Results of Use of Tissue-Engineered Autologous

Oral Mucosa Graft for

Urethral Reconstruction: A Multicenter,
Prospective, Observational Trial
Gouya Ram-Liebig a,⁎, Guido Barbagli b, Axel Heidenreichc, Dirk Fahlenkamp d, Giuseppe Romano e,
Udo Rebmann f, Diana Standhaft f, Hermann van Ahlen g, Samer Schakaki g, Ulf Balsmeyer d,
Maria Spiegler h, Helmut Knispel h
a UroTiss Europe GmbH, Otto-Hahn-Str.15, 44227 Dortmund, Germany
b Centro Chirurgico Toscana, Via dei Lecci, 22, 52100 Arezzo, Italy
c University Clinic and Policlinic for Urology, Kerpener Str. 62, 50937 Cologne, Germany
d Zeisigwald Clinics Bethanien, Department of Urology, Zeisigwaldstrasse 101, 09130 Chemnitz, Germany
e Urology Unit, Ospedale del Valdarno, Santa Maria alla Gruccia, Piazza del Volontariato, 1, 52025 Montevarchi-Arezzo, Italy
f Diakonissen Clinics Dessau, Department of Urology, Gropiusallee 3, 06846 Dessau-Roßlau, Germany
g Osnabrueck Clinic, Department of Urology, Am Finkenhügel 1, 49076 Osnabrück, Germany
h St. Hedwig Hospital, Department of Urology, Große Hamburger Strasse 5-11, 10115 Berlin, Germany
Received 10 June 2017; revised 30 July 2017; accepted 15 August 2017 Available online 16 August 2017

Grace Septi Yudanthi Kerihi | 1408010059

Journal Reading
dr. Alders A. K. Nitbani, Sp.B

SURGERY DEPARTMENT - RSUD PROF. DR. W.Z. JOHANNES KUPANG

FACULTY OF MEDICINE - NUSA CENDANA UNIVERSITY
2018
 Urethral stricture affects up
to 0.6% of the male
population with significant
disease burden
(Alwaal et al., 2014; Liu et al., 2016;Wessells et al., 2017; Latini et
al., 2014)

Over the last two decades,

buccal mucosa became the
Introduction tissue of choice for urethral
reconstruction
(Wessells et al., 2017;Ram-Liebig et al., 2015;Markiewicz et al.,
2007)

Tissue-engineered oral
mucosa graft (TEOMG)
represents an alternative
material for urethroplasty
(Ram-Liebig et al.,2015)
 Materials and Methods
• Study Design and Patients
• Prospective, observational survey conducted at eight German urologic centers,
with < 10 to > 80 urethroplasties/year
• Enrolled were adult male patients with recurrent urethral stricture

• Coordination and Schedules

• For the manufacture of MukoCell®, a tiny oral biopsy is required. The urologist
needs an approval according to German Drug Law from the authority, who
granted the Good Manufacturing Practice (GMP) license for the TEOMG  the
patient agrees for the urethroplasty withMukoCell®  gets a biopsy kit from the
(GMP) laboratory (The biopsy kits are stable for 6 months) and the patient gets a
unique identification code
For safety reasons, the serologic examination must be negative
for specific infectious agents (Human Immunodeficiency
Virus, Hepatitis B and C, Treponema Pallidum), to allow
release of the tissue for manufacture
 Procedures
Manufacture of TEOMG  a tiny oral mucosa
biopsy of 0.5 cm2 was taken from patient's buccal
mucosa and sent to the GMP laboratory for aseptic
manufacturing of the graft

Before urethroplasty, information on demographic and

medical history was gathered. Pre- and post-operatively,
results from physical examination, vital signs
measurements, electrocardiogram, serological
examinations, concomitant medication, and
conventional urological examinations

The TEOMG was implanted in

accordance with the substitution
urethroplasty technique routinely applied
by the surgeon
Fig. 1. Urethroplasty with the autologous tissue-engineered oral mucosa graft MukoCell®. A small oral mucosa biopsy is
taken from the cheek of the patient (A) which is used for the manufacture of the graft. The latter is cut into the desirable
size (B), transferred to the opened urethra (C) and sutured as a ventral onlay graft (D). Pre- (E) and postoperative (F)
voiding urethrography, before and 3 weeks after the implantation of autologous tissue-engineered oral mucosa graft. The
strictured (S) and grafted (G) area are indicated in (E) and (F).
 Outcomes
• The primary outcome was the success rate (SR),
defined as the absence of stricture recurrence, at 12
months after TEOMG implantation
• Definition of stricture recurrence was: evidence of a
postoperative peak flow rate (Qmax) < 15 mL/s on
uroflowmetry plus the urethra is not passable with a
catheter (diameter= 16–18 Ch) or during standard
urethroscopy
 Results
• Results are available for 99
patients. In total, 65 patients
(65.7%) and 39 patients
(39.4%) reached 12 and 24
months of follow-up,
respective- ly
• The stricture was located in
the bulbar urethra (bulbar:
82.0%; penile: 18.0%);
stricture length ranged
between 5 and 130 mm with
an overall mean of 38.0 mm
• In the majority of patients,we observed no stricture recurrence during the observation period
with SR of 67.3% (95% CI 57.6–77.0) at 12 months, and 58.2% (95% CI 47.7–68.7) at 24
months (Kaplan-Meier analysis (Fig. 2A))
• The success rate ranged between 85.7% in the case of high and 0% in the case of low
experience in the surgical method
• The majority of stricture recurrences (70.3%) developed within 8 months of substitution
urethroplasty, and diminished gradually thereafter (Fig. 2).

Fig. 2. Kaplan-Meier plot of re-stricture-free survival. Time calculated from date of urethroplasty surgery. One patient with first
assessment after 12 months was excluded from analysis. Urethral strictures of any etiology, location, length and severity were
included in the study. Re-stricture-free survival rate, based on uncensored data, using age-related Qmax (Ortega & Pena, 2009) as
measure for stricture recurrence.
• After catheter removal, 92.6% (75 of 81 evaluable patients)were able to spontaneously micturate
comparedwith 70.8% (52 of 72) at baseline.
• Preoperatively, mean±SD Qmaxwas 8.3±4.7 mL/s (n=57) increasing to 25.4 ± 14.7 mL/s (n= 51) following
catheter removal.

Fig. 3. Kaplan-Meier plot of re-stricture-free survival by number of previous surgeries (urethrotomy or urethroplasty). One patient
with first assessment after 12 months was excluded from analysis. Urethral strictures of any etiology, location, length and severity
were included in the study
 Discussion

TEOMG for reconstruction

of the bulbar and penile
urethra is feasible, safe, and
efficacious in a heavily pre- Based on the presented
treated population. In our results, we suggest that after
multicenter, prospective, TEOMG implantation, the
observational study in a non- indwelling catheter should
preselected cohort, we not be left in place for longer
observed a satisfactory than 3–4 weeks
clinical outcome after 12 and
24 months in the majority of
patients
 Conclusion
TEOMG represents a safe and efficient alternative
to native oral mucosa as a graft for surgical
substitution of narrowed urethra, which may spare
the patients risk and discomfort at the intra-oral
donor site. Furthermore, our results suggest that
surgical substitution should be performed early in
disease before interventions repeatedly have
failed, and that the surgeon's experience and
appropriate post-surgical management (e.g. early
catheter removal) are key for a favorable
outcome.
Results of Use of Tissue-Engineered Autologous
Oral Mucosa Graft for
Urethral Reconstruction: A Multicenter,
Prospective, Observational Trial
Gouya Ram-Liebig a,⁎, Guido Barbagli b, Axel Heidenreichc, Dirk Fahlenkamp d, Giuseppe Romano e,
Udo Rebmann f, Diana Standhaft f, Hermann van Ahlen g, Samer Schakaki g, Ulf Balsmeyer d,
Maria Spiegler h, Helmut Knispel h
a UroTiss Europe GmbH, Otto-Hahn-Str.15, 44227 Dortmund, Germany
b Centro Chirurgico Toscana, Via dei Lecci, 22, 52100 Arezzo, Italy
c University Clinic and Policlinic for Urology, Kerpener Str. 62, 50937 Cologne, Germany
d Zeisigwald Clinics Bethanien, Department of Urology, Zeisigwaldstrasse 101, 09130 Chemnitz, Germany
e Urology Unit, Ospedale del Valdarno, Santa Maria alla Gruccia, Piazza del Volontariato, 1, 52025 Montevarchi-Arezzo, Italy
f Diakonissen Clinics Dessau, Department of Urology, Gropiusallee 3, 06846 Dessau-Roßlau, Germany
g Osnabrueck Clinic, Department of Urology, Am Finkenhügel 1, 49076 Osnabrück, Germany
h St. Hedwig Hospital, Department of Urology, Große Hamburger Strasse 5-11, 10115 Berlin, Germany
Received 10 June 2017; revised 30 July 2017; accepted 15 August 2017 Available online 16 August 2017
Grace Septi Yudanthi Kerihi | 1408010059
Journal Reading
dr. Alders A. K. Nitbani, Sp.B

SURGERY DEPARTMENT - RSUD PROF. DR. W.Z. JOHANNES KUPANG

FACULTY OF MEDICINE - NUSA CENDANA UNIVERSITY
2018