generally accepted as the greatest medical achievement in preventing cancer?

Send your answer to the following e-mail: info-quiz@keelpno.gr

The December quiz answer: Polyxeni Kontomichalou. Regarding the plasmid-encoded β-lactamases enzyme, it was named TEM after the surname of the Greek patient (Mr Temonieras) from whom it was isolated.

For more information:http://cmr.asm.org/content/14/4/933.full.pdf+html

One person answered correctly.

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Outbreak news, January 2012

Avian influenza [1]

As of 20 January 2012, the Ministry of Health of Vietnam has announced a confirmed case of human infection with avian influenza A (H5N1) virus. Of the 120 cases confirmed to date in Vietnam, 60 have been fatal.

As of 19 January 2012, the Ministry of Health of Indonesia has announced two new confirmed cases of human infection with avian influenza A (H5N1) virus. Of the 184 cases confirmed to date in Indonesia, 152 have been fatal.

As of 19 January 2012, the Ministry of Health and Population of Egypt has announced three cases of human infection with avian influenza A (H5N1) virus. Of the 159 cases confirmed to date in Egypt, 55 have been fatal.

As of 16 January 2012, the Ministry of Health of the Kingdom of Cambodia has announced a confirmed case of human infection with avian influenza A (H5N1) virus. Of the 19 cases confirmed to date in Cambodia, 17 have been fatal.

As of 5 January 2012, the Ministry of Health of China has announced a human case of avian influenza A (H5N1) virus infection. Of the 41 cases confirmed to date in China, 27 have been fatal.

References:

1. World Health Organization (WHO). Available at http://www.who.int/csr/don/ [accessed 23 January 2012]

Travel Medicine Office, Department for Interventions in Health Care Facilities

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Interview

Interview with Professor Dimitrios Trichopoulos

You were one of the first scientists to prove that passive smoking is linked to ill health and especially cancer. What made you to initially bring forward and then investigate the case of passive smoking?

To be accurate I was the first one to publish that passive smoking is related to lung cancer. But this is not of special importance. The link would have been made sooner or later, because tobacco smoke contains genotoxic substances with the ability to cause carcinogenic lesions without a safety limit.

You have played a very important role in the discovery of significant risk factors in the epi-demiology and etiology of cancer. What is the contribution of the environment in relation to heredity?

The role of the environment is extremely important, because smoking alone is responsible for one-quarter of the deaths from cancer world-wide. However, there is often a synergy of en-vironmental and genetic factors. I would like to point out that the molecular sublayer of each cancer type contains gene lesions that primarily concern body cells and are not inherited.

In the past few years more and more frequently it is said that cancer can be prevented through lifestyle and healthy diet (Mediterranean diet). Do you agree or disagree and what do you think about that? What, in your opinion, is the importance of diet in cancer prevention?

A proper diet, which at least in western societies appears to be represented by the traditional Mediterranean diet, may lead to a reduction in cancer deaths by 5–10%

From your multicultural experience, particularly in the USA, what is your opinion about the pre-vention policy in Greece compared with other EU countries and the USA?

Preventive measures in the USA were implemented much earlier than in our country, but the Greek population had an advantage because our traditional diet has been healthier than other countries’ dietary habits, industrialization affected our lives much later in history, and physical exercise, until a few years ago, has been an integral part of our everyday life.

There are indications in the literature that the Greek population’s health, and I’m particularly referring to chronic diseases such as cardiovascular disease and cancer, has deteriorated over the last decades. What changes or interventions do you believe should be made in order to alter this situation?

In reality, the health of the Greek population has improved over time, but the pace of improve-ment is lower than the pace that is being observed in a lot of other populations, particularly in the western world. The result is that we are gradually losing our comparative advantage over other countries, something that became apparent in the 1960s. Regarding the necessary inter-ventions, these should focus on fighting our catastrophic smoking habits, maintaining our tra-ditional diet, integrating physical activity in our everyday life and minimizing industrial hazards and risk factors, wherever they still exist.

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Often the public is being confused by the results of studies and clinical trials, some of which claim that something is good for our health, while others claim that this is bad. What do you believe can be done in order to reduce this confusion?

I believe that there has to be caution in publicizing the results, and when results become pub-lic the degree of certainty must be expressed explicitly without any exaggeration. In general, studies on humans are better than studies on animals. Regarding studies on humans, clinical trials and prospective studies over time (cohort studies) are more reliable in terms of results.

Epidemiology and epidemiologic surveillance provide the scientific base for public health. What is your opinion and what actions do you believe should be taken in Greece for monitoring chronic diseases?

Indeed, epidemiology is the scientific basis of preventive medicine, and the fact that there is to-day the prospect of a properly operated National Cancer Registry is an important step forward.

What is the future of prevention?

Prevention will continue to play an important role, although in my opinion therapeutic medicine has better prospects. However, let us not forget that prevention and treatment are mutually complementary and not mutually exclusive.

What basic questions would you like epidemiology to answer in the next decade?

My personal desire would be the clarification of the role of in utero exposure effects in the etiol-ogy of breast cancer and perhaps other cancers in adult life. The clarification of the epidemiol-ogy and subsequently the etiology of neurodegenerative diseases would be also an important contribution.

What advice would you give to future scientists?

Be committed and modest.

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Myths and truths

about cancer

Myths Truths

Is lung cancer hereditary? Lung cancer, like most other cancer types, is not hereditary

Cancer is contagious There is no reason at all to avoid a person with cancer. You cannot catch it! There is nothing wrong with spending time with someone with cancer; in fact, your support is valuable and needed

Chemotherapy is painful Chemotherapy causes no pain. It is a treatment that is usually infused intravenously, and the infu-sion of the drug does not cause any pain

Wearing an enhancing bra can cause cancer

Such a claim is absolutely false!

A noticeable lump in the breast is cancer

80% of malformations of the breast are non-ma-lignant. However, they must be investigated by a physician to determine their progression

All types of HPV virus cause cervical cancer

Only certain types of HPV virus are linked with cervical cancer, the so-called high-risk types

A good sunscreen is enough to provide sun protection

No sunscreen alone provides 100% sun protec-tion. Wearing a hat, appropriate clothes and seeking shade are all necessary sun protection measures

Polyps of the colon is cancer Colon polyps are not cancer. However, they often appear with increasing age. Some of them belong to pre-cancerous lesions and must be removed because they can progress to cancer

The radiation of a mammogram can cause cancer

The radiation to which a woman is exposed to with a mammogram is minimal! The risk is negli-gible. On the contrary, it is advisable, for women over 40, to have a mammogram regularly. This can reduce the incidence of breast cancer

In comparison with urban air pollu-tion and environmental contamination, smoking is a relatively harmless habit

Smoking is the most common cause of cancer, regardless of other environmental risk factors, and accounts for approximately 30% of all cancer deaths

Maria Demonakou-Vatopoulou, Director of the laboratory of pathological anatomy, ‘Sismanogleion’ general hospital of Athens

Vasia Roumelioti, Head of the Health Services Evaluation Office, HCDCP

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Hellenic non-governmental organizations and associations for cancer

With World Cancer Day taking place every year on 4 February, we have decided to include, in the Hellenic Center for Disease Control and Prevention (HCDCP) monthly newsletter, all non-governmental organizations (NGO) and associations, operating within our country’s borders, concerned with cancer prevention and general public education and psychological support and relief for cancer patients and their close friends and relatives.

The work of volunteers and voluntary bodies adds to the national fight against cancer, especially when it is implemented in co-ordination with official bodies, such as the Hellenic Ministry for Health and Social Solidarity, national institutions (i.e. hospitals), HCDCP and the Hellenic Cancer Registry. The advisory and medical services offered do not always have the same focus, and jointly can supplement each other. For example, some bodies focus on breast cancer prevention, or on childhood cancers, others on supporting patients and their close ones and others on palliative care and patient relief.

The voluntary bodies and non-profit, or non-governmental, organizations for cancer and cancer patients are, for the majority, registered in the National Directory of Voluntary Social Care Providers. Our sources of information for collecting and presenting the following NGOs have been the official site of the Hellenic Ministry for Health and Social Solidarity (www.yyka.gov.gr), the www.anticancer.gov.gr portal designed within the framework of the National Cancer Plan and, of course, research on the Web.

In the case of inaccuracies or poor presentation of the NGOs, please contact the Office of the Hellenic Cancer Registry and Rare Diseases, on telephone numbers +30 210 5212172 and +30 210 5212822, or via email ean@keelpno.gr

NGO URL or TELEPHONE

‘AGAPAN’ COMPASSIONATE AND PALLIATIVE CARE www.agapan.gr

‘AGKALIAZO’ ASSOCIATION OF VOLUNTEERS AGAINST CANCER www.oekk.gr

‘ALMA ZOIS’ PANHELLENIC ASSOCIATION OF WOMEN WITH BREAST CANCER www.almazois.gr

‘ALMA ZOIS’ ASSOCIATION OF WOMEN WITH BREAST CANCER IN THESSALONIKI www.almazoisthes.gr

ANOIXTI AGKALIA ASSOCIATION www.fkpanoixtiagalia.gr

ASSOCIATION OF CANCER PATIENTS OF VERIA-IMATHIA ‘AGHIOS PARTHENIOS’ http://sylkark.blogspot.com

ASSOCIATION OF CANCER PATIENTS OF GIANNITSA +30 2382028075

ASSOCIATION OF CANCER PATIENTS OF DRAMAhttp://syllogoskarkinopathondramas.blogspot.com

ASSOCIATION OF CANCER PATIENTS OF EDESSA http://skepedessas.blogspot.com

ASSOCIATION OF CANCER PATIENTS OF EORDEA +30 24630 53035

ASSOCIATION OF CANCER PATIENTS IN KATERINI-PIERIA ‘AGHIA AIKATERINI’

http://syllogoskkp.blogspot.com

ASSOCIATION OF CANCER PATIENTS OF KOZANI +30 24610 41094

ASSOCIATION OF CANCER PATIENTS OF LARISSA +30 2410 626914

ASSOCIATION OF CANCER PATIENTS OF KILKIS ‘AGHIOS EVGENIOS’ +30 23410 76560

ASSOCIATION OF PARENTS AND GUARDIANS OF CHILDREN WITH CANCER OF THE GENERAL HOSPITAL ‘AGHIA SOFIA’-‘PISTI’ www.pisti.gr

ASSOCIATION OF CANCER PATIENTS OF MACEDONIA-THRACE www.sillogoskarkinopathon.gr

ASSOCIATION OF CHILDHOOD CANCER PARENT ‘FLOGA’ www.floga.org.gr

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ASSOCIATION OF BREAST CANCER IN FLORINA +30 2385046385

ARCHEGONO KYTTARO-VOLUNTEERS OF CLINICAL HAEMATOLOGY DEP. IN “G.GENNIMATAS” HOSPITAL www.oeak.gr

BE STRONG

BREAST CANCER ACTION FUND

www.bestrong.org.gr

www.bcactionfund.org

ELPIDA ASSOCIATION www.elpida.gr

EF-ZO ASSOCIATION www.efzo.gr

EUROPA DONNA HELLAS http://petitioneuropadonna.mind-work.gr/europadonna

FRIENDS OF CANCER PATIENTS OF ‘METAXA’ ONCOLOGY HOSPITAL http://filoiasthenwn-metaxa.blogspot.com

FRIENDS OF THE ONCOLOGY HOSPITAL ‘AGHIOI ANARGYROI’ www.sfgonk.gr

FRIENDS OF THE HELLENIC CANCER SOCIETY www.cancer-society.gr

HELLENIC RED CROSS www.redcross.gr

JENNY KAREZI FOUNDATION www.jkf.gr

KEFI ASSOCIATION www.anticancerath.gr

LAMPSI ASSOCIATION http://lampsi.org

MERIMNA SOCIETY FOR THE CARE OF CHILDREN AND FAMILIES FACING ILLNESS AND DEATH www.merimna.gr

PARHSYA-HELLENIC SOCIETY OF PALLIATIVE AND SYMPTOMATIC CARE OF CANCER AND NON CANCER PATIENTS http://www.grpalliative.gr/

STORGI ASSOCIATION +30 2310 544320

Eleni Papantoniou, National Cancer Registry and Rare Diseases Office

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News from the HCDCP administration

The customary cutting of Vasilopita in HCDCP

The traditional celebration of the cutting of vasilopita (i.e. a surviving pagan good luck custom) associated with the feast of New Year’s Day, was held on 16 January 2012 at the conference center of the Hellenic Center for Disease Control and Prevention (HCDCP).

The event was attended by the Deputy Minister for health and social solidarity Mr. M. Timosidis, the General Secretary of the Ministry of Health Mr. N. Polyzos, the General Secretary of public health Mr. A. Dimopoulos, the former Deputy Minister for Health and Social Solidarity Mr. Ch. Aidonis, the Ppresident of the National Drug Organization Mr. I. Tountas, the dean of the National School of Public Health Professor G. Kyriopoulos, and members of the board and numerous associates.

Meeting on European public health programs

On 16 January 2012 a meeting was held at the headquarters of the Ministry of Health and Social Solidarity regarding public health programs launched by the European Commission for 2012, under the auspices of the ministry of health and HCDCP.

The new website for the National Focal Point (NFP) was presented, providing useful information about the role of NFP and the significance of these public health programs for Greece.

For more information:

http://ec.europa.eu/health/ph_programme/agency/docs/nfp_en.pdf

7th postgraduate course in Infections & Antimicrobial Therapy in Primary Care

At the request of the European Center for Disease Control, the National School of Public Health in collaboration with HCDCP successfully organized the 7th postgraduate course on Infections & Antimicrobial Therapy in Primary Care’, in the town of Alexandroupoli, on 26 and 27 January 2012.

HCDCP

HELLENIC CENTER FORDISEASE CONTROL & PREVENTION

ÊÅÍÔÑÏ ÅËÅÃ×ÏÕ & ÐÑÏËÇØÇÓÍÏÓÇÌÁÔÙÍ (ÊÅ.ÅË.Ð.ÍÏ.)

Graphic Design:Ε. Lazana

Editors:Τ. Kourea- KremastinouHCDCP President

T. PapadimitriouHCDCP Director