EURURO Vol. 71 No. 4

690 692

Re: Analysis of Papillary Urothelial Carcinomas of the
Bladder with Grade Heterogeneity: Supportive Evidence
for an Early Role of CDKN2A Deletions in the FGFR3
Pathway
Downes MR, Weening B, van Rhijn BW, Have CL, Treurniet KM,
van der Kwast TH
Histopathology 2017;70:281–9
Experts’ summary:
This pathology study examines histologically heterogeneous
cases of papillary non–muscle-invasive bladder carcinoma
(NMIBC) at the morphologic, protein, and molecular levels.
The working hypothesis is that molecular alterations have
already taken place in histological low-grade features of het-
erogeneous tumours and that these changes predate the
morphological appearance.
The authors show that even low-grade features exhibit
several molecular changes, such as increased expression of
MIB-1, representing the proliferation index of the tumour.
This is particularly true for areas affected by the FGFR3
mutant pathway, known to be overexpressed in low-grade
tumours. Furthermore, they show that homozygous deletions
of CDKN2A on 9p21, which occur frequently and probably
play a role in stage progression, are found in low- and high-
grade areas, suggesting that these deletions occur before
morphological changes can be detected microscopically.
Experts’ comments:
NMIBC grade is an important prognostic factor. A major chal-
lenge in pathology is the grading of heterogeneous (low and
high grade) lesions. The current convention suggests classifi-
cation as high grade if the high-grade component represents
more than 5% of the tumor . Recent data from clinical studies
have shown that even a cutoff of 10% could be acceptable for
considering a lesion still as low grade . Some newer studies
show that if untreated, these mixed carcinomas might have a
higher rate of grade progression, but little is known about the
carcinogenesis in the different tumor areas and the different
pathways, which might impact on grading
From a clinical point of view, the study findings
underline the current practice of reporting the highest
grade for such mixed NMIBCs, even if the high-grade part
represents only a small proportion of the tumour (5%).
Increased MIB-1 expression and several mutations already
occur in the histologically low-grade parts.
One of the major problems of the study is the low sample
number (19 cases); however, the results are very clear, with
88% of individuals exhibiting a homozygous CDKN2A
deletion in low-grade areas and increased expression of
MIB-1 in 12/19 cases. The cutoff of 5% should probably be
reconsidered. Perhaps all heterogeneous tumours, indepen-
dent of the proportion of high-grade disease, should be
considered as high-grade lesions. However, larger studies
are required to gain further insights into one of the most
difficult problems in uropathology.
Conflicts of interest: The authors have nothing to disclose.
References
[1]
[2]
[3]
[4]
Justine Varinot, Eva Compe´rat *
Department of Pathology, Hoˆpital Tenon, Assistance Publique-Hoˆpitaux de
Paris, UPMC Paris VI, Paris, France
*Corresponding author. Department of Pathology, Hoˆpital Tenon,
Assistance Publique-Hoˆpitaux de Paris, UPMC Paris VI, 4, Rue de la Chine,
Paris 75020, France.
E-mail address: (E. Compe´rat).
# 2017 European Association of Urology.
Published by Elsevier B.V. All rights reserved.
Re: The Important Role for Intravenous Iron in
Perioperative Patient Blood Management in Major
Abdominal Surgery: A Randomized Controlled Trial
Froessler B, Palm P, Weber I, Hodyl NA, Singh R, Murphy EM
Ann Surg 2016;264:41–6
Experts’ summary:
This recent randomised control trial has highlighted the ben-
efits of addressing anaemia in surgical patients undergoing
major abdominal surgery. In this paper a single dose of 15 mg/
kg of intravenous ferric cardoxymaltose pre-operatively, fol-
lowed by 0.5 mg of ferric cardoxymaltose/1 ml of blood loss (if
total blood loss was greater than 100 ml) (n = 40) was com-
pared to standard practice (n = 32).
A significant increase in haemoglobin four weeks
after discharge was found in the intervention group
(p < 0.001), as well as a significant reduction in number of
allogenic blood transfusions (ABTs) and units transfused
(p = 0.079 and p < 0.001, respectively). Length of admission
was 3 days less in the intervention group ( p = 0.05).
Experts’ comments:
Should urologists be considering how their patients’ anaemia is
managed peri-operatively? Is it possible that the importance of
the patient’s haemoglobin level has been over shadowed by
efforts to restore gut function and length of stay as part of
enhanced recovery after surgery (ERAS) protocols?
Published cystectomy ERAS protocols do not specifi-
cally mention anaemia. This maybe because clinicians
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