Grafts in Peyronie’s surgery without the use of prostheses: a systematic review and meta-analysis

Abstract

Peyronie’s disease (PD) is characterized by abnormal penile curvature, and various surgical methods have been developed using different graft materials. However, there is currently no universal agreement on which type of graft is the best. The objective of this review was to evaluate the available literature and identify the most effective graft material for penile curvature correction in PD. A literature search was conducted using electronic databases, including PubMed, Scopus, and the Cochrane Library. The patients, intervention, comparison, and outcome (PICO) approach was used to define the eligibility of studies. Two authors independently selected studies, evaluated them, and extracted data. Random-effect models using the DerSimonian–Laird method were used. Most studies were single-arm studies and had a high risk of bias. Buccal mucosa grafts (BMG) were found to result in the highest penile straightening rates and were associated with the least de novo erectile dysfunction. TachoSil grafts demonstrated a high success rate in straightening despite a higher mean preoperative curvature, while Tutoplast grafts had a higher incidence of postoperative erectile dysfunction. BMG had the highest percentage of postoperative penile straightening. Overall, the TachoSil graft showed the best performance when preoperative curvature is taken into account. Based on the available literature, BMG appear to be the most effective for penile curvature correction in PD, but this is offset by the requirement for low preoperative curvature. The TachoSil graft shows the best overall performance when preoperative curvature is considered. Comparative randomized clinical trials are still needed to determine graft superiority.

INTRODUCTION

Peyronie’s disease (PD) is an acquired penile deformity of unknown cause, with a prevalence estimated to be between 11% and 20%.1 One possible theory is that genetic factors may predispose the corpus cavernosum to develop a collagen plaque in response to trauma.2

If the degree of penile curvature causes unsatisfactory sexual intercourse or negatively affects the quality of erections, surgery may be recommended. The decision to undergo surgery depends on the degree of penile curvature.3 Tunica albuginea plication (TAP), plaque incision and grafting (PIG), and plaque excision and grafting (PEG) with or without the use of a penile prosthesis implant (PPI) represent different operative choices for PD. While Kadıoğlu et al.4 recommend PPI as the preferred approach in PD patients with erectile dysfunction (ED), patients with normal erectile function have a wider range of corrective options, such as intralesional injection therapy, vacuum devices, and penile traction devices.

The European Society for Sexual Medicine (ESSM) has recently published the official treatment guidelines for PD.5 According to the ESSM guidelines, when corrective surgery might lead to penile shortening of 20% or more, grafting techniques should be used in patients with a curvature of more than 60°, significant waist deformity or ossified plaque. PIG and PEG procedures can also help treat more severe indentations and hourglass deformities. Before choosing a specific grafting technique, preoperative sexual function should always be assessed and considered for the best treatment modality choice. Despite the availability of various graft options, there is still a lack of clear evidence on which one is the most effective. Ideally, the graft should have a low infection rate, not induce a loss of erectile function, be cost-effective, and not cause an inflammatory response.6

There are many types of grafts available to achieve optimal results, including autologous grafts (venous grafts, such as a penile dorsal vein or saphenous vein, buccal mucosa grafts [BMG], dermal grafts, tunica albuginea [TA] grafts, and tunica vaginalis [TV] grafts), allografts (cadaveric fascia lata and human pericardium, such as Tutoplast® from Coloplast, Minneapolis, MN, USA), synthetic grafts (Gore-Tex® from Gore & Associates, Inc., Newark, DE, USA; Dacron™ from Invista, Gloucester, UK and Advansa, Hamm, Germany; and collagen fleece hemostatic patches, such as TachoSil® from Corza Medical, Westwood, MA, USA), or xenografts (small intestinal submucosa [SIS], such as Surgisis® from Cookmedical, Bloomington, IN, USA, and bovine pericardium).6 Currently, not all of the above-mentioned grafts are in use, and ongoing research, especially in the field of tissue engineering, is being conducted in the quest for new grafts.7

Long-term studies have helped exclude some unsuitable grafts, such as dermal grafts or Dacron, but the data on many of the grafts being used are still inconsistent.5 The ESSM and European Association of Urology (EAU) guidelines provide some insight into the available graft choices.3,5 Despite the available information, reconstructive urology surgeons need more guidance to choose the best graft for their patients.

The aim of this comprehensive systematic review and meta-analysis was to gather and compile all available information on different grafts used in PD surgery to aid in the selection of the optimal graft.

MATERIALS AND METHODS

A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PRISMA checklist; Supplementary Figure 1 ^{(105.5KB, tif)} ). The PubMed, Scopus, and Cochrane databases were queried using search terms (and medical subject headings [MeSH] terms) specified in Supplementary Methods, with study publication dates ranging from January 1992 to January 2023. The initial search of the scientific publication databases yielded 539 results.

The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in December 2022 (ID: CRD42022306996).

The inclusion criteria encompassed retrospective, prospective, comparative, and noncomparative primary clinical studies that utilized grafts in PD patients.

The exclusion criteria comprised studies with fewer than 10 patients or patients under 18 years of age, those focusing on congenital penile curvature and PPI use, conference abstracts, case reports or small case series, reviews, animal studies, editorial comments, and studies utilizing plication procedures without grafts.

Study selection, data extraction, and outcomes

Following the above-mentioned criteria, two reviewers (AN and SK) used standardized data extraction sheets to independently extract data from studies, and all discrepancies were resolved by a third reviewer (PD). The reviewers extracted the following information: name of the study, first author and year of publication, study design and blinding, number of patients, mean curvature, length of follow-up period, graft choice, postoperative success, and postoperative ED. The primary outcomes of interest were the rates of postoperative success and postoperative ED. The secondary outcome was the postoperative penile length.

Risk of bias assessment

Since no multi-arm studies were included in the meta-analysis, there was no need to use the Cochrane risk of bias assessment scale (RoB-2 Tool). Single-arm trials have an inherently high risk of bias. Therefore, only studies clearly within our review question and without the chance of any bias, as determined by the ROBINS-I-template, were included.8

Statistical analyses

Open Meta-Analyst software (http://www.cebm.brown.edu/openmeta) was used to calculate random-effects models for the meta-analysis and to generate forest plots using the DerSimonian–Laird random-effects method. A correction factor of 0.5 and a confidence level of 95.0 were used.9 Total percentage variation was calculated with the I² statistic to indicate study heterogeneity.

RESULTS

The literature search yielded 539 publications. After excluding articles based on the criteria listed in Supplementary Figure 1 ^{(105.5KB, tif)} , 58 articles were included in the meta-analysis. Their study characteristics are presented in Supplementary Table 1, which reports the success rate of curvature resolution after graft surgery for PD in relation to the preoperative curvature and the follow-up period, as well as de novo ED and postoperative penile length and International Index of Erectile Function (IIEF) score when available.

Supplementary Table 1.

Data extraction

Study author name	Year	Study type	Graft used	Technique	Follow-up time	Patient number	Mean preoperative curvature (°)	Postoperative curvature correction in patient (%)	ED worse in patient (%)	IIEF preoperative score	IIEF postoperative score	Mean Δ size (cm)	Comment
Collagen fleece graft – TachoSil
Hatzichristodoulou et al.13	2021	Prospective 1 arm	TachoSil	pPEG	47.2 months	319	NA	93.7	15.7	NA	NA	+1.1 cm
Fernandez-Pascual et al.61	2020	Prospective 1 arm	TachoSil	PIG (80%) and pPEG (13%)	5.2 months	52	72.8	92.3	16.7	19.5	19.3	NA	19.2% of patients with PPS
Hatzichristodoulou12	2018	Prospective 1 arm	TachoSil	pPEG	17.8 months	12	98.3	83.3	8.3	16.6	18.1	+0.7 cm	All patients with ventral curvatures
Yafi et al.62	2016	Retrospective 2 arm	TachoSil	pPEG	20.7 months	26	70.8	85	0	22.2	21.9	NA	All with hourglass deformity (PEG vs PPI)
Rosenhammer et al.28	2019	Retrospective 2 arm	TachoSil	pPEG	39.6 months	43	80	100	5	17.8	18.8	NA	5% PPS (TachoSil vs Surgisis)
Horstmann et al.14	2011	Retrospective 2 arm	TachoSil	pPEG or cPEG	59 months	43	74	93	21	NA	NA	NA	93% self reported PPS (TachoSil vs NESBIT)
Venous graft
Güler63	2022	Retrospective 1 arm	SVG	PIG	37 months	71	62	86.8	9.4	22.4	21.2	−0.2 cm	11.3% of patients with PPS
Tavakoli Tabassi et al.Group 164	2022	Prospective 2 arm	SVG	Group 1: Double Y incision	18.5 months	26	59.8	100	25	20.2	17.9	NA	41% of patients PPS (Double Y incision vs transverse incisions)
Tavakoli Tabassi et al.Group 264	2022	Prospective 2 arm	SVG	Two transverse incisions	19.1 months	26	60.5	100	12	20.3	19.6	NA	54.5% of patients with PPS
Danacioglu et al.17	2021	Retrospective 2 arm	SVG	PIG	18 months	18	70	86.9	13.1	19.2	19.8	+1.7 cm	SVG vs BMG
Kayigil et al.65	2019	Retrospective 2 arm	SVG	NA if PIG or PEG +/− plication	37 months	26	60	77	0	18	18	NA	Acellular porcine pericardium versus venous graft. +/−plication
Kadioglu et al.66	2018	Retrospective 3 arm	SVG	PIG (Y incision) +/− plication	51.1 months	144	58.4	84	33	NA	NA	NA	All reported PPS (NESBIT vs PIG vs PPI)
Wimpissinger et al.49	2016	Prospective 1 arm	Deep dorsal +/− SVG	PIG + plication in 6 patients	13 years	30	90	86.7	37	NA	NA	NA	13 years follow-up. 43% reported PPS
Kayigil et al.67	2010	Prospective 1 arm	SVG	PIG +/− plication	21 months	15	71.3	100	0	18.5	21.4	NA	13.3% of patients reported PPS
Kadioglu et al.68	2007	Prospective 3 arm	SVG	PIG (+ plication in 25%)	41.7 months	75	61.6	89.8	8.6	NA	NA	NA	NESBIT vs PIG vs PPI
Hsu et al.69	2007	Prospective 1 arm	Deep dorsal vein	NA	43.8 months	85	52.6	100	3.5	19.7	21.6	NA	4.7% of patients reported PPS
Kalsi et al.70	2005	Retrospective 1 arm	SVG or dorsal vein	PIG	12 months	113	64.5	86	15	NA	NA	NA	PPS in 35% of patients. 51 patients had a 5 years follow-up
Backhaus et al.71	2003	Prospective 1 arm	SVG	PIG and plication	6 months	17	87	89	17	NA	NA	NA	PPS in 25% of patients
Metin et al.72	2002	Retrospective 1 arm	SVG	PIG	17 months	18	60	88.8	0	NA	NA	NA	PPS in 16.6% of pts
Venous graft
Adeniyi et al.40	2002	Prospective 1 arm	SVG or deep dorsal vein	PIG. Also plication in 22%	16 months	51	57	82	8	NA	NA	NA	PPS in 35% of patients
Yurkanin et al.16	2001	Prospective 1 arm	SVG	PIG +/− plication	13.4 months	24	62	66	33	NA	NA	+2.1 cm
Montorsi et al.15	2000	Prospective 1 arm	SVG	PIG (in 12% also plication)	32 months	50	60	80	6	NA	NA	+0.6 cm	40% of patients reported PPS
Kadioglu et al.73	1999	Prospective 1 arm	SVG	PIG	13 months	20	NA	75	5	NA	NA	NA	Pretreated with rmTNFa
Arena et al.74	1999	Retrospective 1 arm	Dorsal vein	PIG	24 months	23	70	96	13	NA	NA	NA	52% of patients reported PPS
El-Sakka et al.75	1998	Prospective 1 arm	SVG	PIG (33% patients also plication)	>6 months	145	NA	95.5	12	NA	NA	NA	17% of patients reported PPS
Bovine pericardium graft
Diao et al.18	2021	Retrospective 1 arm	Bovine pericardium (lyoplant)	ETG	59 months	19	42	NA	0	NA	NA	+0 cm	ETG
Fiorillo et al.51	2021	Retrospective 2 arm (dermal vs bovine pericardium)	Bovine pericardium (veritas)	PIG (Y incision)	32 months	34	80	76	23	NA	NA	NA	PPS in 80%
Choi and Lee76	2021	Retrospective 1 arm	Bovine pericardium (PeriGuard®)	H-incision	14 months	21	70	100	0	NA	NA	NA	Additional plication sutures in complex deformity
Otero et al.19	2017	Prospective 1 arm	Bovine pericardium (Peri-Guard®	cPEG	14 months	41	78	80.5	24	NA	NA	+0.7 cm	Complete plaque excision
Silva-Garreton et al.50	2017	Retrospective 1 arm	Bovine pericardium (SURGIFOC®)	PEG	66.8 months	28	74	59	44.4	NA	NA	NA	75% of patients reported PPS
Sansalone et al.77	2011	Retrospective 1 arm	Bovine pericardium (veritas)	PIG. Y incision	20 months	157	NA	88	0	16	22.5	+2.5 cm
Egydio et al.21	2002	Retrospective 1 arm	Bovine pericardium (HP Bioproteses)	PIG	19.4 months	33	67.6	87.9	0	NA	NA	+2.2 cm	Intraoperative size measurement
Human pericardium graft - Tutoplast graft
Abdelsayed et al.35	2019	Retrospective 3 arm	Tutoplast	PEG	43 months	22	78	95	22	NA	NA	NA	PPI vs TAP vs PEG
Chow et al.22	2018	Retrospective 2 arm	Tutoplast	PEG	61 months	79	73	87.6	31	NA	NA	+0.57 cm	TAP + PEG vs PEG
Taylor et al.78	2012	Retrospective 2 arm	Tutoplast	PEG	91 months	115	75	NA	21	NA	NA	NA	PEG vs TAP
Human pericardium graft - Tutoplast graft
Flores et al.23	2011	Retrospective 1 arm	Tutoplast	PIG (H-or Egydio)	22 months	56	52	NA	46	23	17	+0.4 cm	4 patients had surgisis
Chung et al.11	2011	Retrospective 3 arm	Tutoplast	PIG	79 months	23	NA	87	65	15.1	10.8	NA	Dermal vs Tutplast vs Stratasis. IIEF across all study arms
Taylor and Levine24	2008	Retrospective 2 arm	Tutoplast	PEG	58 months	81	75	97.6	39	NA	NA	+0.2 cm	PEG vs TAP
Usta et al.79	2003	Retrospective 3 arm	Tutoplast	PEG or PIG	21 months	19	60.5	78.9	15.7	NA	NA	NA	PEG vs PPI vs PPI + PEG
Levine and Estrada25	2003	Retrospective 1 arm	Tutoplast	PEG	22 months	40	69.1	98	30	NA	NA	+0.7 cm	PEG
Hellstrom and Reddy80	2000	Prospective 1 arm	Tutoplast	PEG	14 months	11	70	91	9	NA	NA	NA	No PPS
SIS
Morgado et al.26	2018	Prospective 1 arm	Surgisis	PIG	49.6 months	32	60–120	75	53.8	23.3	19	+0.6 cm	13 patients with >90° curvature. H-incision
Valente et al.27	2017	Prospective 1 arm	Surgisis	PEG+PIG	18 months	28	80.1	82	7	NA	NA	Overall +	PIG 92% PEG 2%
Sayedahmed et al.81	2017	Prospective 1 arm	Surgisis	PIG	33 months	43	73.8	74.4	6.9	16	20	0	Improvement in EF score
Cosentino et al.82	2016	Retrospective 1 arm	Surgisis	PIG	19.2 months	44	60	NA	4.5	NA	NA	NA
Rosenhammer et al.83	2019	Retrospective 2 arm	Surgisis	PIG	31.4 months	43	80	91	7	16.1	20.6	NA	28% PPS, improvement in EF
Chung et al.11	2011	Retrospective 2 arm	Stratasis	PIG	75.5 months	17	71	76.5	NA	15.1	10.8	NA	Study reports self-reported penile length. 65% of patients were dissatisfied. IIEF reported across all study arms
Staerman et al.29	2010	Retrospective 1 arm	Surgisis	PIG	28.8 months	28	90	67	11	NA	NA	NA	Small cohort with up to 3 years follow-up. Subjective PPS in 25%
Lee et al.53	2008	Retrospective 1 arm	Stratasis	PIG	14 months	13	71	100	54	NA	NA	NA
Knoll et al.84	2007	Prospective 1 arm	Surgisis	PIG	38 months	162	70	91	20	NA	NA	NA	PPS in 5%
Knoll85	2001	Prospective 1 arm	Surgisis	PIG	11 months	12	80	92	0	NA	NA	NA	No report of PPS
Buccal mucosa graft
Fabiani et al.86	2021	Retrospective 1 arm	BMG	PIG	28.3 months	27	61.9	100	7.4	22.5	23.1	NA	EF improved. PPS in 2 patients
Danacioglu et al.17	2021	Retrospective 2 arm	BMG	PIG	18 months	23	75	88.8	16.6	18.9	20.5	+1.8 cm	SVG vs BMG
Ainayev et al.30	2021	Prospective 1 arm	BMG	PIG	24 months	20	45	95	0	17.5	21.3	+1.6 cm
Cormio et al.32	2019	Prospective 1 arm	BMG	PIG	62 months	72	71.3	100	0	21.3	NA	+2.4 cm	No PPS
Zucchi et al.87	2015	Prospective 1 arm	BMG	PIG	43 months	32	63.75	96.5	3.5	21.5	22.6	NA
Fabiani et al.88	2016	Retrospective 1 arm	BMG	PIG and PEG	22.5 months	17	57.4	NA	5.8	22.2	23.3	NA
Cormio et al.31	2009	Prospective 1 arm	BMG	PIG	12.1 months	15	72	100	0	21.3	22.9	+1.8 cm	No PPS
Shioshvili and Kakonashvili57	2005	Prospective 1 arm	BMG	PEG	38.4 months	26	NA	92.3	7.7	8.1	22.3	NA	PPS in 15.4% of patients

ED: erectile dysfunction; IIEF: International Index of Erectile Function; Δ: difference; PEG: plaque excision and grafting; pPEG: partial PEG; PIG: plaque incision and grafting; NA: not available; cPEG: complete PEG; PPI: penile prosthesis implant; PPS: postoperative penile shortening; SVG: saphenous vein graft; BMG: buccal mucosa graft; TAP: tunica albuginea plication; rmTNFa: recombinant monoclonal tumor necrosis factor alpha; ETG: extratunical grafting; EF: erectile function; SIS: small intestinal submucosa

Multi-arm studies are summarized in Supplementary Table 2. Kovac et al.10 and Chung et al.11 were the only multi-arm studies examining the same grafts (Tutoplast graft and dermal graft). The number of patients in the included articles ranged from 11 patients to 319 patients. A total of 495 patients, 977 patients, 333 patients, 446 patients, 422 patients, and 282 patients were in the TachoSil, venous, pericardial, Tutoplast, SIS, and BMG groups, respectively. The follow-up period ranged from 6 months to 13 years.

Supplementary Table 2.

Multiarm studies and surgical technique used as control or comparative study arm

Study	Year	TachoSil	PPI	SIS	NESBIT	TAP	SVG	BMG	Porcine pericardium	Bovine pericardium	Porcine dermal graft	Human pericardium/Tutoplast	Dermal graft	Tunica vaginalis graft
Yafi et al.62	2016	X	X
Rosenhammer et al.83	2019	X		X
Horstmann et al.14	2011	X			X
Tavakoli Tabassi et al.64	2022						X
Danacioglu et al.17	2021						X	X
Ainayev et al.89	2022							X						X
Kayigil et al.65	2019						X		X
Kadioglu et al.66	2018		X		X		X
Kadioglu et al.34	2008		X		X		X
Fiorillo et al.51	2020									X	X
Abdelsayed et al.35	2019		X			X						X
Taylor et al.78	2012					X						X
Chung et al.11	2011			X								X	X
Taylor and Levine24	2008					X						X
Usta et al.79	2003		X									X
Chun et al.90	2001											X	X
Levine and Lenting91	1997		X										X	X
O’Donnell92	1992		X		X									X
Kovac and Brock10	2007			X								X	X

X: the graft used in each study-arm; PPI: penile prosthesis implant; SIS: small intestinal submucosa; TAP: tunica albuginea plication; SVG: saphenous vein graft; BMG: buccal mucosa graft

Postoperative curvature

Figure 1–3 contain six different forest plots, one for each graft type, representing the rate of postoperative success regarding penile curvature. The BMG forest plot yielded the lowest heterogeneity of all the grafts, and the venous graft forest plot yielded the highest (I²: 0 and 80%, respectively). While BMG resulted in the highest success rate for penile straightness, bovine pericardium grafts had the lowest success rate (98.5% and 84.2%, respectively). The second-best postoperative straightness was achieved with the TachoSil graft, with the study heterogeneity (I²) of 53.7%. As shown in Supplementary Figure 2 ^{(89.8KB, tif)} and 3 ^{(53.9KB, tif)} , there was no significant difference in the success rate for postoperative penile straightness between the PEG and PIG techniques in an indirect comparison, with similar study heterogeneity. Supplementary Table 2 lists the ranges of mean preoperative curvatures. BMG study arms are on the lower end of the curvature degree scale, with the lowest mean of 45° and the highest mean of 75°. TachoSil study arms are on the higher end of the curvature degree scale, starting at a mean preoperative curvature of 70° and reaching a top mean of 98.3°. The postoperative success rate regarding penile straightness was the highest in the BMG study arms, with the TachoSil study arms coming second. Study arms of other grafts resulted in comparable postoperative success rates (Supplementary Table 3). Moreover, an analysis of the postoperative success rate revealed no difference between studies in which the mean preoperative curvature degree was above 75° or below 65° (Supplementary Figure 4 ^{(90.1KB, tif)} ).

Figure 1.

Postoperative penile curvature resolution using different grafts. (a) TachoSil graft. (b) Venous graft. CI: confidence interval.

Figure 3.

Postoperative penile curvature resolution using buccal mucosa graft. CI: confidence interval.

Supplementary Table 3.

Range of mean preoperative curvatures in comparison to postoperative penile straightness according to graft type

	Range of mean preoperative curvature, ° (number of studies)	Range of postoperative penile straightness, % (number of studies)
Tachosil graft	70.8–98.3 (5)	83.3–100 (6)
Venous graft	52.6–90 (17)	66–100 (19)
Bovine pericardium graft	42–80 (6)	59–100 (7)
Tutoplast graft	52–78 (8)	78.9–97.6 (7)
SIS graft	60–90 (10)	67–100 (9)
Buccal mucosa graft	45–75 (7)	88.8–100 (7)
Plaque incision and grafting	45–90	66–100
Plaque excision and grafting	70–98.3	59–100

SIS: small intestinal submucosa

Figure 2.

Postoperative penile curvature resolution using different grafts. (a) Bovine pericardium graft. (b) Tutoplast graft. (c) Surgisis. CI: confidence interval.

Postoperative de novo ED and IIEF

The incidence of de novo ED after using different grafts was analyzed through meta-analyses, and the results are presented in Figure 4–6. BMG had the lowest incidence of ED at 2.8%, with a heterogeneity of 18%. On the other hand, Tutoplast grafts had the highest incidence of ED at 30.8%, with a heterogeneity of 78.2%. Bovine pericardium grafts had the second lowest incidence of ED at 8.8%, followed by TachoSil grafts at 10.9%. Furthermore, using the PEG technique resulted in an ED incidence of 20.1% compared to 11.6% when using PIG, as shown in Supplementary Figure 5 ^{(97.7KB, tif)} and 6 ^{(55.6KB, tif)} .

Figure 4.

Postoperative erectile dysfunction using different grafts. (a) TachoSil. (b) Venous graft. CI: confidence interval.

Figure 6.

Postoperative erectile dysfunction using buccal mucosa graft. CI: confidence interval.

Figure 5.

Postoperative erectile dysfunction using different grafts. (a) Bovine pericardium graft. (b) Tutoplast. (c) Surgisis. CI: confidence interval.

All study arms using BMG reported an increase in IIEF score, as presented in Supplementary Table 4. Tutoplast had no reported increase in postoperative IIEF scores, but two study arms showed a decrease in the IIEF score (Supplementary Table 4). The range of postoperative incidence of de novo ED for PIG was 0–65%, and for PEG, it was 0–44.4%, as shown in Supplementary Table 5. The smallest range for de novo ED was observed in the BMG groups (0–16.6%), while the largest range was observed in the Tutoplast groups (9%–65%), as shown in Supplementary Table 5. TachoSil had the second-smallest range, with studies reporting the incidence of postoperative ED from 0 to 21%.

Supplementary Table 4.

Number of studies reporting mean increase or decrease in postoperative International Index of Erectile Function depending on graft type

	Increase in postoperative IIEF score number of studies	Decrease in postoperative IIEF score number of studies
TachoSil graft	2	2
Venous graft	3	1
Bovine pericardium graft	1	-
Tutoplast graft	-	2
SIS graft	3	2
Buccal mucosa graft	7	0
Plaque incision and grafting	10	6
Plaque excision and grafting	3	1

IIEF: International Index of Erectile Function; SIS: small intestinal submucosa

Supplementary Table 5.

Range of postoperative de novo erectile dysfunction depending on graft type

	De novo postoperative ED, % (number of studies)
TachoSil	0–21 (6)
Venous graft	0–37 (18)
Bovine pericardium	0–44 (7)
Tutoplast	9–65 (9)
SIS graft	0–54 (9)
Buccal mucosa graft	0–16.6 (8)
Plaque incision and grafting	0–65 (34)
Plaque excision and grafting	0–44 (14)

ED: erectile dysfunction; SIS: small intestinal submucosa

When studies were stratified according to the mean preoperative curvature, those patients with a higher mean degree of preoperative curvature had a higher incidence of de novo ED (pooled estimate incidence rate of 10.9% versus 17.0%; Supplementary Figure 7 ^{(104.1KB, tif)} ).

Penile length after grafting

Two studies by Hatzchristodoulou et al.12,13 reported an average increase in penile length of 0.7 cm and 1.1 cm, respectively, after TachoSil surgery. However, a study by Horstmann et al.14 showed that 93% of patients reported penile shortening after TachoSil surgery. For the venous graft, three studies reported a mean added length ranging from −0.2 cm to 2.1 cm.15,16,17 Although Montorsi et al.15 reported a positive mean added length, 40% of patients still reported penile shortening. Penile shortening using the venous graft ranged from 4.7% to 52%. Bovine pericardium was assessed in four studies, which reported an added penile length of 0 cm to 2.5 cm, while self-reported penile shortening ranged from 75% to 80%.18,19,20,21 Tutoplast resulted in added penile length ranging from 0.2 cm to 0.7 cm.22,23,24,25 SIS had an overall mean added length of 0.6 cm, with self-reported penile shortening ranging from 5% to 65%.26,27,28,29 BMG resulted in the highest overall added penile length of 1.6 cm to 2.4 cm and low level of penile shortening ranging from 0 to 15.4%.17,30,31,32 Supplementary Table 6 provides a summary of different international guidelines on grafts, as mentioned by each association. Supplementary Table 7 outlines the ranges of postoperative penile lengths.

Supplementary Table 6.

Grafts and statements by the European Society of Sexual Medicine, European Association of Urology, and Canadian Urological Association in comparison

Graft type	ESSM	EAU	CUA
Polyester (Dacron®)	No longer used	Increased Infectious risk, fibrosis	Increased infectious risk, fibrosis
Polytetrafluoroethylene (Gore-Tex®)	No longer used	Increased Infectious risk, fibrosis	Increased infectious risk, fibrosis
Cadaveric dura mater	NA	Increased infectious risk, fibrosis	NA
Autologous fascia lata	Additional surgical incision and surgical time, encouraging results, high patient satisfaction rates	Good biological stability and mechanical resistance	Complications at the donor tissue site and extra surgical times
Autologous temporalis fascia grafts	Additional surgical incision and surgical time	Good biological stability and mechanical resistance	Complications at the donor tissue site and extra surgical times
Tunica albuginea grafts	Additional surgical incision and surgical time	Perfect histological properties but with some limitations, the size that can be harvested, the risk of weakening penile support	NA
Tunica vaginalis grafts	Additional surgical incision and surgical time	NA	Complications at the donor tissue site and extra surgical times
Dermal grafts	Long-term failure, contracture risk, inflammatory reaction, and infection	NA	NA
Saphenous vein graft	Promising results	NA	Promising results
SIS graft	Promotes tissue-specific regeneration and angiogenesis	Promotes tissue-specific regeneration and angiogenesis	NA
Collagen fleece (TachoSil)	Reduction in operative time, satisfactory outcomes, straightening, does not allow for full rigid erection to assess residual curvature intraoperatively, missing long-term results	Easy application and an additional hemostatic effect	NA
Bovine pericardium	Encouraging results, high patient satisfaction rates	Good tensile strength and adaptability, and good host tolerance	NA
Cadaveric human pericardium (Tutoplast)	NA	Good tensile strength and multidirectional elasticity	NA

NA: not available; ESSM: European Society of Sexual Medicine; EAU: European Association of Urology; CUA: Canadian Urological Association; SIS: small intestinal submucosa

Supplementary Table 7.

Range of postoperative penile length loss or gain according to graft type

	Range of PPL, cm (number of studies)	Range of self-reported penile shortening, % (number of studies)
TachoSil graft	0.7–1.1 (2)	5–93 (3)
Venous graft	−0.2–2.1 (4)	4.7–54.4 (9)
Bovine pericardium graft	0–2.5 (4)	75–80 (2)
Tutoplast graft	0.2–0.7 (4)	0 (1)
SIS graft	0.6 (1)	5–65 (4)
Buccal mucosa graft	1.6–2.4 (4)	0–15.4 (4)
Plaque incision and grafting	0.4–2.5 (11)	0–80 (18)
Plaque excision and grafting	0.2–1.1 (6)	0–95 (5)

PPL: postoperative penile length; SIS: small intestinal submucosa

DISCUSSION

PD studies

While PD can be treated with various techniques and grafts, choosing the most effective option requires objective outcome measurements and criteria. The ESSM provides guidance on the important outcome measurements and criteria needed for PD, but comparative studies differentiating between graft types have yet to be published.5 Despite this, the authors of this meta-analysis have aimed to quantify the available data on grafts to facilitate objective decision-making.

The lack of complete consensus on graft choice has been previously discussed in a systematic review by Bajic et al.33 The literature on PD is abundant, but there is a shortage of randomized controlled trials. Unfortunately, almost all studies reviewed in this paper carry a high risk of bias despite the high prevalence of PD. There are no published randomized trials at present, and while guidelines on reporting and study design have been proposed, analogous publications are still missing. In addition, a search on clinicaltrials.gov revealed no ongoing trials comparing different grafts.

The review identified only few trials that compared different grafts or techniques. In most of these studies, the PPI or plication procedure was used as the second/comparative study arm. However, the comparison between the two procedures can be problematic because, in most study arms using the plication method, the mean curvature is lower than that for patients undergoing the PEG or PIG procedures.14,34,35 Multi-arm meta-analysis was not possible because there is only one multi-arm study that compares the same surgical technique with different grafts (Supplementary Table 2), except for the studies by Kovac et al.10 and Chung et al.11

In addition, the American Urological Association (AUA) guidelines on PD were not included in this analysis because they were published in 2015 and are considered outdated.36,37

Techniques in PD surgery

Various techniques are used in PD grafting surgery, such as PIG, PEG, or extratunical grafting (ETG). Different techniques within PIG, such as H-incision, Y-incision, double line incision, transverse incision, and Egydio, have been reported. Some surgeons perform complete plaque excision in PEG, while others do partial excision.21,38,39,40 Recent studies on ETG by Diao et al.18 and Reed-Maldonado et al.41 have also shown promising results. These studies suggest that avoiding the neurovascular bundle can reduce the chance of hypoesthesia or ED. When deciding on a surgical technique for PD, several factors need to be considered, including the extent of penile length loss, the nature and severity of the deformity, the quality of erections, and the preferences of the patient.42

In a systematic review by Barbosa et al.,43 which compared TA incision to no incision when no grafts were used, the authors found that opening TA had higher failure rates for penile straightening and a higher rate of glans hypoesthesia. Unfortunately, preoperative penile curvature was not reported in this study. Less invasiveness not only reduces postoperative complications but also decreases the chance of penile straightening. A comparison between plaque excision and plaque incision regarding postoperative residual curvature revealed no difference in indirect analysis.

While PEG has the advantage over PIG in achieving penile length, it does so at the cost of higher rates of ED.44,45 Interestingly, penile length loss was not more common in the PIG group. Contrarily, the BMG study arms using PIG had the highest added penile length, with a penile shortening rate of only 0–15%.

Grafts in PD surgery

While gathering data for this meta-analysis, the following grafts were excluded based on specific criteria. Synthetic grafts such as polyester (Dacron®) and polytetrafluoroethylene (Gore-Tex®) are generally not recommended by most guidelines (CUA, ESSM, and EAU) due to their association with increased infection risk, allergies, and fibrosis.3,5,44 In addition, the EAU discourages the use of cadaveric dura mater due to increased infection risk, and the ESSM reports long-term failure of dermal grafts due to contracture risk and inflammatory reactions. TA grafts also have limitations, including the maximum size that can be harvested and the weakening of penile support.46 Therefore, these grafts were excluded from this study. Grafts used in PPI surgery were also excluded as they were outside the scope of this review, which focuses primarily on graft choice in PD in patients with sufficient preoperative erectile function.

The optimal graft for PD surgery should be cheap and readily available, and it should not cause contracture, infection, inflammatory reactions, ED, or penile shortening.5 The elasticity profile of the graft has narrow margins: if it is too stiff, it will not allow proper penile enlargement; and if it is too loose, it will lead to sacculation. The grafts that meet these criteria are autologous grafts (fascia lata, venous grafts, TV grafts, BMG, and lingual mucosa), allografts (cadaveric pericardium [Tutoplast]), xenografts (SIS and bovine pericardium), and collagen fleece.

However, due to insufficient data on autologous grafts such as the fascia lata, TV, and lingual mucosa, these grafts were excluded from this analysis. Only two studies investigated fascia lata grafts in a total of 26 patients, and four studies examined the TV graft in a total of 54 patients. The xenform® (acellular fetal bovine dermal) graft was investigated in only one study and was not included in this analysis.46 In addition, four studies examined the TV graft in a total of 54 patients; one study examined only five patients, and the most recent study with 20 patients conducted by Ainayev et al.47 had a relatively low mean preoperative curvature of 48°. The literature search yielded only one study on lingual grafts.48 Consequently, due to insufficient data on these grafts, autologous grafts such as the fascia lata, TV, and lingual mucosa were excluded from this analysis. Although the EAU and the ESSM have reported encouraging results for autologous fascia temporalis and fascia lata grafts with good biological stability and mechanical resistance, more studies supporting these results are necessary.

The most extensively researched graft in the PD literature is the venous graft. Two compelling reasons to favor the venous graft are its durability and the abundance of available long-term data. Wimpissinger et al.49 reported a remarkable mean follow-up of 13 years, the longest follow-up period of any graft. As stated by Lue and El-Sakka38 in 1998, the venous graft is closest in histology and anatomy to the TV and is thus the best theoretical fit for it.

BMG appears to be the best graft in terms of postoperative straightness, de novo ED, and penile length. However, it is essential to note that the results of the BMG study arms should be taken with some reservation because patients in these study arms had the lowest mean degree of preoperative curvatures. In addition, crucial factors to consider when utilizing autologous grafts are the amount of time required for graft harvesting and the risk of infection at the harvesting site.

The second-largest group of patients in this meta-analysis was treated with TachoSil. Despite the highest average preoperative curvature compared to all the other graft study groups, this cohort achieved the second-highest percentage of postoperative straightness. Furthermore, TachoSil demonstrated promising results in terms of de novo ED and penile length postoperatively. Notably, one significant advantage of TachoSil is that it does not require suturing or harvesting, thereby reducing considerable operative time. It is essential to note that TachoSil is our department’s preferred graft of choice. However, one disadvantage of this graft is that a full intraoperative erection should be avoided after placement, which limits the assessment of residual curvature during the operation.

According to the EAU guidelines, Tutoplast (human pericardium) has good tensile strength and multidirectional elasticity.3 However, in this meta-analysis, the Tutoplast graft had the worst results on almost every parameter studied, especially regarding de novo ED. Chung et al.11 and Flores et al.23 reported postoperative ED rates for Tutoplast of 65% and 46%, respectively.

In comparison, the bovine pericardium had better performance regarding de novo ED than human pericardium.50 The ESSM also reports high patient satisfaction rates for bovine pericardium grafts.5 Interestingly, in studies by Silva-Garetton et al.50 and Fiorillo et al.,51 75% and 80% of patients, respectively, reported penile shortening.

Regarding Surgisis, the findings of this study are in line with the negative experience from John et al.52 in their initial use of the graft. Two studies reported de novo ED in 54% of their patients. The EAU states that Surgisis promotes tissue-specific regeneration and angiogenesis, which would translate into better postoperative erectile function. However, only two studies out of ten reported improvements in postoperative erectile function.26,53

Ahmadnia et al.54 describe a technique that involves plaque excision and suturing of TA without using graft material, which resulted in good postoperative function. However, this method is only suitable for small defects and low curvature degrees. Hegarty et al.55 conducted a similar study, comparing a multi-incision approach with or without grafting, and obtained promising results. When severe curvature (over 60°) is present without underlying ED, the EAU recommends tunical lengthening procedures.3

In the future, tissue-engineered grafts are likely to become more common. Edler Zandoná et al.56 recently investigated a new bioabsorbable polyglycolic acid polymer graft (Gore-Tex®) with high refractory ED, but further research is needed.

Penile length

Penile length is a major concern for men undergoing PD surgery. Cormio et al.31 reported a significant mean increase of 2.4 cm when using BMG. Overall, studies using BMG had the highest gains in postoperative penile length.57 However, self-reported postoperative length is highly subjective and prone to bias. Li et al.58 recently conducted a comparative study using only plication, and they stratified patients into high-degree (over 60°) and low-degree curvature groups. In the high-degree curvature group, all patients experienced shortening, compared to 60% in the lower-degree curvature group. This highlights the need for techniques such as PIG, especially if penile length restoration or maintenance is desired. This may explain why most BMG studies report relatively good postoperative results. However, this may not have been the case if the mean preoperative curvature degree was as high as that in the TachoSil study arms.

Final considerations

Overall, the BMG graft appeared to perform the best in terms of postoperative residual curvature, IIEF score, de novo ED, and penile length, while the Tutoplast graft had the worst outcomes in indirect comparison. It is important to note that the major differences between studies using Tutoplast and BMG were the operative technique and preoperative curvature. In Supplementary Table 1, it is evident that all Tutoplast study arms, except one, used PEG, while in the BMG study arms, all, except one, preferred PIG. Drawing immediate conclusions from these observations would be unwise. The superiority of the BMG may be attributed to patients’ lower preoperative mean penile curvature. On the other hand, the TachoSil study arms demonstrated a relatively low incidence of de novo ED and a high success rate for penile curvature correction despite the high preoperative mean curvature. However, further investigation is needed to determine whether it was the technique, the graft type, or both that contributed to the observed differences.

It is important to note the continuously advancing field of tissue engineering aimed at discovering grafts that closely resemble the histology of the cavernosal bodies.7 A recently developed artificial TA shows promising potential for creating even more effective grafts in the future.59

Limitations

There are several limitations to this review. First, the majority of studies regarding grafts in PD is retrospective and has a single study arm with no graft comparison, which limits the ability to draw conclusions regarding the differences in success rates between grafts. Second, most studies included in this meta-analysis were single-arm studies, introducing a high likelihood of bias. In addition, it is important to note that the IIEF has no formal approval for use in PD, which may impact the accuracy of reported results. Furthermore, although Peyronie’s disease questionnaire (PDQ) is available, it was not included in almost any of the studies.60 Finally, a limitation of this review is the inhomogeneous study design and the frequent lack of data in some studies, which may reduce the generalizability of the findings.

CONCLUSION

The wide variety of available grafts for PD can be overwhelming for surgeons. This meta-analysis serves as a useful tool to help identify the most effective graft options. By incorporating data from the last three decades, this study adds to the current guidelines and reinforces the need for evidence-based decision-making when selecting grafts. However, the lack of available evidence for most grafts is concerning. More comprehensive randomized controlled trials involving larger patient populations are urgently needed to inform surgical decision-making. Surgeons should also be familiar with various surgical techniques available for treating PD to achieve optimal outcomes.

AUTHOR CONTRIBUTIONS

AN was responsible for research design, data acquisition, analysis, and manuscript writing. VT, EL, and PK were responsible for analysis, manuscript writing, and critical revision. SK was responsible for research design, data acquisition, and manuscript revision. SW was involved in the analysis and critical revision of the manuscript. KG, MO, AP, and KP were involved in the data acquisition, analysis, and paper draft. CP carried out statistics and research design. PD was responsible for project supervision and management. All authors read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.

Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.

Supplementary Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 flow diagram for new systematic reviews which included searches of databases and registers only.

Supplementary Figure 2

Postoperative penile curvature resolution after plaque incision and grafting.

Supplementary Figure 3

Postoperative penile curvature resolution after plaque excision and grafting.

Supplementary Figure 4

Postoperative penile curvature resolution. (a) Studies with mean preoperative curvature above 75°; (b) studies with mean preoperative curvature below 65°.

Supplementary Figure 5

Postoperative erectile dysfunction after plaque incision and grafting.

Supplementary Figure 6

Postoperative erectile dysfunction after plaque excision and grafting.

Supplementary Figure 7

Postoperative erectile dysfunction in studies depending on preoperative mean curvature. (a) studies with mean preoperative curvature above 75°; (b) studies with mean preoperative curvature below 65°.

SUPPLEMENTARY METHODS

SEARCH STRING FOR MEDICAL DATABASES

COCHRANE N = 5

Using MeSH Term Penile Induration AND (graft OR bovine pericardium OR dorsal vein OR patch OR hemostatic patch OR tachosil OR acelullar dermal matrix OR fibrin patch OR small intestinal submucosa)

SCOPUS N = 47

(ALL (peyronie OR peyronie’s AND disease OR induratio AND penis OR induratio AND penis AND plastica OR penile AND curvature ) AND ALL (graft OR bovine AND pericardium OR dorsal AND vein OR hemostatic AND patch OR tachosil OR fibrin AND patch OR patch OR acellular AND dermal AND matric OR epiflex OR small AND intestinal AND submucosa ) )

MEDLINE SEARCH STRING WITH DATES N = 487

((“peyronie”[All Fields] OR “peyronie s”[All Fields] OR “peyronies”[All Fields] OR (“induratio”[All Fields] AND (“penis”[MeSH Terms] OR “penis”[All Fields])) OR (“penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“induratio”[All Fields] AND “penis”[All Fields] AND “plastica”[All Fields]) OR “induratio penis plastica”[All Fields]) OR (“penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“peyronie s”[All Fields] AND “disease”[All Fields]) OR “peyronie s disease”[All Fields])) AND (((“intestine, small”[MeSH Terms] OR (“intestine”[All Fields] AND “small”[All Fields]) OR “small intestine”[All Fields] OR (“small”[All Fields] AND “intestinal”[All Fields]) OR “small intestinal”[All Fields]) AND (“submucosa”[All Fields] OR “submucosae”[All Fields])) OR (“graft s”[All Fields] OR “grafted”[All Fields] OR “graftings”[All Fields] OR “transplantation”[MeSH Subheading] OR “transplantation”[All Fields] OR “grafting”[All Fields] OR “transplantation”[MeSH Terms] OR “grafts”[All Fields] OR “transplants”[MeSH Terms] OR “transplants”[All Fields] OR “graft”[All Fields]) OR ((“fibrin”[MeSH Terms] OR “fibrin”[All Fields] OR “fibrins”[All Fields] OR “fibrine”[All Fields]) AND (“patch”[All Fields] OR “patch s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields])) OR (“acellular dermis”[MeSH Terms] OR (“acellular”[All Fields] AND “dermis”[All Fields]) OR “acellular dermis”[All Fields] OR (“acellular”[All Fields] AND “dermal”[All Fields] AND “matrix”[All Fields]) OR “acellular dermal matrix”[All Fields]) OR “epiflex”[All Fields] OR (“tachosil”[Supplementary Concept] OR “tachosil”[All Fields] OR “tachosil”[All Fields] OR “fibrinogen”[MeSH Terms] OR “fibrinogen”[All Fields] OR “fibrinogens”[All Fields] OR “fibrinogen s”[All Fields] OR “fibrinogene”[All Fields] OR “thrombin”[MeSH Terms] OR “thrombin”[All Fields] OR “thrombin s”[All Fields] OR “thrombine”[All Fields] OR “thrombins”[All Fields]) OR ((“haemostat”[All Fields] OR “haemostatically”[All Fields] OR “haemostatics”[All Fields] OR “hemostatics”[Pharmacological Action] OR “hemostatics”[MeSH Terms] OR “hemostatics”[All Fields] OR “haemostats”[All Fields] OR “hemostasis”[MeSH Terms] OR “hemostasis”[All Fields] OR “haemostatic”[All Fields] OR “hemostat”[All Fields] OR “hemostatically”[All Fields] OR “hemostatic”[All Fields] OR “hemostats”[All Fields]) AND (“patch”[All Fields] OR “patch s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields])) OR (“deep”[All Fields] AND (“dorsal”[All Fields] OR “dorsale”[All Fields] OR “dorsally”[All Fields] OR “dorsals”[All Fields]) AND (“veins”[MeSH Terms] OR “veins”[All Fields] OR “vein”[All Fields])) OR ((“bovin”[All Fields] OR “cattle”[MeSH Terms] OR “cattle”[All Fields] OR “bovine”[All Fields] OR “bovines”[All Fields]) AND (“pericardium”[MeSH Terms] OR “pericardium”[All Fields] OR “pericardiums”[All Fields])))) AND (1992/1/1:2023/1/1[pdat])

Translations

peyronie: “peyronie”[All Fields] OR “peyronie’s”[All Fields] OR “peyronies”[All Fields]

penis: “penis”[MeSH Terms] OR “penis”[All Fields]

induratio penis plastica: “penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“induratio”[All Fields] AND “penis”[All Fields] AND “plastica”[All Fields]) OR “induratio penis plastica”[All Fields]

peyronie’s disease: “penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“peyronie’s”[All Fields] AND “disease”[All Fields]) OR “peyronie’s disease”[All Fields]

small intestinal: “intestine, small”[MeSH Terms] OR (“intestine”[All Fields] AND “small”[All Fields]) OR “small intestine”[All Fields] OR (“small”[All Fields] AND “intestinal”[All Fields]) OR “small intestinal”[All Fields]

submucosa: “submucosa”[All Fields] OR “submucosae”[All Fields]

graft: “graft’s”[All Fields] OR “grafted”[All Fields] OR “graftings”[All Fields] OR “transplantation”[Subheading] OR “transplantation”[All Fields] OR “grafting”[All Fields] OR “transplantation”[MeSH Terms] OR “grafts”[All Fields] OR “transplants”[MeSH Terms] OR “transplants”[All Fields] OR “graft”[All Fields]

fibrin: “fibrin”[MeSH Terms] OR “fibrin”[All Fields] OR “fibrins”[All Fields] OR “fibrine”[All Fields]

patch: “patch”[All Fields] OR “patch’s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields]

acellular dermal matrix: “acellular dermis”[MeSH Terms] OR (“acellular”[All Fields] AND “dermis”[All Fields]) OR “acellular dermis”[All Fields] OR (“acellular”[All Fields] AND “dermal”[All Fields] AND “matrix”[All Fields]) OR “acellular dermal matrix”[All Fields]

tachosil: “TachoSil”[Supplementary Concept] OR “TachoSil”[All Fields] OR “tachosil”[All Fields] OR “fibrinogen”[MeSH Terms] OR “fibrinogen”[All Fields] OR “fibrinogens”[All Fields] OR “fibrinogen’s”[All Fields] OR “fibrinogene”[All Fields] OR “thrombin”[MeSH Terms] OR “thrombin”[All Fields] OR “thrombin’s”[All Fields] OR “thrombine”[All Fields] OR “thrombins”[All Fields]

hemostatic: “haemostat”[All Fields] OR “haemostatically”[All Fields] OR “haemostatics”[All Fields] OR “hemostatics”[Pharmacological Action] OR “hemostatics”[MeSH Terms] OR “hemostatics”[All Fields] OR “haemostats”[All Fields] OR “hemostasis”[MeSH Terms] OR “hemostasis”[All Fields] OR “haemostatic”[All Fields] OR “hemostat”[All Fields] OR “hemostatically”[All Fields] OR “hemostatic”[All Fields] OR “hemostats”[All Fields]

patch: “patch”[All Fields] OR “patch’s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields]

dorsal: “dorsal”[All Fields] OR “dorsale”[All Fields] OR “dorsally”[All Fields] OR “dorsals”[All Fields]

vein: “veins”[MeSH Terms] OR “veins”[All Fields] OR “vein”[All Fields]

bovine: “bovin”[All Fields] OR “cattle”[MeSH Terms] OR “cattle”[All Fields] OR “bovine”[All Fields] OR “bovines”[All Fields]

pericardium: “pericardium”[MeSH Terms] OR “pericardium”[All Fields] OR “pericardiums”[All Fields]

MEDLINE SEARCH STRING GENERAL

(“peyronie”[All Fields] OR “peyronie s”[All Fields] OR “peyronies”[All Fields] OR (“induratio”[All Fields] AND (“penis”[MeSH Terms] OR “penis”[All Fields])) OR (“penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“induratio”[All Fields] AND “penis”[All Fields] AND “plastica”[All Fields]) OR “induratio penis plastica”[All Fields]) OR (“penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“peyronie s”[All Fields] AND “disease”[All Fields]) OR “peyronie s disease”[All Fields])) AND (((“intestine, small”[MeSH Terms] OR (“intestine”[All Fields] AND “small”[All Fields]) OR “small intestine”[All Fields] OR (“small”[All Fields] AND “intestinal”[All Fields]) OR “small intestinal”[All Fields]) AND (“submucosa”[All Fields] OR “submucosae”[All Fields])) OR (“graft s”[All Fields] OR “grafted”[All Fields] OR “graftings”[All Fields] OR “transplantation”[MeSH Subheading] OR “transplantation”[All Fields] OR “grafting”[All Fields] OR “transplantation”[MeSH Terms] OR “grafts”[All Fields] OR “transplants”[MeSH Terms] OR “transplants”[All Fields] OR “graft”[All Fields]) OR ((“fibrin”[MeSH Terms] OR “fibrin”[All Fields] OR “fibrins”[All Fields] OR “fibrine”[All Fields]) AND (“patch”[All Fields] OR “patch s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields])) OR (“acellular dermis”[MeSH Terms] OR (“acellular”[All Fields] AND “dermis”[All Fields]) OR “acellular dermis”[All Fields] OR (“acellular”[All Fields] AND “dermal”[All Fields] AND “matrix”[All Fields]) OR “acellular dermal matrix”[All Fields]) OR “epiflex”[All Fields] OR (“tachosil”[Supplementary Concept] OR “tachosil”[All Fields] OR “tachosil”[All Fields] OR “fibrinogen”[MeSH Terms] OR “fibrinogen”[All Fields] OR “fibrinogens”[All Fields] OR “fibrinogen s”[All Fields] OR “fibrinogene”[All Fields] OR “thrombin”[MeSH Terms] OR “thrombin”[All Fields] OR “thrombin s”[All Fields] OR “thrombine”[All Fields] OR “thrombins”[All Fields]) OR ((“haemostat”[All Fields] OR “haemostatically”[All Fields] OR “haemostatics”[All Fields] OR “hemostatics”[Pharmacological Action] OR “hemostatics”[MeSH Terms] OR “hemostatics”[All Fields] OR “haemostats”[All Fields] OR “hemostasis”[MeSH Terms] OR “hemostasis”[All Fields] OR “haemostatic”[All Fields] OR “hemostat”[All Fields] OR “hemostatically”[All Fields] OR “hemostatic”[All Fields] OR “hemostats”[All Fields]) AND (“patch”[All Fields] OR “patch s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields])) OR (“deep”[All Fields] AND (“dorsal”[All Fields] OR “dorsale”[All Fields] OR “dorsally”[All Fields] OR “dorsals”[All Fields]) AND (“veins”[MeSH Terms] OR “veins”[All Fields] OR “vein”[All Fields])) OR ((“bovin”[All Fields] OR “cattle”[MeSH Terms] OR “cattle”[All Fields] OR “bovine”[All Fields] OR “bovines”[All Fields]) AND (“pericardium”[MeSH Terms] OR “pericardium”[All Fields] OR “pericardiums”[All Fields])))

Translations

peyronie: “peyronie”[All Fields] OR “peyronie’s”[All Fields] OR “peyronies”[All Fields]

penis: “penis”[MeSH Terms] OR “penis”[All Fields]

induratio penis plastica: “penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“induratio”[All Fields] AND “penis”[All Fields] AND “plastica”[All Fields]) OR “induratio penis plastica”[All Fields]

peyronie’s disease: “penile induration”[MeSH Terms] OR (“penile”[All Fields] AND “induration”[All Fields]) OR “penile induration”[All Fields] OR (“peyronie’s”[All Fields] AND “disease”[All Fields]) OR “peyronie’s disease”[All Fields]

small intestinal: “intestine, small”[MeSH Terms] OR (“intestine”[All Fields] AND “small”[All Fields]) OR “small intestine”[All Fields] OR (“small”[All Fields] AND “intestinal”[All Fields]) OR “small intestinal”[All Fields]

submucosa: “submucosa”[All Fields] OR “submucosae”[All Fields]

graft: “graft’s”[All Fields] OR “grafted”[All Fields] OR “graftings”[All Fields] OR “transplantation”[Subheading] OR “transplantation”[All Fields] OR “grafting”[All Fields] OR “transplantation”[MeSH Terms] OR “grafts”[All Fields] OR “transplants”[MeSH Terms] OR “transplants”[All Fields] OR “graft”[All Fields]

fibrin: “fibrin”[MeSH Terms] OR “fibrin”[All Fields] OR “fibrins”[All Fields] OR “fibrine”[All Fields]

patch: “patch”[All Fields] OR “patch’s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields]

acellular dermal matrix: “acellular dermis”[MeSH Terms] OR (“acellular”[All Fields] AND “dermis”[All Fields]) OR “acellular dermis”[All Fields] OR (“acellular”[All Fields] AND “dermal”[All Fields] AND “matrix”[All Fields]) OR “acellular dermal matrix”[All Fields]

tachosil: “TachoSil”[Supplementary Concept] OR “TachoSil”[All Fields] OR “tachosil”[All Fields] OR “fibrinogen”[MeSH Terms] OR “fibrinogen”[All Fields] OR “fibrinogens”[All Fields] OR “fibrinogen’s”[All Fields] OR “fibrinogene”[All Fields] OR “thrombin”[MeSH Terms] OR “thrombin”[All Fields] OR “thrombin’s”[All Fields] OR “thrombine”[All Fields] OR “thrombins”[All Fields]

hemostatic: “haemostat”[All Fields] OR “haemostatically”[All Fields] OR “haemostatics”[All Fields] OR “hemostatics”[Pharmacological Action] OR “hemostatics”[MeSH Terms] OR “hemostatics”[All Fields] OR “haemostats”[All Fields] OR “hemostasis”[MeSH Terms] OR “hemostasis”[All Fields] OR “haemostatic”[All Fields] OR “hemostat”[All Fields] OR “hemostatically”[All Fields] OR “hemostatic”[All Fields] OR “hemostats”[All Fields]

patch: “patch”[All Fields] OR “patch’s”[All Fields] OR “patche”[All Fields] OR “patches”[All Fields] OR “patching”[All Fields] OR “patchs”[All Fields]

dorsal: “dorsal”[All Fields] OR “dorsale”[All Fields] OR “dorsally”[All Fields] OR “dorsals”[All Fields]

vein: “veins”[MeSH Terms] OR “veins”[All Fields] OR “vein”[All Fields]

bovine: “bovin”[All Fields] OR “cattle”[MeSH Terms] OR “cattle”[All Fields] OR “bovine”[All Fields] OR “bovines”[All Fields]

pericardium: “pericardium”[MeSH Terms] OR “pericardium”[All Fields] OR “pericardiums”[All Fields]

subject))

The search strategy was developed for PubMed and modified accordingly for the other databases.