Transcript In the name of god

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A 62-year-old man was diagnosed
with bladder TCC since 7 month ago
.A tumoral TUR was performed and
intravesical BCG instillations once a
week for 4 weeks were started .
One day after the last cycle ;the patient
was referred to the hospital because of :
Chills-Fever-Dyspnea-HypotensionAltered of LOC & icter.
He was admitted to ICU immediately and
took corticosteroid & hydration for 24
hours.
After 24 hours ; he became alert and his
blood pressure was normal ;but fever and
chills continued .
He was referrerd to gastrointestinal ward
with : icter- fever &chills for more
investigations
Past medical history
 Hypertension
 Diabetes
 History
since 10 years ago.
mellitus since 5 years ago.
of hematuria since 8 month ago.
 Opium addict.
 Heavy smoker until 7 years ago.
 Tab- Atenolol 100 mg daily.
 Cap-tamsulosin Qhs
No familial and allergy history
Physical examination
Sclera was icteric
No lymphadenopathy
Lungs bilateral were clear
Heart sounds were normal without murmur
Abdomen was normal no organomegaly
No edema-cyanosis-clubbing
Neuromuscular examinations was normal.
General appearance(After 24 hours): An
old man nearly obese ‘ alert’ not ill & toxic.
he was icteric
Vital sign at the first visit:
BP=70/p HR:110 T:38.1 RR:18 O2sat:95%
Laboratory tests
WBC 9.1
5.6
2.8
Hb 15.1
12.5
8.7
Plt 77000
24000
22000
Na=135 K=4 Ca=9 P=4
PBS= Toxic granulation: 1+ Shistocyte :neg
Blood culture : neg
AST=198
109 ALT=226
ALKph=206
Bil(D:8.2
PT=17
124
403
3.6 T:14.9
13.5 PTT=49
6.3)
39 INR=1.7
1
HBSAg: neg HCVAb: neg HBCAb :neg
HIV Ab:neg
U/A(pro= neg WBC =2-4 RBC=3-5 Bact-)
Urine 24h(vol=3900 pr=257 cr=1833)
LDH=618 Serum Alb=4 TP=6.4
BS=243 ESR=10
Urea:110
Cr:3.6
179
4.7
75
2.8
Paraclinic evaluations
 Abdomio
–pelvic sonography was normal
 Echocardiography : EF=60% PAP=NL No
evidence of PTE
 BMA & BIOPSY : Hypercellular marrow with
increased megakaryocyte Negetive for
granulomatous inflammation
 PPD
test:neg
 Doppler
 Chest
 EKG:
sonography of lower extremites: normal
x Ray was normal
normal sinus rhythm.
Problem list:

A 62 –year –old man

Known case of TCC of bladder since 7 month ago.

He was taken intravesical BCG instillation weekly after TUR

After the last dose(fourth dose) he admitted in hospital with:
Fever-Chills - Hypotension - Dyspnea -Altered of LOC and icter

He was referred to gastrointestinal field after 24 hours management
in ICU fore more investigations.
Differential diagnosis

Hypoglycemia

Overdose of opiate

Uremia

Infections(Septicemia -Meningitis- BCG sepsis)

Pulmonary embolism

Hypoxia or Hypercarbia

Siezure

CVA

MI and CHF

Anaphylactic shock

Hepatic encephalopathy

Syncopal attack
About Bacille -Calmette-Gu’erin(B.C.G)

B.C.G has been used for more than 90 years with safety
records as a vaccine against TB that derivated from live
mycobacterium bovis.(M.bovis is slow-growing aerobic
bacterium and the causative agent of tuberculosis in
cattle).

Intravesical B.C.G used about 35 years ago for nonmuscle bladder cancer. B.C.G has been shown the most
effective agent against superficial bladder tumors. B.C.G
therapy prevents or reduce tumor recurrence.
Indications of intravesical BCG
Indications for intravesical B.C.G

Papillary or flat Tis.(carcinoma in situ)

Papillary tumors as non invasive .tumors confined to urothelium(Ta)

Superficially invasive.tumors invading the lamina properia(T1)
Mechanism of intravesical BCG

1) An immune mechanism of BCG induced antitumor activity(cytotoxic
effect)an intact immune system particularly the cellular system is required for
antitumor activity.

2)Infiltration of bladder wall by immunocompetent cells together with secretion
of cytokines into the urine part the intense local immune activation.
Complications of intravesical BCG
Localized complications of BCG
 BCG

cystitis
Granulomatous prostatitis &Epididymitis
 Hematuria
 Swelling
 Painful
of testicle
urination
Systemic complications of BCG

Chills-Fever-Cough-Body pain-Weakness-Vomiting-Flulike
symptoms

Acute renal failure-Granulomatous nephritis-Mesangial GN

Arthralgia - Reactive arthritis - septic arthritis - Osteomyelitis

Hepatitis-Hepatic granuloma –granulomatous collangitis

Serious allergic reactions(Intractable anaphylaxia)

F.U.O-Night sweats-Anorexia-Fatigue-Weight loss

Hematologic disorders
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Mycotic aneurysms

Loss of vision in elderly patients due to endophtalmitis

Respiratory disorders(ARDS-Pneumonitis-Cough)

BCG sepsis & septic shock

Pityriasis rosea like rash
Systemic
complications
of BCG
treatment
Sepsis
The classic sepsis syndrome can occur with:
Fever-Hypotension-DIC & respiratory failure.
These manifastations are probably due to high levels of
cytokines released directly into the bloodstream as part of
the hypersensivity response(so called cytokine storm)
Hepatitis

Granulomatous hepatitis is early or late
complication of BCG intravesical instillations
that presents with :fever-jaundice in the first
week after BCG instillation
 Hepatitis represents similar to granulomatous
hepatitis with:
(fever-jaundice and anorexia)
Pneumonitis
Milliary nodular or interstitial pattern on
routine chest X-R or CT scan
Accompanied by fever-malaisedyspnea
Usually occurs with sepsis
Osteomyelitis
 Usually
involves spine due to spread
from urinary tract through Batson’s
plexus
 Presents
with low back pain-motor
weakness-rigors-sweats
Arthralgia & Arthritis
 Arthralgia
 Reactive
extremitis.
is the most common presentation .
arthritis:
usually
predominantly
involves
lower
2 weeks after instillation occurs.it
associated with genitourinary symptoms. in one study
55% had HLA B27.
 Septic
arthritis
can
due
to
1)Bacterial
(monoarthritis) 2)M.bovis infection(polyarthritis)
infection
Hematologic complications

Anemia due to chronic disease

Leukopenia

Coagulopathy disorders such as DIC or Thrombocytopenia

Pancytopenia due to granulomatous reaction
Coclusions about
complications of BCG

1-Hypersensivity reactions gained based upon
the presence of granuloma and absence of
organism
(Hepatitis-prostatitis-bone marrow involvement…….)

2-Ungoing active infection due to M-bovis spreading
Southern medical journal.2008;101(1):91-95
The journal of urology .printed in USA .March 2010. page:598
Active infection(BCGosis or BCG sepsis)

BCGosis occur following systemic absorption of BCG into
blood stream via disturbed mucosa due to traumatic
catheterization and recent bladder tumor resection.

If fever exceeding 38.5’c lasting over 24hours despite
antipyretic therapy or recorded fever higher than 39.5’c
should prompt a hight clinical suspicion of BCGosis
In this patient fever &chills were
discontinued after two days.He felt
wellbeing .icter diminished and
laboratory tests nearly improved and
discharged after one week
He was followed for two month by urologist and nephrologist.
The last laboratory tests:
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WBC=4600 HB=12.9 Plt=211000
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Urea=24

AST=36 ALT=34
Cr=1.6
Alk ph=138
References:
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UP-TO-DATE
version:21-3
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Brazillian journal of urology
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European urology supplement 2012
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Journal of urology 2008 (page 1-5) American urological
association.
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Journal of urology 2010 (page 596-600) printed in USA.
(SEP-OCT) 2013
(page 488-502)
(page 542-547)