Marijan Šitum

Results of long-term follow-up of patients with superficial bladder carcinoma treated with intravesically applied bacillus Calmette-Guerin vaccine according to the schedule of 6 weekly + 6 monthly instillations

BACKGROUND The efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in the prevention of local recurrence and disease progression in patients with superficial bladder cancer is very well documented. This study reports the effect of BCG on disease-specific and overall survival. PATIENTS AND METHODS In this retrospective trial, we have analyzed 170 patients with stage Ta and T1 superficial bladder cancer. Patients in the control group (87 patients) we followed-up only (median follow-up of 119 months) and treated surgically or with other oncologic modalities when progression of disease was diagnosed. The BCG group consisted of 83 patients treated with 6 weekly followed by 6 monthly instillations, and they have been followed-up of median 124 months. RESULTS Patients receiving BCG had statistically significant better 10-year disease specific survival (83% vs. 69%, P = 0.03). At the same time point, the local recurrence rate was 48 % and the progression rate 19% for patients treated with BCG, while 77% (P < 0.001) and 38% (P = 0.007) were results in control group. Despite numerically better in the BCG group, overall survival is not significantly different in the 2 groups (P = 0.14). CONCLUSION BCG immunotherapy significantly increases the disease-specific survival in patients with superficial bladder carcinoma.

Are we estimating the adverse effects of shock-wave lithotripsy on a faulty scale?

The adverse effect of shock-wave lithotripsy (SWL) for renal stones on blood pressure is currently defined as its post-treatment increase. On the contrary, we hypothesize that even mild, unilateral renal obstruction initiates an increase in blood pressure. Then, in absence of treatment-induced injury, the stone removal should decrease the blood pressure. We derived the formula to assess the expected change in the mean arterial pressure following relief of renal obstruction without affecting the kidney functions. The predictions were well replicated in the cohort of patients with renal stone treated with parenchyma-saving open surgery, with 6.4 mmHg decrease at 3 months. On the contrary, in SWL cohort, instead of the expected 4.7 mmHg decrease, the blood pressure was unchanged. In conclusion, the absence of decrease in blood pressure is a very common adverse effect of SWL, leading to an epidemiologically significant increase in the risk of arterial vascular events.

The urinary microbiome associated with bladder cancer

Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.

Wrong perspective obscures the adverse effects of shock-wave lithotripsy

Using animal model Yilmaz et al. [1] have shown that shock waves acutely impair renal artery contraction/ relaxation properties. This agrees with the observed acute deterioration of renal hemodynamics following shock wave lithotripsy (SWL) [2]. We want to stress that this issue has far reaching implications that are not generally recognized. Obviously, the long-term, chronic collateral effects of SWL are more important than reversible acute impairments. In this respect, the exposure to shock waves was associated with the long-term effects on kidney functions [2], blood pressure [3], and possibly also erythropoiesis [4]. However, the findings of the new-onset hypertension and development of diabetes mellitus have not been consistent across the reports [3] and currently these potential serious adverse effects of SWL do not restrict indications for the method. We argue that this is wrong. The cohort studies on the incidence of the new-onset hypertension following SWL rely on unproven assumption that relatively mild, often unilateral renal obstruction, as seen in majority of SWL patients, does not alter hemodynamics. However, our patients scheduled for SWL presented with roughly doubled renal vascular resistance of the affected kidney, which persisted at 3 months after treatment. In contrast, in patients with renal calculi treated with parenchyma saving open surgery, only slightly more elevated renal vascular resistance at baseline chronically normalized and their arterial blood pressure decreased [5]. Since each kidney accommodates about one-tenth of cardiac output, doubling the vascular resistance of a kidney requires some 5 mmHg increase in arterial pressure to preserve the cardiac output. Thus, the unchanged blood pressure following SWL may not prove the absence of adverse effect, but a balance between renal injury and relief of obstruction. The proper question could be: why SWL did not lower the blood pressure in my patient? Next, every couple of mmHg change in blood pressure translates to a several fold larger change in the risk of arterial vascular events and induction of blunt hypertension is insensitive measure in this respect [6]. The adverse effects of SWL may be blurred by the beneficial effects of relief of obstruction. In this case, judging the effects of treatment by the post-interventional changes may be using the faulty scale. Reported comparisons of SWL with other minimally invasive methods like ureteroscopy or percutaneous nephrolithotomy focused on stone-free rates [7]. Future studies should compare SWL against these methods in terms of chronic adverse effects and try to identify their predictors, both those related to a method and a patient.

Ureterorenoscopic treatment of ureteral stones – influence of operator’s experience and skill on the procedure outcome

Aim To observe the influence of operating urologist’s education and adopted skills on the outcome of ureterorenoscopy treatment of ureteral stones. Methods The study included 422 patients (234 men, 55.4%) who underwent ureterorenoscopy to treat ureteral stones at the Urology Department of Clinical Hospital Center Split, Croatia, between 2001 and 2009. All interventions were carried out with a semi-rigid Wolf ureteroscope and an electropneumatic generator used for lithotripsy. The operating specialists were divided into two groups. The first group included 4 urologists who had started learning and performing endoscopic procedures at the beginning of their specialization and the second group included 4 urologists who had started performing endoscopic procedures later in their careers, on average more than 5 years after specialization. Results Radiology tests confirmed that 87% (208/238) of stones were completely removed from the distal ureter, 54% (66/123) from the middle ureter, and 46% (28/61) from the proximal ureter. The first group of urologists completed significantly more procedures successfully, especially for the stones in the distal (95% vs 74%; P = 0.001) and middle ureter (66% vs 38%; P = 0.002), and their patients spent less time in the hospital postoperatively. Conclusion Urologists who started learning and performing endoscopic procedures at the beginning of their specialization are more successful in performing ureteroscopy. It is important that young specialists receive timely and systematic education and cooperate with more experienced colleagues.