From my experience and your observations, obviously yes. Your paper proves this.

Dominique:

Thanks for introducing this stimulating and important topic. I will add a few modest observations and commentary below in the hope of furthering and enriching the discussion:

Using sophisticated scanning electron microscopy (SEM) technology, our topic moderator (above) Dr. Dominque Bazin and his colleagues [1] have provided further invaluable data to bear to support a potentially etiological role, past or present, of likely asymptomatic infection in prostatic calculi development, given the remarkable spherical shape and clustering pattern exhibited in the observed bacterial imprints of these calculi (with some 78% occurrence of bacterial imprints in such calculi), and further propose that the infecting organisms may be staphylococci, something wholly consonant with the aggregate findings of several previous studies that (1) Staphylococcus spp. may be implicated in bacterial prostatitis, and that (2) Staphylococcus spp. have also been isolated from prostatectomy specimens.

There are however some nuances here that suggest caution - and to their credit the authors are properly circumspect in their conclusions. So I will note here that studies using transrectal ultrasonography [2] find that the incidence rate of prostatic calculi in middle aged and elderly men is quite high (75% in middle-aged and 100% in aged men), suggesting as Chinese researchers Jie Yang and Ning-Hong Song have posited that bacterial infections are not a necessary condition for the formation of genitourinary calculi [3], and that at least for enlarged prostatic utricles (EPUs), the calculous matrix might be derived from organic matter, an amalgam of continuously concentrated EPU liquid plus deciduous epithelial cells of EPUs without necessarily the participation of infections [4]. In addition, it still remains unclear whether infection-driven inflammation necessarily influences carcinogenesis in this context, as some studies [5] observe that prostatic calculi in fact have no significant association with chronic inflammation (nor with BPH clinical parameters).

These are important issues reflecting some divergent perspectives on the question of prostatic calculi, especially their association with current or previous infection and the role of such infection in driving inflammatory processes that may be implicated in oncogenic transformation, and although these require further studies to clarify and resolve more dispositively, nonetheless my own ad hoc review and others [6] suggests, largely in agreement with Dr. Bazin and colleagues, that the role of prostatic, GI/GU, and renal infection continues to be more intimate than previously suspected in these contexts and that still further valuable insights and clinical lessons may derive in the not too distant future from additional close study of bacterial imprints in such calculi and the associated infection-inflammation nexus and its relationship to the cancer process.

REFERENCES

1. Dessombz A, Méria P, Bazin D and Daudon M. Prostatic stones: Evidence of a specific chemistry related to infection and presence of bacterial imprints. PLoS One 2012; 7: e51691.

2. Shoskes DA, Lee CT, Murphy D., Kefer J., Wood HM. Incidence and significance of prostatic stones in men with chronic prostatitis/chronic pelvic pain syndrome. Urology. 2007; 70 (2): 235–238.

3. Song NH, Wu HF, Xu N., Yang J.. The composition and structure of stones in enlarged prostatic utricles (EPU). J Androl. 2012; 33: 45–49.

4. Yang J, Song N-H. Infections Are Not a Necessary Condition for the Formation of Genitourinary Calculi. J Androlog 2012; 33(1):52

5. Kim SH, Jung KI, Koh JS, Min KO, Cho SY, Kim HW. Lower urinary tract symptoms in benign prostatic hyperplasia patients: orchestrated by chronic prostatic inflammation and prostatic calculi?. Urol Int 2013; 90(2):144-9.

6. Sfanos KS, Isaacs WB, De Marzo AM. nfections and inflammation in prostate cancer. Am J Clin Exp Urol 2013;1(1):3-11.

Thanks for your excellent answer. By the way, are you interested by Breast calcifications ?

Dominique:

Thanks.

And yes, breast calcifications are an area of special interest.

Constantine

If you have published some investigations on breast (or any kind of calcifiations) please send me them. We try from a general point of view to establish a relationship between pathology and chemical nature of CP. Such research is described in our last chem rev in 2012.

Take Care

Dominique

Dominique:

As soon as what I have reaches more final state, I will let you know.

In the meantime, I have publsihed by invitation an Open Review of your paper on ResearchGate which you may be interested in reading, as I have added some considerable and important additional data in support of your position.

Constantine

Article Prostatic Stones: Evidence of a Specific Chemistry Related t...

Thanks for these exciting comments. Your remarks are also in line with a publication we have recently publish (but in french) where we start by a simple question. Are al the calcifications pathological? In some cases, calcifications are observed for very young patients (Mitsuyama H, Healey RM, Terkeltaub RA,Coutts RD, Amiel D. Calcification of human articular knee cartilage is primarily an effect of aging rather than osteoarthritis. Osteoarthritis Cartilage 2007;15:559-65.). Then calcifications are generally observed but their chemical nature is not given. Moreover, staining procedures to determine their chemical nature are not significant (Bonewald, L. F.; Harris, S. E.; Rosser, J.; Dallas, M. R.; Dallas, S.L.; Camacho, N. P.; Boyan, B.; Boskey, A. Calcif. Tissue Int. 2003, 72,

537.). For these reasons, a lot of research has to be performed on pathological calcifications and some times results are different because characterisation techniques gives different point of views regarding their structural and chemical chracteristics.

For example, you take the case of kidney stones (10% of the population). You can find apatite Inside by DRX for example ( a technique which is usually performed). Unfortunatly, DRX doesn't give the carbonatation rate , a parameter which is linked to infection (Relationships Between Carbonation Rate of Carbapatite and Morphologic Characteristics of Calcium Phosphate Stones and Etiology,Xavier Carpentier, Michel Daudon, Olivier Traxer, Paul Jungers, Aurélie Mazouyes,

Guy Matzen, Emmanuel Véron, and Dominique Bazin,UROLOGY 73: 968–975, 2009.) So if you try to made a correlation between infection and kidney analysis through DRX), you will not have the same results than a study of the same correlation but with FTIR.

What do you think ?

Sincerely

Dominique

Dominique:

Here are my thoughts:

You raise some important concerns about the variability of detection precision using diverse metric tools, such as DRX versus FTIR (or even, more wildly, electron microscope if we believe in the theorizing that nanobacteria may be implicated in some calculi development). Indeed, I am largely in agreement and would argue further that, in addition to variability introduced by different stone types and by the measurement tools themselves, we also appear to have gender dependencies which in turn also show target organ dependencies (urinary tract versus renal versus prostate, etc.) as observed recently [1]. Furthermore, your observation re DRX makes sense, given that DRX would necessarily be a suboptimal choice for determining carbonate level due to apatite's infamous poor crystalline structure (and I note in passing only that FTIR brings its own set of issues: since it measures the absorption rate of a beam of light as a whole, the individual absorption rates of each wavelength of light must be inferred - we cannot "know" it directly).

But there is a larger issue here as well: even with FTIR assessment of carbonation rate, it appears that carbonate levels are only weakly predictive of positive stone culture, since in one recent study [2] over half of stones that were non-struvite and non-apatite - so-called non-infection type stones - show a positive stone culture and hence harbor culturable organisms, and more telling still, a third of patients with struvite or apatite stones were negative on stone culture, making mineral type or stone composition an unreliable predictor of the presence of infectious organisms in a renal stone, from which we can further conclude that there simply does not appear to be any simple relationship between FTIR-confirmed highly carbonated apatite in stones on the one hand and the presence of culturable bacteria in renal calculi.

I also note that James Williams' team at Indiana University [2] offer a speculative but highly intriguing possible explanation: infected stones (ones formed in the presence of infection) can be sterilized by subsequent antibiotic therapy, thus removing detectable culturable organisms. To me at any rate, this is not so far fetched: I was never particularly convinced by the oft-repeated claim that the mineral-encasement of infective organisms in stones provides a completely unassailable barrier assuring strong treatment resistance. All these minerals have some degree of porosity and hence permeability and it cannot be demonstrated that no active antimicrobial assault can penetrate significantly, and I rather think the opposite may be possible. In this sense, my view is that mineral encasement of infective organisms is much like the blood-brain barrier (BBB) which is never completely impassable despite its clear functional intent for the brain as an inviolate sanctuary, but rather across which we can identify certain conditions and certain oncotherapeutic agents that can effectively enable cross-BBB activity.

So, in studying the infection-calculi relationship, we need studies that control for the occurrence or lack thereof of subsequent antibiotic therapy, and we also need some guidelines, even if largely empirical and ad hoc for the present, of the different capabilities, and optimal choice, of rival measurement tools, in order to begin some embryonic consensus on how robust well-controlled future studies should be conducted to maximize reliability as well as the possibility of reproduction of results. And for that, we probably need the articulation of a research agenda that specifies the multiple factors and issues involved in order to clarify the role of infection - and inflammation - in calculi development. Sounds like something of a "Unified Theory" of calculi development, with advances in physics, instrumentation, physiology and new-found knowledge of the infection-inflammation - and possibly also - oncogenesis nexus. Grand thinking yes, complex, absolutely, but worthy? Indisputably. And your own research (and I did read your paper in La Presse Médicale; my French is not fluent but it is sufficiently serviceable to appreciate the contribution) has critically started the march with invaluable findings and insights.

REFERENCES

1. Schwartsburd PM, Agababov R, Vainshtein M. Gender difference in calcification diseases: is it the result of gender-specific ways of nano-bacterial expansion? Med Hypotheses 2013; 81(5):911-2.

2. Englert KM, McAteer JA, Lingeman JE, Williams JC. High carbonate level of apatite in kidney stones implies infection, but is it predictive. Urolithiasis 2013; 41(5):389-9.

Dominique:

Separate request: could you copy and post your last contribution commenting on my review also in the comments section of the review itself, and I will then follow it, as here, with my own response and commentary. This may seem duplicative, but I believe ResearchGate wants to start expanding the use of their Open Review (within which my review appeared) so that not only the review of the paper appears, but also any commentary by the original authors, by the reviewer, or any other interested scholar.

Thanks

Constantine

We would like to start a collaboration on prostate biopsy (presence of calcifications & cancer). are you interested by such investigation?

take care

Dominique 

Dominique:

Yes, I am interested to participate and contribute whatever I can. Let me know as things crystallize.

Constantine

By the way, i will submit a paper on breast cancer in september. As soon as it is accepted, i will send you it. Probably a new opportunity to build something.

Take care

Dominique

Dominique:

Great - look forward to the collaboration!

Constantine

It could be a result of infection and a cause for reinfection.