PERANAN HYALURONAN PADA PENDERITA

-Interstitial Cystitis -Recurrent Bacterial Cystitis -Radiation Induced Cystitis

DR. dr. Budi Iman Santoso, SpOG(K)

PENDAHULUAN

Latar Belakang
Infeksi saluran kemih(ISK)paling umum terjadi Lebih banyak pada perempuan Jenis ISK yang paling umum terjadicystitis

Anatomi

Anatomi

Anatomi

Anatomi

Cystitis
Cystitis inflamasi kandung kemih/ bladder
lapisan glycosaminoglycan (GAG) pada dinding mukosa kandung kemih (urothelium) mengalami kerusakan Rentan iritasi dan peradangan Mengganggu fungsi kandung kemih Gejala : frekuensi, urgensi, hematuria, disuria, nyeri panggul

90% pasien wanita

Interstitial Cystitis (IC) / Bladder Pain Syndrome (PBS)

inflamasi kronik pada dinding kandung kemih Tanda : Gejala primernya adalah nyeri kronik dan gangguan berkemih Test kultur negatif dan tidak merespon terhadap terapi antibiotik konvensional Terdapat poin perdarahan dinding kandung kemih atau retak atau bekas luka/ ulcer Hunner selama cystoscopy

Mucosa Bladder Normal

Mucosa Bladder BPS/IC

Reccurent Bacterial Cystitis (RBC)

Infeksi kandung kemih atau infeksi saluran kemih (ISK) Tanda : Test kultur positif dan first line terapi adalah antibiotik ISK rekuren/RBC 3/lebih episode ISK dalam waktu 12 bulan Diperkirakan hampir 50% wanita mengalami min 1 kali ISK seumur hidupnya, 27% persen diantaranya mengalami rekurensi dalam waktu 6 bulan setelah infeksi awal

Radiation Induced Cystitis (RIC)

Efek samping dari pengobatan radiasi untuk kasus pelvik kanker diantaranya adalah kanker kandung kemih, prostat, rahim, serviks, atau kanker ovarium Tanda : Gejala sistitis dapat terjadi segera setelah radioterapi sampai 10 tahun setelah terapi Frekuensi terjadinya RIC dapat bervariasi tergantung paparan radiasi Bisa terjadi hematuria

Faktor risiko
-Panjang urethra

-Faktor usia
-Wanita hamil -Faktor hormonal -Gangguan pada anatomi dan fisiologis urin -Pengguna kateter

Patofisiologi

Patofisiologi

Patofisiologi pasti belum diketahui, beberapa dugaan faktor penyebab : -respon autoimun -aktivasi sel mast -perubahan neuropatik -kandungan toksik pada urin -defek primer lapisan GAG pada mukosa kandung kemih

Patofisiologi
Bakteri vagina dari uretra ke kandung kemih Kuman-kuman: 80% E koli, sisanya streptokokus,

stafilokokkus, basillus proteus dll

Frequency Urgency/incontinensia Disuria Nyeri panggul Hematuria

Medical Hystory Self Test (VAS Score) Urine Test Cytoscopy

Manajemen
Istirahat Antibiotik Hyaluronan Pembedahan

 GAG adalah polisakarida panjang dan linear

Fungsi GAG Melindungi permukaan sebagai penghalang permeabilitas dengan cara mengikat air & meningkatkan volumenya Saat ini ada 4 substituen GAG yang telah dipasarkan, yaitu: Hyaluronan Heparin Kondroitin sulfat Heparinoid (pentosan polisulfat) per oral

Prinsip-prinsip HA :
1. 2. 3. 4. Ground Substance Fungsi Fisik dan Biokimia Moisturizing Ukuran Berat Molekul

 Ground Substance Hyaluronan adalah Glikosaminoglikan (GAG) yang merupakan unsur paling dominan pada substansi dasar sel Fungsi Fisik dan Biokimia Sifat fisik dan biokimia HA yang spesifik, mendukung komponen struktural yang ideal Ukuran Berat Molekul Hyaluronan memiliki berat molekul yang besar. barrier yaitu menghambat masuknya organisme dan molekul lainnya di ekstrasesuler Moisturizing HA sangat hidrofilik, yaitu bisa mengikat air sampai 1000 kali volumenya sehingga mendukung regenerasi sel urothelium

Maintains excellent patient response rates for 5 years

1. Engelhardt PF, Morakis N, Daha LK, Esterbauer B, Riedl CR. Long-term results of intravesical hyaluronan therapy in Bladder Pain Syndrome / Interstitial Cystitis. Int Urogynecol J 2011; 22(4): 401-405.

50% of patients initially treated with Cystistat did not need additional therapy after 5 years2

(P=0.0001

Significant reduction in VAS score after therapy

1. Engelhardt PF, Morakis N, Daha LK, Esterbauer B, Riedl CR. Long-term results of intravesical hyaluronan therapy in Bladder Pain Syndrome / Interstitial Cystitis. Int Urogynecol J 2011; 22(4): 401-405.

The initial VAS score was reduced from 8.15 to 2.70 six months after therapy, with an even lower score of 2.14 five years later 85.4% (41/48) patients experienced a decrease in VAS score of > 2

Significant reduction in VAS score after therapy (P=0.0001

Significantly reduces time to recurrence

2. Constantinides C, Manousakas T, Nikolopoulos P, Stanitsas A, Haritopoulos K, Giannopoulos A. Prevention of recurrent bacterial cystitis by intravesical administration of hyaluronic acid: a pilot study. Br J Urol Int 2004; 93(9): 1262-1266.

40 female patients (mean age of 35 years) with a history of recurrent urinary tract infection (UTI) received intravesical instillations of Cystistat once weekly for 4 weeks then once monthly for 4 months 96 days to recurrence before treatment with Cystistat3 498 days to recurrence after treatment with Cystistat3 70% of patients had no recurrence after 12 months3

Reduces radiation-induced cystitis

3. Delgado JM, Samper P, Rivire M. Hyaluronic acid in the prevention of radiation-induced cystitis. Presented at the 41st Annual Meeting of the Infectious Diseases Society of America, October 9-12, 2003. San Diego, California. Poster: #03-AB-424-IDSA.

90 female patients with cervical or uterine cancer stage FIGO 3 in the same centre with the same radiation protocol treatment. 45 patients received standard care and 45 patients were treated with Cystistat

Cystistat allows the completion of radiotherapy on schedule 75% decrease in UTI occurrence with no adverse events4

Delivers consistently high patient response rates

hyaluronic acid unrivalled clinical experience In 7 studies*, 266 patients, 8 weeks to 5 years * Sommariva, et al. 2010, Morales, et al. 1996, Lipovac, et al. 2007, Constantinides, et al. 2004, Ahmad, et al. 2007, Kallestrup, et al. 2005, Engelhardt, et al. 2007

Works fast to improve patients cystitis with chemotherapy

Sommariva ML, Sandri SD, Ceriani V. Efficacy of sodium hyaluronate in the management of chemical and radiation cystitis. Minerva Urol Nefrol 2010; 62: 145-150.

Visual Analogue Scale (VAS) scores before and after treatment in patients with chemical cystitis

Prospective, sub analysis of 54 male patients who had been receiving intravesical immunochemotherapy for non-invasive transitional cell carcinoma of the bladder and had presented symptoms of cystitis with severe complaint.
n=69 patients (54 - chemotherapy; 15 radiotherapy) The mean VAS score dropped from 8.6 to 0.9 at the end of treatment16 Overall 97% (67/69) of patients reported complete relief of dysuria and pain16