1. TB Presented by : Dr.Talal Alanzi Presented By : Dr.Talal Alanzi Supervised by: Dr. Mohammad Zaher Jahra Hospital Dr.Hasan Alewa TB center

2.  History of disease.  Geographic distribution.  Incidence in worldwide+ Kuwait.  Transmission.  Pathogenesis.  Signs & symptoms.  NICE + European guideline.  Management.  Article review  Therapeutic trail of anti-TB.  Common organs, sites, surgical procedure.  New modality for investigating GU TB.

3.  Akhenaton and his wife Nefertiti died of TB.  TB was identified march.24.1882 by Robort Koch.  The 4 th most common killing in UK. History

4. Epidemiology World Health Organization. Global tuberculosis control 2012.

6.  In 2012, 8.6 million people developed TB.  1.3 million died,including 320 000 (HIV).  The rate of decline (2% per year) remains slow.  Globally by 2012, the TB mortality rate had been reduced by 45% since 1990. World Health Organization. Global tuberculosis control 2012 Incidence

7.  GUTB is the second most common form of extrapulmonary TB (EPTB).  EPTB accounts for ~10% of overall TB.  GUTB TB accounts for 30% to 40% of all extrapulmonary TB. World Health Organization. Global tuberculosis control 2012 Incidence

8. World Health Organization. Global tuberculosis control 2012 Kuwait

9. KUWAIT

10.  Usually hematogenous dissemination.  Kidney,epididymis,fallopian tube can be primary site.  Prostate can get infected by urine.  Sexual transmission of TB is rare. World Health Organization. Global tuberculosis control 2012 Transmission

11.  Intravesical BCG.  BCG is a live attenuated strain of Mycobacterium bovis.  Asymptomatic granulomatous prostatitis 20-30%.  epididymitis (0.2%)  R. Spence, R. Hay, and P. Johnston, Infection in the Cancer Patient a Practical Guide, Oxford University Press, 2006. Other route

12.  Most common mycobacterium tuberculosis bacillius.  Followed by tubercles bovis.  Mycobacterium avium Microbiology

13.  Non motile rod-shaped  Obligate aerobe  Divides every 15–20 hours  Survive in a dry state for weeks Murray PR, Rosenthal KS, Pfaller MA (2005). Medical Microbiology. Elsevier Mosby. Mycobacterium characteristic

14.  Inhaled tubercle bacilli implanted in bronchioles and alveoli.  Interaction between bacteria and host immunity.  Infection: mycobacteria slowly divide within alveolar macrophage (12 week). Spread through lymph node or blood stream.  Intact immunity: macrophages, T & B, fibroblast aggregate to form granuloma. Prevent dissemination. Pathogenesis

15.  Genitourinary TB is very uncommon in children because the symptoms of renal TB do not appear for 3 to 10 or more years after the primary infection. Warren D, Johnson JR, JohnsonCW, Franklin C. Lowe: Genitourinary TuberculosisCampbell’s Urology. 8th ed. Saunders; 2002.

16. Kidney:  Hematogenous.  Lodge in renal capillaries(cortex) good blood and O2.  Leucocyte T,B cell infiltration.  Causing dormant TB foci.  Results in: sloughing of papilla-infundibular narrowing- PUJ scarring.  Gibson MS, Puckett ML, Shelly ME. Renal tuberculosis. Radiographics 2004;24:251-6. Pathology :

17. Adrenal:  Less than 6%.  Usually B/L.  Lead to necrosis and addision disease.  Gland enlarge-thickened capsule-irregular nodular surface-calcification.  56% subnormal cortisol response.

18. ureter:  Direct extension from kidney.  Usually low 1/3 ureter. (UVJ).  Mucosal ulceration-fibrosis- and obstruction.

19. Beaded ureter

21. Bladder:  2 nd to kidney.  Urothelium is very resistant to TB.  Takes years to develop UB TB.  Common site (surrounding ureter-trigone).  Rarely lead to ulceration. (Worm-eaten). Figueiredo AA, Lucon AM, Junior RF et al: Epidemiology of urogenital tuberculosis worldwide. Int J Urol 2008; 15: 827.

23.  Epididymis (head)  Hematogenous spread.  Inflammation and fibrous narrowing and obliteration of the lumen.  Sinus can occur at post surface of scrotum.  Wise GJ and Shteynshlyuger A: An update on lower urinary tract tuberculosis.Curr Urol Rep 2008; 9: 305.

25.  Testis  2 nd to epididymis  Lead to caseous material and fibrosis.  Diff to distinguish from testicular mass.

26.  Prostate:  Rarely affected.  Hematogenous spread.  Often incidentally found in TUR specimen.  Lead to noticeable reduction of semen volume. Figueiredo AA, Lucon AM, Arvellos AN et al: A better understanding of urogenital tuberculosis pathophysiology based on radiological findings. Eur J Radiol 2009; Epub ahead of print.

27. Seminal vesicle:  Spread from epididymis  Rare.  The classical finding is that of a beaded (dense fibrosis).

28.  Penis and urethra:  Rare.  2 nd to kidney and bladder.  Formation of infected granulation tissue, infiltrate glandular and cavernous body and urethra.  Can present as an ulcer at the genitalia in both sex.

29.  Has been reported in young Jewish boys following circumcision !!!!!  Gesundheit B, Grisaru-Soen G, Greenberg D, et al. Neonatal genital herpes simplex virus type 1 infection after Jewish ritual circumcision: modern medicine and religious tradition. Pediatrics 2004;114:259–63. Penile TB

31. Orthodox Judaism prescribes circumcision as a religious ritual, to be performed according to strict Talmudic laws. According to those laws, the man who circumcises the infant, the mohel, must suck the infant's bleeding penis with his mouth!!!

32.  Babylonian Talmud, Tractate Shabbath 133a Soncino 1961 Edition, pages 668-669.Tractate Shabbath 133a  Mezizah: By this is meant the sucking of the blood from the wound. The mohel takes some wine in his mouth and applies his lips to the part involved in the operation, and exerts suction, after which he expels the mixture of wine and blood into a receptacle provided for the purpose. This procedure is repeated several times, and completes the operation, except as to the control of the bleeding and the dressing of the wound.

36.  Tuberculosis can often mimic a wide range of nonspecific urologic symptoms.  Many cases of genitourinary TB are easily overlooked.  M 2:1 f  4 th decade Clinical finding

37.  50% present with LUTS  1/3 LOIN PAIN+hematuria.  10% passage of caseous material,necrotic renal papillary tissue,clots,stone  20% constitutional symptoms.  recurrent hemospermia (???)  Testicular pain.  Infertility. Symptoms

38.  Limited value in diagnostic process.  Most abnormal finding is scrotal examination.  Beaded vas deference  Epididymal + kidney fistula late sign.  Prostatic nodule on exam. Examination:

39.  25% present with sterile pyuria.  13% gross or microscopic hematuria.  Renal impairment in 7.4%  Tb should be considered in all cases of recurrent hemospermia. Lab inv

40. Urinalysis and c/s:  Ziehl-neelsen staining of urine for acid fast bacilli often negative.  GUTB : often have sterile pyuria+ hematuria+ proteinuria.  20% superimposed bacterial infection. Lab inv

41.  Urine c/s: egg-base(Lowenstein-Jensen medium ) or agar based media.  With use of aniline dyes inhibit growth of bacterial contamination.  Agar facility diagnosed within 4-6 wk.

42.  Intermittent release of organism in urine makes multiple sampling necessary.  3-5 sample early morning should be c/s soon after collection.

44.  Chronic renal lesion may no longer discharge TB material.  Urine c/s sensitive 80%-90%.  Specific 100%.

45.  Radiometric detection: inoculation of specimen with radiolabelled 14c-palmitate, result in liberation of 14 co2 by mycobacteria. Detected by BACTEC 460TB.

46.  14,745 clinical specimens  1,381 strains  81.5 and 99.6% sensitivity  85.8 and 99.9% specifity.  1990 to June 2003.

48.  FLUOROMETRIC TECHNOLOGY : detect o2 consumption. MGIT.  The BBL MGIT System creates and environment suitable for rapid mycobacterial growth.  Positive tests emit a vivid orange fluorescent glow at the tube base.

49.  Sensitivity 95.2%  and specificity 99.2%  10 to 14 days  3,832 specimen.  755 were MGIT growth positive.

51.  Purified protein derivative (Mantoux):  5 units of tuberculin 0.1 ml inj intradermal.  T-cell mediated delayed type hypersensitivity reaction occur 48-72 hr.  Pt who have been exposed to TB, or BCG have immune response to ppd.

52. PCR: (urinary)  Nucleic acid amplification test.  High specificity for extra pulmonary TB.  Multiple sample are required.  Sensitivity 87-95%  Specificity 92-99.8%.  SUPERIOR to other test.  Result available 1-2 days

53. plain x-ray  50% show + finding chest x-ray  Calcification(caseating leson) seen 30% of cases in kidney.  Calculi  Ureteric calcification  Bladder calcification late stage.  Prostatic and seminal vesical calcification 10%. Radiographic

55. U/S:  Limited role.  Useful in diagnosing epididymal and testicular lesion.  TRUS: prostatic+seminal vesicular lesion.

56. IVU  majority will show hydrocalycosis,hydronepherosis.  Moth eaten appearance of calyceal erosion and papillary irregularity.  Cavity lesion ccommunicate with collecting system and ureter.  Scarring and angulation UPJ.  Kerr’s kink  Tb of ureter seen as (pipe stem)

58.  Kerr’s kink

59.  Mouth eaten

61.  CT-URO: parenchymal mass and scarring  caseating granulomata lead to (tuberculoma).  most sensitive in detecting renal calcification.  Most CT finding non-specific. Should be interpreted with the clinical picture.  Good for adrenal calcification& atrophy.  Detecting prostatic abscess.

68.  Retrograde and antegrade study:  Has superseded by noninvasive imaging.  Cystoscopy +ureteroscopy:  Limited role.  No pathognomonic finding.  Ulcer mimic cancer  Biopsy done when in doubt of malignancy.  Golf hole ureteric orifice.

70.  Fine-Needle Aspiration: minimally invasive technique plays a prime role in the diagnosis of tubercular (TB) epididymitis and epididymo-orchitis.

71.  Criteria to reach the definitive diagnosis of GUTB: The presence of one major and/or two minor criteria. MAJOR: Granulomatous lesion on histopathology AFB positivity in urine or histopathology Positive PCR Minor: IVU/CT or MRI Hematruria Raised ESR Pulmonary change of old healed TB Mapukata A, Andronikou S, Fasulakis S, McCulloch M, Grobbelaar M, Jee L. Modern imaging of renal tuberculosis in children. Australia Radiol. 2007;51:538–42

72.  THE AIMS OF TREATMENT ARE: 1. To cure patients and render them non-infectious 2. To reduce morbidity and mortality 3. To prevent relapse 4.prevent emergence of resistant tubercle bacilli. 5.To prevent GU TB complication Management

73.  Superinfection  Abscess  Sinus formation  Renal hypertension  Scarring of renal parenchyma  Stricture and obstruction  Sexual transmission  Fistula formation Complication

74.  First agent for treatment was streptomycin 1944.  Mycobacterium exist in different environment in GU.  Largest population :more active in alkaline agent.  Another population acidic environment.  Smaller population :slowly dividing organism at neutral PH. Medical treatment

75.  Coverage of 6 months.  First 2 months : rifampicin-isoniazi-pyrazinamide.  If resistant to isoniazid, ethambutol added.  Last 4 months rifampicin and isoniazid. OD, BD, TID/week. First line treatment

76.  IMP to obtain adequate specimens for C/S before starting treatment.

78. Second line treatment

79.  Hepatic enzyme  Bilirubin  Creatinine  CBC  MONTHLY BASES F/U. Baseline measurement:

80.  Isoniazid: inhibit cell wall lipid synthesis.  Hepatic toxicity 10-20% -peripheral neuropathy  Rifampicin: suppressing DNA synthesis.  Hepatotoxic  Ethambutol: lower host immune response for tissue destruction.  Blurred vision, eye pain.

81.  55% of GU TB will need it.  If diagnosed early, the need for surgery reduce.  More than 50% of surgery is reconstructive.  Best to interfere after 3-6 weeks of treatment. Surgical therapy:

82.  Relieving obstruction.  Definitive local treatment.  Upper and Lower urinary tract reconstructive.  TB of genitalia. Indication for surgery:

83.  Uremia – sepsis.  Retrograde ureteric stenting is preferable.  Avoid high-contrast injection pressure.  PCN and antegrade stenting.  PCN lead to fistula formation. Relieving obstruction

84.  No longer preferred.  Decision should build on parenchymal destruction, and kidney function.  Partial nephrectomy. Nephrectomy

85.  Tb of ureter lead to mucosal ischemia, fibrosis.  Lower 1/3 ureter are the commonest form, often require surgical intervention.  Stricture formation, with early stenting and anti-TB treatment. Yield best result.  Possible steroidal therapy. ureteric surgery

86.  TB scarring at PUJ more challenging than congenital.  Short segment : dismembered pyeloplasty.  Flap pyeloplasty for longer segment.  Ureterocalicostomy. PUJ

87.  Upper and middle 1/3 ureter, excision and ureteroureterostomy if endo faild.  Lower ureter, ureteroneocystostomy.  Psoas hitch can bridge 5 cm gap.  Boari flap bridge gap of 10 cm. Ureteric stricture 2cm >

88.  If bladder capacity less than 100 ml:  Augmented cystoplasty and bladder substitution. Contracted bladder(THIMBLE),with 20 ml capacity. orthotopic bladder substitution. Bladder surgery

89.  Bladder neck contracture & granulomatous prostatitis. TURP / BNI.  TB prostatic abscess. TRUS Drainage or aspiration.  Urethral stricture. VIU or substitution urethroplasty.   Urethral fistula. SPC and delayed reconstructive surgery. Prostate & urethera

90.  when not responding to chemotherapy.  Epididymectomy..etc  IF testis involved, scrotal orchiectomy. Genital TB

92.  Several randomized control trials (RCTs) over the last two decades have established Short- Course Chemotherapy (SCC). Therapeutic trail

93.  Studied on 2,843 pt.  Overall 28 % of EPTB cases were diagnosed on clinical grounds.  GU TB 33 cases. (1.2 %)

94.  EPTB 8-14 %.  Male=female.

95.  RNTCP treatment guidelines depending on categorization, and is consistent with international recommendations by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD).

98.  Treatment regimens of 6-12 month  favorable response 87-99 % in all forms of EPTB.  Except in TB meningitis.

99. percentageCases 4%relapse rates 1.5-2%died 91%continued their medication 6-8%discontinued

100. Favorable resultF/UDuration 97%36 months6 monthsStrep-Iso-Rif (2 months) Strep-Iso (4 months) 94%60 months6 monthsIso-Rif-Pyra (2 months) Iso-Rif (4 months)

101.  The introduction of SCC for EPTB has made surgery less important.  Therefore a high index of suspicion is necessary to make an early diagnosis.

102.  The ideal regimen and duration of treatment have not yet fully been resolved.

103.  New Delhi, India  N. P. Gupta+A. K. Hemal  1987 to December 2003. (17 YRS)  Published 2006. The Journal Of Urology.  241 patients with GU TB.  Most involved organ kidney. 130 case (54%)  Most common symptoms LUTS. N. P. Gupta,* Rajeev Kumar, Reconstructive Surgery for the Management of Genitourinary Tuberculosis: A Single Center Experience. THE JOURNAL OF UROLOGY. Vol. 175, 2150-2154, June 2006 Study

104.  All received anti-TB for 9 months.  Complication 19 cases (7.8%).  Bacteriological cure in all cases.  RFT 44 of 54 patients (81.5%).

109.  Korean J Urol. 2013 Feb;54(2):123-6. doi: 10.4111/kju.2013.54.2.123. Epub 2013 Feb 18. Korean J Urol.  Feasibility of the Interferon-γ Release Assay for the Diagnosis of Genitourinary Tuberculosis in an Endemic Area.  Kim JK, Bang WJ, Oh CY, Yoo C, Cho JS. Kim JKBang WJOh CYYoo CCho JS  Author information Author information  Abstract  PURPOSE:  To evaluate the feasibility of the interferon- gamma release assay (IGRA) as a supplementary diagnostic tool for the diagnosis of genitourinary tuberculosis (GUTB).

110. Thank You For Listening