CHRONIC - part 1

Why not heal it?

Federico Guercini MD, consultant urologist Assistant Professor

Index

INTRODUCTION Although prostatitis is extremely frequent, affecting from 30-50% of sexually active males, it has been called the wastebasket of clinical knowledge (Stamey, 1980). The study of this invalidating disease has not been supported by extensive research as urologists tend to concentrate on major pathologies such as benign hypertrophy (BPH) and cancer. Aware of the worldwide need for valid therapy for prostatitis, this “malignant Cinderella of Medicine”, we decided to investigate its causes and treatment. The results we obtained over 20 years have been published in many international scientific journals but the benefits of our work have been extended only to the few hundreds of outpatients we have personally treated. We are convinced our physiological hypotheses and therapeutical strategies should be shared by urologists. Encouraged and supported by our patients we have decided to use the Web to divulge our approach as widely as possible.

Many of the causes of prostatitis have been hypothesized internationally and we have tested and proven them. Our therapeutical strategies have not been fully accepted because of diverging views, lack of practical and technological know-how e.g. in the field of ultrasound and limited ability in administering ultrasound-guided therapy. Despite this, what we propose can be reproduced and tested by any urologist with a basic knowledge of these techniques and ability to use them. Should the experience of others lead to improvements in our methods and techniques we would 2 welcome the opportunity to revise, correct and expand our knowledge in this field. Furthermore, should any specialist, who has obtained good results which are as yet unpublished on the Web or elsewhere, like to contact us it would be an honour and a pleasure to pool our resources in an attempt to cure this pressing and invalidating disease which affects millions of men.

For them it is, in fact, extremely frustrating to be really ill, to refer obvious symptoms of a disease with a clear aetiology and pathological process and to be treated as hypochondriacs or to be given advice such as “Don’t dwell upon it! There’s nothing to be done in any case!”

Now let’s have a closer look at the prostate and the causes of its becoming diseased. 3

CHRONIC PROSTATITIS Part 2

WORK IN PROGRESS

ANATOMY AND PHYSIOLOGY

Federico Guercini MD, consultant urologist

Macroscopic Anatomy Microscopic Anatomy Prostate Canals and Bladder Neck

Macroscopic Anatomy In shape the prostate is usually described as a squashed cone with the base upwards, the apex downwards and four sides with rounded corners. The four sides are known as the anterior, posterior and lower-lateral faces. A normal prostate is 4 mm in length, 3 mm at the cross-section and 2.5 mm at the antero-posterior section. Weight ranges from 15 to 20 gr.

Lodged in the pelvis, the prostate adheres strongly to the bladder neck and is anchored to the pelvic bones (mainly anteriorly to the pubis) by many ligaments and other supporting structures e.g. the urogenital diaphragm (see fig. 1). 4

Microscopic Anatomy Thirty percent of the prostate is muscle fibre and the other 70% is made up of glandular cells which are grouped together in 30 glandular units known as acini.

The prostate can be divided into three areas: the peripheral, the central and the periurethral transitional area (fig.2). This subdivision is extremely important as prostate tumours almost always originate in the peripheral area and BPH in the transitional. Depending on its causes, prostatitis originates in the periurethral or peripheral areas and causes different symptoms in each instance.

Prostate Canals The prostate contains three large canals, a small central canal known as the utriculus and as many small canals as there are acini. The three major canals are:

- the urethra (1) through which urine flows from the bladder;

- to the right (2) and left (3) of the urethra the ejaculatory ducts which join the urethra at the veru montanum and through which pass from the seminal vesicles.

 The utriculus is a small duct which joins the veru montanum between the two ejaculatory ducts. It is considered a pre-sex differentiation embryological remnant of what becomes the uterus in females. After birth in males the utriculus may atrophy and almost totally disappear as become a closed canal, dilate and form cysts (utricular cysts) which may cause prostatitis-like symptoms if inflamed.

 During fluid produced by each acinus flows through the minor canals (which also join the urethra at the veru montanum) to mix with the sperm from the seminal vesicles. This prostatic fluid is essential for and vitality and indeed, in the course of prostate inflammation, abnormalities in it may impair fecundity. 5

Seminal Vesicles and Bladder Neck Any presentation of the anatomy of the prostate is incomplete without a description of the seminal vesicles and the bladder neck. Although not part of the prostate these organs play in integral part in its functioning. As the name suggests the seminal vesicles are two small, internally pluriseptate sacs (mean diameter 5x4 cm) which contain the sperm produced by the - By means of strong pelvic muscle contractions during orgasm the sperm are forced into the ejaculatory ducts which join the urethra. There they are mixed with the prostatic fluid from the acini before being ejaculated.

The bladder neck is the area at the base of the bladder which opens into a funnel at micturition to allow urine to flow along the lines of minimal force in the proximal urethra. It distends when urine is passing and when pulled by specific extra- urethral muscles.

From the above description we can now provide an answer to a common question “What is the prostate for?”

The function of the prostate is to produce and store the prostatic fluid which is secreted by its glandular acini because this fluid nourishes and propels the spermatozoi in the sperm, which is stored in the seminal vesicles. During orgasm the pelvic muscles force the prostatic fluid and the sperm into the urethra at the same time. There they are mixed and ejaculated. 6

CHRONIC PROSTATITIS part 3

WORK IN PROGRESS

PATHOLOGY AND PATHOGENESIS

Federico Guercini MD , consultant urologist Classification Acini and Minor Canaliculi Urethral-Prostate Reflux A-Bacterial Prostatitis? Spread of Utriculus Seminal Vesicles

As university professor I could now describe all the anatomical and pathological pictures which are present during states of acute and/or chronic inflammation of the urethra and prostate but in so doing I would simply be repeating what has already been said by my predecessors who have not been able, in fact, to cure prostatitis. Those of you who wish to study the pathology as described in standard texts might like to consult, for example, Campbell’s , which is the urologist’s Bible.

Those of you who want new insights into the problem can follow me!

To start with, let’s set aside Drach’s 1978 classification of prostatitis which divides the disease into acute and chronic, bacterial and non-bacterial forms and adds prostatodynia to cover a multitude of disturbances (e.g. painful male urethral disease) in patients with few (<10 per field) inflammatory cells and typical prostate pain who do not fit into any of the other categories. 7

Let’s go back to the complex of organs that I described in part 3 and let’s consider them as a single bladder neck-urethral-prostatic-vesiclar organ (a term which you will not find in any textbook of anatomy) so that we can identify weak areas and consequently provide the right remedy.

ACINI and MINOR CANALICULI We said the minor canaliculi serve to transport prostatic secretions from the acini to the urethra. The canaliculi draining the central acini are tortuous in form while those draining the peripheral acini are straight and joined to the urethra in a position which is countercurrent to the urine stream (fig.4). These anatomical details prompt the following inference: given the course of their canaliculi, periurethral acini are more easily obstructed by inflammation and are more likely to release substances and even produce stones. Peripheral acini with their straight canaliculi are more subject to urinary reflux and urethral bacteria.

This has major therapeutical implications because if true, periurethral prostatitis might benefit temporarily from strong gland expression while no improvement would be seen in cases of peripheral prostatitis because the straight canaliculi are not prone to stasis. 8

URETHRAL-PROSTATE REFLUX When discussing the peripheral acini we mentioned the urethral-prostate reflux. This is the abnormal passage of urine from the urethra into the prostate. Like all fluids urine flows where pressure is lowest and finds it “convenient” to leave the urethra and flow into the prostate only under certain pathological conditions. These include 1) increased endourethral pressure due to urethral narrowing below the prostate, the most common causes being nerve-based periurethral musculature rigidity, congenital stenosis or stenotic outcome of previous episodes of prostatitis; 2) abnormalities in the first urethral tract due to a narrow or poorly elastic bladder neck i.e. bladder neck sclerosis or dysectasia, which may be congenital or develop early in life.

In the first tract of the prostatic urethra urine flows hard against the posterior wall rather than parallel to the lateral walls. Unable to withstand this high pressure the posterior wall cedes and urine filters into the prostate (fig.5). Barbalias (1997) recently confirmed this hypothesis with his finding of high urethral closure pressure in patients with abacterial prostatitis who benefitted from a course of alpha-blockers and antibiotics. Kirby (1982) instilled water containing carbon microspheres into the bladders of 10 patients with chronic prostatitis and found the microspheres in 70% of prostate sections taken during transurethral resection (TURP) a few days later. In samples of prostatic secretion from patients with urethral-prostate reflux Persson and Ronquist (1996) found high urate and creatinine levels which not only facilitate stone formation but which also by their very presence induce an inflammatory response in prostate tissue.

A transrectal ultrasound scan performed during the dynamic phase of micturition visualizes signs of widespread prostatitis when urethral stenosis is present and shows prostatitis is localized in the periurethral area immediately below the bladder neck when bladder neck sclerosis is present (fig.6).

Obviously prostatitis cannot be cured until the anatomic abnormalities which are the underlying cause are rectified. 9

ABACTERIAL PROSTATITIS? Although mechanical causes are among the factors leading to the onset of acute or chronic prostatitis, microbial super-infection ALWAYS produces the devastating effects of the disease. But, I can hear you object, what about the abacterial forms of prostatitis? I am sorry to disillusion you gentle reader but abacterial forms of prostatitis practically do not exist. And what of all the studies? All the papers? All the laboratory tests showing no bacteria in the prostate secretion, sperm and urine? Are they all wrong? 10

Surely not but let’s ask ourselves and our trusted urologist two questions! First was every single type of microorganism including the saphrophytes or non-pathogens found and cultured? And were the cultures always done in the right medium with the right laboratory timing to promote development? And if, as we have seen, some glandular acini become obstructed under the inflammatory stimulus might not some microorganisms remain entrapped inside and unavailable for detection in laboratory tests on fresh samples or cultures? If you have found no satisfactory answers to these questions anywhere else I can provide the following replies:

1) Bacteria like staphylococcus aureus or staphylococcus epidermis and so forth which are usually found as normal inhabitants of the skin but not the prostate cannot be considered non-pathogens. You may object that whenever these pathogens were found they did not come from the prostate but were collected in the prostate secretion, maybe in the tract closest to the urethra or even outside on the penis. To confute this hypothesis we performed transrectal ultrasound- guided sampling of prostate secretion directly from inflamed areas of the prostate and found high concentrations of these bacteria with an incubation of at least 5 days. This type of study had already been carried out by Berger and Krieger in 1996 but their results were different. Their mistake was to take a blind harvest of the endoprostatic sample rather than use ultrasound as a guide so they did not collect samples from specifically inflamed areas of the prostate. 2) By using the same technique i.e. taking micro-samples of tissue from obstructed acini we have always found multiple microbial agents even when samples of prostatic secretion collected by standard methods resulted sterile. 3) Some microorganisms such as Chlamydia or Ureaplasma are difficult to detect in fresh samples and hard to culture so that even when they are present results are negative for infection. Many can be detected by IGG and IGM titres in blood i.e. as expression of their circulating antibodies. 11

4) Fungi are another question particularly Candida albicans. Cultures and antibiogrammes have only recently been developed and are done only in advanced laboratories.

SPREAD OF INFECTION Spread of infection into prostate tissue appears to be achieved by three pathways:

5) along the urethral canal after intercourse (very frequent) 6) through the lymphatic pathways from the ampulla of the rectum (frequent) 7) by the hematogenic via (rare)

UTRICULUS This embryological remnant may be another cause of disturbances in the prostate. The opening of this structure into the urethra may facilitate the passage of germs inside of it and thus give rise to acute or chronic inflammation. Utricular cysts and dilation may also cause prostatitis-like symptoms which can be cured only with proper therapy.

SEMINAL VESICLES The seminal vesicles are not always but quite often involved in forms of prostatitis. Because of their anatomy eradicating an infection in them can be difficult and requires specific therapy. When describing the anatomy of the seminal vesicles we referred to the ejaculatory ducts through which the sperm passes on its way to the urethra. Sometimes stones may form in the ducts and their typical “rosary bead” form can be seen during an ultrasound scan. The stones may cause pain during intercourse, reduce the quantity of ejaculate and when persistent, increase obstruction. 12

CHRONIC PROSTATITIS PART 4

WORK IN PROGRESS

SYMPTOMS

Federico Guercini MD, consultant urologist The symptoms of chronic prostatitis can be classified as follows:

Pain Urinary disorders Sexual disorders Reproductive disorders They may be present alone or in association.

PAIN This is usually the earliest symptom and easily leads the urologist to diagnose prostatitis. Some types of pain are undoubtedly pathognostic. See for example mono- or bi-lateral testicular soreness, painful heaviness in the perineum and occasionally a lancing burning pain and a feeling of something extraneous in the anus or ampulla of the rectum. Other less frequent but no less indicative symptoms are mono- or bi- lateral inguinal pain, a sensation of tight underpants, suprapubic heaviness, pain in the buttocks or at the base of the spinal column. Special mention must be made of burning at the tip of the penis at the beginning and/or end of micturition or during ejaculation. The tip of the penis must be considered as the external projection of the bladder neck. An inflamed bladder neck makes itself felt when it opens or closes during micturition or ejaculation because of the high pressure which is exerted on it. On the other hand pain or burning along the lower tract of the penis which is continuous or felt only during micturition is a symptom of acute urethral inflammation which may or may not be complicated by prostatitis. 13

All these symptoms may improve, worsen or remain unchanged after ejaculation. They may worsen or reappear with the change of season, particularly when autumn changes to winter or winter to spring. URINARY SYMPTOMS When urinary disorders are present, age is the factor which differentiates prostatitis from BPH. The patient with prostatitis is usually a young man while the patient with BPH is generally elderly. Often passing small quantities of urine (pollakuria), nocturnal micturition (nicturia), hestitation at the start of micturition and the annoying final dripping are linked to bladder muscle hyperactivity in both groups of patients. Inflammation is the cause in cases of prostatitis and obstruction in cases of BPH. However, as I have already stated, obstruction due to congenital or post- inflammatory bladder neck rigidity (bladder neck sclerosis or dysectasia) can sometimes be found in young men. SEXUAL AND BEHAVIOURAL SYMPTOMS These are usually found in patients with a long history of prostatitis and from the medical point of view are the hardest to cure because of overlapping psychological difficulties such as performance anxiety, need for self-defence after a poor performance etc. The most frequent symptoms are premature ejaculation, blood in the sperm (hemospermia) and . The first two are easily explained and cured if they are caused by prostatitis. In a 1994 study on 115 patients of ours ultrasound scans visualized one or more fibrous calcifications near the veru montanum in patients affected by premature ejaculation. As we know the veru montanum regulates the times of orgasm. Hemospermia is often associated with stone formation in the ejaculatory ducts. Insufficient erection, loss of libido and more rarely refusing to have intercourse or being unable to reach orgasm (anorgasmia) are often present. In our experience psychotherapy is usually required for these patients particularly if the disturbances started at an early age. We work in collaboration with a specialist in psycho-sexual counselling. RERODUCTIVE SYMPTOMS As we have already seen after ejaculation prostate fluid serves to nourish and 14 propel spermatozoi towards the egg. If the prostate fluid is abnormal or contains blood because of inflammation the spermatozoi may lose mobility (astenospermia) or even become completely immobile and have a shortened life-span. If the ejaculatory ducts are also inflamed due to direct obstruction or to pressure exerted by surrounding prostate tissue the sperm will contain fewer spermatozoi (oligospermia) and will be ejaculated with little force into the vagina. Difficulties will ensue in trying to overcome the barrier of the female cervical mucous. If the seminal vesicles are infected symptoms will be more severe and more evident. 15

CHRONIC PROSTATITIS - PART 5

WORK IN PROGRESS

DIAGNOSTIC TECHNIQUES Federico Guercini MD Consultant Urologist Main Page Preliminary Interview General Clinical Examination Prostate Examination Laboratory Tests Transrectal Prostate Ultrasound (TRUS) TRUS and TRUS and Chronic Prostatitis Cystoscopy X-Rays

*The diagnostic value which is cited at the beginning of each section as reference value is entirely arbitrary and is based on our own personal experience. We hope it will help the patient and the doctor who may not be an expert in this field.

PRELIMINARY INTERVIEW (*Diagnostic value = 10) A fundamental part of any approach, this is when the man with prostatitis refers his symptoms to the attending physician and decides whether to entrust in him. The symptoms which the physician must investigate have already been described. I recommend that at this stage doctors be particularly patient with cases of prostatitis. Enquiries about symptoms must be repeated for symptoms alone and in association and they should be investigated in depth. Often the person in front of the doctor is a mature or a young man who has lost faith in the medical profession, who may even have been frightened in many preceding consultations and who may feel his trust has been misplaced. Sometimes he will tend to underrate some aspects of his disease and 16 overestimate others. It is up to the attending physician to put things into a more balanced perspective. GENERAL CLINICAL EXAMINATION (*Diagnostic Value = 5) Some of the symptoms referred in the course of prostatitis may be caused by other pathologies which must be eliminated in the differential diagnosis. To be excluded are: 8) incomplete or complete inguinal or crural hernia which can cause inguinal or suprapubic pain; 9) haemorrhoids, perianal fistulas or rhagades which can cause anal or perianal soreness or pain; 10) torn muscles which in young men can cause pubic or crural pain 11) epidydmitis or can induce testicular soreness and heaviness DIGITAL RECTAL EXAMINATION (DRE) (*Diagnostic Value = 7) I do not think it a waste of time to emphasize the exploratory finger should be inserted into the rectum with great gentleness so that any contraction of the elevator muscles of the anal is not missed through the patient’s understandable reaction to rough handling. The contraction can be hypothesized indirectly if the patients complains of elective pain of the pudendus nerves at the sacrospinal ligament. In our experience this is never he primary cause of perineal pain. Caused by chronic contraction of the elevator anus muscles, it is always secondary to either primary prostate pain or repeated microtraumas due to hard bicycle or horse saddles or vibrations from mopeds etc. In any case, even when secondary, it should always be treated. 17

** The DRE may, for teaching purposes, be divided into the lower (rectal sphincter, haemorrhoid area, perineal floor muscles), middle (prostate apex and organ) and upper (prostate base and seminal vesicles) tracts. After training the patient may perform the DRE himself and obtain information on the course of his disease during treatment. In our experience self-examination may not have any real therapeutic value but it certainly helps reduce the anxiety factor and makes the patient aware of exactly where the origin of his illness - the prostate - actually lies. In the course of prostatitis the prostate may be soft and enlarged, normal in size and normal or hardened when palpated in acute phase inflammation. The DRE may cause pain irradiating to the penis tip particularly when the inflamed area is felt. In the older age group or in patients with hemospermia the DRE should exclude the presence of tumours which, we must remember, cannot be distinguished by palpation alone, from calcified nodules or granulomatous prostatitis. When diagnosis is uncertain blood concentrations of the prostatic specific antigen (PSA) should be dosed to clarify the picture. The final stage of the DRE is palpation of the seminal vesicles to determine their consistency, volume and whether pain is present. LABORATORY TESTS (*Diagnostic Value = 8) When we started our work in the field of prostatitis we prescribed, as other urologists did, Stamey’s four-glass test (1968), that is, we looked for inflammatory cells and microbes in the urine before and after prostate massage. We do not now prescribe this test even though it is still in widespread use. We opt for the following tests: 12) Urine culture with antibiogram; 13) Sperm culture with antibiogram for common germs, protozoi mycetes and saphrophytes on enriched culture medium; 18

14) Urethral swab after prostate massage for Chlamydia in fresh and cultured samples, Ureaplasma, common pathogens and human papilloma virus (HPV) and human herpes simplex virus (HSV) (using PCR); 15) IGG and IGM for Chlamydia and Mycoplasma. If we suspect the patient’s partner is infected we also prescribe 16) Vaginal swab for tests on fresh and cultured samples of common bacteria, mycetes and protozoi; If sexual disturbances are present we recommend dosing 17) total testosterone levels; 18) free testosterone levels; 19) DEHA and DEHAS; 20) LH, FSH and . If we suspect fertility is impaired we request: 21) Spermiogram; 22) Nemasperm penetration test; 23) Post Coital Test. 19

TRANSRECTAL PROSTATE ULTRASOUND (*Diagnostic Value = 10) (see Glossary of Ultrasound Terminology)

Ultrasound scanning of the patient with prostatitis is fundamental in the diagnostic and, as we shall see, therapeutic flow charts. Like everything else the scan must be done properly with the proper instrument. The patient’s bladder should be full (but not over-full) and the scan must be carried out by the transrectal route under basal conditions and during the dynamic phase of micturition, that is during urination. From experience we prefer to have the patient standing to facilitate micturition during scanning. For this reason the probe must be of the fine, new generation type so as to avoid bladder neck comprEsSion. As at least two planes are required for prostate scanning the probe must bi- or multi- plane and the crystal vibration in the range of 7- 10 MHz. Only once these technical requisites are satisfied can we be sure of scanning the prostate properly. Under basal conditions the following ultrasound patterns must be monitored: 24) prostate volume; 25) capsule profile; 26) tissue echogenicity; 27) presence or absence of calcified fibrous formations, 28) ejaculatory duct course and echogenicity; 29) vein calibre in the peri-prostate plexus. During micturition the following patterns must be monitored: 30) profile and echogenicity of the bladder floor (trigone); 31) elasticity and morphology of the bladder neck; 32) distension capacity of the prostatic urethra; 33) profile and echogenicity of the prostatic urethra walls; 34) profile and echogenicity of the veru montanum. 20

ACUTE PROSTATITIS In cases of acute prostatitis the prostate remains normal in size and lobe symmetry. In the early stages of mild forms a hypoechogenic peri-urethral halo is visualized which is due to oedema. As the disease progresses hypoechogenic intra- glandular filaments are observed. Caused by inflammation-induced blood vessel dilation they are associated with dilation of the Santorini periprostatic vein plexus. In severe forms of acute prostatitis the prostate is enlarged and areas of hypoechogenic tissue are larger because the inflammation is more extended. In older patients or in patients with compromised immunological systems a prostatic abscess may develop. On the ultrasound screen the abscess appears as a transonic area with irregular edges (fig.7). 21

CHRONIC PROSTATITIS Prostate Parenchyma The prostate capsule and size are usually normal. Ultrasound abnormalities may be found throughout the parenchyma or only in the periurethral or peripheral areas. In cases of mild chronic inflammation a high resolution ultrasound probe is essential for detection of minimal signs of the disease which are irregularly-shaped, highly echogenic oval areas. Reactive dilation of peri-prostatic veins is always present. In more severe cases of chronic inflammation three ultrasound patterns are found in the parenchyma: 35) strongly hypoechogenic areas with edges merging into the surrounding parenchyma (fig.8); 36) areas with a homogenous hyperechogenicity and well-defined saw-tooth edges (fig.9); 37) strongly hyperechogenic areas which are sometimes surrounded by a hypoechogenic halo due to the acute reaction in the surrounding gland (fig.10).

FIBROUS CALCIFICATIONS Fibrous calcifications appear as highly hyperechogenic round, irregular ovoid or dot-like (the so-called calcium spray) images which, depending on their density, may have an underlying posterior shadow cone. The diagnostic value of this finding is closely correlated with the patient’s age. In an elderly man calcification in the peripheral area of a prostatic adenoma is caused by calcium precipitation inside the gland due to adenoma compression and is not usually symptomatic. In a young man this type of calcification is found in 85% of patients with symptoms of prostatitis and in about 12-15% of symptom-free subjects. 22

In young patients the calcification is, for anatomic reasons, usually localized in the periurethral area and is caused by crystal precipitation inside the periurethral acini whose ducts are obstructed by inflammation. Calcification is never a real concrete formation like a kidney stone but always a tenacious, weak aggregate which must be destroyed to ensure therapy is efficacious (see film). Calcifications are a major associated cause of the symptoms of prostatitis and they perpetrate the disease by maintaining the microbial agents within, like the beseiged in a fortified city. These microbes are the source of re-infection. Symptoms associated with calcification vary with the localization and are as follows: 38) periurethral sub-bladder neck: micturitional disturbances, stabbing pain radiating to the penis tip at the start and/or end of micturition (fig.11); 39) median periurethral area: perineal tension or no symptoms (fig.12); 40) peri-Veru montanum: premature ejaculation, ejaculation pain, feeling of obstruction in the passage of sperm, hemospermia (fig.13); 41) peri- or intra- ejaculatory ducts: symptoms are the same as those of peri- Veru montanum calcifications (fig.14). As I have already said these calcifications have a high urate, creatinine, xanthine and uridine content. Consequently some authors have attempted to cure prostatitis by administering anti-uric substances by the general route. Symptoms improved to a certain extent but only for as long as the drug was taken. EJACULATORY DUCTS When normal, the ejaculatory ducts can be visualized, particularly during micturition, as two hypoechogenic streaks converging on the veru montanum. They can be imaged one at a time on a linear plane. When acutely inflamed the image is even clearer because the wall oedema enhances visibility. In cases of chronic inflammation the walls become hyperechogenic because of thickening and fibrosis. Sometimes fibrosis is associated with intraluminal calculi which are visualized as echo-lucent spots in a circular rosary-bead formation. Symptoms associated with ejaculatory duct inflammation are manifested during orgasm and include pain or burning during ejaculation, sometimes 23 hemospermia, a feeling of obstruction, reduced sperm quantity and impaired quality and even no ejaculate. SEMINAL VESICLES When normal the seminal vesicles are clearly visible above the prostate base (especially after a period of sexual abstinence). They appear as two hypoechogenic oval structures with many internal hypoechogenic septates. When inflamed they are usually dilated because voiding is obstructed by oedema in the ampoule or ejaculatory ducts. In cases of major chronic inflammation due, for example, to trichomonas or gonorrhea, the vesicles sometimes appear sclerotic with hyperechogenic walls. When inflamed the seminal vesicles usually cause a continual, dull pain which may intensify during defecation, thus producing reflex constipation and giving rise to a vicious circle harder faeces and more pain during defecation. Because of their anatomical configuration the seminal vesicles are often the last area to be cured of inflammation and treatment must be monitored very carefully. UTRICULUS Normally this involuted organ is invisible during an ultrasound scan. Sometimes it remains active and may dilate and form cysts which can be visualized as asonic areas near the median urethra. Even with cysts the patient may be asymptomatic but if pain is present or generated by the cysts it can be cured with the appropriate therapy. 24

BLADDER NECK AND TRIGONE Functional ultrasound scanning of this area is possible only during micturition. In normal subjects the start of micturition corresponds to a gradual homogenous opening of the bladder neck. The anterior and posterior parts form a cone with its base on the trigone and its apex continuing into the urethra (fig 15). In the presence of bladder neck sclerosis or dysectasia ultrasound visualizes the slow opening of a rigid, not soft, bladder neck (shutter opening). A clear endoluminal protuberance appears in the posterior portion (posterior lip). The physiological funnel shape is changed (fig 16) and the space for the stream of urine is markedly reduced which causes an accelerated flow rate. Consequently an abnormal bladder neck closure at the end of micturition appears as a shutter closure and leaves a small trapped quantity of urine which drips out after micturition is ended. When bladder neck sclerosis is present it must be corrected to prevent the development of chronic prostatitis. Primary or secondary inflammatory abnormalities in the trigone (trigonitis) are hard to detect in an ultrasound scan unless they are very marked and associated with mucous extroflexion (papillary trigonitis). The image shows much tiny digitation on the vessel wall. URETHRA The urethra, like the bladder neck, can only be studied during the dynamic phase of micturition. In normal subjects after bladder neck funnelling the prostatic urethra distends to a maximum of 10 mm. The walls are thin and very slightly more echogenic than the surrounding glandular tissue (fig. 17). In cases of urethritis the distension seems rigid and the walls are markedly more hyperechogenic and thicker and have an irregular profile. The clearest indirect sign of urethral narrowing (stenosis) below the tract visualized by the ultrasound probe is overdilation of the prostatic urethra with no other sign of disease. These patients must then undergo radiography during micturition (urethrocystography) to confirm the diagnosis. 25

RADIOGRAPHY (*Diagnostic Value = 10 when necessary!) In patients with chronic prostatitis in whom urethral narrowing (stenosis) is suspected the only useful radiographic test is micturitional retrograde urethrocystography. After instilling radio-opaque contrast medium into the bladder the test images the shape and calibre of the entire urethra during physiological micturition. This test is essential to confirm urethral stenosis. CYSTOSCOPY (*Diagnostic Value = 0/1) In our experience with patients affected by prostatitis cystoscopy is of little value and does not add to the data obtained from the other tests I have mentioned. In cases of urethro-prostatitis cystoscopy before endoscopy such as bladder neck resection or removal of urethral stenosis shows the urethra and the bladder neck are very reddened and have dilated, easily ruptured blood vessels. In the prostatic lodge blackish granules i.e. calculi in the periprostatic acini, are often observed. In cases of urethral-prostate reflux the walls of the prostatic lodge are no longer pink in colour but present with a greyish-mother-of-pearl colour because of the fibrosis caused by the chronic inflammation. Obviously this urethral tract will have lost its physiological elasticity and burning will ensue during micturition because of lack of distension during the passage of urine. 26

CHRONIC PROSTATITIS - PART 6

WORK IN PROGRESS THERAPY Federico Guercini MD, consultant urologist Guidelines Technique Antibiotic Cocktail Ancillary Medical Therapy Ancillary Surgery

GUIDELINES The guidelines for therapy which we apply in cases of chronic prostatitis follow logically from what we have expounded in the preceding sections. • Prostatitis is always caused by microbes whether they are detected or not by standard laboratory procedures • Evidence of Chlamydia, Mycoplasma, Human Papilloma Virus and herpes simplex virus is very hard to obtain in cultures or fresh samples of prostatic secretions. Anti-Chlamydia, anti-Mycoplasma, anti-HPV or anti-HSV antibodies are often found in blood samples • In the course of prostatitis the content of prostatic secretions undergoes major modifications. It becomes alkaline and concentrations of zinc, a powerful anti- bacterial agent, are reduced. • During infection the prostate tries to circumscribe the infected area by surrounding it with a polysaccaride shield which cannot be penetrated by antibiotics that are administered systemically • Bacteria exist inside the infected, obstructed calculi and acini which cannot be reached by antibiotics and which become the source of recurrent infection. 27

In patients with long-term chronic prostatitis T-cells, which are reactive to normal prostatic protein, are frequently detected (Alexander, 1977) suggesting prostatitis may be an auto-immune disease • When prostatitis is caused or perpetuated by urethral-prostate reflux because of anatomical abnormalities (bladder neck sclerosis or urethral stenosis) these causes must be removed to ensure a complete cure. The conclusion to these premises is as follows: Using ultrasound to guide therapy needs to be administered directly into the inflamed areas or inside any fibrous calcifications which amy be present. Therapy is based on a cocktail of antibiotics with an acid pH, powerful anti-bacterial agents - because bacteria cause most prostatitis - and a strong anti-inflammatory agent like cortisone which reduces oedema in the canaliculi and acini, re-establishes the normal flow of prostatic secretions and inhibits any auto-immune process which may have been triggered. At the same time a long-lasting anaesthesthetic is injected into the pelvic floor to stop spasm of the elevator anus muscles. The course of therapy I have just described is repeated three times at 15-day intervals even though symptoms may have disappeared after the first cycle. TECHNIQUE The patient is placed in the lithotomic position. After carefully disinfecting the skin with a sterile soap solution a 15 cm, 23 G mandrinate needle is inserted transperineally under ultrasound guide as far as the pelvic floor. The needle must be inserted 10 mm to the left or right of the median rafe and 10-15 mm in front of the rectal sphincter. Using a trajectory which is parallel to the horizontal plane this entry point corresponds to the prostate apex. Choice of right or left of the median rafe is dictated by the inflammation site and if inflammation is bi-lateral the procedure must be repeated on the other side. If the manoeuvre is skilfully done discomfort is slight and indeed, it has always been accepted with no bother by our patients. 15cc Carbocaine in a 2% solution are infiltrated into the pelvic floor muscles and diaphragm. After waiting a few seconds for the anaesthetic to take effect the needle is passed over the urogenital diaphragm. This is an extremely sensitive structure and if 28 not properly anaesthesized, the procedure can be very painful. The needle moves inside the lesions which have to be infiltrated (see film) with the antibiotic cocktail and cortisone (4 mg demethazone).When the infiltration is finished the needle is withdrawn and the ultrasound probe removed from the rectum. The prostate is massaged vigorously to ensure the drugs are uniformly distributed. ANTIBIOTIC COCKTAIL Correctly choosing antibiotics is fundamental to the success of therapy. As an enormous range is available on the market I shall just indicate the drugs we use and give the reasons for our choice. When bacteria have been isolated in cultures we use the most specific antibiotic indicated on the antibiogram. If the isolated bacteria is Gram- we combine the specific antibiotic with gentamycin (*Gentalyn fl 80 mg) or tobramycin (*Nebicin fl 100 mg) to provide wide spectrum cover against Gram+ germs. If the isolated bacteria is Gram+ we add aztreonam (*Azactam fl 1 gr) to cover Gram- bacteria. When Chlamydia or Mycoplasma are detected in fresh or cultured samples or specific IGG and IGM are positive we administer erythromycine (*Erythrocine fl 1 gr) together with gentamycine or tobramycine (as above). If no bacteria can be isolated (as in most cases) we administer tobramycine (as above) to eradicate Gram+ germs in association with aztreonam (as above) to combat Gram- germs. Keep in mind that administration of 1gr antibiotic directly into the prostatic capsule is the equivalent of a systemic dose 100-300 times higher. ANCILLARY MEDICAL THERAPY Before proceeding to infiltrate an antibiotic cocktail into a patient who has never before been treated for prostatitis we always attempt a 15-day oral therapy with the specific antibiotic if the bacteria has been isolated in cultures and if not, with ciprofloxacine (*Ciproxim 500 mg capsules) which also acts upon Chlamydia and Mycoplasma. This treatment is combined with a 10-day cycle of suppositories containing desametazone and tetracycline (*Mictasone). 29

If the ultrasound scan is indicative of bladder neck dyscrasia we provisionally try to reduce spasma with alphalithic drugs (Omnic 2 mg tablets) for 4-6 months. We rarely prescribe any other drugs except for capsules containing mineral supplements and zinc.

ANCILLARY SURGERY Surgery is required when anatomical abnormalities cause or perpetuate chronic prostatitis. Indications include bladder neck sclerosis, suppurating utricular cysts, urethral stenosis, ejaculatory duct obstruction. In cases of bladder neck sclerosis we remove the excess tissue endoscopically (TURP) or by simple incision (TUIP) in younger patients. The operation may cause which is reported in 8-10% of cases so it is not recommended in single men of marriageable age. When suppurating utricular cysts are present we drain the cavity transperitoneally under ultrasound guidance and inject antibiotics and cortisone. In relapses we make a large transperitoneal incision of the utriculus opening. In cases of urethral stenosis endoscopic removal of the obstruction is mandatory. When infiltrations fail in cases of ejaculatory duct obstruction or impacted stone in the Veru montanum we proceed with transurethral incision. 30

CHRONIC PROSTATITIS - PART 7

WORK IN PROGRESS Federico Guercini MD, Consultant urologist Various Life-style Diet The following section provides a series of rules for lifestyle and diet that are dictated more by common sense than by any rationale derived from clinical practice.. In our experience we have found them helpful in combating the disease. LIFESTYLE Gram- germs are the cause of most cases of prostatitis. They are found stably in the intestine and in high concentrations in faeces. Germs such as E.Coli, Klebsielle, Proteus etc. become dangerous for the prostate only if they stagnate in the ampoule of the rectum because they can be conveyed to the prostate through the lymph vessels. Consequently constipation must be counteracted as must colics and diarrhea. Besides a fibre-rich diet and anti-spasm drugs we recommend repeated cycles of high concentration lactic zymes. In patients with haemorrhoids worsening provokes the reappearance of the symptoms of prostatitis because the whole small pelvis is inflamed. We always prescribe antibiotics and local anti-inflammatory agents to cure the venous inflammation. In more serious cases we recommend surgery (haemorrhoidectomy). Some sexual habits should be avoided as they can worsen prostatitis. Intercourse should neither be prolonged or concluded suddenly (coitus interruptus). Some patients report episodes of unprotected intercourse. If the patient cannor or will not use a condom we prescribe 500 mg of a new generation quinolonic drug to be taken at least 1 hour before intercourse. 31

Some sports like cycling, motorcross and horse-riding may cause or worsen prostatitis and I can only advise stopping. Some occupations like bus or train drivers, travelling salesmen, can cause prostatitis through venous stasis due to chronic, prolonged compression of the prostate by the perineum. Every two hours 5 minutes of bending over re-establishes good circulation in the area. DIET I always advise my patients to drink 1 litre of fluids every day in the form of water, weak tea or fruit juice. This serves to dilute the urine and reduce its irritative effect on inflamed tissues. Some apparently innocuous foods make urine more acid and may worsen irritative symptoms particularly in the urethra. Such foods include tomatoes, grapes, peppers, citrus fruits etc. Other foodstuffs such as pepper, alcoholic drinks (especially robust wines) and spirits are clearly irritative. Drinking large quantities of strong tea and coffee can increase symptoms of dysuria by acting on the bladder neck.