Changes in Tumor Nekrosis Factor Alpha and Interleukin 6 Levels in Patients with Obstructive Jaundice due to Pancreatobiliary Cancer Who Underwent Biliary Drainage

ORIGINAL ARTICLE

  

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Adang Sabarudin*, Rino Alvani Gani**, Murdani Abdullah***,

C Martin Rumende****

• Department of Internal Medicine, Mitra Keluarga Bekasi Timur Hospital, Bekasi ** Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo General National Hospital, Jakarta ***Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo General National Hospital, Jakarta **** Division of Pulmonology, Department of Internal Medicine,Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo General National Hospital, Jakarta

  Corresponding author:

Rino Alvani Gani. Division of Hepatobiliary, Department of Internal Medicine, Dr. Cipto Mangunkusumo

General National Hospital. Jl. Diponegoro No.71 Jakarta Indonesia. Phone: +62-21-31900924;

Facsimile: +62-21-3918842. E-mail: personaly@yahoo.com $%675$&7

Background: Obstructive jaundice represents the most common complication of biliary tract malignancy.

  

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present study was designed to determine levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6

(IL-6) in preprocedure of either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous

transhepatic biliary drainage (PTBD) and postprocedure of them in obstructive jaundice patient caused by

pancreatobiliary cancer.

  

Method: The study method was before-and-after case study design with consecutive sampling. Blood was

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immunosorbed assay (ELISA) was used to determine TNF-alpha and IL-6.

  

Results: Forty subjects were included in this study which consisted of 22 men and 18 women. The age was

55.3 (SD 13.7) years old. According to the results of imaging and endoscopy procedure, twenty-two people were

diagnosed cholangicarcinoma, ten people were diagnosed ampulla vateri and eigth people were diagnosed

pancreatic tumor. In preprocedure, the TNF-alpha concentration was 4.81 (SD 2.91) pg/mL, the IL-6 concentration

was 7.79 (SD 1.57) pg/mL and the bilirubin concentration was 15.5 (SD 6,9) mg%. In postprocedure, the TNF-

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  concentration (p = 0.52). The bilirubin concentration was 11.3 (SD 6,5) mg%.

  Conclusion:

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SURFHGXUH 2Q WKH RWKHU KDQG WKHUH ZDV QRW DQ\ VLJQL¿FDQW GHFUHDVH LQ WKH PHDQ FRQFHQWUDWLRQ YDOXH RI ,/ after biliary drainage procedure. Changes in Tumor Nekrosis Factor Alpha and Interleukin 6 Levels in Patients with Obstructive Jaundice due to Pancreatobiliary Cancer Keywords: obstructive jaundice, pancreaticobilliary cancer, tumor necrosis factor alpha (TNF-alpha),

interleukin 6 (IL-6), endoscopic retrograde cholangiopancreatography (ERCP), percutaneus transhepatic

biliary drainage (PTBD) ABSTRAK Latar belakang: Ikterus obstruktif merupakan salah satu komplikasi tersering keganasan sistem bilier.

  

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bertujuan untuk mengetahui kadar tumor necrosis faktor alfa (TNF-alfa) dan interleukin 6 (IL-6) sebelum

dan sesudah endoscopic retrograde cholangiopancreatography (ERCP) atau percutaneus transhepatic biliary

drainage (PTBD) pada penderita ikterus obstruksi etiologi kanker pankreatobilier.

  Metode: Desain penelitian adalah penelitian satu kelompok sebelum dan setelah dengan pemilihan sampel

secara konsekutif. Sampel darah diambil sebelum dan lima hari sesudah ERCP atau PTBD. Pengukuran kadar

TNF-alfa dan IL-6 dengan cara enzyme linked immunosorbed assay (ELISA).

  Hasil: Terdapat 40 orang responden yang diikutsertakan dalam penelitian ini, 22 laki laki dan 18 perempuan

dengan usia rata rata 55,3 (SD 13.7) tahun. Berdasarkan imaging dan endoskopi, ditegakkan diagnosis

kolangiokarsinoma sebanyak 22 orang, tumor ampulla vateri 10 orang, dan tumor pankreas 8 orang. Kadar

rata-rata TNF- alfa sebelum tindakan 4,81 (SD 2,91) pg/mL dan sesudah tindakan 8,05 (SD 6,7) pg/mL, terdapat

peningkatan yang bermakna setelah tindakan drainase bilier (p = 0,02). Kadar rata-rata IL-6 sebelum tindakan

7,79 (SD 1,57) pg/mL dan sesudah tindakan 7,75 (SD 1,76) pg/mL, tidak terdapat perbedaan yang bermakna

setelah tindakan drainase bilier (p = 0.52). Kadar rata-rata bilirubin sebelum tindakan 15,5 (SD 6,9) mg% dan

sesudah tindakan 11,3 (SD 6,5) mg%.

  Simpulan: Terjadi peningkatan kadar rata-rata TNF-alfa secara bermakna setelah drainase. Tidak ada penurunan yang bermakna kadar rata-rata IL-6. Kata kunci: ikterus obstruksi, kanker pankreatobilier, tumor necrosis factor alpha (TNF-alfa), interleukin 6

  

(IL-6), endoscopic retrograde cholangiopancreatography (ERCP), percutaneus transhepatic biliary drainage

(PTBD) ,1752'8&7,21

  including interleukin 6 (IL-6) and tumour necrosis ₆ factor alpha (TNF-alpha).

  (YHU\ \HDU LW LV SUHGLFWHG WKDW WKHUH DUH of new pancreatobiliary cancer cases with mortality In patients suffering from obstructive jaundice One of the complications of

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  LV DQ REVWUXFWLRQ LQ WKH ELOLDU\ ÀRZ IURP OLYHU WR the survival rate of malignant obstructive jaundice duodenum.

  .XUQLDZDQ HW DO IRXQG WKDW FDXVHV ZKR XQGHUZHQW ELOLDU\ GUDLQDJH ZDV QRW VLJQL¿FDQW of obstructive jaundice was malignancy in patients Biliary drainage procedure will decrease bilirubin level hospitalized in Cipto Mangunkusumo Hospital in in the blood and is expected to decrease hepatocytes

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  LV GHFUHDVHG +RZHYHU WKH GUDLQDJH SURFHGXUH DORQH of the head of pancreas which were the most common possesses the risk of trauma and infection after the procedure which can stimulate proinflammatory

  FDXVH RI PDOLJQDQW REVWUXFWLYH MDXQGLFH ! Biliary tract obstruction causes decrease of bile level cytokines. TNF-alpha and IL-6 were the main LQ GXRGHQXP DQG ELOH DFFXPXODWLRQ LQ WKH ELOLDU\ WUDFW SURLQÀDPPDWRU\ F\WRNLQHV 7KH PDLQ VRXUFHV RI 71) WKXV DOWHUDWLRQV LQ LQWHVWLQDO QRUPDO ÀRUD LQWHVWLQDO DOSKD DQG ,/ DUH PDFURSKDJHV DQG PRUH WKDQ of macrophages in the body are located in the liver PXFRVD HSLWKHOLDO EDUULHU LPSDLUPHQW DQG LQWHVWLQDO bacteria translocation occur. Bile accumulation causes as Kuppfer cells. Some experts stated that biliary impairment of Kuppfer cells and hepatocytes which drainage in patients suffering from obstructive jaundice with malignancy aetiology would decrease TNF-alpha

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  and IL-6 levels. were presented in Table 1. This study included 40

  0HDQZKLOH VRPH RWKHUV VWDWHG WKDW biliary drainage did not decrease TNF-alpha and IL-6 obstructive jaundice patients due to pancreatobiliary

  10 levels.

  This study was aimed to understand the 6' \HDUV ROG &KRODQJLRFDUFLQRPD ZDV WKH PRVW pathogenesis of inflammation which occur after FRPPRQ DHWLRORJ\ IRXQG LQ LQGLYLGXDOV IROORZHG biliary drainage in patients with obstructive jaundice E\ DPSXOOD YDWHUL WXPRXU IRXQG LQ LQGLYLGXDOV due to pancreatobiliary cancer by measuring alteration DQG SDQFUHDWLF WXPRXU IRXQG LQ LQGLYLGXDOV (5&3 in TNF-alpha and IL-6 levels before and after biliary

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  0(7+2' Female 18 (45) Mean age (years old) 55.3 (SD 13.7)* Diagnosis

  This study was a prospective longitudinal

  Cholangiocarcinoma 22 (55)

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  Ampulla vateri tumour 10 (25)

  performed in Internal Medicine Inpatient Ward Cipto Pancreatic tumour 8 (20)

  ERCP Procedure 34 (85)

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  PTBD Procedure 6 (15)

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  Average Levels of TNF-Alpha (pg/mL)

  Inclusion criteria included patients aged > \HDUV old with diagnosis of obstructive jaundice due to P=0.02

  8.05 (6.7)

  pancreatobiliary cancer. Exclusion criteria in this study

  4.81 (2.91)

  were patients who had undergone PTBD or ERCP SUHYLRXVO\ DQG SDWLHQWV ZKR UHIXVHG WR SDUWLFLSDWH LQ the study.

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  P=0.52 7.79 (1.57)

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  TNF-alpha levels before and after biliary drainage Basic characteristics of 40 research participants

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  0HDQZKLOH *ZDQJGDH HW DO GLG QRW IRXQG VLJQL¿FDQW changes of IL-6 in obstructive jaundice patients with cholangiocarcinoma aetiology (16 individuals) and SDQFUHDWLF WXPRXU LQGLYLGXDOV ZKR XQGHUZHQW ERCP or PTBD. This study also obtained no changes in IL-6 level and cholangiocarcinoma as the most common aetiology. This is in accordance with the theory that cholangiocarcinoma is closely related to FKURQLF LQÀDPPDWLRQ SURFHVV DQG PLFURHQYLURQPHQW.

  The success rate of biliary drainage in this study DYHUDJH OHYHO RI ELOLUXELQ GHFUHDVHG IURP PJ WR PJ ZDV QRW IROORZHG ZLWK VLJQLILFDQW GHFUHDVH RI ,/ 3DGLOOR HW DO REWDLQHG VLJQL¿FDQW decrease of IL-6 in obstructive jaundice with benign or malignant aetiology who underwent ERCP. This difference is possibly caused by the bilirubin level ZKLFK FRQWLQXHG WR VWD\ KLJK DIWHU GUDLQDJH L H PJ LQ WKLV VWXG\ +LJK OHYHO RI ELOLUXELQ ZLOO lead to hepatocyte impairment and will stimulate .XSSIHU FHOOV WR UHOHDVH SURLQÀDPPDWRU\ F\WRNLQHV

  VSHFL¿F FULWHULD UHJDUGLQJ WKH VXFFHVV UDWH RI ELOLDU\ GUDLQDJH EXW .XUQLDZDQ HW DO LQ WKHLU SUHOLPLQDU\ VWXG\ stated that a biliary drainage is considered successful LI WKHUH LV D GHFUHDVHG OHYHO RI ELOLUXELQ PRUH WKDQ PJ LQ GD\V 4XL et al in their analysis suggested that biliary drainage was said to be successful if after GUDLQDJH ZDV SHUIRUPHG ELOLUXELQ OHYHO GHFUHDVHG WR PRUH WKDQ RU ZLWK LPDJLQJ HYDOXDWLRQ WKH ZLGWK of biliary tract was back to the normal size. ¹⁴ In this study we did not evaluate the width of biliary tract.

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  ,Q WKLV VWXG\ ZH IRXQG LQGLYLGXDOV VXIIHUHG from pancreatitis which was manifested as complaint of stomachache and increased amylase serum to more WKDQ WLPHV RI XSSHU QRUPDO OLPLW (5&3 SURFHGXUH PD\ FDXVH ORFDO RHGHPD WKXV FDXVLQJ REVWUXFWLRQ WR WKH SDQFUHDWLF GXFW DQG OHDG WR SDQFUHDWLF HQ]\PH UHÀX[ Incidence of pancreatitis post ERCP in this study was similar to other studies.

  It was found that single dose administration of NSAIDs FHOHFR[LE DQG NHWRURODF LQ KHDOWK\ LQGLYLGXDOV ZLOO GHFUHDVH WKH OHYHO RI 3* ( DQG LQFUHDVH WKH OHYHO RI TNF-alpha. TNF-alpha level will return to normal after DGPLQLVWUDWLRQ RI 3J( LQWUDYHQRXVO\

  Excessive apoptosis may stimulate the release of SURLQÀDPPDWRU\ F\WRNLQHV 2WKHU IDFWRU ZKLFK ZDV thought to play role in the increase of TNF-alpha was 16$,'V XVH ,Q WKLV VWXG\ DOO SDWLHQWV EHIRUH DQG DIWHU procedure received NSAIDs (ketorolac or ketoprofen).

  ,Q WKLV VWXG\ ZH XVHG XURJUDSKLQ GXULQJ ERCP. Urographin is an ionized iodine contrast which has high osmolality and has cytotoxic effect upon mucous cells of the biliary tract. Michele and Quintavalle stated that iodine contrast medium may increase apoptosis of endothelial cells and kidney WXEXODU FHOOV ZKLFK PD\ FDXVH DFXWH NLGQH\ LQMXU\ therefore the possibility of apoptosis in endothelial cells of biliary tract and hepatocytes could be assumed.

  FRXQW LQFUHDVHG QXPEHU RI SDWLHQWV VXIIHULQJ IURP 6,56 LQGLYLGXDOV LQGLYLGXDOV VXIIHUHG IURP pancreatitis accompanied with increased average RI 71) DOSKD OHYHO WKXV WKH SRVVLELOLW\ RI LQIHFWLRQ needs to be considered. Abeed et al through an in vitro study found that lipopolysaccharide-stimulated monocyte cells from patients with obstructive jaundice with malignancy aetiology secrete lesser TNF-alpha FRPSDUHG WR QRUPDO LQGLYLGXDO WKHUHIRUH LW FRXOG EH concluded that they are more prone to be infected by bacteria.

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• DVWURHQWURO DQG +HSDWRO $EXG + &DPXUD 0 3DQDUXV / =DLWRQ $ ,PPXQH G\VIXQFWLRQ in patient with obstructive jaundice before and after endoscopic Retrograd cholangiopancreatography. British J

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