Banchob SripaTropical Disease Research LaboratoryDepartment of PathologyFaculty of Medicine, Khon Kaen University

Geographical Distribution of Liver Cancer and Current Status of Opisthorchis viverrini Infection

in Khon Kaen ProvinceFaculty of Medicine Annual Conference, 17 October 2007

Geographical Distribution of Liver Cancer and Current Status of Opisthorchis viverrini Infection

in Khon Kaen ProvinceFaculty of Medicine Annual Conference, 17 October 2007

Liver Cancer

Hepatocytes (Hepatic cells)Hepatocellular carcinoma

Bile duct epitheliumCholangiocarcinoma

TH

GLOBAL LIVER CANCER

01020304050607080

Thailand, Nort h-East : Khon Kaen

Korea: Busan

The Gambia

Korea: Seoul, Daegu

Japan: Hiroshima, Osaka, Saga Pref ect ures

China: Jiashan, Hong Kong Regions

Mali

Korea: Kangwha Count y

Zimbabwe

Japan: Nagasaki Pref ect ure

Thailand, Nort h: Chiang Mai, Lampang

Viet Nam and Philippines

China: Beijing, Tianjin Regions

Singapore: Chinese, Malays

USA, Calif ornia: Chinese and Koreans

Japan: Miyagi, Yamagat a Pref ect ures

It aly, Out er regions including Parma

Thailand, Cent ral: Bangkok

USA, New Mexico: American Indians

France, Nort hern and Cent ral

Aust ralia, Nort hern Territ ory

It aly, Cent ral excluding Parma

Singapore: Indians

Uganda

Kuwait , Oman, Pakist an

Cent ral Europe, Spain and Port ugal*

Thailand, Sout h: Songkhla

USA: Blacks

Yugoslavia, Vojvodina, Croat ia

Cent ral America*

Russia

France, Sout hern and Islands

USA: Whit es

Canada*

Sout h America*

New Zealand, Aust ralia except NT

Israel*

India*

Nort hern Europe*

Malt a

Alger ia

World Age Standardised Rate (per 100 000 people)

OtherCCAHCC

(WHO, 2002)

Liver cancer in Thailand (1998-2000)

ASR (world) Cancer in Thailand, Vol. IV (2007)

Top 10 Diseases with high DALYs in Thailand

Males Females

DALYs DALYs

Rank Disease (X 100,000) % Rank Disease (X 100,000) %

1 HIV/AIDS 9.6 17% 1 HIV/AIDS 3.7 11%

2 Traffic injury 5.1 9% 2 Stroke 2.8 6%

3 Stroke 2.7 5% 3 Diabetes 2.7 6%

4 Liver cancer 2.5 4% 4 Depression 1.5 3%

5 Diabetes 1.7 3% 5 Liver cancer 1.2 3%

6 IHD 1.6 3% 6 Osteoarthritis 1.1 3%

7 COPD (emphysemal)

1.6 3% 7 Traffic injury 1.1 3%

8 Homicide violence 1.6 3% 8 Anemia 1.1 3%

9 Suicides 1.5 3% 9 IHD 1.1 3%

10 Drug dependence 1.4 2% 10 Cataracts 1.0 2%

Weekly Epidemiological Surveillance Report 2004, 35(2): 19-22.

Liver Fluke

Carcinogens Others

Risk factors of Cholangiocarcinoma : community-based studies

Risk factors n Adjusted odd ratio

OV egg count0 410 1

1-1500 753 1.67 (0.2-16.3)1500-6000 477 3.23 (0.4-29.5)> 6000 167 14.08 (1.67-118.6)

Antibody to OVOD<0.2 180 1OD>0.2 73 27.09 (6.3-116.57)

SexFemale 950 1.0Male 857 3.0 (0.8-11.2)

Age24-34 563 135-49 754 4.57(0.5-38.5)>50 490 9.21 (1.1-74.69)

Praziquantel treatment0 200 11 200 3.4

2-4 200 4.6

(Haswell-Elkins et al, 1994: Chuenroongroj, 2000; Honjo et al., 2005)

Life cycle of Opisthorchis viverrini

(Sripa, 2003)

Nitric oxide and other oxygen free radicals

MacrophageEosinophilEpithelium NO

Immunosuppression(37 kDa OV antigen)

Inhibit DNA repair(BER-inflammation)8-oxodG (G:C-T:A)

GenotoxicNO & metabolites NDMA adduct

DNA damage amines(8-oxodG)

Inflammation

T cells

IFN, TNFCYP

iNOS nitrotyrosine

Inflammation (H&E)

Cell proliferation (BrdU labeling)

Oxidative DNA damage (8-oxodG)

Apoptosis (TUNEL)

Liver flukeinfection

Epithelial desquamationParasite molecules

Epithelial hyperplasiaGoblet cell metaplasia

Adenomatous hyperplasia

DNAdamage

Genetic alterations

Malignant transformation

Cholangiocarcinoma

Periductal fibrosis

Inflammation(macrophages, mast cells, eosinophils

lymphocytes)

Bile stasisAscendingcholangitis

Exogenous N. (dietary)

Endogenous N.

NO

iNOS

amines

ROI

ImmunopathologyMechanical

Director SecretaryViceDirector

Member Member Member Member Member Member

50150250350450550650750850950

10501150125013501450

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Year

num

ber o

f cas

es

Liver Cervix Lung Blood Breast

Ovary Nasopharynx Lymph Node Thyroid Colon

จํานวนผูปวยใหมในมะเร็ง 10 อันดับแรกในระยะ 10 ป (1997-2006) โ รงพยาบาลศรีนครินทร คณะแพทยศาสตร มหาวทิยาลัยขอนแกน

Tumor Registry, Srimagarind Hospital-KKU (1997-2007)

SUMSUNG

NONG RUA

BAN FANG

KHOK PHO CHAI

MUANG

PHOLNONG SONG HONG

PHRA YUN

BAN HAED

NAM PHONG

WAENG NOI

CHUM PHAE

CHONNABOT

NON SILA

BAN PHAI

SI CHOM PHU

PUAINOI

WAENG YAI

PHU PHAMANPHU WIENG

MANCHAKHIRI

NONG NA KAMUBONRAT

KRANUAN

KHAO SUAN KWANG

0-27.57

27.57-55.14

55.14-82.72

> 82.72

Myanmar

Cambodia

Lao

Gulf ofThailand

And

aman

sea

Bangkok

Songkla

Chiang Mai

CCA incidence = 65.47 (26.46-110.08) per 100,000

OV prevalence = 30%

Malaysia

Incidence of CCA (per 100,000) and prevalence of OV infection in Khon Kaen (1986-2005)

Khon KaenKhon Kaen

ASR (Male) = 96.52ASR (Female) = 38.47

Liver cancer incidence (ASR) (All age group - male)at sub-district level of Khon Kaen Province (1986-2005)

< 40

40-80

80-120

>120

Water reservoirs

Chi River

Field works

Age distribution of people examined for Opisthorchis viverrini from 5 villagesin Khon Kaen

Overall prevalence 29.8 %(Range 24.5%-51.3%)

4 year-old boy Age groups

Num

ber o

f cas

es

N = 1,276

0

10

20

30

40

50

60

70

80

90

100

0-5y r 5-10y r 10-15y r 15-20y r 20-25y r 25-30y r 30-35y r 35-40y r 40-45y r 45-50y r 50-55y r 55-60y r 60-65y r >65y r

Age

PZQ

trea

tmen

t(s)

No

1

2

3

>3

Frequency of praziquantel treatment in different age-groups in people from 5 villages in Khon Kaen

ขอขอบคุณหนวยมะเร็ง โรงพยาบาลศรีนครินทร

คณะแพทยศาสตร มหาวิทยาลัยขอนแกนProfessor J. Malone

President, Global Network for Geospatial Health