Bilharzial Urinary Bladder Carcinoma in Egyptians... New LookNew Look & & New Treatment New TreatmentGamal MoustafaProf. of Surgery Faculty of Medicine, Cairo University. ASCO & EACR Member

gamal44@hotmail.com

The 15th congress of the Modern Egyptian Surgical Society and the 2nd Congress of the Pan Arab Surgical Obesity Society Aswan 2014

AcknowledgementAcknowledgement

Prof. Dr M. Nae’em (American University in Cairo, Faculty of Engineering )

for Statistical revision

Prof. Dr A. Khalil (Ex-Chairman Pathology Dept. Cairo University)

for his expert helps in revising pathological data

Bilharziasis Bilharziasis Affected Ancient Egyptians Affected Ancient Egyptians thousands of years before its thousands of years before its discovery. Calcified eggs were discovery. Calcified eggs were

found in the kidneys of two found in the kidneys of two mummies from mummies from Egypt’s 20th

dynasty (1250-1000 BC).

AAAAAA1.1. it was referred to as the ‘it was referred to as the ‘AAAAAA’ ’ in their in their

medical papyrimedical papyri , signifying the disease , signifying the disease of the menstruating men.of the menstruating men.

2.2. Up till now, blood in urine of Up till now, blood in urine of inhabitants of Upper Egypt where the inhabitants of Upper Egypt where the disease was endemic, is regarded as a disease was endemic, is regarded as a sign of puberty in boyssign of puberty in boys

Bilharziasis = a a aBilharziasis = a a a

In the Urinary BladderIn the Urinary Bladder

Granulomatous Granulomatous PolypsPolyps

Cystitis GlandularisCystitis Glandularis

PseudotuberclesPseudotubercles Bladder Neck Bladder Neck StenosisStenosis

Sandy PatchesSandy Patches Bladder ContractureBladder ContractureChronic UlcersChronic Ulcers Stone FormationStone FormationCystitis Cystica Cystitis Cystica Leukoplakia Leukoplakia

In the Urinary BladderIn the Urinary Bladder

Leukoplakia Leukoplakia

Squamous metaplasia then malignancySquamous metaplasia then malignancy

Bilharzial CarcinogenesisBilharzial CarcinogenesisNeeds UrineNeeds Urine

1. carcinogenesis induced by products of abnormal tryptophan metabolism .

2. Secondary infection : infecting bacteria secrete β-glucuronidase enzyme catalyzing the liberation of carcinogenic nitrosamines carcinogenic nitrosamines from their precursors in urine increasing them by 3 fold

There are 2 types of Bladder Cancer There are 2 types of Bladder Cancer

in EGYPTin EGYPT

Only in EGYPTOnly in EGYPT

1.Bilharzial 2.Non Bilharzial

Bilharzial Carcinoma:Bilharzial Carcinoma: 2 Types or 2 Diseases? 2 Types or 2 Diseases?

1. The tumor affects younger age2. Aggressive3. Has the tendency to recur locally. Late metastases4. Patients usually present late. 5. The tumor is massive mostly of the fungating type,6. The prostate, prostatic urethera and seminal vesicles

were rarely involved 7. Histologically, : typically (SCC).8. Regional lymph nodes involvement is uncommon 9. Simultaneous rise of both serum and urinary (CEA)

Normal TCC in situ

TCC SCC

HistopathologyHistopathology

TCC SCC

60% in Bilharzial Ca

in screeningin screening

Urine Cytology Urine Cytology Positive yield Positive yield 0.2 %0.2 %

New :New : Urinary CEA Determination Urinary CEA Determinationraised levels were detected in raised levels were detected in

bilharzial carcinoma compared to bilharzial carcinoma compared to nonbilharzial nonbilharzial attributed to the associated

cystitis

Theory Quarter of urinary bladder carcinoma cases in Egypt

examined for the first time was considered inoperable. This had 2 reasons:

1. the first was the difficulty -on the patient side- to differentiate between symptoms of chronic bilharzial cystitis and those of complicating malignancy.

2. The second, was the presence- on the treating physician side - of miss concepts about the local inoperability of the tumor

. The mass is not totally a tumor but alloyalloy : which forms a large fixed mass not because it is advanced, but because it is composed of the bilharzial alloy: granulomatous, fibrous and malignant tissues. This made surgery impossible in some cases and radiotherapy inappropriate in others due tumor resistance.

The mass is not totally a tumor but alloyalloy : which forms a large fixed mass not because it is advanced, but because it is composed of the bilharzial alloy: granulomatous, fibrous and malignant tissues. This made surgery impossible in some cases and radiotherapy inappropriate in others due tumor resistance.

Urine carcinoembryonic antigen levels aremore useful than serum levels for early detection of Bilharzial and non-Bilharzial urinary bladder carcinoma: Observations of

43Egyptian cases

Gamal MoustafaGamal MoustafaWafaa H El-Metenawy , Mohamed S Elwan and Nazar R

Dessouki http://www.wjso.com/content/5/1/4 2007

20072007

Non Bilharzial Non Bilharzial TCC TCC • Surgery, either alone or along with

other treatments, • Chemotherapy before or after surgery.• Radiation therapy (may also be given

before or after surgery and may be given at the same time )• Immunotherapy to enhance body's

natural defenses

Bilharzial SCC SCCSURGERY was the only hope

1. Patients with organ confined tumors were best treated by cystectomy with urinary diversion offering the greatest prospect for cure with minimal locoregional recurrence

2. Due to associated fibrosis, radiotherapy was of little benefit, used only as a neoadjuvant in operable cases.

3. The 5-year survival rate approaches 33 % regardless of the histological type, being linked more to the disease stage and/or tumor grade

SURGERYSURGERYThe indications for cystectomy (radical, total or

partial) in group A patients were superficial tumors having large size, and large infiltrating ones placed at the bladder base

1.1.TotalTotal2.2.PartialPartial3.3.TUR TUR 4.4.TURBT: Triple- sequence therapy (TUR + TURBT: Triple- sequence therapy (TUR +

radiation + systemic chemotherapy))radiation + systemic chemotherapy))

2Radical Cystectomy plus

1.1. CystectomyCystectomy is the standard operation for operable cases

2. Followed by urinary diversion urinary diversion (continent or non-continent)

3. Patients reject having a wet stoma or change in body image

Radical CystectomyRadical CystectomyPostoperative Mortality 14%14%

Postoperative Morbidity. [Mostly Septic complications ]

34% 34%

Survival rate End of the first yearEnd of the third year

61.7% 61.7% 39%39%

Local pelvic recurrence (72.%)(72.%)A. EL-SAID, et al Bilharzial Bladder Cancer in Egypt — A Review of 420 Cases of Radical Cystectomy —Jpn. J. Clin. Oncol. (1979) 9 (1): 117-122.

22DIVERSIONSDIVERSIONS

1.1. 1851 - Ureteroproctostomy (Simon)1851 - Ureteroproctostomy (Simon)2.2. 1878 - Ureterosigmoidostomy (direct anastomosis) (Smith)1878 - Ureterosigmoidostomy (direct anastomosis) (Smith)

3.3. 1898 - Rectal bladder (Gersuny)1898 - Rectal bladder (Gersuny)4.4. 1950s - Ileal loop (Bricker)1950s - Ileal loop (Bricker)5.5. 1959 - Ileal neobladder (Camay)1959 - Ileal neobladder (Camay)6.6. 1970s - Koch pouch1970s - Koch pouch7.7. Early 1980s - Indiana pouchEarly 1980s - Indiana pouch

8.8. Late 1980s - Orthotopic diversionLate 1980s - Orthotopic diversion

DIVERSIONsDIVERSIONsRECTAL BLADDERRECTAL BLADDER 1898 1898

The commonesturinary diversion

in Egypt in Egypt (51 %) (51 %)

Others: Ileal Conduit

Others : Indiana Pouch

Ileal Conduit Indiana Pouch Orthotopic Neobladder

Others : Orthotopic Neobladder

Orthotopic Neobladder

LOCALLOCAL Egyptian Egyptian

ReconstructionsReconstructions

• RifaatRifaat: rectal vesicourethroplasty: rectal vesicourethroplasty• KhafagyKhafagy ileocecal bladder ileocecal bladder • Gamal SaiedGamal Saied: rectosigmoid cystoplasty: rectosigmoid cystoplasty

Rifaat Rifaat Used rectumUsed rectum

Khafagy Used ileocecum

Gamal SaiedGamal SaiedSpared trigone Spared trigone

Ileocecal BladderIleocecal BladderThe ileocecal region was used as an The ileocecal region was used as an

artificial bladder, its valve artificial bladder, its valve protecting the kidneys from back protecting the kidneys from back pressure exerted by the external pressure exerted by the external urethral sphincter. The ureters urethral sphincter. The ureters were anastomosed to the ileal were anastomosed to the ileal part and the cecum was part and the cecum was anastomosed to the prostatic anastomosed to the prostatic urethra in 7 men and to the urethra in 7 men and to the bladder neck in 2 women and 1 bladder neck in 2 women and 1 man.man.

The Rectum as a bladder Substitute

• Rifaat was the first to use the rectum as a bladder substitute based on unique anatomical, embryological, neurological and functional criteria. The advantage of using the rectum are many, but most important was its excellent fitting as a urine decanter. The transplanted rectum adapts easily to its new function without the risk of stone formation, renal damage or biochemical derangements

The RectumThe Rectum as a bladder Substitute as a bladder Substitute

RADIOTHERAPYRADIOTHERAPY1. The accelerated x- ray beams (energy 6 -15 MV) were

focused on the bladder, targeting the tumor area harboring radiosensitive microscopic residue, cautiously sparing the surrounding normal tissues.

2. Doses delivered were 52.5-55 Gy in 20 daily fractions over 4 weeks.

3. In basal tumors the prostatic urethra was included to minimize local `recurrence.

4. To boost the effect of radiotherapy, concomitant cisplatin radiosensitization was constantly given.

5. BCG installations into the bladder followed radiotherapy in patients left with in situ lesions.

IMMUNOTHERAPYBCGBCG VACCINE

• Bacillus Chalmette-Guerin, or BCGBacillus Chalmette-Guerin, or BCG. This vaccine against tuberculosis is useful for treating primary bladder cancer. When BCG is installed into the bladder through a catheter , the body's immune system responds by attacking the malignant cells.

• BCG may be used ALONE to treat early-stage cancer, or to prevent recurrence of noninvasive after surgery or TUR

CHANGECHANGE• After many years of struggle, the incidence of bilharziasis in

Egypt has dramatically dropped, particularly over the last 2 decades, and new infestation is now almost eliminated .

• Concomitantly, a spectacular change in the epidemiology and makeup of the intimately bound bladder carcinoma was observed, acquiring a new look,

• This new look was fully described by contemporary researchers [1972- 2012].

• Moreover there is a significant increase in TCC significant increase in TCC from 20% to 66% with a paradoxical decline in SCC from decline in SCC from 73% to 25% without remarkable differences in the tumor stage, grade or incidence of lymph nodes metastases

20072007

20072007

الصحة وزير

اقيم والذى الهضمى والجهاز الكبد امراض فى الجديد لدراسة المصرية للمجموعة العاشر السنوى المؤتمر خاللفى 2011أبريل 22باالسكندرية

الصحة وزيرالبلهارسيا من تماما خالية مصر

2012في

Is this change everlasting?Is this change everlasting?

However, uncertainty was constantly However, uncertainty was constantly present whether these new present whether these new

features represent an everlasting features represent an everlasting change in the inherent properties of change in the inherent properties of

the tumor requiring a change in the tumor requiring a change in treatment strategy, or stillness is treatment strategy, or stillness is

required for some time?required for some time?

•

66 Patients (2010 – 2013)66 Patients (2010 – 2013)

66 patients (2010-2013)66 patients (2010-2013)

Results extracted from the present work demonstrated that this inclination is still

manifest. The relative frequency of SCC in enrolled patients slump to 41.1% and TCC

climbed to 58.9% , associated with a change in the cystoscopic gross features of the tumor to

brands not commonly seen before; like the flat (in situ), superficial and the noninvasive

papillary types

We need a Change in treatment guidelines

Egyptian surgeons have to change their treatment guidelines,

keeping untouched the 3 inventive objectives: cure, prevention of local, pelvic or systemic recurrence and preservation of both urinary & sexual functions.

We need a Change in Treatment Guidelines

In the mean time reconsideration of the criteria of what was considered locally advanced tumors is mandatory: massive and fixed lesions are not exclusively a neoplasm, but an alloy of granulomatous, fibrous and neoplastic components. Labeling these tumors (in the past) as locally advanced was inaccurate locally advanced was inaccurate and deprived patients from appropriate surgery in the proper time .

ADVANCES1. Improved results OF Surgery than beforeImproved results OF Surgery than beforea) With time, results of surgery have even improved more and

more owing to advances in surgical techniques, availability of blood transfusion, major improvement in anesthesia, formulation of new antimicrobials and evolution of intensive care medicine .

b) Unfortunately, both operation and radiotherapy were associated with a non negligible incidence of impotence and/or ejaculatory problems caused via different complex mechanisms

c) This can’t be avoided by autonomic nerve preservation at surgery, or by their protection from fibrosis induced by radiation therapy

ADVANCESADVANCES

2. Diversion or …?2. Diversion or …?a) Patients undergoing cystectomy must be willing to

accept urine diversion or

b) be rewarded by building up of an orthotopic orthotopic neobladder.neobladder. Recently, serious trials thinking about the development of a

c) Neo-urinary conduit seeded with autologous smooth autologous smooth muscle cellsmuscle cells are going on, and may potentially eliminate the complications associated with the current schemes and greatly facilitate recovery from operation

River NileRiver Nile