Pediatric laparoscopic pyeloplasty: Lessons learned from the first 52 cases

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Abstract
The use of laparoscopy for pediatric pyeloplasty is increasing. We review our experience with our first 50 cases and describe the main technical points learned during this experience. We retrospectively reviewed the charts of all patients who underwent laparoscopic pyeloplasties (LP) over a 4-year period (January 2004 to January 2008) at our institution. Patient demographics, operative details, hospital stay, outcomes, and complications were examined. Fifty-two patients underwent LP from for primary repair of ureteropelvic junction obstruction (UPJO). Thirty-six male and 16 female were operated on at an average age and weight (range) of 51.8 months (3 weeks to 216 months) and 20 kg (3.9-74.2 kg), respectively. Intraoperatively, 47/52 (90%) underwent retrograde ureteropyelography (RUPG), and 51/52 (98%) had a ureteral stent placed during surgery. Nine crossing vessels (17%) were identified at the time of surgery. The anastomoses were performed with a running absorbable suture. Operative time was 248 min (range 120-693 min). The average hospital stay was 3 days (range 1-7). A bladder catheter usually remained indwelling for 2 days and a perirenal drain for 3 days; they were removed before hospital discharge. The stent remained in place on average 39 days (range 11-127 d) and was removed with the patient under a brief general anesthetic. Anastomotic patency was seen in 51/52 (98%) patients determined by improvement on postoperative renal ultrasonography and/or resolution of symptoms. Mean follow-up was 20 months (range 3-50 mos). Complications included recurrence of UPJO necessitating redo LP (1), dislodgement of a nephrostomy (1), stent replacement (1), ileus (2), and vascular injuries treated laparoscopically (2). No patients needed conversion to open surgery. LP has supplanted open pyeloplasty at our institution. We have noted improved success by performing RUPG to define the anatomy and stent placement at the beginning of the case, using purple 5-0 or 6-0 poliglecaprone suture for the anastomosis and a 5-mm wide-angle lens for visualization. We found no disadvantages for the transperitoneal approach, although we find it necessary to leave a drain. With the increased use of LP in pediatric urology, we hope these observations from our experience will help improve the learning curve for others making this transition.

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Available from: Ricardo Gonzalez, Mar 08, 2016
Pediatric Laparoscopic Pyeloplasty:
Lessons Learned from the First 50 Cases
AU1 c
Job K. Chacko, Lisandro A. Piaggio, Amos Neheman, and Ricardo Gonza´ lezAU2 c
Abstract
Background and Purpose: The use of laparoscopy for pediatric pyeloplasty is increasing. We review our
experience with our first 50 cases and describe the main technical points learned during this experience.
Patients and Methods: We retrospectively reviewed the charts of all patients who underwent laparoscopic
pyeloplasties (LP) over a 4-year period ( January 2004 through 2008) at our institution. Patient demographics,
operative details, hospital stay, outcomes, and complications were examined.
Results: Fifty-two patients underwent LP from for primary repair of ureteropelvic junction obstruction (UPJO).
Thirty-six male and 16 female were operated on at an average age and weight (range) of 51.8 months (3 weeks to
216 months) and 20 kg (3.9–74.2 kg), respectively. Intraoperatively, 47=52 (90%) underwent retrograde ureter-
opyelography (RUPG), and 51=52 (98%) had a ureteral stent placed during surgery. Nine crossing vessels (17%)
were identified at the time of surgery. The anastomoses were performed with a running absorbable suture.
Operative time was 248 min (range 120–693 min). The average hospital stay was 3 days (range 1–7) A bladder
catheter usually remained indwelling for 2 days and a perirenal drain for 3 days; they were removed before
hospital discharge. The stent remained in place on average 39 days (range 11–127 d) and was removed with the
patient under a brief general anesthetic. Anastomotic patency was seen in 51=52 (98%) patients determined by
improvement on postoperative renal ultrasonography and=or resolution of symptoms. Mean follow-up was 20
months (range 3–50 mos). Complications included recurrence of UPJO necessitating redo LP (1), dislodgement of
a nephrostomy (1), stent replacement (1), ileus (2), and vascular injuries treated laparoscopically (2). No patients
needed conversion to open surgery.
Conclusion: LP has supplanted open pyeloplasty at our institution. We have noted improved success by per-
forming RUPG to define the anatomy and stent placement at the beginning of the case, using purple 5-0 or 6-0
poliglecaprone suture for the anastomosis and a 5-mm wide-angle lens for visualization. We found no disad-
vantages for the transperitoneal approach, although we find it necessary to leave a drain. With the increased use
of LP in pediatric urology, we hope these observations from our experience will help improve the learning curve
for others making this transition.
Introduction
The use of laparoscopic pyeloplasty with or without
robot assistance is well established in adults and is
gaining acceptance in pediatrics, as evidenced by the number
of publications.
1,2
As with any surgical technique, there is a
learning curve, which is particularly long with pyeloplasty
because of the delicate suturing involved. We have previously
reported our initial experience with 37 cases compared with
open pyeloplasty.
3
Here we present our experience with our first 52 cases at
our institution with emphasis on key points that we believe
can assist surgeons who are adopting laparoscopic surgery in
a safe and effective way to treat ureteropelvic junction ob-
struction (UPJO) in children.
Patients and Methods
An Institutional Review Board approved, retrospective
chart review was performed including all records of patients
who underwent laparoscopic repair of a primary UPJO be-
tween January 2004 and January 2008. bAU3
Patients with bilateral
repairs or redo pyeloplasties were excluded.
We reviewed patient demographics, operative details,
hospital stay, outcomes, and complications. All procedures
Department of Surgery, Division of Urology, Alfred I. duPont Hospital for Children, Wilmington, Delaware, and Thomas Jefferson
University, Philadelphia, Pennsylvania.
JOURNAL OF ENDOUROLOGY
Volume 23, Number 0, 2009
ªMary Ann Liebert, Inc.
Pp. &&&&&&
DOI: 10.1089=end.2009.0057
1
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Type: research-article
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were performed by one of four surgeons in conjunction with a
trainee.
All patients underwent a dismembered pyeloplasty using
a transperitoneal approach. The majority of patients had
retrograde ureteropyelography (RUPG) and Double-J stent
placement before the laparoscopic procedure. This was per-
formed with the patient in the dorsal lithotomy position. After
the stent placement the patients were repositioned in the su-
pine position with a roll elevating the affected side. In patients
who weighed fewer than 10 kg, the entire body below the
costal margin was prepped and included in the sterile field to
avoid repositioning.
4
In this subgroup of patients, tempera-
ture loss precautions, such as the use of waterproof drapes,
adequate room temperature, and insufflation with preheated
CO
2
, are important.
5
The laparoscopic portion was performed transperitoneally.
Access was gained using the Bailez technique,
6
which is a
modification of the Hasson technique. It consists of perform-
ing a 5 to 7 mm incision along the caudal edge of the umbilicus
and lifting the skin until the aponeurosis is seen and the re-
sulting opening in the peritoneum is identified. A 5-mm port
was then introduced bluntly for the camera. The use of a 5-
mm 30-degree wide-angle lens (Karl Storz GmbH & Co. KG,
Tuttlingen, Germany) was particularly advantageous in small
children. Two 3- or 5-mm working ports were placed under
direct vision. For a left-sided operation, the ports were placed
just left of the ligamentum teres in the epigastrium and in the
hypogastrium at the level of the midclavicular line. For the
right side, we placed the upper port to the right of midline to
help with right-handed suturing and the left port close to the
midline for better triangulation. The ports were sutured in
place to prevent inadvertent removal. Some surgeons pre-
ferred to use one 5-mm working port to facilitate introduction
of the needles and more efficient suction.
The use of short (20 cm) instruments was very helpful in
small children. A traction loop using umbilical tape was
placed on the camera port to tent up the abdomen to al-
low better visualization in small abdomens. In a right-sided
laparoscopic pyeloplasty, a fourth percutaneous placement of
a grasping instrument in the left lateral abdomen was occa-
sionally needed for liver retraction in one patient.
On inspection of the operative field, the distended pelvis
can sometimes be seen through the descending mesocolon on
the left side. In these cases, the repair was made through a
transmesocolonic window (six patients).
7
Otherwise, the co-
lon was mobilized to gain access to the renal pelvis. On the
right, the colon was always mobilized.
Percutaneous hitch stitches are placed (4-0 polypropylene),
one at the proximal and medial portion of the pelvis and one
taking the distal end of the ureterotomy and pyelotomy These
sutures suspended the area of anastomosis and decreased the
need to manipulate the tissues and to use suction. Depending
on the size of the pelvis, a segment of it was excised and the
ureter was left with a small segment of pelvis attached. This
was useful for traction and to assist in the orientation for the
lateral spatulation of the ureter.
The ureteropelvic anastomosis was performed using ab-
sorbable suture. Initially we used polyglycolic acid and
polydioxanone along with poliglecaprone. Our experience,
however, has led us to use 5-0 or 6-0 poliglecaprone
(Monocryl,
RB-1 needle, purple dyed) (Novartis Ethicon,
special order suture) exclusively, because it has good tensile
strength, has minimal memory, and glides through the tis-
sues smoothly. When using 3-mm ports, the suture was
passed through the 5-mm camera port to prevent blunting
the needle. We routinely cut the suture to a 10 to 12 cm
length and place a knot at 8 to 10 cm from the needle to
facilitate identifying its end (personal communication,
V. Jayanthi, M.D.).
The posterior wall was sutured first in a running fashion
starting proximally. A second suture was used for the anterior
wall or pelvis closure when the first one was not long enough
to complete the anastomosis. If at the end of the procedure
there was a question about the distal stent position, fluoros-
copy or cystoscopy was used to confirm it. A small Silastic
drain was placed near the anastomosis and brought out
through the port site in the hypogastrium.
Complications were divided into intraoperative and post-
operative. Postoperative complications were grouped ac-
cording to a modified Clavien classification.
8
Results
Patient characteristics
Fifty-two patients (36 males) were identified as undergoing
primary LP over a 4-year period. Thirty-six males and 16 fe-
males were operated on at an average age and weight (range)
of 51.8 months (3 weeks to 216 months) and 20 kg (3.9–74.2),
respectively.
Operative details
Operative time was measured from the start of cystoscopy
to the placement of the port dressings. The average laparo-
scopic procedure time was 248 minutes (range 120–693 min).
The average cystoscopy, RUPG, and stent placement time was
37.4 minutes (range 10–97 min). Intraoperatively, 47=52 (90%)
underwent RUPG with retrograde stent placement at that
time. In four of the patients who did not have RUPG, it was
difficult to pass a wire into the ureter. Of these, three were
under 3 months of age, and one was 14 months and had an
associated small ureterocele. Another patient who did not
undergo RUPG was a 10-year-old girl who had a traumatic
rupture of the pelvis ,and RUPG and stent placement were
performed 2 days before.
Ultimately, 51=52 (98%) had a ureteral stent placed by
the end of the procedure. The patient who did not have a
stent placed was a 6-week-old boy in whom the stent
could not to be placed in either a retrograde or antegrade
fashion. This patient had a percutaneous nephroureteral
stent.
Hospital course and outcomes
After surgery, patients were admitted to the general pedi-
atric ward and were started on a clear diet ad libitum. The
average hospital stay was 3 days (range 1–7 d). The bladder
catheter was removed at a mean of 2 days, and the drain was
kept in place for a mean of 3 days.
The stent was removed with the patient under a brief bAU4
general anesthetic at a mean of 39 days (range 11–127 d) after
the LP. Anastomosis patency was seen in 51=52 (98%) patients
as determined by improvement on postoperative renal ul-
trasonography and=or resolution of symptoms. Mean follow-
up was 20 months (range 3–50 mos).
2 CHACKO ET AL.
END-2009-0057-Chacko_1P.3d 06/20/09 3:47am Page 2
Complications
There were two intraoperative complications that involved
vascular injuries. One small lower pole vessel was divided
without apparent consequences. In another patient, the left
renal vein was injured and repaired laparoscopically after the
placement of two additional ports.
There were five postoperative complications. Three Cla-
vien grade 3b complications included a recurrent obstruction
necessitating redo LP, dislodgement of a nephroureteral stent,
and need for stent replacement. The patient who needed the
redo LP had the ureterotomy performed from distal to cranial
beginning with a transverse cut of the ureter. He eventually
had an avulsion of the ureter needing a new ureterotomy and
an anastomosis under some tension. He was reoperated la-
paroscopically using a pelvic flap technique.
Two Clavien grade 2 complications included a urinary leak
and prolonged ileus in two patients, all of which resolved
spontaneously. No patients needed conversion to open
surgery.
Discussion
The senior author (RG) initiated the program of laparo-
scopic pyeloplasty at our institution in August of 2004 after
having considerable experience with laparoscopic ablative
surgery in children. He was self-taught and expanded his
knowledge with a 1-week visit to an established center for
pediatric laparoscopic surgery. The senior author mentored
the remaining of the staff and fellows in training. Initially,
this approach was offered only to children older than 5 years
of age but was gradually expanded to all ages and to re-
operative pyeloplasty.
9
As the experience of the senior au-
thor increased, three other surgeons also participated, often
collaborating with one another. This experience has also
been used as part of our training program for pediatric
urology that now runs the sixth generation of fellows em-
bracing this technique. Performing open pyeloplasty has
become a rarity at our institution. The laparoscopic approach
has in no way changed the indications for the operation or
the follow-up routine.
Our preference has been to use the transperitoneal ap-
proach. Others prefer a retroperitoneal approach, but no clear
advantages have been demonstrated.
10
The theoretical dis-
advantage of the transperitoneal approach is the potential for
intra-abdominal visceral injury. The transperitoneal ap-
proach, however, is superior in a number of ways. The visu-
alization of the structures is outstanding even in small infants,
particularly when using short wide-angle optics. The larger
working space allows easier suturing, and crossing vessels are
readily identified. In addition, when using a 5-mm umbilical
port and two 3-mm working ports, the cosmetic results are far
better than with the retroperitoneoscopic approach in which
the port used to develop the retroperitoneal space is usually
bigger and in a more visible place.
In our experience with laparoscopic renal surgery, we have
not experienced any injury to an intraperitoneal organ. Also,
we think the Bailez technique
6
to gain access to the perito-
neum is the safest available.
The incidence of crossing vessels in our series was 18%,
lower than reported in adults and other pediatric series,
2,11
probably reflecting the larger number of infants in our series.
We have routinely transposed the ureter ventral to the cross-
ing vessels, a maneuver that facilitates the anastomosis, but
we are not certain that it is important for success.
The use of the percutaneous holding sutures has been ex-
tremely useful. These essentially act as additional instruments
for holding and manipulating the renal pelvis and ureter. In
addition to the decreased trauma to the tissues by using hitch
stitches, they stabilize the operative site, bringing it away
from the posterior abdominal wall where fluid tends to ac-
cumulate, allowing for the anastomosis to be performed in a
larger area with the instruments more free to move, and
minimizing the need for suction.
Traditionally, mobilization of the colon is performed for
LP. This is the approach we use for right-sided pyeloplasty.
On the left, often a transmesocolonic approach can be used.
This has been described in adults, and in children, with de-
creased operative times and hospital stays.
7,12
Our experience
has been that this is especially true in children with little
mesentery fat that can appear almost translucent. We started
using this approach later in our learning experience.
The ureteropelvic anastomosis is the most important por-
tion of the operation. Reduction of the size of the pelvis has
been performed rarely and does not improve the results.
13
Because the orientation of the ureter can be confusing, the cuff
of pelvis left attached to the ureter facilitates the spatulation in
the lateral aspect of the ureter.
We now perform the ureterotomy from cranial to caudal
introducing one of the scissors’ blades in the cuff of the pelvis
and progressing it to the stenotic part of the ureter. The Storz
(Karl Storz GmbH & Co. KG, Tuttlingen, Germany) pyelo-
plasty scissors with longer blades have been particularly
useful for this maneuver. The cut should be cold, and use of
cautery around the ureter should be kept to a minimum. Be-
cause the sharpness of the reusable scissors is variable, we
have find that the disposable 2-mm scissors (US Surgical,
Norwalk, CT) gives a crisp, clean cut and an edge that is easier
to visualize during the suturing.
The choice of suture has been a progression by trial and
experience. We found that the polyglactin suture we initially
used was more difficult to pass through tissue because it is
braided. Polydioxanone was better for sliding through the
tissue, but curling, memory, and easier breaking when tying
made us switch to 5-0 or 6-0 poliglecaprone (Monocryl, pur-
ple dyed, Novartis Ethicon, special order suture). Since
changing, we have noticed an improvement in the ease of
performing the anastomosis.
The benefits of a stented anastomosis are well docu-
mented.
14
The routine use of stents may have been an im-
portant factor for the better success we reported with LP
over open pyeloplasty.
3
After some trial and error, we have
opted for the routine use of RUPG and retrograde stent
placement. Although others advocate the antegrade place-
ment of a stent or the use of external stents, we have en-
countered greater difficulties with these methods. We still
think that imaging the ureter avoids strategic errors, such as
missing a distal obstruction or a long stenotic segment, as
was the case in the only patient in whom failure occurred in
this series.
15,16
Stents and drains after LP are used to prevent urinoma
formation near and around the anastomosis while this is
healing. In our patients, the stent was invariably well toler-
ated. Although there is a report of stentless laparoscopic
pyeloplasty in a small number of adults,
11
the majority of
PEDIATRIC LAPAROSCOPIC PYELOPLASTY 3
END-2009-0057-Chacko_1P.3d 06/20/09 3:47am Page 3
urologists use stents and=or drains in adults and children, and
the advantages seem clear.
14
The drain was removed before the patient’s discharge, but
the patients return for a second anesthetic for stent removal,
which is a disadvantage compared with adults. Some have
proposed leaving the dangling string and removing the stent
in the office after pediatric laparoscopic pyeloplasty,
12
but we
have not found this to be practical, because it has not been
well accepted by parents or children. Also, we have noted an
increased rate of urinary tract infection in other reconstructive
procedures when using this approach.
We believe that a stent is essential. In our experience, we
did not have any postoperative urinomas or prolonged leaks.
The only patient in whom urinary leak occurred, the leak
resolved shortly after urethral catheter replacement with no
other consequence than prolonging the hospital stay for
2 days. The only patient in whom we could not place a stent
had an external nephroureteral stent that malfunctioned and
necessitated a percutaneous nephrostomy.
Other complications have included two cases of prolonged
ileus, which resolved with conservative measures. An inad-
vertent lesion of the left renal vein during the dissection of the
pelvis was repaired without conversion by placing additional
ports for clamps. No long-term adverse effects were observed
in this patient.
Resolution of the obstruction was judged by absence of
symptoms with improvement on the degree of ultrasono-
graphic
AU5 cdilation of the pelvis and calices or improvement in
the excretory curve seen on the diuretic renogram. By these
standards, the success rate was 98%. We recognize that with
longer follow-up, problems may develop in a few additional
patients, but in our experience, this is a low possibility.
17
The
only failure necessitating a redo LP has been previously re-
ported.
7
No additional failures have occurred on primary
repairs of UPJO.
The mean surgical time of 249 minutes, including cys-
toscopy, RUPG, and stent placement, has remained stable
and is comparable to other series
1,2,18
but longer than in
others.
19,20
Although personal surgical time for individual
surgeons improves with time, in the 4 years of this expe-
rience, new faculty and fellows have been added to the
team, thus extending the learning curve. At present, the
senior author performs most pyeloplasties in less then
3 hours. In the future, robot-assisted pyeloplasty may re-
duce the effort involved in learning this demanding pro-
cedure; however, at present, no distinct advantage has been
demonstrated.
21
Nevertheless, the cost of the robot pres-
ently available and the relatively low number of pediatric
procedures that may benefit from its use makes it unlikely
that most children’s hospitals will have a robot in the near
future. Thus, training of staff and pediatric urology fellows
in performing reconstructive laparoscopic surgery continues
to be needed. In our experience, patients, families, and
surgeons have been satisfied with LP, and performing an
open pyeloplasty in our unit has become exceptional.
Conclusion
The use of laparoscopy in pediatrics is increasing, espe-
cially in the management of UPJO. We hope that some of the
lessons learned from our experience can be applied to help
other pediatric urologists. As technology moves forward, we
must also provide different options for management for the
common problems we see daily.
Disclosure Statement bAU6
No competing financial interests exist.
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Address correspondence to:
Prof. Ricardo Gonza
´lez
Department of Surgery
University Children’s Hospital
Steinwiesstrasse 75
Zurich
8032 Switzerland
E-mail: ricardo_gonzalez33154@yahoo.com
Abbreviations Used
LP ¼laparoscopic pyeloplasty
RUPG ¼retrograde ureteropyelography
UPJO ¼ureteropelvic junction obstruction
PEDIATRIC LAPAROSCOPIC PYELOPLASTY 5
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AUTHOR QUERY FOR END-2009-0057-CHACKO_1P
AU1: The article discusses 52 patients. Should this be reflected in the title?
AU2: Please insert author degrees ( M.D., Ph.D., etc.)
AU3: Abstract says January 2004 through 2008. Here it is January 2004 to January 2008. Which is correct? Please clarify.
AU4: Do you mean short-acting?
AU5: Ultrasonographic observed dilation?
AU6: Is the Disclosure Statement correct?
AU7: Current reference not found. Do you mean? Piaggio LA, Franc-Guimond J, Noh PH, Wehry M, Figueroa TE,
Barthold J, Gonza
´lez R. Transperitoneal laparoscopic pyeloplasty for primary repair of ureteropelvic junction
obstruction in infants and children: Comparison with open surgery. J Urol 2007;178:1579–1583.
AU8: Do you mean? J Urol 2003;170:936–938.
AU9: Do you mean? Antegrade pyelography before pyeloplasty via dorsal lumbar incision.
END-2009-0057-Chacko_1P.3d 06/20/09 3:47am Page 7
    • "An initial series of LPs in the pediatric population was reported in the 1990s [4]. Since then, multiple series have demonstrated high success rates (92–100%) and low perioperative morbidity, with only a few of them including >100 cases (Table 2)141516171819202122. The indications for LP in very young children has been questioned because of the likelihood of failure, concerns about technical difficulty, risk of complications, and undefined benefit over open surgery. "
    [Show abstract] [Hide abstract] ABSTRACT: Over the last two decades, minimally invasive treatment options for ureteropelvic junction obstruction (UPJO) have been developed and popularized. To critically analyze the current status of laparoscopic and robotic repair of UPJO. A systematic literature review was performed in November 2012 using PubMed. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Multiple series of laparoscopic pyeloplasty have demonstrated high success rates and low perioperative morbidity in pediatric and adult populations, with both the transperitoneal and retroperitoneal approaches. Data on pediatric robot-assisted pyeloplasty are increasingly becoming available. A larger number of cases have also been reported for adult patients, confirming that robotic pyeloplasty represents a viable option for either primary or secondary repair. Robot-assisted redo pyeloplasty has been mostly described in the pediatric population. Different technical variations have been implemented with the aim of tailoring the procedure to each specific case. The type of stenting, retrograde versus antegrade, continues to be debated. Internal-external stenting as well as a stentless approach have been used, especially in the pediatric population. Comparative studies demonstrate similar success and complication rates between minimally invasive and open pyeloplasty in both the adult and pediatric setting. A clear advantage in terms of hospital stay for minimally invasive over open pyeloplasty was observed only in the adult population. Laparoscopy represents an efficient and effective less invasive alternative to open pyeloplasty. Robotic pyeloplasty is likely to emerge as the new minimally invasive standard of care whenever robotic technology is available because its precise suturing and shorter learning curve represent unique attractive features. For both laparoscopy and robotics, the technique can be tailored to the specific case according to intraoperative findings and personal surgical experience.
    Full-text · Article · Jul 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Two cyclic nitrosamines, nitrosothiomorpholine and 1-nitrosopiperazine, have been tested by long term feeding to rats in drinking water, at 50 mg/l and 200 mg/l. Nitrosothiomorpholine produced tumors, both benign and malignant, of the esophagus and tongue. Nitrosopiperazine appeared to be definitely tumorigenic, although it showed no selectivity of site for tumor induction and induced tumors in a wide range of organs and tissues. Nitrosopiperazine was very much less acutely toxic than dinitrosopiperazine.Zwei cyclische Nitrosamine, nitroso-thiomorpholine und 1-Nitrosopiperazine, wurden Ratten in Langzeit-Versuchen im Trinkwasser appliziert (50 mg/l bzw. 200 mg/l). Nitroso-thiomorpholine fhrte zu benignen und malignen Tumoren des Oesophagus und der Zunge. Nitroso-pieerazine zeigte ebenfalls tumorigene Wirkung fr eine groe Zahl von Organen und Geweben, allerdings keine Organ-Spezifitt. Nitroso-piperazine erwies sich als von sehr viel geringerer akuter Toxicitt als Dinitroso-piperazin.
    Article · Jun 1970
  • Article · Feb 1979
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