الفهرس 
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Abstract
Chapter 6
SUMMARY AND CONCLUSIONS
The present study has examined several approaches to the
prognostic evaluation of bladder cancer including:
clinicopathological evaluation, ultrastructural study and
immunohistochemical markers.
The clinicopathological study was carried out upon 52 cases
of bladder cancer from Urology Department of the Benha
University Hospital. The study included analysis of the
results of clinical and pathological examinations of the 52
cases.
In the current study bladder tumours were predominant in
males (88.69%). The overall mean age of the 52 cases was
54.5. The mean ages for bilharzial and non-bilharzial
cancer were 50.5 and 57.5 respectively. Clinical evaluation
of the patients revealed that haematuria was the most
common symptom at first presentation (40.40%). 31 patients
(59.62%) had previous history of treatment for
bilharziasis, 22 (42.30%) of whom showed bilharzial
associated changes of the urinary bladder. History of
chronic tobacco smoking was found in 29 cases (55.77%).
Cystoscopic examination revealed that the primary tumours
were located most commonly in the posterior wall (30.76%)
and the lateral walls (21.14%).
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TNM system was applied for staging all the tumours. 86.54%
of the tumours were muscle invasive at the time of first
presentation. Advanced stages of bladder tumours were
associated with greater incidence of LN and distant organ
metastasis.
Histopathological diagnosis and grading was carried out by
examination of specimens taken by cystoscopic biopsy of the
tumours. Of the 52 cases, 26 cases were TCC, 19 cases were
SqCC, 3 cases were adenocarcinoma, 2 cases were mixed
carcinoma, one case was undifferentiated carcinoma and one
case was rhabdomyosarcoma. In the tumours associated with
bilharziasis, SqCC was the most common histopathology
(50%), whereas in the non-bilharzial tumours TCC was
prevalent (58.62%). 44.23% of the tumours were moderately
differentiated (G2).
The ultrastructural study has examined the fine structure
of normal bladder urothelium as well as that of TCC and
SqCC using TEM. The study has also defined the differences
between low and high grades of bladder tumours at the
subcellular level.
The normal urothelium was characterised by the presence of
large superficial ”umbrella” cells which had specialized
luminal membrane with AUM plaques.
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changes in the topography of superficial cells in the form
of absence of AUM plaques and development of numerous
pleomorphic microvilli was one of the fixed features of all
grades of bladder tumours. Apart from these changes in the
luminal surface of the cells, many ultrastructural features
of low grade bladder tumours were found similar to normal
urothelium. However, the nuclei were larger and usually had
one or more infoldings of the nuclear membrane.
Nuclear pleomorphism, cytoplasmic simplicity, dark cell
phenomenon, cellular necrotic changes, widening of the
intercellular spaces and loss of pattern of differentiation
were features of high grade TCC. Dramatic changes at the
tumour stromal junction were also observed to be associated
with poorly differentiated tumours including,
disintegration of the basement membrane, as well as
increased vascularity and thli!frequent presence of mast
cells in the lamina propria subjacent to the tumour base.
The mucosa of the bladder adjacent to the tumour in some
areas were found to have pleomorphic microvilli and
membrane changes comparable to those seen in the tumour
although appeared normal by light microscopy. This may
indicate that these changes in cell topography may be one
of the earliest neoplastic markers in urothelium.
SqCC was defined by its flattened cells with surface
keratinization. It is also characterized by the presence of
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desmosomes and intercellular tonofilaments whatever the
grade of the tumour which may help in identifying squamous
differentiation in poorly differentiated tumours.
The immunocytochemical study revealed that the expression
of CK-20 in normal urothelium was confined to the
superficial ”umbrella” cells. In TCC of the bladder, the
degree and pattern of expression of CK-20 were parallel to
the outcome of the tumour, so that the tumours which
retained high degree of expression of CK-20 were most
likely to have a benign clinical course, whereas the
tumours which yielded negative or altered (heterogenous)
expression pattern were likely to progress and/or
metastasize. If this hypothesis is supported by further
investigations, CK-20 may offer the capability of
identifying the low grade low stage bladder tumours that
are destined to invade or metastasize while they are at a
curable stage.
Two specimens taken from non-tumour bearing mucosa in cases
with TCC of the bladder showed abnormal expression of CK-20
in intermediate epithelial cells. This observation
indicates that change in the normal pattern of expression
of CK-20 could be an early event in the process of
development of bladder cancer or it may be an indirect
consequence of Tce in other parts of the bladder. This
point needs further investigations.
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CONCLUSIONS
1. Bilharzial bladder cancer is a distinctive clinicopathological
entity with unique epidemiological,
clinical and pathological features which should be
considered in designation of the methods of
management.
2. Early changes in surface topography in the form of
loss of AUM and development of pleomorphic microvilli
can be used as a markers of malignant transformation
in TCC of the bladder.
3. There are distinctive ultrastructural differences
between low and high grades of bladder TCC.
4. Subcellular changes in non-involved mucosa may have
prognostic importance.
s. The expression of, CK-20 can be used as a valuable
marker for prediction of malignant potential of
bladder cancer.
RECOMMENDATIONS:
1. The need for effective screening method for early
detection of bladder cancer in high risk groups.
2. The importance of primary preventive measures for
Schistosomiasis in the control of bladder cancer in
Egypt.