- Statistical Analysis
Statistical analysis was performed using the SPSS ver. 22.0 (IBM
Corporation, NY, USA). The prognostic value of each mast cell mediators
and clinical parameters were assessed by chi-square test. The
differences in the urinary mast cell mediators levels between the
patients with NMIBC and healthy participants were examined using the
Mann–Whitney U test. The relationship between the urinary mast cell
mediator levels and the patients’ response to immunotherapy was also
evaluated using the Mann–Whitney U test. The serial changes in the
urinary mast cell mediators measured at four different visits were
analyzed by the Wilcoxon signed rank and Friedman tests. A p-value of
less than 0.05 was accepted as statistically significant.
Results
The average age at the time of immunotherapy was 56.1 (37-79) years in
patients diagnosed with NMIBC. There were 13 men and 6 women. Fourteen
patients were diagnosed with Ta high-grade and 5 with T1 high-grade
bladder cancer. During the follow-up, while 18 patients completed
two-year maintenance BCG therapy, one underwent radical cystectomy. The
cystoscopic evaluations undertaken at three-month intervals revealed
that 7 of 19 patients did not respond to immunotherapy (non-responders)
and 12 patients responded well (responders). Among the non-responders,
recurrence was observed in six patients and progression in one patient.
The average time to recurrence or progression was 9.4 (3-18) months. The
mean age was 52.2 ± 10.5 years in responders and 61.4 ± 10.6 years in
non-responders (p = 0.098). The remaining baseline clinicopathological
findings are shown in Table 1 .
The serial changes in estimated marginal means of urinary
N-methylhistamine, histamine, and tryptase levels in responders and
non-responders are shown in Figure 1 . There was no
statistically significant difference between the immunotherapy
responders and non-responders in terms of the urinary N-methylhistamine,
histamine and tryptase levels (p > 0.05). However, a
statistically significant increase was observed in the estimated
marginal means of urinary N-methylhistamine (p = 0.027) and histamine (p
= 0.004) levels measured at the second visit compared to the first visit
in patients treated with BCG (Table 2 ). Although there were no
statistically significant differences between the second and third
visits (p = 0.053 and p = 0.26), a statistically significant decrease
was detected in the estimated marginal means of N-methylhistamine levels
measured at the last visit compared to the previous visit in patients
treated with BCG (p = 0.013). Concerning the urinary tryptase levels, no
statistically significant differences were obtained in terms of
immunotherapy response and changes of urinary tryptase levels at
different visits in patients treated with BCG (p > 0.05).
The estimated marginal means of urinary N-methylhistamine, histamine,
and tryptase levels measured at the first visit before immunotherapy in
patients with NMIBC and measured at a single visit in healthy
participants are given in Table 2 . There were no statistically
significant differences in the estimated marginal means of urinary
histamine (p = 0.307) and tryptase (p = 0.816) levels between the
patients diagnosed with NMIBC and healthy participants. However, the
estimated marginal means of urinary N-methylhistamine levels were
measured to be significantly higher in patients with NMIBC (p = 0.005).
The mast cell response to initial intravesical BCG immunotherapy between
BCG responders and non-responders is also evaluated. The increase in the
estimated marginal means of urinary N-methylhistamine was 27.24 nmol/ml
in responders and 41.51 nmol/ml in non-responders (p = 340). The
increase in the estimated marginal means of urinary histamine was 19.03
nmol/ml in responders and 27.64 nmol/ml in non-responders (p = 801). The
increase in the estimated marginal means of urinary tryptase was 5.21
nmol/ml in responders and the increase in the estimated marginal means
of urinary tryptase was 7.51 nmol/ml in non-responders (p = 108)