Porcine small intestinal submucosa is not an ideal graft material for Peyronie's disease surgery

PURPOSE: The incidence of Peyronie's disease is up to 7% in some series. While there are numerous nonsurgical methods of treatment, they do not have a high rate of success. Nesbit plication was once the accepted surgery for Peyronie's disease. Tunical lengthening procedures became popular because they avoided penile shortening caused by the Nesbit procedure. More urologists now perform plaque incision or excision, followed by grafting with different materials. Small intestinal submucosa offered promise as an ideal graft material. It is available off the shelf as 1 or 4-ply graft material. In several studies it appeared to function as a collagen based scaffold with graft incorporation in host tissue. MATERIALS AND METHODS: A single reconstructive urologist performed plaque incision and small intestinal submucosa grafting in 4 cases of Peyronie's disease using the same surgical technique. RESULTS: Although early results were positive, we have achieved less than satisfactory results with this material. The penis was straight in the immediate postoperative period but there was recurrent curvature in 3 of the 4 patients, of whom 2 had recurrence within 4 months of the procedure. CONCLUSIONS: We observed disappointing results with small intestinal submucosa for Peyronie's disease surgery with a high percent of recurrent curvature. Further studies are needed to determine if 1 or 4-ply small intestinal submucosa is an ideal graft material for the tunica albuginea.     

Complications of porcine small intestine submucosa graft for Peyronie's disease

PURPOSE: We report outcomes and complications of the use of porcine small intestine submucosa for correcting penile curvature due to Peyronie's disease. MATERIALS AND METHODS: A retrospective study was performed in patients with severe penile curvature (greater than 60 degrees) requiring surgical correction for sexual function. Preoperatively all patients underwent evaluation, including history, physical and penile duplex ultrasound. Of these patients 19 underwent tunical grafting with 1-layer Surgisis small intestine submucosa. Postoperatively patients were evaluated with clinic visits and telephone interviews to assess results. RESULTS: A total of 19 patients 46 to 69 years old (mean age 54) were treated with tunical incision or excision and grafting with small intestine submucosa between March 2002 and July 2005. Average followup was 15 months (range 3 to 43). Patients reported less penile pain with intercourse after surgery. There was no difference in Sexual Health Inventory for Men scores. Preoperatively 12 men (63%) had erectile dysfunction, defined as Sexual Health Inventory for Men less than 21, while 10 (53%) reported postoperative erectile dysfunction. Seven of the 19 patients (37%) had recurrent penile curvature (greater than 10 degrees) and 5 (26%) had recurrent Peyronie's disease plaque. Our complication rate was 37%, including hematoma at the graft site in 5 cases (26%), graft infection in 1 (5%) and Peyronie's disease recurrence requiring plication in 1 (5%). CONCLUSIONS: Small intestine submucosa carries potential for grafting applications because it is easy to use and readily available. Our experience resulted in a 37% complication rate, which exceeds those previously reported with saphenous vein graft repair.     

Factors affecting the loss of length associated with tunica albuginea plication for correction of penile curvature

PURPOSE: Loss of length is a common postoperative complaint of the patient who undergoes surgical correction of penile curvature. We investigate the factors influencing complications in patients who have undergone TAP for PD and chordee. MATERIALS AND METHODS: A total of 102 patients underwent TAP for PD (68) or chordee (34) between 1997 and 2004. Data were gathered on each patient's preoperative complaints, physical examination, Doppler ultrasound, operative data and postoperative complaints. For the purposes of this study penile length was measured from pubis to corona along the dorsal surface of the stretched phallus. RESULTS: Mean ages at surgery for men with PD and chordee were 53 and 24, respectively. A range of 1 to 6 plications were performed on each patient (mean 3) with an acceptably straight penis (curve less than 20 degrees) being achieved in 99% of patients. Mean followup for our patient population was 29 months and revealed only 1 patient with residual curvature. The mean loss in length after TAP was 0.36 +/- 0.5 cm with a range of 0 to 2.5 cm. When calculated as a percent of length lost from preoperative length, the postoperative percent length lost was 2.4%. When stratified into groups based on direction of curvature, the patients with ventral or ventrolateral curve had the highest percent loss of length. A 1-way ANOVA of these groups proved the differences between each group to be statistically significant (p = 0.04). Length change also significantly correlated with preoperative stretched penile length and the severity of curvature as measured in degrees in the operating room at time of surgery. Parameters that did not demonstrate a statistically significant impact on penile shortening included patient age, number of plications performed, plaque size, and hinge/narrowing effect due to a PD plaque. CONCLUSIONS: The TAP procedure is a safe and effective means of correcting penile curvature, with similar overall outcomes between patients with PD and chordee. Shortening of the penis does commonly occur but is dependent on direction and degree of curvature, as well as the length of the phallus.     

Transdermal application of verapamil gel to the penile shaft fails to infiltrate the tunica albuginea

PURPOSE: There currently exists no universally accepted pharmacotherapy for Peyronie's disease. Recently interest has grown in transdermal agents, including verapamil. We evaluated the ability of a commercially available verapamil gel applied to the penile skin to infiltrate the tunica albuginea. MATERIALS AND METHODS: In men scheduled to undergo penile prosthesis surgery for erectile dysfunction verapamil gel was applied to the penile shaft the night before and morning of surgery. Urine was obtained at the commencement of the implant operation and tunical samples were excised from each corporeal body intraoperatively. Verapamil quantification was performed in all specimens using high pressure liquid chromatography. RESULTS: All patients tolerated verapamil gel application without any adverse events. A mean of 1.1 gm. tunical tissue was excised. Mean verapamil concentration in the urine was 46 ng./ml. No verapamil was detected in any tunical specimens. CONCLUSIONS: These data indicate that applying transdermal verapamil gel to the penile shaft results in a small amount of systemic absorption but the gel does not infiltrate the tunica albuginea. Based on these findings the use of transdermal verapamil for Peyronie's disease has no scientific basis.     

Corporoplasty using tunica albuginea free grafts for penile curvature: surgical technique and long-term results

PURPOSE: A Nesbit or plication procedure for correcting penile deformities is associated with penile shortening, especially in patients with excessive curvature and/or rotation. On the other hand, grafting procedures are associated with poor postoperative results due to graft shrinkage and veno-occlusive dysfunction. To minimize penile shortening and preserve potency we describe a new surgical technique combining the Nesbit procedure with tunica albuginea free grafting. Long-term functional results and patient satisfaction are reported. MATERIALS AND METHODS: We treated 17 potent patients with a mean age plus or minus standard deviation of 46.1 +/- 14.5 years, including 4 with congenital penile deviation and 13 with stabilized Peyronie's disease. Opposite the point of maximal curvature a typical Nesbit procedure was performed. The excised tunica albuginea segment consequently served as a free graft. A symmetrical incision was made at the opposite site and the preserved elliptical tunica albuginea graft was placed in the defect. Further elliptical excisions and grafting followed as needed to correct the deformity. RESULTS: At a mean followup of 39.5 +/- 13.7 months (range 18 to 62) all patients reported penile straightening and functional erection, while ultrasonography of the corpora cavernosa revealed no changes in graft ultrastructure. There was penile shortening in 8 patients (47%) but only 2 (11.7%) considered it significant. All patients with a minimum 2-year followup were positive in regard to recommending the operation to others or repeating it if necessary. CONCLUSIONS: The newly described technique may be considered as a treatment option in patients with excessive penile curvature since shortening of the penile shaft is eliminated by 50% compared with the result of the Nesbit procedure. Tunica albuginea seems to be an appropriate grafting material since it prevents postoperative corporeal veno-occlusive dysfunction.     

Corporoplasty for advanced Peyronie's disease using venous and/or dermis patch grafting: new surgical technique and long-term patient satisfaction

PURPOSE: We evaluated long-term results and patient satisfaction after corporoplasty using saphenous vein and/or dermis patch grafting in patients with advanced Peyronie's disease. MATERIALS AND METHODS: A total of 20 patients who underwent venous and/or dermis patch corporoplasty were followed a mean of 19 months. Postoperatively patients satisfaction was assessed using the International Index of Erectile Function questionnaire. The mean preoperative grade of deviation in this collective was 86 degrees, frequently associated with additional malrotation. RESULTS: Intraoperatively the deviation was straightened in all cases. Postoperatively 20% of patients complained of 1 or 2 cm. penile shortening and in 25% there was a slight deviation relapse of 5 to 15 degrees. Only 2 patients had recurrence (30 and 70 degrees, respectively. In 3 cases (15%) postoperative erectile dysfunction was treated successfully with sildenafil or prostaglandin E. Overall postoperative sexual satisfaction score on the International Index of Erectile Function was 2.76 of a possible 5, although erection and cohabitation status were rated higher with at 3 and 2.94, respectively. CONCLUSIONS: Saphenous vein interposition is safe and effective for high grade Peyronie's disease. In cases of insufficient vein anatomy additional dermis patch interposition is a good alternative. The limited median postoperative patient satisfaction score even for minor procedures with good objective results indicates only moderate overall satisfaction at a mean of 19 months postoperatively, which was likely due to high preoperative patient expectation of surgical correction.     

Tunica albuginea tissue analysis after electromotive drug administration

PURPOSE: To minimize patient discomfort electromotive drug administration has been used as noninvasive transdermal therapy for Peyronie's disease. We directly measured the tissue concentration of verapamil after electromotive drug administration to investigate whether this treatment modality is an effective drug delivery system. MATERIALS AND METHODS: A total of 19 tunica albuginea samples from 16 men undergoing surgical treatment for Peyronie's disease were used for analysis. Of these 16 men 14 underwent electromotive drug administration, including 12 with 10 mg. verapamil and 2 with 10 mg. verapamil plus 0.05 mg. epinephrine. In 2 men partial plaque excision was performed and the tunica albuginea samples were directly injected with verapamil. Another 3 men who served as controls had no exposure to verapamil. Electromotive drug administration was performed at an output of 2 mA. for 20 minutes. Tissue analysis was done using liquid chromatography-tandem mass spectrometry. RESULTS: Control tunica albuginea samples showed a verapamil level that was undetectable up to 109 ng./gm. The 14 verapamil electromotive drug administration treated specimens demonstrated undetectable to 37,510 ng./gm. verapamil. Overall 10 of the 14 electromotive drug administration treated tunica albuginea specimens (71.5%) contained measurable levels of verapamil. Adding epinephrine to the drug solution did not appear to enhance drug delivery. The concentration of verapamil in the 2 direct verapamil injection tunica albuginea samples was 166,898 and 118,411 ng./gm., respectively. There were no surgery or electromotive drug administration related complications. CONCLUSIONS: Electromotive drug administration is a safe and noninvasive treatment modality. Verapamil was detected in 71.5% of tunica albuginea specimens after electromotive drug administration with a wide range of verapamil levels. To our knowledge whether these levels affect change in Peyronie's disease plaque, resulting in improvement in penile deformity, is unknown and requires further placebo controlled trials.     

Correction of penile curvature using the 16-dot plication technique: a review of 132 patients

PURPOSE: We review the results of 132 cases of congenital and acquired penile curvature corrected with our 16 or 24-dot, minimal tension technique using multiple parallel plications performed under papaverine induced erection. MATERIALS AND METHODS: Chart and telephone interviews were conducted on 132 consecutive patients 16 to 79 years old who underwent penile plication between December 1995 and November 2000. Patient data as well as outcomes were analyzed. RESULTS: We were unable to contact 8 patients. Of the patients 16 had congenital penile curvature, including 4 in whom the Nesbit procedure performed elsewhere had failed, and 116 had Peyronie's disease, including 8 in whom a previous Nesbit procedure had failed. Preoperative complaints included persistent penile pain with erection for more than 1 year in 15 of 132 cases, difficult intercourse or partner discomfort in 106 and poor self-image in 11. Curvature ranged from 30 to 120 degrees. Erections were evaluated preoperatively with duplex ultrasound after intracavernous injection and self-stimulation. Of the patients 63% had good erections, 25% moderate erections requiring sildenafil and 12% poor erections requiring injection therapy. Foreskin edema necessitating subsequent circumcision and an organized hematoma requiring evacuation occurred in 1 case each. At 6 months 93% of patients reported straight erections and 7% reported almost straight but acceptable erections. Recurrence of curvature was reported by 15% of patients at a mean of 2.6 years of followup. Four patients reported worsening of erectile function after the procedure. CONCLUSIONS: Penile plication is a simple, safe method to correct congenital and acquired penile curvature. Using a minimal tension parallel plication technique, excellent durable results can be attained. This simplified repair avoids the neurovascular bundles and has a minimal to no detrimental affect on erectile function. Preoperative counseling must be given regarding penile shortening and the palpable small bumps from the nonabsorbable sutures.     

Evaluation of small intestinal submucosa as scaffolds for intestinal tissue engineering

BACKGROUND: Biodegradable scaffolds have been used for regenerating the small intestine. The aim of this study was to evaluate the feasibility of small intestinal submucosa (SIS) as scaffolds for intestinal regeneration in a rat model. MATERIALS AND METHODS: A tubular one-ply or four-ply SIS was interposed between isolated jejunal segments in rats. The scaffolds were harvested at 2, 4, and 8 weeks after implantation, and the specimens were examined grossly and histologically. RESULTS: Significant contractions were observed in SIS scaffolds after implantation. The one-ply SIS contracted to 44% of its initial length at 2 weeks and continued to contract to 6% of its initial length at 8 weeks. The contraction of four-ply SIS scaffolds was less than that of the one-ply SIS, reaching 29% of its initial length at 8 weeks. Minimal epithelial and smooth muscular regeneration was observed in the SIS scaffolds after implantation. CONCLUSIONS: A significant shrinkage was observed in the SIS scaffolds after implantation. Although the four-ply SIS contracted less than the one-ply SIS, neither scaffold supported significant amount of intestinal regeneration.     

Experimental evaluation of small intestinal submucosa as a microvascular graft material

The evaluation of porcine small intestine submucosa (SIS) in a microsurgical model was conducted using an interpositional graft in the rat femoral artery. The SIS grafts were fabricated from processed porcine material that was wrapped around a glass tube and oversewn longitudinally to produce a tubular structure. Of the 42 animals studied, 7 received grafts of untreated SIS (group I), 7 of the grafts were presoaked (PSH) in heparin (Group II), 7 animals were treated with systemic heparin prior to implantation of PSH-SIS (group III), 7 animals received SIS grafts crosslinked to heparin (group IV), 7 animals received SIS grafts crosslinked to urokinase (group V), and 7 animals received untreated autologous epigastric vein grafts (group VI). Patency was assessed postoperatively and selected grafts were evaluated by histology. All SIS grafts failed to maintain patency beyond the first postoperative hour. Histologic examination of the thrombosed graft surfaces revealed a smooth luminal surface with a thick layer of attached fibrin and platelets with a central occluding thrombus. The thickness of the induced fibrin layer appears to narrow intraluminal space significantly at the microvascular level. While having excellent success at vessel diameters greater than 3 mm, and in a variety of nonporcine animal models without xenographic rejection, SIS in this model was thrombogenic despite a favorable surface morphology as demonstrated by SEM. Even with use of heparin and urokinase SIS graft thrombosis occurred. © 1994 Wiley-Liss, Inc.     

Small intestinal submucosa as a small-diameter arterial graft in the dog

Autogenous saphenous vein, human umbilical vein, modified bovine collagen, Dacron, and PTFE have been used as small-diameter arterial grafts with moderate success. We tested autogenous small intestine submucosa as a small-diameter arterial graft in both a carotid and femoral artery (mean ID 4.3 mm) of 18 dogs (total of 36 grafts). All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by Doppler ultrasound techniques and angiography. Two grafts ruptured and 5 grafts occluded by 21 days after surgery. One graft became occluded at 14 weeks. Fifteen dogs were sacrificed at periodic intervals until 48 weeks after surgery. Patent grafts had no evidence of infection, propagating thrombus, or intimal hyperplasia. Graft aneurysmal dilation occurred in 4 grafts (11%). The grafts were composed of a dense organized collagenous connective tissue with no evidence of endothelial cell growth on the smooth luminal surface. Three dogs are alive at 76 to 82 weeks after surgery. Overall, graft patency was 75%. Graft patency after cessation of anticoagulation therapy was 92.3% (12 of 13 grafts). We conclude that autogenous small intestinal submucosa can be used as a small-diameter arterial graft in the dog and is worthy of further investigation.     

Trauma as the cause of Peyronie's disease: penile fracture as a model of trauma

PURPOSE: This study was performed to determine whether patients with penile fracture or a long history of forcefully bending the erect penis (taqaandan), as models of acute and chronic penile trauma, had an increased rate of Peyronie's disease (PD). MATERIALS AND METHODS: The study included 193 surgical cases of penile fracture (average followup 85 months), 150 cases of long history of taqaandan, and 50 cases of PD. All 3 groups of patients were interviewed and physically examined. RESULTS: Signs of PD were found in only 1 case of long-term taqaandan and in no case of penile fracture. None of the 50 cases of PD had a history of penile fracture. CONCLUSIONS: Severe, acute trauma of penile fracture and moderate, chronic buckling injury of taqaandan are not associated with later development of PD. These findings question whether the hypothesis that trauma, trauma-induced smoldering inflammatory cascade and aberrant wound healing are the main causes of PD. Alternative, plausible, evidence based explanations should be sought for the etiology of PD. Any theory on the etiology of PD should provide an explanation for total lack of occurrence of PD following the trauma of penile fracture.     

Porcine small intestinal submucosa as a percutaneous mid-urethral sling: 2-year results

OBJECTIVE: To report the 2-year follow-up results on patients treated with a novel minimally invasive outpatient procedure for placing a mid-urethral sling, using porcine small intestinal submucosa (SIS). PATIENTS AND METHODS: Thirty-four women with urodynamic evidence of stress urinary incontinence (SUI, 19) or of SUI with a positive cough test (15) were treated. A curved ligature carrier was used to create a tract between bilateral suprapubic stab incisions and a 2-cm mid-urethral vaginal incision. A suture secured to each end of the SIS sling was placed through the eyelet of the ligature carrier. Extraction was used to position the sling at the mid-urethra, providing a backboard of support that was remodelled with ingrowth of the patient's autologous tissue. RESULTS: SUI was reportedly cured in 27 of the 34 women (79%) at the 2-year follow-up; three (9%) of those with no complete resolution were pleased with their results, because the improvement allowed them to wear an average one or fewer pads per day. One patient developed de novo urge incontinence. Three patients (9%) developed suprapubic inflammation at 10, 21 and 45 days after surgery; all resolved, but one had a recurrence of SUI. No prolonged retention, erosion or other complications were noted. CONCLUSIONS: Early results with the percutaneous mid-urethral placement of SIS are promising and potentially comparable with those after using synthetic minimally invasive slings.     

Small intestinal submucosa as a large diameter vascular graft in the dog

Autogenous saphenous vein and synthetic materials, such as Dacron and expanded polytetrafluoroethylene, have been used extensively as vascular grafts with moderate success. Improved success rates for vascular graft surgery may be possible if superior graft material was available. We tested the use of autogenous small intestinal submucosa (SIS) as a large diameter (10 mm) vascular graft in the infrarenal aorta of 12 dogs. One dog died with graft thrombosis within 48 hr of surgery. Nine dogs were sacrificed at various times during a 52-week post-surgical period and showed patent grafts without infection, thrombosis, intimal hyperplasia, or adverse effects upon blood pressure. There was no ultrastructural evidence of endothelial cell growth on the luminal surface of the SIS graft which was composed of a dense, non-thrombogenic, organized collagenous connective tissue. The SIS material was approximately one order of magnitude less elastic than natural aorta and showed an immediate dilatation of approximately 18% after exposure to the systemic blood pressure. However, there was no progressive dilatation during the 52-week postsurgical period. Two dogs remain alive at 8 and 52 weeks post-surgery with patent grafts as determined by positive contrast radiography and Doppler studies. We conclude that autogenous small intestinal submucosa can be successfully used as a large diameter arterial graft in the dog and is worthy of further investigation.     

Use of single layer small intestinal submucosa for long segment ureteral replacement: a pilot study

PURPOSE: Previous studies have demonstrated successful use of small intestinal submucosa (SIS) as a tube for replacing short segment (11 mm) proximal ureteral defects. However, such small segment ureteral defects could be managed by resection re-anastomosis. We evaluated the use of 1-layer SIS as a tube for the replacement of long segment ureteral defects. MATERIALS AND METHODS: The ureters of 5 female mongrel dogs were accessed through a median laparotomy incision. A 4 cm segment of mid ureter was resected on the right side. The right ureteral segments were replaced by tubularized SIS segments using 6-zero polydioxanone interrupted sutures. Internal pigtail stents were left for 6 weeks. All animals were sacrificed at 12 weeks. Ureteral patency was assessed by excretory urography and magnetic resonance urography 7 and 12 weeks after the initial procedures. Inflammation and regeneration were assessed histologically. RESULTS: At 12 weeks all ureters on the experimental side were completely occluded with significant hydroureteronephrosis and the subsequent deterioration of kidney function. At autopsy there was failure to calibrate any of the experimental ureters with a 3Fr catheter. Although histologically urothelium and muscular cells had proliferated over the graft, they were embedded in an intense fibrotic and inflammatory process. CONCLUSIONS: Technically 1-layer SIS was easily modeled, providing the conditions for watertight anastomosis. The regeneration of urothelium and muscle was induced and supported by the graft. However, functional replacement was not successful. One-layer SIS is not a suitable material for replacing long segment (4 cm) ureteral defects.