SARI PUSTAKA

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

PERANAN HYALURONAN PADA PENDERITA -Interstitial Cystitis-Recurrent Bacterial Cystitis-Radiation Induced Cystitis

PENDAHULUAN

Infeksi saluran kemih(ISK)paling umum terjadiLebih banyak pada perempuanJenis ISK yang paling umum terjadicystitisLatar Belakang

AnatomiAnatomi

Anatomi

AnatomiCystitisCystitis 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

Cystitis Chronic

Penipisan

Titik perdarahanUlkus/lukaCystitis(Mikroorganisme, radiasi, Autoimun, pemakaian cateter,Agen iritan, toksin)

Tanda2 penampakan urothelium (sitoskopi) bisa berupa

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

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

Mucosa Bladder NormalMucosa Bladder BPS/IC

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 bulanDiperkirakan hampir 50% wanita mengalami min 1 kali ISK seumur hidupnya, 27% persen diantaranya mengalami rekurensi dalam waktu 6 bulan setelah infeksi awalReccurent Bacterial Cystitis (RBC)

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

Radiation Induced Cystitis (RIC)

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

Faktor risiko

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 PatofisiologiBakteri vagina dari uretra ke kandung kemihKuman-kuman: 80% E koli, sisanya streptokokus, stafilokokkus, basillus proteus dllPatofisiologi

Frequency Urgency/incontinensia Disuria Nyeri panggulHematuria

Gejala Cystitis :Diagnosis:Medical Hystory Self Test (VAS Score)Urine TestCytoscopy

IstirahatAntibiotikHyaluronanPembedahanManajemen

(GAG)

Glikosaminoglikan (GAG)GAG adalah polisakarida panjang dan linear

Fungsi GAG Melindungi permukaan sebagai penghalang permeabilitas dengan cara mengikat air & meningkatkan volumenyaSaat ini ada 4 substituen GAG yang telah dipasarkan, yaitu:HyaluronanHeparinKondroitin sulfatHeparinoid (pentosan polisulfat) per oral

Glikosaminoglikan (GAG)

Prinsip-prinsip HA :

Ground SubstanceFungsi Fisik dan BiokimiaMoisturizingUkuran 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

HyaluronanHyaluronan Vs GAG lain

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

Maintains excellent patient response rates for 5 years(P=0.00011. 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=0.00011. 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.Significant reduction in VAS score after therapySignificantly reduces time to recurrence

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 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.Reduces radiation-induced cystitis

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

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 Delivers consistently high patient response rates

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.Works fast to improve patients cystitis with chemotherapyProspective, sub analysis of 54 male patients who had been receiving intravesical immuno-chemotherapy 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 Visual Analogue Scale (VAS) scores before and after treatment in patients with chemical cystitisThank You32