Urological concern after nuclear accidents.

This article[1] has cited the letter[2] along with several reports on the urinary bladder carcinogenesis.[3456] Moreover, the statement “at least, chronic exposure to ionizing radiation is considered as an important stress and can result in deoxyribonucleic acid dysfunction,”[1] given with references to,[24] does not agree with.[2] In fact, the letter[2] is commenting on the studies.[46] The following should be added to the previously published comments.[27]

In the research series,[3456789101112] in different groups of patients with benign prostatic hyperplasia (BPH), from the contaminated areas after the Chernobyl accident and the city of Kiev (not officially counting to the contaminated territories), severe urothelial dysplasia and/or carcinoma in situ (CIS) were found by bladder biopsy as frequently as in 56-96% of all randomly selected cases.[36] The random character of the bladder specimens was pointed out: “The Institute of Urology (Academy of Medical Sciences of Ukraine) in Kiev during 1994-2006 collected all BPH patients who underwent suprapubic prostatectomy and all these patients were included in our study in different years without exception, along with a small number of females with chronic cystitis.”[3] The following was stated about the patients with BPH studied by the bladder biopsy: “Irradiation cystitis with multiple foci of severe urothelial dysplasia/CIS and some invasive transitional cell carcinoma (TCC) were observed in 96/66, 76/56 and 56/8% of patients in groups I, II and III respectively” (the group III was from non-contaminated areas).[8] In the Handout by the same authors, distributed at the XXIII International Congress of the International Academy of Pathology on October 15-20, 2000 in Nagoya, Japan, the following was written: “Histologically the different forms of proliferative cystitis, which were frequently combined and had features of irradiation cystitis with multiple areas of severe dysplasia and CIS, sometimes associated with small TCC, occurred in 97% of patients from the radiocontaminated areas of Ukraine.” These percentages are obviously unrealistic and indicative of false-positivity.

Looking at the figures in the earlier articles,[1011] it appears probable that overdiagnosis of dysplastic and neoplastic bladder lesions could have happened also before: both articles[1011] used one and the same image of bladder leukoplakia with invasion (according to the legend). However, invasive growth is not clearly recognizable [Figure 1]. Furthermore, the illustrations from the article,[3] available online, should be commented (compare Figures 2 and 3 available at http://www.carcin.oxfordjournals.org/content/30/11/1821.long Figure 2. From the caption: “Small developing papillary urothelial carcinoma with severe dysplasia (G-L),”[3] our comment: thick sections; in some plates the nuclei are insufficiently stained. No severe dysplasia is recognizable. A small papilloma or papillary cystitis cannot be excluded [Figure 3]. From the caption: “…dysplasia (A-D) and small papillary urothelial carcinoma (E-G),”[3] Comment: mild to moderate atypia might be present; but neither severe dysplasia nor carcinoma are recognizable. All the slides are obviously too thick for reliable diagnostics. Insufficient quality of specimens could have been caused also by fixation, processing-related factors and electrocoagulation. The same is true for the similar images in the article[9] available at http://www.onlinelibrary.wiley.com/doi/10.1002/(SICI) 1097-0215 (20000615) 86:6%3C790:AID-IJC6%3E3.0.CO; 2-Q/full. Figure 4a from[9] and Figure 2g from[3] are identical. Note that overdiagnosis could have entailed over-manipulation (cystoscopy) and overtreatment. It cannot be excluded that the above-mentioned irradiation cystitis or “Chernobyl cystitis,”[312] characterized among others by the “reactive epithelial proliferation associated with hemorrhage, fibrin deposits, fibrinoid vascular changes and multinuclear stromal cells”[12] was at least in part caused and/or maintained by repeated cystoscopies with mapping biopsies, electrocoagulation etc.

Figure 1

Bladder leukoplakia with invasion. Poor quality of the images and obviously also of the specimens. The invasive growth is not clearly recognizable. The images top left and bottom right are identical. Commented in the text

Figure 2

Histological and imunohistochemical findings: CIS (a-f), small developing papillary urothelial carcinoma with dysplasia (g-r). (a, g and m) H and E, (b, h and n) p53 expression, (c, l and o) Cox2 expression, (d, j and p) iNOS expression, (e, k and q) H-ras expression and (f, l and r) 8-OHdG expression. Magnification ×100

Figure 3

Urothelial dysplasia (a-d) and small papillary urothelial carcinoma (e-g). (a) H and E, (b) p65 expression, (c) p50 expression, (d) p38 expression, (e) H and E, (F) p65 expression and (g) p50 expression. Magnification ×100

Figure 4

Small developing papillary TCC with severe dysplasia. (a) H and E. (B) p53 expression. (c) H-ras expression. (d) COX-2 expression. (e) iNOS expression. (f) 8-OHdG expression. Magnification x100

Furthermore, the cesium-137 activity concentration in urine (the mean value in the most exposed group was 6.47 Bq/L), reported,[36] and possible radiation doses that could have resulted from it, were discussed.[713] It was concluded that the doses would be too low to cause any increase in bladder malignancy or the “radiation induced chronic proliferative atypical cystitis,” reportedly characterized by multiple areas of severe dysplasia and CIS.[3] Retractions are on the up today,[14] but not in the former Soviet Union, where, as far as we know, no articles have been retracted so far.[15] The authors of the papers[3456] should consider retraction to prevent repetition of suboptimal practices.[16] Although some screening programs are very effective at saving lives, excessive screening for cancer and precancerous lesions can be associated with a risk of overdiagnosis and overtreatment,[17] especially if diagnostic facilities are not perfect, including at the same time invasive manipulations.

Pathology of the prostate gland and erectile dysfunctions after the Chernobyl accident, discussed[1] are different topics, deserving a separate review of the literature. However the study,[18] not cited in,[1] should be mentioned, the more so as histopathological data are absent from the PubMed abstract of this article published in the principal journal of Russian pathologists “Arkhiv Patologii” (Archives of Pathology): in 75.6% of testicles picked at random (forensic cases, residents of Kaluga district of Russian Federation) was found paucity or absence of germ cells, affecting > 10% of spermatic tubules, which was interpreted as “hypospermatogenesis” associated with decreased fertility and attributed to the radiation exposure due to the Chernobyl accident.[18]

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