Clinical Remission of Chronic Refractory Pelvic Symptoms in Three Men

Bradley R. Hennenfent, MD
Antonio Espinosa Feliciano, Jr., MD
The Prostatitis Foundation and the Manila GenitourinaryClinic

Abstract

We report on three American men with chronic refractorypelvic pain, urinary symptoms, and sexual dysfunction who traveled to thePhilippines for treatment. In the Manila Genitourinary Clinic, the patientswere treated with microbial diagnosis, antimicrobial therapy, and 19, 27,and 21 prostatic massages respectively. All three patients underwent resolutionof symptoms.

Key words: prostatitis, prostatodynia, prostaticmassage, sexual dysfunction, infection, prostate, pelvic pain

Introduction

Attempts are being made to better define the chronic pelvicand genital syndromes that involve pelvogenital pain, urinary symptoms,sexual dysfunction, and in some cases systemic symptoms such as myalgias,arthralgias, fatigue, cognitive dysfunction, night sweats, fever, or feelingsof fever.

In prostatic fluid, ten or more white blood cells (WBCs)per oil immersion field (OIF, 1000 times magnification) are often usedas the cutoff between prostatitis and prostatodynia. Both entities aredefined as chronic when the symptoms are more than 3 months in duration.

Patients labeled chronic "non-bacterial" prostatitis orlabeled chronic prostatodynia often become incurable patients who go fromdoctor to doctor without resolution of their symptoms.

Case #1

Patient #1, a 47-year-old single sexually active male,and computer software engineer from Austin, Texas, USA, appeared at theManila Genitourinary Clinic with a chief complaint of sitting pain. Thepatient ranked his pain at nine out of ten in severity on a scale of 0to 10; with ten being the worst. Patient #1 traveled with a doughnut shapedpillow to sit on. The patient's history included a onetime episode of urethraldischarge lasting a few days, progressive testicular pain, periodic suprapubicpain, groin tenderness, slight constriction of urinary flow, intermittentpain during masturbation, pain after ejaculation, less forceful ejaculation,and decreased semen volume. The patient's symptoms were of 7 months durationat the time of presentation.

Patient #1 saw several physicians prior to coming to Manila.At a sexually transmitted disease clinic, Human Immunodeficiency Virus(HIV), syphilis, Neisseria gonorrhea, Chlamydia, and urethral swab forculture were all negative.

The first urologist seen by patient #1 noted a urinalysis(UA) that was "strongly positive" for a urinary tract infection (UTI).Microscopic examination of the expressed prostatic secretions (EPS) revealed50-60 WBCs and 10-15 red blood cells (RBCs). Diagnoses of UTI and prostatitiswere given. The patient was treated with ciprofloxacin bid for 6 weeksand then was switched to ofloxacin for several weeks without resolutionof symptoms.

The second urologist seen by patient #1 recorded a tenderprostate with "loaded" WBCs in the EPS. Chlamydia culture of the EPS wasnegative. Routine cultures of the EPS were negative. Semen cultures werenegative. Prostatitis was diagnosed. Azithromycin for one dose, and doxycyclinefor 7 days were prescribed. The patient's symptoms did not resolve. Cardurawas tried without significant relief. Ibuprofen was also not significantlyeffective.

Patient #1's last consultation was at the University ofWashington (UW). The University of Washington at that time was the onlyAmerican university receiving funding from the National Institutes of Healthfor prostatitis research, and has been pledged 3.2 million dollars in privatefunding by the Paul Allen Foundation for prostatitis research.

Patient #1's results at UW revealed 0 urethral WBCs anda urethral culture for Neisseria gonococcus was negative. The Meares andStamey 4 Glass revealed voiding bladder one (VB1): 0 WBC and 1420 colony/mlStaphylococcus coagulase negative; VB2: 0 WBC and 110 colony/ml Staphylococcuscoagulase negative; EPS 1-5 WBC/HPF and 200 colony/ml Staphylococcus coagulasenegative; and VB3: less than 1 WBC/HPF and 500 colony/ml Staphylococcuscoagulase negative. EPS cultures for Neisseria gonorrhea, Chlamydia, Mycoplasma,Ureaplasma, and Trichomonas were all negative. Rectal color Doppler ultrasoundshowed increased blood flow to the prostate. The University of Washingtonwas doing a study where they biopsied prostates and used PCR primers todetect microorganisms, but the patient #1 declined to participate in theinvasive study. No etiology of illness was discovered, and no treatmentwas offered the patient.

In the Manila Genitourinary Clinic, the patient was anormal appearing circumcised male. A direct immunofluorescence (DIF) teston a urethral smear for Chlamydia was negative. Urethral Gram's stain showed4 to 10 WBCs, yeast, and Gram-positive cocci. Digital rectal examinationdetermined the prostate to be normal in size. The examining physician felta popping sensation during prostatic massage, which to him indicated therelease of obstructed prostatic ducts. Two drops of cloudy prostatic fluidwith precipitates were expressed. EPS cultures were done for aerobic andanaerobic bacteria. The EPS was also cultured for Mycoplasma, Ureaplasma,and Trichomonas. The only organism that grew was Staphylococcus epidermidis.A urinalysis after prostatic massage was performed which revealed 0 to6 WBCs.

In the Manila Genitourinary Clinic, prostatic fluid WBCcounts are done by collecting the first drop of EPS and examining twentyfields of the Gram's stain under oil immersion field (1000 power). Thehigh and the low count in specimens are recorded. Patient #1 had 19 massageswith collection of his EPS and Gram's stain. The first EPS WBC count in patient#1 was 10 to 25. The changes in patient #1's EPS WBC counts over 19 massagesare shown in figure1.

At the first visit, patient #1 was given fluconazole 150mg as a single dose for yeast seen in the Gram's stain of a urethral swab.Patient #1 was also given metronidazole 2 grams p.o. empirically as a singledose because of the high white blood cell count in the EPS.

At the second massage ofloxacin 400 mg bid and doxycycline100 mg bid were started based on the sensitivities of the Staphylococcusepidermidis to antibiotics. Urethral inflammation disappeared after thesecond visit.

At the third visit, yeast was again seen in the EPS andfluconazole 150 mg as a single dose was repeated. The ofloxacin and doxycyclinewere continued.

At the ninth visit, metronidazole 2 grams p.o. times onedose was again given because of the high number of WBCs in the EPS. Atthe 11th massage, doxycycline was stopped because the patientwas having difficulty tolerating the medication. At the 14thmassage, minocycline was added because Staphylococcus Epidermidis grewagain and was sensitive. At the 17th massage, antibiotics werestopped. Itraconazole 200 mg bid times for one day, then 100 mg oncea day for two days was given empirically to prevent yeast overgrowth. Patient#1's Gram's stains and cultures are summarized in table1.

Using the 0 to 10 symptom score, with zero being no symptomsand ten being the worst possible symptoms, patient #1 started out at 9on his symptomscore. The symptoms dropped to 0 at theninth massage, and consistently stayed at 0 after the 13th massage (figure2). The last three cultures for Staphylococcus epidermidis were allnegative.

During treatment, patient #1 was prescribed a total of5 different antimicrobials. These are summarized in table2.

Case #2

Patient #2, a forty-year-old single sexually active male,a medical equipment salesman from Philadelphia, Pennsylvania, USA presentedto the Manila GU Clinic with a chief complaint of intermittent perinealpain for one and one-half years. He also complained of left testicularpain, rectal pain, pain in the lower back, pain in the penis, pain duringurination, pain in the upper thighs, the bladder not feeling completelyempty after urination, the need to urinate again less than 2 hours afterurinating, stopping and starting during urination, difficulty postponingurination, weak urinary stream, having to push or strain to urinate, gettingup one or more times a night to urinate, difficulty ejaculating, difficultymaintaining an erection, night sweats, and reported intermittent low-gradefever for several months, myalgias, and arthralgias.

Patient #2 saw several physicians prior to arrival inthe Philippines. At an STD clinic, Neisseria gonorrhea, syphilis, Chlamydia,and HIV were negative, as was a urethral swab for culture. Patient #2 wentto multiple other physicians including three urologists. Repeated urinalyseswere negative. One urologist at Temple University attempted a Meares andStamey localization procedure but no EPS was obtained. Patient #2 was treatedwith many antibiotics including doxycycline, sulfamethoxazole, ofloxacin,amoxicillin/clavulanate, fluconazole, and metronidazole. He was given variousdifferent diagnoses including prostatitis, urethritis, and epididymitis.Ibuprofen was taken without effect.

During the first visit at the Manila Genitourinary Clinic,the physical examination revealed normal circumcised genitalia. The Gram'sstain of the urethra showed 0 to 2 WBCs. The prostate was enlarged andboggy. A Gram's stain of the EPS revealed 0 to 4 WBCs. A UA after prostaticmassage was normal. Cultures for aerobes, anaerobes, Mycoplasma, Ureaplasma,and trichomonas were done, and were negative. A direct immunofluorescencetest for Chlamydia of the urethra was also done. Ofloxacin 400 mg bid wasstarted empirically.

The patients Chlamydia DIF was known to be positive atthe second visit, and minocycline 100 mg bid was added. At the third massageitraconazole 100 mg 2 caps bid times 1 day was given for yeast in the urethraand the EPS. At the fourth visit, ofloxacin was stopped because of CNSside effects. Minocycline was continued until the 12th massage.

At the 13th visit, all cultures were repeated.Chlamydia DIF was negative. Itraconazole 100mg 2 caps bid times one day,and then 100 mg a day was started empirically because of the course ofantibiotics. Because of RBCs seen in the EPS by the 14th massage(usually associated with Staphylococcus epidermidis or yeast in the clinic'sexperience), a switch in antifungals to ketoconazole 400 mg per day wasmade.

At the 15th visit, Staphylococcus epidermidishad grown.
Amoxicillin/clavulanate 625 mg tid was started. At the 22ndmassage, ketoconazole 400 mg a day was started.

Cultures at the 23rd massage were negative.The Amoxicillin/clavulanate was stopped. Fungus was seen in the EPS ofthe 23rd, 24th, and 25th massages. Antifungaltherapy was switched to itraconazole 200 mg bid x one day, then 100 mgq day x 19 days. No Staphylococcus or fungus was present at the 26thmassage or the 27th (last) massage.

A summary of patient#2's Gram's stains and cultures are in table3. The EPS WBC counts over 27 massages in Figure3. Patient #3 received a total of 5 different antimicrobials (table4).

By the end of massage therapy, Patient #2's prostate wasdecompressed by the massages and the consistency of his prostate had improved.His symptom score started at 10 out of 10 in severityand dropped to 0 (no symptoms) by the end of the treatment protocol (figure4).

Case #3

Patient #3, a 40 year-old divorced sexually active criminalinvestigator, presented to the Manila Genitourinary Clinic with suprapubicpain and lower back pain of 15 months duration. He also complained of pre-matureejaculation, pain after ejaculation, intermittent impotence, decreasedquality of erections, myalgia, arthralgias, fatigue, and feelings of fever.

The patient's first entry into the health care systemhad been to the emergency department New York City after sudden onset ofpelvic pain and feeling feverish. He was given muscle relaxants, whichdid not relieve his symptoms.

Patient #3's local urologist noted prostate tendernessand microscopic hematuria. A cystoscopic examination revealed redness ofthe prostatic urethra. A ten-day course of ofloxacin was given with reliefof symptoms. Symptoms returned 2 days after coming off the antibiotic.Ofloxacin for 6 weeks was given, with some relief, but again symptoms returnedafter the antibiotic was stopped.

At Mount Sinai Medical Center in New York, a urologistperformed an ultrasound and did another cystoscopy. Again, erythema ofthe prostatic urethra was noted. Doxycycline for 4 weeks and a non-steroidalantiinflammatory was given with intermittent relief of symptoms. Ciprofloxacinwas prescribed but symptoms continued. The patient tried various herbaltherapies without relief. The patient visited a urologist at Cornell MedicalCenter, where he was told he would have to live with his symptoms.

An obstetrician-gynecologist gave patient #3 intravenousgentamicin and clindamycin with a decrease in symptoms. Symptoms returnedafter the medications were stopped.

Another physician prescribed diazepam, which gave transientrelief of symptoms. The nonsteroidal antiinflammatory oxaprozin (Daypro)also had temporary benefit.

At the Manila GU Clinic, the physical exam revealed normalcircumcized genitalia. The urethral WBC count was 0-1. A Gram's stain ofthe urethra showed Gram-negative coccobacilli and Gram-positivecocci. The EPS WBC was 0-2. Changes in this patient's EPS WBC count astherapy continued are shown (figure5). At the second massage, Gram-negative diplococci (extracellular)were seen in the EPS.

At the third massage Staphylococcus aureus had grown andminocycline 100 mg bid was started. Since multiple bacteria were seen onthe Gram's stain of the fourth massage's EPS, ciprofloxacin was added.

The 4th massage revealed 5-20 WBCs in the EPS, and metronidazole,2 grams p.o., as a single dose was given empirically.
Ciprofloxacin was stopped at the 13th massageand minocycline was stopped at he 14th massage. Itraconazolewas started empirically at the 13th massage. A summary of patient#3's Gram stains and cultures are shown in table5.

Patient's #3's symptom score went from10 (worst possible) to 0.5 (on the 0 to 10 symptomscore) by the end of treatment (figure6). While in Manila, patient #3 received a totoal of 4 different antimicrobials(table6). For financial reasons, patient #3 returned to the USA where hesought out a physician willing to continue to do massages and give antimicrobialtherapy. He received both massages and antibiotics for several more weeks.Finally, even the last 0.5 of his symptoms resolved. He remains completelyasymptomatic today.

Discussion

This paper presents the case reports of three patientswith symptomatic cures of chronic refractory pelvic symptoms, and describestheir diagnostic and treatment protocols in detail. That these patients'symptoms are consistent with what is commonly diagnosed as nonbacterialprostatitis or prostatodynia is clear by comparison to recent studies,1,2and from the results of their laboratory studies.

This study is too small to make any valid conclusionsabout correlation between white blood cell counts and symptom scores. Nevertheless,correlation coefficientswere calculated. In 5 of 6 instancesa weak correlation was found between the WBC counts and the symptom scores(table 7).It is hoped that a future study with greater sample size will determineif a true relationship exists between WBCs in the EPS and symptom scores.

According to the pathologist John McNeal, the prostategland is the most commonly diseased internal organ of the human body.3Of the three major prostate diseases: prostate cancer, benign prostatichyperplasia, and prostatitis; prostatitis results in the most physicianvisits.4

Prostatitis is separated into four categories: acute bacterial,chronic bacterial, nonbacterial, and prostatodynia by cultures and theWBC count in the EPS. Ten or more white blood cells per oil immersion field(OIF 1000 x magnification) is arbitrarily used as the division betweenprostatodynia and prostatitis.5,6,7,8 The authors have shownin prior work that a one-time collection of EPS is misleading for makinga diagnosis and does not allow for the most purulent specimens to be collectedfor Gram's stain and culture.9 Urologist Gordon Pilmer reachedthe same conclusion in 1962, when he wrote: "Often six or eight 'provocative'massages will be necessary before pus can be found in the secretion."10

The Meares and Stamey localization test has been consideredthe gold standard for diagnosing the prostatitis syndromes since 1968 whenit was published based on only 6 patients.11 Using this methodapproximately 90% of patients with chronic pelvic symptoms are labeledchronic nonbacterial prostatitis or prostatodynia.12,13

In early 1996, reports started appearing on the InternetUsenet newsgroup, sci.med.prostate.prostatitis from men claiming to havebeen cured of chronic nonbacterial prostatitis or prostatodynia by a treatmentprotocol in the Philippines. These reports were noteworthy because someof these men had been to multiple urologists and had undergone extensiveworkups.

The Manila Genitourinary (GU) Clinic's protocol consistsof thrice-weekly (or more frequent) prostatic massage, microbial testingand antimicrobial therapy. The protocol essentially combines two "goldstandard" therapies for prostatitis: repetitive prostate massage and antibiotics.Pathologists recognize obstruction as a component of prostatitis;14however, the concept of prostatic massage was largely dropped as a therapyafter the introduction of antibiotics in the 1970's without proper clinicalstudies ever being done. The Manila treatment protocol is based on theprinciple that to cure infection, obstruction must also be relieved.15

It is the intent of the physicians in the Manila GU Clinicto completely drain the entire prostate of secretions by thrice-weekly,or more frequent, prostatic massage. Massage is done in the direction inwhich the glands drain. The prostate is not pressed straight down upon.Pressure is applied from the lateral margins obliquely towards the midlinegrove down one side of the prostate and then the other, from the superiorpole of the prostate to the inferior apex to drain the peripheral zone.The central zone glands drain more directly straight down from the backof the prostate to the verumontanum in a cephalad to caudal direction.The massages are meticulous, with every aspect of the reachable prostatebeing drained. Increasing pressure is applied during the thrice-weeklymassages as tolerated by the patients.

The anatomic feature of the prostate that makes drainageof the gland possible by DRE is that all glandular tissue is posteriorto the urethra. The anterior prostate is fibromuscular tissue not glandular.The Manila GU Clinic physicians do not believe that the prostate itselfcan be damaged if it is massaged in an anatomically correct manner. Theoreticalconcerns with thrice-weekly prostatic massage are bradycardia, syncope,16exacerbation of heart disease, anal fissure, or irritation of hemorrhoids.No harmful side effects were seen in these three patients.

Using the above technique of prostatic massage one ofthe authors (Feliciano) obtained EPS in 100% of attempts in these threepatients.

Despite Gram-positive infections of the prostate documentedby the Meares and Stamey technique, and electron microscopic evidence ofGram-positive organisms in prostate tissue biopsies, the role of Gram-positivebacteria as pathogens in prostatitis remains controversial.17,18,19,20Since assuming Gram-positives are contaminants puts the majority of prostatitispatients into the incurable category of nonbacterial prostatitis or prostatodynia,21,22,23the Manila Genitourinary Clinic assumes that Gram-positive bacteria areeither primary or secondary bacterial pathogens, and assumes that the prostaticfluid should be sterile as seen on Gram's stain and by culture. This approachis opposite the conventional wisdom in North America and Europe, however;it is a recognized surgical principle that indigenous microbial flora cancause disease when local host barriers break down.24

There has been a movement to remove prostatodynia fromthe classification of prostatitis syndromes.25 In light of thepaper by Tulane researchers demonstrating bacteria (mostly coagulase negativestaphylococci) in prostatodynia patients that was not present in controls,26prostatodynia deserves a second look using the technique of repetitiveprostatic massage.

A criticism has been made, suggesting that repetitiveprostate massage causes white blood cells to appear in the prostate fluid.The authors have done a Medline search and a manual literature search andhave not found a documented case in the medical literature suggesting thatmassage of any gland in the human body causes pus to occur in its secretions.Nonetheless, further study is warranted.

The authors do not discount the idea that some as yetunidentified bacteria may be responsible for prostatitis in many cases.In lieu of the use of DNA technology to conquer other inflammatory diseases27once of unknown etiology such as Cat-scratch disease, bacillary angiomatosis,Whipple's disease and ulcer disease, the authors suggest using DNA technologyon the most purulent prostatic fluid secretions to see if unculturableorganisms are involved. Krieger, et al., found bacterial 16s rRNA in 77%of patients with "nonbacterial" prostatitis from perineal prostate biopsyspecimens in which skin contamination was controlled. In addition, another8% of the patients had Mycoplasma genitalium, Chlamydia trachomatis, orTrichomonas Vaginalis.

These 3 patients were cultured for anaerobes, and eventhough the cultures were negative the patients were still treated empiricallywith metronidazole.29 Anaerobes have been implicated in prostatedisease, even causing prostatic abscess.30,31,32,33,34,35 TheManila Genitourinary Clinic treats anaerobes empirically on the assumptionthat all these bacteria cannot be cultured or are too expensive to culturewith current culture methods.36 This is similar to how pelvicinflammatory disease in women is treated.

Antifungal agents were prescribed on the basis of buddingyeast seen in the Gram's stains of the urethral smears or EPS, or empiricallyafter courses of antibiotics.

The authors believe that new technology must be broughtto bear against the chronic urogenital syndromes. DNA technology shouldbe used to map out the normal flora of the urogenital system using thelocalization technique of Meares and Stamey, while also controlling forthe organisms on the skin of the penis. EPS should be examined using allculture methods and all DNA techniques in order to delineate completelyall pathogens. It is important to note that the Meares and Stamey localizationtechnique either was not done, or did not play a role in the cure, of anyof these patients.

Finally, and independent study appears to support theconcept of repetitive prostatic massage combined with antimicrobial therapyin patients with chronic pelvic symptoms. The study's abstract by urologistDaniel Shoskes, entitled, Evaluation of Combined Antibiotic Therapyand Regular Prostatic Massage for Chronic Prostatitis is presentlyon the World Wide Web at http://www.ben2.ucla.edu/~dshoskes/abstracts.html. Dr. Shoskes treated 28 patients who had been seen by an average of 4.5physicians prior to treatment without clinical cure. Forty-three percentof the patients in the study; however, underwent complete resolution ofsymptoms, and 36% had some improvement in symptoms with repetitive prostaticmassage and antimicrobials.37

Conclusion

Three continuously symptomatic patients with chronic refractorypelvic pain syndromes are presented who had been diagnosed as prostatitisafter being seen at reputable institutions. The patients were entered intothe Manila Genitourinary Clinic protocol of thrice-weekly prostatic massage,antimicrobial diagnosis, and antimicrobial therapy. All three patientsunderwent resolution of their symptoms as determined by a global symptomscore, and remain free of symptoms after treatment at 29 months, 26 months,and 15 months respectively.

The consultant statisticians for this paper were JesusN. Sarol, Jr., Msc, and Raphael Isingo, from the University of the Philippines College of Public Health. Thanks to patient #1, patient #2, and patient#3 for opening their medical records to the authors, for proofreading the article, and for providing letters to accompany this article verifying its accuracy and authenticity.

References

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