Penile perfusion index (PPI for the non-invasive evaluation of the vascularization of the penis

ORIGINAL PAPER

Marco Grasso 1, Salvatore Ivano Blanco 1, Caterina Lania 2, Emanuele Grasso 3, Vittorio Segramora 3 .

1 Dept of Urology, San Gerardo Hospital Monza (MB), Italy; 2 Dept of Urology, San Raffaele Institute, Milano, Italy; 3 Dept of Vascular Surgery, San Gerardo Hospital Monza (MB), Italy.

dynamics (flow velocity) have been used in the evaluation of the single dorsal and cavernous arteries. This method, however, involves the use of drugs injected into the corpora cavernosa to induce a pharmacological erection, without which these evaluations are not possible in the penile area where, in conditions of rest, the vessels are small. The development of increasingly valid drugs for the treatment of erectile dysfunction (we refer to phosphodiesterase inhibitor drugs) has in fact remodeled the therapeutic approach to ED that today benefits from the use of these drugs, also tailoring the choice according to the patient`s performance requests. We have wondered whether it is still appropriate to submit patients to an examination that requires time, highly qualified personnel and high-tech and cost-effective tools, but above all, that requires mandatory invasive intracavernous injection of prostaglandins. This procedure, besides being painful, can lead to local complications, especially the fearful post-injection priapism. For this purpose, expert staff must be available for 24 hours after the exam. In the early 1980s we started using a new parameter which is the relationship between humeral pressure and cavernous pressure. We have

SUMMARY Objectives. The aim of the study is to define if PPI can be considered a sensitive, noninvasive param eter to predict the effectiveness of therapy. Material and Methods. From June 2003 to September 2016 we evaluated 422 patients for ED. We performed vascular penile evaluation with a non invasive method. In basal condition we considered the ratio between penile and humeral pressure and the response to PDE5in during follow-up. The values of PPI were compared to the recovery of erection. Results. the results show that the recovery of valid erections both after taking the drug and spontaneously occurs mainly with PPI higher than 0.8. Conclusion. A PPI value > of 0.8 proved to be an effective “predictor” of a valid response to phosphodiesterase inhibitors and therefore an indicator of correct vascularization. A value of IPP <0.8 should lead to a complete cardio-vascular study. We believe that it is no longer motivated to submit the patient to the risks of color Doppler with FIC, not producing any further diagnostic element useful to the patient.

KEY WORDS: Penile, ED, PDE5in, Doppler.

INTRODUCTION

The spread of phosphodiesterase inhibitors (PDE5in) has completely changed the approach strategies to erectile dysfunction (ED). It is still considered important in the first approach to the patient to rule out hormonal or metabolic problems and evaluate the vascularization of the penis. In the diagnosis of ED, Doppler ultrasound with drug induced erection is now performed all over the world. We believe that this examination can be replaced by a less invasive test which is the evaluation of the PPI (Penile Perfusion Index). Since the early 1980s, the evaluation of the vascularization of the penis using Doppler technology has entered in the common practice for diagnosing erectile dysfunction (1). At the beginning, simple velocimeters with pencil probes were used. Subsequently, with the development of an increasingly advanced technology designed for other districts in which lumen diameter and flow velocity are essential parameters, we switched to the use of eco-color / power doppler instrumentation. With these more modern tools, the evidence of morphological parameters (patency and diameter) as well as

defined this parameter as the penile perfusion index (2). We have, after having performed hundreds of tests and compared the results with parameters of healthy volunteers, defined as normal a PPI equal to or greater than 0.8. This parameter is easily detected by bilaterally measuring the cavernous pressure at the balanus preputial sulcus. This test can be easily performed either with a pencil probe (velocimeter) or, with higher technical difficulties, with a small linear probe. In both cases, it is not necessary to induce an erection pharmacologically. The aim of the work is to define whether PPI can be considered a valid predictive test that therefore makes a more invasive and dangerous examination useless. We then evaluated the response to phosphodiesterase inhibitors in patients with PPI lower or higher than 0.8.

MATERIALS AND METHODS

From June 2003 to September 2016 we evaluated 422 patients for ED excluding those with diabetes, known arterial disease or endocrinopathy. All patients underwent: 1. Dosage of: LH, Testosterone, Prolactin, TSH, CBC, Glycemia, Creatinine. 2. Evaluation of the arteries of the penis using either a Doppler velocimeter with a pencil probe or an Echocolordoppler with a linear probe (Figure 1, 2). With both methods, the two dorsal and cavernous arteries were identified and recorded in basal conditions. The systolic pressure of the cavernous arteries identified in the balano-preputial sulcus was measured using an inflatable neonatal sphinx-manometer positioned at the base of the penis. The systolic pressure of the humeral artery was then recorded. PPI is determined by the ratio of cavernous systolic pressure to systolic brachial pressure. Patients included in the study were treated with PDES inhibitors (sildenafil 25/50 mg, tadalafil 5/20 mg, vardenafil 10/20 mg) in accordance with the standard schedules of administration of these drugs. In all cases the lowest effective dose was used. In order to make the clinical response data simple and reproducible, we used the Sexual Encounter Profile SEP which uses a series of questions regarding sexual intercourse. We considered SEP Q2 that quantifies the penetration “Have you ever been able to insert the penis into your partner's vagina?”, and SEP Q3 which gives the real measure of therapeutic success “Did your erection last long enough to define intercourse satisfactory?”.

Figure 1. Linear probe RESULTS

The patients were all reviewed within one year after the start of therapy. We evaluated the obtaining of a positive response, that is appropriate for a satisfactory sexual inter-

Figure 2. Pencil probe

course (SEP-Q3) regardless of continuous or sporadic use. The correlation between PPI and response rate (SEP Q3 valid erection) for the various blood pressure ranges was as follows: - PPI > 0.8 = 75% (315pts, 308pts responders), - PPI > 0.7 and < 0.8 = 20% (86pts; 44pts responders), - PPI < 0.7 = 5% (21pts; 2pts responders).

In the group of patients with PPI ≥ 0.8, 46% recovered adequate natural intercourse without further taking the drug after a treatment period of 3 to 6 months. In the group with PPI < 0.8 only 8% of patients had occasionally intercourse without using drugs. There were no significant differences between the three groups of drugs used.

DISCUSSION

We have to thank Christian Andreas Doppler (Salzburg, Austria, November 29, 1803 / Venice, Italy, March 17, 1853) for his pioneering studies: “Changes in the frequency of transmitted waves when relative motion exists between the source of the wave and the observer”. In medicine, by exploiting the application of this effect to ultrasound, it is possible to study the functionality of blood vessels. The first medical applications of the Doppler effect date back to the mid-60s of the twentieth century, with the creation of a small instrument (the Flowmeter Doppler) for percutaneous measurement of blood flow. With the development of ultrasound, the combination of Flowmeter Doppler and ultrasound probe takes place in a single instrument, thus creating the Duplex Doppler technique which allows the operator to more easily identify the target point to be measured (3). In the Diagnostic evaluation of ED patients CDDU (Dynamic color duplex doppler ultrasound) is not considered mandatory in all cases. After having collected a detailed medical and sexual history of patient and having made a careful physical examination, the Dynamic duplex ultrasound of the penis, even if a second-level diagnostic test, is still today considered a decisive examination in the differential diagnosis between ED due to vascular cause (vasculogenic) or non-vascular (neurogenic, anatomical, hormonal, druginduced and / or psychogenic). It is well known to all that the objective interpretation of the examination results is very difficult due to the existing differences in the execution of the procedure between centers /hospitals due to the lack of standardization (4). CDDU is used for a morphological study of the penis (anatomy and echotexture) and vascular, usually using a 7.5-12MHz linear array U / S probe for small parts in Bmode, doppler mode should be set with an angle of 60° e 4. The target arteries of the vascular study are the intracavernosal, these are sampled before and after pharmacologically induced erection, with ICI of PGE1 at the initial dosage of 10 µg. Normally the following data are recorded: PSV (Peak sysolic velocity), EDV (End-diastolic velocity), RI (Resistive index). A PSV after ICI between 25 and 30 cm / sec is considered normal, EDV> 6cm / sec and RI <0.6 are indicative of the presence of a normal venous leak (5-6). In view of the considerable invasiveness of ICI and the reticence of many patients to this type of procedure, several authors have explored alternative evaluations. Color Duplex Doppler ultrasound without ICI can be a valid alternative, a cutoff PSV value of 10 cm / second in the flaccid state could be considered accurate in predicting arterial insufficiency (7). The cavernous arteries of the penis, if sampled at the distal end of the corpus cavernosum, are easily identifiable with a small Doppler flowmeter, even without the aid of ultrasound detection. In order to perform a simple, repeatable, fast and non-invasive evaluation of the arterial vascularization of the penis, flowmeter Doppler can be considered a valid and current technique, sufficient to diagnose ED caused by arterial disease. The method we have described and used for years is of simple execution, feasible even with a “low cost” instrument, such as the Doppler velocimeter (Figure 3). Being achieved without induced erection it practically eliminates local complications and the risk of prolonged erection. A PPI value > of 0.8 proved to be an effective “predictor” of a valid response to phosphodiesterase inhibitors and therefore an indicator of correct vascularization. A value of IPP <0.8 should lead to a complete cardio-vascular study. We believe that it is no longer motivated to submit the patient to the risks of color Doppler with FIC, not producing any further diagnostic element useful to the patient.

Figure 3. Portable Doppler Velocimeter

CONCLUSIONS

It is advisable to consider what is the sense of carrying out an invasive study of the vascularity of the penis since the therapy that can be proposed in any case includes the use of phosphodiesterase inhibitors. The baseline study with evaluation of the PPI is sufficient to determine the efficiency of the arterial system and, consequently, the possibility of a pharmacological response.

REFERENCES

1. Annoni F, Lania C, Grasso M, et al. Evaluation of penile circulation with the Doppler Technique. J. of Andrology. 1984; 5:131-134. 2. Grasso M, Lania C, Blanco S, Castelli M. Penile Perfusion Index (PPI) is an effective marker of efficacy for PDE5 inhibitors. J Urol Vol. 2012; 187,e465. 3. Dev Maulik. Doppler Ultrasound in Obstetrics and Gynaecology, Springer, 2005. 4. Sikka SC, et al. Standardization of vascular assessment of erectile dysfunction: standard operating procedures for duplex ultrasound. J Sex Med. 2013; 10:120-129. 5. Lue TF, Hricak H, Marich KW, Tanagho EA. Vasculogenic impotence evaluated by high-resolution ultrasonography and pulsed Doppler spectrum analysis. Radiology. 1985; 155(3):777-81. 6. Lee B, Sikka SC, Randrup ER, et al. Standardization of penile blood flow parameters in normal men using intracavernous prostaglandin E1 and visual sexual stimulation. J Urol. 1993; 149(1):49-52. 7. Roy C, Saussine C, Tuchmann C, et al. Duplex Doppler sonography of the flaccid penis: potential role in the evaluation of impotence. Clin Ultrasound. 2000; 28(6):290-4.

CORRESPONDENCE Marco Grasso Dept of Urology, San Gerardo Hospital Monza (MB), Italy E-mail: m.grasso@asst-monza.it Phone. + 39 3386356677